A Multinational Study Comparing the Long-term Efficacy and Safety of Two Medicines, Solifenacin Succinate and Mirabegron Taken Together, or Separately, in Subjects With Symptoms of Overactive Bladder (SYNERGY II)

Astellas

Status and phase: Completed; Phase 3

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

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

Study type: Interventional

Funder types: Industry

Identifiers

NCT02045862

178-CL-102

2012-005736-29 (EudraCT Number)

Details and patient eligibility

About

The purpose of this study was to examine how well the combination of two medicines (solifenacin succinate and mirabegron) worked compared to each medicine alone in the treatment of bladder problems, and how safe they were for long term use.

Enrollment: 1,829 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

Main Inclusion at Screening (Visit 1):

• Subject had completed study 178-CL-101 or study 905-EC-012 (This inclusion criterion would no longer apply once the recruitment for study 178-CL-101 and study 905-EC-012 had been completed. In that case the subject had to have symptoms of "wet" OAB (urinary frequency and urgency with incontinence) for at least 3 months);
• 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;

Main Inclusion at Randomization (Visit 2):

• Subject had a micturition frequency of on average ≥ 8 times per 24-hour period during the last 7 days of the micturition diary period (incontinence episode should not be counted as a micturition).
• Subject had experienced at least 3 incontinence episodes during the last 7 days of the micturition diary period.
• Subject had experienced on average at least 1 urgency episode (grade 3 or 4 on Patient Perception of Intensity of Urgency Scale [PPIUS]) per 24-hour period during the 7-day micturition diary period.

Exclusion criteria

Main Exclusion at Screening (Visit 1):

• Subject had clinically significant bladder outflow obstruction at risk of urinary retention;
• Subject had significant PVR volume (> 150 mL);
• Subject had significant stress incontinence or mixed stress/urgency incontinence where stress is the predominant factor;
• Subject has an indwelling catheter or practices intermittent self-catheterization;
• Subject had evidence of a UTI (urine culture containing > 100,000 cfu/mL), chronic inflammation such as interstitial cystitis, bladder stones, previous pelvic radiation therapy or previous or current malignant disease of the pelvic organs;
• Subject had intravesical treatment in the past 12 months with e.g., botulinum toxin, resiniferatoxin, capsaicin;

Main Exclusion at Randomization (Visit 2):

• Subject had evidence of a urinary tract infection (UTI) (urine culture containing > 100,000 cfu/mL) as assessed in the Screening visit (V1) samples. The subject could be rescreened after successful treatment of the UTI (confirmed by a dipstick negative for nitrite).
• Subject had an average total daily urine volume > 3000 mL as recorded in the micturition diary period.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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1,829 participants in 3 patient groups

Mirabegron 50 mg

Active Comparator group

Description:

Participants received mirabegron 50 mg once a day for 52 weeks.

Treatment:

Drug: Mirabegron

Drug: Placebo to match solifenacin

Solifenacin 5 mg

Active Comparator group

Description:

Participants received solifenacin 5 mg once a day for 52 weeks.

Treatment:

Drug: Solifenacin succinate

Drug: Placebo to match mirabegron

Solifenacin 5 mg + Mirabegron 50 mg

Experimental group

Description:

Participants received solifenacin 5 mg and mirabegron 50 mg once a day for 52 weeks.

Treatment:

Drug: Mirabegron

Drug: Solifenacin succinate