E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Body processes [G] - Physical Phenomena [G01] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10059617 |
E.1.2 | Term | Overactive bladder |
E.1.2 | System Organ Class | 100000004857 |
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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 safety and tolerability of long-term combination treatment of solifenacin (5 mg) with mirabegron (50 mg) compared to solifenacin and mirabegron monotherapy in subjects with overactive bladder (OAB) |
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E.2.2 | Secondary objectives of the trial |
To evaluate efficacy of long-term combination treatment with solifenacin and mirabegron
To evaluate Patient Reported Outcomes (PRO) during long-term combination treatment with solifenacin and mirabegron
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Subject is male or female and at least 18 years of age;
• Subject is willing and able to complete the micturition diary and questionnaires correctly and able to measure his/her vital signs at home at stipulated time points, using the device provided by the study personnel, and to adequately record the readings;
• Subject has symptoms of “wet” OAB for at least three months |
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E.4 | Principal exclusion criteria |
• Subject has neurological cause for detrusor overactivity (e.g.
neurogenic bladder, diabetic neuropathy or systemic or central
neurological disease such as multiple sclerosis and Parkinson's disease).
• Subject has chronic inflammation such as bladder pain syndrome /
interstitial cystitis, symptomatic bladder stones or any previous or
current radiation cystitis.
• Subject has moderate to severe hepatic impairment
• Subject has severe renal impairment
• Subject has a clinically significant abnormal ECG
• Subject has a concurrent malignancy or history of cancer (except
noninvasive skin cancer) within the last 5 years prior to screening.
• Subject has a QTcF interval > 450 ms for males or > 470 ms for
females or is at risk of QT prolongation (e.g., family history of long QT
syndrome, hypokalaemia).
• Subject has severe hypertension, which is defined as a sitting
average systolic blood pressure ≥ 180 mmHg and/or average diastolic
blood pressure ≥ 110 mmHg.
• In the opinion of the investigator the subject has clinically significant bladder outflow obstruction at risk of urinary retention;
• Subject has significant PVR volume (> 150 mL);
• Subject has significant stress incontinence or mixed stress/urgency incontinence where stress is the predominant factor as determined by the investigator;
• Subject has an indwelling catheter or practices intermittent self-catheterization;
• Subject has evidence of urinary tract infection (UTI), chronic inflammation such as interstitial cystitis, bladder stones, previous pelvic radiation therapy or previous or current malignant disease of the pelvic organs;
• Subject has had intravesical treatment in the past 12 months with e.g., botulinum toxin, resiniferatoxin, capsaicin; |
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E.5 End points |
E.5.1 | Primary end point(s) |
• Incidence and severity of treatment emergent adverse events (TEAEs)
Primary Efficacy Variables
• Change from baseline in mean number of incontinence episodes per 24 hours at EoT
• Change from baseline in mean number of micturitions per 24 hours at EoT |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
• Vital signs
• Laboratory test
• ECG parameters
• PVR
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | Yes |
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 | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
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.8.4.1 | Number of sites anticipated in Member State concerned | 8 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 188 |
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 | No |
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 |
Argentina |
Australia |
Belgium |
Brazil |
Bulgaria |
Canada |
Chile |
China |
Colombia |
Czech Republic |
Denmark |
Estonia |
Finland |
France |
Germany |
Greece |
Hong Kong |
Hungary |
India |
Indonesia |
Italy |
Korea, Republic of |
Latvia |
Lithuania |
Malaysia |
Mexico |
Netherlands |
New Zealand |
Norway |
Peru |
Philippines |
Poland |
Romania |
Russian Federation |
Singapore |
Slovakia |
Slovenia |
South Africa |
Spain |
Sweden |
Taiwan |
Thailand |
Turkey |
Ukraine |
United Kingdom |
United States |
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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 | 2 |
E.8.9.1 | In the Member State concerned months | 1 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 1 |
E.8.9.2 | In all countries concerned by the trial days | 0 |