Weill Cornell Medical College, New York, NY 10021-7917, USA.
Int J Obes (Lond). 2010 May;34(5):919-35. doi: 10.1038/ijo.2010.21. Epub 2010 Feb 16.
To evaluate the efficacy, safety and tolerability of taranabant in obese and overweight patients.
Double-blind, randomized, placebo-controlled study.
Patients were >or=18 years old, with body mass index of 27-43 kg m(-2), and 51% with metabolic syndrome (MS) randomized to placebo (N=417) or taranabant 2 mg (N=414), 4 mg (N=415) or 6 mg (N=1256) for 104 weeks.
Key efficacy measurements included body weight, waist circumference (WC), lipid and glycemic end points.
On the basis of risk/benefit assessments, the 6-mg dose was discontinued during year 1 (patients on 6 mg were down-dosed to 2 mg or placebo) and the 4-mg dose was discontinued during year 2 (patients on 4 mg were down-dosed to 2 mg). Changes from baseline in body weight at week 52 (all-patients-treated population, last observation carried forward analysis) were -2.6, -6.6 and -8.1 kg, respectively, for placebo and taranabant 2 and 4 mg (both doses P<0.001 vs placebo). For patients who completed year 1, changes from baseline in body weight at week 104 were -1.4, -6.4 and -7.6 kg for placebo and taranabant 2 and 4 mg, respectively (both doses P<0.001 vs placebo). The proportions of patients at weeks 52 and 104 who lost at least 5 and 10% of their baseline body weight were significantly higher and the proportions of patients who met criteria for MS were significantly lower for taranabant 2 and 4 mg vs placebo. The incidence of adverse experiences classified in the gastrointestinal, nervous, psychiatric, cutaneous and vascular organ systems were generally observed to be dose related with taranabant vs placebo.
Taranabant at the 2- and 4-mg dose was effective in achieving clinically significant weight loss over 2 years and was associated with dose-related increases in adverse experiences. On the basis of these and other data, an assessment was made that the overall safety and efficacy profile of taranabant did not support its further development for the treatment of obesity.
评估 taranabant 在肥胖和超重患者中的疗效、安全性和耐受性。
双盲、随机、安慰剂对照研究。
患者年龄≥18 岁，体重指数为 27-43kg/m²，51%合并代谢综合征（MS），随机分为安慰剂（N=417）或 taranabant 2mg（N=414）、4mg（N=415）或 6mg（N=1256），治疗 104 周。
主要疗效测量包括体重、腰围（WC）、血脂和血糖终点。
基于风险/获益评估，6mg 剂量在第 1 年（6mg 组患者剂量下调至 2mg 或安慰剂）中停用，4mg 剂量在第 2 年（4mg 组患者剂量下调至 2mg）中停用。第 52 周（全患者治疗人群，末次观察值结转分析）时体重与基线相比的变化分别为安慰剂和 taranabant 2mg 和 4mg 组的-2.6、-6.6 和-8.1kg（均 P<0.001 与安慰剂相比）。对于完成第 1 年的患者，第 104 周时体重与基线相比的变化分别为安慰剂和 taranabant 2mg 和 4mg 组的-1.4、-6.4 和-7.6kg（均 P<0.001 与安慰剂相比）。第 52 周和第 104 周时，体重至少减轻 5%和 10%的患者比例以及符合 MS 标准的患者比例均显著高于安慰剂组，而 taranabant 2mg 和 4mg 组的比例均显著高于安慰剂组。与安慰剂相比，胃肠道、神经、精神、皮肤和血管系统器官分类的不良事件发生率通常与 taranabant 剂量相关。
taranabant 2mg 和 4mg 剂量在 2 年内有效实现了临床显著的体重减轻，且与剂量相关的不良事件发生率增加相关。基于这些和其他数据，评估认为 taranabant 的总体安全性和疗效特征不支持其进一步开发用于肥胖治疗。
