E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Stress Urinary Incontinence |
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MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective is to evaluate the efficacy of cizolirtine citrate 200 mg twice daily, 300 mg twice daily, and 400 mg twice daily versus placebo in decreasing the frequency of incontinence episodes.
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E.2.2 | Secondary objectives of the trial |
The secondary objectives are to · evaluate the efficacy of cizolirtine citrate 200 mg twice daily, 300 mg twice daily, and 400 mg twice daily versus placebo with respect to secondary endpoints · evaluate the dose-response relationship between cizolirtine 200 mg twice daily, 300 mg twice daily,and 400 mg twice daily for primary and secondary endpoints · evaluate the change in subjective QoL experience of the treatment. · evaluate the short term (12-week) safety |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
1. Females 18-75 years of age. 2. Signed informed consent form. 3. Clinical diagnosis of stress urinary incontinence for at least 3 months confirmed by medical history and documented in the subject’s file. 4. Presence of: -more or equal to 4 incontinence episodes per week. An episode is defined as an easily noticeable leakage of urine that wets a pad or clothing and occurs in association with a physical stress such as coughing, sneezing, or exercise. - Urinary diurnal frequency less or equal to 7 per day - Urinary nocturnal frequency less or equal to 2 per day 5. Ability to in supine position tolerate filling of the bladder with 400 ml saline without a first leakage at <100 ml. 6. Positive cough stress test (visualisation of urine leakage concurrent with cough) 7. Positive standardised 1 hour stress pad test (leakage of > 2.0 g) 8. Sterile urine and normal basic urinalysis (analyses available at Visit 2) 9. Subjects willing and able to co-operate 10. Subjects able to accurately complete the patient diary on more or equal to 4 days during 1 week in the placebo run-in period (assessed at Visit 3). |
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E.4 | Principal exclusion criteria |
1. Evidence of mixed incontinence or urge incontinence, or incontinence due to surgical treatment, according to investigator’s opinion 2. Evidence of exclusively nocturnal enuresis 3. Polyuria known from medical history and confirmed during run-in 4. Concomitant treatment with drugs introduced within 3 months or with <3 months of stable dosing and that can be supposed to have effects on the lower urinary tract such as antidepressants, neuroleptics, and calcium blocking agents. 5. Lower tract urological pathology in the investigator’s opinion potentially responsible for incontinence known from medical history for the last 3 months 6. Urinary tract infection defined in terms of clinical signs and symptoms, with or without microbiological confirmation, within 2 weeks prior to placebo run-in (i.e. Visit 2) 7. Mechanical obstructive uropathy known from medical history 8. Increased frequency and/or nocturia only due to renal or cardiac insufficiency known from medical history 9. Neurological disorder associated with incontinence, e.g. Parkinson’s disease or Multiple Sclerosis, or influencing the bladder function 10. Urogenital surgery, e.g. surgical procedure for treatment of incontinence or prolapse,within the last 2 years 11. Known allergy or hypersensitivity to any components of the study medication or structurally related drugs 12. Respiratory, renal (serum creatinine > 2.5 mg/dl or > 211 mmol/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 13. Obstructive disease of the gastrointestinal tract such as paralytic ileus, intestinal atony, megacolon (including toxic), chronic inflammatory bowel disease known from the medical history 14. Any clinically significant heart disease 15. Known severe or malignant hypertension 16. Unstable diabetes that requires changes of the treatment with either insulin or other antidiabetic agents. 17. Any history of cerebral stroke. 18. Haematuria of unknown origin or haematuria secondary to malignant disease. 19. Interstitial cystitis (diagnosed by symptoms) 20. Previous participation in this study (participation in former cizolirtine studies is allowed) 21. Participation in another study of an investigational drug within the last 30 days prior to the screening visit or current participation in another study of an investigational drug. 22. Chronic alcohol or drug abuse within the last 6 months 23. Pregnant or nursing women, and women of childbearing potential not using reliable contraceptive methods. 24. Any planned major surgery within the duration of the study. 25. Any other condition or symptoms preventing the subject from entering the study, according to the investigator’s judgement. 26. Clinically relevant abnormal ECG as judged by the investigator. Neither will the subject be included if one of the following criteria are fulfilled at the baseline visit: 27. Clinically relevant abnormal values from the laboratory tests on haematology, serum chemistry and urinalysis. 28. Initiated or changed pelvic floor muscle training within 2 months before the baseline visit or planned such therapy during the study. 29. Any treatment with clean intermittent self catheterisation or indwelling catheter within 2 weeks before baseline visit. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint is the change in frequency of incontinence episodes per 24 hours from baseline to last evaluable visit. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 9 |