Table 4.

Completed, longer term, randomized, controlled, phase III double-blind clinical trials of cariprazine for schizophrenia

Study	Randomized, n	Cariprazine dose (and dose of active control if applicable)	Comments, including regarding dose titration and tolerability
Durgam et al,19 NCT01412060, RGH-MD-06	200	Flexible-dose range 3–9 mg/day About 50% of all cariprazine patients were receiving 9 mg/day at randomization, 37% 6 mg/day, and 14% 3 mg/day	The aim of this study was to assess longer term maintenance treatment with cariprazine. The study included 20 weeks of open-label treatment with cariprazine for all patients, followed by a variable- length randomized phase where stable patients received either cariprazine or placebo. Cariprazine was started at 1.5 mg/day and increased to 3 mg/day on day 2. For patients with inadequate response and no significant tolerability issues, dosage increases were allowed on day 6 (6 mg/day [interim increase to 4.5 mg/day on day 4]) and day 10 (9 mg/day) if needed. Dose decreases to 3 or 6 mg/day were allowed for significant tolerability issues. During double-blind treatment, cariprazine was administered at the same fixed dose as in the stabilization phase. Patients were required to be hospitalized during screening and for the first 2 weeks in the run-in phase. The most commonly observed AEs during the open-label phase were akathisia (19%), insomnia (14%), and headache (12%). During open-label treatment, akathisia and other EPS AEs (excluding akathisia or restlessness) each led to discontinuation in ~1% of patients. No EPS-related AEs led to discontinuation during double-blind treatment.
Németh et al,27 EudraCT 2012-005485-36, RGH-188–005	461	Fixed dose 4.5 mg/day (risperidone dose 4 mg/day)	The aim of this study was to assess the efficacy of cariprazine on negative symptoms. From random- ization (day 0) to day 6, patients received cariprazine 1.5 mg/day or risperidone 2 mg/day. On days 7–13, patients received 3 mg/day of their respective study drug, and on day 14, patients received the target dose of cariprazine 4.5 mg/day or risperidone 4 mg/day. Antipsychotic treatment taken during the lead-in period was downtitrated during this period and discontinued on day 14. The dose of the double-blind study medication could be decreased to 3 mg/day in case of poor tolerability. In casesof impending psychotic deterioration, the dose could be increased to 6 mg/day. The mean dose for cariprazine was 4.2 mg/day and that for risperidone 3.8 mg/day. AEs (eg, insomnia, akathisia, worsening of schizophrenia, headache, anxiety) were reported in 54% of patients treated with cariprazine and 57% of patients treated with risperidone. The most common AE for cariprazine was akathisia (8%), which was also observed for 5% of persons randomized to risperidone.

Abbreviations: AEs, adverse events; EPS, extrapyramidal symptoms.