|The following article is part of conference coverage from the 2018 American Psychiatric Association (APA) Annual Meeting in New York, New York. Psychiatry Advisor’s staff will be reporting breaking news associated with research conducted by leading experts in psychiatry. Check back for the latest news from APA 2018.|
NEW YORK — ALKS 5461, a novel treatment approach in major depressive disorder (MDD) consisting of a combination of buprenorphine (a μ-opioid receptor partial agonist and κ-antagonist) and samidorphan (a sublingually bioavailable μ-opioid antagonist), showed lasting antidepressant effects up to 52 weeks of treatment, according to findings from the ongoing 12-month open-label ALK5461-208 Study (ClinicalTrials.gov identifier: NCT02141399) presented at the 2018 American Psychiatric Association (APA) Annual Meeting, held May 5-9, 2018, in New York City. The drug was also well tolerated and had an adverse event profile consistent with that found in short-term trials, in which it has already shown efficacy compared with placebo.
The researchers enrolled patients who participated in one of four short-term studies, including ALK5461-205 (ClinicalTrials.gov identifier: NCT02158533), ALK5461-206 (ClinicalTrials.gov identifier: NCT02158546), ALK5461-207 (ClinicalTrials.gov identifier: NCT02218008), and ALK5461-210 (ClinicalTrials.gov identifier: NCT02085135), as well as new patients. All patients had a confirmed diagnosis of MDD, as well as a history of insufficient response to standard antidepressant therapy.
All participants were treated with an adequate dose of an established antidepressant therapy for at least 8 weeks before initiation of the study drug, and although the dose of the antidepressant agent could be titrated, no change in the antidepressant therapy was permitted. All participants in the study received sublingual ALKS 5461 as adjunctive treatment for up to 52 weeks.
The primary efficacy measure was change from baseline on the Montgomery-Åsberg Depression Rating Scale (MADRS-10), with baseline defined as time of ALKS 5461 initiation (in ALK5461-208 or prior short-term study). Remission was defined as MADRS-10 ≤10 and was also evaluated using last observation carried forward. Kaplan-Meier methods were used to analyze time to remission, defined as time from ALKS 5461 initiation to MADRS-10 ≤10. Safety was analyzed via adverse events, vital signs, laboratory analytes, and electrocardiography.
Of 1454 enrolled participants, 49% completed the 1-year study, 11% discontinued due to an adverse event, and 3% remain enrolled.
The average MADRS-10 scores decreased from baseline, and this decrease was maintained at the end of the study. Remission rate at 12 months was 52.5%, and Kaplan-Meier median time to remission was 59 days. Adverse events occurring with a frequency of >10% were nausea, headache, constipation, dizziness, and somnolence. Upon discontinuation of treatment with ALKS 5461, there was no evidence of withdrawal. ALKS 5461 was also not associated with any change in laboratory or metabolic parameters or bodyweight.
“Overall, ALKS 5461 showed durability of antidepressant effect up to 52 weeks of treatment in patients with [major depressive disorder]. ALKS 5461 was well tolerated with an [adverse event] profile consistent with that reported in the short-term trials,” the researchers concluded.
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Thase ME, Stanford AD, Memisoglu A, et al. Long-term efficacy, safety and tolerability of adjunctive ALKS 5461 in patients with major depressive disorder enrolled in an ongoing phase 3 study. American Psychiatric Association (APA) Annual Meeting; New York, NY; May 5-9. Abstract 48.