A Trial to Investigate Efficacy, Safety and Tolerability of FE 201836 for Nocturia Due to Nocturnal Polyuria in Adults

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

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

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