A Trial Comparing Combination Treatment (Solifenacin Plus Mirabegron) With One Treatment Alone (Solifenacin) (BESIDE)

Astellas

Status and phase: Completed; Phase 3

Conditions: Urinary Bladder Diseases; Urinary Bladder Overactive; Urologic Diseases

Treatments: Drug: mirabegron 25 mg matching placebo; Drug: mirabegron 50 mg; Drug: solifenacin 5 mg matching placebo; Drug: solifenacin 10 mg matching placebo; Drug: mirabegron 25 mg; Drug: solifenacin 10 mg; Drug: mirabegron 50 mg matching placebo; Drug: solifenacin 5 mg

Study type: Interventional

Funder types: Industry

Identifiers

NCT01908829

905-EC-012

2012-005401-41 (EudraCT Number)

Details and patient eligibility

About

The purpose of this study was to see if adding a new type of medication recently approved to treat overactive bladder (mirabegron) to an antimuscarinic treatment (solifenacin) would be more effective in controlling incontinence than when using the antimuscarinic treatment alone.

Enrollment: 2,174 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Main Inclusion at Screening:

  1. Subject has symptoms of OAB (urinary frequency and urgency with urgency incontinence) for >= 3 months prior to the screening visit
  2. Subject is willing and able to complete the micturition diary and questionnaires correctly, including collection and measurement of urine output for 3 days prior to each visit;
  3. Subject has symptoms of "wet" OAB (urinary frequency and urgency with incontinence or mixed incontinence with predominant urgency incontinence), and reports an average of at least 2 incontinence episodes per day.

• Main Inclusion at Run-in (Visit 2):

  1. Subject experiences on average at least 1 episode of urgency (grade 3 or 4) with or without incontinence per 24-hour period during the 3-day micturition diary period.
  2. Subject experiences on average at least 2 incontinence episodes per 24-hour period during the 3-day micturition diary period.
  3. Subject experiences on average at least 8 micturitions (excluding incontinence episodes) per 24-hour period during the 3-day micturition diary period.

• Main Inclusion at Randomization (Visit 3):

  1. Subject experiences at least 1 incontinence episode during the 3-day micturition diary period and wishes to increase their treatment for OAB symptoms.

Exclusion criteria

• Main Exclusion at Screening:

  1. Subject in the opinion of the investigator has clinically significant Bladder Outlet Obstruction (BOO).
  2. Subject has significant Post-void residual (PVR) volume (PVR > 150 ml).
  3. Subject has significant stress incontinence or mixed stress/urgency incontinence where stress is the predominant factor as determined by the investigator
  4. Subject has an indwelling catheter or practices intermittent self catheterization.
  5. Subject has evidence of a UTI.
  6. Subject has chronic inflammation such as interstitial cystitis, bladder stones, previous pelvic radiation therapy, or previous or current malignant disease of the pelvic organs
  7. Subject has moderate to severe hepatic impairment
  8. Subject has severe renal impairment or End Stage Renal disease
  9. Subject has a clinically significant abnormal Electrocardiogram (ECG)
  10. Subject has a concurrent malignancy or history of cancer (except noninvasive skin cancer) within the last 5 years prior to screening.
  11. 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).
  12. Subject has received intravesical treatment in the past 12 months with e.g., botulinum toxin, resiniferatoxin, capsaicin.
  13. Subject has severe uncontrolled hypertension, which is defined as a sitting average systolic blood pressure ≥ 180 mmHg and/or average diastolic blood pressure ≥ 110 mmHg.

• Main Exclusion at Randomization (visit 3):

  1. Subject has achieved 100% continence from Visit 2 to Visit 3 (no incontinence episodes are recorded in the 3 day diary administered for 3 days prior to Visit 3).
  2. Subject does not desire an increase in study medication.
  3. Subject has an average total daily urine volume > 3000ml as recorded in the micturition diary.
  4. Subject has severe uncontrolled hypertension, which is defined as a sitting average systolic blood pressure ≥ 180 mmHg and/or average diastolic blood pressure ≥ 110 mmHg.
  5. Subject has a clinically significant abnormal ECG

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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2,174 participants in 3 patient groups

Combination (solifenacin + mirabegron)

Experimental group

Description:

Participants received solifenacin 5 mg, mirabegron 25 mg and solifenacin 10 mg matching placebo once daily for the first 4 weeks of double-blind period. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron tablet was replaced by a 50 mg mirabegron tablet. Placebo was given for the 2 week single-blind safety follow-up period.

Treatment:

Drug: solifenacin 5 mg

Drug: mirabegron 25 mg

Drug: solifenacin 10 mg matching placebo

Drug: mirabegron 50 mg

Solifenacin 5 mg

Active Comparator group

Description:

Participants received solifenacin 5 mg, mirabegron 25 mg matching placebo and solifenacin 10 mg matching placebo once daily. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron matching placebo tablet was replaced by a 50 mg mirabegron matching placebo tablet (to maintain the blind). Placebo was given for the 2 week single-blind safety follow-up period

Treatment:

Drug: solifenacin 5 mg

Drug: mirabegron 50 mg matching placebo

Drug: solifenacin 10 mg matching placebo

Drug: mirabegron 25 mg matching placebo

Solifenacin 10 mg

Active Comparator group

Description:

Participants received solifenacin 5 mg matching placebo, mirabegron 25 mg matching placebo and solifenacin 10 mg once daily. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron matching placebo tablet was replaced by a 50 mg mirabegron matching placebo tablet (to maintain the blind). Placebo was given for the 2 week single-blind safety follow-up period.

Treatment:

Drug: mirabegron 50 mg matching placebo

Drug: solifenacin 10 mg

Drug: solifenacin 5 mg matching placebo

Drug: mirabegron 25 mg matching placebo