BACKGROUND:IPX066 is an oral, extended-release, capsule formulation of carbidopa-levodopa. We aimed to assess this extended-release formulation versus immediate-release carbidopa-levodopa in patients with Parkinson's disease and motor fluctuations. METHODS: We did a phase 3, randomised, double-blind, double-dummy study at 68 academic and clinical centres in North America and Europe. Patients with Parkinson's disease who had at least 2·5 h per day of off-time underwent 3 weeks of open-label immediate-release carbidopa-levodopa dose adjustment followed by 6 weeks of open-label extended-release carbidopa-levodopa dose conversion. These patients were then randomly allocated (1:1), by use of an interactive web-response system, to 13 weeks of double-blind treatment with extended-release or immediate-release carbidopa-levodopa plus matched placebos. The primary efficacy measure was off-time as a percentage of waking hours in all patients randomly allocated to treatment groups, adjusted for baseline value. This study is registered with ClinicalTrials.gov, number NCT00974974. FINDINGS:Between Sept 29, 2009, and Aug 16, 2010, we enrolled 471 participants, of whom 393 (83%) were randomly allocated in the double-blind maintenance period and were included in the main efficacy analyses. As a percentage of waking hours, 201 patients treated double-blind with extended-release carbidopa-levodopa (mean 3·6 doses per day [SD 0·7]) had greater reductions in off-time than did 192 patients treated double-blind with immediate-release carbidopa-levodopa (mean 5·0 doses per day [1·2]). Covariate-adjusted end-of-study means were 23·82% (SD 14·91) for extended-release carbidopa-levodopa and 29·79% (15·81) for immediate-release carbidopa-levodopa (mean difference -5·97, 95% CI -9·05 to -2·89; p<0·0001). Extended-release carbidopa-levodopa reduced daily off-time by, on average, an extra -1·17 h (95% CI -1·69 to -0·66; p<0·0001) compared with immediate-release carbidopa-levodopa. During dose conversion with extended-release carbidopa-levodopa, 23 (5%) of 450 patients withdrew because of adverse events and 13 (3%) withdrew because of a lack of efficacy. In the maintenance period, the most common adverse events were insomnia (seven [3%] of 201 patients allocated extended-release carbidopa-levodopa vs two [1%] of 192 patients allocated immediate-release carbidopa-levodopa), nausea (six [3%] vs three [2%]), and falls (six [3%] vs four [2%]). INTERPRETATION: Extended-release carbidopa-levodopa might be a useful treatment for patients with Parkinson's disease who have motor fluctuations, with potential benefits including decreased off-time and reduced levodopa dosing frequency. FUNDING: Impax Laboratories.
RCT Entities:
BACKGROUND: IPX066 is an oral, extended-release, capsule formulation of carbidopa-levodopa. We aimed to assess this extended-release formulation versus immediate-release carbidopa-levodopa in patients with Parkinson's disease and motor fluctuations. METHODS: We did a phase 3, randomised, double-blind, double-dummy study at 68 academic and clinical centres in North America and Europe. Patients with Parkinson's disease who had at least 2·5 h per day of off-time underwent 3 weeks of open-label immediate-release carbidopa-levodopa dose adjustment followed by 6 weeks of open-label extended-release carbidopa-levodopa dose conversion. These patients were then randomly allocated (1:1), by use of an interactive web-response system, to 13 weeks of double-blind treatment with extended-release or immediate-release carbidopa-levodopa plus matched placebos. The primary efficacy measure was off-time as a percentage of waking hours in all patients randomly allocated to treatment groups, adjusted for baseline value. This study is registered with ClinicalTrials.gov, number NCT00974974. FINDINGS: Between Sept 29, 2009, and Aug 16, 2010, we enrolled 471 participants, of whom 393 (83%) were randomly allocated in the double-blind maintenance period and were included in the main efficacy analyses. As a percentage of waking hours, 201 patients treated double-blind with extended-release carbidopa-levodopa (mean 3·6 doses per day [SD 0·7]) had greater reductions in off-time than did 192 patients treated double-blind with immediate-release carbidopa-levodopa (mean 5·0 doses per day [1·2]). Covariate-adjusted end-of-study means were 23·82% (SD 14·91) for extended-release carbidopa-levodopa and 29·79% (15·81) for immediate-release carbidopa-levodopa (mean difference -5·97, 95% CI -9·05 to -2·89; p<0·0001). Extended-release carbidopa-levodopa reduced daily off-time by, on average, an extra -1·17 h (95% CI -1·69 to -0·66; p<0·0001) compared with immediate-release carbidopa-levodopa. During dose conversion with extended-release carbidopa-levodopa, 23 (5%) of 450 patients withdrew because of adverse events and 13 (3%) withdrew because of a lack of efficacy. In the maintenance period, the most common adverse events were insomnia (seven [3%] of 201 patients allocated extended-release carbidopa-levodopa vs two [1%] of 192 patients allocated immediate-release carbidopa-levodopa), nausea (six [3%] vs three [2%]), and falls (six [3%] vs four [2%]). INTERPRETATION: Extended-release carbidopa-levodopa might be a useful treatment for patients with Parkinson's disease who have motor fluctuations, with potential benefits including decreased off-time and reduced levodopa dosing frequency. FUNDING: Impax Laboratories.