The efficacy of FANAPT in the treatment of schizophrenia was supported by 2 placebo- and active-controlled short-term (4- and 6-week) trials and one long-term placebo-controlled randomized withdrawal trial. All trials enrolled patients who met the DSM-III/IV criteria for schizophrenia. 

Three instruments were used for assessing psychiatric signs and symptoms in these studies. The Positive and Negative Syndrome Scale (PANSS) and Brief Psychiatric Rating Scale (BPRS) are both multi-item inventories of general psychopathology usually used to evaluate the effects of drug treatment in schizophrenia. The Clinical Global Impression (CGI) assessment reflects the impression of a skilled observer, fully familiar with the manifestations of schizophrenia, about the overall clinical state of the patient.

Study 1, a 6-week, placebo-controlled trial (n=706), involved 2 flexible dose ranges of FANAPT (12 mg to 16 mg/day or 20 mg to 24 mg/day) compared to placebo and an active control (risperidone). For the 12 mg to 16 mg/day group, the titration schedule of FANAPT was 1 mg twice daily on Days 1 and 2, 2 mg twice daily on Days 3 and 4, 4 mg twice daily on Days 5 and 6, and 6 mg twice daily on Day 7. For the 20 mg to 24 mg/day group, the titration schedule of FANAPT was 1 mg twice daily on Day 1, 2 mg twice daily on Day 2, 4 mg twice daily on Day 3, 6 mg twice daily on Days 4 and 5, 8 mg twice daily on Day 6, and 10 mg twice daily on Day 7. The primary endpoint was change from baseline on the BPRS total score at the end of treatment (Day 42). Both the 12 mg to 16 mg/day and the 20 mg to 24 mg/day dose ranges of FANAPT were superior to placebo on the BPRS total score. The active control antipsychotic drug appeared to be superior to FANAPT in this trial within the first 2 weeks, a finding that may in part be explained by the more rapid titration that was possible for that drug. In patients in this study who remained on treatment for at least 2 weeks, iloperidone appeared to have had comparable efficacy to the active control.

Study 2 (NCT00254202), a 4-week, placebo-controlled trial (n=604), involved one fixed-dose of FANAPT (24 mg/day) compared to placebo and an active control (ziprasidone). The titration schedule for this study was similar to that for the 6-week study. This study involved titration of FANAPT starting at 1 mg twice daily on Day 1 and increasing to 2, 4, 6, 8, 10, and 12 mg twice daily on Days 2, 3, 4, 5, 6, and 7. The primary endpoint was change from baseline on the PANSS total score at the end of treatment (Day 28). The 24 mg/day FANAPT dose was superior to placebo in the PANSS total score. FANAPT appeared to have similar efficacy to the active control drug which also needed a slow titration to the target dose.

In a longer-term trial (Study 3; NCT01291511), clinically stable adult outpatients (n=303) meeting DSM-IV criteria for schizophrenia who remained stable following 12 weeks of open-label treatment with flexible doses of FANAPT (8 mg to 24 mg/day administered as twice daily doses) were randomized to placebo or to continue on their current FANAPT dose (8 mg to 24 mg/day administered as twice daily doses) for observation for possible relapse during the double-blind relapse prevention phase. Stabilization during the open-label phase was defined as being on an established dose of FANAPT that was unchanged due to efficacy in the 4 weeks prior to randomization, having CGI-Severity score of ≤4 and PANSS total score ≤70, a score of ≤4 on each of the following individual PANSS items (P1-delusions, P2-conceptual disorganization, P3-hallucinatory behavior, P6-suspiciousness/persecution, P7-hostility, or G8-uncooperativeness), and no hospitalization or increase in level of care to treat exacerbations. Relapse or impending relapse during the double-blind relapse prevention phase was defined as any of the following: hospitalization due to worsening of schizophrenia, increase (worsening) of the PANSS total score ≥30%, CGI-Improvement score ≥6, patient had suicidal, homicidal, or aggressive behavior, or need for any other antipsychotic medication.

Figure 2: Kaplan Meier Estimation of Percent Relapse/Impending Relapse (Study 3)

Based on the interim analysis, an independent data monitoring committee decided the study should be discontinued early due to evidence of efficacy. Based on results from the interim analysis, which were confirmed by the final analysis dataset, patients treated with FANAPT experienced a statistically significant longer time to relapse or impending relapse than patients who received placebo. Figure 2 displays the estimated cumulative proportion of patients with relapse or impending relapse based on the final data set.