Safety and Tolerability of Ataluren in a Phase 3 Study of Patients with Nonsense Mutation Duchenne Muscular Dystrophy (P3.164)
Bibliographic record
Abstract
Objective: Examine the safety/tolerability of ataluren in the Ataluren Confirmatory Trial in Duchenne Muscular Dystrophy (ACT DMD), a randomized, double-blind, placebo-controlled Phase 3 study of patients with nonsense mutation DMD (nmDMD). Background: A randomized, double-blind, placebo-controlled Phase 2b study of ataluren in patients with nmDMD reported that ataluren was generally well tolerated. Design/Methods: In this Phase 3, ACT DMD, multicenter study, males aged 7-16 years with nmDMD, baseline six-minute walk distance (6MWD) ≥150m and ≤80[percnt] of predicted, and steroid use ≥6 months were randomized 1:1 to ataluren 10, 10, 20 mg/kg or placebo orally 3 times daily for 48 weeks. Results: 230 patients were randomized (ataluren, n=115; placebo, n=115). Demographics were well balanced across treatment arms. Overall, 96.1[percnt] of patients completed the 48-week trial, and 97[percnt] of those chose to continue in the extension study. 103 (89.6[percnt]) patients on ataluren and 100 (87.0[percnt]) patients on placebo experienced treatment-emergent adverse events (TEAEs). The most common TEAEs in the ataluren and placebo arms, respectively, were vomiting (22.6[percnt] and 18.3[percnt]), nasopharyngitis (20.9[percnt] and 19.1[percnt]), fall (19.1[percnt] and 17.4[percnt]), headache (18.3[percnt] for both), and cough (16.5[percnt] and 11.3[percnt]). Four patients in each arm had at least 1 serious adverse event (SAEs). In the ataluren arm, these SAEs were pneumonia and bronchiolitis in 1 patient, pneumonia and post-traumatic pain in 1 patient, tendon disorder in 1 patient, and adenoidal and nasal turbinate hypertrophy in 1 patient; none were considered ataluren-related by the investigator. Only 1 patient in each arm discontinued treatment due to TEAEs: 1 patient discontinued ataluren due to Grade 2 constipation considered possibly related to treatment, and 1 patient discontinued placebo due to loss of ambulation. Conclusions: Ataluren was generally well-tolerated by patients with nmDMD, and the spectrum and severity of adverse events was consistent with previous studies. Supported By: PTC Therapeutics Inc.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.003 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".