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Kopelman P.,St George's, University of London | De H. Groot G.,Nederlandse Obesitas Kliniek | Rissanen A.,Obesity Reserach Unit | Rossner S.,Karolinska University Hospital | And 5 more authors.
Obesity | Year: 2010

The objective of this multicenter, randomized, double-blind study was to determine the efficacy and safety of cetilistat and orlistat relative to placebo in obese patients with type 2 diabetes, on metformin. Following a 2-week run-in, patients were randomized to placebo, cetilistat (40, 80, or 120 mg three times daily), or orlistat 120 mg t.i.d., for 12 weeks. The primary endpoint was absolute change in body weight from baseline. Secondary endpoints included other measures of obesity and glycemic control. Similar reductions in body weight were observed in patients receiving cetilistat 80 or 120 mg t.i.d. or 120 mg t.i.d. orlistat; these reductions were significant vs. placebo (3.85 kg, P = 0.01; 4.32 kg, P = 0.0002; 3.78 kg, P = 0.008). In the 40 mg t.i.d. and placebo groups, reductions were 2.94 kg, P = 0.958 and 2.86 kg, respectively. Statistically significant reductions in glycosylated hemoglobin (HbA 1c) were noted. Cetilistat was well tolerated, and showed fewer discontinuations due to adverse events (AEs) than in the placebo and orlistat groups. Discontinuation in the orlistat group was significantly worse than in the 120 mg cetilistat and placebo groups and was entirely due to gastrointestinal (GI) AEs. Treatment with cetilistat 80 or 120 mg t.i.d., or with orlistat 120 mg t.i.d., significantly reduced body weight and improved glycemic control relative to placebo in obese diabetic patients. Cetilistat was well tolerated with the number of discontinuations due to AEs being similar to placebo.

Lembo A.J.,Beth Israel Deaconess Medical Center | Cremonini F.,Beth Israel Deaconess Medical Center | Meyers N.,Alizyme Therapeutics Ltd | Hickling R.,Alizyme Therapeutics Ltd
Alimentary Pharmacology and Therapeutics | Year: 2010

Background Renzapride, a 5-hydroxytryptamine type-4 (5-HT4) receptor agonist and 5-HT3 receptor antagonist, has been proposed as a new treatment of irritable bowel syndrome with constipation (IBS-C). Aim To assess the efficacy and safety of renzapride in women with IBS-C. Methods Women with IBS-C were randomized to renzapride 4 mg daily, 2 mg b.d. or placebo for 12 weeks. The primary outcome measure was global relief of IBS symptoms. A subset of patients were enrolled in a 12-month, open-label study of renzapride 4 mg daily. Results A total of 1798 patients were included in the efficacy analysis and 971 patients entered the long-term study. The mean (S.E.M.) number of months with relief of overall IBS symptoms was 0.55 (0.04), 0.60 (0.04) and 0.44 (0.04) in the renzapride 4 mg daily, 2 mg b.d. and placebo groups (P = 0.027 and P = 0.004 respectively). Small yet statistically significant differences in favour of renzapride were observed on stool consistency and frequency, and bloating/abdominal distension scores. Renzapride was generally well tolerated; however, three episodes of ischaemic colitis were reported in the long-term study. Conclusion Given the limited increase in efficacy over placebo and the incidence of ischaemic colitis observed, our data suggest that the benefit/risk ratio of renzapride is not sufficient to warrant further study in IBS-C. © 2010 Blackwell Publishing Ltd.

Alizyme Therapeutics Ltd | Date: 2010-08-31


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