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 - ND

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2005-005431-97-IT
• Date of registration: 14/03/2006
• 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 - ND
• 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 - ND
• Date of first enrolment: 11/04/2006
• 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: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no

Countries of recruitment

Finland, Germany, Italy, Latvia, Spain

Key inclusion & exclusion criteria

Inclusion criteria:
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 Screening serum and at Day 0 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 8805; 19 kg/m2 but 31 kg/m2. BMI weight kg / height m2 3. Subjects must have a pre-dose mean systolic/diastolic blood pressure reading of 8804;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 8805; 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 8805; 1 incontinence episode/24 hrs over the three day diary recording period Mean of 8805; 1 urgency episode/24 hrs over the three day diary recording period Mean volume voided of 8804; 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:
Previous or Current Medical Conditions 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 pelvic organ prolapse with or without cystocele Refer to SRM 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 positive dipstick and abnormal microscopic evaluation at Screening , recent within 30 days , chronic or recurrent 4/year urinary tract infections or bladder stones. Refer to SRM 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 See Appendix 5 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. History of clinically significant drug hypersensitivity 13. Subjects with current within 2 years urogenital neoplasms or malignancies including bladder, uterine or cervical cancer 14. 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 15. Subjects with diabetes insipidus 16. Subjects with a fasting plasma glucose FPG 180 mg/dL at Day 0 Visit 2 17. Clinically significant or unstable, endocrine, hepatic, renal, immunologic, or lung disease i.e., glomerulonephritis, AIDS, asthma , or malignancy other than nonmelanomatous skin cancer 32 18. History of diagnosed gastrointestinal obstructive disorders 19. Chronic severe constipation Concomitant Medications 20. 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. 21. Administration of any other medication that would be considered a safety risk for co - administration with a 3 agonist e.g. antiarrhythmics or absorption, distribution, metabolism, or excretion 22. Subjects currently taking tricyclic antidepressants, diuretics or alpha blockers who have not been on a stable dose of these medications for at least one month will be excluded


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

Health Condition(s) or Problem(s) studied

Overactive bladder
MedDRA version: 6.1 Level: PT Classification code 10046543

Intervention(s)

Product Name: Solabegron
Product Code: GW427353
Pharmaceutical Form: Tablet
CAS Number: 451470-34-1
Current Sponsor code: GW427353
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
Product Code: GW427353
Pharmaceutical Form: Tablet
CAS Number: 451470-34-1
Current Sponsor code: GW427353
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)

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.

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.

Primary end point(s): Percentage change from baseline to Week 8 in the number of incontinence episodes/24 hrs

Secondary ID(s)

2005-005431-97-FI

B3P104833