Efficacy and safety of bifeprunox in patients with an acute exacerbation of schizophrenia: results from a randomized, double-blind, placebo-controlled, multicenter, dose-finding study.
BACKGROUND
Bifeprunox is a partial dopamine agonist with a unique receptor-binding profile and potential antipsychotic properties.


OBJECTIVE
The current study evaluated the efficacy and safety of bifeprunox in patients with an acute exacerbation of schizophrenia.


METHODS
In this 6-week, double-blind, placebo-controlled study, 589 patients were randomly assigned to once-daily treatment with bifeprunox 5, 10, or 20 mg, placebo, or risperidone 6 mg. Efficacy was assessed by changes in symptom rating scales [Positive and Negative Syndrome Scale (PANSS) total and subscale scores; PANSS-derived BPRS scores; Clinical Global Impression--Severity (CGI--S) and Clinical Global Impression--Improvement (CGI--I) scores]. Safety and tolerability were assessed by monitoring adverse events, extrapyramidal symptoms (EPS), laboratory values, electrocardiograms, prolactin levels, and weight.


RESULTS
Compared with placebo, bifeprunox 20 mg produced a statistically significantly greater reduction from baseline to last assessment in the primary efficacy variable (PANSS total score; effect size = -0.339), as well as most secondary efficacy measures. No statistically significant differences in efficacy were seen with lower doses of bifeprunox. The most common treatment-emergent adverse events (TEAEs) noted with bifeprunox were gastrointestinal; no clear dose-related trend in the incidence of any TEAE was observed in the bifeprunox groups. Compared to placebo, treatment with bifeprunox led to small but statistically significant decreases in weight and prolactin levels. EPS were comparable between bifeprunox and placebo. The active reference in this study, risperidone 6 mg, showed statistically significant differences from placebo for the primary efficacy parameter (effect size = -0.628) and all secondary efficacy parameters.


CONCLUSIONS
These data suggest that 20 mg of bifeprunox may be efficacious in improving symptoms in patients with an acute exacerbation of schizophrenia. Bifeprunox appeared to be safe and well tolerated by patients in this 6-week study.
Casey
Daniel E
DE
UHN 80 Department of Psychiatry, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA. caseyd@ohsu.edu
Sands
Earl E
EE
Heisterberg
Jens
J
Yang
Hwa-Ming
HM
D000208:Acute Disease; D000328:Adult; D014150:Antipsychotic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001583:Benzoxazoles / Q000008:administration & dosage* / Q000009:adverse effects; D001835:Body Weight / Q000187:drug effects; D002784:Cholesterol / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004409:Dyskinesia, Drug-Induced / Q000097:blood / Q000175:diagnosis; D004562:Electrocardiography / Q000187:drug effects; D005260:Female; D005767:Gastrointestinal Diseases / Q000097:blood / Q000139:chemically induced; D006801:Humans; D008297:Male; D008875:Middle Aged; D009460:Neurologic Examination / Q000187:drug effects; D010879:Piperazines / Q000008:administration & dosage* / Q000009:adverse effects; D011388:Prolactin / Q000097:blood; D011569:Psychiatric Status Rating Scales; D018967:Risperidone / Q000009:adverse effects / Q000627:therapeutic use; D012559:Schizophrenia / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D016896:Treatment Outcome; D014280:Triglycerides / Q000097:blood
D014150:Antipsychotic Agents; D001583:Benzoxazoles; D010879:Piperazines; D014280:Triglycerides; D011388:Prolactin; D002784:Cholesterol; C509981:bifeprunox; D018967:Risperidone