Advice
Evidence table
Evidence table
Table 4 Ferreira J et al. 2016 (BIPARK I)
Study reference |
Ferreira JJ, Lees A, Rocha JF, et al. (2016) Opicapone as an adjunct to levodopa in patients with Parkinson's disease and end-of-dose motor fluctuations: a randomised, double-blind, controlled trial The Lancet Neurology 15(2), 154−65 |
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Unique identifier |
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Study type |
RCT |
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Aim of the study |
To assess the safety and efficacy of opicapone as an adjunct to levodopa compared with placebo or entacapone in people with Parkinson's disease and motor fluctuations |
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Study dates |
Between March 2011 and November 2013 |
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Setting |
106 specialist centres across 19 European countries (excluding the UK) and Russia |
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Number of participants |
n=600 randomised |
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Population |
Aged 30 to 83 years with Parkinson's disease with end-of-dose motor fluctuations on a stable optimised dose of levodopa and other medicines for Parkinson's disease Participant's demographics, baseline Parkinson's disease characteristics and treatment history did not differ between the different groups |
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Inclusion criteria |
Clinical diagnosis of Parkinson's disease of at least 3 years' duration; Hoehn and Yahr stage 1 to 3 during on time; at least 1 year of clinical improvement with levodopa treatment; on a stable optimised treatment of 3 to 8 daily doses of levodopa and other Parkinson's disease medicines for at least 4 weeks before screening; signs of end-of-dose motor fluctuations for at least 4 weeks before screening; mean total awake time in the off state of at least 1.5 hours, not including morning akinesia. Participants also had to be able to keep reliable diaries of motor fluctuations |
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Exclusion criteria |
Previous treatment with entacapone; a dyskinesia disability score >3 on item 33 (disability) of the UPDRS; severe or unpredictable periods in the off state, or both; previous surgery or deep brain stimulation for Parkinson's disease; history of neuroleptic malignant syndrome or non-traumatic rhabdomyolysis; concomitant use of tolcapone, apomorphine, entacapone (other than that supplied in the study), neuroleptics, venlafaxine, MAO inhibitors (except selegiline up to 10 mg/day orally or up to 1.25 mg/day buccal and rasagiline up to 1 mg/day) or anti-emetics with antidopaminergic action (except domperidone). Participants with clinically significant unstable cardiovascular disease, psychiatric illness or any other medical condition that increase risks were also excluded |
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Intervention(s) |
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Comparator(s) |
2 comparators:
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Length of follow-up |
14 to 15 weeks. The participants visited the investigators 7 times: visit 1, screening; visit 2, randomisation (baseline); visit 3, 1 week after baseline; visit 4, depended on need for levodopa adjustment (between 2 and 3 weeks after baseline); thereafter assessments occurred at 4‑week intervals for visits 5, 6 and 7 |
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Outcomes |
Primary outcome:
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Secondary outcomes:
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Safety outcomes:
ECG recordings and physical, neurological and dermatological examinations were done at baseline and at the end of the double-blind period (visit 7). Standard laboratory safety tests, the Columbia suicide severity rating scale, and the modified Minnesota impulsive disorder interview were done at baseline and visits 4 to 7 |
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Source of funding |
BIAL |
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Overall risk of bias/quality assessment |
Did the trial address a clearly focused issue? |
Yes |
Was the assignment of patients to treatments randomised? |
Yes |
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Were patients, health workers and study personnel blinded? |
Yesa |
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Were the groups similar at the start of the trial? |
Yes |
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Aside from the experimental intervention, were the groups treated equally? |
Yesb |
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Were all of the patients who entered the trial properly accounted for at its conclusion? |
Yes |
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How large was the treatment effect? |
See table 5 |
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How precise was the estimate of the treatment effect? |
See table 5 |
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Can the results be applied in your context? (or to the local population) |
Unclearc |
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Were all clinically important outcomes considered? |
Yes |
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Are the benefits worth the harms and costs? |
See key points |
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Study limitations |
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Comments |
a Participants were randomly assigned (1:1:1:1) at baseline using a computer-generated scheme to each study arm using blocks of 8 to 10 depending on regimen stratified by centre. Participants and investigators were masked to treatment throughout the study b There were 3 main population sets: intention-to-treat analysis (full set) included all randomly assigned participants who took at least 1 dose of study medicine and had at least 1 assessment of time in the off state after baseline; per-protocol set included all participants in the full analysis set who did not majorly deviate from the protocol and; safety set included all participants who received at least 1 dose of study medicine c There were no UK centres used in the study. The study was conducted in Austria (n=3), Bosnia-Herzegovina (n=16), Bulgaria (n=50), Croatia (n=14), Czech Republic (n=51), France (n=15), Germany (n=35), Hungary (n=10), Italy (n=14), Latvia (n=7), Lithuania (n=15), Poland (n=90), Portugal (n=22), Romania (n=53), Russia (n=34), Serbia (n=36), Slovakia (n=19), Spain (n=37) and Ukraine (n=79) Opicapone enhances the effects of levodopa so the daily dose of levodopa was reduced (but not frequency) between baseline and up to 3 weeks according to clinical response |
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Abbreviations: CGI‑C, clinician global impression of change; DDCI, DOPA decarboxylase inhibitor; MAO, monoamine oxidase; NMSS, non-motor symptoms scale; PDQ‑39, 39‑item Parkinson's disease questionnaire; PDSS, Parkinson's disease sleep scale; PGI‑C, patient global impression of change; RCT, randomised controlled trial; SD, standard deviation; UPDRS, unified Parkinson's disease rating scale; TEAE; treatment-emergent adverse event. |