A double-blind, randomized, placebo-controlled study with JNJ-37822681, a novel, highly selective, fast dissociating D₂ receptor antagonist in the treatment of acute exacerbation of schizophrenia.

JNJ-37822681 is a novel, highly selective dopamine D₂ receptor antagonist characterized by a rapid dissociation rate from the dopamine D₂ receptor. This profile was hypothesized to confer antipsychotic efficacy and improved tolerability. In this 12-week study, the efficacy and safety of JNJ-37822681 were evaluated in patients with an acute exacerbation of schizophrenia, randomly assigned (1:1:1:1:1) to JNJ-37822681 (10-, 20- or 30-mg bid), olanzapine (15 mg once-daily), or placebo (for 6 weeks followed by olanzapine for 6 weeks). Of 498 randomized patients, 298 (60%) completed the study. All JNJ-37822681 dose groups and the olanzapine group showed significantly greater reduction in PANSS total score from baseline to week 6 versus placebo (all p-values < 0.001). Least-squares adjusted mean changes from baseline to week 6 in PANSS total score were: -6.4 (placebo); -18.4 (10 mg JNJ-37822681), -17.7 (20 mg JNJ-37822681), -20.0 (30 mg JNJ-37822681) and -22.9 (olanzapine). All JNJ-37822681 groups showed significant improvement versus placebo from baseline to week 6 in the PANSS subscales, Marder factors, Clinical Global Impression of Severity, and in the Subjective Well-Being on Neuroleptics scale (all p-values < 0.05). The most common treatment-emergent adverse events with JNJ-37822681 were insomnia (17%) and akathisia (13%). Incidences of extrapyramidal symptoms were dose-related and were comparable for JNJ-37822681 10 mg bid and olanzapine groups. All JNJ-37822681 dose groups showed lesser weight gain compared with olanzapine. The efficacy and tolerability profile of the JNJ-37822681 10 mg bid was consistent with the study hypothesis.