E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Symptoms of overactive bladder |
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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 |
To assess the efficacy of YM178 25 mg qd and YM178 50 mg qd against placebo in the treatment of subjects with symptoms of overactive bladder. |
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E.2.2 | Secondary objectives of the trial |
To assess the safety and tolerability of YM178 25 mg qd and YM178 50 mg qd against placebo in the treatment of subjects with symptoms of overactive bladder. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Inclusion Criteria Subject is eligible for the study if all of the following apply:
Inclusion Criteria at Visit 1/Screening 1. Male or female subject ≥ 18 years of age. 2. Institutional Review Board (IRB)-/Independent Ethics Committee (IEC)-approved written Informed Consent and privacy language as per national regulations (e.g., HIPAA Authorization for U.S. sites) is obtained from the subject or legally authorized representative prior to any study-related procedures (including withdrawal of prohibited medication, if applicable). 3. Subject is willing and able to complete the micturition diary and questionnaires correctly. 4. Subject has symptoms of overactive bladder (urinary frequency and urgency with or without incontinence) for ≥ 3 months.
Inclusion Criteria at Visit 2/Baseline 5. Subject must experience frequency of micturition on average ≥ 8 times per 24-hour period during the 3-day micturition diary period. 6. Subject must experience at least 3 episodes of urgency (grade 3 or 4) with or without incontinence during the 3-day micturition diary period. 7. Subject must still fulfill all inclusion criteria and none of the exclusion criteria of Visit 1.
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E.4 | Principal exclusion criteria |
1. Subject is breastfeeding, pregnant, intends to become pregnant during the study, or of childbearing potential, sexually active and not practicing a highly reliable method of birth control (these are methods with a failure quotient of <1% per year such as hormonal implants, injectable contraceptives, oral contraceptives of combination type, intra-uterine pessaries restricted to hormone contraceptive coil, sexual abstinence or vasectomy of the partner). The pregnancy test (-HCG in serum) at visit 1 needs to be negative in women of childbearing potential. 2. Subject has significant stress incontinence or mixed stress/urge incontinence where stress is the predominant factor as determined by the investigator (for female subjects confirmed by a cough provocation test). 3. Subject has an indwelling catheter or practices intermittent self-catheterization. 4. Subject has diabetic neuropathy. 5. Subject has evidence of urinary tract infection, chronic inflammation such as interstitial cystitis, bladder stones, previous pelvic radiation therapy or previous or current malignant disease of the pelvic organs. 6. Subject receives current non-drug treatment including electro-stimulation therapy (a bladder training program or pelvic floor exercises which started more than 30 days prior to entry into the study can be continued). 7. Subject is using medications intended to treat OAB or prohibited medications listed in Appendix 1, Part A of the protocol. Subject is excluded if using restricted medications (Appendix 1, Part B of the protocol) and the criteria specified in Appendix 1, Part B of the protocol are not met. 8. Subject has severe hypertension, which is defined as a sitting average systolic blood pressure ≥ 180 mmHg and/or average diastolic blood pressure ≥ 110 mmHg (see section 5.4.1. Vital Signs). 9. Subject has a known or suspected hypersensitivity to YM178, other ß3 agonists, or any of the inactive ingredients. 10. Subject has any clinically significant condition, which in the opinion of the investigator makes the subject unsuitable for the study. 11. Subject has been part of any clinical study within 30 days (90 days in the UK) prior to Visit 1/screening, or has participated in any previous study with YM178. 12. Subject is an employee of the Astellas Group, third parties associated with the study, or the clinical study site team.
Exclusion criteria at Visit 2/Baseline 13. Subject had an average total daily urine volume > 3000 mL as recorded in the 3-day micturition diary period. 14. Subject has serum creatinine >150 μmol/L or AST or ALT > 2x upper limit of normal range (ULN), or γ-GT > 3x ULN as assessed in Visit 1 samples and considered clinically significant by the investigator. 15. Subject has severe hypertension, which is defined as a sitting average systolic blood pressure ≥ 180 mmHg and/or average diastolic blood pressure ≥ 110 mmHg (see section 5.4.1. Vital Signs). 16. Subject has an abnormal ECG, which in the opinion of the investigator makes the subject unsuitable for the study.
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E.5 End points |
E.5.1 | Primary end point(s) |
Co-primary efficacy variables: • Change from baseline in mean number of micturitions/24 h based on a 3-day micturition diary, • Change from baseline in mean number of incontinence episodes/24 h based on a 3-day micturition diary.
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Information not present in EudraCT |
E.6.2 | Prophylaxis | Information not present in EudraCT |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Information not present in EudraCT |
E.6.8 | Bioequivalence | Information not present in EudraCT |
E.6.9 | Dose response | Information not present in EudraCT |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | Information not present in EudraCT |
E.6.12 | Pharmacoeconomic | Yes |
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) | Information not present in EudraCT |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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 | Yes |
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 | 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 | No |
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 | 0 |
E.8.9.1 | In the Member State concerned months | 8 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |