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Oral Antipsychotic Shows Promise in Schizophrenia Trial
Positive results have been reported from a phase II study of ALKS 3831 (Alkermes), an investigational, oral atypical antipsychotic drug candidate designed as a broad-spectrum treatment for schizophrenia.
ALKS 3831 consists of samidorphan, a new mu-opioid antagonist, in combination with the established antipsychotic drug olanzapine. The medication is designed to attenuate olanzapine-induced metabolic adverse effects, including weight gain, in patients with schizophrenia and to have utility in the treatment of schizophrenia in patients with alcohol use.
The phase II, randomized, double-blind, active-controlled, dose-ranging study was designed to assess the efficacy, safety, and tolerability of ALKS 3831, as well as to evaluate the effect of ALKS 3831 on weight and other metabolic factors, in comparison with olanzapine alone in adult patients with stable schizophrenia. A total of 309 patients were enrolled into the study, and 300 patients who had at least one post-baseline Positive and Negative Syndrome Scale (PANSS) assessment were included in the full study population.
After a 1-week oral lead-in of olanzapine, the patients were randomly assigned to receive olanzapine or one of three doses of ALKS 3831 (olanzapine + 5 mg, 10 mg, or 20 mg samidorphan) for 12 weeks.
The study’s primary efficacy endpoint was the change from baseline at week 12 in the PANSS total score, used to assess the equivalence of ALKS 3831 to olanzapine. Secondary endpoints evaluated the effects of ALKS 3831 on weight gain and other metabolic factors.
ALKS 3831 achieved the trial’s primary efficacy endpoint, demonstrating equivalence to olanzapine in the reduction from baseline in PANSS total scores at week 12.
ALKS 3831 also met the study’s principal secondary endpoint, demonstrating a 37% lower mean weight gain compared with olanzapine at week 12 in the full study population (P = 0.006), and a 51% lower mean weight gain compared with olanzapine at week 12 in a pre-specified subset of patients who gained weight in the 1-week olanzapine lead-in (P < 0.001).
Additional analyses focused on patients with weight gain of at least 5%, 7%, or 10% of their baseline body weight at week 12. Although the study was not powered for statistical significance on these endpoints, the results showed the effect of ALKS 3831 in attenuating significant weight gain in these clinically significant cohorts compared to olanzapine alone.
Across the full study population, the risk of weight gain of at least 10% of baseline body weight with olanzapine was 2.7 times that of ALKS 3831 (P = 0.023). Moreover, in the early weight gain population, the risk of weight gain of at least 10% of baseline body weight with olanzapine was 4.1 times that of ALKS 3831(P = 0.008).
The most common adverse events in the ALKS 3831 treatment groups were somnolence, sedation, and dizziness.
Source: Alkermes; January 7, 2015.