Pomaglumetad Methionil (LY2140023 Monohydrate) and Aripiprazole in Patients with Schizophrenia: A Phase 3, Multicenter, Double-Blind Comparison

David H Adams, Lu Zhang, Brian A Millen, Bruce J Kinon, Juan-Carlos Gomez, David H Adams, Lu Zhang, Brian A Millen, Bruce J Kinon, Juan-Carlos Gomez

Abstract

We tested the hypothesis that long-term treatment with pomaglumetad methionil would demonstrate significantly less weight gain than aripiprazole in patients with schizophrenia. In this 24-week, multicenter, randomized, double-blind, Phase 3 study, 678 schizophrenia patients were randomized to either pomaglumetad methionil (n = 516) or aripiprazole (n = 162). Treatment groups were also compared on efficacy and various safety measures, including serious adverse events (SAEs), discontinuation due to adverse events (AEs), treatment-emergent adverse events (TEAEs), extrapyramidal symptoms (EPS), and suicide-related thoughts and behaviors. The pomaglumetad methionil group showed significantly greater weight loss at Week 24 (Visit 12) compared with the aripiprazole group (-2.8 ± 0.4 versus 0.4 ± 0.6; P < 0.001). However, change in Positive and Negative Syndrome Scale (PANSS) total scores for aripiprazole was significantly greater than for pomaglumetad methionil (-15.58 ± 1.58 versus -12.03 ± 0.99; P = 0.045). The incidences of SAEs (8.2% versus 3.1%; P = 0.032) and discontinuation due to AEs (16.2% versus 8.7%; P = 0.020) were significantly higher for pomaglumetad methionil compared with aripiprazole. No statistically significant differences in the incidence of TEAEs, EPS, or suicidal ideation or behavior were noted between treatment groups. In conclusion, long-term treatment with pomaglumetad methionil resulted in significantly less weight gain than aripiprazole. This trial is registered with ClinicalTrials.gov NCT01328093.

Figures

Figure 1
Figure 1
Patient disposition.
Figure 2
Figure 2
Kaplan-Meier plots showing time-to-discontinuation (all causality, due to lack of efficacy, and due to adverse events) for intent-to-treat (ITT) patients with schizophrenia in pomaglumetad methionil (N = 511) and aripiprazole (N = 161) treatment groups for 24 weeks of double-blind treatment.
Figure 3
Figure 3
Least-squares mean change of the weight from mixed-effects model repeated measures among intent-to-treat (ITT) patients with schizophrenia in pomaglumetad methionil (N = 511) and aripiprazole (N = 161) treatment groups for 24 weeks of double-blind treatment. *P ≤ 0.05. P values are from type III tests of LS mean differences between treatments at each visit from MMRM. LS mean: least-squares means, MMRM: mixed-effects model with repeated measures, and SE: standard error.

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