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

Phase 3

Completed

Conditions: Nocturia

Interventions: Drug: Placebo
Drug: Desmopressin

Registration Number: NCT01223937

Lead Sponsor: Ferring Pharmaceuticals

Brief 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: Female

Target Recruitment: 268

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

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
Urinary retention or a post void residual volume in excess of 150 mL as confirmed by bladder ultrasound performed after suspicion of urinary retention
Habitual or psychogenic polydipsia (fluid intake resulting in a urine production exceeding 40 mL/kg/24 hours)
Central or nephrogenic diabetes insipidus
Syndrome of inappropriate anti-diuretic hormone secretion
Current or a history of urologic malignancies e.g. bladder 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 e.g., loop diuretics (furosemide, torsemide, ethacrynic acid) and any other investigational drug
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
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

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Participants took 1 orally disintegrating tablet of placebo every night approximately 1 hour before bedtime for the entire duration of the 3-month treatment period.
Desmopressin 25 μg	Desmopressin	Participants took 1 orally disintegrating tablet of desmopressin 25 μg every night approximately 1 hour before bedtime for the entire duration of the 3-month treatment period.

Primary Outcome Measures

Name	Time	Method
Change From Baseline in Mean Number of Nocturnal Voids Averaged Over a 3-Month Period	Day 1 (Baseline); Week 1, Months 1, 2, 3 (3-month treatment 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.
Adjusted Probability of Participants Achieving a >33% Reduction From Baseline in Number of Nocturnal Voids for All During-Treatment Visits up to Month 3	Day 1 (Baseline); Week 1, Months 1, 2, 3 (3-month treatment period)	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.

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in Mean Number of Nocturnal Voids at Month 3	Day 1 (Baseline), 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.
Adjusted Probability of Participants Achieving a >33% Reduction From Baseline in Number of Nocturnal Voids at Month 3	Day 1 (Baseline), 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.
Change From Baseline in Mean Time to First Nocturnal Void at Month 3	Day 1 (Baseline), 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.
Change From Baseline in Nocturnal Urine Volume at Month 3	Day 1 (Baseline), 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.
Change From Baseline in 24-Hour Urine Volume at Month 3	Day 1 (Baseline), 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.
Summary of Participants With Treatment-Emergent Adverse Events (TEAEs)	Day 1 up to 3 months	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.
Minimum Post-Treatment Serum Sodium Levels	Day 1 up to 3 months	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.

Trial Locations

Locations (37): Medical Affiliated Research Center Inc.
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Huntsville, Alabama, United States
Family Medical Center
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Foothill Ranch, California, United States
Front Range Clinical Research
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Wheatridge, Colorado, United States
Avail Clinical Research, LLC
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DeLand, Florida, United States
Southeastern Institute
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Columbus, Georgia, United States
Sunrise Medical Research
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Lauderdale Lakes, Florida, United States
DMI Research
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Pinellas Park, Florida, United States
FutureCare Studies
🇺🇸
Springfield, Massachusetts, United States
Southeastern Medical Research Institute
🇺🇸
Columbus, Georgia, United States
Remedica, LLC
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Rochester, Michigan, United States
Bay State Clinical Trials, Inc.
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Watertown, Massachusetts, United States
Beyer Research
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Paw Paw, Michigan, United States
Anderson & Collins Clinical Research Inc
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Edison, New Jersey, United States
ACCUMED Research Associates
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Garden City, New York, United States
Center for Urologic Research of WNY, LLC
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Williamsville, New York, United States
Urologic Consultants of SE PA
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Bala Cynwyd, Pennsylvania, United States
Carolina Urologic Research Center
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Myrtle Beach, South Carolina, United States
Urology Associates/Urologic Medical Research
🇨🇦
Kitchener, Ontario, Canada
Radiant Research Inc.
🇺🇸
Dallas, Texas, United States
Axis Clinical Trials
🇺🇸
Los Angeles, California, United States
South Florida Medical Research
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Aventura, Florida, United States
Women's Medical Research Group, LLC
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Clearwater, Florida, United States
FPA Clinical Research
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Kissimmee, Florida, United States
NorthShore University HealthSystem
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Evanston, Illinois, United States
Accelovance
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South Bend, Indiana, United States
Radiant Research, Inc.
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San Antonio, Texas, United States
CanMed Clinical Research Inc.
🇨🇦
Victoria, British Columbia, Canada
Community Research
🇺🇸
Cincinnati, Ohio, United States
Complete HealthCare for Women
🇺🇸
Columbus, Ohio, United States
HWC Women's Research Center
🇺🇸
Englewood, Ohio, United States
Philadelphia Clinical Research, LLC
🇺🇸
Philadelphia, Pennsylvania, United States
Quality Research, Inc.
🇺🇸
San Antonio, Texas, United States
Exemplar Research Inc.
🇺🇸
Morgantown, West Virginia, United States
The Male/Female Health Research Center
🇨🇦
Barrie, Ontario, Canada
Investigational site
🇨🇦
North Bay, Ontario, Canada
Downtown Woman's Health Care
🇺🇸
Denver, Colorado, United States
Radiant Research
🇺🇸
Las Vegas, Nevada, United States