Effect of naltrexone plus bupropion on weight loss in overweight and obese adults (COR-I): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial
Effect of naltrexone plus bupropion on weight loss in overweight and obese adults (COR-I): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial
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DOI：
10.1016/s0140-6736(10)60888-4
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发表时间：
2010-08-21
期刊：
影响因子：
168.9
通讯作者：
Dunayevich, Eduardo
中科院分区：
文献类型：
--
作者：
Greenway, Frank L.;Fujioka, Ken;Dunayevich, Eduardo
背景尽管公众对肥胖的关注与日俱增，但几乎没有安全有效的药物治疗方法。纳曲酮缓释剂和安非他酮联合治疗是为了在调节体重的中枢神经系统通路中产生互补作用。对照肥胖研究I(COR-I)研究评估了这种治疗对超重和肥胖者体重的影响。方法18-65岁的男性和女性，体重指数(BMI)30-45 kg/m(2)，无并发症肥胖或BMI 27-45 kg/m(2)合并血脂异常或高血压，有资格参加这项在美国34个地点进行的随机、双盲、安慰剂对照的第三阶段试验。受试者接受轻度低热量饮食和运动，并按1：1：1的比例随机分配，分别接受纳曲酮缓释32毫克/天加缓释安非他酮360毫克/天合并固定剂量片剂(也称为NB32)、纳曲酮缓释16毫克/天加缓释安非他酮360毫克/天合并固定剂量片剂(也称为NB16)或匹配的安慰剂每天两次口服，为期56周。试验包括为期3周的剂量递增。随机化是通过使用一个集中的、计算机生成的、基于网络的系统进行的，并由研究中心进行分层。56周时的共同主要疗效终点是体重的百分比变化和体重下降5%或更多的参与者的比例。初步分析包括所有随机参与者，在服用研究药物(最后一次观察)时，进行基线体重测量和基线后体重测量。这项研究在ClinicalTrials.gov上注册，编号为NCT00532779。结果1742名参与者参加了随机双盲治疗(纳曲酮32毫克+安非他酮，n=583；纳曲酮16毫克+安非他酮，n=578；安慰剂，n=581)。870名(50%)参与者完成了56周的治疗(分别为296例；284例；290例)和1453例(83%)进入初步分析(471例；471例；511例)。平均体重变化安慰剂组为-1.3%(SE 0.3)，纳曲酮32 mg+安非他酮组为-6.1%(0.3)(P
Background Despite increasing public health concerns regarding obesity, few safe and effective drug treatments are available. Combination treatment with sustained-release naltrexone and bupropion was developed to produce complementary actions in CNS pathways regulating bodyweight. The Contrave Obesity Research I (COR-I) study assessed the effect of such treatment on bodyweight in overweight and obese participants.Methods Men and women aged 18-65 years who had a body-mass index (BMI) of 30-45 kg/m(2) and uncomplicated obesity or BMI 27-45 kg/m(2) with dyslipidaemia or hypertension were eligible for enrolment in this randomised, double-blind, placebo-controlled, phase 3 trial undertaken at 34 sites in the USA. Participants were prescribed mild hypocaloric diet and exercise and were randomly assigned in a 1:1:1 ratio to receive sustained-release naltrexone 32 mg per day plus sustained-release bupropion 360 mg per day combined in fixed-dose tablets (also known as NB32), sustained-release naltrexone 16 mg per day plus sustained-release bupropion 360 mg per day combined in fixed-dose tablets (also known as NB16), or matching placebo twice a day, given orally for 56 weeks. The trial included a 3-week dose escalation. Randomisation was done by use of a centralised, computer-generated, web-based system and was stratified by study centre. Co-primary efficacy endpoints at 56 weeks were percentage change in bodyweight and proportion of participants who achieved a decrease in bodyweight of 5% or more. The primary analysis included all randomised participants with a baseline weight measurement and a post-baseline weight measurement while on study drug (last observation carried forward). This study is registered with ClinicalTrials.gov, number NCT00532779.Findings 1742 participants were enrolled and randomised to double-blind treatment (naltrexone 32 mg plus bupropion, n=583; naltrexone 16 mg plus bupropion, n=578; placebo, n=581). 870 (50%) participants completed 56 weeks of treatment (n=296; n=284; n=290, respectively) and 1453 (83%) were included in the primary analysis (n=471; n=471; n=511). Mean change in bodyweight was -1.3% (SE 0.3) in the placebo group, -6.1% (0.3) in the naltrexone 32 mg plus bupropion group (p