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A Study to Evaluate Long-Term Maintenance Treatment With Once Daily Crisaborole Ointment 2% in Pediatric and Adult Participants With Mild-to-Moderate Atopic Dermatitis

Primary Purpose

Atopic Dermatitis

Status

Completed

Phase

Phase 3

Locations

International

Study Type

Interventional

Intervention

Crisaborole 2%

Vehicle

About this trial

This is an interventional treatment trial for Atopic Dermatitis focused on measuring Eczema, Crisaborole

Eligibility Criteria

3 Months - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Male or female
3 months of age and older
Confirmed diagnosis of atopic dermatitis according to Hanifin and Rajka criteria
Minimum of 5% BSA affected by atopic dermatitis
ISGA score of Mild (2) or Moderate (3)

Exclusion Criteria:

- Has any clinically significant medical disorder, condition, or disease (including active or potentially recurrent non AD dermatological conditions and known genetic dermatological conditions that overlap with AD, such as Netherton syndrome).

Sites / Locations

First OC Dermatology
Center for Dermatology Clinical Research, Inc.
Asthma and Allergy Associates, PC
Colorado Springs Dermatology Clinic, PC
Skin Care Research LLC
Clinical Neuroscience Solutions, Inc
Olympian Clinical Research
Baumann Cosmetic and Research Institute
Clinical Neuroscience Solutions, Inc
The Indiana Clinical Trials Center, PC
Meridian Clinical Research, LLC
Great Lakes Research Group, Inc.
Skin Specialists PC
Ohio Pediatric Research Association, Inc.
Lynn Health Science Institute
Oklahoma State University - Center for Health Sciences
Clinical Neuroscience Solutions, Inc.
Innovate Research, LLC
Austin Institute for Clinical Research
Austin Institute for Clinical Research, Inc.
Center for Clinical Studies, LTD. LLP
Jordan Valley Dermatology Center
PI-Coor Clinical Research LLC
Dermatology Specialists of Spokane
Principle Research Solutions
Australian Clinical Research Network
SimcoDerm Medical and Surgical Dermatology Center
Milestone Research , Inc
North York Research Inc.
Manna Research Toronto
Skinsense Medical Research
Peking University First Hospital
The First Affiliated Hospital of Fujian Medical University
Dermatology Hospital of Southern Medical University
Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology
Dermatology Hospital of Jiangxi Province
Huashan Hospital Fudan University/Dermatology Department
Tianjin Medical University General Hospital
First Affiliated Hospital of Kunming Medical University
Hangzhou Third Hospital
Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University
The Chaim Sheba Medical Center
Bezmialem Vakıf University Medical Faculty
Erciyes University Medical Faculty

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Crisaborole 2%

Vehicle

Arm Description

Crisaborole 2% ointment applied once daily (QD)

Vehicle ointment applied once daily (QD)

Outcomes

Primary Outcome Measures

Duration of Flare-Free Maintenance Until Onset of First-Flare During the Double Blind (DB) Period

The duration of flare-free maintenance was the time from randomization to the last Investigator's Static Global Assessment (ISGA) and was right censored, if an intercurrent event (eg, death, dropout, loss to follow up, or end of study) occurred before the first flare. When a flare occurred first, the duration of flare free maintenance was the time from randomization to the first flare and was not censored. Duration of flare free maintenance was estimated using the Kaplan-Meier method.

Number of Participants With Treatment Emergent Adverse Events (TEAEs)

An adverse event (AE) was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE was considered a TEAE if the event started on or after the treatment period start date and before end of study (at least 28 days after last dose of study intervention).

Secondary Outcome Measures

Number of Flare-Free Days During the DB Period

Flare - free days was the sum of the duration of flare-free maintenance during the DB maintenance period for each participant.

Number of Flares During the DB Period

Flare was defined as an ISGA score of >=2. The ISGA is a 5-point scale (range 0 to 4), reflecting a global assessment of AD severity based on erythema, induration/papulation, and oozing/crusting. ISGA score of 2: mild (faint pink erythema with mild induration/papulation and no oozing/crusting) 3: moderate (pink-red erythema with moderate induration/papulation with or without oozing/crusting) and 4: severe (deep or bright red erythema with severe induration/papulation and with oozing/crusting).

Secondary: Duration of Pruritus Response Maintenance Until Onset of First Flare During the DB Period: Participants Aged >=12 Years With Baseline Peak Pruritus Numerical Rating Scale (PP NRS) >=3, >=4 and >=3, >=4 Points Reduction in PP NRS

Duration of pruritus response maintenance=time from randomization to loss of pruritus response or first flare onset(ISGA>=2) during 52-week DB period evaluated among pruritus responders at randomization. Responders=participants with success in ISGA and EASI50 criteria. Pruritus response maintenance=maintenance of >=50% improvement in pruritus from baseline obtained at randomization. If event (e.g., death, first flare[ISGA >=2], lost to follow up or end of study) occurred before loss of pruritus response for first flare-free period, duration of pruritus response maintenance was time from randomization to last assessment and was censored. Here,pruritus response maintenance duration was presented for participants aged >=12 years with OL baseline PP NRS >=3, >=4 and >=3, >=4 points reduction from OL baseline to randomization in PP NRS. PP NRS: Participants were asked to rate their itch at worst moment during previous 24 hours on a scale of 0 to 10; 0=no itch and 10=worst itch imaginable".

Secondary: Duration of Pruritus Response Maintenance Until Onset of First Flare During the DB Period: Participants Aged 6 to <12 Years With Baseline Patient Reported Itch Severity (PRIS) >=2 and >=2 Points Reduction in PRIS

Duration of pruritus response maintenance=time from randomization to loss of pruritus response or first flare onset (ISGA>=2) during 52-week DB period. Evaluated among pruritus responders at randomization. Responders were defined as participants with success in ISGA and EASI50 criteria. Pruritus response maintenance=maintenance of >=50% improvement in pruritus from baseline that was obtained at randomization. If an event (e.g., death, first flare [ISGA >=2], lost to follow up, or end of study) occurred before loss of pruritus response for first flare-free period, duration of maintenance of pruritus response was time from randomization to last assessment and was censored. Here, pruritus response maintenance duration was presented for participants aged 6 to <12 years with baseline PRIS >=2 and >=2 points reduction from baseline to randomization in PRIS. PRIS: a 5-point scale (range: 0=no itch to 4=worst itch imaginable) and was completed by participants.

Duration of Pruritus Response Maintenance Until Onset of First Flare During the DB Period: Observer Reported Itch Severity Scale (ORIS) in Participants Aged 3 to <6 Months

Duration of pruritus response maintenance=time from randomization to loss of pruritus response or first flare onset(ISGA>=2)during52-weekDB period. Evaluated among pruritus responders (success in ISGA, EASI 50) at randomization. Pruritus response maintenance=maintenance of >=50% improvement in pruritus from baseline obtained at randomization. If event(e.g., death, first flare[ISGA >=2], lost to follow up, or end of study) occurred before loss of pruritus response for first flare-free period, duration of maintenance of pruritus response was time from randomization to last assessment and was censored. Here, pruritus response maintenance duration was presented for participants aged 3 to <6 months with OL baseline ORIS>=3 or >=4 and >=3 or >=4 points reduction from OL baseline to randomization in ORIS. Caregivers were asked to rate observation of their child's itch(scratching, rubbing) at worst moment during previous 24 hours on a scale of 0 to 10;0=no itch,10=worst itch imaginable.

Duration of Maintenance of >=50% Reduction in Eczema Area and Severity Index (EASI) Total Score Until Onset of First Flare During the DB Period

EASI assessed severity of AD, based on severity of lesion clinical signs (erythema [E], induration/papulation [I], excoriation [Ex], lichenification [L]) and % body surface area (BSA) affected. Each of clinical signs scored separately for each of 4 body regions (head and neck [h], upper limbs [u], trunk [t] [including axillae and groin], lower limbs [l] [including buttocks]) on 4-point scale: 0= absent; 1= mild; 2= moderate; 3= severe. EASI area score (A) according to %BSA with AD: 0 (0%), 1(>0 to <10%), 2(10 to <30%), 3(30 to <50%), 4(50 to <70%), 5(70 to <90%), 6 (90 to 100%). Total EASI score =0.1*Ah*(Eh + Ih + Exh + Lh) + 0.2*Au*(Eu + Iu + ExU + Lu) + 0.3*At*(Et +It + Ext + Lt) + 0.4*Al*(El + Il + Exl + Ll). Total EASI score ranged from 0.0 to 72.0, higher score = greater severity of AD. EASI response maintenance = score that does not lose more than 50% of achieved reduction from Day1/Baseline run-in EASI score.

Duration of Maintenance of Dermatology Life Quality Index (DLQI) Response Until Onset of First Flare During the DB Period

Duration of DLQI maintenance=time from randomization to loss of DLQI response during 52-week DB period for responders at randomization. If event(e.g., death, first flare[ISGA >=2], lost to follow up or end of study) occurred before loss of DLQI response, duration of maintenance of DLQI response=time from randomization to last assessment and censored. Responders=participants with success in ISGA,EASI50 criteria. DLQI response maintenance=response that does not lose more than minimal clinical important difference. DLQI =10-item questionnaire, measured impact of skin disease in participants aged >=16 years. Children's DLQI (CDLQI): participants aged 4 to15 years. Each question in DLQI and CDLQI evaluated on 4-point scale (range 0=not at all to 3=very much). Scores from10 items were added for DLQI/CDLQI total score, range:0 (not at all) to 30 (very much). Higher scores=more impact on quality of life of participants/children.

Duration of Maintenance of Patient Oriented Eczema Measure (POEM) Response Until Onset of First Flare During the DB Period

POEM was a 7-item participant reported outcome measure used to assess the impact of AD (dryness, itching, flaking, cracking, sleep loss, bleeding and weeping) over the past week. Each item was scored as: no days=0, 1-2 days=1, 3-4 days=2, 5-6 days=3 and every day=4. The total score ranged from 0 to 28, where higher score indicated greater severity. POEM response maintenance was defined as the response that does not lose more than minimal clinical important difference. Duration of POEM maintenance was time from randomization to loss of POEM response during 52-week DB period for responders at randomization. Responders were defined as participants with success in ISGA and EASI50 criteria. If an event (e.g., death, first flare [ISGA >=2], lost to follow up, or end of study) occurred before loss of POEM response, duration of maintenance of POEM response was time from randomization to last assessment and was censored. Proxy POEM was used for participants aged 3 months to <12 years.

Investigator's Static Global Assessment (ISGA) Score for the First Flare Period

ISGA:5- point global assessment scale of AD severity, used to characterize overall disease severity across all treatable AD lesions (excluding the scalp). Score ranged from 0 to 4: where 0= clear(minor residual hypo/hyperpigmentation; no erythema or induration/papulation; no oozing/crusting), 1= almost clear (trace faint pink erythema, with barely perceptible induration/papulation and no oozing/crusting), 2= mild (faint pink erythema with mild induration/papulation and no oozing/crusting), 3= moderate (pink-red erythema with moderate induration/papulation with or without oozing/crusting), 4= severe (deep or bright red erythema with severe induration/papulation and with oozing/crusting). Higher scores indicate greater severity of AD. First flare period was the time from the onset of flare (ISGA>=2) during DB maintenance period where the participant was switched to receive open-label crisaborole ointment 2%, BID for up to 12 weeks until resolution of flares.

EASI Score for the First Flare Period

EASI assessed severity of AD, based on severity of lesion clinical signs (erythema[E], induration/papulation[I], excoriation[Ex], lichenification[L]) and % body surface area(BSA) affected.Each of clinical signs scored separately for each of 4 body regions (head and neck[h], upper limbs[u], trunk[t] [including axillae and groin], lower limbs[l] [including buttocks]) on 4-point scale: 0= absent; 1=mild; 2= moderate; 3= severe.EASI area score(A) according to %BSA with AD: 0 (0%), 1(>0 to <10%), 2(10 to <30%), 3(30 to <50%), 4(50 to <70%), 5(70 to <90%), 6 (90 to 100%). Total EASI score =0.1*Ah*(Eh + Ih + Exh + Lh) + 0.2*Au*(Eu + Iu + ExU + Lu) + 0.3*At*(Et +It + Ext + Lt) + 0.4*Al*(El + Il + Exl + Ll). Total EASI score ranged from 0.0 to 72.0, higher score = greater severity of AD.First flare period=time from onset of flare(ISGA>=2) during DB maintenance period where participant was switched to receive open-label crisaborole ointment 2%,BID for up to 12 weeks until resolution of flares.

Duration (Days) of Flare Period

Duration of flare period was average duration calculated from sum of durations divided by number of flares for each participant.

Percent Change From Baseline in EASI Scores at Weeks 2, 4, 6 and 8: OL Run-in Period

Percent Change From Baseline in EASI Scores at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52: DB Period

Percent Change From Baseline in EASI Scores at Weeks 0, 4, 8 and 12: First Flare Treatment Period

EASI assessed severity of AD, based on severity of lesion clinical signs (erythema [E], induration/papulation [I], excoriation [Ex], lichenification [L]) and % body surface area (BSA) affected. Each of clinical signs scored separately for each of 4 body regions (head and neck [h], upper limbs [u], trunk [t] [including axillae and groin], lower limbs [l] [including buttocks]) on 4-point scale: 0= absent; 1= mild; 2= moderate; 3= severe. EASI area score (A) according to % BSA with AD: 0 (0%), 1(>0 to <10%), 2(10 to <30%), 3(30 to <50%), 4(50 to <70%), 5(70 to <90%), 6 (90 to 100%). Total EASI score =0.1*Ah*(Eh + Ih + Exh + Lh) + 0.2*Au*(Eu + Iu + ExU + Lu) + 0.3*At*(Et +It + Ext + Lt) + 0.4*Al*(El + Il + Exl + Ll). Total EASI score ranged from 0.0 to 72.0, higher score = greater severity of AD.

Percent Change From Baseline in EASI Scores at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52: First Flare Free Period

Change From Baseline in ISGA Scores at Weeks 2, 4, 6 and 8 for OL run-in Period

ISGA is a 5- point global assessment scale, used to characterize overall disease severity across all treatable AD lesions (excluding the scalp). Score ranged from 0 to 4: where 0= clear(minor residual hypo/hyperpigmentation; no erythema or induration/papulation; no oozing/crusting), 1= almost clear (trace faint pink erythema, with barely perceptible induration/papulation and no oozing/crusting), 2= mild (faint pink erythema with mild induration/papulation and no oozing/crusting), 3= moderate (pink-red erythema with moderate induration/papulation with or without oozing/crusting), 4= severe (deep or bright red erythema with severe induration/papulation and with oozing/crusting). Higher scores indicate greater severity of AD.

Change From Baseline in ISGA Scores at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52 for DB Period

Change From Baseline in ISGA Scores at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52 for First Flare Free Period

Change From Baseline in ISGA Scores at Weeks 0, 4, 8 and 12 for First Flare Treatment Period

ISGA:5-point global assessment scale, used to characterize overall disease severity across all treatable AD lesions (excluding scalp). Score ranged:0 to 4,where 0=clear(minor residual hypo/hyperpigmentation; no erythema or induration/papulation; no oozing/crusting), 1=almost clear(trace faint pink erythema, with barely perceptible induration/papulation and no oozing/crusting), 2=mild(faint pink erythema with mild induration/papulation and no oozing/crusting), 3=moderate(pink-red erythema with moderate induration/papulation with or without oozing/crusting), 4=severe(deep or bright red erythema with severe induration/papulation and with oozing/crusting). Higher scores indicate greater severity of AD. The period for which OL crisaborole 2% ointment BID was initiated for treatment of flare developed during DB maintenance until resumption of DB treatment was defined as flare treatment period.

Change From Baseline in Treatable Percent Body Surface Area (% BSA): OL Run-in Period

The extent (%) to which a body region was involved with AD was determined using handprint method. Four body regions evaluated: head and neck (hn), upper limbs (ul), trunk (tr) (including axillae) and lower limbs (ll) (including buttocks). Total number of handprints=10 for hn, 20 for ul, 30 for tr, 40 for ll in participants aged >=8 years; 20 for hn, 20 for ul, 30 for tr, 30 for ll in participants aged 3 months to 7 years. Surface area of body region equivalent to 1 handprint: 10% for hn, 5% for ul, 3.33% for tr, 2.5% for ll in participants aged >=8 years; 5% for hn, 5% for ul, 3.33% for tr, 3.33% for ll in participants aged 3 months to 7 years. % BSA for a body region= total number of handprints in a body region * % surface area equivalent to 1 handprint. Overall % BSA for an individual=sum of % BSA across all 4 body regions and ranged from 0 to 100%, with higher values representing greater extent of BSA involvement with AD.

Change From Baseline in Treatable %BSA: DB Period

Change From Baseline in Treatable %BSA: First Flare Free Period

Change From Baseline in Treatable %BSA: First Flare Period

Change From Baseline in Most Commonly Affected Atopic Dermatitis (AD) % BSA: DB Period

The investigators were required to draw the skin areas affected by AD for each participant in a body map and the most commonly affected BSA was documented.

Night Time Itch Score for Participants >=12 Years of Age: OL Run-in Period

The severity and frequency of itch (pruritus) during the night due to AD was assessed using a horizontal scale. Participants 12 years of age or older were asked to assess their worst itching and frequency of itching due to AD during their most recent night's sleep on a scale of 0 to 10, where 0= no itch and 10= worst itch imaginable. Higher scores indicated worse itch. Scale range of Frequency of night time itch was 0 to 10, where 0=no and 10=the most frequency imaginable. Higher score indicated higher frequency.

Night Time Itch Score for Participants >=12 Years of Age: DB Period

Night Time Itch Score for Participants >=12 Years of Age: First Flare Period

Night Time Itch Score for Participants >=12 Years of Age: First Flare Free Period

AD Skin Pain Scores for Participants >=12 Years of Age: OL Run-in Period

Participants 12 years of age or older were asked to assess their worst skin pain due to AD at the analysis time, with the question: 'AD skin pain right now' using the skin pain numerical rating scale (NRS). Skin pain NRS was a 11-point horizontal scale anchored at 0 and 10, with 0 representing "no pain" and 10 representing "worst pain imaginable." Higher scores indicated worse pain.

AD Skin Pain Scores for Participants >=12 Years of Age: DB Period

AD Skin Pain Scores for Participants >=12 Years of Age: First Flare Period

AD Skin Pain Scores: for Participants >=12 Years of Age First Flare Free Period

Participants 12 years of age or older were asked to assess their worst skin pain due to AD at the analysis time, with the question: 'AD skin pain right now' using the skin pain NRS. Skin pain NRS was a 11-point horizontal scale anchored at 0 and 10, with 0 representing "no pain" and 10 representing "worst pain imaginable." Higher scores indicated worse pain.

Patient/Observer Global Impression of Severity Score: OL Run-in Period

Patient/Observer Global Impression of Severity (PGIS/OGIS) is a single item participant or observer rated measure of the participant's AD condition severity at a given point in time using a 7-point rating scale, which ranges from 1 to 7, where 1=not present to 7=extremely severe. The PGIS was completed by all participants >=12 years of age and OGIS was completed by the observer for participants 3 months-<12 years of age.

Patient/Observer Global Impression of Severity Score: DB Period

PGIS/OGIS is a single item participant or observer rated measure of the participant's AD condition severity at a given point in time using a 7-point rating scale, which ranges from 1 to 7, where 1=not present to 7=extremely severe. The PGIS was completed by all participants >=12 years of age and OGIS was completed by the observer for participants 3 months-<12 years of age.

Patient/Observer Global Impression of Severity Score: First Flare Period

Patient/Observer Global Impression of Severity Score: First Flare Free Period

Patient/Observer Global Impression of Change Score: OL Run-in Period

Patient/Observer Global Impression of Change (PGIC/OGIC) is a single item instrument using 7-point rating scale and was used to determine global improvement at a given point in time since the start of study drug. The scores ranged from 1=very much improved to 7=very much worse. The PGIC was completed by all participants >=12 years of age and OGIC was completed by the observer for participants 3 months-<12 years of age.

Patient/Observer Global Impression of Change Score: DB Period

PGIC/OGIC is a single item instrument using 7-point rating scale and was used to determine global improvement at a given point in time since the start of study drug. The scores ranged from 1=very much improved to 7=very much worse. The PGIC was completed by all participants >=12 years of age and OGIC was completed by the observer for participants 3 months-<12 years of age.

Patient/Observer Global Impression of Change Score: First Flare Period

Patient/Observer Global Impression of Change Score: First Flare Free Period

Medical Outcome Study Sleep Scale Score in Participants >=12 Years of Age: OL Run-in Period

The Medical Outcomes Study (MOS) Sleep Scale is a 12-item measure that is segregated into subscales addressing seven sleep domains (i.e. sleep disturbance, snoring, short of breath or headache, adequacy of sleep, somnolence, sleep problems index I and sleep problems index II) and a single item assessing quantity of sleep. Quantity of sleep scores ranged from 0 to 24 (number of hours slept) and Optimal Sleep score ranged from 0 (no) to 1(yes) based on whether the participant slept for 7-8 hours per night, All other subscales including sleep problems index 1 and 2:were scored on a range of 0 to 100 where, higher scores=greater impairment. Observed scores for each individual sleep domain and quantity of sleep are reported in this outcome measure.

Medical Outcome Study Sleep Scale Score in Participants >=12 Years of Age: DB Period

MOS Sleep Scale is a 12-item measure that is segregated into subscales addressing seven sleep domains (i.e. sleep disturbance, snoring, short of breath or headache, adequacy of sleep, somnolence, sleep problems index I and sleep problems index II) and a single item assessing quantity of sleep. Quantity of sleep scores ranged from 0 to 24 (number of hours slept) and Optimal Sleep score ranged from 0 (no) to 1(yes) based on whether the participant slept for 7-8 hours per night, All other subscales including sleep problems index 1 and 2:were scored on a range of 0 to 100 where, higher scores=greater impairment. Observed scores for each individual sleep domain and quantity of sleep are reported in this outcome measure.

Medical Outcome Study Sleep Scale Score in Participants >=12 Years of Age: First Flare Period

Medical Outcome Study Sleep Scale Score in Participants >=12 Years of Age: First Flare Free Period

European Quality of Life-5 Dimension 5-Level (EQ-5D-5L) Index Score in Participants Greater Than or Equal to (>=) 18 Years of Age: OL Run-in Period

EQ-5D-5L: standardized participant completed questionnaire consisted of 2 components: a health state profile/a single utility index value and an optional VAS. EQ-5D health state profile/a single utility index value had 5 dimensions: mobility, self-care, usual activities, pain/discomfort, anxiety/depression. Each dimension has 5 levels: 1= no problems, 2= slight problems, 3= moderate problems, 4= severe problems and 5= extreme problems. Responses to 5 dimensions comprised a health state/a single utility index value. E.g. if a participant responded "no problems" for each 5 dimensions, then health state was coded as "11111" with a predefined index value to it. Every health state (coded as combination of responses on each of 5 dimensions) had a unique predefined utility index value assigned to it, by EuroQol. US value sets (with all possible health states) was used for adults in the study and total scores ranged from 1 to -0.109. Higher (positive) scores = better health state.

European Quality of Life-5 Dimension Youth (EuroQoL EQ-5D Y) Index Score in Participants Between 8-17 Years of Age: OL Run-in Period

EQ-5D-Y: child-friendly version of EQ-5D questionnaire related to health status. Health state profile assessed health in 5 dimensions (mobility; looking after myself; doing usual activities; having pain or discomfort; feeling worried, sad or unhappy) used to obtain an index score, each of which had three levels of response (no problems/no pain/not worried, some problems/some pain/a bit worried, a lot of problems/a lot of pain/very worried). Participants indicated their health state by choosing the appropriate level from each dimension. The 5 digit health states thus obtained for each dimension were then converted into a single median index value. A health state index score was calculated from individual health profiles using a USA scoring algorithm. Health state index scores generally ranged from -0.109 to 1, where,-0.109= the worst health status, 1= full health. Higher the score the better the health status. A positive change from baseline indicated improvement in health status.

EuroQoL EQ-5D Y Proxy Index Scores in Participants Between 2-7 Years of Age: OL Run-in Period

EQ-5D-Y:child-friendly version of EQ-5D questionnaire related to health status.Health state profile assessed health in 5 dimensions(Mobility;Looking After Myself;Doing Usual Activities;Having Pain or Discomfort;Feeling Worried,Sad or Unhappy)used to obtain index score,each of which had three levels of response(no problems/no pain/not worried,some problems/some pain/a bit worried,a lot of problems/a lot of pain/very worried).Participants indicated health state by choosing appropriate level from each dimension.5-digit health states obtained for each dimension were converted into single median index value using index value calculator,recommended by EuroQoL group.Health state index score calculated from individual health profiles using USA scoring algorithm. Scores ranged from -0.109 to 1,where, -0.109=worst health status, 1=full health. Higher score=better health status.Positive change from baseline indicated improvement in health status.Proxy version filled by care-giver of participant

EuroQoL EQ-5D-5L Visual Analog Scale (VAS) Score in Participants >= 18 Years of Age: OL Run-in Period

EQ-5D-5L VAS was used to record participant's rating for current health-related quality of life state on vertical VAS (0-100);0=worst imaginable health state;100=best imaginable health state.

EuroQoL EQ-5D Y VAS Scores in Participants Between 8-17 Years of Age : OL-Run-in Period

EQ-5D Y VAS was used to record participant's rating for his/her current health-related quality of life state on vertical VAS (0-100);0 = worst imaginable health state and 100 = best imaginable health state.

EuroQoL EQ-5D Y Proxy VAS Scores in Participants Between 2-7 Years of Age: OL Run-in Period

EQ-5D Y proxy VAS assessed the caregiver's impression of participants health state on a vertical VAS (range: 0 to 100), where, 0 (the worst imaginable health) to 100 (the best imaginable health).

EuroQoL EQ-5D-5L Index Scores in Participants >= 18 Years of Age: DB Period

EQ-5D-5L: standardized participant completed questionnaire consisted of 2 components: a health state profile/a single utility index value and an optional VAS. EQ-5D health state profile/a single utility index value had 5 dimensions: mobility, self-care, usual activities, pain/discomfort, anxiety/depression. Each dimension has 5 levels: 1= no problems, 2= slight problems, 3= moderate problems, 4= severe problems and 5= extreme problems. Responses to 5 dimensions comprised a health state/a single utility index value. E.g. if a participant responded "no problems" for each 5 dimensions, then health state was coded as "11111" with a predefined index value to it. Every health state (coded as combination of responses on each of 5 dimensions) had a unique predefined utility index value assigned to it, by EuroQoL. US value sets (with all possible health states) was used for adults in the study and total scores ranged from 1 to -0.109. Higher (positive) scores = better health state.

EuroQoL EQ-5D Y Index Scores in Participants Between 8-17 Years of Age: DB Period

EuroQoL EQ-5D Y Proxy Index Scores in Participants Between 2-7 Years of Age: DB Period

EuroQoL EQ-5D-5L VAS Scores in Participants >= 18 Years of Age: DB Period

EQ-5D-5L VAS to record participant's rating for current health-related quality of life state on vertical VAS (0-100);0=worst imaginable health state;100=best imaginable health state.

EuroQoL EQ-5D Y VAS Scores in Participants Between 8-17 Years of Age: DB Period

EQ-5D Y VAS was a child-friendly version of EQ-5D questionnaire related to health status used to record participant's rating for his/her current health-related quality of life state on vertical VAS (0-100);0 = worst imaginable health state and 100 = best imaginable health state.

EuroQoL EQ-5D Y Proxy VAS Scores in Participants Between 2-7 Years of Age: DB Period

EQ-5D Y proxy VAS assessed the caregiver's impression of participants health state on a vertical VAS (range: 0 to 100), where, 0 (the worst imaginable health) to 100 (the best imaginable health).

EuroQoL EQ-5D-5L Index Scores in Participants >= 18 Years of Age: First Flare Period

EuroQoL EQ-5D Y Index Scores in Participants Between 8-17 Years of Age: First Flare Period

EuroQoL EQ-5D Y Proxy Index Scores in Participants Between 2-7 Years of Age: First Flare Period

EuroQoL EQ-5D-5L VAS Scores in Participants >= 18 Years of Age: First Flare Period

EQ-5D-5L VAS was used to record participant's rating for his/her current health-related quality of life state on a vertical VAS (0-100), where 0 = worst imaginable health state and 100 = best imaginable health state.

EuroQoL EQ-5D Y VAS Scores in Participants Between 8-17 Years of Age: First Flare Period

EuroQoL EQ-5D Y Proxy VAS Scores in Participants Between 2-7 Years of Age: First Flare Period

EQ-5D Y proxy VAS assessed the caregiver's impression of participants health state on a vertical VAS (range: 0 to 100), where, 0 (the worst imaginable health) to 100 (the best imaginable health).

EuroQoL EQ-5D Y Index Scores in Participants >= 18 Years of Age: First Flare Free Period

EuroQoL EQ-5D Y Index Scores in Participants Between 8-17 Years of Age: First Flare Free Period

EuroQoL EQ-5D Y Proxy Index Scores in Participants Between 2-7 Years of Age: First Flare Free Period

EuroQoL EQ-5D-5L VAS Scores in Participants >= 18 Years of Age: First Flare Free Period

EQ-5D-5L VAS was used to record participant's rating for current health-related quality of life state on vertical VAS (0-100);0=worst imaginable health state;100=best imaginable health state.

EuroQoL EQ-5D Y VAS Scores in Participants Between 8-17 Years of Age: First Flare Free Period

EuroQoL EQ-5D Y Proxy VAS Scores in Participants Between 2-7 Years of Age: First Flare Free Period

EQ-5D Y proxy VAS assessed the caregiver's impression of participants health state on a vertical VAS (range: 0 to 100), where, 0 (the worst imaginable health) to 100 (the best imaginable health).

Percent Work Time Missed Using Work Productivity and Activity Impairment (WPAI) Questionnaire Plus Classroom Impairment Questions (CIQ): OL Run-in Period

WPAI plus CIQ was a 10-item questionnaire used to assess degree to which AD affected work productivity and regular activities over past 7 days. Questions were: Q1= currently employed; Q2= work hours missed due to health problems; Q3= work hours missed due to other reasons; Q4= hours actually worked; Q5= degree health affected productivity while working (0-10 scale, higher scores = less productivity); Q6= classes attended in academic setting or not; Q7= class hours missed due to health problems; Q8= class hours actually attended; Q9= degree health affected productivity while attending (0-10 scale, high scores= less productivity); Q10= degree health affected productivity in regular daily activities (0-10 scale, higher scores = less productivity). Percent work time missed was calculated as: Q2*100/(Q2+Q4) and score ranged from 0-100%, higher scores = greater impairment and less productivity.

Percent Impairment While Working Using Work Productivity and Activity Impairment (WPAI) Questionnaire Plus Classroom Impairment Questions (CIQ): OL Run-in Period

WPAI+CIQ:10-item questionnaire used to assess degree to which AD affected work productivity and regular activities over past 7 days. Questions were:Q1= currently employed;Q2= work hours missed due to health problems; Q3=work hours missed due to other reasons; Q4= hours actually worked; Q5 = degree health affected productivity while working (0-10 scale, high scores=less productivity);Q6=classes attended in academic setting or not;Q7= class hours missed due to health problems; Q8= class hours actually attended; Q9= degree health affected productivity while attending(0-10 scale, high scores= less productivity); Q10= degree health affected productivity in regular daily activities (0-10 scale, high scores=less productivity). Percent impairment while working due to health problem was calculated as: 100*Q5/10 and score ranged from 0-100%,higher scores =greater impairment and less productivity.

Percent Overall Work Impairment Using Work Productivity and Activity Impairment (WPAI) Questionnaire Plus Classroom Impairment Questions (CIQ): OL Run-in Period

WPAI+CIQ:10-item questionnaire to assess degree to which AD affected work productivity and regular activities over past 7 days.Questions:Q1=currently employed;Q2=work hours missed due to health problems;Q3=work hours missed due to other reasons;Q4=hours actually worked;Q5=degree health affected productivity while working(0-10 scale, high scores=less productivity);Q6=classes attended in academic setting or not;Q7=class hours missed due to health problems;Q8=class hours actually attended;Q9=degree health affected productivity while attending(0-10 scale, high scores= less productivity);Q10=degree health affected productivity: regular daily activities (0-10 scale, high scores =less productivity). Percent overall impairment while working due to health problem calculated as:100*{Q2/(Q2+Q4)+[(1- Q2/(Q2+Q4))×(Q5/10)]},score ranged:0-100%,high numbers=greater impairment and less productivity.

Percent Class Time Missed Using Work Productivity and Activity Impairment Questionnaire Plus Classroom Impairment Questions: OL Run-in Period

WPAI+CIQ:10-item questionnaire to assess degree to which AD affected work productivity and regular activities over past 7 days. Questions: Q1=currently employed; Q2=work hours missed due to health problems; Q3=work hours missed due to other reasons; Q4=hours actually worked; Q5=degree health affected productivity while working (0-10 scale, high scores=less productivity); Q6=classes attended in academic setting or not; Q7=class hours missed due to health problems; Q8=class hours actually attended; Q9=degree health affected productivity while attending(0-10 scale, high scores= less productivity); Q10=degree health affected productivity in regular daily activities(0-10 scale, high scores =less productivity).Percent class time missed due to health problem calculated as: Q7*100/(Q7+Q8) and score ranged from 0-100% where higher numbers=greater impairment and less productivity.

Percent Impairment While in Class Using Work Productivity and Activity Impairment Questionnaire Plus Classroom Impairment Questions: OL Run-in Period

WPAI+CIQ:10-item questionnaire used to assess degree to which AD affected work productivity and regular activities over past 7 days. Questions: Q1=currently employed; Q2=work hours missed due to health problems; Q3=work hours missed due to other reasons; Q4=hours actually worked; Q5 = degree health affected productivity while working (0-10 scale, high scores=less productivity); Q6=classes attended in academic setting or not; Q7=class hours missed due to health problems; Q8=class hours actually attended; Q9=degree health affected productivity while attending (0-10 scale, high scores= less productivity); Q10=degree health affected productivity in regular daily activities (0-10 scale, high scores =less productivity). Percent impairment while in class was calculated as: 100*Q9/10 and score ranged from 0-100% where higher numbers indicate greater impairment and less productivity.

Percent Overall Class Impairment Using Work Productivity and Activity Impairment Questionnaire Plus Classroom Impairment Questions: OL Run-in Period

WPAI+CIQ:10-item questionnaire to assess degree to which AD affected work productivity and regular activities over past7days.Questions:Q1=currently employed;Q2=work hours missed due to health problems;Q3=work hours missed due to other reasons;Q4=hours actually worked;Q5=degree health affected productivity while working (0-10 scale, high scores=less productivity);Q6=classes attended in academic setting or not;Q7=class hours missed due to health problems;Q8=class hours actually attended;Q9=degree health affected productivity while attending(0-10 scale, high scores= less productivity);Q10=degree health affected productivity in regular daily activities(0-10 scale, high scores =less productivity).Percent overall class impairment due to health problem calculated as: 100*{Q7/(Q7+Q8)+[(1- Q7/(Q7+Q8))×(Q9/10)]},score range:0-100%,higher numbers=greater impairment and less productivity.

Percent Activity Impairment Using Work Productivity and Activity Impairment Questionnaire Plus Classroom Impairment Questions: OL Run-in Period

WPAI+CIQ: 10-item questionnaire used to assess degree to which AD affected work productivity and regular activities over past 7 days. Questions:Q1=currently employed;Q2=work hours missed due to health problems; Q3=work hours missed due to other reasons; Q4=hours actually worked; Q5=degree health affected productivity while working (0-10 scale, high scores=less productivity); Q6=classes attended in academic setting or not; Q7=class hours missed due to health problems; Q8=class hours actually attended; Q9=degree health affected productivity while attending(0-10 scale, high scores= less productivity); Q10=degree health affected productivity in regular daily activities(0-10 scale, high scores =less productivity). Percent activity impairment due to health problem calculated as: 100*Q10/10, score ranged from 0-100%,higher numbers=greater impairment and less productivity.

Percent Work Time Missed Using Work Productivity and Activity Impairment Questionnaire Plus Classroom Impairment Questions: DB Period

WPAI+CIQ:10-item questionnaire used to assess degree to which AD affected work productivity and regular activities over past 7 days. Questions were: Q1=currently employed; Q2=work hours missed due to health problems; Q3=work hours missed due to other reasons;Q4=hours actually worked; Q5 = degree health affected productivity while working (0-10 scale, high scores=less productivity);Q6=classes attended in academic setting or not;Q7=class hours missed due to health problems;Q8=class hours actually attended;Q9=degree health affected productivity while attending(0-10 scale, high scores = less productivity);Q10=degree health affected productivity in regular daily activities(0-10 scale, high scores=less productivity). Percent work time missed due to health problem calculated as: Q2*100/(Q2+Q4) and score ranged from 0-100%,higher numbers=greater impairment and less productivity.

Percent Impairment While Working Using Work Productivity and Activity Impairment Questionnaire Plus Classroom Impairment Questions: DB Period

WPAI+CIQ:10-item questionnaire used to assess degree to which AD affected work productivity and regular activities over past 7 days. Questions:Q1=currently employed; Q2=hours missed due to health problems; Q3=hours missed due to other reasons; Q4=hours actually worked; Q5=degree health affected productivity while working (0-10 scale, high scores=less productivity); Q6=classes attended in academic setting or not; Q7=hours missed due to health problems; Q8=hours actually attended; Q9=degree health affected productivity while attending(0-10 scale, high scores= less productivity); Q10=degree health affected productivity in regular daily activities(0-10 scale, high scores =less productivity). Percent impairment while working due to health problem calculated as: 100*Q5/10 score ranged from 0-100%,higher numbers=greater impairment and less productivity.

Percent Overall Work Impairment Using Work Productivity and Activity Impairment Questionnaire Plus Classroom Impairment Questions: DB Period

WPAI+CIQ:10-item questionnaire to assess degree to which AD affected work productivity and regular activities over past 7 days. Questions: Q1=currently employed;Q2=work hours missed due to health problems;Q3=work hours missed due to other reasons;Q4=hours actually worked;Q5=degree health affected productivity while working(0-10 scale, high scores=less productivity);Q6=classes attended in academic setting or not;Q7=class hours missed due to health problems;Q8=class hours actually attended;Q9=degree health affected productivity while attending(0-10 scale, high scores= less productivity);Q10=degree health affected productivity: regular daily activities(0-10 scale, high scores =less productivity). Percent overall impairment while working due to health problem calculated as:100*{Q2/(Q2+Q4)+[(1- Q2/(Q2+Q4))×(Q5/10)]}, score ranged: 0-100%, high numbers=greater impairment and less productivity.

Percent Class Time Missed Using Work Productivity and Activity Impairment Questionnaire Plus Classroom Impairment Questions: DB Period

WPAI+CIQ:10-item questionnaire to assess degree to which AD affected work productivity and regular activities over past 7 days. Questions: Q1=currently employed; Q2=work hours missed due to health problems; Q3=work hours missed due to other reasons; Q4=hours actually worked; Q5=degree health affected productivity while working(0-10 scale, high scores =less productivity); Q6=classes attended in academic setting or not;Q7=class hours missed due to health problems; Q8=class hours actually attended; Q9=degree health affected productivity while attending(0-10 scale, high scores= less productivity); Q10=degree health affected productivity in regular daily activities(0-10 scale, high scores =less productivity). Percent class time missed due to health problem calculated as: Q7*100/(Q7+Q8) and score ranged from 0-100% where higher numbers=greater impairment and less productivity.

Percent Impairment While in Class Using Work Productivity and Activity Impairment Questionnaire Plus Classroom Impairment Questions: DB Period

WPAI+CIQ: 10-item questionnaire used to assess degree to which AD affected work productivity and regular activities over past 7 days. Questions: Q1=currently employed; Q2=work hours missed due to health problems; Q3=work hours missed due to other reasons; Q4=hours actually worked; Q5 = degree health affected productivity while working (0-10 scale, high scores=less productivity); Q6=classes attended in academic setting or not; Q7=class hours missed due to health problems; Q8=class hours actually attended; Q9=degree health affected productivity while attending(0-10 scale, high scores = less productivity); Q10=degree health affected productivity in regular daily activities (0-10 scale, high scores =less productivity). Percent impairment while in class was calculated as: 100*Q9/10 and score ranged from 0-100% where higher numbers indicate greater impairment and less productivity.

Percent Overall Class Impairment Using Work Productivity and Activity Impairment Questionnaire Plus Classroom Impairment Questions: DB Period

WPAI+CIQ: 10-item questionnaire to assess degree to which AD affected work productivity and regular activities over past 7 days. Questions: Q1=currently employed; Q2=work hours missed due to health problems; Q3=work hours missed due to other reasons; Q4=hours actually worked; Q5=degree health affected productivity while working (0-10 scale, high scores =less productivity); Q6=classes attended in academic setting or not; Q7=class hours missed due to health problems; Q8=class hours actually attended; Q9=degree health affected productivity while attending(0-10 scale, high scores = less productivity); Q10=degree health affected productivity in regular daily activities (0-10 scale, high scores =less productivity). Percent overall class impairment due to health problem calculated as: 100*{Q7/(Q7+Q8)+[(1- Q7/(Q7+Q8))×(Q9/10)]}, score range:0-100%, higher numbers=greater impairment and less productivity.

Percent Activity Impairment Using Work Productivity and Activity Impairment Questionnaire Plus Classroom Impairment Questions: DB Period

WPAI+CIQ:10-item questionnaire used to assess degree to which AD affected work productivity and regular activities over past 7 days. Questions: Q1=currently employed; Q2=work hours missed due to health problems; Q3=work hours missed due to other reasons; Q4=hours actually worked; Q5=degree health affected productivity while working (0-10 scale, high scores=less productivity); Q6=classes attended in academic setting or not; Q7=class hours missed due to health problems; Q8=class hours actually attended; Q9=degree health affected productivity while attending(0-10 scale, high scores= less productivity); Q10=degree health affected productivity in regular daily activities(0-10 scale, high scores =less productivity). Percent activity impairment due to health problem calculated as: 100*Q10/10, score ranged from 0-100%,higher numbers=greater impairment and less productivity.

Percent Work Time Missed Using Work Productivity and Activity Impairment Questionnaire Plus Classroom Impairment Questions: First Flare Free Period

WPAI+CIQ:10-item questionnaire used to assess degree to which AD affected work productivity and regular activities over past 7 days. Questions were: Q1=currently employed; Q2=work hours missed due to health problems;Q3=work hours missed due to other reasons; Q4=hours actually worked; Q5= degree health affected productivity while working (0-10 scale, high scores =less productivity); Q6=classes attended in academic setting or not; Q7=class hours missed due to health problems; Q8=class hours actually attended; Q9=degree health affected productivity while attending(0-10 scale, high scores = less productivity); Q10=degree health affected productivity in regular daily activities(0-10 scale, high scores =less productivity). Percent work time missed due to health problem calculated as: Q2*100/(Q2+Q4) and score ranged from 0-100%, higher numbers=greater impairment and less productivity.

Percent Impairment While Working Using Work Productivity and Activity Impairment Questionnaire Plus Classroom Impairment Questions: First Flare Free Period

WPAI+CIQ: 10-item questionnaire used to assess degree to which AD affected work productivity and regular activities over past 7 days. Questions: Q1=currently employed; Q2=hours missed due to health problems; Q3=hours missed due to other reasons; Q4=hours actually worked; Q5=degree health affected productivity while working (0-10 scale, high scores =less productivity); Q6=classes attended in academic setting or not; Q7=hours missed due to health problems; Q8=hours actually attended; Q9=degree health affected productivity while attending(0-10 scale, high scores = less productivity); Q10=degree health affected productivity in regular daily activities(0-10 scale, high scores =less productivity). Percent impairment while working due to health problem calculated as: 100*Q5/10 score ranged from 0-100%, higher numbers=greater impairment and less productivity.

Percent Overall Work Impairment Using Work Productivity and Activity Impairment Questionnaire Plus Classroom Impairment Questions: First Flare Free Period

WPAI+CIQ: 10-item questionnaire to assess degree to which AD affected work productivity and regular activities over past 7 days. Questions: Q1=currently employed; Q2=work hours missed due to health problems; Q3=work hours missed due to other reasons; Q4=hours actually worked; Q5=degree health affected productivity while working (0-10 scale, high scores =less productivity); Q6=classes attended in academic setting or not; Q7=class hours missed due to health problems; Q8=class hours actually attended; Q9=degree health affected productivity while attending (0-10 scale, high scores = less productivity); Q10=degree health affected productivity: regular daily activities(0-10 scale, high scores =less productivity). Percent overall impairment while working due to health problem calculated as:100*{Q2/(Q2+Q4)+[(1- Q2/(Q2+Q4))×(Q5/10)]}, score ranged:0-100%, high numbers=greater impairment and less productivity.

Percent Class Time Missed Using Work Productivity and Activity Impairment Questionnaire Plus Classroom Impairment Questions: First Flare Free Period

WPAI+CIQ:10-item questionnaire to assess degree to which AD affected work productivity and regular activities over past 7 days. Questions: Q1=currently employed; Q2=work hours missed due to health problems; Q3=work hours missed due to other reasons; Q4=hours actually worked; Q5=degree health affected productivity while working(0-10 scale, high scores =less productivity); Q6=classes attended in academic setting or not; Q7=class hours missed due to health problems; Q8=class hours actually attended; Q9=degree health affected productivity while attending(0-10 scale, high scores = less productivity); Q10=degree health affected productivity in regular daily activities(0-10 scale, high scores =less productivity). Percent class time missed due to health problem calculated as: Q7*100/(Q7+Q8) and score ranged from 0-100% where higher numbers=greater impairment and less productivity.

Percent Impairment While in Class Using Work Productivity and Activity Impairment Questionnaire Plus Classroom Impairment Questions: First Flare Free Period

WPAI+CIQ:10-item questionnaire used to assess degree to which AD affected work productivity and regular activities over past 7 days. Questions: Q1=currently employed; Q2=work hours missed due to health problems; Q3=work hours missed due to other reasons; Q4=hours actually worked; Q5 = degree health affected productivity while working (0-10 scale, high scores =less productivity); Q6=classes attended in academic setting or not; Q7=class hours missed due to health problems; Q8=class hours actually attended; Q9=degree health affected productivity while attending (0-10 scale, high scores = less productivity); Q10=degree health affected productivity in regular daily activities(0-10 scale, high scores =less productivity). Percent impairment while in class was calculated as: 100*Q9/10 and score ranged from 0-100% where higher numbers indicate greater impairment and less productivity.

Percent Overall Class Impairment Using Work Productivity and Activity Impairment Questionnaire Plus Classroom Impairment Questions: First Flare Free Period

WPAI+CIQ:10-item questionnaire to assess degree to which AD affected work productivity and regular activities over past 7 days. Questions: Q1=currently employed; Q2=work hours missed due to health problems; Q3=work hours missed due to other reasons; Q4=hours actually worked; Q5=degree health affected productivity while working (0-10 scale, high scores =less productivity); Q6=classes attended in academic setting or not; Q7=class hours missed due to health problems; Q8=class hours actually attended; Q9=degree health affected productivity while attending(0-10 scale, high scores = less productivity); Q10=degree health affected productivity in regular daily activities (0-10 scale, high scores =less productivity). Percent overall class impairment due to health problem calculated as: 100*{Q7/(Q7+Q8)+[(1- Q7/(Q7+Q8))×(Q9/10)]}, score range:0-100%,higher numbers=greater impairment and less productivity.

Percent Activity Impairment Using Work Productivity and Activity Impairment Questionnaire Plus Classroom Impairment Questions: First Flare Free Period

WPAI+CIQ:10-item questionnaire used to assess degree to which AD affected work productivity and regular activities over past 7 days. Questions: Q1=currently employed; Q2=work hours missed due to health problems; Q3=work hours missed due to other reasons; Q4=hours actually worked; Q5=degree health affected productivity while working (0-10 scale, high scores =less productivity); Q6=classes attended in academic setting or not; Q7=class hours missed due to health problems; Q8=class hours actually attended; Q9=degree health affected productivity while attending (0-10 scale, high scores = less productivity); Q10=degree health affected productivity in regular daily activities(0-10 scale, high scores =less productivity). Percent activity impairment due to health problem calculated as: 100*Q10/10, score ranged from 0-100%,higher numbers=greater impairment and less productivity.

Percent Work Time Missed Using Work Productivity and Activity Impairment Questionnaire Plus Classroom Impairment Questions: First Flare Period

WPAI+CIQ:10-item questionnaire used to assess degree to which AD affected work productivity and regular activities over past 7 days. Questions were: Q1=currently employed; Q2=work hours missed due to health problems; Q3=work hours missed due to other reasons; Q4=hours actually worked; Q5 = degree health affected productivity while working (0-10 scale, high scores =less productivity); Q6=classes attended in academic setting or not; Q7=class hours missed due to health problems; Q8=class hours actually attended; Q9=degree health affected productivity while attending (0-10 scale, high scores = less productivity); Q10=degree health affected productivity in regular daily activities (0-10 scale, high scores=less productivity). Percent work time missed due to health problem calculated as: Q2*100/(Q2+Q4) and score ranged from 0-100%, higher numbers=greater impairment and less productivity.

Percent Impairment While Working Using Work Productivity and Activity Impairment Questionnaire Plus Classroom Impairment Questions: First Flare Period

WPAI+CIQ: 10-item questionnaire used to assess degree to which AD affected work productivity and regular activities over past 7 days. Questions were: Q1=currently employed; Q2=hours missed due to health problems; Q3=hours missed due to other reasons; Q4=hours actually worked; Q5=degree health affected productivity while working (0-10 scale, high scores =less productivity); Q6=classes attended in academic setting or not; Q7=hours missed due to health problems; Q8=hours actually attended; Q9=degree health affected productivity while attending(0-10 scale, high scores = less productivity); Q10=degree health affected productivity in regular daily activities (0-10 scale, high scores =less productivity). Percent impairment while working due to health problem calculated as: 100*Q5/10 score ranged from 0-100%, higher numbers=greater impairment and less productivity.

Percent Overall Work Impairment Using Work Productivity and Activity Impairment Questionnaire Plus Classroom Impairment Questions: First Flare Period

WPAI+CIQ: 10-item questionnaire to assess degree to which AD affected work productivity and regular activities over past 7 days. Questions were: Q1=currently employed; Q2=work hours missed due to health problems; Q3=work hours missed due to other reasons; Q4=hours actually worked; Q5=degree health affected productivity while working(0-10 scale, high scores =less productivity); Q6=classes attended in academic setting or not; Q7=class hours missed due to health problems; Q8=class hours actually attended; Q9=degree health affected productivity while attending (0-10 scale, high scores = less productivity); Q10=degree health affected productivity in regular daily activities(0-10 scale, high scores =less productivity). Percent overall impairment while working due to health problem calculated as:100*{Q2/(Q2+Q4)+[(1- Q2/(Q2+Q4))×(Q5/10)]}, score ranged:0-100%, high numbers=greater impairment and less productivity.

Percent Class Time Missed Using Work Productivity and Activity Impairment Questionnaire Plus Classroom Impairment Questions: First Flare Period

WPAI+CIQ:10-item questionnaire to assess degree to which AD affected work productivity and regular activities over past 7 days. Questions were: Q1=currently employed; Q2=work hours missed due to health problems; Q3=work hours missed due to other reasons; Q4=hours actually worked; Q5=degree health affected productivity while working (0-10 scale, high scores =less productivity); Q6=classes attended in academic setting or not; Q7=class hours missed due to health problems; Q8=class hours actually attended; Q9=degree health affected productivity while attending(0-10 scale, high scores = less productivity); Q10=degree health affected productivity in regular daily activities(0-10 scale, high scores =less productivity). Percent class time missed due to health problem calculated as: Q7*100/(Q7+Q8) and score ranged from 0-100% where higher numbers=greater impairment and less productivity.

Percent Impairment While in Class Using Work Productivity and Activity Impairment Questionnaire Plus Classroom Impairment Questions: First Flare Period

WPAI+CIQ:10-item questionnaire used to assess degree to which AD affected work productivity and regular activities over past 7 days. Questions:Q1=currently employed;Q2=work hours missed due to health problems;Q3=work hours missed due to other reasons;Q4=hours actually worked; Q5 = degree health affected productivity while working (0-10 scale, high scores =less productivity); Q6=classes attended in academic setting or not;Q7=class hours missed due to health problems;Q8=class hours actually attended;Q9=degree health affected productivity while attending(0-10 scale, high scores = less productivity);Q10=degree health affected productivity in regular daily activities(0-10 scale, high scores =less productivity). Percent impairment while in class was calculated as: 100*Q9/10 and score ranged from 0-100% where higher numbers indicate greater impairment and less productivity.

Percent Overall Class Impairment Using Work Productivity and Activity Impairment Questionnaire Plus Classroom Impairment Questions: First Flare Period

WPAI+CIQ:10-item questionnaire to assess degree to which AD affected work productivity and regular activities over past 7 days. Questions were: Q1=currently employed; Q2=work hours missed due to health problems; Q3=work hours missed due to other reasons; Q4=hours actually worked; Q5=degree health affected productivity while working (0-10 scale, high scores =less productivity); Q6=classes attended in academic setting or not; Q7=class hours missed due to health problems; Q8=class hours actually attended; Q9=degree health affected productivity while attending (0-10 scale, high scores = less productivity); Q10=degree health affected productivity in regular daily activities(0-10 scale, high scores =less productivity). Percent overall class impairment due to health problem calculated as: 100*{Q7/(Q7+Q8)+[(1- Q7/(Q7+Q8))×(Q9/10)]}, score range:0-100%, higher numbers=greater impairment and less productivity.

Percent Activity Impairment Using Work Productivity and Activity Impairment Questionnaire Plus Classroom Impairment Questions: First Flare Period

WPAI+CIQ:10-item questionnaire used to assess degree to which AD affected work productivity and regular activities over past 7 days. Questions: Q1=currently employed; Q2=work hours missed due to health problems; Q3=work hours missed due to other reasons; Q4=hours actually worked; Q5=degree health affected productivity while working (0-10 scale, high scores =less productivity); Q6=classes attended in academic setting or not; Q7=class hours missed due to health problems; Q8=class hours actually attended; Q9=degree health affected productivity while attending(0-10 scale, high scores = less productivity);Q10=degree health affected productivity in regular daily activities(0-10 scale, high scores =less productivity). Percent activity impairment due to health problem calculated as: 100*Q10/10, scores ranged from 0-100%,higher numbers=greater impairment and less productivity.

Total Anxiety and Depression Scores Measured Using Hospital Anxiety and Depression Scale (HADS): OL Run-in Period

HADS was a validated 14-item questionnaire to assess states of anxiety and depression over the past week. HADS consisted of 2 subscales: HADS-anxiety (HADS-A) and HADS-depression (HADS-D), each of which comprised of 7 items. Each item was rated on a 4-point scale, with scores ranging from 0 to 3, where higher scores indicated more anxiety/depression symptoms. HADS-A assessed state of generalized anxiety. HADS-A total score = sum of all 7 items with score ranging from 0 (no presence of anxiety) to 21 (severe feeling of anxiety); higher score indicated greater severity of anxiety. HADS-D assessed the state of lost interest and diminished pleasure response. HADS-D total score = sum of all 7 items with score ranging from 0 (no presence of depression) to 21 (severe feeling of depression); higher score indicated greater severity of depression symptoms.

Total Anxiety and Depression Scores Measured Using Hospital Anxiety and Depression Scale: DB Period

HADS was a validated 14-item questionnaire to assess states of anxiety and depression over the past week. HADS consisted of 2 subscales: HADS-A and HADS-D, each of which comprised of 7 items. Each item was rated on a 4-point scale, with scores ranging from 0 to 3, where higher scores indicated more anxiety/depression symptoms. HADS-A assessed state of generalized anxiety. HADS-A total score = sum of all 7 items with score ranging from 0 (no presence of anxiety) to 21 (severe feeling of anxiety); higher score indicated greater severity of anxiety. HADS-D assessed the state of lost interest and diminished pleasure response. HADS-D total score = sum of all 7 items with score ranging from 0 (no presence of depression) to 21 (severe feeling of depression); higher score indicated greater severity of depression symptoms.

Total Anxiety and Depression Scores Measured Using Hospital Anxiety and Depression Scale: First Flare Period

Total Anxiety and Depression Scores Measured Using Hospital Anxiety and Depression Scale: First Flare Free Period

Full Information

NCT ID

NCT04040192

First Posted

July 30, 2019

Last Updated

February 7, 2023

Sponsor

Pfizer

1. Study Identification

Unique Protocol Identification Number

NCT04040192

Brief Title

A Study to Evaluate Long-Term Maintenance Treatment With Once Daily Crisaborole Ointment 2% in Pediatric and Adult Participants With Mild-to-Moderate Atopic Dermatitis

Official Title

A Phase 3, Randomized, Double-Blind, Vehicle-Controlled Study to Evaluate the Efficacy and Safety of Maintenance Treatment and Flare Reduction With Crisaborole Ointment, 2%, Once Daily Over 52 Weeks in Pediatric and Adult Participants (Ages 3 Months and Older) With Mild-to-Moderate Atopic Dermatitis, Who Responded to Twice Daily Crisaborole Ointment, 2%, Treatment

Study Type

Interventional

2. Study Status

Record Verification Date

February 2023

Overall Recruitment Status

Completed

Study Start Date

September 12, 2019 (Actual)

Primary Completion Date

January 19, 2022 (Actual)

Study Completion Date

January 19, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Pfizer

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

This study will evaluate crisaborole therapy once daily (QD) as a long-term topical maintenance therapy for the reduction of flare in responders to crisaborole twice daily (BID) treatment.

Detailed Description

Approximately 700 participants will be enrolled in an run-in period to receive crisaborole, BID for up to a maximum of 8 weeks to identify crisaborole responders. A responder is defined as a participant who achieves both ISGA and EASI50 success. ISGA success is defined as achieving a score of 0 or 1 with at least 2 grade improvement from baseline; and the EASI50 success is defined as at least 50% improvement from baseline. Non responders at the end of the 8-week run-in period will be discontinued from the study. Approximately 250 responders will be randomized (1:1 ratio) to enter the double-blind maintenance treatment period to receive crisaborole or vehicle QD for 52 weeks, with follow-up assessments every 4 weeks. If a flare occurs and if the participant meets the criteria for having a flare (ISGA ≥2), the participant will switch to enter a flare treatment period to receive open-label crisaborole BID for up to 12 weeks with follow-up assessments every 4 weeks. If the flare has resolved (ISGA ≤1) the participant will resume maintenance treatment and respective visit schedule. If a flare does not resolve after 3 consecutive treatment courses the participant will discontinue the study. A flare treatment period may comprise up to 3 consecutive treatment courses with crisaborole BID (each course is 4 weeks). An end of study (EOS) safety follow-up is required 4 weeks after the last study treatment of any treatment period.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Atopic Dermatitis

Keywords

Eczema, Crisaborole

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

620 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Crisaborole 2%

Arm Type

Experimental

Arm Description

Crisaborole 2% ointment applied once daily (QD)

Arm Title

Vehicle

Arm Type

Placebo Comparator

Arm Description

Vehicle ointment applied once daily (QD)

Intervention Type

Drug

Intervention Name(s)

Crisaborole 2%

Intervention Description

Crisaborole ointment 2%

Intervention Type

Drug

Intervention Name(s)

Vehicle

Intervention Description

Vehicle ointment

Primary Outcome Measure Information:

Title

Duration of Flare-Free Maintenance Until Onset of First-Flare During the Double Blind (DB) Period

Description

Time Frame

From randomization to first flare or last ISGA assessment (up to 52 weeks)

Title

Number of Participants With Treatment Emergent Adverse Events (TEAEs)

Description

Time Frame

Crisaborole 2% BID: From start of study intervention in OL period up to 8 weeks ; Vehicle QD and crisaborole 2% QD: From start of study intervention in DB period up to 28 days after last dose of study intervention (maximum of 56 weeks)

Secondary Outcome Measure Information:

Title

Number of Flare-Free Days During the DB Period

Description

Flare - free days was the sum of the duration of flare-free maintenance during the DB maintenance period for each participant.

Time Frame

Up to maximum of 52 weeks

Title

Number of Flares During the DB Period

Description

Time Frame

Up to maximum of 52 weeks

Title

Description

Time Frame

From randomization up to loss of pruritus response or onset of first flare or the last assessment (maximum of 52 weeks)

Title

Description

Time Frame

From randomization up to loss of pruritus response or onset of first flare or the last assessment (maximum of 52 weeks)

Title

Duration of Pruritus Response Maintenance Until Onset of First Flare During the DB Period: Observer Reported Itch Severity Scale (ORIS) in Participants Aged 3 to <6 Months

Description

Duration of pruritus response maintenance=time from randomization to loss of pruritus response or first flare onset(ISGA>=2)during52-weekDB period. Evaluated among pruritus responders (success in ISGA, EASI 50) at randomization. Pruritus response maintenance=maintenance of >=50% improvement in pruritus from baseline obtained at randomization. If event(e.g., death, first flare[ISGA >=2], lost to follow up, or end of study) occurred before loss of pruritus response for first flare-free period, duration of maintenance of pruritus response was time from randomization to last assessment and was censored. Here, pruritus response maintenance duration was presented for participants aged 3 to <6 months with OL baseline ORIS>=3 or >=4 and >=3 or >=4 points reduction from OL baseline to randomization in ORIS. Caregivers were asked to rate observation of their child's itch(scratching, rubbing) at worst moment during previous 24 hours on a scale of 0 to 10;0=no itch,10=worst itch imaginable.

Time Frame

From randomization up to loss of pruritus response or onset of first flare or the last assessment (maximum of 52 weeks)

Title

Duration of Maintenance of >=50% Reduction in Eczema Area and Severity Index (EASI) Total Score Until Onset of First Flare During the DB Period

Description

Time Frame

From randomization to loss of EASI response or onset of first flare or the last EASI assessment (up to maximum of 52 weeks)

Title

Duration of Maintenance of Dermatology Life Quality Index (DLQI) Response Until Onset of First Flare During the DB Period

Description

Time Frame

From randomization to loss of DLQI response or onset of first flare or the last assessment up to first flare (up to maximum of 52 weeks)

Title

Duration of Maintenance of Patient Oriented Eczema Measure (POEM) Response Until Onset of First Flare During the DB Period

Description

Time Frame

From randomization to loss POEM response or onset of first flare or the last assessment up to the first flare (up to maximum of 52 weeks)

Title

Investigator's Static Global Assessment (ISGA) Score for the First Flare Period

Description

Time Frame

Week 0 (Day 1), Week 4, Week 8 and Week 12

Title

EASI Score for the First Flare Period

Description

EASI assessed severity of AD, based on severity of lesion clinical signs (erythema[E], induration/papulation[I], excoriation[Ex], lichenification[L]) and % body surface area(BSA) affected.Each of clinical signs scored separately for each of 4 body regions (head and neck[h], upper limbs[u], trunk[t] [including axillae and groin], lower limbs[l] [including buttocks]) on 4-point scale: 0= absent; 1=mild; 2= moderate; 3= severe.EASI area score(A) according to %BSA with AD: 0 (0%), 1(>0 to <10%), 2(10 to <30%), 3(30 to <50%), 4(50 to <70%), 5(70 to <90%), 6 (90 to 100%). Total EASI score =0.1*Ah*(Eh + Ih + Exh + Lh) + 0.2*Au*(Eu + Iu + ExU + Lu) + 0.3*At*(Et +It + Ext + Lt) + 0.4*Al*(El + Il + Exl + Ll). Total EASI score ranged from 0.0 to 72.0, higher score = greater severity of AD.First flare period=time from onset of flare(ISGA>=2) during DB maintenance period where participant was switched to receive open-label crisaborole ointment 2%,BID for up to 12 weeks until resolution of flares.

Time Frame

Week 0 (Day 1), Week 4, Week 8 and Week 12

Title

Duration (Days) of Flare Period

Description

Duration of flare period was average duration calculated from sum of durations divided by number of flares for each participant.

Time Frame

Up to 52 weeks

Title

Percent Change From Baseline in EASI Scores at Weeks 2, 4, 6 and 8: OL Run-in Period

Description

Time Frame

Baseline (last observation up to and including Day 1 of OL period), Weeks 2, 4, 6 and 8

Title

Percent Change From Baseline in EASI Scores at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52: DB Period

Description

Time Frame

Baseline (last observation up to and including the randomization day), Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52

Title

Percent Change From Baseline in EASI Scores at Weeks 0, 4, 8 and 12: First Flare Treatment Period

Description

EASI assessed severity of AD, based on severity of lesion clinical signs (erythema [E], induration/papulation [I], excoriation [Ex], lichenification [L]) and % body surface area (BSA) affected. Each of clinical signs scored separately for each of 4 body regions (head and neck [h], upper limbs [u], trunk [t] [including axillae and groin], lower limbs [l] [including buttocks]) on 4-point scale: 0= absent; 1= mild; 2= moderate; 3= severe. EASI area score (A) according to % BSA with AD: 0 (0%), 1(>0 to <10%), 2(10 to <30%), 3(30 to <50%), 4(50 to <70%), 5(70 to <90%), 6 (90 to 100%). Total EASI score =0.1*Ah*(Eh + Ih + Exh + Lh) + 0.2*Au*(Eu + Iu + ExU + Lu) + 0.3*At*(Et +It + Ext + Lt) + 0.4*Al*(El + Il + Exl + Ll). Total EASI score ranged from 0.0 to 72.0, higher score = greater severity of AD.

Time Frame

Baseline (last observation up to and including the randomization day of DB period),Weeks 0, 4, 8 and 12

Title

Percent Change From Baseline in EASI Scores at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52: First Flare Free Period

Description

Time Frame

Baseline (last observation up to and including the randomization day of DB period), Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52

Title

Change From Baseline in ISGA Scores at Weeks 2, 4, 6 and 8 for OL run-in Period

Description

Time Frame

Baseline (last observation up to and including Day 1 of OL period), Weeks 2, 4, 6 and 8

Title

Change From Baseline in ISGA Scores at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52 for DB Period

Description

Time Frame

Baseline (last observation up to and including the randomization day), Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52

Title

Change From Baseline in ISGA Scores at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52 for First Flare Free Period

Description

Time Frame

Baseline (last observation up to and including the randomization day), Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52

Title

Change From Baseline in ISGA Scores at Weeks 0, 4, 8 and 12 for First Flare Treatment Period

Description

Time Frame

Baseline (last observation up to and including the randomization day), Weeks 0, 4, 8 and 12

Title

Change From Baseline in Treatable Percent Body Surface Area (% BSA): OL Run-in Period

Description

Time Frame

Baseline (last observation up to and including the randomization day) Weeks 2, 4, 6 and 8

Title

Change From Baseline in Treatable %BSA: DB Period

Description

Time Frame

Baseline (last observation up to and including the randomization day), Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52

Title

Change From Baseline in Treatable %BSA: First Flare Free Period

Description

Time Frame

Baseline (last observation up to and including the randomization day), Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52

Title

Change From Baseline in Treatable %BSA: First Flare Period

Description

Time Frame

Baseline (last observation up to and including the randomization day), Weeks 0, 4, 8 and 12

Title

Change From Baseline in Most Commonly Affected Atopic Dermatitis (AD) % BSA: DB Period

Description

The investigators were required to draw the skin areas affected by AD for each participant in a body map and the most commonly affected BSA was documented.

Time Frame

Baseline (last observation up to and including the randomization day), Weeks 24 and 52

Title

Night Time Itch Score for Participants >=12 Years of Age: OL Run-in Period

Description

Time Frame

Baseline (last observation up to and including Day 1 of OL period), Weeks 2, 4, 6 and 8

Title

Night Time Itch Score for Participants >=12 Years of Age: DB Period

Description

Time Frame

Baseline (last observation up to and including the randomization day), Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52

Title

Night Time Itch Score for Participants >=12 Years of Age: First Flare Period

Description

Time Frame

Weeks 0, 4, 8 and 12

Title

Night Time Itch Score for Participants >=12 Years of Age: First Flare Free Period

Description

Time Frame

Baseline (last observation up to and including the randomization day), Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52

Title

AD Skin Pain Scores for Participants >=12 Years of Age: OL Run-in Period

Description

Time Frame

Baseline (the last observation up to and including Day 1 of OL period), Weeks 2, 4, 6 and 8

Title

AD Skin Pain Scores for Participants >=12 Years of Age: DB Period

Description

Time Frame

Baseline (the last observation up to and including Day 1 of DB period), Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52

Title

AD Skin Pain Scores for Participants >=12 Years of Age: First Flare Period

Description

Time Frame

Weeks 0, 4, 8, 12

Title

AD Skin Pain Scores: for Participants >=12 Years of Age First Flare Free Period

Description

Time Frame

Baseline (the last observation up to and including Day 1 of DB period), Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52

Title

Patient/Observer Global Impression of Severity Score: OL Run-in Period

Description

Time Frame

Baseline (the last observation up to and including Day 1 of OL period), Weeks 2, 4, 6 and 8

Title

Patient/Observer Global Impression of Severity Score: DB Period

Description

Time Frame

Baseline (the last observation up to and including Day 1 of DB period), Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52

Title

Patient/Observer Global Impression of Severity Score: First Flare Period

Description

Time Frame

Weeks 0, 4, 8 and 12

Title

Patient/Observer Global Impression of Severity Score: First Flare Free Period

Description

Time Frame

Baseline (the last observation up to and including Day 1 of DB period), Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52

Title

Patient/Observer Global Impression of Change Score: OL Run-in Period

Description

Time Frame

Weeks 2, 4, 6 and 8

Title

Patient/Observer Global Impression of Change Score: DB Period

Description

Time Frame

Baseline (the last observation up to and including Day 1 of DB period), Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52

Title

Patient/Observer Global Impression of Change Score: First Flare Period

Description

Time Frame

Weeks 0, 4, 8 and 12

Title

Patient/Observer Global Impression of Change Score: First Flare Free Period

Description

Time Frame

Baseline (the last observation up to and including Day 1 of DB period), Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52

Title

Medical Outcome Study Sleep Scale Score in Participants >=12 Years of Age: OL Run-in Period

Description

Time Frame

Baseline (the last observation up to and including Day 1 of OL period), Weeks 2, 4, 6 and 8

Title

Medical Outcome Study Sleep Scale Score in Participants >=12 Years of Age: DB Period

Description

Time Frame

Baseline (the last observation up to and including Day 1 of DB period),Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52

Title

Medical Outcome Study Sleep Scale Score in Participants >=12 Years of Age: First Flare Period

Description

Time Frame

Weeks 0, 4, 8 and 12

Title

Medical Outcome Study Sleep Scale Score in Participants >=12 Years of Age: First Flare Free Period

Description

Time Frame

Baseline (the last observation up to and including Day 1 of DB period), Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52

Title

European Quality of Life-5 Dimension 5-Level (EQ-5D-5L) Index Score in Participants Greater Than or Equal to (>=) 18 Years of Age: OL Run-in Period

Description

Time Frame

Baseline (the last observation up to and including Day 1 of OL period), Weeks 2, 4, 6 and 8

Title

European Quality of Life-5 Dimension Youth (EuroQoL EQ-5D Y) Index Score in Participants Between 8-17 Years of Age: OL Run-in Period

Description

Time Frame

Baseline (the last observation up to and including Day 1 of OL period), Weeks 2, 4, 6 and 8

Title

EuroQoL EQ-5D Y Proxy Index Scores in Participants Between 2-7 Years of Age: OL Run-in Period

Description

Time Frame

Baseline (the last observation up to and including Day 1 of OL period), Weeks 2, 4, 6 and 8

Title

EuroQoL EQ-5D-5L Visual Analog Scale (VAS) Score in Participants >= 18 Years of Age: OL Run-in Period

Description

EQ-5D-5L VAS was used to record participant's rating for current health-related quality of life state on vertical VAS (0-100);0=worst imaginable health state;100=best imaginable health state.

Time Frame

Baseline (the last observation up to and including Day 1 of OL period), Weeks 2, 4, 6 and 8

Title

EuroQoL EQ-5D Y VAS Scores in Participants Between 8-17 Years of Age : OL-Run-in Period

Description

Time Frame

Baseline (the last observation up to and including Day 1 of OL period), Weeks 2, 4, 6 and 8

Title

EuroQoL EQ-5D Y Proxy VAS Scores in Participants Between 2-7 Years of Age: OL Run-in Period

Description

EQ-5D Y proxy VAS assessed the caregiver's impression of participants health state on a vertical VAS (range: 0 to 100), where, 0 (the worst imaginable health) to 100 (the best imaginable health).

Time Frame

Baseline (the last observation up to and including Day 1 of OL period), Weeks 2, 4, 6 and 8

Title

EuroQoL EQ-5D-5L Index Scores in Participants >= 18 Years of Age: DB Period

Description

EQ-5D-5L: standardized participant completed questionnaire consisted of 2 components: a health state profile/a single utility index value and an optional VAS. EQ-5D health state profile/a single utility index value had 5 dimensions: mobility, self-care, usual activities, pain/discomfort, anxiety/depression. Each dimension has 5 levels: 1= no problems, 2= slight problems, 3= moderate problems, 4= severe problems and 5= extreme problems. Responses to 5 dimensions comprised a health state/a single utility index value. E.g. if a participant responded "no problems" for each 5 dimensions, then health state was coded as "11111" with a predefined index value to it. Every health state (coded as combination of responses on each of 5 dimensions) had a unique predefined utility index value assigned to it, by EuroQoL. US value sets (with all possible health states) was used for adults in the study and total scores ranged from 1 to -0.109. Higher (positive) scores = better health state.

Time Frame

Baseline (the last observation up to and including Day 1 of DB period), Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52

Title

EuroQoL EQ-5D Y Index Scores in Participants Between 8-17 Years of Age: DB Period

Description

Time Frame

Baseline (the last observation up to and including Day 1 of DB period), Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52

Title

EuroQoL EQ-5D Y Proxy Index Scores in Participants Between 2-7 Years of Age: DB Period

Description

Time Frame

Baseline (the last observation up to and including Day 1 of DB period), Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52

Title

EuroQoL EQ-5D-5L VAS Scores in Participants >= 18 Years of Age: DB Period

Description

EQ-5D-5L VAS to record participant's rating for current health-related quality of life state on vertical VAS (0-100);0=worst imaginable health state;100=best imaginable health state.

Time Frame

Baseline (the last observation up to and including Day 1 of DB period), Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52

Title

EuroQoL EQ-5D Y VAS Scores in Participants Between 8-17 Years of Age: DB Period

Description

Time Frame

Baseline (the last observation up to and including Day 1 of OL period), Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52

Title

EuroQoL EQ-5D Y Proxy VAS Scores in Participants Between 2-7 Years of Age: DB Period

Description

EQ-5D Y proxy VAS assessed the caregiver's impression of participants health state on a vertical VAS (range: 0 to 100), where, 0 (the worst imaginable health) to 100 (the best imaginable health).

Time Frame

Baseline (the last observation up to and including Day 1 of DB period),Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52

Title

EuroQoL EQ-5D-5L Index Scores in Participants >= 18 Years of Age: First Flare Period

Description

Time Frame

Weeks 0, 4, 8 and 12

Title

EuroQoL EQ-5D Y Index Scores in Participants Between 8-17 Years of Age: First Flare Period

Description

Time Frame

Weeks 0, 4, 8 and 12

Title

EuroQoL EQ-5D Y Proxy Index Scores in Participants Between 2-7 Years of Age: First Flare Period

Description

Time Frame

Weeks 0, 4, 8 and 12

Title

EuroQoL EQ-5D-5L VAS Scores in Participants >= 18 Years of Age: First Flare Period

Description

Time Frame

Weeks 0, 4, 8 and 12

Title

EuroQoL EQ-5D Y VAS Scores in Participants Between 8-17 Years of Age: First Flare Period

Description

Time Frame

Weeks 0, 4, 8 and 12

Title

EuroQoL EQ-5D Y Proxy VAS Scores in Participants Between 2-7 Years of Age: First Flare Period

Description

EQ-5D Y proxy VAS assessed the caregiver's impression of participants health state on a vertical VAS (range: 0 to 100), where, 0 (the worst imaginable health) to 100 (the best imaginable health).

Time Frame

Weeks 0, 4, 8 and 12

Title

EuroQoL EQ-5D Y Index Scores in Participants >= 18 Years of Age: First Flare Free Period

Description

Time Frame

Baseline (the last observation up to and including randomization day), Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52

Title

EuroQoL EQ-5D Y Index Scores in Participants Between 8-17 Years of Age: First Flare Free Period

Description

Time Frame

Baseline (the last observation up to and including randomization day of DB period), Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52

Title

EuroQoL EQ-5D Y Proxy Index Scores in Participants Between 2-7 Years of Age: First Flare Free Period

Description

Time Frame

Baseline (the last observation up to and including randomization day of DB period), Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52

Title

EuroQoL EQ-5D-5L VAS Scores in Participants >= 18 Years of Age: First Flare Free Period

Description

EQ-5D-5L VAS was used to record participant's rating for current health-related quality of life state on vertical VAS (0-100);0=worst imaginable health state;100=best imaginable health state.

Time Frame

Baseline (the last observation up to and including randomization day of DB period), Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52

Title

EuroQoL EQ-5D Y VAS Scores in Participants Between 8-17 Years of Age: First Flare Free Period

Description

Time Frame

Baseline (the last observation up to and including randomization day of DB period), Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52

Title

EuroQoL EQ-5D Y Proxy VAS Scores in Participants Between 2-7 Years of Age: First Flare Free Period

Description

EQ-5D Y proxy VAS assessed the caregiver's impression of participants health state on a vertical VAS (range: 0 to 100), where, 0 (the worst imaginable health) to 100 (the best imaginable health).

Time Frame

Baseline (the last observation up to and including randomization day of DB period), Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52

Title

Percent Work Time Missed Using Work Productivity and Activity Impairment (WPAI) Questionnaire Plus Classroom Impairment Questions (CIQ): OL Run-in Period

Description

Time Frame

Baseline (last observation up to and including Day 1 of OL period), Weeks 2, 4, 6 and 8

Title

Percent Impairment While Working Using Work Productivity and Activity Impairment (WPAI) Questionnaire Plus Classroom Impairment Questions (CIQ): OL Run-in Period

Description

Time Frame

Weeks 0, 2, 4, 6 and 8

Title

Percent Overall Work Impairment Using Work Productivity and Activity Impairment (WPAI) Questionnaire Plus Classroom Impairment Questions (CIQ): OL Run-in Period

Description

Time Frame

Weeks 0, 2, 4, 6 and 8

Title

Percent Class Time Missed Using Work Productivity and Activity Impairment Questionnaire Plus Classroom Impairment Questions: OL Run-in Period

Description

WPAI+CIQ:10-item questionnaire to assess degree to which AD affected work productivity and regular activities over past 7 days. Questions: Q1=currently employed; Q2=work hours missed due to health problems; Q3=work hours missed due to other reasons; Q4=hours actually worked; Q5=degree health affected productivity while working (0-10 scale, high scores=less productivity); Q6=classes attended in academic setting or not; Q7=class hours missed due to health problems; Q8=class hours actually attended; Q9=degree health affected productivity while attending(0-10 scale, high scores= less productivity); Q10=degree health affected productivity in regular daily activities(0-10 scale, high scores =less productivity).Percent class time missed due to health problem calculated as: Q7*100/(Q7+Q8) and score ranged from 0-100% where higher numbers=greater impairment and less productivity.

Time Frame

Baseline (last observation up to and including Day 1 of OL period), Weeks 2, 4, 6 and 8

Title

Percent Impairment While in Class Using Work Productivity and Activity Impairment Questionnaire Plus Classroom Impairment Questions: OL Run-in Period

Description

Time Frame

Baseline (last observation up to and including Day 1 of OL period), Weeks 2, 4, 6 and 8

Title

Percent Overall Class Impairment Using Work Productivity and Activity Impairment Questionnaire Plus Classroom Impairment Questions: OL Run-in Period

Description

WPAI+CIQ:10-item questionnaire to assess degree to which AD affected work productivity and regular activities over past7days.Questions:Q1=currently employed;Q2=work hours missed due to health problems;Q3=work hours missed due to other reasons;Q4=hours actually worked;Q5=degree health affected productivity while working (0-10 scale, high scores=less productivity);Q6=classes attended in academic setting or not;Q7=class hours missed due to health problems;Q8=class hours actually attended;Q9=degree health affected productivity while attending(0-10 scale, high scores= less productivity);Q10=degree health affected productivity in regular daily activities(0-10 scale, high scores =less productivity).Percent overall class impairment due to health problem calculated as: 100*{Q7/(Q7+Q8)+[(1- Q7/(Q7+Q8))×(Q9/10)]},score range:0-100%,higher numbers=greater impairment and less productivity.

Time Frame

Baseline (last observation up to and including Day 1 of OL period), Weeks 2, 4, 6 and 8

Title

Percent Activity Impairment Using Work Productivity and Activity Impairment Questionnaire Plus Classroom Impairment Questions: OL Run-in Period

Description

WPAI+CIQ: 10-item questionnaire used to assess degree to which AD affected work productivity and regular activities over past 7 days. Questions:Q1=currently employed;Q2=work hours missed due to health problems; Q3=work hours missed due to other reasons; Q4=hours actually worked; Q5=degree health affected productivity while working (0-10 scale, high scores=less productivity); Q6=classes attended in academic setting or not; Q7=class hours missed due to health problems; Q8=class hours actually attended; Q9=degree health affected productivity while attending(0-10 scale, high scores= less productivity); Q10=degree health affected productivity in regular daily activities(0-10 scale, high scores =less productivity). Percent activity impairment due to health problem calculated as: 100*Q10/10, score ranged from 0-100%,higher numbers=greater impairment and less productivity.

Time Frame

Baseline (last observation up to and including Day 1 of OL period), Weeks 2, 4, 6 and 8

Title

Percent Work Time Missed Using Work Productivity and Activity Impairment Questionnaire Plus Classroom Impairment Questions: DB Period

Description

WPAI+CIQ:10-item questionnaire used to assess degree to which AD affected work productivity and regular activities over past 7 days. Questions were: Q1=currently employed; Q2=work hours missed due to health problems; Q3=work hours missed due to other reasons;Q4=hours actually worked; Q5 = degree health affected productivity while working (0-10 scale, high scores=less productivity);Q6=classes attended in academic setting or not;Q7=class hours missed due to health problems;Q8=class hours actually attended;Q9=degree health affected productivity while attending(0-10 scale, high scores = less productivity);Q10=degree health affected productivity in regular daily activities(0-10 scale, high scores=less productivity). Percent work time missed due to health problem calculated as: Q2*100/(Q2+Q4) and score ranged from 0-100%,higher numbers=greater impairment and less productivity.

Time Frame

Baseline (the last observation up to and including randomization day), Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52

Title

Percent Impairment While Working Using Work Productivity and Activity Impairment Questionnaire Plus Classroom Impairment Questions: DB Period

Description

Time Frame

Baseline (the last observation up to and including randomization day), Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52

Title

Percent Overall Work Impairment Using Work Productivity and Activity Impairment Questionnaire Plus Classroom Impairment Questions: DB Period

Description

WPAI+CIQ:10-item questionnaire to assess degree to which AD affected work productivity and regular activities over past 7 days. Questions: Q1=currently employed;Q2=work hours missed due to health problems;Q3=work hours missed due to other reasons;Q4=hours actually worked;Q5=degree health affected productivity while working(0-10 scale, high scores=less productivity);Q6=classes attended in academic setting or not;Q7=class hours missed due to health problems;Q8=class hours actually attended;Q9=degree health affected productivity while attending(0-10 scale, high scores= less productivity);Q10=degree health affected productivity: regular daily activities(0-10 scale, high scores =less productivity). Percent overall impairment while working due to health problem calculated as:100*{Q2/(Q2+Q4)+[(1- Q2/(Q2+Q4))×(Q5/10)]}, score ranged: 0-100%, high numbers=greater impairment and less productivity.

Time Frame

Baseline (the last observation up to and including randomization day), Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52

Title

Percent Class Time Missed Using Work Productivity and Activity Impairment Questionnaire Plus Classroom Impairment Questions: DB Period

Description

WPAI+CIQ:10-item questionnaire to assess degree to which AD affected work productivity and regular activities over past 7 days. Questions: Q1=currently employed; Q2=work hours missed due to health problems; Q3=work hours missed due to other reasons; Q4=hours actually worked; Q5=degree health affected productivity while working(0-10 scale, high scores =less productivity); Q6=classes attended in academic setting or not;Q7=class hours missed due to health problems; Q8=class hours actually attended; Q9=degree health affected productivity while attending(0-10 scale, high scores= less productivity); Q10=degree health affected productivity in regular daily activities(0-10 scale, high scores =less productivity). Percent class time missed due to health problem calculated as: Q7*100/(Q7+Q8) and score ranged from 0-100% where higher numbers=greater impairment and less productivity.

Time Frame

Baseline (the last observation up to and including randomization day), Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52

Title

Percent Impairment While in Class Using Work Productivity and Activity Impairment Questionnaire Plus Classroom Impairment Questions: DB Period

Description

WPAI+CIQ: 10-item questionnaire used to assess degree to which AD affected work productivity and regular activities over past 7 days. Questions: Q1=currently employed; Q2=work hours missed due to health problems; Q3=work hours missed due to other reasons; Q4=hours actually worked; Q5 = degree health affected productivity while working (0-10 scale, high scores=less productivity); Q6=classes attended in academic setting or not; Q7=class hours missed due to health problems; Q8=class hours actually attended; Q9=degree health affected productivity while attending(0-10 scale, high scores = less productivity); Q10=degree health affected productivity in regular daily activities (0-10 scale, high scores =less productivity). Percent impairment while in class was calculated as: 100*Q9/10 and score ranged from 0-100% where higher numbers indicate greater impairment and less productivity.

Time Frame

Baseline (the last observation up to and including randomization day), Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52

Title

Percent Overall Class Impairment Using Work Productivity and Activity Impairment Questionnaire Plus Classroom Impairment Questions: DB Period

Description

WPAI+CIQ: 10-item questionnaire to assess degree to which AD affected work productivity and regular activities over past 7 days. Questions: Q1=currently employed; Q2=work hours missed due to health problems; Q3=work hours missed due to other reasons; Q4=hours actually worked; Q5=degree health affected productivity while working (0-10 scale, high scores =less productivity); Q6=classes attended in academic setting or not; Q7=class hours missed due to health problems; Q8=class hours actually attended; Q9=degree health affected productivity while attending(0-10 scale, high scores = less productivity); Q10=degree health affected productivity in regular daily activities (0-10 scale, high scores =less productivity). Percent overall class impairment due to health problem calculated as: 100*{Q7/(Q7+Q8)+[(1- Q7/(Q7+Q8))×(Q9/10)]}, score range:0-100%, higher numbers=greater impairment and less productivity.

Time Frame

Baseline (the last observation up to and including randomization day), Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52

Title

Percent Activity Impairment Using Work Productivity and Activity Impairment Questionnaire Plus Classroom Impairment Questions: DB Period

Description

WPAI+CIQ:10-item questionnaire used to assess degree to which AD affected work productivity and regular activities over past 7 days. Questions: Q1=currently employed; Q2=work hours missed due to health problems; Q3=work hours missed due to other reasons; Q4=hours actually worked; Q5=degree health affected productivity while working (0-10 scale, high scores=less productivity); Q6=classes attended in academic setting or not; Q7=class hours missed due to health problems; Q8=class hours actually attended; Q9=degree health affected productivity while attending(0-10 scale, high scores= less productivity); Q10=degree health affected productivity in regular daily activities(0-10 scale, high scores =less productivity). Percent activity impairment due to health problem calculated as: 100*Q10/10, score ranged from 0-100%,higher numbers=greater impairment and less productivity.

Time Frame

Baseline (the last observation up to and including randomization day), Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52

Title

Percent Work Time Missed Using Work Productivity and Activity Impairment Questionnaire Plus Classroom Impairment Questions: First Flare Free Period

Description

WPAI+CIQ:10-item questionnaire used to assess degree to which AD affected work productivity and regular activities over past 7 days. Questions were: Q1=currently employed; Q2=work hours missed due to health problems;Q3=work hours missed due to other reasons; Q4=hours actually worked; Q5= degree health affected productivity while working (0-10 scale, high scores =less productivity); Q6=classes attended in academic setting or not; Q7=class hours missed due to health problems; Q8=class hours actually attended; Q9=degree health affected productivity while attending(0-10 scale, high scores = less productivity); Q10=degree health affected productivity in regular daily activities(0-10 scale, high scores =less productivity). Percent work time missed due to health problem calculated as: Q2*100/(Q2+Q4) and score ranged from 0-100%, higher numbers=greater impairment and less productivity.

Time Frame

Baseline (the last observation up to and including randomization day), Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52

Title

Percent Impairment While Working Using Work Productivity and Activity Impairment Questionnaire Plus Classroom Impairment Questions: First Flare Free Period

Description

WPAI+CIQ: 10-item questionnaire used to assess degree to which AD affected work productivity and regular activities over past 7 days. Questions: Q1=currently employed; Q2=hours missed due to health problems; Q3=hours missed due to other reasons; Q4=hours actually worked; Q5=degree health affected productivity while working (0-10 scale, high scores =less productivity); Q6=classes attended in academic setting or not; Q7=hours missed due to health problems; Q8=hours actually attended; Q9=degree health affected productivity while attending(0-10 scale, high scores = less productivity); Q10=degree health affected productivity in regular daily activities(0-10 scale, high scores =less productivity). Percent impairment while working due to health problem calculated as: 100*Q5/10 score ranged from 0-100%, higher numbers=greater impairment and less productivity.

Time Frame

Baseline (the last observation up to and including randomization day), Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52

Title

Percent Overall Work Impairment Using Work Productivity and Activity Impairment Questionnaire Plus Classroom Impairment Questions: First Flare Free Period

Description

WPAI+CIQ: 10-item questionnaire to assess degree to which AD affected work productivity and regular activities over past 7 days. Questions: Q1=currently employed; Q2=work hours missed due to health problems; Q3=work hours missed due to other reasons; Q4=hours actually worked; Q5=degree health affected productivity while working (0-10 scale, high scores =less productivity); Q6=classes attended in academic setting or not; Q7=class hours missed due to health problems; Q8=class hours actually attended; Q9=degree health affected productivity while attending (0-10 scale, high scores = less productivity); Q10=degree health affected productivity: regular daily activities(0-10 scale, high scores =less productivity). Percent overall impairment while working due to health problem calculated as:100*{Q2/(Q2+Q4)+[(1- Q2/(Q2+Q4))×(Q5/10)]}, score ranged:0-100%, high numbers=greater impairment and less productivity.

Time Frame

Baseline (the last observation up to and including randomization day), Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52

Title

Percent Class Time Missed Using Work Productivity and Activity Impairment Questionnaire Plus Classroom Impairment Questions: First Flare Free Period

Description

WPAI+CIQ:10-item questionnaire to assess degree to which AD affected work productivity and regular activities over past 7 days. Questions: Q1=currently employed; Q2=work hours missed due to health problems; Q3=work hours missed due to other reasons; Q4=hours actually worked; Q5=degree health affected productivity while working(0-10 scale, high scores =less productivity); Q6=classes attended in academic setting or not; Q7=class hours missed due to health problems; Q8=class hours actually attended; Q9=degree health affected productivity while attending(0-10 scale, high scores = less productivity); Q10=degree health affected productivity in regular daily activities(0-10 scale, high scores =less productivity). Percent class time missed due to health problem calculated as: Q7*100/(Q7+Q8) and score ranged from 0-100% where higher numbers=greater impairment and less productivity.

Time Frame

Baseline (the last observation up to and including randomization day), Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52

Title

Percent Impairment While in Class Using Work Productivity and Activity Impairment Questionnaire Plus Classroom Impairment Questions: First Flare Free Period

Description

WPAI+CIQ:10-item questionnaire used to assess degree to which AD affected work productivity and regular activities over past 7 days. Questions: Q1=currently employed; Q2=work hours missed due to health problems; Q3=work hours missed due to other reasons; Q4=hours actually worked; Q5 = degree health affected productivity while working (0-10 scale, high scores =less productivity); Q6=classes attended in academic setting or not; Q7=class hours missed due to health problems; Q8=class hours actually attended; Q9=degree health affected productivity while attending (0-10 scale, high scores = less productivity); Q10=degree health affected productivity in regular daily activities(0-10 scale, high scores =less productivity). Percent impairment while in class was calculated as: 100*Q9/10 and score ranged from 0-100% where higher numbers indicate greater impairment and less productivity.

Time Frame

Baseline (the last observation up to and including randomization day), Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52

Title

Percent Overall Class Impairment Using Work Productivity and Activity Impairment Questionnaire Plus Classroom Impairment Questions: First Flare Free Period

Description

WPAI+CIQ:10-item questionnaire to assess degree to which AD affected work productivity and regular activities over past 7 days. Questions: Q1=currently employed; Q2=work hours missed due to health problems; Q3=work hours missed due to other reasons; Q4=hours actually worked; Q5=degree health affected productivity while working (0-10 scale, high scores =less productivity); Q6=classes attended in academic setting or not; Q7=class hours missed due to health problems; Q8=class hours actually attended; Q9=degree health affected productivity while attending(0-10 scale, high scores = less productivity); Q10=degree health affected productivity in regular daily activities (0-10 scale, high scores =less productivity). Percent overall class impairment due to health problem calculated as: 100*{Q7/(Q7+Q8)+[(1- Q7/(Q7+Q8))×(Q9/10)]}, score range:0-100%,higher numbers=greater impairment and less productivity.

Time Frame

Baseline (the last observation up to and including randomization day), Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52

Title

Percent Activity Impairment Using Work Productivity and Activity Impairment Questionnaire Plus Classroom Impairment Questions: First Flare Free Period

Description

WPAI+CIQ:10-item questionnaire used to assess degree to which AD affected work productivity and regular activities over past 7 days. Questions: Q1=currently employed; Q2=work hours missed due to health problems; Q3=work hours missed due to other reasons; Q4=hours actually worked; Q5=degree health affected productivity while working (0-10 scale, high scores =less productivity); Q6=classes attended in academic setting or not; Q7=class hours missed due to health problems; Q8=class hours actually attended; Q9=degree health affected productivity while attending (0-10 scale, high scores = less productivity); Q10=degree health affected productivity in regular daily activities(0-10 scale, high scores =less productivity). Percent activity impairment due to health problem calculated as: 100*Q10/10, score ranged from 0-100%,higher numbers=greater impairment and less productivity.

Time Frame

Baseline (the last observation up to and including randomization day), Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52

Title

Percent Work Time Missed Using Work Productivity and Activity Impairment Questionnaire Plus Classroom Impairment Questions: First Flare Period

Description

WPAI+CIQ:10-item questionnaire used to assess degree to which AD affected work productivity and regular activities over past 7 days. Questions were: Q1=currently employed; Q2=work hours missed due to health problems; Q3=work hours missed due to other reasons; Q4=hours actually worked; Q5 = degree health affected productivity while working (0-10 scale, high scores =less productivity); Q6=classes attended in academic setting or not; Q7=class hours missed due to health problems; Q8=class hours actually attended; Q9=degree health affected productivity while attending (0-10 scale, high scores = less productivity); Q10=degree health affected productivity in regular daily activities (0-10 scale, high scores=less productivity). Percent work time missed due to health problem calculated as: Q2*100/(Q2+Q4) and score ranged from 0-100%, higher numbers=greater impairment and less productivity.

Time Frame

Weeks 0, 4, 8 and 12

Title

Percent Impairment While Working Using Work Productivity and Activity Impairment Questionnaire Plus Classroom Impairment Questions: First Flare Period

Description

WPAI+CIQ: 10-item questionnaire used to assess degree to which AD affected work productivity and regular activities over past 7 days. Questions were: Q1=currently employed; Q2=hours missed due to health problems; Q3=hours missed due to other reasons; Q4=hours actually worked; Q5=degree health affected productivity while working (0-10 scale, high scores =less productivity); Q6=classes attended in academic setting or not; Q7=hours missed due to health problems; Q8=hours actually attended; Q9=degree health affected productivity while attending(0-10 scale, high scores = less productivity); Q10=degree health affected productivity in regular daily activities (0-10 scale, high scores =less productivity). Percent impairment while working due to health problem calculated as: 100*Q5/10 score ranged from 0-100%, higher numbers=greater impairment and less productivity.

Time Frame

Weeks 0, 4, 8 and 12

Title

Percent Overall Work Impairment Using Work Productivity and Activity Impairment Questionnaire Plus Classroom Impairment Questions: First Flare Period

Description

Time Frame

Weeks 0, 4, 8 and 12

Title

Percent Class Time Missed Using Work Productivity and Activity Impairment Questionnaire Plus Classroom Impairment Questions: First Flare Period

Description

WPAI+CIQ:10-item questionnaire to assess degree to which AD affected work productivity and regular activities over past 7 days. Questions were: Q1=currently employed; Q2=work hours missed due to health problems; Q3=work hours missed due to other reasons; Q4=hours actually worked; Q5=degree health affected productivity while working (0-10 scale, high scores =less productivity); Q6=classes attended in academic setting or not; Q7=class hours missed due to health problems; Q8=class hours actually attended; Q9=degree health affected productivity while attending(0-10 scale, high scores = less productivity); Q10=degree health affected productivity in regular daily activities(0-10 scale, high scores =less productivity). Percent class time missed due to health problem calculated as: Q7*100/(Q7+Q8) and score ranged from 0-100% where higher numbers=greater impairment and less productivity.

Time Frame

Weeks 0, 4, 8 and 12

Title

Percent Impairment While in Class Using Work Productivity and Activity Impairment Questionnaire Plus Classroom Impairment Questions: First Flare Period

Description

WPAI+CIQ:10-item questionnaire used to assess degree to which AD affected work productivity and regular activities over past 7 days. Questions:Q1=currently employed;Q2=work hours missed due to health problems;Q3=work hours missed due to other reasons;Q4=hours actually worked; Q5 = degree health affected productivity while working (0-10 scale, high scores =less productivity); Q6=classes attended in academic setting or not;Q7=class hours missed due to health problems;Q8=class hours actually attended;Q9=degree health affected productivity while attending(0-10 scale, high scores = less productivity);Q10=degree health affected productivity in regular daily activities(0-10 scale, high scores =less productivity). Percent impairment while in class was calculated as: 100*Q9/10 and score ranged from 0-100% where higher numbers indicate greater impairment and less productivity.

Time Frame

Weeks 0, 4, 8 and 12

Title

Percent Overall Class Impairment Using Work Productivity and Activity Impairment Questionnaire Plus Classroom Impairment Questions: First Flare Period

Description

WPAI+CIQ:10-item questionnaire to assess degree to which AD affected work productivity and regular activities over past 7 days. Questions were: Q1=currently employed; Q2=work hours missed due to health problems; Q3=work hours missed due to other reasons; Q4=hours actually worked; Q5=degree health affected productivity while working (0-10 scale, high scores =less productivity); Q6=classes attended in academic setting or not; Q7=class hours missed due to health problems; Q8=class hours actually attended; Q9=degree health affected productivity while attending (0-10 scale, high scores = less productivity); Q10=degree health affected productivity in regular daily activities(0-10 scale, high scores =less productivity). Percent overall class impairment due to health problem calculated as: 100*{Q7/(Q7+Q8)+[(1- Q7/(Q7+Q8))×(Q9/10)]}, score range:0-100%, higher numbers=greater impairment and less productivity.

Time Frame

Weeks 0, 4, 8 and 12

Title

Percent Activity Impairment Using Work Productivity and Activity Impairment Questionnaire Plus Classroom Impairment Questions: First Flare Period

Description

WPAI+CIQ:10-item questionnaire used to assess degree to which AD affected work productivity and regular activities over past 7 days. Questions: Q1=currently employed; Q2=work hours missed due to health problems; Q3=work hours missed due to other reasons; Q4=hours actually worked; Q5=degree health affected productivity while working (0-10 scale, high scores =less productivity); Q6=classes attended in academic setting or not; Q7=class hours missed due to health problems; Q8=class hours actually attended; Q9=degree health affected productivity while attending(0-10 scale, high scores = less productivity);Q10=degree health affected productivity in regular daily activities(0-10 scale, high scores =less productivity). Percent activity impairment due to health problem calculated as: 100*Q10/10, scores ranged from 0-100%,higher numbers=greater impairment and less productivity.

Time Frame

Weeks 0, 4, 8 and 12

Title

Total Anxiety and Depression Scores Measured Using Hospital Anxiety and Depression Scale (HADS): OL Run-in Period

Description

Time Frame

Baseline (last observation up to and including Day 1 of OL period), Weeks 2, 4, 6 and 8

Title

Total Anxiety and Depression Scores Measured Using Hospital Anxiety and Depression Scale: DB Period

Description

Time Frame

Baseline (last observation up to and including randomization day), Week 8, 16, 32 and end of treatment [Week 52]

Title

Total Anxiety and Depression Scores Measured Using Hospital Anxiety and Depression Scale: First Flare Period

Description

Time Frame

Weeks 0, 4, 8 and 12

Title

Total Anxiety and Depression Scores Measured Using Hospital Anxiety and Depression Scale: First Flare Free Period

Description

Time Frame

Baseline (last observation up to and including the randomization day of DB period), Weeks 8, 16 and 32

10. Eligibility

Sex

All

Minimum Age & Unit of Time

3 Months

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Male or female 3 months of age and older Confirmed diagnosis of atopic dermatitis according to Hanifin and Rajka criteria Minimum of 5% BSA affected by atopic dermatitis ISGA score of Mild (2) or Moderate (3) Exclusion Criteria: - Has any clinically significant medical disorder, condition, or disease (including active or potentially recurrent non AD dermatological conditions and known genetic dermatological conditions that overlap with AD, such as Netherton syndrome).

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Pfizer CT.gov Call Center

Organizational Affiliation

Pfizer

Official's Role

Study Director

Facility Information:

Facility Name

First OC Dermatology

City

Fountain Valley

State/Province

California

ZIP/Postal Code

92708

Country

United States

Facility Name

Center for Dermatology Clinical Research, Inc.

City

Fremont

State/Province

California

ZIP/Postal Code

94538

Country

United States

Facility Name

Asthma and Allergy Associates, PC

City

Colorado Springs

State/Province

Colorado

ZIP/Postal Code

80907

Country

United States

Facility Name

Colorado Springs Dermatology Clinic, PC

City

Colorado Springs

State/Province

Colorado

ZIP/Postal Code

80910

Country

United States

Facility Name

Skin Care Research LLC

City

Boca Raton

State/Province

Florida

ZIP/Postal Code

33486

Country

United States

Facility Name

Clinical Neuroscience Solutions, Inc

City

Jacksonville

State/Province

Florida

ZIP/Postal Code

32256

Country

United States

Facility Name

Olympian Clinical Research

City

Largo

State/Province

Florida

ZIP/Postal Code

33770

Country

United States

Facility Name

Baumann Cosmetic and Research Institute

City

Miami

State/Province

Florida

ZIP/Postal Code

33137

Country

United States

Facility Name

Clinical Neuroscience Solutions, Inc

City

Orlando

State/Province

Florida

ZIP/Postal Code

32801

Country

United States

Facility Name

The Indiana Clinical Trials Center, PC

City

Plainfield

State/Province

Indiana

ZIP/Postal Code

46168

Country

United States

Facility Name

Meridian Clinical Research, LLC

City

Baton Rouge

State/Province

Louisiana

ZIP/Postal Code

70808

Country

United States

Facility Name

Great Lakes Research Group, Inc.

City

Bay City

State/Province

Michigan

ZIP/Postal Code

48706

Country

United States

Facility Name

Skin Specialists PC

City

Omaha

State/Province

Nebraska

ZIP/Postal Code

68144

Country

United States

Facility Name

Ohio Pediatric Research Association, Inc.

City

Dayton

State/Province

Ohio

ZIP/Postal Code

45414

Country

United States

Facility Name

Lynn Health Science Institute

City

Oklahoma City

State/Province

Oklahoma

ZIP/Postal Code

73112

Country

United States

Facility Name

Oklahoma State University - Center for Health Sciences

City

Tulsa

State/Province

Oklahoma

ZIP/Postal Code

74127

Country

United States

Facility Name

Clinical Neuroscience Solutions, Inc.

City

Memphis

State/Province

Tennessee

ZIP/Postal Code

38119

Country

United States

Facility Name

Innovate Research, LLC

City

Fort Worth

State/Province

Texas

ZIP/Postal Code

76244

Country

United States

Facility Name

Austin Institute for Clinical Research

City

Houston

State/Province

Texas

ZIP/Postal Code

77056

Country

United States

Facility Name

Austin Institute for Clinical Research, Inc.

City

Pflugerville

State/Province

Texas

ZIP/Postal Code

78660

Country

United States

Facility Name

Center for Clinical Studies, LTD. LLP

City

Webster

State/Province

Texas

ZIP/Postal Code

77598

Country

United States

Facility Name

Jordan Valley Dermatology Center

City

South Jordan

State/Province

Utah

ZIP/Postal Code

84095

Country

United States

Facility Name

PI-Coor Clinical Research LLC

City

Burke

State/Province

Virginia

ZIP/Postal Code

22015

Country

United States

Facility Name

Dermatology Specialists of Spokane

City

Spokane

State/Province

Washington

ZIP/Postal Code

99202

Country

United States

Facility Name

Principle Research Solutions

City

Spokane

State/Province

Washington

ZIP/Postal Code

99204

Country

United States

Facility Name

Australian Clinical Research Network

City

Maroubra

State/Province

New South Wales

ZIP/Postal Code

2035

Country

Australia

Facility Name

SimcoDerm Medical and Surgical Dermatology Center

City

Barrie

State/Province

Ontario

ZIP/Postal Code

L4M 7G1

Country

Canada

Facility Name

Milestone Research , Inc

City

London

State/Province

Ontario

ZIP/Postal Code

N5W 6A2

Country

Canada

Facility Name

North York Research Inc.

City

North York

State/Province

Ontario

ZIP/Postal Code

M2M 4J5

Country

Canada

Facility Name

Manna Research Toronto

City

Toronto

State/Province

Ontario

ZIP/Postal Code

M9W 4L6

Country

Canada

Facility Name

Skinsense Medical Research

City

Saskatoon

State/Province

Saskatchewan

ZIP/Postal Code

S7K 2C1

Country

Canada

Facility Name

Peking University First Hospital

City

Beijing

State/Province

Beijing

ZIP/Postal Code

100034

Country

China

Facility Name

The First Affiliated Hospital of Fujian Medical University

City

Fuzhou

State/Province

Fujian

ZIP/Postal Code

350005

Country

China

Facility Name

Dermatology Hospital of Southern Medical University

City

Guangzhou

State/Province

Guangdong

ZIP/Postal Code

510091

Country

China

Facility Name

Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology

City

Wuhan

State/Province

Hubei

ZIP/Postal Code

430030

Country

China

Facility Name

Dermatology Hospital of Jiangxi Province

City

Nanchang

State/Province

Jiangxi

ZIP/Postal Code

330000

Country

China

Facility Name

Huashan Hospital Fudan University/Dermatology Department

City

Shanghai

State/Province

Shanghai

ZIP/Postal Code

200040

Country

China

Facility Name

Tianjin Medical University General Hospital

City

Tianjin

State/Province

Tianjin

ZIP/Postal Code

300052

Country

China

Facility Name

First Affiliated Hospital of Kunming Medical University

City

Kunming

State/Province

Yunnan

ZIP/Postal Code

650032

Country

China

Facility Name

Hangzhou Third Hospital

City

Hangzhou

State/Province

Zhejiang

ZIP/Postal Code

310009

Country

China

Facility Name

Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University

City

Hangzhou

State/Province

Zhejiang

ZIP/Postal Code

310016

Country

China

Facility Name

The Chaim Sheba Medical Center

City

Ramat - Gan

ZIP/Postal Code

5265601

Country

Israel

Facility Name

Bezmialem Vakıf University Medical Faculty

City

Istanbul

ZIP/Postal Code

34093

Country

Turkey

Facility Name

Erciyes University Medical Faculty

City

Kayseri

ZIP/Postal Code

38039

Country

Turkey

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

IPD Sharing URL

https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests

Links:

URL

https://pmiform.com/clinical-trial-info-request?StudyID=C3291035

Description

To obtain contact information for a study center near you, click here.

Learn more about this trial

A Study to Evaluate Long-Term Maintenance Treatment With Once Daily Crisaborole Ointment 2% in Pediatric and Adult Participants With Mild-to-Moderate Atopic Dermatitis

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