ABSTRACT: Abstract Background: Several atypical antipsychotics are approved to treat adolescent patients with schizophrenia. However, risk for antipsychotic-associated weight gain and metabolic dysfunction underscores the need to identify additional evidence-based treatments that are both efficacious and well tolerated in this vulnerable patient population. Lurasidone is an atypical antipsychotic agent that has demonstrated efficacy in the treatment of adults with schizophrenia in the dose range of 40–160?mg/d. The objective of this randomized, double-blind, placebo-controlled study was to evaluate the efficacy and safety of lurasidone in adolescent patients with schizophrenia. Methods: Adolescent patients (13–17 years old) who met DSM-IV-TR criteria for schizophrenia were randomized to 6 weeks of double-blind treatment with fixed-dose lurasidone 40?mg/d, 80?mg/d, or placebo. An MMRM analysis was performed to assess change from baseline to Week 6 on the primary (PANSS total score) outcome measure. An ANCOVA using an LOCF approach was performed to assess change from baseline on secondary endpoints: Pediatric Quality of Life Enjoyment and Satisfaction Questionnaire (PQ-LES-Q) and Children’s Global Assessment Scale (CGAS). Safety and tolerability assessments included adverse event reporting, weight, and laboratory measures. Results: A total of 327 patients (mean age = 15.4 years old) were randomized to receive lurasidone 40?mg/d (N = 108), 80?mg/d (N = 106) or placebo (N = 113). Performance on the PANSS total score at Week 6 demonstrated a placebo-adjusted LS mean improvement of ?8.0 (P < .001) for the 40?mg/d group and ?7.7 (P < .001) for the 80?mg/d group. Placebo-adjusted LS mean improvement at Week 6 on the PQ-LES-Q was 5.3 (P = .001) and 5.8 (P < .001) for the 40?mg/d and 80?mg/d groups, respectively; and, on the CGAS was 4.6 (P = .002) and 4.9 (P < .001) for the 40?mg/d and 80?mg/d groups, respectively. Study discontinuation due to adverse events was 8.0% in the placebo group and 3.7% in lurasidone treated patients. The most common adverse events (?5% in either lurasidone group and at least twice the rate of placebo) were: nausea, somnolence, akathisia, vomiting, and sedation. LS mean change in weight at week 6 for the lurasidone 40?mg/d, 80?mg/d, and placebo groups was 0.17?kg, 0.49?kg, and 0.05?kg, respectively. Median change at Week 6 (LOCF) in total cholesterol was ?4.0?mg/dL, ?2.0?mg/dL, and ?7.0?mg/dL, respectively; in triglycerides was ?2.0?mg/dL, 7.0?mg/dL, and ?2.0?mg/dL, respectively; and in glucose was 0.0?mg/dL, 1.0?mg/dL, and 0.0?mg/dL, respectively. Conclusion: Adolescent patients with schizophrenia treated with lurasidone demonstrated significant improvement in symptoms, quality of life, and function. Lurasidone was generally well tolerated and associated with minimal changes in weight and metabolic parameters. Sponsored by Sunovion Pharmaceuticals Inc. ClinicalTrials.gov identifier: NCT01911429
