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 | 17.1 |
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 with autonomic component or bladder involvement, or systemic or central
neurological disease such as multiple sclerosis and Parkinson's disease with autonomic component or bladder involvement). An autonomic component can be inferred when autonomic functions are affected, including heart rate, blood pressure, perspiration and digestion.
• 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 based on the triplicate ECGs completed at Screening 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 | 12 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 163 |
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 |
Germany |
Greece |
Hong Kong |
Hungary |
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 |