Few safe and effective drug treatments are available. A combination treatment with sustained-release naltrexone and bupropion has been developed to produce complementary actions in CNS pathways regulating bodyweight. Two key systems are identified, the hypothalamic melanocortin sytem which integrates input related to energy balance and produces anorexigenic signalling and mesolimbic reward system which modulates reward value and goal orientated behaviour.
The Contrave Obesity Research I (COR-I) study assessed the effect of such treatment on bodyweight in overweight and obese participants.
1742 men and women aged 18-65 years who had a body-mass index (BMI) of 30-45 kg/m2 and uncomplicated obesity or BMI 27-45 kg/m2 with dyslipidaemia or hypertension were recruited to this randomised, double-blind, placebo-controlled, phase 3 trial.
Participants were prescribed mild hypo caloric 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 NBI6), or matching placebo twice a day, given orally for 56 weeks. The trial included a 3-week dose escalation.
The endpoints at 56 weeks were percentage change in bodyweight and proportion of participants who achieved a decrease in bodyweight of 5% or more.
Pparticipants were enrolled and randomised to double-blind treatment (naltrexone 32 mg plus bupropion, n=583; naltrexone 16 mg plus bupropion, and completed 56 weeks of treatment Mean change in bodyweight was -1• 3% in the placebo group, -6 •1% in the naltrexone 32 mg plus bupropion group and -5•0% (0•3) in the naltrexone 16 mg plus bupropion group
84 (16%) participants assigned to placebo had a decrease in bodyweight of 5% or more compared with 226 (48%) assigned to naltrexone 32 mg plus bupropion (p
Greenway et al 2010 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 The Lancet vol 376 595-605
- Martin Eastwood