A Study to Evaluate the Efficacy, Safety and Tolerability of Mirabegron and Solifenacin Succinate Alone and in Combination for the Treatment of Overactive Bladder
Condition: Urologic Diseases; Urinary Bladder Diseases; Urological Manifestations; Signs and Symptoms; Urinary Bladder, Overactive
MeSH terms: Urinary Bladder, Overactive; Urologic Diseases; Urinary Bladder Diseases; Urological Manifestations
Intervention: Mirabegron; Solifenacin succinate; Placebo
Intervention description: oral; oral; oral
Intervention MeSH terms: Mirabegron; Solifenacin Succinate
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Factorial Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 1307.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Urinary incontinence; Overactive bladder (OAB); Micturition; Frequency; YM178; Urgency incontinence; Urgency

Summary:

      The purpose of this study is to examine how well two medicines in combination (solifenacin
      succinate and mirabegron) work in the treatment of bladder problems over a 12-week period.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Inclusion Criteria at Visit 1/Screening:

               -  Subject has a Body Mass Index (BMI) of between 18 and 35 kg/m^2 and a total body
                  weight between 50 and 95 kg;

               -  Subject is willing and able to complete the micturition diary and questionnaires
                  correctly and is willing 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 overactive bladder (OAB; urinary frequency, urgency
                  and/or urgency incontinence) for at least 3 months.

          -  Inclusion Criteria at Visit 3/Baseline:

               -  Subject has experienced frequency of micturition on average ≥ 8 times per 24-hour
                  period during the 3-day micturition diary period (incontinence episode should not
                  be counted as a micturition);

               -  Subject must experience at least 1 episode of urgency (grade 3 or 4) per 24-hour
                  period (with or without urgency incontinence) during the 3 day micturition diary
                  period.

        Exclusion Criteria:

          -  Exclusion Criteria at Visit 1/Screening:

               -  Subject is breastfeeding, pregnant or intends to become pregnant during the
                  study. The pregnancy test (Beta Human Chorionic Gonadotropin in serum) at
                  Screening must be negative in women of childbearing potential;

               -  Female subjects of childbearing potential and not using a highly effective method
                  of birth control during the study and for 30 days after final study drug
                  administration.

               -  Male subjects (unless surgically sterile) with female spouses/partners who are of
                  childbearing potential, and not using a barrier method of contraception during
                  the study and for 30 days after final study drug administration. In addition,
                  female spouses/partners of male subjects and who are of childbearing potential
                  should also use a highly effective method of birth control during the study and
                  for 30 days after final study drug administration. Highly effective methods of
                  birth control are defined as those, alone or in combination, that result in a low
                  failure rate (i.e. less than 1% per year) when used consistently and correctly.

               -  Subject has significant post-void residual (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 (for
                  female subjects confirmed by the cough provocation test);

               -  Subject has a neurological cause for detrusor overactivity;

               -  Subject has an indwelling catheter or practices intermittent
                  self-catheterization;

               -  Subject has diabetic neuropathy;

               -  Subject has 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 previous lower urinary tract or pelvic floor surgery (except
                  cystoscopy);

               -  Subject has had intravesical treatment in the past 12 months with e.g., botulinum
                  toxin, resiniferatoxin, capsaicin;

               -  Subject has uncontrolled narrow angle glaucoma, urinary or gastric retention,
                  severe ulcerative colitis or Crohn's Disease, toxic megacolon, myasthenia gravis
                  or any other condition which makes the use of anticholinergics contraindicated;

               -  Subject has clinically significant cardiovascular or cerebrovascular diseases
                  within 6 months prior to Screening, such as myocardial infarction, uncontrolled
                  angina, significant ventricular arrhythmias, heart failure and stroke;

               -  Subject is receiving current non-drug treatment including electro-stimulation
                  therapy (with the exception of a bladder training program or pelvic floor
                  exercises which started more than 30 days prior to Screening);

               -  Subject is using medications intended to treat OAB or prohibited medications.

               -  Subject has known or suspected hypersensitivity to solifenacin succinate,
                  mirabegron or any of their excipients;

               -  Subject has any significant neurological disease or defect affecting bladder
                  function (e.g., neurogenic bladder, systemic or central neurological disease such
                  as multiple sclerosis [MS] and Parkinson's disease);

               -  Subject has severe hypertension which is defined as a sitting average systolic
                  blood pressure ≥ 180 mmHg and/or an average diastolic blood pressure ≥ 110 mmHg;

          -  Exclusion Criteria at Visit 2/Placebo Run-In:

               -  Subject has evidence of a urinary tract infection (UTI) (urine culture containing
                  > 100,000 cfu/mL). The subject can be enrolled into the study after successful
                  treatment of the UTI (confirmed by a laboratory result of negative urine
                  culture). However, the subject must be re screened if the initial screening visit
                  was > 28 days;

               -  Subject has a QT interval > 450 ms or is at risk of QT prolongation (e.g., family
                  history of long QT syndrome, hypokalaemia) or is on drug treatment known to be
                  associated with QT prolongation;

               -  Subject has clinically significant abnormalities on the 12 lead electrocardiogram
                  (ECG);

               -  Subject has serum creatinine > 150 µmol/L, aspartate aminotransferase (AST)
                  and/or alanine aminotransferase (ALT) > 2x upper limit of normal (ULN),
                  gamma-glutamyltransferase (γ-GT) > 3x ULN, or total bilirubin > 2x ULN, as
                  assessed in Screening samples;

          -  Exclusion Criteria at Visit 3/Baseline:

               -  Subject had an average total daily urine volume > 3000 mL as recorded in the
                  micturition diary period;

               -  Subject has severe hypertension which is defined as a sitting average systolic
                  blood pressure ≥ 180 mmHg and/or an average diastolic blood pressure ≥ 110 mmHg.