| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 8.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10059617 |
|
| 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 |
| To evaluate the dose-response relationship of SVT-40776 on efficacy |
|
| E.2.2 | Secondary objectives of the trial |
1) To compare 4 weeks efficacy of different doses of SVT-40776 to that of placebo in patients suffering from OAB.
2) To compare the tolerability of different doses of SVT-40776 to that of placebo in patients suffering from OAB.
3) To compare 4 weeks efficacy and tolerability of tolterodine 4 mg to that of placebo in patients suffering from OAB.
4) To obtain exposure-response data of SVT-40776 in a subgroup of patients. |
|
| E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
| E.3 | Principal inclusion criteria |
Subject eligibility will be based on the presence of symptoms of OAB and a willingness to participate in the study.
Screening Visit: Patients fulfilling the following criteria at this visit are eligible for participation in the study:
•Male or female patients aged 18 to 80 years. Female patients must be of non child-bearing potential or using effective contraception, e.g. use of oral contraceptives with an additional barrier method (since the study drug may impair the effectiveness of oral contraceptives), double barrier methods (diaphragm with spermicidal gel or condoms with contraceptive foam), Depo-Provera, partner vasectomy, total abstinence, and willing to continue the effective contraception method for 2 weeks after study completion. Pregnancy testing and birth control measures are required for younger women who are amenorrheic for >12 months without confirmation of surgical sterilization or postmenopausal status by FSH levels.
•Females of childbearing potential, including those currently using accepted forms of reliable contraception, must have a negative pregnancy test prior to enrolment and not be, in the opinion of the investigator, at appreciable risk of becoming pregnant.
•Patients suffering from OAB based on three cardinal symptoms (urgency with or without urge incontinence, usually accompanied by frequency or nocturia) for at least 6 months prior to inclusion.
•Patients must be able to adhere to the study visit schedule and other protocol requirements.
•Patients must be able and willing to correctly and independently complete their diary cards.
•Patients must be able to use the toilet without assistance.
•Patients must understand and voluntarily sign informed consent before screening, following an explanation of the nature and purpose of this study.
Visit 1 (Day 0) - (start of double-blind treatment period): Patients must continue to fulfil the Screening visit criteria for participation in the study. In addition, patients fulfilling both the following criteria at this visit are eligible for randomisation to the double-blind period of the study:
•Patients who document, during the 14 day placebo run-in period, an average of ≥ 10 micturitions/ 24 hours in the patient diary (recorded for the last three consecutive days before Visit 1).
•Patients who document, during the 14 day placebo run-in period, either a total of ≥ 3 incontinence episodes or a total of ≥ 3 urgency episodes in the patient diary (recorded for the last three consecutive days before Visit 1). |
|
| E.4 | Principal exclusion criteria |
Screening visit:
•Clinically significant bladder neck obstructions defined as post-void residual urine volumes greater than 100 mL.
•Peak free uroflow <15 mL/sec in males or <10 mL/sec in females.
•Clinically predominant stress incontinence (≥ 2 episodes of stress incontinence per week).
•Known hypersensitivity to any component of the drug product, such as excipients.
•Neurological diseases that could cause neurogenic incontinence such as multiple sclerosis, Parkinson, medullar affections, severe cerebral arteriosclerosis.
•Significant urogenital disease such as recurrent urinary tract infection (more than 2/year), bladder calculi, interstitial cystitis, urothelial tumours, hysterectomy or prostatectomy in the previous 6 months.
•Bladder surgeries performed within the previous 6 months, or those who have had surgeries leading to complications such as fistula.
•Females diagnosed with bladder cancer within the previous 6 months or currently receiving therapies for bladder cancer.
•Males diagnosed with bladder cancer, prostate cancer or chronic prostatitis within the previous 6 months, or currently taking therapies for bladder cancer.
•Prior pelvic malignancies requiring radiation therapy, or whose surgery for such has led to complications such as fistulas, etc.
•Females with history of sling procedure within the previous 6 months.
•Indwelling catheters or requiring intermittent catheterisation.
•Pelvic prolapse of grade III or higher (Baden’s classification ).
•Obstructive disease of the gastrointestinal tract, intestinal inflammatory disease, any ulcerative colitis, inflammatory bowel disease, toxic megacolon, intestinal atony or paralytic ileum.
•Any renal or liver insufficiency, or clinically significant renal or hepatic disease (ranges available in Laboratory Manual for this study).
•Patients referring dry mouth, parotid glands swelling or inability to swallow without liquid aid, during the past 3 months.
•Any medical or psychiatric condition that in the investigator’s opinion could compromise the patient's ability to participate in the trial.
•Myasthenia gravis.
•Diabetic neuropathy.
•Severe constipation defined as less than two bowel movements per week.
•Clinically relevant arrhythmias, unstable angina pectoris, myocardial infarct, or are using a pacemaker.
•Closed angle glaucoma or stenosis of the anterior chamber and/ or intraocular pressure >21 mmHg.
•Any contraindication to antimuscarinic drugs (e.g. urinary retention).
•Patients who in the past 3 months have undergone and/ or are anticipated to begin or change to other non-medicinal therapies such as lower urinary tract rehabilitation, electrical stimulation, catheterisation, bladder reflex triggering or bladder expression.
•History of chronic alcoholism or drug addiction in the preceding 6 months.
• Concomitant medications that, in the investigator’s opinion, would interfere with patient’s suitability and/or effective participation in the trial.
• Patients participating in another clinical trial or receiving a non-approved drug in the 4 weeks before the Screening visit.
Visit Day 14:
•Active urinary tract infection, i.e. screening urinalysis must be negative.
•Uninvestigated haematuria.
•Clinically significant abnormal laboratory values (haematology, clinical chemistry).
•Positive serology for Hepatitis B or Hepatitis C. Known positive test for HIV (human immunodeficiency virus).
•Females who are pregnant, breast feeding, or of child-bearing potential and who are not willing to use reliable contraception during the study.
•Males with prostate-specific antigen (PSA) >4 ng/mL.
•QTc interval (Bazett formula) >430 msec (in males) or >450 msec (in females) detected by ECG.
Visit Day 0:
•Average total volume voided greater than 3000 mL per day, as documented in the patient’s diary card for at least 2 consecutive days prior to the Day 0 visit.
•Total average volume voided greater than 250 mL per void, as documented in the patient’s diary card for at least 2 consecutive days prior to the Day 0 visit.
•Patients taking any of the non-permitted drugs specified in Section 4.2 of the protocol in the 2 weeks before the Day 0 visit.
•Patients taking antidepressants specified in the protocol or neuroleptics in the 4 weeks before the Day 0 visit.
•Patients with poor run-in treatment period compliance (four or more capsules not taken). |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| The primary efficacy endpoint will be the change in the number of micturitions per 24 hours from baseline to the end of the double-blind treatment period. |
|
| 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 | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | Yes |
| 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 | No |
| E.6.13 | Others | Information not present in EudraCT |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | Information not present in EudraCT |
| E.7.1.1 | First administration to humans | Information not present in EudraCT |
| E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
| E.7.1.3 | Other | Information not present in EudraCT |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | Information not present in EudraCT |
| E.7.4 | Therapeutic use (Phase IV) | Information not present in EudraCT |
| 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 | Information not present in EudraCT |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | Information not present in EudraCT |
| 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 | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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| 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
|
| Last visit of the last subject |
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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 | 5 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial months | 7 |
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