麻豆传媒

Schizophrenia patients receiving a fixed-dose combination of samidorphan and olanzapine (ALK 3831) had less weight gain than those receiving regular olanzapine (Zyprexa) in the phase III , in top-line results released by drugmaker Alkermes.

The once-daily combination pill met both co-primary endpoints in the study: percentage of body weight gained (4.2% for the combination vs 6.6% for olanzapine alone) and the proportion of patients gaining 10% or more of baseline body weight (17.8% vs 29.8%, respectively).

ALK 3831 also met a key secondary endpoint, with fewer participants on the combo pill gaining 7% or more of their baseline body weight (27.5% vs 42.7%).

The randomized, multicenter study included 561 adults with stable schizophrenia. ENLIGHTEN-2 was led by Joseph McEvoy, MD, of Augusta University in Georgia and Duke University Medical Center in North Carolina.

"Samidorphan is believed to limit the pleasure of food intake that has been enhanced by olanzapine," McEvoy explained to 麻豆传媒. Many so-called atypical antipsychotics have weight gain as a side effect. This is perhaps most prominent with olanzapine, but the drug remains a staple in the antipsychotic arsenal.

"Most of the products available are incomplete in their effects, and they are often used in combination -- this product has now been shown to have an effect, not as complete as we might dream of, but one that can be part of a larger strategy, perhaps in combination with other agents," McEvoy said. "Olanzapine is the most efficacious non-clozapine antipsychotic medication, and we want to be able to use it more, while managing its adverse effects. This study demonstrates a helpful mechanism to be able to do that."

The combination also showed a similar safety profile to olanzapine, both with weight gain and somnolence as two of the most common adverse events reported., Dry mouth was also commonly reported with ALKS 3831. The rate of serious adverse events was slightly higher with the investigational treatment, however, occurring in 3.6% of participants vs 2.5% of those on standard olanzapine.

The new findings build upon , the drug's first phase III trial, which focused on antipsychotic efficacy. That study showed a significant reduction in Positive and Negative Syndrome Scale scores and improvement in the Clinical Global Impression-Severity scale when compared with placebo, showing similar efficacy to standard olanzapine.

Alkermes said those who completed ENLIGHTEN-2 may participate in a 12-month extension to examine longer-term safety. The company said it plans to file for marketing approval next year.

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