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
Overview
- Phase
- Phase 2
- Intervention
- FE 201836
- Conditions
- Nocturia
- Sponsor
- Ferring Pharmaceuticals
- Enrollment
- 302
- Locations
- 71
- Primary Endpoint
- Change From Baseline in Aggregated Mean Number of Nocturnal Voids During 12 Weeks of Treatment
- Status
- Completed
- Last Updated
- 4 years ago
Overview
Brief Summary
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
Investigators
Eligibility Criteria
Inclusion Criteria
- •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
Exclusion Criteria
- •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
Arms & Interventions
FE 201836 500 μg (Randomized Treatment Period)
FE 201836 500 μg oral solution and placebo orally disintegrating tablet (ODT), administered once daily
Intervention: FE 201836
FE 201836 500 μg (Randomized Treatment Period)
FE 201836 500 μg oral solution and placebo orally disintegrating tablet (ODT), administered once daily
Intervention: Placebo ODT
FE 201836 350 μg (Randomized Treatment Period)
FE 201836 350 μg oral solution and placebo ODT, administered once daily
Intervention: FE 201836
FE 201836 350 μg (Randomized Treatment Period)
FE 201836 350 μg oral solution and placebo ODT, administered once daily
Intervention: Placebo ODT
FE 201836 250 μg (Randomized Treatment Period)
FE 201836 250 μg oral solution and placebo ODT, administered once daily
Intervention: FE 201836
FE 201836 250 μg (Randomized Treatment Period)
FE 201836 250 μg oral solution and placebo ODT, administered once daily
Intervention: Placebo ODT
FE 201836 150 μg (Randomized Treatment Period)
FE 201836 150 μg oral solution and placebo ODT, administered once daily
Intervention: FE 201836
FE 201836 150 μg (Randomized Treatment Period)
FE 201836 150 μg oral solution and placebo ODT, administered once daily
Intervention: Placebo ODT
FE 201836 100 μg (Randomized Treatment Period)
FE 201836 100 μg oral solution and placebo ODT, administered once daily
Intervention: FE 201836
FE 201836 100 μg (Randomized Treatment Period)
FE 201836 100 μg oral solution and placebo ODT, administered once daily
Intervention: Placebo ODT
FE 201836 50 μg (Randomized Treatment Period)
FE 201836 50 μg oral solution and placebo ODT, administered once daily
Intervention: FE 201836
FE 201836 50 μg (Randomized Treatment Period)
FE 201836 50 μg oral solution and placebo ODT, administered once daily
Intervention: Placebo ODT
Placebo (Randomized Treatment Period)
Placebo oral solution and placebo ODT, administered once daily
Intervention: Placebo oral solution
Placebo (Randomized Treatment Period)
Placebo oral solution and placebo ODT, administered once daily
Intervention: Placebo ODT
Desmopressin 25 μg (Randomized Treatment Period)
Desmopressin 25 μg ODT and placebo oral solution, administered once daily (female subjects)
Intervention: Desmopressin
Desmopressin 25 μg (Randomized Treatment Period)
Desmopressin 25 μg ODT and placebo oral solution, administered once daily (female subjects)
Intervention: Placebo oral solution
Desmopressin 50 μg (Randomized Treatment Period)
Desmopressin 50 μg ODT and placebo oral solution, administered once daily (male subjects)
Intervention: Desmopressin
Desmopressin 50 μg (Randomized Treatment Period)
Desmopressin 50 μg ODT and placebo oral solution, administered once daily (male subjects)
Intervention: Placebo oral solution
Outcomes
Primary Outcomes
Change From Baseline in Aggregated Mean Number of Nocturnal Voids During 12 Weeks of Treatment
Time Frame: 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.
Secondary Outcomes
- 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)