Ketter TA et al. – The study evaluated the safety and tolerability of longer term open–label treatment with cariprazine in patients who had responded to cariprazine for acute bipolar mania. Open–label cariprazine 3 to 12 (mean 6.2) mg/d for up to 16 weeks was well tolerated, with low (<10%) rates of sedation and ≥7% weight gain. Akathisia occurred in 32.6% of the patients, which led to discontinuation of the treatment in <5% of the patients.

Methods

• Multinational, multicenter, open–label, flexible–dose study administered cariprazine 3 to 12 (mean 6.2) mg/d up to 16 weeks (mean treatment duration 57.7 days) in patients (N = 402, 18–65 years) with bipolar mania.
• Safety was evaluated based on adverse events (AEs), laboratory values, vital signs, and extrapyramidal symptom scales.
• Based on Young Mania Rating Scale (YMRS), symptom change was evaluated by total score change from baseline using the last observation carried forward approach.

Results

• A total of 33% patients completed the trial.
• Discontinuation was because of withdrawal of consent (20%), AEs (16%), and protocol violation (14%).
• Common AEs that led to discontinuation was akathisia (4.7%) and depression (1.5%).
• Incidence of serious AEs was 7.5%, of which most common were mania (2.2%) and depression (1.2%).
• Treatment–emergent AEs were 83.3%, which included akathisia (32.6%), headache (16.7%), constipation (10.7%), and nausea (10.4%).
• Mean body weight increased <1 kg; 9.3% had ≥7% weight gain; 5.7% had sedation; 3% had somnolence.
• Clinically insignificant parameters were mean changes in laboratory values, vital signs, ECGs, and ophthalmology parameters.
• At week 16, a decrease in mean YMRS total score by –15.2 was observed.