New Phase II trial data suggest ACP-103 is effective, safe, and motorically tolerable for patients with Parkinson’s disease and treatment-induced psychosis. At the same time, the drug manufacturer provided an update on its ongoing open-label extension study for patients with Parkinson's disease and reported that some patients have been treated with ACP-103 for over one year.

"The trial results are encouraging and suggest that ACP-103 may provide an important advance in the therapy for patients with Parkinson's disease. The drug treatment of Parkinson's disease produces a high incidence of hallucinations and paranoid delusions, which in turn are the most common causes for nursing home placement. Treatment for this is inadequate. ACP-103 appears to combine efficacy, tolerability and safety in a way that current treatment paradigms do not," said Joseph H. Friedman, M.D., Principal Investigator and Clinical Professor at Brown University.

"Currently, the treatment options for these patients are limited. Whereas antipsychotics are used off-label, it is a challenge for physicians to find the balance between antipsychotic activity and tolerability. There is a large unmet medical need for new therapies that will effectively treat the psychosis and other dysfunctions that result from the use of dopamine replacement drugs without causing excess sedation, orthostatic hypotension or impairing motor function."

The Phase II clinical trial was a multi-center, double-blind, placebo-controlled study designed to evaluate the motoric tolerability, antipsychotic efficacy, and safety of ACP-103 in patients with Parkinson's disease and treatment-induced psychosis. The trial enrolled 60 patients at multiple clinical sites in the United States.

The study involved once-daily oral administration of either ACP-103 or placebo for a 28-day period to patients who also received their stable dopamine replacement therapy. The design of the study permitted escalation of the initial 20 mg dose of ACP-103 to 40 mg and then to 60 mg at two scheduled intervals during the study. Fewer patients on ACP-103 were escalated to higher doses than were placebo-treated patients, and the mean total dose of ACP-103 was significantly less than the mean total dose of placebo.

The difference in dose escalation between the two groups as indicated by physicians' answers to a trial questionnaire was mainly due to positive clinical responses in those patients who were not escalated rather than any dose limitation due to tolerability.

The primary endpoint of the clinical trial was met by the demonstration that there was no statistical difference between the ACP-103-treated group and the placebo-treated group in motoric function as measured by subsections Parts II and III of the UPDRS. The primary endpoint evaluated absolute change from baseline to study day 28 between ACP-103 and placebo groups on the UPDRS for the intent-to-treat population. The lack of statistical significance between ACP-103 and placebo-treated groups showed that ACP-103 did not worsen motor functions in patients with Parkinson's disease suffering from treatment-induced psychosis.

The study also included secondary endpoints of antipsychotic efficacy using three different rating scales: Part I of the UPDRS, which measures mental impairments, including an item rating severity of psychosis; the Scale for the Assessment of Positive Symptoms (SAPS), which measures hallucinations and delusions; and the Clinical Global Impression - Severity of Illness scale (CGI-S), which reflects a general assessment of a patient's overall severity of mental illness.

ACP-103 demonstrated statistically significant improvement compared with placebo on the UPDRS Part I; this result was attributable to effects on hallucinations and delusions. ACP-103 also showed a statistical trend compared with placebo on total SAPS score as measured by the absolute change from baseline.

Post-hoc analyses showed a significant difference from placebo for ACP-103 using a relative percent change from baseline analysis for the SAPS. ACP-103 did not show a significant effect compared with placebo on the CGI-S. However, more patients in the ACP-103 group (42 percent) showed a reduction in CGI-S score compared with placebo patients (18 percent).