Stocchi, F;
Rascol, O;
Hauser, RA;
Huyck, S;
Tzontcheva, A;
Capece, R;
Ho, TW;
... Preladenant Early Parkinson Disease Study Group; + view all
(2017)
Randomized trial of preladenant, given as monotherapy, in patients with early Parkinson disease.
Neurology
, 88
(23)
pp. 2198-2206.
10.1212/WNL.0000000000004003.
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Abstract
OBJECTIVE: To evaluate the adenosine 2a receptor antagonist preladenant as a nondopaminergic drug for the treatment of Parkinson disease (PD) when given as monotherapy. METHODS: This was a randomized, 26-week, placebo- and active-controlled, parallel-group, multicenter, double-blind trial conducted in adults diagnosed with PD for <5 years who were not yet receiving l-dopa or dopamine agonists. Patients with a Unified Parkinson's Disease Rating Scale (UPDRS) part 3 (motor function) score ≥10 and Hoehn & Yahr score ≤3 were randomized 1:1:1:1:1 to preladenant 2, 5, or 10 mg twice daily, rasagiline 1 mg (active-control) once daily, or placebo. The primary endpoint was the change from baseline at week 26 in the sum of UPDRS parts 2 (activities of daily living) and 3 scores (UPDRS2+3). RESULTS: The number of patients treated was 1,007. Neither preladenant nor rasagiline was superior to placebo after 26 weeks. The differences vs placebo (95% confidence interval) in UPDRS2+3 scores (with a negative difference indicating improvement vs placebo) were preladenant 2 mg = 2.60 (0.86, 4.30), preladenant 5 mg = 1.30 (-0.41, 2.94), preladenant 10 mg = 0.40 (-1.29, 2.11), and rasagiline 1 mg = 0.30 (-1.35, 2.03). Post hoc analyses did not identify a single causal factor that could explain the finding of a failed trial. Preladenant was generally well-tolerated with few patients discontinuing due to adverse events (preladenant 7%, rasagiline 3%, placebo 4%). CONCLUSIONS: No evidence supporting the efficacy of preladenant as monotherapy was observed in this phase 3 trial. The lack of efficacy of the active control rasagiline makes it difficult to interpret the results. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov: NCT01155479. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that for patients with early PD, preladenant is not effective as monotherapy at the doses studied (2, 5, 10 mg).
| Type: | Article |
|---|---|
| Title: | Randomized trial of preladenant, given as monotherapy, in patients with early Parkinson disease |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1212/WNL.0000000000004003 |
| Publisher version: | http://doi.org/10.1212/WNL.0000000000004003 |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| Keywords: | Activities of Daily Living, Adenosine A2 Receptor Antagonists, Antiparkinson Agents, Dose-Response Relationship, Drug, Double-Blind Method, Female, Humans, Indans, Internationality, Male, Middle Aged, Motor Activity, Parkinson Disease, Pyrimidines, Severity of Illness Index, Treatment Failure, Triazoles |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Clinical and Movement Neurosciences |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1562553 |
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