This Was a Multinational Study Comparing the Efficacy and Safety of Two Medicines , Solifenacin Succinate and Mirabegron Taken Together, or Separately, or a Mock Treatment (Placebo) in Subjects With Symptoms of Overactive Bladder (SYNERGY)

Astellas

Status and phase: Completed; Phase 3

Conditions: Urgency Incontinence; Urinary Bladder Diseases\Urologic Diseases; Urinary Bladder Overactive; Overactive Bladder

Treatments: Drug: Solifenacin succinate; Drug: Mirabegron; Drug: Placebo to match mirabegron; Drug: Placebo to match solifenacin succinate

Study type: Interventional

Funder types: Industry

Identifiers

NCT01972841

U1111-1153-9095 (Other Identifier)

2012-005735-91 (EudraCT Number)

178-CL-101

Details and patient eligibility

About

The purpose of this study was to examine how well two medicines (solifenacin succinate and mirabegron) combined work compared to each medicine alone in the treatment of bladder problems.

Enrollment: 3,527 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Subject was 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 had symptoms of "wet" OAB (urinary frequency and urgency with incontinence) for at least 3 months;

Exclusion criteria

• Subject had significant PVR volume (> 150 mL);
• Subject had a 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 could be inferred when autonomic functions were affected, including heart rate, blood pressure, perspiration and digestion.
• Subject had an indwelling catheter or practices intermittent self catheterization.
• Subject had chronic inflammation such as bladder pain syndrome /interstitial cystitis, symptomatic bladder stones or any previous or current radiation cystitis.
• Subject had received intravesical treatment in the past 12 months with e.g., botulinum toxin, resiniferatoxin, capsaicin.
• Subject had moderate to severe hepatic impairment
• Subject had severe renal impairment
• Subject had a clinically significant abnormal ECG
• Subject had a concurrent malignancy or history of cancer (except noninvasive skin cancer) within the last 5 years prior to screening.
• Subject had an average 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 had severe hypertension, which is defined as a sitting average systolic blood pressure ≥ 180 mmHg and/or average diastolic blood pressure ≥ 110 mmHg.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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3,527 participants in 6 patient groups, including a placebo group

1: Solifenacin 5 mg + Mirabegron 25 mg

Experimental group

Description:

Participants who received solifenacin 5 mg and mirabegron 25 mg once a day for 12 weeks.

Treatment:

Drug: Placebo to match mirabegron

Drug: Mirabegron

Drug: Solifenacin succinate

2: Solifenacin 5 mg + Mirabegron 50 mg

Experimental group

Description:

Participants who received solifenacin 5 mg and mirabegron 50 mg once a day for 12 weeks.

Treatment:

Drug: Placebo to match mirabegron

Drug: Mirabegron

Drug: Solifenacin succinate

3: Placebo

Placebo Comparator group

Description:

Participants who received matching placebo once a day for 12 weeks.

Treatment:

Drug: Placebo to match solifenacin succinate

Drug: Placebo to match mirabegron

4: Solifenacin 5 mg

Active Comparator group

Description:

Participants who received solifenacin 5 mg once a day for 12 weeks.

Treatment:

Drug: Placebo to match mirabegron

Drug: Solifenacin succinate

5:Mirabegron 25 mg

Active Comparator group

Description:

Participants who received mirabegron 25 mg once a day for 12 weeks.

Treatment:

Drug: Placebo to match solifenacin succinate

Drug: Placebo to match mirabegron

Drug: Mirabegron

6: Mirabegron 50 mg

Active Comparator group

Description:

Participants who received mirabegron 50 mg once a day for 12 weeks.

Treatment:

Drug: Placebo to match solifenacin succinate

Drug: Placebo to match mirabegron

Drug: Mirabegron