A Trial to Investigate Efficacy, Safety and Tolerability of FE 201836 for Nocturia Due to Nocturnal Polyuria in Adults
Condition: Nocturia
MeSH terms: Polyuria; Nocturia
Intervention: FE 201836; Desmopressin; Placebo oral solution; Placebo ODT
Intervention description: Oral solution for daily intake; Desmopressin Orally Disintegrating Tablet (ODT); Manufactured to mimic experimental drug; Manufactured to mimic experimental drug
Intervention MeSH terms: Deamino Arginine Vasopressin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
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.
Masking: Double (Participant, Investigator)
Masking description: 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.
Enrollment: 302.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

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