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
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 395
- 试验地点
- 46
- 主要终点
- Change From Baseline in Mean Number of Nocturnal Voids Averaged Over a 3-Month Period
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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
研究组 & 干预措施
Desmopressin 50 μg Double-Blind / 100 μg Open-Label
Participants took 1 orally disintegrating tablet of desmopressin 50 μg every night approximately 1 hour prior to bedtime for the entire duration of the 3-month double-blind treatment period. Participants completing the double-blind period were switched to desmopressin 100 μg for the 1-month open-label extension period.
干预措施: Desmopressin (Drug)
Desmopressin 75 μg Double-Blind / 100 μg Open-Label
Participants took 1 orally disintegrating tablet of desmopressin 75 μg every night approximately 1 hour prior to bedtime for the entire duration of the 3-month double-blind treatment period. Participants completing the double-blind period were switched to desmopressin 100 μg for the 1-month open-label extension period.
干预措施: Desmopressin (Drug)
Placebo Double-Blind / Desmopressin 100 μg Open-Label
Participants took 1 orally disintegrating tablet of placebo every night approximately 1 hour prior to bedtime for the entire duration of the 3-month double-blind treatment period. Participants completing the double-blind period were switched to desmopressin 100 μg for the 1-month open-label extension period.
干预措施: Desmopressin (Drug)
Placebo Double-Blind / Desmopressin 100 μg Open-Label
Participants took 1 orally disintegrating tablet of placebo every night approximately 1 hour prior to bedtime for the entire duration of the 3-month double-blind treatment period. Participants completing the double-blind period were switched to desmopressin 100 μg for the 1-month open-label extension period.
干预措施: Placebo (Drug)
结局指标
主要结局
Change From Baseline in Mean Number of Nocturnal Voids Averaged Over a 3-Month Period
时间窗: Day 1 (Baseline), Week 1, Months 1, 2, 3 (3-month double-blind 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 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.
Adjusted Probability of Participants Achieving a >33% Reduction From Baseline in Number of Nocturnal Voids for All During-Treatment Visits up to Month 3
时间窗: Day 1 (Baseline), Week 1, Months 1, 2, 3 (3-month double-blind 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 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.
次要结局
- Summary of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Open-Label Period(Month 1 of open-label period (Month 4 of treatment))
- Minimum Post-Treatment Serum Sodium Levels in the Double-Blind Period(Day 1 through Month 3 (double-blind period))
- Minimum Post-Treatment Serum Sodium Levels in the Open-Label Period(Month 1 of open-label period (Month 4 of treatment))
- 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) in the Double-Blind Period(From Day 1 through Month 3 (double-blind period))