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T.P.3.05: Reproducibility and correlation of pretreatment outcome measures in phase 2b study of ataluren (PTC124 (TM)) in nonsense mutation Duchenne and Becker muscular dystrophy (nmDMD/BMD)

Lookup NU author(s): Dr Michelle Eagle, Lisa Atkinson


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Background: Ataluren is an investigational, orally bioavailable, small molecule with potential clinical utility in treating genetic disorders through induction of ribosomal readthrough of nonsense (premature stop codon) mutations in mRNA and production of full-length, functional proteins. Methods: A Phase 2b, randomized, double-blinded, placebo-controlled, dose-ranging study is assessing the efficacy and safety of 48 weeks of ataluren in 174 patients with nmDMD/BMD enrolled at 37 centers. Screening and baseline evaluations (6 weeks apart) included 6-minute walk distance (6MWD); timed function tests (TFTs) (10-meter walk/run, 4-stair climb, 4-stair descent, and stand from supine); and myometry (shoulder abduction, elbow and knee flexion/extension). Correlations and predictive factors were explored. Results: Pretreatment data from screening and baseline visits are available for 174 patients (median [range] age = 8 [5–20] years, height = 123 [97–174] cm, weight = 27 [15–80] kg, corticosteroid usage = 123/174 [71%], cardiac medication usage = 20/174 [12%]). The median [range] between-test interval was 42 [0–91] days. Mean [SD] 6MWD was 357 [93] m at screening and 356 [96] m at baseline. Test–retest correlations were high: 6MWD (r = .91), TFTs (range r = .78 to .90), and myometry (range r = .78 to .92). 6MWD correlated better with TFTs (range r = − .79 to −.67) than with myometry (range r = .35 to .68). As expected, younger age and use of steroids, as predefined by study stratification factors of age (<9 versus >9 years) and corticosteroid usage (yes versus no), predicted for improved 6MWD and performance on other tests. Conclusions: Pretreatment data show that clinical evaluations are reproducible in this multicenter, international study. 6MWD correlates with other functional measures of disease severity and with factors known to predict for disease severity.

Publication metadata

Author(s): Florence J, Abresch RT, Eagle M, Gappmaier E, Glanzman AM, Henricson E, Reha A, Elfring GL, Miller LL, Atkinson L

Publication type: Article

Publication status: Published

Journal: Neuromuscular Disorders

Year: 2009

Volume: 19

Issue: 8-9

Pages: 611-612

ISSN (print): 0960-8966

ISSN (electronic): 1873-2364

Publisher: Elsevier Ltd


DOI: 10.1016/j.nmd.2009.06.212


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