Investigation of the Superiority Effect of Desmopressin to Placebo in Terms of Night Voids Reduction in Nocturia Adult Female Patients

Nocturia Clinical Trial

— COMFORT  

Official title:

A Multi-centre, Randomised, Double-blind, Placebo-controlled, Parallel-group Trial to Demonstrate the Efficacy and Safety of Desmopressin Orally Disintegrating Tablet for the Treatment of Nocturia in Adult Females

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01223937
• Other study ID #: FE992026 CS40
• Status: Completed
• Phase: Phase 3
• First received: October 18, 2010
• Last updated: September 16, 2015
• Start date: November 2010
• Est. completion date: November 2011

Study information

• Verified date: September 2015
• Source: Ferring Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationCanada: Health Canada
• Study type: Interventional

Clinical Trial Summary

A multicenter, randomized, double-blind, placebo-controlled, parallel-group trial to investigate the safety and efficacy of desmopressin oral melt tablets against placebo during 3 months of treatment in adult females with nocturia.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 268
• Est. completion date: November 2011
• Est. primary completion date: November 2011
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Written informed consent prior to performance of any trial-related activity

• Female sex 18 years of age or older

• At least 2 voids every night in a consecutive 3-day period during the screening period

Exclusion Criteria:

1. Evidence of severe daytime voiding dysfunction defined as:

• Urge urinary incontinence (more than 1 episode/day in the 3-day diary period)

• Urgency (more than 1 episode/day in the 3-day diary period)

• Frequency (more than 8 daytime voids/day in the 3-day diary period)

2. Interstitial cystitis

3. Urinary retention or a post void residual volume in excess of 150 mL as confirmed by bladder ultrasound performed after suspicion of urinary retention

4. Habitual or psychogenic polydipsia (fluid intake resulting in a urine production exceeding 40 mL/kg/24 hours)

5. Central or nephrogenic diabetes insipidus

6. Syndrome of inappropriate anti-diuretic hormone secretion

7. Current or a history of urologic malignancies e.g. bladder cancer

8. Genitourinary tract pathology e.g., infection or stone in the bladder and urethra causing symptoms

9. Neurogenic detrusor activity (detrusor overactivity).

10. Suspicion or evidence of cardiac failure

11. Uncontrolled hypertension

12. Uncontrolled diabetes mellitus

13. Hyponatraemia: Serum sodium level must be within normal limits

14. Renal insufficiency: Serum creatinine must be within normal limits and estimated glomerular filtration rate must be more than or equal to 50 mL/min

15. 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 more than 1.5 mg/dL

16. History of obstructive sleep apnea

17. Previous desmopressin treatment for nocturia

18. Treatment with another investigational product within 3 months prior to screening

19. Concomitant treatment with any prohibited medication e.g., loop diuretics (furosemide, torsemide, ethacrynic acid) and any other investigational drug

20. Pregnancy, breastfeeding, or a plan to become pregnant during the period of the clinical trial. Subjects of reproductive age must have documentation of a reliable method of contraception. All pre-and perimenopausal subjects have to perform pregnancy tests. Amenorrhea of more than 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

21. Known alcohol or substance abuse

22. Work or lifestyle that may interfere with regular nighttime sleep e.g., shift workers

23. Any other medical condition, laboratory abnormality, psychiatric condition, mental incapacity, or language barrier that, in the judgment of the Investigator, would impair participation in the trial

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Nocturia

Intervention

Drug:
• Desmopressin

• Placebo

Locations

Country	Name	City	State
Canada	The Male/Female Health Research Center	Barrie	Ontario
Canada	Urology Associates/Urologic Medical Research	Kitchener	Ontario
Canada	Investigational site	North Bay	Ontario
Canada	CanMed Clinical Research Inc.	Victoria	British Columbia
United States	Radiant Research, Inc.	Akron	Ohio
United States	South Florida Medical Research	Aventura	Florida
United States	Urologic Consultants of SE PA	Bala Cynwyd	Pennsylvania
United States	Radiant Research Inc.	Chicago	Illinois
United States	Community Research	Cincinnati	Ohio
United States	Women's Medical Research Group, LLC	Clearwater	Florida
United States	Complete HealthCare for Women	Columbus	Ohio
United States	Southeastern Institute	Columbus	Georgia
United States	Southeastern Medical Research Institute	Columbus	Georgia
United States	Radiant Research Inc.	Dallas	Texas
United States	Avail Clinical Research, LLC	DeLand	Florida
United States	Downtown Woman's Health Care	Denver	Colorado
United States	Radiant Research, Inc.	Edina	Minnesota
United States	Anderson & Collins Clinical Research Inc	Edison	New Jersey
United States	HWC Women's Research Center	Englewood	Ohio
United States	NorthShore University HealthSystem	Evanston	Illinois
United States	Family Medical Center	Foothill Ranch	California
United States	ACCUMED Research Associates	Garden City	New York
United States	Radiant Research, Inc.	Greer	South Carolina
United States	Medical Affiliated Research Center Inc.	Huntsville	Alabama
United States	FPA Clinical Research	Kissimmee	Florida
United States	Radiant Research	Las Vegas	Nevada
United States	Sunrise Medical Research	Lauderdale Lakes	Florida
United States	Axis Clinical Trials	Los Angeles	California
United States	Exemplar Research Inc.	Morgantown	West Virginia
United States	Carolina Urologic Research Center	Myrtle Beach	South Carolina
United States	Beyer Research	Paw Paw	Michigan
United States	Accelovance	Peoria	Illinois
United States	Philadelphia Clinical Research, LLC	Philadelphia	Pennsylvania
United States	DMI Research	Pinellas Park	Florida
United States	Remedica, LLC	Rochester	Michigan
United States	Quality Research, Inc.	San Antonio	Texas
United States	Radiant Research, Inc.	San Antonio	Texas
United States	Radiant Research Inc.	Santa Rosa	California
United States	Radiant Research Inc.	Scottsdale	Arkansas
United States	Accelovance	South Bend	Indiana
United States	FutureCare Studies	Springfield	Massachusetts
United States	Radiant Research, Inc.	St. Louis	Missouri
United States	Bay State Clinical Trials, Inc.	Watertown	Massachusetts
United States	Front Range Clinical Research	Wheatridge	Colorado
United States	Center for Urologic Research of WNY, LLC	Williamsville	New York

Sponsors (1)

Lead Sponsor	Collaborator
Ferring Pharmaceuticals

Countries where clinical trial is conducted

United States,  Canada, 

References & Publications (1)

Sand PK, Dmochowski RR, Reddy J, van der Meulen EA. Efficacy and safety of low dose desmopressin orally disintegrating tablet in women with nocturia: results of a multicenter, randomized, double-blind, placebo controlled, parallel group study. J Urol. 201 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in Mean Number of Nocturnal Voids Averaged Over a 3-Month Period	The number of nocturnal voids was the average over 3 consecutive 24-hour periods prior to Day 1 and prior to the during-treatment visits (Week 1, Months 1, 2, 3) as recorded in participant diaries. The first morning void was not counted as a nocturnal void. Change from baseline values for Week 1, and Months 1, 2 and 3 are reported below.; Comparison of the mean number of nocturnal voids at baseline and over a 3-month treatment period (obtained by longitudinal analysis of Week 1, and Months 1, 2 and 3) are reported in the statistical analysis. This was the first co-primary endpoint. The trial was to be declared positive only if the 25 µg desmopressin group had a statistically significant positive effect as compared to placebo on both co-primary endpoints.	Day 1 (Baseline); Week 1, Months 1, 2, 3 (3-month treatment period)	No
Primary	Adjusted Probability of Participants Achieving a >33% Reduction From Baseline in Number of Nocturnal Voids for All During-Treatment Visits up to Month 3	Probability of participants achieving 33% responder status during 3 months of treatment employed a longitudinal analysis assessing nocturnal void information captured in the 3-day diary. A 33% responder was defined as a participant with a decrease of at least 33% in the mean number of nocturnal voids relative to baseline. The number of nocturnal voids was the average over 3 consecutive 24-hour periods prior to Day 1 and prior to the during treatment visits (Week 1, Months 1, 2, 3) as recorded in participant diaries. The first morning void was not counted as a nocturnal void.; This was the second co-primary endpoint. The trial was to be declared positive only if the 25 µg desmopressin group had a statistically significant positive effect as compared to placebo on both co-primary endpoints.	Day 1 (Baseline); Week 1, Months 1, 2, 3 (3-month treatment period)	No
Secondary	Change From Baseline in Mean Number of Nocturnal Voids at Month 3	The number of nocturnal voids was the average over 3 consecutive 24-hour periods prior to Day 1 and prior to the during-treatment visits (Month 3 for this outcome) as recorded in participant diaries. The first morning void was not counted as a nocturnal void.; Secondary efficacy outcomes (#3-7) used a hierarchical step-down approach in the order listed.	Day 1 (Baseline), Month 3	No
Secondary	Adjusted Probability of Participants Achieving a >33% Reduction From Baseline in Number of Nocturnal Voids at Month 3	Probability of participants achieving 33% responder status at Month 3 employed a longitudinal analysis assessing nocturnal void information captured in the 3-day diary. A 33% responder was defined as a participant with a decrease of at least 33% in the mean number of nocturnal voids relative to baseline. The number of nocturnal voids was the average over 3 consecutive 24-hour periods prior to Day 1 and prior to the Month 3 visit as recorded in participant diaries. The first morning void was not counted as a nocturnal void.; The secondary efficacy outcomes (#3-7) used a hierarchical step-down approach in the order listed.	Day 1 (Baseline), Month 3	No
Secondary	Change From Baseline in Mean Time to First Nocturnal Void at Month 3	The time to first void was defined as the time from going to bed with the intention of sleeping until first nocturnal void or until waking in the morning in cases where there was no nocturnal void. The time to first void was derived from the sleep and voiding diary. The mean time to first void was calculated as the average over 3 consecutive 24-hour periods prior to the Month 3 visit.; The secondary efficacy outcomes (#3-7) used a hierarchical step-down approach in the order listed.	Day 1 (Baseline), Month 3	No
Secondary	Change From Baseline in Nocturnal Urine Volume at Month 3	The nocturnal urine volume was derived from the 3-day urine volume diary. The nocturnal urine volume included the volume of the first morning void. Mean urine volumes were calculated as the average over 3 consecutive 24-hour periods prior to the Month 3 visit.; The secondary efficacy outcomes (#3-7) used a hierarchical step-down approach in the order listed.	Day 1 (Baseline), Month 3	No
Secondary	Change From Baseline in 24-Hour Urine Volume at Month 3	Twenty-four hour urine volume was derived from the 3-day urine volume diary. Mean urine volumes were calculated as the average over 3 consecutive 24-hour periods prior to the Month 3 visit.; The secondary efficacy outcomes (#3-7) used a hierarchical step-down approach in the order listed.	Day 1 (Baseline), Month 3	No
Secondary	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 1 day of the last dose of desmopressin. An adverse drug reaction (ADR) was any AE assessed by the Investigator as possibly/probably related to study drug.	Day 1 up to 3 months	Yes
Secondary	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. The serum sodium level must have been within the normal reference range at the Screening Visit for the participant to be eligible for enrollment. A participant was to be withdrawn from the trial if the serum sodium level was <=125 mmol/L at any time.	Day 1 up to 3 months	Yes