Efficacy and safety of opicapone in patients with Parkinson’s disease and motor fluctuations: 1-year follow-up (bipark I)

Objective: To evaluate the safety profile of opicapone (OPC) as add-on to levodopa over 1-year of treatment in patients with Parkinson’s disease (PD) and motor-fluctuations. Methods: After completion of the placebo- and active-controlled double-blind (DB) part, 495 (82.5%) patients continued to a 1-year OL-part, in which all were treated with OPC (5, 25 or 50-mg OPC). All subjects began with 25-mg OPC once-daily for 1-week, then investigator freely adjusted the levodopa therapy and/or OPC based on the dopaminergic response and/or associated adverse events (AEs). Efficacy was assessed as the change in absolute OFF-time, based on patient diaries. Secondary endpoints include proportion of responders, UPDRS, PDQ-39, NMSS, PDSS. Safety was assessed by AEs, laboratory, vital-signs, ECG, physical and neurological examination, modified Minnesota Impulsive Disorders Interview (mMIDI) and Columbia Suicide Severity Rating Scale (C-SSRS). Results: After 1-year treatment with OPC, reduction in absolute OFF-time in relation to the DB-baseline was consistent with that observed at DB-part (~2.0-h). For subjects that were under placebo in the DB-part, a decrease of ~1.2-h in relation to OL-baseline and a relevant decrease of ~2.2-h in relation to the DB-baseline, were observed. For subjects that were under entacapone in the DB-part, a decrease of ~0.7-h in relation to OL-baseline and a relevant decrease of ~2.2-h in relation to the DB-baseline, were observed. OPC was safe and well tolerated. Conclusion: Long-term use of OPC was safe, well tolerated, presented a sustained efficacy in reducing the OFF-time in PD patients on levodopa-therapy and with motor-fluctuations and offered an additional 0.7-h reduction in OFF-time in patients switched from ENT.