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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

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Abstract

Rationale

Bifeprunox is a partial dopamine agonist with a unique receptor-binding profile and potential antipsychotic properties.

Objectives

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

Materials and 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.

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Notes

  1. Post hoc analyses between risperidone and placebo were based on an ANCOVA model separate from that for bifeprunox versus placebo: these analyses were based on a model that included all treatment groups, but only tested risperidone versus placebo.

  2. See Footnote 1.

  3. See Footnote 1.

  4. See Footnote 1.

  5. See Footnote 1.

  6. See Footnote 1.

  7. See Footnote 1.

  8. See Footnote 1.

  9. Confidence intervals and pairwise comparisons were based on a model including all treatment groups.

  10. See Footnote 9.

  11. See Footnote 9.

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  14. See Footnote 9.

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Acknowledgements

This work was sponsored by H. Lundbeck A/S, Solvay Pharmaceuticals, Inc., and Wyeth Pharmaceuticals. Editorial support was provided by Centron.

Financial disclosure

Dr Casey is a consultant to Abbott Laboratories, Bristol-Myers Squibb, Janssen Pharmaceuticals, Pfizer Inc., Solvay Pharmaceuticals, Inc., Dainippon Sumitomo Pharmaceuticals, and Wyeth Pharmaceuticals. He is on the speakers bureau for Abbott Laboratories, Bristol-Myers Squibb, Janssen Pharmaceuticals, and Pfizer Inc. and receives financial support from the Danicas Foundation. Earl Sands and Hwa-Ming Yang are employees of Solvay Pharmaceuticals, Inc. Jens Heisterberg is an employee of H. Lundbeck A/S.

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Authors and Affiliations

  1. UHN 80 Department of Psychiatry, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, OR, 97239, USA

    Daniel E. Casey

  2. Solvay Pharmaceuticals, Inc., Marietta, GA, USA

    Earl E. Sands & Hwa-Ming Yang

  3. H. Lundbeck A/S, Valby, Copenhagen, Denmark

    Jens Heisterberg

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  1. Daniel E. Casey
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  2. Earl E. Sands
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Correspondence to Daniel E. Casey.

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Casey, D.E., Sands, E.E., Heisterberg, J. et al. 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. Psychopharmacology 200, 317–331 (2008). https://doi.org/10.1007/s00213-008-1207-7

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