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
Trial Snapshot
- Phase
- Phase 3
- Status
- Completed
- Sponsor
- Ferring Pharmaceuticals
- Enrollment
- 268
- Locations
- 37
- Primary Endpoint
- Change From Baseline in Mean Number of Nocturnal Voids Averaged Over a 3-Month Period
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Double (Participant, Investigator)
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- Female
- Accepts Healthy Volunteers
- No
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
Arms & Interventions
Desmopressin 25 μg
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.
Intervention: Desmopressin (Drug)
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.
Intervention: Placebo (Drug)
Outcomes
Primary Outcomes
Change From Baseline in Mean Number of Nocturnal Voids Averaged Over a 3-Month Period
Time Frame: 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
Time Frame: 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 Outcomes
- Change From Baseline in Mean Number of Nocturnal Voids at Month 3(Day 1 (Baseline), Month 3)
- Adjusted Probability of Participants Achieving a >33% Reduction From Baseline in Number of Nocturnal Voids at Month 3(Day 1 (Baseline), Month 3)
- Change From Baseline in Mean Time to First Nocturnal Void at Month 3(Day 1 (Baseline), Month 3)
- Change From Baseline in Nocturnal Urine Volume at Month 3(Day 1 (Baseline), Month 3)
- Change From Baseline in 24-Hour Urine Volume at Month 3(Day 1 (Baseline), Month 3)
- Summary of Participants With Treatment-Emergent Adverse Events (TEAEs)(Day 1 up to 3 months)
- Minimum Post-Treatment Serum Sodium Levels(Day 1 up to 3 months)