A Randomised, Double-blind, Placebo-controlled, Response-adaptive Dose-finding Trial Investigating the Efficacy, Safety and Tolerability of Oral Doses of FE 201836, With Desmopressin Orally Disintegrating Tablet as a Benchmark, During 12 Weeks of Treatment for Nocturia Due to Nocturnal Polyuria in Adults
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 302
- 试验地点
- 71
- 主要终点
- Change From Baseline in Aggregated Mean Number of Nocturnal Voids During 12 Weeks of Treatment
研究概览
简要总结
The purpose of this trial was to investigate the efficacy, safety and tolerability of different oral doses of FE 201836, with desmopressin as a benchmark, during 12 weeks of treatment for nocturia due to nocturnal polyuria in adults
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)
盲法说明
Each subject will receive 2 medications (an oral solution and an orally disintegrating tablet (ODT) formulation) throughout the trial, in order to keep the treatment blinded.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adults ≥18 years of age (at the time of written consent)
- •Medical history of, or subject reported nocturia symptoms during the 6 months prior to Visit 1
- •≥2 nocturnal voids (an average over 3 days) as documented in the 3-day e-Diary prior to Visit 2
- •The largest single voided volume must be ≥200 mL (at least 1 void ≥200 mL) as documented in the 3-day e-Diary prior to Visit 2
- •Nocturnal polyuria, defined as Nocturnal Polyuria index >33%, a ratio of Nocturnal Urine Volume in excess of 33% of total daily (24-hour) urine volume as documented in the 3-day e-Diary prior to Visit 2
- •≥20% decrease in the nocturnal diuresis rate (mL/min) (that was recorded at Visit 2) as documented in the 3-day e-Diary prior to Visit 3
排除标准
- •Current diagnosis of Obstructive Sleep Apnoea (OSA)
- •Restless Legs Syndrome (RLS)
- •Bladder Outlet Obstruction (BOO) or urine flow <5 mL/s, as confirmed by uroflowmetry upon suspicion during screening prior to Visit 2
- •Urinary incontinence defined as an average of >1 episode/day in the 3-day e-Diary prior to Visit 2 (occasional urge incontinence during daytime or at night on the way to void is not necessarily exclusionary)
- •Any pelvic or lower urinary tract surgery and/or radio therapy or previous pelvic irradiation within the past 6 months prior to Visit
- •Including e.g., transurethral resection for Bladder Outlet Obstruction or Benign Prostatic Hyperplasia, hysterectomy or female incontinence procedures
- •Genito-urinary tract pathology that can in the investigator's opinion be responsible for urgency or urinary incontinence e.g., symptomatic or recurrent urinary tract infections, interstitial cystitis, bladder-related pain, chronic pelvic pain syndrome, or stone in the bladder or urethra causing symptoms
- •A history of cancer with the last date of disease activity/presence of malignancy within the last 12 months prior to Visit 1, except for adequately treated basal cell carcinoma of the skin
- •History of any neurological disease affecting bladder function or muscle strength (e.g., Multiple Sclerosis, Parkinson's, spinal cord injury, spina bifida)
- •Habitual (fluid intake >3L per day) or psychogenic polydipsia
- •Uncontrolled hypertension, as judged by the investigator
- •Uncontrolled diabetes mellitus, as judged by the investigator
- •Central or nephrogenic diabetes insipidus
- •Known history of Syndrome of Inappropriate Antidiuretic Hormone (SIADH) secretion
- •History of gastric retention
- •Suspicion or evidence of congestive heart failure, (New York Heart Association (NYHA) class II, III, IV)
- •Hyponatraemia:
- •Serum sodium level <135 mmol/L at Visit 1(re-tested, with results available within 7 days)
- •Serum sodium level <130 mmol/L at Visit 3 (re-tested, with results available within 7 days)
- •Use of any prohibited therapy listed below:
- •Current or former (within 3 months prior to screening) treatment with any other investigational medicinal product (IMP)
- •Unstable electrostimulation or behavioural bladder training program less than 3 months prior to screening (stable electrostimulation or behavioural bladder training program started at least 3 months before screening are acceptable)
- •Thiazide diuretics
- •Antiarrhythmic agents
- •V2-receptor antagonists/agonists (e.g., vaptans/desmopressin, vasopressin)
- •Loperamide
- •Botulinum toxin (cosmetic non-urological use is acceptable)
- •Valproate
研究组 & 干预措施
FE 201836 500 μg (Randomized Treatment Period)
FE 201836 500 μg oral solution and placebo orally disintegrating tablet (ODT), administered once daily
干预措施: FE 201836 (Drug)
FE 201836 500 μg (Randomized Treatment Period)
FE 201836 500 μg oral solution and placebo orally disintegrating tablet (ODT), administered once daily
干预措施: Placebo ODT (Drug)
FE 201836 350 μg (Randomized Treatment Period)
FE 201836 350 μg oral solution and placebo ODT, administered once daily
干预措施: FE 201836 (Drug)
FE 201836 350 μg (Randomized Treatment Period)
FE 201836 350 μg oral solution and placebo ODT, administered once daily
干预措施: Placebo ODT (Drug)
FE 201836 250 μg (Randomized Treatment Period)
FE 201836 250 μg oral solution and placebo ODT, administered once daily
干预措施: FE 201836 (Drug)
FE 201836 250 μg (Randomized Treatment Period)
FE 201836 250 μg oral solution and placebo ODT, administered once daily
干预措施: Placebo ODT (Drug)
FE 201836 150 μg (Randomized Treatment Period)
FE 201836 150 μg oral solution and placebo ODT, administered once daily
干预措施: FE 201836 (Drug)
FE 201836 150 μg (Randomized Treatment Period)
FE 201836 150 μg oral solution and placebo ODT, administered once daily
干预措施: Placebo ODT (Drug)
FE 201836 100 μg (Randomized Treatment Period)
FE 201836 100 μg oral solution and placebo ODT, administered once daily
干预措施: FE 201836 (Drug)
FE 201836 100 μg (Randomized Treatment Period)
FE 201836 100 μg oral solution and placebo ODT, administered once daily
干预措施: Placebo ODT (Drug)
FE 201836 50 μg (Randomized Treatment Period)
FE 201836 50 μg oral solution and placebo ODT, administered once daily
干预措施: FE 201836 (Drug)
FE 201836 50 μg (Randomized Treatment Period)
FE 201836 50 μg oral solution and placebo ODT, administered once daily
干预措施: Placebo ODT (Drug)
Placebo (Randomized Treatment Period)
Placebo oral solution and placebo ODT, administered once daily
干预措施: Placebo oral solution (Drug)
Placebo (Randomized Treatment Period)
Placebo oral solution and placebo ODT, administered once daily
干预措施: Placebo ODT (Drug)
Desmopressin 25 μg (Randomized Treatment Period)
Desmopressin 25 μg ODT and placebo oral solution, administered once daily (female subjects)
干预措施: Desmopressin (Drug)
Desmopressin 25 μg (Randomized Treatment Period)
Desmopressin 25 μg ODT and placebo oral solution, administered once daily (female subjects)
干预措施: Placebo oral solution (Drug)
Desmopressin 50 μg (Randomized Treatment Period)
Desmopressin 50 μg ODT and placebo oral solution, administered once daily (male subjects)
干预措施: Desmopressin (Drug)
Desmopressin 50 μg (Randomized Treatment Period)
Desmopressin 50 μg ODT and placebo oral solution, administered once daily (male subjects)
干预措施: Placebo oral solution (Drug)
结局指标
主要结局
Change From Baseline in Aggregated Mean Number of Nocturnal Voids During 12 Weeks of Treatment
时间窗: Baseline, during 12 weeks of treatment
Nocturnal voids were defined as voids occuring from 5 minutes after bedtime until rising in the morning. The number of nocturnal voids at each visit was calculated as the average over the 3 consecutive 24 hour periods just prior to the respective visit. The visit-specific means were aggregated into a mean of current and preceding visits. Level estimated for baseline value of mean number of nocturnal voids equal to 2, and 95% credibility interval (2.5 and 97.5 percentiles of the posterior distribution) instead of confidence interval are presented in this endpoint.
次要结局
- Change From Baseline in Mean Number of Nocturnal Voids at Week 1(Baseline, Week 1)
- Change From Baseline in Mean Number of Nocturnal Voids at Week 4(Baseline, Week 4)
- Change From Baseline in Mean Number of Nocturnal Voids at Week 8(Baseline, Week 8)
- Change From Baseline in Mean Number of Nocturnal Voids at Week 12(Baseline, Week 12)
- Responder Rate in Nocturnal Voids at Week 1(Week 1)
- Responder Rate in Nocturnal Voids at Week 4(Week 4)
- Responder Rate in Nocturnal Voids at Week 8(Week 8)
- Responder Rate in Nocturnal Voids at Week 12(Week 12)
- Responder Rate in Nocturnal Voids During 12 Weeks of Treatment(During 12 weeks of treatment)
- Change From Baseline in Mean NI Diary Total Score at Week 1(Baseline, Week 1)
- Change From Baseline in Mean NI Diary Total Score at Week 4(Baseline, Week 4)
- Change From Baseline in Mean NI Diary Total Score at Week 8(Baseline, Week 8)
- Change From Baseline in Mean NI Diary Total Score at Week 12(Baseline, Week 12)
- Change From Baseline in Aggregated Mean NI Diary Total Score During 12 Weeks of Treatment(Baseline, during 12 weeks of treatment)
- Percentage of Nights With at Most One Nocturnal Void During 12 Weeks of Treatment(During 12 weeks of treatment)
- Percentage of Nights With No Nocturnal Voids During 12 Weeks of Treatment(During 12 weeks of treatment)
- Change From Baseline in Mean NI Diary Overall Impact Score at Week 1(Baseline, Week 1)
- Change From Baseline in Mean NI Diary Overall Impact Score at Week 4(Baseline, Week 4)
- Change From Baseline in Mean NI Diary Overall Impact Score at Week 8(Baseline, Week 8)
- Change From Baseline in Mean NI Diary Overall Impact Score at Week 12(Baseline, Week 12)
- Change From Baseline in Aggregated Mean NI Diary Overall Impact Score During 12 Weeks of Treatment(Baseline, during 12 weeks of treatment)
- Patient Global Impression of Improvement (PGI-I) Urinary Symptoms Scores at Week 1(Week 1)
- Patient Global Impression of Improvement (PGI-I) Urinary Symptoms Scores at Week 4(Week 4)
- Patient Global Impression of Improvement (PGI-I) Urinary Symptoms Scores at Week 8(Week 8)
- Patient Global Impression of Improvement (PGI-I) Urinary Symptoms Scores at Week 12(Week 12)
- Change From Baseline in Patient Global Impression of Severity (PGI-S) Scores at Week 1(Baseline, Week 1)
- Change From Baseline in PGI-S Scores at Week 4(Baseline, Week 4)
- Change From Baseline in PGI-S Scores at Week 8(Baseline, Week 8)
- Change From Baseline in PGI-S Scores at Week 12(Baseline, Week 12)
- Change From Baseline in Hsu 5-point Likert Bother Scale at Week 1(Baseline, Week 1)
- Change From Baseline in Hsu 5-point Likert Bother Scale at Week 4(Baseline, Week 4)
- Change From Baseline in Hsu 5-point Likert Bother Scale at Week 8(Baseline, Week 8)
- Change From Baseline in Hsu 5-point Likert Bother Scale at Week 12(Baseline, Week 12)
- Change From Baseline in Mean Duration of FUSP at Week 4(Baseline, Week 4)
- Change From Baseline in Mean Duration of FUSP at Week 8(Baseline, Week 8)
- Change From Baseline in Mean Duration of FUSP at Week 12(Baseline, Week 12)
- Change From Baseline in Nocturnal Diuresis Rate Profiles at Week 12(Baseline, Week 12)
- Change From Baseline in Mean NUV in Week 1(Baseline, Week 1)
- Change From Baseline in Mean NUV at Week 12(Baseline, Week 12)
- Change From Baseline in ISI at Week 8(Baseline, Week 8)
- Change From Baseline in ISI at Week 4(Baseline, Week 4)
- Change From Baseline in ISI at Week 12(Baseline, Week 12)
- Change From Baseline in Mean Duration of First Undisturbed Sleep Period (FUSP) at Week 1(Baseline, Week 1)
- Change From Baseline in Aggregated Mean Duration of FUSP During 12 Weeks of Treatment(Baseline, During 12 Weeks of Treatment)
- Change From Baseline in Nocturnal Diuresis Rate Profiles at Week 1(Baseline, Week 1)