Long-term safety and tolerability of asenapine: A double-blind, uncontrolled, long-term extension trial in adults with an acute manic or mixed episode associated with bipolar I disorder.

BACKGROUND: Asenapine (ASN) is approved in the United States as monotherapy and adjunctive therapy (to lithium or valproate) in adults with bipolar mania, and as monotherapy in pediatric patients with bipolar mania. This is the first long-term study evaluating safety and tolerability of ASN fixed doses in this population.

METHODS: After completing a 3-week, randomized, placebo (PBO)-controlled acute trial, patients could enroll in this 26-week, fixed-dose (5 or 10mg twice daily), double-blind extension study. Select predefined treatment-emergent adverse events (TEAEs) and metabolic parameters were reported.

RESULTS: Overall, 164 patients were treated; 88 completed the study. The incidence of ≥1 TEAE was greater for PBO/ASN 5mg (68.3%) versus ASN 5mg/ASN 5mg (54.7%) and ASN 10mg/ASN 10mg (51.0%) with sedation, headache, somnolence, akathisia, and dizziness occurring as the most prevalent TEAEs. Predefined TEAEs were more common for PBO/ASN 5mg (33.3%) versus ASN 5mg/ASN 5mg (15.1%) and ASN 10mg/ASN 10mg (15.7%). Weight gain (≥7% increase from baseline to endpoint) was more frequent for ASN 10mg/ASN 10mg (16.3%) versus ASN 5mg/ASN 5mg (13.7%) and PBO/ASN 5mg (8.9%). No clinically significant metabolic changes were observed. The incidence of serious AEs was low and primarily related to underlying bipolar I disorder.

LIMITATIONS: This study lacked a comparator group and was not powered for direct comparisons of ASN regimens. Results may not be applicable to the general bipolar population.

CONCLUSIONS: ASN was generally safe and well tolerated in adults with an acute manic or mixed episode associated with bipolar I disorder.