Table 5.

Longer-term studies of asenapine for bipolar disorder.

Study	Study design	Duration (weeks)	Disease state	Randomized (n)	Asenapine dose (n)	Active control dose (n)	Placebo (n)	Comments regarding efficacy outcomes
McIntryre et al.33	Double-blind, extension trial of two double-blind, flexible-dose, randomized control trials31,32	9	Manic or mixed episode, bipolar I disorder	504	Patients randomized to placebo in either of two 3-week acute trials were blindly randomized to asenapine 5 mg or 10 mg BID (94) Patients that received asenapine in the acute trials continued the same regimen (181)	Olanzapine 5–20 mg/day (229)	None	At study endpoint, mean YMRS change from baseline was −24.4 (8.7) and −23.9 (7.9) for asenapine and olanzapine respectively, and there was no statistical difference Rates of response and remission were similar between groups; study completers were eligible to enroll in a 40-week extension trial34
McIntyre et al.34	Double-blind, flexible-dose, extension trial of a prior 9-week extension trial33	40	Manic or mixed episode, bipolar I disorder	218	Patients were continued on pre-established treatment from a prior 9-week extension trial: placebo/asenapine 5 or 10 mg BID (32) or asenapine 5 mg or 10 mg BID (79)	Olanzapine 5–20 mg/day (107)	None	Mean change in YMRS were comparable between asenapine and olanzapine; the mean ± SD change in YMRS total score from baseline in the ITT population at week 52 was −28.6 ± 8.1 for asenapine versus −28.2 ± 6.8 for olanzapine; rates of response and remission were also nearly identical
Ketter et al.38	Double-blind, fixed-dose, extension trial of a prior 3-week trial37	26	Manic or mixed episode, bipolar I disorder	164	Asenapine 5 mg BID (53) or asenapine 10 mg BID (51) Patients that received placebo in the acute trial received asenapine 5 mg BID (placebo/asenapine group; 60)	None	None	Mean change in YMRS total score from acute trial baseline to extension trial endpoint was similar across treatment groups (−22.3, −22.9, −22.0, in placebo/asenapine, asenapine 5 mg and asenapine 10 mg BID, respectively); response rates increased in each group from extension trial baseline (+43.6% in the placebo/asenapine 5 mg group, 87.7% overall responding, +38.0% in the asenapine 5 mg group, 88% overall, and +26.0% in the asenapine 10 mg group, 84% overall)
Szegedi et al.46	Double-blind, randomized, placebo-controlled, augmentation trial	12	Manic or mixed episode, bipolar I disorder Patients had to be continuously treated with lithium or valproate for 2 weeks or longer before screening	326	Adjunctive, flexible-dose, asenapine 5 mg or 10 mg BID with concurrent open-label lithium or valproate treatment	None	166	Adjunctive asenapine was superior to placebo at week 3 with a greater YMRS total score improvement [−10.3 (SD 0.8) versus −7.9 (0.8), p  =  0.026] Asenapine had a significantly greater reduction in YMRS total score compared with placebo at weeks 2, 6, 9, and 12 (p < 0.05 at each time point); the rates of asenapine and placebo YMRS response did not significantly differ at week 3 (34.2% versus 27%), but did at week 12 (47.7% versus 34.4%; p  =  0.0152); rates of YMRS remission were significantly greater for asenapine versus placebo-treated patients, with an NNT for asenapine versus placebo of 9 (95% CI, 4.5–43) and 8 (95% CI, 4.2–37.7) at weeks 3 and 12, respectively
Szegedi et al.46	Double-blind, placebo-control extension trial of an acute augmentation trial	40	Manic or mixed episode, bipolar I disorder, continuing to receive lithium or valproate	77	Adjunctive, flexible-dose, asenapine 5 mg or 10 mg BID with concurrent open-label lithium or valproate treatment	None	36	Mean YMRS total score changes at the extension trial end point were not significantly different between asenapine and placebo groups. Rates of YMRS response (asenapine, 68.4%; placebo, 78.8%) and remission (asenapine, 65.8%; placebo, 78.8%) at week 52 were not statistically different
Findling et al40	Flexible-dose, open-label extension study of an acute trial46	50	Adolescents aged 10–17 years with manic or mixed episode, bipolar I disorder	321	Patients treated with placebo (80) in the antecedent acute phase trial were transitioned to treatment with flexible-dose asenapine; the remaining patients (241) were also treated with flexible-dose asenapine (5–20 mg/day); overall, 31 (9.7%) patients received a modal dose of asenapine 2.5 mg BID, 105 (32.7%) patients received 5 mg BID, and 170 (53.0%) patients received 10 mg BID 15 patients (4.7%) received treatment for <8 days for which no modal dose was determined	None	None	Mean change in YMRS total score from open-label extension baseline at week 50 was −15.2 in the placebo/asenapine group and −6.5 in the asenapine/asenapine group; of 141 patients who were YMRS responders at the end of the acute trial, 46 patients (32.6%) failed to maintain this response; at the end of 26 weeks of treatment, 118 (79.2%) of patients remaining in the trial achieved YMRS response, whereas 102 (68.5%) of remaining patients had achieved YMRS remission
Sajatovic et al.47	Open-label, adjunct asenapine	12	Older-adult (mean age 68.6 years) outpatients with bipolar 1 or 2 disorder having a suboptimal response to current psychotropic treatment	15	Patients were started on asenapine 5 mg/day and titrated to a mean dose of 11.2 mg/day (SD 6.2) as an augmentation to their existing pharmacologic treatment	None	None	Based on baseline YMRS, HAM-D, and MADRS, the majority of participants had moderate-to-severe depression at baseline, while a smaller proportion had manic symptoms; among patients with manic symptoms, there was an improvement in YMRS scores (p < 0.01) Among individuals with depressive symptoms, there was a trend for significant improvement on MADRS (p = 0.06) and HAM-D (p = 0.01) scores

BID, twice-daily; CI, confidence interval; HAM-D, Hamilton Depression Rating Scale⁴⁸; ITT, intention to treat; MADRS, Montgomery–Åsberg Depression Rating Scale; SD, standard deviation; YMRS, Young Mania Rating Scale.