Double-blind placebo-controlled proof of concept study with the µ-receptor agonist KN203 in patients with overactive bladder syndromeDouble-blind, randomized, parallel groups prospective phase II-a study for 8 weeks with two dosages of KN203 (20 and 40 mg b.i.d.) and placebo - KN0203Y-001

• Conditions: Women with urgency-frequency syndrome with urinary incontinence due to detrusor instability diagnosed by cystometry.oderPatients with overactive bladder with or without urinary urge incontinence due to detrusor instability whereby the diagnosis is based on the patient’s history and and bladder diaries.; MedDRA version: 12.0Level: LLTClassification code 10059617Term: Overactive bladder; MedDRA version: 12.0Level: LLTClassification code 10012548Term: Detrusor instability

• Registration Number: EUCTR2009-013334-24-DE
• Lead Sponsor: KeyNeurotek Pharma GmbH

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2009-11-19
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Female
• Target Recruitment: 180

Inclusion Criteria

1) Female patients of any racial origin with overactive bladder syndrome with or without urinary urge incontinence

2) Age 18 – 70 years inclusive

3) Likely to meet both criteria at study entry in 4 week:
?????? at least 10 micturitions per 24 h
?????? at least 2 episodes of urinary urge/urgency per 24 h

4) Willingness to undergo a diagnostic cystometry (for a subgroup).

5) For women with child-bearing potential: negative pregnancy test at trial start and highly effective double contraceptive methods throughout the study. Acceptable methods of birth control include: hormonal contraceptives for at least the 28 days (one cycle) before study enrolment or an intra-uterine device (IUD), either of which combined with a barrier method (male or female condom, diaphragm).

6) Written Informed Consent given and able to understand the Consent Form

7) Patient is mentally able to fulfill the study requirements
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1) Clinically significant stress urinary incontinence (defined as leakage following more strenuous activity such as climbing stairs, e.g. Stamey grade II or III)
2) Previous surgery affecting bladder function
3) Diabetes mellitus
4) Chronic obstipation with regular use of laxatives
Pelvic organ prolapse stage III and IV
5) Urinary incontinence due to neurological disease
6) Pelvic organ prolapse stage III and IV
7) Symptoms of urge due to bladder stones, interstitial cystitis, tumour, tuberculosis, or radiotherapy
8) Symptomatic or recurrent urinary tract infection (more than 3 episodes per year), or a urinary tract infection within two weeks before study enrolment
9) Significant post voided residual urine (>100 ml) detected by sonography
10) Polyuria of more than 3 litres per 24 hours
11) Non-medicinal treatment of urgency and/or incontinence within 3 months before study enrolment (e.g. bladder training). (note: starting non-medicinal treatment for urgency and/or incontinence before study entry is not allowed.)
12) Electrostimulation implants for urinary incontinence
13) Indwelling or intermittent catheterisation
14) Known contraindication/hypersensitivity to opioids
15) Prescription or over-the-counter medications (including herbal remedies) started within 28 days before study enrolment, unless used for no more than 10 days in total. Paracetamol, acetyl salicylic acid, metoclopramide, or preparations for topical use without systemic effect can be used without restriction (note: the starting of medication before study entry is not allowed)
16) Therapy within the last 28 days with
- opioids (including buprenorphine and tramadol, and patches applied to
the skin thereof)
- monoamine oxidase (MAO) inhibitors
- dexamethasone, cimetidine, fluoxetine, fluvoxamine, indomethacin,
ketoconazole, lansoprazole, omeprazole, paroxetine, probenicid, ticlopidine
Note: these medications are not permitted during the study
17) Therapy with diuretics if the patient has had or is planned to have initiation, discontinuation, or change in dose of diuretics 28 days before or during treatment with study medication
18) Unwillingness to stop therapy with other medicinal treatments for urgency and/or incontinence if these are being taken
19) Participation in an investigational drug study or device study within one month, of study enrolment, or previous participation in this study, or parallel participation in another study
20) Known to or suspected of not being able to comply with the study protocol (including completion of patient diary)
21) Not able to communicate meaningfully with the investigator and staff
22) Pregnancy and/or lactation
23) History of alcohol, medication or drug dependency
24) History of major psychiatric illness, dementia, Parkinson’s disease, epilepsy or suicide risk
25) Poor general health status ; e.g. NYHA class =3; uncontrolled hypertension
26) Known chronic disease (e.g. hepatic, renal or gastrointestinal) that might effect drug absorption, distribution, metabolism or excretion

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To assess the efficacy of two different dose regimens of KN203 after 8 weeks of treatment in comparison to baseline and between parallel groups and placebo.;Secondary Objective: To assess clinical, laboratory, physical safety as well as quality-of-life parameters (King’s Health Questionnaire) following twice daily oral doses of KN203 for 8 weeks.<br>;Primary end point(s): Frequency of micturition per 24 h at end of treatment (Visit 8); versus baseline (day 1) and between parallel groups including placebo.