In the study, extended-release naltrexone met pre-specified non-inferiority criteria for comparison to buprenorphine-naloxone on all primary endpoints, including retention in treatment, proportion of total number of opioid-negative urine drug tests, and number of days of use of heroin and other illicit opioids. Overall, more patients reported adverse events in the extended-release naltrexone group versus those in the buprenorphine-naloxone group. Ten patients discontinued treatment due to adverse events: four in the extended-release naltrexone group and six in the buprenorphine-naloxone group.
“This study is the first-ever direct comparison of extended-release naltrexone and buprenorphine-naloxone in a randomized-controlled clinical setting. These data showed that treatment with extended-release naltrexone was as effective as buprenorphine-naloxone, the current standard of treatment, in maintaining short-term abstinence from heroin and other illicit opioids,” said study lead investigator, Lars Tanum, M.D. Ph.D., Associate Professor, Norwegian Centre for Addiction Research at the University of Oslo, Norway, and Head of Research Unit, Department of R&D in Mental Health Services, Akershus University Hospital, Norway. “In a disease affecting millions of patients, where there is significant suffering and limited choices for treatment, it is encouraging to see an additional proven treatment option for patients struggling with opioid dependence.”
The article, titled “The Effectiveness of Injectable Extended-Release Naltrexone vs. Daily Buprenorphine-Naloxone for Opioid Dependence: A Randomized Clinical Non-Inferiority Trial,” is available online and will appear in a forthcoming print issue of JAMA Psychiatry. All patients who completed this 12-week study were invited to participate in a 36-week, open-label extension study using extended-release naltrexone. This extension portion of the study has been completed, and results are expected to be submitted to a peer-reviewed journal for publication.
Results of Study Published in JAMA Psychiatry
The open-label, randomized-controlled study compared the use of extended-release naltrexone to buprenorphine-naloxone in patients with opioid dependence at five urban addiction clinics in Norway. Following detoxification, a total of 159 patients were randomly assigned to either daily sublingual buprenorphine-naloxone, 4 to 24 mg/day (target dose of 16 mg/day), or once-monthly injectable extended-release naltrexone 380 mg for a total of 12 treatment weeks. Confidential
Primary Outcomes: Data from the study showed that extended-release naltrexone was non-inferior to buprenorphine-naloxone on all primary endpoints, including retention in treatment (p=0.04), group proportion of total number of opioid-negative urine drug tests (p<0.001), days of heroin use (p<0.001) and days of other illicit opioids use (p<0.001). Extended-release naltrexone patients used significantly less heroin at all timepoints (Week 4 p=0.001, Week 8 p<0.001, Week 12 p=0.003) and significantly less other illicit opioids at Week 4 (p=0.004) and Week 8 (p=0.007) than patients in the buprenorphine-naloxone treatment group.
Secondary Outcomes: At all timepoints in the study, extended-release naltrexone patients reported significantly less heroin craving and thoughts about heroin than buprenorphine-naloxone patients. Satisfaction with treatment and willingness to recommend their treatment to others was significantly higher among extended-release naltrexone patients. Life satisfaction was significantly higher among extended-release naltrexone patients at Weeks 4 and 8. Mental health, as assessed by the Hopkins Symptom Checklist-25 of anxiety and depression, showed no significant differences between the two treatment groups. There were no significant differences found between the extended-release naltrexone and buprenorphine-naloxone treatment groups in days of non-opioid illicit substance use.
Overall, 66% of patients completed the study, with a mean time of retention on treatment of 69.3 days for the extended-release naltrexone group and 63.7 days for the buprenorphine-naloxone group. More patients reported adverse events in the extended-release naltrexone group versus those in the buprenorphine-naloxone group (69.0% vs. 34.7%). A number of events in the extended-release naltrexone group, and to a lesser degree in the buprenorphine-naloxone group, were related to induced or experienced withdrawal symptoms, which the study investigators attribute largely to insufficient opioid detoxification. A change to the detoxification strategy was made during the first year of the study, which reduced the number of new adverse events related to induction of treatment. There were nine serious adverse events in the study, six in the extended-release naltrexone group and three in the buprenorphine-naloxone group; however, none were considered directly related to the given treatment. There was one reported opioid overdose in the buprenorphine-naloxone treatment group, and no deaths were observed in the study. Confidential
Limitations of the study, as noted by the study investigators, include lack of blinding between treatment arms, and the possibility that the patient population in the study may have been motivated to receive the novel antagonist treatment of extended-release naltrexone, which is unavailable in Norway.
Funding for the head-to-head comparison study was provided by unrestricted grants from the Research Council of Norway and the Western Norway Regional Health Authority. Financial support was also received from the Norwegian Centre for Addiction Research, University of Oslo, and from Akershus University Hospital.
Alkermes did not have access to trial data or editorial control of any publication related to the trial. Alkermes contributed extended-release naltrexone in kind through an investigator-initiated trial contract.
Read the full article here