Back to resultsStudy Investigating the Impact Burden of Nocturia Using the Nocturia Impact Diary (IMPACT)
Primary Purpose
Nocturia
Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Desmopressin
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Nocturia
Eligibility Criteria
Inclusion Criteria:
- Written informed consent prior to performance of any study-related activity
- 18 years of age (at the time of written consent) or older
- Previous participation in FE992026 CS40 or FE992026 CS41 with a completion ≥ 30 days prior to Screening. The subject should have responded to active treatment during FE992026 CS40 or FE992026 CS41 or if he/she received placebo during these two studies he/she should have been a non-responder.
- At least two nocturnal voids every night in two consecutive 3-day periods during the screening period (as determined by the two night-time voiding diaries dispensed at Visit 1 and collected at Visit 2)
Exclusion Criteria:
- Chronic prostatitis (males)/chronic pelvic pain syndrome (CPPS)
- Suspicion of bladder outlet obstruction (BOO) or a urine flow of < 5 mL/s as confirmed by uroflowmetry performed after suspicion of BOO
- Surgical treatment, including transurethral resection, for BOO or benign prostatic hyperplasia (males) within the past six months
- Urinary retention or a post void residual volume > 150 mL for females and > 250 mL for males as confirmed by bladder ultrasound performed after suspicion of urinary retention
- Central or nephrogenic diabetes insipidus
- Syndrome of inappropriate antidiuretic hormone
- Current or a history of urologic malignancies e.g. bladder cancer
- Genito-urinary tract pathology e.g. infection or stone in the bladder and urethra causing symptoms
- Neurogenic detrusor activity (detrusor overactivity)
- Suspicion or evidence of cardiac failure
- Chronic prostatitis (males)/chronic pelvic pain syndrome (CPPS)
- Uncontrolled hypertension
- Uncontrolled diabetes mellitus
- Hyponatraemia: serum sodium level must be within normal limits
- Renal insufficiency: Serum creatinine must be within normal limits and estimated glomerular filtration rate must be ≥ 50 mL/min
- Hepatic and/or biliary diseases: Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) levels must not be more than twice the upper limit of normal range. Total bilirubin level must not be > 1.5 mg/dL
- History of obstructive sleep apnea
- Treatment with another investigational product (except desmopressin) within three months prior to screening and throughout the study
- Concomitant treatment with loop diuretics (furosemide, torsemide, ethacrynic acid)
- Pregnancy, breastfeeding, or an intention of becoming pregnant during the period of the clinical study. Female subjects of reproductive age must have documentation of a reliable method of contraception. All pre-and perimenopausal female subjects have to perform pregnancy tests. Amenorrhea of > 12 months duration based on the reported date of the last menstrual period is sufficient documentation of post-menopausal status and does not require a pregnancy test
- Known alcohol or substance abuse
- Work or lifestyle that may interfere with regular night-time sleep e.g. shiftworkers 23. Any other medical condition, laboratory abnormality, psychiatric condition, mental incapacity, or language barrier which, in the judgment of the Investigator, would impair participation in the study
Sites / Locations
- South Florida Medical Research
- Avail Clinical Research, LLC
- Accelovance
- DM Clinical Research
- Beyer Research
- Remedica LLC
- Accumed Research Associates
- Radiant Research, Inc.
- Quality Research, Inc.
- Radiant Research, Inc.
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Placebo Comparator
Experimental
Placebo Comparator
Arm Label
Female - Desmopressin 25 μg
Female - Placebo
Male - Desmopressin 75 μg
Male - Placebo
Arm Description
Female participants took 1 tablet of 25 μg every night, approximately 1 hour prior to bedtime (with the intention to sleep), for a period of 1 month.
Female participants took 1 tablet of placebo every night, approximately 1 hour prior to bedtime (with the intention to sleep), for a period of 1 month.
Male participants took 1 tablet 75 μg every night, approximately 1 hour prior to bedtime (with the intention to sleep), for a period of 1 month.
Male participants took 1 tablet of placebo every night, approximately 1 hour prior to bedtime (with the intention to sleep), for a period of 1 month.
Outcomes
Primary Outcome Measures
The Pearson Correlation Coefficient Between Change From Baseline to Month 1 in Number of Nocturnal Voids and Change From Baseline to Month 1 in Nocturia Impact (NI) Diary Total Score
This outcome is a measure of sensitivity of the NI Diary to change in nocturia.
The NI Diary is a 12-item instrument consisting of 11 core items and an overall impact question (Q12). Responses are scored from 0 (no impact) to 4 (highest impact); a lowering of score equals a decrease in impact caused by nocturia. The NI total score is the sum of the 11 core items scores. The NI total score was analyzable only if all 11 items (Q1-Q11) had non-missing responses. Otherwise, it was defined as missing. Missing values were not imputed. The average over the 3-day diary period prior to baseline (Day 1) and Month 1 was used for the overall impact score.
The correlation was estimated using Fisher's z transformation, i.e. the NI total score was based on a standardized scale from 0 (lowest impact) to 100 (highest impact).
Corresponding adjusted partial correlation coefficients were based on adjustments for mean number of Baseline voids, Baseline NI total score, age, and gender.
Difference in Mean Change From Baseline to Month 1 in Nocturia Impact (NI) Total Scores and Overall Impact Question for Responders and Non-Responders
This outcome is a measure of sensitivity of the NI Diary to change in nocturia.
The NI Diary is a 12-item instrument consisting of 11 core items and an overall impact question (Q12). The NI total score is defined as the sum of the 11 core items scores.
The overall impact question (Q12) and the NI total score were transformed using Fisher's z transformation, i.e. the scores were based on a standardized scale from 0 (lowest impact) to 100 (highest impact).
The difference in mean change in NI total score for subjects who experienced a reduction from baseline of <33% in nocturnal voids at the Month 1 visit (non-responders) versus those with a reduction in nocturnal voids from Baseline of ≥33% (responders) was estimated.
Cohen's D Effect Size in Responsiveness in the Nocturia Impact (NI) Total Scores and Overall Impact Question as Measured From Baseline (Day 1) to Month 1
The responsiveness of the NI Diary was measured with Cohen's D effect size. The effect size was calculated for active treatment versus placebo, based on change from Baseline to Month 1. The effect size was evaluated as "small," "medium," or "large" if D was <=0.35, >0.35 - 0.65, or >0.65, respectively.
Mean values are the Cohen's D effect size. Standard deviation is the pooled standard deviation.
Secondary Outcome Measures
Internal Consistency of the Nocturia Impact (NI) Total Score for Each Day NI Diaries Were Completed Assessed as Cronbach's Alpha Values
Cronbach's alpha (CA) is a measure of the internal consistency of the Nocturia Impact (NI) Total scores. Higher scores indicate a more reliable (precise) instrument. A value of 0.70 set as the benchmark for declaring the scale as internally consistent.
Cronbach's alpha was assessed for each of the three consecutive days NI diaries were completed during screening (Day -20 to Day -18), baseline (Day -2 to Day 1) and Month 1 (Day 28 to Day 30).
Construct Validity For the Nocturia Impact (NI) Total Scores and Overall Impact Question (Q12) for Participants With High/Low Number of Nocturnal Voids
The known group validity was assessed by comparing participants who experienced ≥3 nocturnal voids to those who experienced <3 nocturnal voids, using the average over 3 days for the Screening and Baseline diaries. Results are reported for the NI Total Scores and the Overall Impact Question (Q12).
The NI Diary is a 12-item instrument consisting of 11 core items and an overall impact question (Q12). The NI total score is defined as the sum of the 11 core items scores.
The overall impact question (Q12) and the NI total score were transformed using Fisher's z transformation, i.e. the scores were based on a standardized scale from 0 (lowest impact) to 100 (highest impact).
Change From Baseline to Month 1 on Nocturia Impact (NI) Total Score
The NI Diary is a 12-item instrument consisting of 11 core items and an overall impact question (Q12). Responses are scored from 0 (no impact) to 4 (highest impact); the NI total score is the sum of the 11 core items scores (range of 0-44) which is then transformed to a 0-100 scale (high score indicates high impact). The NI total score was analyzable only if all 11 items (Q1-Q11) had non-missing responses. Otherwise, it was defined as missing. Missing values were not imputed. The average over the 3-day diary period prior to baseline (Day 1) and Month 1 was used for the overall impact score. Negative change from baseline scores indicate a decrease in impact caused by nocturia.
Minimum Post-Treatment Serum Sodium Levels
Serum sodium levels were monitored since hyponatremia is a potential serious adverse event associated with daily doses of desmopressin. A participant was to be withdrawn from the trial if the serum sodium level was <=125 mmol/L at any time.
Summary of Participants With Treatment-Emergent Adverse Events (TEAEs)
A TEAE was any adverse event occurring after start of treatment and within the time of residual drug effect, i.e. within one day of the last dose of desmopressin.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01552343
Brief Title
Study Investigating the Impact Burden of Nocturia Using the Nocturia Impact Diary
Acronym
IMPACT
Official Title
A Double-blind, Randomized, Placebo-controlled Study Investigating the Impact Burden of Nocturia Using the Nocturia Impact Diary
Study Type
Interventional
2. Study Status
Record Verification Date
June 2017
Overall Recruitment Status
Completed
Study Start Date
March 2012 (undefined)
Primary Completion Date
May 2012 (Actual)
Study Completion Date
June 2012 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Ferring Pharmaceuticals
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of this study is to assess psychometric properties (reliability and validity) of the Nocturia Impact (NI) diary.
To assess the association between reduction of number of nocturnal voids and the mean changes in NI scores (sensitivity of the NI total score to change in nocturia).
To assess which NI diary items account for the main difference in change in total NI score in treatment versus placebo.
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 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
56 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Female - Desmopressin 25 μg
Arm Type
Experimental
Arm Description
Female participants took 1 tablet of 25 μg every night, approximately 1 hour prior to bedtime (with the intention to sleep), for a period of 1 month.
Arm Title
Female - Placebo
Arm Type
Placebo Comparator
Arm Description
Female participants took 1 tablet of placebo every night, approximately 1 hour prior to bedtime (with the intention to sleep), for a period of 1 month.
Arm Title
Male - Desmopressin 75 μg
Arm Type
Experimental
Arm Description
Male participants took 1 tablet 75 μg every night, approximately 1 hour prior to bedtime (with the intention to sleep), for a period of 1 month.
Arm Title
Male - Placebo
Arm Type
Placebo Comparator
Arm Description
Male participants took 1 tablet of placebo every night, approximately 1 hour prior to bedtime (with the intention to sleep), for a period of 1 month.
Intervention Type
Drug
Intervention Name(s)
Desmopressin
Other Intervention Name(s)
FE992026, MINIRIN®, Nocturin®
Intervention Description
Desmopressin orally disintegrating tablets. Female participants took a 25 μg tablet and male participants took a 75 μg tablet one hour prior to bedtime for one month.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo to match the 25 μg tablet of active drug taken by female participants or the 75 μg tablet taken by males. One placebo tablet taken one hour prior to bedtime for one month.
Primary Outcome Measure Information:
Title
The Pearson Correlation Coefficient Between Change From Baseline to Month 1 in Number of Nocturnal Voids and Change From Baseline to Month 1 in Nocturia Impact (NI) Diary Total Score
Description
This outcome is a measure of sensitivity of the NI Diary to change in nocturia.
The NI Diary is a 12-item instrument consisting of 11 core items and an overall impact question (Q12). Responses are scored from 0 (no impact) to 4 (highest impact); a lowering of score equals a decrease in impact caused by nocturia. The NI total score is the sum of the 11 core items scores. The NI total score was analyzable only if all 11 items (Q1-Q11) had non-missing responses. Otherwise, it was defined as missing. Missing values were not imputed. The average over the 3-day diary period prior to baseline (Day 1) and Month 1 was used for the overall impact score.
The correlation was estimated using Fisher's z transformation, i.e. the NI total score was based on a standardized scale from 0 (lowest impact) to 100 (highest impact).
Corresponding adjusted partial correlation coefficients were based on adjustments for mean number of Baseline voids, Baseline NI total score, age, and gender.
Time Frame
Day 1 (Baseline), Month 1
Title
Difference in Mean Change From Baseline to Month 1 in Nocturia Impact (NI) Total Scores and Overall Impact Question for Responders and Non-Responders
Description
This outcome is a measure of sensitivity of the NI Diary to change in nocturia.
The NI Diary is a 12-item instrument consisting of 11 core items and an overall impact question (Q12). The NI total score is defined as the sum of the 11 core items scores.
The overall impact question (Q12) and the NI total score were transformed using Fisher's z transformation, i.e. the scores were based on a standardized scale from 0 (lowest impact) to 100 (highest impact).
The difference in mean change in NI total score for subjects who experienced a reduction from baseline of <33% in nocturnal voids at the Month 1 visit (non-responders) versus those with a reduction in nocturnal voids from Baseline of ≥33% (responders) was estimated.
Time Frame
Day 1 (Baseline), Month 1
Title
Cohen's D Effect Size in Responsiveness in the Nocturia Impact (NI) Total Scores and Overall Impact Question as Measured From Baseline (Day 1) to Month 1
Description
The responsiveness of the NI Diary was measured with Cohen's D effect size. The effect size was calculated for active treatment versus placebo, based on change from Baseline to Month 1. The effect size was evaluated as "small," "medium," or "large" if D was <=0.35, >0.35 - 0.65, or >0.65, respectively.
Mean values are the Cohen's D effect size. Standard deviation is the pooled standard deviation.
Time Frame
Day 1 (Baseline), Month 1
Secondary Outcome Measure Information:
Title
Internal Consistency of the Nocturia Impact (NI) Total Score for Each Day NI Diaries Were Completed Assessed as Cronbach's Alpha Values
Description
Cronbach's alpha (CA) is a measure of the internal consistency of the Nocturia Impact (NI) Total scores. Higher scores indicate a more reliable (precise) instrument. A value of 0.70 set as the benchmark for declaring the scale as internally consistent.
Cronbach's alpha was assessed for each of the three consecutive days NI diaries were completed during screening (Day -20 to Day -18), baseline (Day -2 to Day 1) and Month 1 (Day 28 to Day 30).
Time Frame
Screening (Day -20 to Day -18), Baseline (Day -2 to Day 1) and Treatment (Day 28 to Day 30)
Title
Construct Validity For the Nocturia Impact (NI) Total Scores and Overall Impact Question (Q12) for Participants With High/Low Number of Nocturnal Voids
Description
The known group validity was assessed by comparing participants who experienced ≥3 nocturnal voids to those who experienced <3 nocturnal voids, using the average over 3 days for the Screening and Baseline diaries. Results are reported for the NI Total Scores and the Overall Impact Question (Q12).
The NI Diary is a 12-item instrument consisting of 11 core items and an overall impact question (Q12). The NI total score is defined as the sum of the 11 core items scores.
The overall impact question (Q12) and the NI total score were transformed using Fisher's z transformation, i.e. the scores were based on a standardized scale from 0 (lowest impact) to 100 (highest impact).
Time Frame
Screening (Day -20), Baseline (Day 1)
Title
Change From Baseline to Month 1 on Nocturia Impact (NI) Total Score
Description
The NI Diary is a 12-item instrument consisting of 11 core items and an overall impact question (Q12). Responses are scored from 0 (no impact) to 4 (highest impact); the NI total score is the sum of the 11 core items scores (range of 0-44) which is then transformed to a 0-100 scale (high score indicates high impact). The NI total score was analyzable only if all 11 items (Q1-Q11) had non-missing responses. Otherwise, it was defined as missing. Missing values were not imputed. The average over the 3-day diary period prior to baseline (Day 1) and Month 1 was used for the overall impact score. Negative change from baseline scores indicate a decrease in impact caused by nocturia.
Time Frame
Baseline (Day -2 to Day 1), Treatment (Day 28-30)
Title
Minimum Post-Treatment Serum Sodium Levels
Description
Serum sodium levels were monitored since hyponatremia is a potential serious adverse event associated with daily doses of desmopressin. A participant was to be withdrawn from the trial if the serum sodium level was <=125 mmol/L at any time.
Time Frame
Day 1 up to 1 month
Title
Summary of Participants With Treatment-Emergent Adverse Events (TEAEs)
Description
A TEAE was any adverse event occurring after start of treatment and within the time of residual drug effect, i.e. within one day of the last dose of desmopressin.
Time Frame
Day 1 up to 1 month
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Written informed consent prior to performance of any study-related activity
18 years of age (at the time of written consent) or older
Previous participation in FE992026 CS40 or FE992026 CS41 with a completion ≥ 30 days prior to Screening. The subject should have responded to active treatment during FE992026 CS40 or FE992026 CS41 or if he/she received placebo during these two studies he/she should have been a non-responder.
At least two nocturnal voids every night in two consecutive 3-day periods during the screening period (as determined by the two night-time voiding diaries dispensed at Visit 1 and collected at Visit 2)
Exclusion Criteria:
Chronic prostatitis (males)/chronic pelvic pain syndrome (CPPS)
Suspicion of bladder outlet obstruction (BOO) or a urine flow of < 5 mL/s as confirmed by uroflowmetry performed after suspicion of BOO
Surgical treatment, including transurethral resection, for BOO or benign prostatic hyperplasia (males) within the past six months
Urinary retention or a post void residual volume > 150 mL for females and > 250 mL for males as confirmed by bladder ultrasound performed after suspicion of urinary retention
Central or nephrogenic diabetes insipidus
Syndrome of inappropriate antidiuretic hormone
Current or a history of urologic malignancies e.g. bladder cancer
Genito-urinary tract pathology e.g. infection or stone in the bladder and urethra causing symptoms
Neurogenic detrusor activity (detrusor overactivity)
Suspicion or evidence of cardiac failure
Chronic prostatitis (males)/chronic pelvic pain syndrome (CPPS)
Uncontrolled hypertension
Uncontrolled diabetes mellitus
Hyponatraemia: serum sodium level must be within normal limits
Renal insufficiency: Serum creatinine must be within normal limits and estimated glomerular filtration rate must be ≥ 50 mL/min
Hepatic and/or biliary diseases: Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) levels must not be more than twice the upper limit of normal range. Total bilirubin level must not be > 1.5 mg/dL
History of obstructive sleep apnea
Treatment with another investigational product (except desmopressin) within three months prior to screening and throughout the study
Concomitant treatment with loop diuretics (furosemide, torsemide, ethacrynic acid)
Pregnancy, breastfeeding, or an intention of becoming pregnant during the period of the clinical study. Female subjects of reproductive age must have documentation of a reliable method of contraception. All pre-and perimenopausal female subjects have to perform pregnancy tests. Amenorrhea of > 12 months duration based on the reported date of the last menstrual period is sufficient documentation of post-menopausal status and does not require a pregnancy test
Known alcohol or substance abuse
Work or lifestyle that may interfere with regular night-time sleep e.g. shiftworkers 23. Any other medical condition, laboratory abnormality, psychiatric condition, mental incapacity, or language barrier which, in the judgment of the Investigator, would impair participation in the study
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Development Support
Organizational Affiliation
Ferring Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
South Florida Medical Research
City
Aventura
State/Province
Florida
Country
United States
Facility Name
Avail Clinical Research, LLC
City
DeLand
State/Province
Florida
Country
United States
Facility Name
Accelovance
City
Peoria
State/Province
Illinois
Country
United States
Facility Name
DM Clinical Research
City
Springfield
State/Province
Massachusetts
Country
United States
Facility Name
Beyer Research
City
Kalamazoo
State/Province
Michigan
Country
United States
Facility Name
Remedica LLC
City
Rochester
State/Province
Michigan
Country
United States
Facility Name
Accumed Research Associates
City
Garden City
State/Province
New York
Country
United States
Facility Name
Radiant Research, Inc.
City
Greer
State/Province
South Carolina
Country
United States
Facility Name
Quality Research, Inc.
City
San Antonio
State/Province
Texas
Country
United States
Facility Name
Radiant Research, Inc.
City
San Antonio
State/Province
Texas
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
25236993
Citation
Holm-Larsen T, Andersson F, van der Meulen E, Yankov V, Rosen RC, Norgaard JP. The Nocturia Impact Diary: a self-reported impact measure to complement the voiding diary. Value Health. 2014 Sep;17(6):696-706. doi: 10.1016/j.jval.2014.06.007. Epub 2014 Aug 20.
Results Reference
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Study Investigating the Impact Burden of Nocturia Using the Nocturia Impact Diary
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