Bl-1020, a new γ-aminobutyric acid-enhanced antipsychotic: results of 6-week, randomized, double-blind, controlled, efficacy and safety study.
OBJECTIVE
BL-1020 is a γ-aminobutyric acid (GABA)-enhanced antipsychotic that combines dopamine antagonism with GABA agonist activity. On the basis of animal models, we tested the hypotheses that BL-1020 would be effective in ameliorating both psychotic symptoms and cognitive impairments, with a favorable safety profile in acutely ill schizophrenia patients.


METHODS
363 hospital-based psychiatric patients in India, Romania, and United States aged 18 to 65 years and meeting criteria for DSM-IV-TR diagnosis of chronic schizophrenia were randomized double-blind to receive BL-1020 10 mg/d, BL-1020 20-30 mg/d, placebo, or risperidone (2-8 mg/d) for 6 weeks. The main outcome measures were the positive and negative syndrome scale (PANSS), brief assessment of cognition in schizophrenia, readiness for discharge questionnaire, clinical global impressions scale (CGI) , and extrapyramidal symptom rating scale. The study ran from July 2008 to June 2009.


RESULTS
BL-1020 20-30 mg was significantly better than placebo on PANSS (P = .02) and CGI (P < .001) measurements, with no significant differences noted between BL-1020 20-30 mg and risperidone. There were no significant differences in the maximum change on extrapyramidal symptom rating scale between risperidone and BL-1020 20-30 mg, and both were significantly worse (P < .001) than placebo. BL-1020 20-30 mg was associated with significantly greater improvements on cognitive functioning as measured by the brief assessment of cognition in schizophrenia composite score when compared to placebo (effect size = 0.50, P = .009), risperidone (effect size = 0.43, P = .019), and BL-1020 10 mg (effect size = 0.42, P = .013) after 6 weeks.


CONCLUSIONS
BL-1020 appears to be an effective antipsychotic with possible procognitive effects that will need to be further tested for short- and long-term effects. A further randomized controlled trial using the U.S. Food and Drug Administration-recommended Measurement and Treatment Research to Improve Cognition in Schizophrenia cognitive battery is ongoing.


BACKGROUND
ClinicalTrials.gov identifier: NCT00567710.
Avraham Pharmaceuticals, 42 Hayarkon St, Industrial Zone, Yavneh, 81227, Israel. yg@avphar.com
Yona
Y
Geffen
Richard
R
Keefe
Jonathan
J
Rabinowitz
Ravi
R
Anand
Michael
M
Davidson
D000293:Adolescent; D000328:Adult; D000368:Aged; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D003072:Cognition Disorders / Q000188:drug therapy*; D018492:Dopamine Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D018755:GABA Agonists / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007194:India; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D010546:Perphenazine / Q000031:analogs & derivatives; D018967:Risperidone; D012383:Romania; D012559:Schizophrenia / Q000188:drug therapy*; D014481:United States; D005680:gamma-Aminobutyric Acid / Q000009:adverse effects / Q000627:therapeutic use*
D014150:Antipsychotic Agents; D018492:Dopamine Antagonists; D018755:GABA Agonists; D005680:gamma-Aminobutyric Acid; D010546:Perphenazine; D018967:Risperidone