A Trial Comparing Combination Treatment (Solifenacin Plus Mirabegron) With One Treatment Alone (Solifenacin)
Condition: Urinary Bladder Diseases; Urinary Bladder Overactive; Urologic Diseases
MeSH terms: Urologic Diseases; Urinary Bladder Diseases; Urinary Bladder, Overactive
Intervention: mirabegron 25 mg; mirabegron 50 mg; solifenacin 5 mg; solifenacin 10 mg; mirabegron 25 mg matching placebo; mirabegron 50 mg matching placebo; solifenacin 5 mg matching placebo; solifenacin 10 mg matching placebo
Intervention description: Mirabegron was supplied as the marketed formulation in the 25 mg OCAS (Oral Controlled Absorption System) modified release tablets. Medication was taken orally with a glass of water, with or without food.; Mirabegron was supplied as the marketed formulation in the 50 mg OCAS (Oral Controlled Absorption System) modified release tablets. Medication was taken orally with a glass of water, with or without food.; Solifenacin was provided as the marketed formulation in the 5 mg strength. Medication was taken orally with a glass of water, with or without food.; Solifenacin was provided as the marketed formulation in the 10 mg strength. Medication was taken orally with a glass of water, with or without food.; Matching placebo of mirabegron OCAS 25 mg tablets was supplied. Medication was taken orally with a glass of water, with or without food.; Matching placebo of mirabegron OCAS 50 mg tablets was supplied. Medication was taken orally with a glass of water, with or without food.; Matching placebo of solifenacin succinate 5 mg tablets was supplied. Medication was taken orally with a glass of water, with or without food.; Matching placebo of solifenacin succinate 10 mg tablets was supplied. Medication was taken orally with a glass of water, with or without food.
Intervention MeSH terms: Mirabegron; Solifenacin Succinate
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 2174.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Vesitrim; Betanis; Urgency; Frequency; Mirabegron; YM178; Betmiga; Vesicare; Micturition; YM905; Solifenacin; Urinary incontinence; Overactive Bladder (OAB); Myrbetriq; Vesikur; Urgency incontinence

Summary:

      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.
    

Eligibility criteria:

        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