ALKS 3831 linked to less weight gain, smaller waist size increase vs. olanzapine alone

A combination of olanzapine and samidorphan was well-tolerated and linked to less weight gain and smaller increases in waist circumference vs. olanzapine alone, according to study results published in American Journal of Psychiatry.

“Antipsychotic efficacy of the combination treatment has been established in a phase 3 study in patients with an acute exacerbation of schizophrenia,” Christoph U. Correll, MD, of the department of psychiatry at Zucker Hillside Hospital, Northwell Health, and colleagues wrote. “In preclinical studies, coadministration of olanzapine and samidorphan was found to attenuate olanzapine-associated weight gain and mitigate several olanzapine-associated metabolic abnormalities, independently of effects on weight. In a 12-week phase 2 dose-ranging study in patients with schizophrenia, combined olanzapine/samidorphan treatment resulted in a 37% reduction in weight gain compared with olanzapine.”

In the current phase 3 double-blind trial, Correll and colleagues sought to evaluate the weight profile of this combination treatment, called ALKS 3831 (Alkermes), vs. olanzapine alone among patients with schizophrenia aged 18 years to 55 years. The investigators assigned 280 patients to ALKS 3831 and 281 to olanzapine alone for 24 weeks, and postbaseline weight assessment data were available for 538 patients. Change from baseline in body weight and proportion of patients with 10% or greater weight gain at week 24 served as primary endpoints. The proportion of patients with 7% or greater weight gain served as the key secondary endpoint. The investigators also measured waist circumference and fasting metabolic laboratory parameters.

Results showed the least squares mean percent weight change from baseline at week 24 was 4.21% in the ALKS 3831 group and 6.59% in the olanzapine group, which Correll and colleagues noted was a significant difference. Weight gain of 10% or greater occurred among 17.8% of patients in the ALKS 3831 groups and 29.8% of patients in the olanzapine group, and weight gain of 7% or greater occurred among 27.5% of those in the ALKS 3831 group and 42.7% of those in the olanzapine group. Further, the ALKS 3831 group exhibited smaller increases in waist circumference. Both groups had similar schizophrenia symptom improvement. Adverse events in the respective ALKS 3831 and olanzapine groups included weight gain (24.8% vs. 36.2%), somnolence (21.2% vs. 18.1%), dry mouth (12.8% vs. 8%) and increased appetite (10.9% vs. 12.3%). The researchers observed small and similar metabolic changes between groups.

“[ALKS 3831] was found to mitigate the important side effect of olanzapine-associated weight gain while maintaining the established antipsychotic efficacy of olanzapine,” they wrote. “While the metabolic changes observed at week 24 were similar between treatments, treatment with [ALKS 3831] resulted in a clinically meaningful mitigation of weight gain and increases in waist circumference, two well-established risk factors for cardiovascular disease and diabetes. Thus, [ALKS 3831] represents a potential new treatment option for patients.”