A Randomized, Double-Blind, Placebo-Controlled, Crossover, Phase IIa Study to Evaluate Efficacy and Safety of the beta3-Adrenergic Receptor Agonist Solabegron in Subjects with Irritable Bowel Syndrome - N/A
- Conditions
- Irritable Bowel Syndrome (IBS)
- Registration Number
- EUCTR2005-006118-17-DE
- Lead Sponsor
- GlaxoSmithKline Research and Development Limited
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 100
A subject will be eligible for inclusion in this study only if all of the following criteria apply:
1.The subject signs and dates a written informed consent form prior to the initiation of any study-related activities, including discontinuation of any prohibited medications. (see Section 8.2)
2.The subject must be a male or female age >18 and < 65 years at the time of the Screening Visit.
3.The subject is ambulatory (defined as not depending exclusively on a wheelchair for mobility).
4.The subject has been diagnosed with IBS consistent with the Rome II Criteria as adapted in Appendix 3.
5.The subject has normal results from a colonoscopy, or a flexible sigmoidoscopy plus barium enema, according to subject's age, within 5 years of randomization. Otherwise, the appropriate procedure(s) must be performed and normal results obtained during the 7-day procedure window (prior to randomization):
•If the subject is < 50 years of age and has not had a colonic examination within 5 years of the Screening Visit, flexible sigmoidoscopy plus barium enema, or colonoscopy must be performed.
•If the subject is > 50 years of age and has not had a colonic examination within 5 years of the Screening Visit, a colonoscopy or flexible sigmoidoscopy plus barium enema must be performed.
Colonic procedure results must be known prior to dispensing study medication.
6.During the two-week screening phase, the subject must have conducted self assessments on at least 12 days using the telephone data entry system.
7.During the two-week screening phase, the subject must have reported an average IBS pain or discomfort score =1.5 (on a 5 point scale where 0=none, 1=mild, 2=moderate, 3=severe, 4=very severe).
8.If female; the subject must have a negative serum pregnancy test result at Screen and is eligible to participate if one of the following criteria apply:
•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
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)
F.1.3.1 Number of subjects for this age range
A subject will not be eligible for inclusion in this study if any of the following criteria apply:
Gastrointestinal Conditions
•Subject reported no stool for >= 7 consecutive days during the two-week screening phase.
•Evidence of a biochemical or structural abnormality of the digestive tract. These conditions include (but not limited to):
•Current evidence, or history of (at any time in the past);
•inflammatory bowel disease (Crohn's disease or ulcerative colitis)
•colonic ischemia
•functional dyspepsia
•Lactose intolerance, not on a stable diet
•Celiac Disease
•laxative abuse (in the clinical judgement of the physician)
•gastrointestinal surgery (exceptions include 6 months post-surgery appendectomy, cholecystectomy, fundoplication without gas bloat, or hiatal hernia repair; 3 months post-surgery herniorrhaphy without bowel resection)
•abdominal radiation therapy for any reason within 5 years
•gastroparesis
•GI malignancy
•carcinoid syndrome
•amyloidosis
•chronic pancreatitis
•gastrointestinal adhesions
•toxic megacolon
•gastrointestinal perforation
•gastrointestinal obstruction and/or stricture.
•Current evidence of or within the past 6 months:
i.diverticulitis
ii.ileus
iii.symptomatic cholelithiasis
iv.proctitis.
•Current evidence of Hemoccult (+) stool of unknown etiology.
Abnormal Screening Values
1.Systolic BP >140 mmHg, or 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
2.The subject has a screening ECG with a QTc value of >430msec for males or >450msec for females or a PR interval outside the range 120 to 200msec or an ECG that is not suitable for QT measurements (e.g. poorly defined termination of the T-wave) or any other clinically significant ECG finding.
3.Subjects with a serum potassium of <3.5 meq/L
4.Subjects with a known history of congenital or acquired QT interval prolongation or subjects who are taking medications known to prolong the QT interval (See Appendix 5)
5.Exhibits evidence of hepatic dysfunction, viral hepatitis, or exhibits serum ALT (SGPT), AST (SGOT), alkaline phosphatase or bilirubin values >2.0 times the upper limit of normal.
6.Renal impairment as evidenced by a serum creatinine value >2.0 mg/dl.
7.The subject has a positive antibody test for IgA antibodies to (human) TTG (tissue transglutaminase) using ELISA (positive >= 5 units/ml)
8.Exhibits an abnormal serum thyroid-stimulating hormone (TSH) value (If TSH has not been measured within the past three years, it must be assayed prior to randomization). If a subject with thyroid disease is being managed with medication and is judged to be euthryroid with an abnormal TSH level, then the subject may be randomized to treatment provided the euthryroid medication has been stable for at least 30 days.
Concomitant Medications
1.Is currently taking any of the following medications:
•Any medication for treatment of IBS, such as tricyclic antidepressants, alosetron, tegaserod, mebeverine.
•Any medication known to prolong QTc (See Appendix 5)
•Monoamine oxidase inhibitors
•Systemic corticosteroids (Note: topical hydrocortisone and inhaled corticosteroids are allowed)
•Warfarin or digoxin
•Antiretroviral drugs
•Inhaled beta agonists
•Norepinephrine or dopamine reupt
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method