Investigation of the Superiority Effect of Orally Disintegrating Desmopressin Tablets to Placebo in Terms of Night Voids Reduction in Nocturia Adult Male Patients

Nocturia Clinical Trial

Official title:

A Multi-centre, Randomised, Double-blind, Placebo-controlled, Parallel-group Trial With an Open-label Extension to Demonstrate the Efficacy and Safety of Desmopressin Orally Disintegrating Tablets for the Treatment of Nocturia in Adult Males

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01262456
• Other study ID #: FE992026 CS41
• Status: Completed
• Phase: Phase 3
• First received: December 15, 2010
• Last updated: September 16, 2015
• Start date: February 2011
• Est. completion date: January 2012

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

The purpose of this trial was to confirm/establish long-term safety and efficacy of desmopressin orally disintegrating tablets at dose levels of 50 μg and 75 μg and to further evaluate the safety of an efficacious higher dose level of 100 μg in males with nocturia.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 395
• Est. completion date: January 2012
• Est. primary completion date: January 2012
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

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

• Male sex 18 years of age or older

• At least 2 voids every night in a consecutive 3-day period during the screening period based on the patient diary.

Exclusion Criteria:

• 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)

• Interstitial Cystitis

• Chronic prostatitis/chronic pelvic pain syndrome

• Suspicion of bladder outlet obstruction (BOO) or a urine flow of less than 5 mL/s as confirmed by uroflowmetry performed after suspicion of BOO

• Surgical treatment, including transurethral resection, for BOO or benign prostatic hyperplasia within the past 6 months

• Urinary retention or a post void residual volume in excess of 250 mL as confirmed by bladder ultrasound performed after suspicion of urinary retention

• Habitual or psychogenic fluid intake resulting in a urine production exceeding 40 mL/kg/24 hours

• Central or nephrogenic diabetes insipidus.

• Syndrome of inappropriate anti-diuretic hormone.

• Current or a history of urologic malignancies e.g. urothelium, prostate, or kidney cancer

• Genitourinary 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

• 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 more than or equal to 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 more than 1.5 mg/dL

• History of obstructive sleep apnea

• Previous desmopressin treatment for nocturia

• Treatment with another investigational product within 3 months prior to screening

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

• Known alcohol or substance abuse

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

• 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 and Research Centre	Barrie	Ontario
Canada	Urology Associates / Urologic Medical Research	Kitchener	Ontario
Canada	Investigational Site	North Bay	Ontario
Canada	Sunnybrook Health Sciences Centre	Toronto	Ontario
Canada	Can-Med Clinical Research, Inc.	Victoria	British Columbia
United States	Radiant Research, Inc.	Akron	Ohio
United States	Hartwell Research Group, LLC	Anderson	South Carolina
United States	Pinnacle Research Group, LLC	Anniston	Alabama
United States	Radiant Research, Inc.	Atlanta	Georgia
United States	South Florida Medical Research	Aventura	Florida
United States	Urologic Consultants of SE PA	Bala Cynwyd	Pennsylvania
United States	Medical University of South Carolina	Charleston	South Carolina
United States	ClinSearch, LLC	Chattanooga	Tennessee
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	Columbus	Ohio
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	Genitourinary Surgical Consultants	Denver	Colorado
United States	Radiant Research, Inc.	Denver	Colorado
United States	Radiant Research, Inc.	Edina	Minnesota
United States	Anderson & Collins Clinical Research Inc.	Edison	New Jersey
United States	Urology Center Research Institute	Englewood	New Jersey
United States	Family Medical Center	Foothill Rance	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	Beyer Research	Kalmazoo	Michigan
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	Advanced Pharma CR, LLC	Miami	Florida
United States	Connecticut Clinical Research Center, LLC	Middlebury	Connecticut
United States	Exemplar Research Inc.	Morgantown	West Virginia
United States	Carolina Urologic Research Center	Myrtle Beach	South Carolina
United States	University Urology Associates	New York	New York
United States	Accelovance	Peoria	Illinois
United States	Penn Urology	Philadelphia	Pennsylvania
United States	DMI Research	Pinellas Park	Florida
United States	Quality Research Incorporated	San Antonio	Texas
United States	Radiant Research, Inc.	San Antonio	Texas
United States	Wilford Hall Medical Center	San Antonio	Texas
United States	Radiant Research, Inc.	Santa Rosa	California
United States	Radiant Research, Inc.	Scottsdale	Arizona
United States	Accelovance	South Bend	Indiana
United States	FutureCare Studies, Inc.	Springfield	Massachusetts
United States	Radiant Research, Inc.	St. Louis	Missouri
United States	Pinellas Urology, Inc	St. Petersburg	Florida
United States	Midtown Medical Center	Tampa	Florida
United States	Premiere Pharmaceutical Research	Tempe	Arizona
United States	Advanced Research Institute, Inc.	Trinity	Florida
United States	Bay State Clinical Trials, Inc.	Watertown	Massachusetts
United States	Front Range Clinical Research, LLC	Wheat Ridge	Colorado

Sponsors (1)

Lead Sponsor	Collaborator
Ferring Pharmaceuticals

Countries where clinical trial is conducted

United States,  Canada, 

References & Publications (1)

Weiss JP, Herschorn S, Albei CD, van der Meulen EA. Efficacy and safety of low dose desmopressin orally disintegrating tablet in men with nocturia: results of a multicenter, randomized, double-blind, placebo controlled, parallel group study. J Urol. 2013 — 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 outcome. Superiority to placebo was to be simultaneously demonstrated on the 2 co-primary outcomes in a step-down approach from highest (75 µg) to lowest dose (50 µg), thereby controlling the family-wise error rate at the 5% nominal significance level.	Day 1 (Baseline), Week 1, Months 1, 2, 3 (3-month double-blind 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 outcome. Superiority to placebo was to be simultaneously demonstrated on the 2 co-primary endpoints in a step-down approach from highest (75 µg) to lowest dose (50 µg), thereby controlling the family-wise error rate at the 5% nominal significance level.	Day 1 (Baseline), Week 1, Months 1, 2, 3 (3-month double-blind treatment period)	No
Secondary	Change From Baseline in Mean Number of Nocturnal Voids at Month 3	Comparison of the mean number of nocturnal voids at baseline and at the 3-month visit. The number of nocturnal voids was the average over 3 consecutive 24-hour periods prior to the relevant visits 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. The active treatment groups were compared to placebo using a step-down approach from highest dose (75 µg) to lowest dose (50 µg).	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. The active treatment groups were compared to placebo using a step-down approach from highest dose (75 µg) to lowest dose (50 µg).	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 the case where there was no nocturnal void. The first morning void was not counted as a 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. The active treatment groups were compared to placebo using a step-down approach from highest dose (75 µg) to lowest dose (50 µg).	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. The active treatment groups were compared to placebo using a step-down approach from highest dose (75 µg) to lowest dose (50 µg).	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. The active treatment groups were compared to placebo using a step-down approach from highest dose (75 µg) to lowest dose (50 µg).	Day 1 (Baseline), Month 3	No
Secondary	Summary of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Double-Blind Period	A TEAE was any adverse event (AE) occurring after start of treatment and within the time of residual drug effect, i.e., within 1 day for desmopressin. An adverse drug reaction (ADR) was any AE assessed by the investigator as possibly or probably related to study drug.	From Day 1 through Month 3 (double-blind period)	Yes
Secondary	Summary of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Open-Label Period	A TEAE was any adverse event (AE) occurring after start of treatment and within the time of residual drug effect, i.e., within 1 day for desmopressin. An adverse drug reaction (ADR) was any AE assessed by the investigator as possibly or probably related to study drug.	Month 1 of open-label period (Month 4 of treatment)	Yes
Secondary	Minimum Post-Treatment Serum Sodium Levels in the Double-Blind Period	Serum sodium levels were monitored at each study visit 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 through Month 3 (double-blind period)	Yes
Secondary	Minimum Post-Treatment Serum Sodium Levels in the Open-Label Period	Serum sodium levels were monitored at each study visit 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.	Month 1 of open-label period (Month 4 of treatment)	Yes