Efficacy of idebenone on respiratory function in patients with Duchenne muscular dystrophy not using glucocorticoids (DELOS): a double-blind randomised placebo-controlled phase 3 trial.
Abstract | BACKGROUND: METHODS: In a multicentre phase 3 trial in Belgium, Germany, the Netherlands, Switzerland, France, Sweden, Austria, Italy, Spain, and the USA, patients (age 10-18 years old) with Duchenne muscular dystrophy were randomly assigned in a one-to-one ratio with a central interactive web response system with a permuted block design with four patients per block to receive idebenone (300 mg three times a day) or matching placebo orally for 52 weeks. Study personnel and patients were masked to treatment assignment. The primary endpoint was change in peak expiratory flow (PEF) as percentage predicted (PEF%p) from baseline to week 52, measured with spirometry. Analysis was by intention to treat (ITT) and a modified ITT (mITT), which was prospectively defined to exclude patients with at least 20% difference in the yearly change in PEF%p, measured with hospital-based and weekly home-based spirometry. This study is registered with ClinicalTrials.gov, number NCT01027884. FINDINGS: 31 patients in the idebenone group and 33 in the placebo group comprised the ITT population, and 30 and 27 comprised the mITT population. Idebenone significantly attenuated the fall in PEF%p from baseline to week 52 in the mITT (-3·05%p [95% CI -7·08 to 0·97], p=0·134, vs placebo -9·01%p [-13·18 to -4·84], p=0·0001; difference 5·96%p [0·16 to 11·76], p=0·044) and ITT populations (-2·57%p [-6·68 to 1·54], p=0·215, vs -8·84%p [-12·73 to -4·95], p<0·0001; difference 6·27%p [0·61 to 11·93], p=0·031). Idebenone also had a significant effect on PEF (L/min), weekly home-based PEF, FVC, and FEV1. The effect of idebenone on respiratory function outcomes was similar between patients with previous corticosteroid use and steroid-naive patients. Treatment with idebenone was safe and well tolerated with adverse event rates were similar in both groups. Nasopharyngitis and headache were the most common adverse events ( idebenone, eight [25%] and six [19%] of 32 patients; placebo, nine [26%] and seven [21%] of 34 patients). Transient and mild diarrhoea was more common in the idebenone group than in the placebo group (eight [25%] vs four [12%] patients). INTERPRETATION: FUNDING: Santhera Pharmaceuticals.
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Authors | Gunnar M Buyse, Thomas Voit, Ulrike Schara, Chiara S M Straathof, M Grazia D'Angelo, Günther Bernert, Jean-Marie Cuisset, Richard S Finkel, Nathalie Goemans, Craig M McDonald, Christian Rummey, Thomas Meier, DELOS Study Group |
Journal | Lancet (London, England)
(Lancet)
Vol. 385
Issue 9979
Pg. 1748-1757
(May 02 2015)
ISSN: 1474-547X [Electronic] England |
PMID | 25907158
(Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2015 Elsevier Ltd. All rights reserved. |
Chemical References |
- Antioxidants
- Ubiquinone
- idebenone
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Topics |
- Adolescent
- Antioxidants
(therapeutic use)
- Child
- Double-Blind Method
- Humans
- Male
- Muscular Dystrophy, Duchenne
(complications, drug therapy, physiopathology)
- Peak Expiratory Flow Rate
- Respiration Disorders
(drug therapy, etiology, physiopathology)
- Respiratory Function Tests
- Respiratory Muscles
(physiopathology)
- Treatment Outcome
- Ubiquinone
(analogs & derivatives, therapeutic use)
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