An Eight-Week Randomized, Double-Blind, Placebo-Controlled, Parallel Group Proof of Concept Dose Ranging Study to Assess the Efficacy, Safety and Tolerability as well as the Pharmacokinetic Profile of Oral Solabegron (GW427353) 250mg, 125mg, and 50mg administered Twice Daily vs Placebo, in Women with Overactive Bladder

• Register: EUCTR
• Last refreshed on: 15 July 2013
• Main ID: EUCTR2005-005431-97-SI
• Date of registration: 02/02/2006
• Prospective Registration: Yes
• Primary sponsor: GlaxoSmithKline Research & Development
• Public title: An Eight-Week Randomized, Double-Blind, Placebo-Controlled, Parallel Group Proof of Concept Dose Ranging Study to Assess the Efficacy, Safety and Tolerability as well as the Pharmacokinetic Profile of Oral Solabegron (GW427353) 250mg, 125mg, and 50mg administered Twice Daily vs Placebo, in Women with Overactive Bladder
• Scientific title: An Eight-Week Randomized, Double-Blind, Placebo-Controlled, Parallel Group Proof of Concept Dose Ranging Study to Assess the Efficacy, Safety and Tolerability as well as the Pharmacokinetic Profile of Oral Solabegron (GW427353) 250mg, 125mg, and 50mg administered Twice Daily vs Placebo, in Women with Overactive Bladder
• Date of first enrolment: 16/02/2006
• Target sample size: 256
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2005-005431-97
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: Single blind: Double blind: yes Parallel group: Cross over: Other: If controlled, specify comparator, Other Medicinial Product: Placebo: yes Other:

Countries of recruitment

Finland, Germany, Latvia, Slovenia, Spain

Key inclusion & exclusion 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 <31 kg/m2.
3. Subjects must have a pre-dose mean systolic/diastolic blood pressure reading of <= 140/90 mmHg before randomization can occur.
4. While participating in the one or two week treatment-free run-in periods and three days immediately prior to randomization, Day 0 (Visit 2), subjects must also meet all of the following criteria as recorded in their electronic micturition diaries:
• Mean of = 10 micturitions/24 hrs over the three day diary recording period (micturitions are “toilet voids”. Incontinence episodes not associated with micturitions episodes are not considered micturition episodes)
• Mean of = 1 incontinence episode/24 hrs over the three day diary recording period
• Mean of = 1 urgency episode/24 hrs over the three day diary recording period
• Mean volume voided of ? 250 mL/micturition reported over the three day diary recording period
• Mean total urine volume of <3000 mL/24 hrs reported over the three day diary recording period


Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

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

Age minimum:
Age maximum:
Gender:
Female: yes
Male: no

Health Condition(s) or Problem(s) studied

Overactive bladder (OAB)

Intervention(s)

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: equal
Concentration number: 25-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

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: equal
Concentration number: 100-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

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.

Secondary ID(s)

B3P104833

2005-005431-97-FI