Overactive bladder (OAB)
Conditions
Interventions
Product Name: Solabegron tablets
Product Code: GW427353
Pharmaceutical Form: Tablet
INN or Proposed INN: Solabegron
CAS Number: 451470-34-1
Concentration unit: mg milligram(s)
Concentration type: equa
Sponsors
GlaxoSmithKline Research & Development
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Females with OAB who are >18 years but not older than 80 years of age who have signed the informed consent. • If of non-childbearing potential (i.e. physiologically incapable of becoming pregnant (tubal ligation), including any female who is post-menopausal [>1 year without menstrual period]) or • If of childbearing potential, has had a negative pregnancy test at screen (serum) and at Day 1 (urine) and • Has a male partner who is sterile prior to the female subject's entry into the study and is the sole sexual partner for that female subject, or • Uses double-barrier methods of contraception; condoms with the use of caps (with spermicide) and IUDs are acceptable, or • Uses hormonal contraceptives (oral, depots, patches, etc.) with double-barrier methods of contraception as outlined above, or • Abstains from sexual intercourse, or • Is with a same-sex partner and does not participate in bisexual activities where there is any risk of pregnancy 2. Female subjects with a BMI in the range = 19 kg/m2 but =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Subjects with stress incontinence or mixed stress/urge incontinence where stress incontinence is the predominant component based on prior history 2. Grade III/IV prolapse with cystocele or second or third degree uterine prolapse 3. History of interstitial cystitis or bladder related pain 4. History of pelvic prolapse repair (cystocele or rectocele) or urethral diverticulectomy within six months of screening 5. Subjects with urinary incontinence due to causes other than detrusor over activity (e.g., overflow incontinence or intrinsic sphincter deficiency) 6. Nocturnal enuresis only 7. Urinary retention, or other evidence of poor detrusor function 8. Subjects with concurrent, recent (within 30 days), chronic or recurrent (> 4/year) urinary tract infections or bladder stones. 9. Documented history of myocardial infarction, unstable angina, and/or has undergone coronary artery bypass surgery and/or percutaneous transluminal coronary angioplasty (PTCA) in the past year 10. Congestive heart failure (New York Heart Association Class III or IV heart failure) 11. Any concurrent condition or any clinically significant abnormality on the screening physical examination, laboratory tests, electrocardiogram (including ischemic heart disease), Hepatitis B or C, which, in the opinion of the Investigator, may affect the interpretation of efficacy or safety data, or which otherwise contraindicates participation in a clinical trial with a new chemical entity 12. Subjects with current (within 2 years) urogenital neoplasms or malignancies including bladder, uterine or cervical cancer 13. Subjects with neuropathology that could affect the lower urinary tract or nerve supply, including but not limited to multiple sclerosis, stroke, Parkinsonism, or spinal cord injury 14. Subjects with diabetes insipidus 15. Subjects with a fasting plasma glucose (FPG) >180 mg/dL at Day 0 (Visit 2) 16. Clinically significant or unstable, endocrine, hepatic, renal, immunologic, or lung disease (i.e., glomerulonephritis, AIDS, asthma), or malignancy other than nonmelanomatous skin cancer 17. History of diagnosed gastrointestinal obstructive disorders 18. Chronic severe constipation Concomitant Medications 19. Is currently taking any of the following medications: • Monoamine oxidase inhibitors • Systemic corticosteroids (Note: topical hydrocortisone and inhaled corticosteroids are allowed) • Warfarin or digoxin • Antiretroviral drugs • Inhaled beta agonists • Norepinephrine or dopamine reuptake inhibitors • Bile acid sequestrant, such as cholestyramine or colestipol • Herbal preparations. However, subjects who have been on a stable dose of these preparations prior to entering the study may continue to take these drugs. No new herbal preparations may be introduced or dosage changes initiated while participating in the study. • Anti-arrhythmics 20. Subjects who have not been stable on anti-depressants, diuretics or alpha blockers for less than a month or not stable on SSRIs for 2 months. Abnormal Values of Concern 21. Systolic BP >140 mmHg, diastolic BP >90 mmHg, or HR > 100 beats/minute at screening. If subject is receiving anti-hypertensive medication, then their BP must have been stable over the last month on the same dose of antihypertensives including, but not limited to, ACE inhibitors, diuretics, Ca channel blockers, or ß blockers 22. Post-void residual urine volume >150mL documented on either of two bladder scans at screening 23. QTc interval >450 msec a
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this study is to compare the efficacy of solabegron 250mg, 125mg, and 50mg administered twice daily to that of placebo in female subjects with OAB including symptoms of urgency with urge incontinence and frequency which may be associated with nocturia, but without bladder related pain. ;Secondary Objective: To evaluate the safety and tolerability of solabegron 250mg, 125mg, and 50mg administered twice daily compared to that of placebo in female subjects with OAB including symptoms of urgency with urge incontinence and frequency which may be associated with nocturia, but without bladder related pain. To characterize the pharmacokinetic relationship of solabegron (GW427353B) and its primary metabolite (GW678953X) in female subjects with OAB including symptoms of urgency with urge incontinence and frequency which may be associated with nocturia, but without bladder related pain. ;Primary end point(s): The percentage change from baseline to week 8 in the number of incontinence episodes per 24 hours. Subjects who get worse by more than 100% will be censored at 100% worsening. The last available post-baseline assessment on or before week 8 will be used in the calculation. | — |
Countries
Finland, Germany, Italy, Latvia, Spain
Outcome results
None listed