Clinical trial NCT03201419: A Trial to Investigate Efficacy, Safety and Tolerability of FE 201836 for Nocturia Due to Nocturnal Polyuria in Adults
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Nocturia
Lead sponsor: Ferring Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2017-06-28
Enrollment: 302
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The trial consisted of a 2 week period of screening/lifestyle changes during which no treatment was given, a 2 week enrichment period (including a 1 week single blind active run-in period \[FE 201836 500 µg\] and a 1 week washout period) followed by a 12 week randomized treatment period for each subject. Prior to the first interim analysis, the first 129 subjects were randomized to daily treatment with FE 201836 500 µg, placebo, or desmopressin (25 µg for females and 50 µg for males) in a 2:2:1 ratio. After the first interim analysis, subjects were randomized to daily treatment with FE 201836 (50 µg, 100 µg, 150 µg, 250 µg, 350 µg, or 500 µg), placebo, or desmopressin (25 µg for females and 50 µg for males) using response adaptive allocation probabilities.
Primary purpose: TREATMENT

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


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 1. 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

Primary outcomes:
measure: Change From Baseline in Aggregated Mean Number of Nocturnal Voids During 12 Weeks of Treatment
timeFrame: Baseline, during 12 weeks of treatment
Secondary outcomes:
measure: Change From Baseline in Mean Number of Nocturnal Voids at Week 1
timeFrame: Baseline, Week 1
measure: Change From Baseline in Mean Number of Nocturnal Voids at Week 4
timeFrame: Baseline, Week 4
measure: Change From Baseline in Mean Number of Nocturnal Voids at Week 8
timeFrame: Baseline, Week 8
measure: Change From Baseline in Mean Number of Nocturnal Voids at Week 12
timeFrame: Baseline, Week 12
measure: Responder Rate in Nocturnal Voids at Week 1
timeFrame: Week 1
measure: Responder Rate in Nocturnal Voids at Week 4
timeFrame: Week 4
measure: Responder Rate in Nocturnal Voids at Week 8
timeFrame: Week 8
measure: Responder Rate in Nocturnal Voids at Week 12
timeFrame: Week 12
measure: Responder Rate in Nocturnal Voids During 12 Weeks of Treatment
timeFrame: During 12 weeks of treatment
measure: Change From Baseline in Mean NI Diary Total Score at Week 1
timeFrame: Baseline, Week 1
measure: Change From Baseline in Mean NI Diary Total Score at Week 4
timeFrame: Baseline, Week 4
measure: Change From Baseline in Mean NI Diary Total Score at Week 8
timeFrame: Baseline, Week 8
measure: Change From Baseline in Mean NI Diary Total Score at Week 12
timeFrame: Baseline, Week 12
measure: Change From Baseline in Aggregated Mean NI Diary Total Score During 12 Weeks of Treatment
timeFrame: Baseline, during 12 weeks of treatment
measure: Percentage of Nights With at Most One Nocturnal Void During 12 Weeks of Treatment
timeFrame: During 12 weeks of treatment
measure: Percentage of Nights With No Nocturnal Voids During 12 Weeks of Treatment
timeFrame: During 12 weeks of treatment
measure: Change From Baseline in Mean NI Diary Overall Impact Score at Week 1
timeFrame: Baseline, Week 1
measure: Change From Baseline in Mean NI Diary Overall Impact Score at Week 4
timeFrame: Baseline, Week 4
measure: Change From Baseline in Mean NI Diary Overall Impact Score at Week 8
timeFrame: Baseline, Week 8
measure: Change From Baseline in Mean NI Diary Overall Impact Score at Week 12
timeFrame: Baseline, Week 12
measure: Change From Baseline in Aggregated Mean NI Diary Overall Impact Score During 12 Weeks of Treatment
timeFrame: Baseline, during 12 weeks of treatment
measure: Patient Global Impression of Improvement (PGI-I) Urinary Symptoms Scores at Week 1
timeFrame: Week 1
measure: Patient Global Impression of Improvement (PGI-I) Urinary Symptoms Scores at Week 4
timeFrame: Week 4
measure: Patient Global Impression of Improvement (PGI-I) Urinary Symptoms Scores at Week 8
timeFrame: Week 8
measure: Patient Global Impression of Improvement (PGI-I) Urinary Symptoms Scores at Week 12
timeFrame: Week 12
measure: Change From Baseline in Patient Global Impression of Severity (PGI-S) Scores at Week 1
timeFrame: Baseline, Week 1
measure: Change From Baseline in PGI-S Scores at Week 4
timeFrame: Baseline, Week 4
measure: Change From Baseline in PGI-S Scores at Week 8
timeFrame: Baseline, Week 8
measure: Change From Baseline in PGI-S Scores at Week 12
timeFrame: Baseline, Week 12
measure: Change From Baseline in Hsu 5-point Likert Bother Scale at Week 1
timeFrame: Baseline, Week 1
measure: Change From Baseline in Hsu 5-point Likert Bother Scale at Week 4
timeFrame: Baseline, Week 4
measure: Change From Baseline in Hsu 5-point Likert Bother Scale at Week 8
timeFrame: Baseline, Week 8
measure: Change From Baseline in Hsu 5-point Likert Bother Scale at Week 12
timeFrame: Baseline, Week 12
measure: Change From Baseline in ISI at Week 4
timeFrame: Baseline, Week 4
measure: Change From Baseline in ISI at Week 8
timeFrame: Baseline, Week 8
measure: Change From Baseline in ISI at Week 12
timeFrame: Baseline, Week 12
measure: Change From Baseline in Mean Duration of First Undisturbed Sleep Period (FUSP) at Week 1
timeFrame: Baseline, Week 1
measure: Change From Baseline in Mean Duration of FUSP at Week 4
timeFrame: Baseline, Week 4
measure: Change From Baseline in Mean Duration of FUSP at Week 8
timeFrame: Baseline, Week 8
measure: Change From Baseline in Mean Duration of FUSP at Week 12
timeFrame: Baseline, Week 12
measure: Change From Baseline in Aggregated Mean Duration of FUSP During 12 Weeks of Treatment
timeFrame: Baseline, During 12 Weeks of Treatment
measure: Change From Baseline in Nocturnal Diuresis Rate Profiles at Week 1
timeFrame: Baseline, Week 1
measure: Change From Baseline in Nocturnal Diuresis Rate Profiles at Week 12
timeFrame: Baseline, Week 12
measure: Change From Baseline in Mean NUV in Week 1
timeFrame: Baseline, Week 1
measure: Change From Baseline in Mean NUV at Week 12
timeFrame: Baseline, Week 12
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Achieve Clinical Research, LLC
state: Alabama
city: Mobile
country: United States
facility: Coastal Clinical Research, an AMR company
state: Alabama
city: Lincoln
country: United States
facility: Clinical Trials Research
state: California
city: Murrieta
country: United States
facility: Tri Valley Urology Medical Group
state: California
city: San Diego
country: United States
facility: San Diego Clinical Trials
state: California
city: Westminster
country: United States
facility: Advanced Rx Clinical Research Group, Inc.
state: California
city: Denver
country: United States
facility: Downtown Women's Health Care
state: Colorado
city: Denver
country: United States
facility: Genitourinary Surgical Consultants, P.C.
state: Colorado
city: Aventura
country: United States
facility: South Florida Medical Research
state: Florida
city: Clearwater
country: United States
facility: Women's Medical Research Group, LLC
state: Florida
city: Clearwater
country: United States
facility: Tampa Bay Medical Research, Inc.
state: Florida
city: Coral Gables
country: United States
facility: Clinical Research of South Florida
state: Florida
city: DeLand
country: United States
facility: Avail Clinical Research, LLC
state: Florida
city: Greenacres City
country: United States
facility: Finlay Medical Research Corp
state: Florida
city: Miami
country: United States
facility: Pharmax Research Clinic
state: Florida
city: Miami
country: United States
facility: Doctors Research Institute Corporation
state: Florida
city: Miami
country: United States
facility: Sanitas Research
state: Florida
city: New Port Richey
country: United States
facility: Bayside Clinical Research LLC
state: Florida
city: Pembroke Pines
country: United States
facility: Pines Care Research Center, Inc
state: Florida
city: Pompano Beach
country: United States
facility: Clinical Research Center of Florida
state: Florida
city: Saint Petersburg
country: United States
facility: Meridien Research, Inc.
state: Florida
city: Avon
country: United States
facility: American Health Network of Indiana, LLC
state: Indiana
city: Greenfield
country: United States
facility: American Health Network of Indiana, LLC
state: Indiana
city: Watertown
country: United States
facility: Bay State Clinical Trials, Inc.
state: Massachusetts
city: Kalamazoo
country: United States
facility: Beyer Research
state: Michigan
city: Rochester
country: United States
facility: Remedica LLC
state: Michigan
city: Omaha
country: United States
facility: Quality Clinical Research Center, Inc.
state: Nebraska
city: Las Vegas
country: United States
facility: Clinical Research Consortium, an AMR company
state: Nevada
city: New Windsor
country: United States
facility: Mid Hudson Medical Research, PLLC
state: New York
city: Poughkeepsie
country: United States
facility: Premier Medical Group of the Hudson Valley, PC
state: New York
city: Charlotte
country: United States
facility: American Health Research, Inc.
state: North Carolina
city: Greensboro
country: United States
facility: Medication Management, LLC
state: North Carolina
city: High Point
country: United States
facility: Peters Medical Research
state: North Carolina
city: Raleigh
country: United States
facility: PMG Research of Raleigh, LLC
state: North Carolina
city: Wilmington
country: United States
facility: PMG Research of Wilmington, LLC
state: North Carolina
city: Englewood
country: United States
facility: HWC Women's Research Center
state: Ohio
city: Providence
country: United States
facility: NECCR Primacare Research, LLC
state: Rhode Island
city: Mount Pleasant
country: United States
facility: Coastal Carolina Research Center, Inc
state: South Carolina
city: Mount Pleasant
country: United States
facility: PMG Research of Charleston, LLC
state: South Carolina
city: Houston
country: United States
facility: MCA Research - Partner
state: Texas
city: Clinton
country: United States
facility: Ericksen Research & Development, LLC
state: Utah
city: Ogden
country: United States
facility: Advanced Research Institute
state: Utah
city: Norfolk
country: United States
facility: Clinical Research Associates of Tidewater, an AMR company
state: Virginia
city: Bruxelles
country: Belgium
facility: ULB Hopital Erasme
city: Edegem
country: Belgium
facility: UZ Antwerpen
city: Gent
country: Belgium
facility: Universitair Ziekenhuis Gent
city: Kortrijk
country: Belgium
facility: AZ Groeninge - Campus Vercruysselaan
city: Leuven
country: Belgium
facility: UZ Leuven
city: Pointe-Claire
country: Canada
facility: Ultra-Med Inc.
state: Quebec
city: London
country: Canada
facility: Milestone Research
city: Newmarket
country: Canada
facility: SKDS Research Inc.
city: Quebec
country: Canada
facility: DIEX Recherche Quebec Inc.
city: Québec
country: Canada
facility: Clinique Médicale St-Louis (Recherche) inc d/b/a/ Centre de Recherche Saint-Louis
city: Sarnia
country: Canada
facility: Bluewater Health-Norman Site
city: Sherbrooke
country: Canada
facility: CHUS - Hôpital Fleurimont
city: Sherbrooke
country: Canada
facility: DIEX Recherche Sherbrooke Inc.
city: Toronto
country: Canada
facility: Ferring Investigational Site
city: Victoriaville
country: Canada
facility: DIEX Recherche Victoriaville Inc.
city: Benešov
country: Czechia
facility: Urologie Benešov - Afimed s.r.o.
city: Brno
country: Czechia
facility: Fakultni nemocnice Brno, Dept of Klinika nemoci plicnich a tuberkulozy
city: Liberec
country: Czechia
facility: Krajska nemocnice Liberec, a.s.
city: Plzen
country: Czechia
facility: Urocentrum Plzen
city: Praha
country: Czechia
facility: Thomayerova nemocnice, PARENT
city: Duisburg
country: Germany
facility: Gemeinschaftspraxis fuer Urologie und Andrologie
city: Emmendingen
country: Germany
facility: Urologische Gemeinschaftspraxis
city: Weiden
country: Germany
facility: Klinikum Weiden, Klinik f. Urologie, Andrologie und Kinderurologie
city: Budapest
country: Hungary
facility: Jahn Ferenc Del-pesti Korhaz es Rendelointezet
city: Budapest
country: Hungary
facility: Synexus Magyarorszag Kft.
city: Kecskemet
country: Hungary
facility: Bagoly Egeszseghaz
city: Nyiregyhaza
country: Hungary
facility: SzSzB Megyei Korhazak es Egyetemi Oktatokorhaz, Josa Andras Oktatokorhaz Urologia
city: Szolnok
country: Hungary
facility: Jasz-Nagykun-Szolnok Megyei Hetenyi Geza Korhaz-Rendelointezet
city: Bydgoszcz
country: Poland
facility: Nasz Lekarz Osrodek Badan Klinicznych
Study officials:
affiliation: Ferring Pharmaceuticals
name: Global Clinical Compliance
role: STUDY_DIRECTOR
References:
citation: Hudgens S, Howerter A, Polek E, Andersson FL. Psychometric validation and interpretation of the Nocturia Impact Diary in a clinical trial setting. Qual Life Res. 2022 Jun;31(6):1837-1848. doi: 10.1007/s11136-021-03060-4. Epub 2021 Dec 21.