Influence of baseline off-time in the efficacy response of Parkinson's disease patients with motor fluctuations: Post-hoc analysis from combined BIPARK-I and II

Abstract

To evaluate the impact of baseline OFF-time on the efficacy of opicapone (OPC) in levodopa-treated Parkinson's Disease (PD) patients with motor fluctuations. OPC, a once-daily COMT inhibitor, proved effective in the treatment of motor fluctuations in PD patients in two large, pivotal, multinational trials (BIPARK-I and II) [[1]Ferreira et al.Lancet Neurol. 2016; 15: 154-165Google Scholar,[2]Lees et al.JAMA Neurol. 2017; 74: 197-206Google Scholar]. Patient-level data from matching treatment arms in BIPARK-I and II were combined in placebo (PLC) and OPC-50 mg groups. The studies had similar designs (primary efficacy endpoint: change from baseline in patient diaries-based absolute OFF-time) and eligibility criteria [[1]Ferreira et al.Lancet Neurol. 2016; 15: 154-165Google Scholar,[2]Lees et al.JAMA Neurol. 2017; 74: 197-206Google Scholar]. An exploratory post-hoc analysis was performed to evaluate the influence of baseline OFF-time in efficacy outcomes (i.e., change from baseline in OFF-/ON-time). Linear regression was applied and the slope was statistically tested for deviation from zero. 1027 patients were randomized to BIPARK-I and II; 522 patients took a dose of study medication; Full Analysis Set comprised 517 [PLC (n = 255); OPC-50 mg (n = 262)]. As expected, both treatments arms presented the same increased dependent tendency for OFF-/ON-time at endpoint, i.e., the longer OFF-time at baseline the greater magnitude of response at endpoint (ending in a linear regression slope statistically significant). When OFF-time at endpoint was ‘normalized’ as % of change in relation to baseline, the linear regression slope was found non-significant for both treatment arms, though the increased dependent tendency was still found. Baseline OFF-time appears to impact the magnitude of both OFF- and ON-time responses in a clinical study setting.