ORLANDO, Fla. — ALKS 3831, composed of a flexible dose of olanzapine and a 10-mg fixed dose of the opioid receptor antagonist samidorphan, showed greater antipsychotic efficacy compared with placebo in adults with acute exacerbation of schizophrenia, according to poster data presented here.
ALKS 3831 was generally well-tolerated by patients and demonstrated similar safety and efficacy profiles to olanzapine.
“ALKS 3831 ... is under development for the treatment of schizophrenia to mitigate the weight gain and metabolic effects associated with olanzapine alone,” Jelena Kunovac, MD, MS, founder, CEO and CMO of Altea Research, told Healio Psychiatry. “This study is important to prove that ALKS 3831 is an effective treatment for acute exacerbation of schizophrenia. Preclinical studies have provided evidence for the role of the opioid system in mediating food reward, feeding behavior and metabolism.”
In this phase 3, randomized study, researchers examined the antipsychotic efficacy and safety of ALKS 3831 compared with placebo and olanzapine monotherapy as an active control in patients with acute exacerbation of schizophrenia over a 4-week period.
Adults with schizophrenia received 2 weeks of inpatient treatment followed by 2 weeks of inpatient/outpatient treatment with fixed olanzapine dose. The investigators measured antipsychotic efficacy via the Positive and Negative Syndrome Scale (PANSS), Clinical Global Impression–Severity (CGI-S) scale and CGI–improvement (CGI-I) scale from baseline to week 4. Safety and tolerability were also examined. On average, olanzapine dose was 18.4 mg per day for patients in both active treatment groups.
Overall, 401 patients were randomized to receive ALKS 3831, olanzapine or placebo. The results showed that compared with placebo, least squares mean difference from baseline to 4 weeks in PANSS total score was –6.4 (P < .001) for patients receiving ALKS 3831 and –5.3 (P = .004) for those receiving olanzapine. Least squares mean difference in CGI-S score was –0.38 (P = .002) for the ALKS 3831 group and –0.44 (P < .001) for the olanzapine group compared with placebo, according to the data.
A greater proportion of patients showed improvement in PANSS response in the ALKS 3831 and olanzapine groups compared with placebo at week 4 (59.8% and 53.8% vs. 38.3%). In addition, a greater proportion of patients showed improvement in CGI-I response by week 4 in the active treatment groups compared with placebo (57.6% and 50.8% vs. 33.1%).
Discontinuation due to adverse events was low among all patients and movement disorder did not generally occur among those in the active treatment groups. Common adverse events included weight gain, somnolence, dry mouth, anxiety, headache and schizophrenia.
“Long-term data will clarify the importance of this study for practicing clinicians,” Kunovac told Healio Psychiatry. “Weight gain is a well-documented issue for patients with schizophrenia on olanzapine alone. New therapeutic approaches that are safe and effective for the treatment of schizophrenia that could also potentially address the weight gain issue could have real and practical clinical implications.” – by Savannah Demko
Potkin SG, et al. A phase 3 study to determine the antipsychotic efficacy and safety of ALKS 3831 in adult patients with acute exacerbation of schizophrenia. Presented at: Psych Congress; Oct. 25-28, 2018; Orlando, Fla.
Disclosure: Kunovac reports both research grants and consulting for Alkermes. She also reports research grants and consultation honoraria from Acadia, Allergan, Astelas, Auspex, Axsome, Daiichi, Intracellular Therapeutics, Lundbeck, Nektar Therapeutics, Neurocrine, Otsuka, Sunovion, Synerex and Tonix.