Antipsychotic Efficacy, Safety of ALKS 3831 Evaluated for Acute Schizophrenia

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 3831, a treatment for schizophrenia composed of a flexible dose of olanzapine and a fixed dose of 10 mg samidorphan, demonstrated greater antipsychotic efficacy compared with placebo and a safety profile similar to that of olanzapine. The results of the phase 3 study (ClinicalTrials.gov identifier: NCT02634346) were presented at the American Psychiatric Association (APA) 2018 annual meeting, held May 5 to 9, 2018, in New York City.

Researchers conducted the 4-week, randomized, double-blind, placebo-controlled study to assess the antipsychotic efficacy and safety of ALKS 3831 in patients with acute exacerbations of schizophrenia. A total of 401 participants were randomly assigned to receive ALKS 3831, olanzapine, or placebo; patients who received olanzapine 6 months before screening were excluded from the study. Participants were treated in an inpatient setting for the first 2 weeks of the study and could be treated as in- or outpatients for the remaining 2 weeks.

The investigators assessed antipsychotic efficacy using the Positive and Negative Syndrome Scale (PANSS), Clinical Global Impression-Severity (CGI-S), and CGI-Improvement (CGI-I) scales. The safety profile was evaluated as adverse events.

Results showed that 91%, 89%, and 83% of participants receiving ALKS 3831, olanzapine, and placebo, respectively, completed treatment. The most common reason for treatment discontinuation was withdrawal by patient (6% in the ALKS 3831 and placebo groups, and 7% in the olanzapine group). Baseline mean scores were 101.7 for PANSS total score and 5.1 for CGI-S score. The mean olanzapine dose was 18.4 mg/day in both active treatment groups.

Compared with placebo, least squares mean difference from baseline to 4 weeks in PANSS total score was −6.4 (P <.001) for the ALKS 3831 group and −5.3 (P =.004) for the olanzapine group. When researchers examined the CGI-S scores, least squares mean difference from baseline to 4 weeks was −0.38 (P =.002) for the ALKS 3831 group vs placebo and −0.44 (P <.001) for the olanzapine group vs placebo.

The proportion of patients with an improvement in PANSS response (≥30% improvement from baseline) at 4 weeks was 60%, 54%, and 38% in the ALKS 3831, olanzapine, and placebo groups, respectively. In addition, 58%, 51%, and 33% of participants in the ALKS 3831, olanzapine, and placebo groups, respectively, showed improvements in CGI-I response (score ≤2) at 4 weeks.

The investigators note that discontinuation resulting from adverse events was low in all groups. Common adverse events included weight gain, somnolence, dry mouth, anxiety, headache, schizophrenia, and agitation.

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Reference

Potkin SG, Silverman B, Simmons A, Jiang Y, DiPetrillo L, McDonnell D. A phase 3 study to determine the antipsychotic efficacy and safety of ALKS 3831 in adult patients with acute exacerbation of schizophrenia. Presented at: 2018 American Psychiatric Association (APA) Annual Meeting; New York, NY; May 5-9. Poster 169.