Multicentre, randomised, double-blind, parallel group confirmatory Phase III study to compare the efficacy and safety of cizolirtine citrate 300 mg bid (600 mg/d), cizolirtine citrate 400 mg bid (800 mg/d), placebo, and tolterodine 2 mg bid (4 mg/d) in the treatment of urge urinary incontinence
- Conditions
- rge Urinary Incontinence
- Registration Number
- EUCTR2004-001116-31-GB
- Lead Sponsor
- aboratorios Dr. Esteve S.A.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 690
Criteria for inclusion in the run-in period at Visit 1 (Week -3, Day -21 plus or minus 3 days)
Patients who meet the following criteria are considered for inclusion in the run-in period
•Outpatients
•Both genders
•Age 18 to 80 years
•Premenopausal female patients:
Adequate contraception (in the investigator's opinion) or no childbearing potential (i.e. medically confirmed infertility, operative sterilisation, hysterectomy)
•Urge urinary incontinence for a duration of at least 6 months confirmed by medical history and documented in the patient’s file i.e.
o Involuntary leakage of urine immediately preceded or accompanied by the feeling of urgency,
o Often associated with increased frequency of micturition and/or episodes of urgency not leading to incontinence
•Urge urinary incontinence confirmed by cystometric results in patients having agreed in this examination. If no cystometry is available from within 4 months prior to Visit 1, cystometry will be performed between Visit 1 and Visit 3. At least one of the following criteria must be present:
o Phasic increases in the bladder pressure with an amplitude of 15 mm H2O during medium fill cystometry (filling rate between 10 and 100 ml/min) that, in the investigator’s judgement, are caused by detrusor contractions
o Volume at first desire to micturate below normal range (150 ml – 200 ml; to be judged by investigator individually for each patient)
o Maximal cystometric capacity below normal range (400 ml – 500 ml; to be judged by investigator individually for each patient)
• Patient has given informed consent according to GCP
• Patient is willing and able to comply with all trial requirements
Criteria for inclusion in the randomised, double-blind period at Visit 3 (Day 0):
After completion of the run-in period, patients must meet the following criteria:
•Presence of
o A minimum of 1 episode of the feeling of urgency (strong desire to micturate)
and at least one of the following
o A minimum of 8 micturitions/24 hours, on average
o A minimum of 1 incontinence episode/24 hours, on average, during 7 days prior to the randomisation visit
• Normal basic urinalysis
•Negative urine culture
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
Criteria for exclusion from the run-in period at Visit 1 (Week -3, Day -21 plus or minus 3 days) and from the randomised, double-blind period at Visit 3 (day 0)
The following criteria are to be checked at screening and to be re-checked at the baseline visit:
• Evidence of mixed incontinence with prevailing obstructive component or stress component according to the investigator’s opinion, or treatment (current or within the last week) with any of the following drugs: alpha adrenergic agonists (e.g. phenylpropanolamine) or antagonists (e.g. prazosine, tamsulosine, or terazosine)
• Lower tract urological pathology in the investigator's opinion potentially responsible for incontinence known from medical history for the last 3 months
• Urinary tract infection defined in terms of clinical signs and symptoms
e.g. urgency and/or frequency associated with fever, dysuria, suprapubic pain
with or without microbiological confirmation, within two weeks prior to randomisation
• Any obstructive condition affecting the urethra or any clinically significant prostatic disease requiring therapy
• Mechanical obstructive uropathy known from medical history and/or shown by residual urine volume >200 ml at screening and/or the randomisation visit
•Polyuria (>2500 ml/24h) known from medical history and confirmed during run-in
•Increased frequency and/or nocturia only due to renal or cardiac insufficiency known from medical history
•Neurological disease influencing bladder function (e.g. multiple sclerosis, Parkinson's disease, spinal cord injuries, spina bifida)
•Urogenital surgeryin the patient’s history,
e.g. prostatectomy, or a surgical procedure for the treatment of incontinence
• Known allergy or hypersensitivity to any components of the study medication or structurally related drugs
•Pregnancy or lactation period
•Respiratory, renal (serum creatinine >2.5 mg/dl or >211 µmol/l), hepatic (ALAT >3-fold ULN), gastrointestinal, haematological, endocrine, psychiatric, or any other disease or condition that, in the opinion of the investigator, could affect the evaluation of the study medication
•Obstructive disease of the gastrointestinal tract, paralytic ileus, intestinal atony, megacolon (including toxic), chronic inflammatory bowel disease known from medical history
•Myasthenia gravis
•Untreated narrow angle glaucoma
•In general any clinically significant heart disease
•Known severe or malignant hypertension
•Mild to moderate hypertension not controlled satisfactorily
•Uncontrolled diabetes
•Previous participation in this study (participation in former cizolirtine studies is allowed)
•Participation in another study of an investigational drug within the last 30 days or current participation in another study of an investigational drug
•Chronic alcohol or drug abuse within the last 6 months
•Any condition which, in the opinion of the investigator, can jeopardize or would compromise the subject's ability to participate in this study
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method