A Proof-of-Concept Study Evaluating the Phosphodiesterase 10A Inhibitor PF-02545920 in the Adjunctive Treatment of Suboptimally Controlled Symptoms of Schizophrenia
| Autor: | Nicholas DeMartinis, Rene N. Lopez, David P. Walling, Adam Ogden, Christopher J. Schmidt, Eve H. Pickering, Lev Gertsik |
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| Rok vydání: | 2019 |
| Předmět: |
Adult
Male medicine.medical_specialty Phosphodiesterase Inhibitors medicine.medical_treatment Phases of clinical research Placebo law.invention 03 medical and health sciences 0302 clinical medicine Double-Blind Method Randomized controlled trial law Internal medicine Humans Medicine Pharmacology (medical) Antipsychotic Psychiatric Status Rating Scales Positive and Negative Syndrome Scale business.industry Middle Aged 030227 psychiatry Clinical trial Psychiatry and Mental health Tolerability Adjunctive treatment Quinolines Schizophrenia Pyrazoles Drug Therapy Combination Female business 030217 neurology & neurosurgery Antipsychotic Agents |
| Zdroj: | Journal of Clinical Psychopharmacology. 39:318-328 |
| ISSN: | 1533-712X 0271-0749 |
| DOI: | 10.1097/jcp.0000000000001047 |
| Popis: | Background Effective treatments for managing suboptimal clinical responses to current therapy for schizophrenia remain a critical unmet need. Phosphodiesterase 10A (PDE10A) inhibition represents a mechanistically novel approach to the treatment of schizophrenia, with preclinical studies suggesting improvements in partially responsive symptoms could be achieved via adjunctive use of the PDE10A inhibitor PF-02545920. Therefore, the adjunctive safety, tolerability, pharmacokinetics, and efficacy of multiple repeat doses of PF-02545920 were investigated in a phase 1b study and subsequent phase 2 study. Methods The phase 1b study randomized 37 adult patients with stable symptomatology and stable antipsychotic regimens within 3 cohorts. Study participants received ascending doses of PF-02545920 or placebo for 10 to 18 days. The phase 2 study randomized 240 outpatients with stable symptomatology but suboptimal response to current antipsychotic regimens 1:1:1 to PF-02545920 5 mg, PF-02545920 15 mg, or placebo every 12 hours for 12 weeks. The primary efficacy end point of the phase 2 study was change in the Positive and Negative Syndrome Scale total score from baseline to week 12, with changes in other clinical assessments as secondary end points. Results Treatment was well tolerated, and observed PF-02545920 exposures were within the range predicted to be adequate for demonstrating efficacy. However, no significant differences in the prespecified efficacy end points between the 2 PF-02545920 treatment arms and placebo were observed. Conclusions Current data and results of a prior monotherapy study in which PF-02545920 failed to differentiate from placebo refute the hypothesis that PDE10A inhibitors have use as antipsychotic agents for schizophrenia. |
| Databáze: | OpenAIRE |
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