NIDA-Funded Study Evaluating Extended-Release Injectable Naltrexone Plus Bupropion for the Treatment of Methamphetamine Use Disorder Published in New England Journal of Medicine
DUBLIN, Jan. 14, 2021 /PRNewswire/ -- Results from a National Institute on Drug Abuse (NIDA)-funded study evaluating the efficacy and safety of naltrexone for extended-release injectable suspension (XR-NTX) administered once every three weeks plus oral extended-release bupropion administered daily as a combination treatment for adults with moderate or severe methamphetamine use disorder (MUD) were published today by Dr. Madhukar H. Trivedi et al. in the New England Journal of Medicine (NEJM).1 This is the second published study evaluating this combination regimen for the treatment of MUD.2
The number of adults living with MUD has risen in recent years. In 2019, approximately 1 million adults in the U.S. reported having a methamphetamine use disorder—an increase of more than 50 percent since 2016.3 Currently, there are no FDA-approved medicines for the treatment of MUD.
"Given the scale and severity of the methamphetamine epidemic in the U.S., we applaud the clinical community's efforts and commitment to advancing research focused on treatment options for this critically underserved patient population," said Craig Hopkinson, M.D., Chief Medical Officer and Executive Vice President of Research & Development at Alkermes. "We're encouraged by the publication of this NIDA-funded study in the New England Journal of Medicine, and plan to engage with the FDA to better understand what options may exist for VIVITROL with regards to these data."
VIVITROL (naltrexone for extended-release injectable suspension) is not approved for the treatment of MUD. VIVITROL, developed by Alkermes (Nasdaq: ALKS), was approved by the U.S. Food and Drug Administration (FDA) for the treatment of alcohol dependence in 2006 and for the prevention of relapse to opioid dependence, following opioid detoxification, in 2010. VIVITROL is to be administered once every four weeks as part of a comprehensive management program that includes psychosocial support.
About the ADAPT-2 Study
The "Accelerated Development of Additive Pharmacotherapy Treatment (ADAPT-2) for Methamphetamine Use Disorder" study was a multi-site, double-blind, 12-week trial to evaluate the efficacy and safety of XR-NTX (380 mg every three weeks) plus oral extended-release bupropion (450 mg/day) in adults with moderate or severe MUD. Participants (N=403) with moderate or severe MUD (defined as reported use on at least 18 of the 30 days prior to randomization) were randomized to combination therapy (XR-NTX, 380 mg IM every three weeks, plus bupropion XL, up to 450 mg/d) versus placebo in a two-stage study. Placebo non-responders from stage 1 (6 weeks) were re-randomized in stage 2 for another 6 weeks. The primary outcome was the proportion of "responders," defined as having at least three methamphetamine-negative urine samples out of four samples obtained during weeks 5-6 (for stage 1) or weeks 11-12 (for stage 2). Response rates were higher with XR-NTX plus bupropion than with placebo across both stages (overall weighted treatment effect of 11.1 percentage points; Wald z-test statistic = 4.53; p < 0.001; NNT =9), as well as in each stage [stage 1: (16.5% COMB vs. 3.4% PBO); stage 2: (11.4% COMB vs. 1.8% PBO)]. Secondary outcomes also favored treatment with XR-NTX plus bupropion XL as compared to placebo. Adverse events in the combination treatment group included gastrointestinal disorders, tremor, malaise, hyperhidrosis, and anorexia. Serious adverse events occurred in 8 of 223 participants (3.6%) who received XR-NTX plus bupropion in the study. Alkermes provided XR-NTX and matched placebo free of charge for use in this trial under a written agreement with NIDA.