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

Ferring

Status and phase: Completed; Phase 2

Conditions: Nocturia

Treatments: Drug: Placebo oral solution; Drug: Desmopressin; Drug: Placebo ODT; Drug: FE 201836

Study type: Interventional

Funder types: Industry

Identifiers

NCT03201419

000233

2016-003851-31 (EudraCT Number)

Details and patient eligibility

About

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

Enrollment: 302 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

---

302 participants in 9 patient groups

FE 201836 500 μg (Randomized Treatment Period)

Experimental group

Description:

FE 201836 500 μg oral solution and placebo orally disintegrating tablet (ODT), administered once daily

Treatment:

Drug: FE 201836

Drug: Placebo ODT

FE 201836 350 μg (Randomized Treatment Period)

Experimental group

Description:

FE 201836 350 μg oral solution and placebo ODT, administered once daily

Treatment:

Drug: FE 201836

Drug: Placebo ODT

FE 201836 250 μg (Randomized Treatment Period)

Experimental group

Description:

FE 201836 250 μg oral solution and placebo ODT, administered once daily

Treatment:

Drug: FE 201836

Drug: Placebo ODT

FE 201836 150 μg (Randomized Treatment Period)

Experimental group

Description:

FE 201836 150 μg oral solution and placebo ODT, administered once daily

Treatment:

Drug: FE 201836

Drug: Placebo ODT

FE 201836 100 μg (Randomized Treatment Period)

Experimental group

Description:

FE 201836 100 μg oral solution and placebo ODT, administered once daily

Treatment:

Drug: FE 201836

Drug: Placebo ODT

FE 201836 50 μg (Randomized Treatment Period)

Experimental group

Description:

FE 201836 50 μg oral solution and placebo ODT, administered once daily

Treatment:

Drug: FE 201836

Drug: Placebo ODT

Placebo (Randomized Treatment Period)

Experimental group

Description:

Placebo oral solution and placebo ODT, administered once daily

Treatment:

Drug: Placebo oral solution

Drug: Placebo ODT

Desmopressin 25 μg (Randomized Treatment Period)

Experimental group

Description:

Desmopressin 25 μg ODT and placebo oral solution, administered once daily (female subjects)

Treatment:

Drug: Placebo oral solution

Drug: Desmopressin

Desmopressin 50 μg (Randomized Treatment Period)

Experimental group

Description:

Desmopressin 50 μg ODT and placebo oral solution, administered once daily (male subjects)

Treatment:

Drug: Placebo oral solution

Drug: Desmopressin