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

Ferring Pharmaceuticals395 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

395

Conditions

Nocturia

Interventions

DesmopressinDRUG

PlaceboDRUG

Eligibility

Sex: MALEMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (56)

Outcomes

Primary Outcomes

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.

Time frame: Day 1 (Baseline), Week 1, Months 1, 2, 3 (3-month double-blind treatment period)

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.

Time frame: Day 1 (Baseline), Week 1, Months 1, 2, 3 (3-month double-blind treatment period)

Secondary Outcomes

Change From Baseline in Mean Number of Nocturnal Voids at Month 3

Data from ClinicalTrials.gov

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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).