Back to resultsA Trial to Investigate Efficacy, Safety and Tolerability of FE 201836 for Nocturia Due to Nocturnal Polyuria in Adults
Primary Purpose
Nocturia
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
FE 201836
Desmopressin
Placebo oral solution
Placebo ODT
Sponsored by
About this trial
This is an interventional treatment trial for Nocturia
Eligibility Criteria
Inclusion Criteria:
- Adults ≥18 years of age (at the time of written consent)
- Medical history of, or subject reported nocturia symptoms during the 6 months prior to Visit 1
- ≥2 nocturnal voids (an average over 3 days) as documented in the 3-day e-Diary prior to Visit 2
- The largest single voided volume must be ≥200 mL (at least 1 void ≥200 mL) as documented in the 3-day e-Diary prior to Visit 2
- Nocturnal polyuria, defined as Nocturnal Polyuria index >33%, a ratio of Nocturnal Urine Volume in excess of 33% of total daily (24-hour) urine volume as documented in the 3-day e-Diary prior to Visit 2
- ≥20% decrease in the nocturnal diuresis rate (mL/min) (that was recorded at Visit 2) as documented in the 3-day e-Diary prior to Visit 3
Exclusion Criteria:
- Current diagnosis of Obstructive Sleep Apnoea (OSA)
- Restless Legs Syndrome (RLS)
- Bladder Outlet Obstruction (BOO) or urine flow <5 mL/s, as confirmed by uroflowmetry upon suspicion during screening prior to Visit 2
- Urinary incontinence defined as an average of >1 episode/day in the 3-day e-Diary prior to Visit 2 (occasional urge incontinence during daytime or at night on the way to void is not necessarily exclusionary)
- Any pelvic or lower urinary tract surgery and/or radio therapy or previous pelvic irradiation within the past 6 months prior to Visit 1. Including e.g., transurethral resection for Bladder Outlet Obstruction or Benign Prostatic Hyperplasia, hysterectomy or female incontinence procedures
- Genito-urinary tract pathology that can in the investigator's opinion be responsible for urgency or urinary incontinence e.g., symptomatic or recurrent urinary tract infections, interstitial cystitis, bladder-related pain, chronic pelvic pain syndrome, or stone in the bladder or urethra causing symptoms
- A history of cancer with the last date of disease activity/presence of malignancy within the last 12 months prior to Visit 1, except for adequately treated basal cell carcinoma of the skin
- History of any neurological disease affecting bladder function or muscle strength (e.g., Multiple Sclerosis, Parkinson's, spinal cord injury, spina bifida)
- Habitual (fluid intake >3L per day) or psychogenic polydipsia
- Uncontrolled hypertension, as judged by the investigator
- Uncontrolled diabetes mellitus, as judged by the investigator
- Central or nephrogenic diabetes insipidus
- Known history of Syndrome of Inappropriate Antidiuretic Hormone (SIADH) secretion
- History of gastric retention
- Suspicion or evidence of congestive heart failure, (New York Heart Association (NYHA) class II, III, IV)
Hyponatraemia:
- Serum sodium level <135 mmol/L at Visit 1(re-tested, with results available within 7 days)
- Serum sodium level <130 mmol/L at Visit 3 (re-tested, with results available within 7 days)
Use of any prohibited therapy listed below:
- Current or former (within 3 months prior to screening) treatment with any other investigational medicinal product (IMP)
- Unstable electrostimulation or behavioural bladder training program less than 3 months prior to screening (stable electrostimulation or behavioural bladder training program started at least 3 months before screening are acceptable)
- Thiazide diuretics
- Antiarrhythmic agents
- V2-receptor antagonists/agonists (e.g., vaptans/desmopressin, vasopressin)
- Loperamide
- Botulinum toxin (cosmetic non-urological use is acceptable)
- Valproate
Sites / Locations
- Achieve Clinical Research, LLC
- Coastal Clinical Research, an AMR company
- Clinical Trials Research
- Tri Valley Urology Medical Group
- San Diego Clinical Trials
- Advanced Rx Clinical Research Group, Inc.
- Downtown Women's Health Care
- Genitourinary Surgical Consultants, P.C.
- South Florida Medical Research
- Women's Medical Research Group, LLC
- Tampa Bay Medical Research, Inc.
- Clinical Research of South Florida
- Avail Clinical Research, LLC
- Finlay Medical Research Corp
- Pharmax Research Clinic
- Doctors Research Institute Corporation
- Sanitas Research
- Bayside Clinical Research LLC
- Pines Care Research Center, Inc
- Clinical Research Center of Florida
- Meridien Research, Inc.
- American Health Network of Indiana, LLC
- American Health Network of Indiana, LLC
- Bay State Clinical Trials, Inc.
- Beyer Research
- Remedica LLC
- Quality Clinical Research Center, Inc.
- Clinical Research Consortium, an AMR company
- Mid Hudson Medical Research, PLLC
- Premier Medical Group of the Hudson Valley, PC
- American Health Research, Inc.
- Medication Management, LLC
- Peters Medical Research
- PMG Research of Raleigh, LLC
- PMG Research of Wilmington, LLC
- HWC Women's Research Center
- NECCR Primacare Research, LLC
- Coastal Carolina Research Center, Inc
- PMG Research of Charleston, LLC
- MCA Research - Partner
- Ericksen Research & Development, LLC
- Advanced Research Institute
- Clinical Research Associates of Tidewater, an AMR company
- ULB Hopital Erasme
- UZ Antwerpen
- Universitair Ziekenhuis Gent
- AZ Groeninge - Campus Vercruysselaan
- UZ Leuven
- Ultra-Med Inc.
- Milestone Research
- SKDS Research Inc.
- DIEX Recherche Quebec Inc.
- Clinique Médicale St-Louis (Recherche) inc d/b/a/ Centre de Recherche Saint-Louis
- Bluewater Health-Norman Site
- CHUS - Hôpital Fleurimont
- DIEX Recherche Sherbrooke Inc.
- Ferring Investigational Site
- DIEX Recherche Victoriaville Inc.
- Urologie Benešov - Afimed s.r.o.
- Fakultni nemocnice Brno, Dept of Klinika nemoci plicnich a tuberkulozy
- Krajska nemocnice Liberec, a.s.
- Urocentrum Plzen
- Thomayerova nemocnice, PARENT
- Gemeinschaftspraxis fuer Urologie und Andrologie
- Urologische Gemeinschaftspraxis
- Klinikum Weiden, Klinik f. Urologie, Andrologie und Kinderurologie
- Jahn Ferenc Del-pesti Korhaz es Rendelointezet
- Synexus Magyarorszag Kft.
- Bagoly Egeszseghaz
- SzSzB Megyei Korhazak es Egyetemi Oktatokorhaz, Josa Andras Oktatokorhaz Urologia
- Jasz-Nagykun-Szolnok Megyei Hetenyi Geza Korhaz-Rendelointezet
- Nasz Lekarz Osrodek Badan Klinicznych
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm 7
Arm 8
Arm 9
Arm Type
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Arm Label
FE 201836 500 μg (Randomized Treatment Period)
FE 201836 350 μg (Randomized Treatment Period)
FE 201836 250 μg (Randomized Treatment Period)
FE 201836 150 μg (Randomized Treatment Period)
FE 201836 100 μg (Randomized Treatment Period)
FE 201836 50 μg (Randomized Treatment Period)
Placebo (Randomized Treatment Period)
Desmopressin 25 μg (Randomized Treatment Period)
Desmopressin 50 μg (Randomized Treatment Period)
Arm Description
FE 201836 500 μg oral solution and placebo orally disintegrating tablet (ODT), administered once daily
FE 201836 350 μg oral solution and placebo ODT, administered once daily
FE 201836 250 μg oral solution and placebo ODT, administered once daily
FE 201836 150 μg oral solution and placebo ODT, administered once daily
FE 201836 100 μg oral solution and placebo ODT, administered once daily
FE 201836 50 μg oral solution and placebo ODT, administered once daily
Placebo oral solution and placebo ODT, administered once daily
Desmopressin 25 μg ODT and placebo oral solution, administered once daily (female subjects)
Desmopressin 50 μg ODT and placebo oral solution, administered once daily (male subjects)
Outcomes
Primary Outcome Measures
Change From Baseline in Aggregated Mean Number of Nocturnal Voids During 12 Weeks of Treatment
Nocturnal voids were defined as voids occuring from 5 minutes after bedtime until rising in the morning.
The number of nocturnal voids at each visit was calculated as the average over the 3 consecutive 24 hour periods just prior to the respective visit. The visit-specific means were aggregated into a mean of current and preceding visits.
Level estimated for baseline value of mean number of nocturnal voids equal to 2, and 95% credibility interval (2.5 and 97.5 percentiles of the posterior distribution) instead of confidence interval are presented in this endpoint.
Secondary Outcome Measures
Change From Baseline in Mean Number of Nocturnal Voids at Week 1
Nocturnal voids were defined as voids occuring from 5 minutes after bedtime until rising in the morning.
The number of nocturnal voids at each visit was calculated as the average over the 3 consecutive 24 hour periods just prior to the respective visit. Adjusted visit-specific mean changes from baseline in nocturnal voids are estimated using a baseline value of 2.
MMRM=Mixed Model for Repeated Measurements.
For all visit-specific results, the tables present the number of subjects with an observation of the endpoints in question at the specific visit. All secondary analyses are performed using the observed-case approach based on repeated measurements for all subjects in the ITT-RT population. That is, these secondary analyses are based on all subjects with at least one non-missing post-baseline observation (with a baseline value if relevant).
Change From Baseline in Mean Number of Nocturnal Voids at Week 4
Nocturnal voids were defined as voids occuring from 5 minutes after bedtime until rising in the morning.
The number of nocturnal voids at each visit was calculated as the average over the 3 consecutive 24 hour periods just prior to the respective visit. Adjusted visit-specific mean changes from baseline in nocturnal voids are estimated using a baseline value of 2.
Change From Baseline in Mean Number of Nocturnal Voids at Week 8
Nocturnal voids were defined as voids occuring from 5 minutes after bedtime until rising in the morning.
The number of nocturnal voids at each visit was calculated as the average over the 3 consecutive 24 hour periods just prior to the respective visit. Adjusted visit-specific mean changes from baseline in nocturnal voids are estimated using a baseline value of 2.
Change From Baseline in Mean Number of Nocturnal Voids at Week 12
Nocturnal voids were defined as voids occuring from 5 minutes after bedtime until rising in the morning.
The number of nocturnal voids at each visit was calculated as the average over the 3 consecutive 24 hour periods just prior to the respective visit. Adjusted visit-specific mean changes from baseline in nocturnal voids are estimated using a baseline value of 2.
Responder Rate in Nocturnal Voids at Week 1
Defined as 50% reduction in nocturnal voids from baseline.
Adjusted visit-specific estimated odds of at least 50% in the reduction mean number of nocturnal voids are estimated using a baseline value of 2.
The estimated odd equals the probability of response divided by the probability of non-response; these odds may vary between 0 and infinity. For example, if the probability of responding is 80%, the odd of responding is 4, as it is 4 times more likely to respond (80%) then it is not to respond (20%).
Responder Rate in Nocturnal Voids at Week 4
Defined as 50% reduction in nocturnal voids from baseline.
Adjusted visit-specific estimated odds of at least 50% reduction in the mean number of nocturnal voids are estimated using a baseline value of 2.
The estimated odd equals the probability of response divided by the probability of non-response; these odds may vary between 0 and infinity. For example, if the probability of responding is 80%, the odd of responding is 4, as it is 4 times more likely to respond (80%) then it is not to respond (20%).
Responder Rate in Nocturnal Voids at Week 8
Defined as 50% reduction in nocturnal voids from baseline.
Adjusted visit-specific estimated odds of at least 50% reduction in the mean number of nocturnal voids are estimated using a baseline value of 2.
The estimated odd equals the probability of response divided by the probability of non-response; these odds may vary between 0 and infinity. For example, if the probability of responding is 80%, the odd of responding is 4, as it is 4 times more likely to respond (80%) then it is not to respond (20%).
Responder Rate in Nocturnal Voids at Week 12
Defined as 50% reduction in nocturnal voids from baseline.
Adjusted visit-specific estimated odds of at least 50% reduction in the mean number of nocturnal voids are estimated using a baseline value of 2.
The estimated odd equals the probability of response divided by the probability of non-response; these odds may vary between 0 and infinity. For example, if the probability of responding is 80%, the odd of responding is 4, as it is 4 times more likely to respond (80%) then it is not to respond (20%).
Responder Rate in Nocturnal Voids During 12 Weeks of Treatment
Defined as 50% reduction in nocturnal voids from baseline.
Estimated odds of at least 50% reduction in the aggregated mean number of nocturnal voids for a subject with 2 nocturnal voids at baseline are presented in this endpoint.
The 95% credibility interval (2.5 and 97.5 percentiles of the posterior distribution) instead of confidence interval is presented for this endpoint.
The estimated odd equals the probability of response divided by the probability of non-response; these odds may vary between 0 and infinity. For example, if the probability of responding is 80%, the odd of responding is 4, as it is 4 times more likely to respond (80%) then it is not to respond (20%).
Change From Baseline in Mean NI Diary Total Score at Week 1
The NI Diary is a 12-item questionnaire with 11 core items (Q1-Q11) and an overall quality of life (QoL) impact question (Q12). The NI Diary Total Scores are calculated by summing the 11 core items.Responses are scored from 0 to 4 (lowest t o highest impact). The NI Diary Total is standardized from 0 to 100 (lowest to highest impact).
The score at each visit was calculated as the average over the three consecutive 24 hour periods just prior to the respective visit. Adjusted visit-specific mean changes from baseline in NI Diary Total Score are estimated using a baseline value of 40.
Change From Baseline in Mean NI Diary Total Score at Week 4
The NI Diary is a 12-item questionnaire with 11 core items (Q1-Q11) and an overall QoL impact question (Q12). The NI Diary Total Scores are calculated by summing the 11 core items. Responses are scored from 0 to 4 (lowest to highest impact). The NI Diary Total is standardized from 0 to 100 (lowest to highest impact).
The score at each visit was calculated as the average over the three consecutive 24 hour periods just prior to the respective visit. Adjusted visit-specific mean changes from baseline in NI Diary Total Score are estimated using a baseline value of 40.
Change From Baseline in Mean NI Diary Total Score at Week 8
The NI Diary is a 12-item questionnaire with 11 core items (Q1-Q11) and an overall QoL impact question (Q12). The NI Diary Total Scores are calculated by summing the 11 core items. Responses are scored from 0 to 4 (lowest to highest impact). The NI Diary Total is standardized from 0 to 100 (lowest to highest impact).
The score at each visit was calculated as the average over the three consecutive 24 hour periods just prior to the respective visit. Adjusted visit-specific mean changes from baseline in NI Diary Total Score are estimated using a baseline value of 40.
Change From Baseline in Mean NI Diary Total Score at Week 12
The NI Diary is a 12-item questionnaire with 11 core items (Q1-Q11) and an overall QoL impact question (Q12). The NI Diary Total Scores are calculated by summing the 11 core items. Responses are scored from 0 to 4 (lowest to highest impact). The NI Diary Total is standardized from 0 to 100 (lowest to highest impact).
The score at each visit was calculated as the average over the three consecutive 24 hour periods just prior to the respective visit. Adjusted visit-specific mean changes from baseline in NI Diary Total Score are estimated using a baseline value of 40.
Change From Baseline in Aggregated Mean NI Diary Total Score During 12 Weeks of Treatment
The NI Diary is a 12-item questionnaire with 11 core items (Q1-Q11) and an overall QoL impact question (Q12). The NI Diary Total Scores are calculated by summing the 11 core items. Responses are scored from 0 to 4 (lowest to highest impact). The NI Diary Total is standardized from 0 to 100 (lowest to highest impact).
The score at each visit was calculated as the mean over the three consecutive 24 hour periods just prior to the respective visit. The visit-specific means were aggregated into a mean of current and preceding visits.
Level estimated for baseline value of mean NI Diary Total Score equal to 40 is presented in this endpoint.
The 95% credibility interval (2.5 and 97.5 percentiles of the posterior distribution) instead of confidence interval is presented for this endpoint.
Percentage of Nights With at Most One Nocturnal Void During 12 Weeks of Treatment
The percentages of nights during the treatment period with at most one nocturnal void are presented in this endpoint.
Level estimated for baseline value of mean number of nocturnal voids equal to 2 is presented in this endpoint.
Percentage of Nights With No Nocturnal Voids During 12 Weeks of Treatment
The percentages of nights during the treatment period with complete response, i.e. no nocturnal voids are presented in this endpoint.
Level estimated for baseline value of mean number of nocturnal voids equal to 2 is presented in this endpoint.
Change From Baseline in Mean NI Diary Overall Impact Score at Week 1
The NI Diary is a 12-item questionnaire with 11 core items (Q1-Q11) and an overall QoL impact question (Q12). For the overall impact question (Q12), response options range from 0 (not at all) to 4 (a great deal). The NI Diary Overall Impact Scores are standardized from 0 to 100 (lowest to highest impact).
The score at each visit was calculated as the average over the three consecutive 24 hour periods just prior to the respective visit. Adjusted visit-specific mean changes from baseline in NI Diary Overall Impact Score are estimated using a baseline value of 40.
Change From Baseline in Mean NI Diary Overall Impact Score at Week 4
The NI Diary is a 12-item questionnaire with 11 core items (Q1-Q11) and an overall QoL impact question (Q12). For the overall impact question (Q12), response options range from 0 (not at all) to 4 (a great deal). The NI Diary Overall Impact Scores are standardized from 0 to 100 (lowest to highest impact).
The score at each visit was calculated as the average over the three consecutive 24 hour periods just prior to the respective visit. Adjusted visit-specific mean changes from baseline in NI Diary Overall Impact Score are estimated using a baseline value of 40.
Change From Baseline in Mean NI Diary Overall Impact Score at Week 8
The NI Diary is a 12-item questionnaire with 11 core items (Q1-Q11) and an overall QoL impact question (Q12). For the overall impact question (Q12), response options range from 0 (not at all) to 4 (a great deal). The NI Diary Overall Impact Scores are standardized from 0 to 100 (lowest to highest impact).
The score at each visit was calculated as the average over the three consecutive 24 hour periods just prior to the respective visit. Adjusted visit-specific mean changes from baseline in NI Diary Overall Impact Score are estimated using a baseline value of 40.
Change From Baseline in Mean NI Diary Overall Impact Score at Week 12
The NI Diary is a 12-item questionnaire with 11 core items (Q1-Q11) and an overall QoL impact question (Q12). For the overall impact question (Q12), response options range from 0 (not at all) to 4 (a great deal). The NI Diary Overall Impact Scores are standardized from 0 to 100 (lowest to highest impact).
The score at each visit was calculated as the average over the three consecutive 24 hour periods just prior to the respective visit. Adjusted visit-specific mean changes from baseline in NI Diary Overall Impact Score are estimated using a baseline value of 40.
Change From Baseline in Aggregated Mean NI Diary Overall Impact Score During 12 Weeks of Treatment
The NI Diary is a 12-item questionnaire with 11 core items (Q1-Q11) and an overall QoL impact question (Q12). For the overall impact question (Q12), response options range from 0 (not at all) to 4 (a great deal). The NI Diary Overall Impact Scores are standardized from 0 to 100 (lowest to highest impact).
The score at each visit was calculated as the average over the three consecutive 24 hour periods just prior to the respective visit. The visit-specific means were aggregated into a mean of current and preceding visits.
Level estimated for baseline value of mean NI Diary Overall Impact Score equal to 40 is presented in this endpoint.
The 95% credibility interval (2.5 and 97.5 percentiles of the posterior distribution) instead of confidence interval is presented for this endpoint.
Patient Global Impression of Improvement (PGI-I) Urinary Symptoms Scores at Week 1
The PGI-I is a 1-item questionnaire designed to assess the patient's impression of changes in urinary symptoms. The PGI-I was scored from 1 (very much better) to 7 (very much worse).
Visit-specific PGI-I in urinary symptoms is presented in this endpoint.
Patient Global Impression of Improvement (PGI-I) Urinary Symptoms Scores at Week 4
The PGI-I is a 1-item questionnaire designed to assess the patient's impression of changes in urinary symptoms. The PGI-I was scored from 1 (very much better) to 7 (very much worse).
Visit-specific PGI-I in urinary symptoms is presented in this endpoint.
Patient Global Impression of Improvement (PGI-I) Urinary Symptoms Scores at Week 8
The PGI-I is a 1-item questionnaire designed to assess the patient's impression of changes in urinary symptoms. The PGI-I was scored from 1 (very much better) to 7 (very much worse).
Visit-specific PGI-I in urinary symptoms is presented in this endpoint.
Patient Global Impression of Improvement (PGI-I) Urinary Symptoms Scores at Week 12
The PGI-I is a 1-item questionnaire designed to assess the patient's impression of changes in urinary symptoms. The PGI-I was scored from 1 (very much better) to 7 (very much worse).
Visit-specific PGI-I in urinary symptoms is presented in this endpoint.
Change From Baseline in Patient Global Impression of Severity (PGI-S) Scores at Week 1
The PGI-S is a 1-item questionnaire designed to assess patient's impression of disease severity. The PGI-S was scored from 1 (none) to 4 (severe).
Change from baseline in visit-specific PGI-S is presented in this endpoint.
Level estimated for baseline value of PGI-S equal to 3 is presented in this endpoint.
Change From Baseline in PGI-S Scores at Week 4
The PGI-S is a 1-item questionnaire designed to assess patient's impression of disease severity. The PGI-S was scored from 1 (none) to 4 (severe).
Change from baseline in visit-specific PGI-S is presented in this endpoint.
Level estimated for baseline value of PGI-S equal to 3 is presented in this endpoint.
Change From Baseline in PGI-S Scores at Week 8
The PGI-S is a 1-item questionnaire designed to assess patient's impression of disease severity. The PGI-S was scored from 1 (none) to 4 (severe).
Change from baseline in visit-specific PGI-S is presented in this endpoint.
Level estimated for baseline value of PGI-S equal to 3 is presented in this endpoint.
Change From Baseline in PGI-S Scores at Week 12
The PGI-S is a 1-item questionnaire designed to assess patient's impression of disease severity. The PGI-S was scored from 1 (none) to 4 (severe).
Change from baseline in visit-specific PGI-S is presented in this endpoint.
Level estimated for baseline value of PGI-S equal to 3 is presented in this endpoint.
Change From Baseline in Hsu 5-point Likert Bother Scale at Week 1
The Hsu 5-point Likert Bother scale is a questionnaire designed to assess the subjective bothersomeness and functional disruptiveness of nocturia. The Hsu 5 point Likert Bother Scale was scored from 0 (not at all) to 4 (extremely).
Change from baseline in visit-specific Hsu Bother is presented in this endpoint.
Level estimated for baseline value of Hsu Bother equal to 3 is presented in this endpoint.
Change From Baseline in Hsu 5-point Likert Bother Scale at Week 4
The Hsu 5-point Likert Bother scale is a questionnaire designed to assess the subjective bothersomeness and functional disruptiveness of nocturia. The Hsu 5 point Likert Bother Scale was scored from 0 (not at all) to 4 (extremely).
Change from baseline in visit-specific Hsu Bother is presented in this endpoint.
Level estimated for baseline value of Hsu Bother equal to 3 is presented in this endpoint.
Change From Baseline in Hsu 5-point Likert Bother Scale at Week 8
The Hsu 5-point Likert Bother scale is a questionnaire designed to assess the subjective bothersomeness and functional disruptiveness of nocturia. The Hsu 5 point Likert Bother Scale was scored from 0 (not at all) to 4 (extremely).
Change from baseline in visit-specific Hsu Bother is presented in this endpoint.
Level estimated for baseline value of Hsu Bother equal to 3 is presented in this endpoint.
Change From Baseline in Hsu 5-point Likert Bother Scale at Week 12
The Hsu 5-point Likert Bother scale is a questionnaire designed to assess the subjective bothersomeness and functional disruptiveness of nocturia. The Hsu 5 point Likert Bother Scale was scored from 0 (not at all) to 4 (extremely).
Change from baseline in visit-specific Hsu Bother is presented in this endpoint.
Level estimated for baseline value of Hsu Bother equal to 3 is presented in this endpoint.
Change From Baseline in ISI at Week 4
The ISI is a 7-item questionnaire which comprises of four 'sleep-related' items and three 'wake-related' items. Each item is rated on a 0-4 scale and the total score ranges from 0 to 28 (higher score suggests more severe insomnia).
Change from baseline in visit-specific ISI is presented in this endpoint.
Level estimated for baseline value of ISI equal to 15 is presented in this endpoint.
Change From Baseline in ISI at Week 8
The ISI is a 7-item questionnaire which comprises of four 'sleep-related' items and three 'wake-related' items. Each item is rated on a 0-4 scale and the total score ranges from 0 to 28 (higher score suggests more severe insomnia).
Change from baseline in visit-specific ISI is presented in this endpoint.
Level estimated for baseline value of ISI equal to 15 is presented in this endpoint.
Change From Baseline in ISI at Week 12
The ISI is a 7-item questionnaire which comprises of four 'sleep-related' items and three 'wake-related' items. Each item is rated on a 0-4 scale and the total score ranges from 0 to 28 (higher score suggests more severe insomnia).
Change from baseline in visit-specific ISI is presented in this endpoint.
Level estimated for baseline value of ISI equal to 15 is presented in this endpoint.
Change From Baseline in Mean Duration of First Undisturbed Sleep Period (FUSP) at Week 1
The FUSP is defined as the time in minutes from the time of going to bed to the time of first nocturnal void, or time of awakening if no void occured.
The duration of FUSP at each visit was calculated as the average over the 3 consecutive 24-hour periods just prior to the respective visit. Adjusted visit-specific mean changes from baseline in FUSP are estimated using a baseline value of 180 (min).
Change From Baseline in Mean Duration of FUSP at Week 4
The FUSP is defined as the time in minutes from the time of going to bed to the time of first nocturnal void, or time of awakening if no void occurred.
The duration of FUSP at each visit was calculated as the average over the 3 consecutive 24-hour periods just prior to the respective visit. Adjusted visit-specific mean changes from baseline in FUSP are estimated using a baseline value of 180 (min).
Change From Baseline in Mean Duration of FUSP at Week 8
The FUSP is defined as the time in minutes from the time of going to bed to the time of first nocturnal void, or time of awakening if no void occurred.
The duration of FUSP at each visit was calculated as the average over the 3 consecutive 24-hour periods just prior to the respective visit. Adjusted visit-specific mean changes from baseline in FUSP are estimated using a baseline value of 180 (min).
Change From Baseline in Mean Duration of FUSP at Week 12
The FUSP is defined as the time in minutes from the time of going to bed to the time of first nocturnal void, or time of awakening if no void occurred.
The duration of FUSP at each visit was calculated as the average over the 3 consecutive 24-hour periods just prior to the respective visit. Adjusted visit-specific mean changes from baseline in FUSP are estimated using a baseline value of 180 (min).
Change From Baseline in Aggregated Mean Duration of FUSP During 12 Weeks of Treatment
The FUSP is defined as the time in minutes from the time of going to bed to the time of first nocturnal void, or time of awakening if no void occurred.
The visit-specific means were aggregated into a mean of current and preceding visits.
Level estimated for baseline value of mean duration of FUSP (minutes) equal to 180 is presented in this endpoint.
The 95% credibility interval (2.5 and 97.5 percentiles of the posterior distribution) instead of confidence interval is presented for this endpoint.
Change From Baseline in Nocturnal Diuresis Rate Profiles at Week 1
The nocturnal diuresis rate (mL/min) is calculated as the mean of the nocturnal diuresis for each of the three nights, with the single-night nocturnal diuresis calculated as the ratio of NUV to total time in bed.
Change from baseline in visit-specific mean nocturnal diuresis (mL/min) is presented.
Level estimated for baseline value of mean nocturnal diuresis (mL/min) equal to 1.3 is presented in this endpoint.
Change From Baseline in Nocturnal Diuresis Rate Profiles at Week 12
The nocturnal diuresis rate (mL/min) is calculated as the mean of the nocturnal diuresis for each of the three nights, with the single-night nocturnal diuresis calculated as the ratio of NUV to total time in bed.
Change from baseline in visit-specific mean nocturnal diuresis (mL/min) is presented.
Level estimated for baseline value of mean nocturnal diuresis (mL/min) equal to 1.3 is presented in this endpoint.
Change From Baseline in Mean NUV in Week 1
The NUV is defined as the total urine volume from 5 minutes after bedtime with the intention to sleep including the first void within 30 minutes of rising in the morning.
The NUV at each visit was calculated as the average over the 3 consecutive 24-hour periods just prior to the respective visit. Adjusted visit-specific mean changes from baseline in NUV are estimated using a baseline value of 750 (mL).
Change From Baseline in Mean NUV at Week 12
The NUV is defined as the total urine volume from 5 minutes after bedtime with the intention to sleep including the first void within 30 minutes of rising in the morning.
The NUV at each visit was calculated as the average over the 3 consecutive 24-hour periods just prior to the respective visit. Adjusted visit-specific mean changes from baseline in NUV are estimated using a baseline value of 750 (mL).
Full Information
NCT ID
NCT03201419
First Posted
June 26, 2017
Last Updated
February 17, 2022
Sponsor
Ferring Pharmaceuticals
1. Study Identification
Unique Protocol Identification Number
NCT03201419
Brief Title
A Trial to Investigate Efficacy, Safety and Tolerability of FE 201836 for Nocturia Due to Nocturnal Polyuria in Adults
Official Title
A Randomised, Double-blind, Placebo-controlled, Response-adaptive Dose-finding Trial Investigating the Efficacy, Safety and Tolerability of Oral Doses of FE 201836, With Desmopressin Orally Disintegrating Tablet as a Benchmark, During 12 Weeks of Treatment for Nocturia Due to Nocturnal Polyuria in Adults
Study Type
Interventional
2. Study Status
Record Verification Date
October 2020
Overall Recruitment Status
Completed
Study Start Date
July 27, 2017 (Actual)
Primary Completion Date
October 31, 2019 (Actual)
Study Completion Date
October 31, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Ferring Pharmaceuticals
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of this trial was to investigate the efficacy, safety and tolerability of different oral doses of FE 201836, with desmopressin as a benchmark, during 12 weeks of treatment for nocturia due to nocturnal polyuria in adults
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Nocturia
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
The trial consisted of a 2 week period of screening/lifestyle changes during which no treatment was given, a 2 week enrichment period (including a 1 week single blind active run-in period [FE 201836 500 µg] and a 1 week washout period) followed by a 12 week randomized treatment period for each subject. Prior to the first interim analysis, the first 129 subjects were randomized to daily treatment with FE 201836 500 µg, placebo, or desmopressin (25 µg for females and 50 µg for males) in a 2:2:1 ratio. After the first interim analysis, subjects were randomized to daily treatment with FE 201836 (50 µg, 100 µg, 150 µg, 250 µg, 350 µg, or 500 µg), placebo, or desmopressin (25 µg for females and 50 µg for males) using response adaptive allocation probabilities.
Masking
ParticipantInvestigator
Masking Description
Each subject will receive 2 medications (an oral solution and an orally disintegrating tablet (ODT) formulation) throughout the trial, in order to keep the treatment blinded.
Allocation
Randomized
Enrollment
302 (Actual)
8. Arms, Groups, and Interventions
Arm Title
FE 201836 500 μg (Randomized Treatment Period)
Arm Type
Experimental
Arm Description
FE 201836 500 μg oral solution and placebo orally disintegrating tablet (ODT), administered once daily
Arm Title
FE 201836 350 μg (Randomized Treatment Period)
Arm Type
Experimental
Arm Description
FE 201836 350 μg oral solution and placebo ODT, administered once daily
Arm Title
FE 201836 250 μg (Randomized Treatment Period)
Arm Type
Experimental
Arm Description
FE 201836 250 μg oral solution and placebo ODT, administered once daily
Arm Title
FE 201836 150 μg (Randomized Treatment Period)
Arm Type
Experimental
Arm Description
FE 201836 150 μg oral solution and placebo ODT, administered once daily
Arm Title
FE 201836 100 μg (Randomized Treatment Period)
Arm Type
Experimental
Arm Description
FE 201836 100 μg oral solution and placebo ODT, administered once daily
Arm Title
FE 201836 50 μg (Randomized Treatment Period)
Arm Type
Experimental
Arm Description
FE 201836 50 μg oral solution and placebo ODT, administered once daily
Arm Title
Placebo (Randomized Treatment Period)
Arm Type
Experimental
Arm Description
Placebo oral solution and placebo ODT, administered once daily
Arm Title
Desmopressin 25 μg (Randomized Treatment Period)
Arm Type
Experimental
Arm Description
Desmopressin 25 μg ODT and placebo oral solution, administered once daily (female subjects)
Arm Title
Desmopressin 50 μg (Randomized Treatment Period)
Arm Type
Experimental
Arm Description
Desmopressin 50 μg ODT and placebo oral solution, administered once daily (male subjects)
Intervention Type
Drug
Intervention Name(s)
FE 201836
Other Intervention Name(s)
Velmupressin
Intervention Description
Oral solution for daily intake
Intervention Type
Drug
Intervention Name(s)
Desmopressin
Other Intervention Name(s)
NOCDURNA
Intervention Description
Desmopressin Orally Disintegrating Tablet (ODT)
Intervention Type
Drug
Intervention Name(s)
Placebo oral solution
Intervention Description
Manufactured to mimic experimental drug
Intervention Type
Drug
Intervention Name(s)
Placebo ODT
Intervention Description
Manufactured to mimic experimental drug
Primary Outcome Measure Information:
Title
Change From Baseline in Aggregated Mean Number of Nocturnal Voids During 12 Weeks of Treatment
Description
Nocturnal voids were defined as voids occuring from 5 minutes after bedtime until rising in the morning.
The number of nocturnal voids at each visit was calculated as the average over the 3 consecutive 24 hour periods just prior to the respective visit. The visit-specific means were aggregated into a mean of current and preceding visits.
Level estimated for baseline value of mean number of nocturnal voids equal to 2, and 95% credibility interval (2.5 and 97.5 percentiles of the posterior distribution) instead of confidence interval are presented in this endpoint.
Time Frame
Baseline, during 12 weeks of treatment
Secondary Outcome Measure Information:
Title
Change From Baseline in Mean Number of Nocturnal Voids at Week 1
Description
Nocturnal voids were defined as voids occuring from 5 minutes after bedtime until rising in the morning.
The number of nocturnal voids at each visit was calculated as the average over the 3 consecutive 24 hour periods just prior to the respective visit. Adjusted visit-specific mean changes from baseline in nocturnal voids are estimated using a baseline value of 2.
MMRM=Mixed Model for Repeated Measurements.
For all visit-specific results, the tables present the number of subjects with an observation of the endpoints in question at the specific visit. All secondary analyses are performed using the observed-case approach based on repeated measurements for all subjects in the ITT-RT population. That is, these secondary analyses are based on all subjects with at least one non-missing post-baseline observation (with a baseline value if relevant).
Time Frame
Baseline, Week 1
Title
Change From Baseline in Mean Number of Nocturnal Voids at Week 4
Description
Nocturnal voids were defined as voids occuring from 5 minutes after bedtime until rising in the morning.
The number of nocturnal voids at each visit was calculated as the average over the 3 consecutive 24 hour periods just prior to the respective visit. Adjusted visit-specific mean changes from baseline in nocturnal voids are estimated using a baseline value of 2.
Time Frame
Baseline, Week 4
Title
Change From Baseline in Mean Number of Nocturnal Voids at Week 8
Description
Nocturnal voids were defined as voids occuring from 5 minutes after bedtime until rising in the morning.
The number of nocturnal voids at each visit was calculated as the average over the 3 consecutive 24 hour periods just prior to the respective visit. Adjusted visit-specific mean changes from baseline in nocturnal voids are estimated using a baseline value of 2.
Time Frame
Baseline, Week 8
Title
Change From Baseline in Mean Number of Nocturnal Voids at Week 12
Description
Nocturnal voids were defined as voids occuring from 5 minutes after bedtime until rising in the morning.
The number of nocturnal voids at each visit was calculated as the average over the 3 consecutive 24 hour periods just prior to the respective visit. Adjusted visit-specific mean changes from baseline in nocturnal voids are estimated using a baseline value of 2.
Time Frame
Baseline, Week 12
Title
Responder Rate in Nocturnal Voids at Week 1
Description
Defined as 50% reduction in nocturnal voids from baseline.
Adjusted visit-specific estimated odds of at least 50% in the reduction mean number of nocturnal voids are estimated using a baseline value of 2.
The estimated odd equals the probability of response divided by the probability of non-response; these odds may vary between 0 and infinity. For example, if the probability of responding is 80%, the odd of responding is 4, as it is 4 times more likely to respond (80%) then it is not to respond (20%).
Time Frame
Week 1
Title
Responder Rate in Nocturnal Voids at Week 4
Description
Defined as 50% reduction in nocturnal voids from baseline.
Adjusted visit-specific estimated odds of at least 50% reduction in the mean number of nocturnal voids are estimated using a baseline value of 2.
The estimated odd equals the probability of response divided by the probability of non-response; these odds may vary between 0 and infinity. For example, if the probability of responding is 80%, the odd of responding is 4, as it is 4 times more likely to respond (80%) then it is not to respond (20%).
Time Frame
Week 4
Title
Responder Rate in Nocturnal Voids at Week 8
Description
Defined as 50% reduction in nocturnal voids from baseline.
Adjusted visit-specific estimated odds of at least 50% reduction in the mean number of nocturnal voids are estimated using a baseline value of 2.
The estimated odd equals the probability of response divided by the probability of non-response; these odds may vary between 0 and infinity. For example, if the probability of responding is 80%, the odd of responding is 4, as it is 4 times more likely to respond (80%) then it is not to respond (20%).
Time Frame
Week 8
Title
Responder Rate in Nocturnal Voids at Week 12
Description
Defined as 50% reduction in nocturnal voids from baseline.
Adjusted visit-specific estimated odds of at least 50% reduction in the mean number of nocturnal voids are estimated using a baseline value of 2.
The estimated odd equals the probability of response divided by the probability of non-response; these odds may vary between 0 and infinity. For example, if the probability of responding is 80%, the odd of responding is 4, as it is 4 times more likely to respond (80%) then it is not to respond (20%).
Time Frame
Week 12
Title
Responder Rate in Nocturnal Voids During 12 Weeks of Treatment
Description
Defined as 50% reduction in nocturnal voids from baseline.
Estimated odds of at least 50% reduction in the aggregated mean number of nocturnal voids for a subject with 2 nocturnal voids at baseline are presented in this endpoint.
The 95% credibility interval (2.5 and 97.5 percentiles of the posterior distribution) instead of confidence interval is presented for this endpoint.
The estimated odd equals the probability of response divided by the probability of non-response; these odds may vary between 0 and infinity. For example, if the probability of responding is 80%, the odd of responding is 4, as it is 4 times more likely to respond (80%) then it is not to respond (20%).
Time Frame
During 12 weeks of treatment
Title
Change From Baseline in Mean NI Diary Total Score at Week 1
Description
The NI Diary is a 12-item questionnaire with 11 core items (Q1-Q11) and an overall quality of life (QoL) impact question (Q12). The NI Diary Total Scores are calculated by summing the 11 core items.Responses are scored from 0 to 4 (lowest t o highest impact). The NI Diary Total is standardized from 0 to 100 (lowest to highest impact).
The score at each visit was calculated as the average over the three consecutive 24 hour periods just prior to the respective visit. Adjusted visit-specific mean changes from baseline in NI Diary Total Score are estimated using a baseline value of 40.
Time Frame
Baseline, Week 1
Title
Change From Baseline in Mean NI Diary Total Score at Week 4
Description
The NI Diary is a 12-item questionnaire with 11 core items (Q1-Q11) and an overall QoL impact question (Q12). The NI Diary Total Scores are calculated by summing the 11 core items. Responses are scored from 0 to 4 (lowest to highest impact). The NI Diary Total is standardized from 0 to 100 (lowest to highest impact).
The score at each visit was calculated as the average over the three consecutive 24 hour periods just prior to the respective visit. Adjusted visit-specific mean changes from baseline in NI Diary Total Score are estimated using a baseline value of 40.
Time Frame
Baseline, Week 4
Title
Change From Baseline in Mean NI Diary Total Score at Week 8
Description
The NI Diary is a 12-item questionnaire with 11 core items (Q1-Q11) and an overall QoL impact question (Q12). The NI Diary Total Scores are calculated by summing the 11 core items. Responses are scored from 0 to 4 (lowest to highest impact). The NI Diary Total is standardized from 0 to 100 (lowest to highest impact).
The score at each visit was calculated as the average over the three consecutive 24 hour periods just prior to the respective visit. Adjusted visit-specific mean changes from baseline in NI Diary Total Score are estimated using a baseline value of 40.
Time Frame
Baseline, Week 8
Title
Change From Baseline in Mean NI Diary Total Score at Week 12
Description
The NI Diary is a 12-item questionnaire with 11 core items (Q1-Q11) and an overall QoL impact question (Q12). The NI Diary Total Scores are calculated by summing the 11 core items. Responses are scored from 0 to 4 (lowest to highest impact). The NI Diary Total is standardized from 0 to 100 (lowest to highest impact).
The score at each visit was calculated as the average over the three consecutive 24 hour periods just prior to the respective visit. Adjusted visit-specific mean changes from baseline in NI Diary Total Score are estimated using a baseline value of 40.
Time Frame
Baseline, Week 12
Title
Change From Baseline in Aggregated Mean NI Diary Total Score During 12 Weeks of Treatment
Description
The NI Diary is a 12-item questionnaire with 11 core items (Q1-Q11) and an overall QoL impact question (Q12). The NI Diary Total Scores are calculated by summing the 11 core items. Responses are scored from 0 to 4 (lowest to highest impact). The NI Diary Total is standardized from 0 to 100 (lowest to highest impact).
The score at each visit was calculated as the mean over the three consecutive 24 hour periods just prior to the respective visit. The visit-specific means were aggregated into a mean of current and preceding visits.
Level estimated for baseline value of mean NI Diary Total Score equal to 40 is presented in this endpoint.
The 95% credibility interval (2.5 and 97.5 percentiles of the posterior distribution) instead of confidence interval is presented for this endpoint.
Time Frame
Baseline, during 12 weeks of treatment
Title
Percentage of Nights With at Most One Nocturnal Void During 12 Weeks of Treatment
Description
The percentages of nights during the treatment period with at most one nocturnal void are presented in this endpoint.
Level estimated for baseline value of mean number of nocturnal voids equal to 2 is presented in this endpoint.
Time Frame
During 12 weeks of treatment
Title
Percentage of Nights With No Nocturnal Voids During 12 Weeks of Treatment
Description
The percentages of nights during the treatment period with complete response, i.e. no nocturnal voids are presented in this endpoint.
Level estimated for baseline value of mean number of nocturnal voids equal to 2 is presented in this endpoint.
Time Frame
During 12 weeks of treatment
Title
Change From Baseline in Mean NI Diary Overall Impact Score at Week 1
Description
The NI Diary is a 12-item questionnaire with 11 core items (Q1-Q11) and an overall QoL impact question (Q12). For the overall impact question (Q12), response options range from 0 (not at all) to 4 (a great deal). The NI Diary Overall Impact Scores are standardized from 0 to 100 (lowest to highest impact).
The score at each visit was calculated as the average over the three consecutive 24 hour periods just prior to the respective visit. Adjusted visit-specific mean changes from baseline in NI Diary Overall Impact Score are estimated using a baseline value of 40.
Time Frame
Baseline, Week 1
Title
Change From Baseline in Mean NI Diary Overall Impact Score at Week 4
Description
The NI Diary is a 12-item questionnaire with 11 core items (Q1-Q11) and an overall QoL impact question (Q12). For the overall impact question (Q12), response options range from 0 (not at all) to 4 (a great deal). The NI Diary Overall Impact Scores are standardized from 0 to 100 (lowest to highest impact).
The score at each visit was calculated as the average over the three consecutive 24 hour periods just prior to the respective visit. Adjusted visit-specific mean changes from baseline in NI Diary Overall Impact Score are estimated using a baseline value of 40.
Time Frame
Baseline, Week 4
Title
Change From Baseline in Mean NI Diary Overall Impact Score at Week 8
Description
The NI Diary is a 12-item questionnaire with 11 core items (Q1-Q11) and an overall QoL impact question (Q12). For the overall impact question (Q12), response options range from 0 (not at all) to 4 (a great deal). The NI Diary Overall Impact Scores are standardized from 0 to 100 (lowest to highest impact).
The score at each visit was calculated as the average over the three consecutive 24 hour periods just prior to the respective visit. Adjusted visit-specific mean changes from baseline in NI Diary Overall Impact Score are estimated using a baseline value of 40.
Time Frame
Baseline, Week 8
Title
Change From Baseline in Mean NI Diary Overall Impact Score at Week 12
Description
The NI Diary is a 12-item questionnaire with 11 core items (Q1-Q11) and an overall QoL impact question (Q12). For the overall impact question (Q12), response options range from 0 (not at all) to 4 (a great deal). The NI Diary Overall Impact Scores are standardized from 0 to 100 (lowest to highest impact).
The score at each visit was calculated as the average over the three consecutive 24 hour periods just prior to the respective visit. Adjusted visit-specific mean changes from baseline in NI Diary Overall Impact Score are estimated using a baseline value of 40.
Time Frame
Baseline, Week 12
Title
Change From Baseline in Aggregated Mean NI Diary Overall Impact Score During 12 Weeks of Treatment
Description
The NI Diary is a 12-item questionnaire with 11 core items (Q1-Q11) and an overall QoL impact question (Q12). For the overall impact question (Q12), response options range from 0 (not at all) to 4 (a great deal). The NI Diary Overall Impact Scores are standardized from 0 to 100 (lowest to highest impact).
The score at each visit was calculated as the average over the three consecutive 24 hour periods just prior to the respective visit. The visit-specific means were aggregated into a mean of current and preceding visits.
Level estimated for baseline value of mean NI Diary Overall Impact Score equal to 40 is presented in this endpoint.
The 95% credibility interval (2.5 and 97.5 percentiles of the posterior distribution) instead of confidence interval is presented for this endpoint.
Time Frame
Baseline, during 12 weeks of treatment
Title
Patient Global Impression of Improvement (PGI-I) Urinary Symptoms Scores at Week 1
Description
The PGI-I is a 1-item questionnaire designed to assess the patient's impression of changes in urinary symptoms. The PGI-I was scored from 1 (very much better) to 7 (very much worse).
Visit-specific PGI-I in urinary symptoms is presented in this endpoint.
Time Frame
Week 1
Title
Patient Global Impression of Improvement (PGI-I) Urinary Symptoms Scores at Week 4
Description
The PGI-I is a 1-item questionnaire designed to assess the patient's impression of changes in urinary symptoms. The PGI-I was scored from 1 (very much better) to 7 (very much worse).
Visit-specific PGI-I in urinary symptoms is presented in this endpoint.
Time Frame
Week 4
Title
Patient Global Impression of Improvement (PGI-I) Urinary Symptoms Scores at Week 8
Description
The PGI-I is a 1-item questionnaire designed to assess the patient's impression of changes in urinary symptoms. The PGI-I was scored from 1 (very much better) to 7 (very much worse).
Visit-specific PGI-I in urinary symptoms is presented in this endpoint.
Time Frame
Week 8
Title
Patient Global Impression of Improvement (PGI-I) Urinary Symptoms Scores at Week 12
Description
The PGI-I is a 1-item questionnaire designed to assess the patient's impression of changes in urinary symptoms. The PGI-I was scored from 1 (very much better) to 7 (very much worse).
Visit-specific PGI-I in urinary symptoms is presented in this endpoint.
Time Frame
Week 12
Title
Change From Baseline in Patient Global Impression of Severity (PGI-S) Scores at Week 1
Description
The PGI-S is a 1-item questionnaire designed to assess patient's impression of disease severity. The PGI-S was scored from 1 (none) to 4 (severe).
Change from baseline in visit-specific PGI-S is presented in this endpoint.
Level estimated for baseline value of PGI-S equal to 3 is presented in this endpoint.
Time Frame
Baseline, Week 1
Title
Change From Baseline in PGI-S Scores at Week 4
Description
The PGI-S is a 1-item questionnaire designed to assess patient's impression of disease severity. The PGI-S was scored from 1 (none) to 4 (severe).
Change from baseline in visit-specific PGI-S is presented in this endpoint.
Level estimated for baseline value of PGI-S equal to 3 is presented in this endpoint.
Time Frame
Baseline, Week 4
Title
Change From Baseline in PGI-S Scores at Week 8
Description
The PGI-S is a 1-item questionnaire designed to assess patient's impression of disease severity. The PGI-S was scored from 1 (none) to 4 (severe).
Change from baseline in visit-specific PGI-S is presented in this endpoint.
Level estimated for baseline value of PGI-S equal to 3 is presented in this endpoint.
Time Frame
Baseline, Week 8
Title
Change From Baseline in PGI-S Scores at Week 12
Description
The PGI-S is a 1-item questionnaire designed to assess patient's impression of disease severity. The PGI-S was scored from 1 (none) to 4 (severe).
Change from baseline in visit-specific PGI-S is presented in this endpoint.
Level estimated for baseline value of PGI-S equal to 3 is presented in this endpoint.
Time Frame
Baseline, Week 12
Title
Change From Baseline in Hsu 5-point Likert Bother Scale at Week 1
Description
The Hsu 5-point Likert Bother scale is a questionnaire designed to assess the subjective bothersomeness and functional disruptiveness of nocturia. The Hsu 5 point Likert Bother Scale was scored from 0 (not at all) to 4 (extremely).
Change from baseline in visit-specific Hsu Bother is presented in this endpoint.
Level estimated for baseline value of Hsu Bother equal to 3 is presented in this endpoint.
Time Frame
Baseline, Week 1
Title
Change From Baseline in Hsu 5-point Likert Bother Scale at Week 4
Description
The Hsu 5-point Likert Bother scale is a questionnaire designed to assess the subjective bothersomeness and functional disruptiveness of nocturia. The Hsu 5 point Likert Bother Scale was scored from 0 (not at all) to 4 (extremely).
Change from baseline in visit-specific Hsu Bother is presented in this endpoint.
Level estimated for baseline value of Hsu Bother equal to 3 is presented in this endpoint.
Time Frame
Baseline, Week 4
Title
Change From Baseline in Hsu 5-point Likert Bother Scale at Week 8
Description
The Hsu 5-point Likert Bother scale is a questionnaire designed to assess the subjective bothersomeness and functional disruptiveness of nocturia. The Hsu 5 point Likert Bother Scale was scored from 0 (not at all) to 4 (extremely).
Change from baseline in visit-specific Hsu Bother is presented in this endpoint.
Level estimated for baseline value of Hsu Bother equal to 3 is presented in this endpoint.
Time Frame
Baseline, Week 8
Title
Change From Baseline in Hsu 5-point Likert Bother Scale at Week 12
Description
The Hsu 5-point Likert Bother scale is a questionnaire designed to assess the subjective bothersomeness and functional disruptiveness of nocturia. The Hsu 5 point Likert Bother Scale was scored from 0 (not at all) to 4 (extremely).
Change from baseline in visit-specific Hsu Bother is presented in this endpoint.
Level estimated for baseline value of Hsu Bother equal to 3 is presented in this endpoint.
Time Frame
Baseline, Week 12
Title
Change From Baseline in ISI at Week 4
Description
The ISI is a 7-item questionnaire which comprises of four 'sleep-related' items and three 'wake-related' items. Each item is rated on a 0-4 scale and the total score ranges from 0 to 28 (higher score suggests more severe insomnia).
Change from baseline in visit-specific ISI is presented in this endpoint.
Level estimated for baseline value of ISI equal to 15 is presented in this endpoint.
Time Frame
Baseline, Week 4
Title
Change From Baseline in ISI at Week 8
Description
The ISI is a 7-item questionnaire which comprises of four 'sleep-related' items and three 'wake-related' items. Each item is rated on a 0-4 scale and the total score ranges from 0 to 28 (higher score suggests more severe insomnia).
Change from baseline in visit-specific ISI is presented in this endpoint.
Level estimated for baseline value of ISI equal to 15 is presented in this endpoint.
Time Frame
Baseline, Week 8
Title
Change From Baseline in ISI at Week 12
Description
The ISI is a 7-item questionnaire which comprises of four 'sleep-related' items and three 'wake-related' items. Each item is rated on a 0-4 scale and the total score ranges from 0 to 28 (higher score suggests more severe insomnia).
Change from baseline in visit-specific ISI is presented in this endpoint.
Level estimated for baseline value of ISI equal to 15 is presented in this endpoint.
Time Frame
Baseline, Week 12
Title
Change From Baseline in Mean Duration of First Undisturbed Sleep Period (FUSP) at Week 1
Description
The FUSP is defined as the time in minutes from the time of going to bed to the time of first nocturnal void, or time of awakening if no void occured.
The duration of FUSP at each visit was calculated as the average over the 3 consecutive 24-hour periods just prior to the respective visit. Adjusted visit-specific mean changes from baseline in FUSP are estimated using a baseline value of 180 (min).
Time Frame
Baseline, Week 1
Title
Change From Baseline in Mean Duration of FUSP at Week 4
Description
The FUSP is defined as the time in minutes from the time of going to bed to the time of first nocturnal void, or time of awakening if no void occurred.
The duration of FUSP at each visit was calculated as the average over the 3 consecutive 24-hour periods just prior to the respective visit. Adjusted visit-specific mean changes from baseline in FUSP are estimated using a baseline value of 180 (min).
Time Frame
Baseline, Week 4
Title
Change From Baseline in Mean Duration of FUSP at Week 8
Description
The FUSP is defined as the time in minutes from the time of going to bed to the time of first nocturnal void, or time of awakening if no void occurred.
The duration of FUSP at each visit was calculated as the average over the 3 consecutive 24-hour periods just prior to the respective visit. Adjusted visit-specific mean changes from baseline in FUSP are estimated using a baseline value of 180 (min).
Time Frame
Baseline, Week 8
Title
Change From Baseline in Mean Duration of FUSP at Week 12
Description
The FUSP is defined as the time in minutes from the time of going to bed to the time of first nocturnal void, or time of awakening if no void occurred.
The duration of FUSP at each visit was calculated as the average over the 3 consecutive 24-hour periods just prior to the respective visit. Adjusted visit-specific mean changes from baseline in FUSP are estimated using a baseline value of 180 (min).
Time Frame
Baseline, Week 12
Title
Change From Baseline in Aggregated Mean Duration of FUSP During 12 Weeks of Treatment
Description
The FUSP is defined as the time in minutes from the time of going to bed to the time of first nocturnal void, or time of awakening if no void occurred.
The visit-specific means were aggregated into a mean of current and preceding visits.
Level estimated for baseline value of mean duration of FUSP (minutes) equal to 180 is presented in this endpoint.
The 95% credibility interval (2.5 and 97.5 percentiles of the posterior distribution) instead of confidence interval is presented for this endpoint.
Time Frame
Baseline, During 12 Weeks of Treatment
Title
Change From Baseline in Nocturnal Diuresis Rate Profiles at Week 1
Description
The nocturnal diuresis rate (mL/min) is calculated as the mean of the nocturnal diuresis for each of the three nights, with the single-night nocturnal diuresis calculated as the ratio of NUV to total time in bed.
Change from baseline in visit-specific mean nocturnal diuresis (mL/min) is presented.
Level estimated for baseline value of mean nocturnal diuresis (mL/min) equal to 1.3 is presented in this endpoint.
Time Frame
Baseline, Week 1
Title
Change From Baseline in Nocturnal Diuresis Rate Profiles at Week 12
Description
The nocturnal diuresis rate (mL/min) is calculated as the mean of the nocturnal diuresis for each of the three nights, with the single-night nocturnal diuresis calculated as the ratio of NUV to total time in bed.
Change from baseline in visit-specific mean nocturnal diuresis (mL/min) is presented.
Level estimated for baseline value of mean nocturnal diuresis (mL/min) equal to 1.3 is presented in this endpoint.
Time Frame
Baseline, Week 12
Title
Change From Baseline in Mean NUV in Week 1
Description
The NUV is defined as the total urine volume from 5 minutes after bedtime with the intention to sleep including the first void within 30 minutes of rising in the morning.
The NUV at each visit was calculated as the average over the 3 consecutive 24-hour periods just prior to the respective visit. Adjusted visit-specific mean changes from baseline in NUV are estimated using a baseline value of 750 (mL).
Time Frame
Baseline, Week 1
Title
Change From Baseline in Mean NUV at Week 12
Description
The NUV is defined as the total urine volume from 5 minutes after bedtime with the intention to sleep including the first void within 30 minutes of rising in the morning.
The NUV at each visit was calculated as the average over the 3 consecutive 24-hour periods just prior to the respective visit. Adjusted visit-specific mean changes from baseline in NUV are estimated using a baseline value of 750 (mL).
Time Frame
Baseline, Week 12
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Adults ≥18 years of age (at the time of written consent)
Medical history of, or subject reported nocturia symptoms during the 6 months prior to Visit 1
≥2 nocturnal voids (an average over 3 days) as documented in the 3-day e-Diary prior to Visit 2
The largest single voided volume must be ≥200 mL (at least 1 void ≥200 mL) as documented in the 3-day e-Diary prior to Visit 2
Nocturnal polyuria, defined as Nocturnal Polyuria index >33%, a ratio of Nocturnal Urine Volume in excess of 33% of total daily (24-hour) urine volume as documented in the 3-day e-Diary prior to Visit 2
≥20% decrease in the nocturnal diuresis rate (mL/min) (that was recorded at Visit 2) as documented in the 3-day e-Diary prior to Visit 3
Exclusion Criteria:
Current diagnosis of Obstructive Sleep Apnoea (OSA)
Restless Legs Syndrome (RLS)
Bladder Outlet Obstruction (BOO) or urine flow <5 mL/s, as confirmed by uroflowmetry upon suspicion during screening prior to Visit 2
Urinary incontinence defined as an average of >1 episode/day in the 3-day e-Diary prior to Visit 2 (occasional urge incontinence during daytime or at night on the way to void is not necessarily exclusionary)
Any pelvic or lower urinary tract surgery and/or radio therapy or previous pelvic irradiation within the past 6 months prior to Visit 1. Including e.g., transurethral resection for Bladder Outlet Obstruction or Benign Prostatic Hyperplasia, hysterectomy or female incontinence procedures
Genito-urinary tract pathology that can in the investigator's opinion be responsible for urgency or urinary incontinence e.g., symptomatic or recurrent urinary tract infections, interstitial cystitis, bladder-related pain, chronic pelvic pain syndrome, or stone in the bladder or urethra causing symptoms
A history of cancer with the last date of disease activity/presence of malignancy within the last 12 months prior to Visit 1, except for adequately treated basal cell carcinoma of the skin
History of any neurological disease affecting bladder function or muscle strength (e.g., Multiple Sclerosis, Parkinson's, spinal cord injury, spina bifida)
Habitual (fluid intake >3L per day) or psychogenic polydipsia
Uncontrolled hypertension, as judged by the investigator
Uncontrolled diabetes mellitus, as judged by the investigator
Central or nephrogenic diabetes insipidus
Known history of Syndrome of Inappropriate Antidiuretic Hormone (SIADH) secretion
History of gastric retention
Suspicion or evidence of congestive heart failure, (New York Heart Association (NYHA) class II, III, IV)
Hyponatraemia:
Serum sodium level <135 mmol/L at Visit 1(re-tested, with results available within 7 days)
Serum sodium level <130 mmol/L at Visit 3 (re-tested, with results available within 7 days)
Use of any prohibited therapy listed below:
Current or former (within 3 months prior to screening) treatment with any other investigational medicinal product (IMP)
Unstable electrostimulation or behavioural bladder training program less than 3 months prior to screening (stable electrostimulation or behavioural bladder training program started at least 3 months before screening are acceptable)
Thiazide diuretics
Antiarrhythmic agents
V2-receptor antagonists/agonists (e.g., vaptans/desmopressin, vasopressin)
Loperamide
Botulinum toxin (cosmetic non-urological use is acceptable)
Valproate
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Global Clinical Compliance
Organizational Affiliation
Ferring Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Achieve Clinical Research, LLC
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35216
Country
United States
Facility Name
Coastal Clinical Research, an AMR company
City
Mobile
State/Province
Alabama
ZIP/Postal Code
36608
Country
United States
Facility Name
Clinical Trials Research
City
Lincoln
State/Province
California
ZIP/Postal Code
95648
Country
United States
Facility Name
Tri Valley Urology Medical Group
City
Murrieta
State/Province
California
ZIP/Postal Code
92562
Country
United States
Facility Name
San Diego Clinical Trials
City
San Diego
State/Province
California
ZIP/Postal Code
92120
Country
United States
Facility Name
Advanced Rx Clinical Research Group, Inc.
City
Westminster
State/Province
California
ZIP/Postal Code
92683
Country
United States
Facility Name
Downtown Women's Health Care
City
Denver
State/Province
Colorado
ZIP/Postal Code
80209
Country
United States
Facility Name
Genitourinary Surgical Consultants, P.C.
City
Denver
State/Province
Colorado
ZIP/Postal Code
80220
Country
United States
Facility Name
South Florida Medical Research
City
Aventura
State/Province
Florida
ZIP/Postal Code
33180
Country
United States
Facility Name
Women's Medical Research Group, LLC
City
Clearwater
State/Province
Florida
ZIP/Postal Code
33759
Country
United States
Facility Name
Tampa Bay Medical Research, Inc.
City
Clearwater
State/Province
Florida
ZIP/Postal Code
33761
Country
United States
Facility Name
Clinical Research of South Florida
City
Coral Gables
State/Province
Florida
ZIP/Postal Code
33134
Country
United States
Facility Name
Avail Clinical Research, LLC
City
DeLand
State/Province
Florida
ZIP/Postal Code
32720
Country
United States
Facility Name
Finlay Medical Research Corp
City
Greenacres City
State/Province
Florida
ZIP/Postal Code
33467
Country
United States
Facility Name
Pharmax Research Clinic
City
Miami
State/Province
Florida
ZIP/Postal Code
33126
Country
United States
Facility Name
Doctors Research Institute Corporation
City
Miami
State/Province
Florida
ZIP/Postal Code
33145
Country
United States
Facility Name
Sanitas Research
City
Miami
State/Province
Florida
ZIP/Postal Code
33155
Country
United States
Facility Name
Bayside Clinical Research LLC
City
New Port Richey
State/Province
Florida
ZIP/Postal Code
34655
Country
United States
Facility Name
Pines Care Research Center, Inc
City
Pembroke Pines
State/Province
Florida
ZIP/Postal Code
33026
Country
United States
Facility Name
Clinical Research Center of Florida
City
Pompano Beach
State/Province
Florida
ZIP/Postal Code
33060
Country
United States
Facility Name
Meridien Research, Inc.
City
Saint Petersburg
State/Province
Florida
ZIP/Postal Code
33709
Country
United States
Facility Name
American Health Network of Indiana, LLC
City
Avon
State/Province
Indiana
ZIP/Postal Code
46123
Country
United States
Facility Name
American Health Network of Indiana, LLC
City
Greenfield
State/Province
Indiana
ZIP/Postal Code
46140
Country
United States
Facility Name
Bay State Clinical Trials, Inc.
City
Watertown
State/Province
Massachusetts
ZIP/Postal Code
02472
Country
United States
Facility Name
Beyer Research
City
Kalamazoo
State/Province
Michigan
ZIP/Postal Code
49009
Country
United States
Facility Name
Remedica LLC
City
Rochester
State/Province
Michigan
ZIP/Postal Code
48307
Country
United States
Facility Name
Quality Clinical Research Center, Inc.
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68114
Country
United States
Facility Name
Clinical Research Consortium, an AMR company
City
Las Vegas
State/Province
Nevada
ZIP/Postal Code
89119-5190
Country
United States
Facility Name
Mid Hudson Medical Research, PLLC
City
New Windsor
State/Province
New York
ZIP/Postal Code
12553
Country
United States
Facility Name
Premier Medical Group of the Hudson Valley, PC
City
Poughkeepsie
State/Province
New York
ZIP/Postal Code
12601
Country
United States
Facility Name
American Health Research, Inc.
City
Charlotte
State/Province
North Carolina
ZIP/Postal Code
28207
Country
United States
Facility Name
Medication Management, LLC
City
Greensboro
State/Province
North Carolina
ZIP/Postal Code
27408
Country
United States
Facility Name
Peters Medical Research
City
High Point
State/Province
North Carolina
ZIP/Postal Code
27262
Country
United States
Facility Name
PMG Research of Raleigh, LLC
City
Raleigh
State/Province
North Carolina
ZIP/Postal Code
27609
Country
United States
Facility Name
PMG Research of Wilmington, LLC
City
Wilmington
State/Province
North Carolina
ZIP/Postal Code
28401
Country
United States
Facility Name
HWC Women's Research Center
City
Englewood
State/Province
Ohio
ZIP/Postal Code
45322
Country
United States
Facility Name
NECCR Primacare Research, LLC
City
Providence
State/Province
Rhode Island
ZIP/Postal Code
02908
Country
United States
Facility Name
Coastal Carolina Research Center, Inc
City
Mount Pleasant
State/Province
South Carolina
ZIP/Postal Code
29464
Country
United States
Facility Name
PMG Research of Charleston, LLC
City
Mount Pleasant
State/Province
South Carolina
ZIP/Postal Code
29464
Country
United States
Facility Name
MCA Research - Partner
City
Houston
State/Province
Texas
ZIP/Postal Code
77079
Country
United States
Facility Name
Ericksen Research & Development, LLC
City
Clinton
State/Province
Utah
ZIP/Postal Code
84015
Country
United States
Facility Name
Advanced Research Institute
City
Ogden
State/Province
Utah
ZIP/Postal Code
84405
Country
United States
Facility Name
Clinical Research Associates of Tidewater, an AMR company
City
Norfolk
State/Province
Virginia
ZIP/Postal Code
23507
Country
United States
Facility Name
ULB Hopital Erasme
City
Bruxelles
Country
Belgium
Facility Name
UZ Antwerpen
City
Edegem
Country
Belgium
Facility Name
Universitair Ziekenhuis Gent
City
Gent
Country
Belgium
Facility Name
AZ Groeninge - Campus Vercruysselaan
City
Kortrijk
Country
Belgium
Facility Name
UZ Leuven
City
Leuven
Country
Belgium
Facility Name
Ultra-Med Inc.
City
Pointe-Claire
State/Province
Quebec
Country
Canada
Facility Name
Milestone Research
City
London
Country
Canada
Facility Name
SKDS Research Inc.
City
Newmarket
Country
Canada
Facility Name
DIEX Recherche Quebec Inc.
City
Quebec
Country
Canada
Facility Name
Clinique Médicale St-Louis (Recherche) inc d/b/a/ Centre de Recherche Saint-Louis
City
Québec
Country
Canada
Facility Name
Bluewater Health-Norman Site
City
Sarnia
Country
Canada
Facility Name
CHUS - Hôpital Fleurimont
City
Sherbrooke
Country
Canada
Facility Name
DIEX Recherche Sherbrooke Inc.
City
Sherbrooke
Country
Canada
Facility Name
Ferring Investigational Site
City
Toronto
Country
Canada
Facility Name
DIEX Recherche Victoriaville Inc.
City
Victoriaville
Country
Canada
Facility Name
Urologie Benešov - Afimed s.r.o.
City
Benešov
Country
Czechia
Facility Name
Fakultni nemocnice Brno, Dept of Klinika nemoci plicnich a tuberkulozy
City
Brno
Country
Czechia
Facility Name
Krajska nemocnice Liberec, a.s.
City
Liberec
Country
Czechia
Facility Name
Urocentrum Plzen
City
Plzen
Country
Czechia
Facility Name
Thomayerova nemocnice, PARENT
City
Praha
Country
Czechia
Facility Name
Gemeinschaftspraxis fuer Urologie und Andrologie
City
Duisburg
Country
Germany
Facility Name
Urologische Gemeinschaftspraxis
City
Emmendingen
Country
Germany
Facility Name
Klinikum Weiden, Klinik f. Urologie, Andrologie und Kinderurologie
City
Weiden
Country
Germany
Facility Name
Jahn Ferenc Del-pesti Korhaz es Rendelointezet
City
Budapest
Country
Hungary
Facility Name
Synexus Magyarorszag Kft.
City
Budapest
Country
Hungary
Facility Name
Bagoly Egeszseghaz
City
Kecskemet
Country
Hungary
Facility Name
SzSzB Megyei Korhazak es Egyetemi Oktatokorhaz, Josa Andras Oktatokorhaz Urologia
City
Nyiregyhaza
Country
Hungary
Facility Name
Jasz-Nagykun-Szolnok Megyei Hetenyi Geza Korhaz-Rendelointezet
City
Szolnok
Country
Hungary
Facility Name
Nasz Lekarz Osrodek Badan Klinicznych
City
Bydgoszcz
Country
Poland
12. IPD Sharing Statement
Citations:
PubMed Identifier
34932192
Citation
Hudgens S, Howerter A, Polek E, Andersson FL. Psychometric validation and interpretation of the Nocturia Impact Diary in a clinical trial setting. Qual Life Res. 2022 Jun;31(6):1837-1848. doi: 10.1007/s11136-021-03060-4. Epub 2021 Dec 21.
Results Reference
background
Learn more about this trial
A Trial to Investigate Efficacy, Safety and Tolerability of FE 201836 for Nocturia Due to Nocturnal Polyuria in Adults
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