FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2735778907> ?p ?o ?g. }

• W2735778907 endingPage "1498" @default.
• W2735778907 startingPage "1489" @default.
• W2735778907 abstract "Background Duchenne muscular dystrophy (DMD) is a severe, progressive, and rare neuromuscular, X-linked recessive disease. Dystrophin deficiency is the underlying cause of disease; therefore, mutation-specific therapies aimed at restoring dystrophin protein production are being explored. We aimed to assess the efficacy and safety of ataluren in ambulatory boys with nonsense mutation DMD. Methods We did this multicentre, randomised, double-blind, placebo-controlled, phase 3 trial at 54 sites in 18 countries located in North America, Europe, the Asia-Pacific region, and Latin America. Boys aged 7–16 years with nonsense mutation DMD and a baseline 6-minute walk distance (6MWD) of 150 m or more and 80% or less of the predicted normal value for age and height were randomly assigned (1:1), via permuted block randomisation (block size of four) using an interactive voice-response or web-response system, to receive ataluren orally three times daily (40 mg/kg per day) or matching placebo. Randomisation was stratified by age (<9 years vs ≥9 years), duration of previous corticosteroid use (6 months to <12 months vs ≥12 months), and baseline 6MWD (<350 m vs ≥350 m). Patients, parents and caregivers, investigational site personnel, PTC Therapeutics employees, and all other study personnel were masked to group allocation until after database lock. The primary endpoint was change in 6MWD from baseline to week 48. We additionally did a prespecified subgroup analysis of the primary endpoint, based on baseline 6MWD, which is reflective of anticipated rates of disease progression over 1 year. The primary analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT01826487. Findings Between March 26, 2013, and Aug 26, 2014, we randomly assigned 230 patients to receive ataluren (n=115) or placebo (n=115); 228 patients comprised the intention-to-treat population. The least-squares mean change in 6MWD from baseline to week 48 was −47·7 m (SE 9·3) for ataluren-treated patients and −60·7 m (9·3) for placebo-treated patients (difference 13·0 m [SE 10·4], 95% CI −7·4 to 33·4; p=0·213). The least-squares mean change for ataluren versus placebo in the prespecified subgroups was −7·7 m (SE 24·1, 95% CI −54·9 to 39·5; p=0·749) in the group with a 6MWD of less than 300 m, 42·9 m (15·9, 11·8–74·0; p=0·007) in the group with a 6MWD of 300 m or more to less than 400 m, and −9·5 m (17·2, −43·2 to 24·2; p=0·580) in the group with a 6MWD of 400 m or more. Ataluren was generally well tolerated and most treatment-emergent adverse events were mild to moderate in severity. Eight (3%) patients (n=4 per group) reported serious adverse events; all except one event in the placebo group (abnormal hepatic function deemed possibly related to treatment) were deemed unrelated to treatment. Interpretation Change in 6MWD did not differ significantly between patients in the ataluren group and those in the placebo group, neither in the intention-to-treat population nor in the prespecified subgroups with a baseline 6MWD of less than 300 m or 400 m or more. However, we recorded a significant effect of ataluren in the prespecified subgroup of patients with a baseline 6MWD of 300 m or more to less than 400 m. Baseline 6MWD values within this range were associated with a more predictable rate of decline over 1 year; this finding has implications for the design of future DMD trials with the 6-minute walk test as the endpoint. Funding PTC Therapeutics. Duchenne muscular dystrophy (DMD) is a severe, progressive, and rare neuromuscular, X-linked recessive disease. Dystrophin deficiency is the underlying cause of disease; therefore, mutation-specific therapies aimed at restoring dystrophin protein production are being explored. We aimed to assess the efficacy and safety of ataluren in ambulatory boys with nonsense mutation DMD. We did this multicentre, randomised, double-blind, placebo-controlled, phase 3 trial at 54 sites in 18 countries located in North America, Europe, the Asia-Pacific region, and Latin America. Boys aged 7–16 years with nonsense mutation DMD and a baseline 6-minute walk distance (6MWD) of 150 m or more and 80% or less of the predicted normal value for age and height were randomly assigned (1:1), via permuted block randomisation (block size of four) using an interactive voice-response or web-response system, to receive ataluren orally three times daily (40 mg/kg per day) or matching placebo. Randomisation was stratified by age (<9 years vs ≥9 years), duration of previous corticosteroid use (6 months to <12 months vs ≥12 months), and baseline 6MWD (<350 m vs ≥350 m). Patients, parents and caregivers, investigational site personnel, PTC Therapeutics employees, and all other study personnel were masked to group allocation until after database lock. The primary endpoint was change in 6MWD from baseline to week 48. We additionally did a prespecified subgroup analysis of the primary endpoint, based on baseline 6MWD, which is reflective of anticipated rates of disease progression over 1 year. The primary analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT01826487. Between March 26, 2013, and Aug 26, 2014, we randomly assigned 230 patients to receive ataluren (n=115) or placebo (n=115); 228 patients comprised the intention-to-treat population. The least-squares mean change in 6MWD from baseline to week 48 was −47·7 m (SE 9·3) for ataluren-treated patients and −60·7 m (9·3) for placebo-treated patients (difference 13·0 m [SE 10·4], 95% CI −7·4 to 33·4; p=0·213). The least-squares mean change for ataluren versus placebo in the prespecified subgroups was −7·7 m (SE 24·1, 95% CI −54·9 to 39·5; p=0·749) in the group with a 6MWD of less than 300 m, 42·9 m (15·9, 11·8–74·0; p=0·007) in the group with a 6MWD of 300 m or more to less than 400 m, and −9·5 m (17·2, −43·2 to 24·2; p=0·580) in the group with a 6MWD of 400 m or more. Ataluren was generally well tolerated and most treatment-emergent adverse events were mild to moderate in severity. Eight (3%) patients (n=4 per group) reported serious adverse events; all except one event in the placebo group (abnormal hepatic function deemed possibly related to treatment) were deemed unrelated to treatment. Change in 6MWD did not differ significantly between patients in the ataluren group and those in the placebo group, neither in the intention-to-treat population nor in the prespecified subgroups with a baseline 6MWD of less than 300 m or 400 m or more. However, we recorded a significant effect of ataluren in the prespecified subgroup of patients with a baseline 6MWD of 300 m or more to less than 400 m. Baseline 6MWD values within this range were associated with a more predictable rate of decline over 1 year; this finding has implications for the design of future DMD trials with the 6-minute walk test as the endpoint." @default.
• W2735778907 created "2017-07-21" @default.
• W2735778907 creator A5000530451 @default.
• W2735778907 creator A5001131087 @default.
• W2735778907 creator A5002499186 @default.
• W2735778907 creator A5003235209 @default.
• W2735778907 creator A5005994885 @default.
• W2735778907 creator A5007470485 @default.
• W2735778907 creator A5012227405 @default.
• W2735778907 creator A5014011351 @default.
• W2735778907 creator A5014037430 @default.
• W2735778907 creator A5014572993 @default.
• W2735778907 creator A5015437955 @default.
• W2735778907 creator A5019504361 @default.
• W2735778907 creator A5021745284 @default.
• W2735778907 creator A5024765873 @default.
• W2735778907 creator A5027358823 @default.
• W2735778907 creator A5028291652 @default.
• W2735778907 creator A5028939294 @default.
• W2735778907 creator A5031960202 @default.
• W2735778907 creator A5032162324 @default.
• W2735778907 creator A5032493439 @default.
• W2735778907 creator A5033266587 @default.
• W2735778907 creator A5036179762 @default.
• W2735778907 creator A5036366864 @default.
• W2735778907 creator A5036560782 @default.
• W2735778907 creator A5038988072 @default.
• W2735778907 creator A5039444149 @default.
• W2735778907 creator A5039453462 @default.
• W2735778907 creator A5040344219 @default.
• W2735778907 creator A5040374766 @default.
• W2735778907 creator A5041763238 @default.
• W2735778907 creator A5042269980 @default.
• W2735778907 creator A5043572107 @default.
• W2735778907 creator A5043897574 @default.
• W2735778907 creator A5044404481 @default.
• W2735778907 creator A5044962245 @default.
• W2735778907 creator A5045978747 @default.
• W2735778907 creator A5046451291 @default.
• W2735778907 creator A5047421271 @default.
• W2735778907 creator A5048193467 @default.
• W2735778907 creator A5049128844 @default.
• W2735778907 creator A5050280688 @default.
• W2735778907 creator A5050411909 @default.
• W2735778907 creator A5050704861 @default.
• W2735778907 creator A5052120668 @default.
• W2735778907 creator A5053684012 @default.
• W2735778907 creator A5055105180 @default.
• W2735778907 creator A5057477002 @default.
• W2735778907 creator A5059742070 @default.
• W2735778907 creator A5063362332 @default.
• W2735778907 creator A5063662661 @default.
• W2735778907 creator A5064897502 @default.
• W2735778907 creator A5066191468 @default.
• W2735778907 creator A5068294141 @default.
• W2735778907 creator A5070537902 @default.
• W2735778907 creator A5071163954 @default.
• W2735778907 creator A5073529571 @default.
• W2735778907 creator A5076402259 @default.
• W2735778907 creator A5076684353 @default.
• W2735778907 creator A5078093755 @default.
• W2735778907 creator A5080614978 @default.
• W2735778907 creator A5081312750 @default.
• W2735778907 creator A5081481886 @default.
• W2735778907 creator A5082501640 @default.
• W2735778907 creator A5084459237 @default.
• W2735778907 creator A5085169851 @default.
• W2735778907 creator A5085418762 @default.
• W2735778907 creator A5085970575 @default.
• W2735778907 creator A5086201681 @default.
• W2735778907 creator A5087363192 @default.
• W2735778907 creator A5089234882 @default.
• W2735778907 creator A5089734098 @default.
• W2735778907 creator A5090595212 @default.
• W2735778907 creator A5091538602 @default.
• W2735778907 date "2017-09-01" @default.
• W2735778907 modified "2023-10-18" @default.
• W2735778907 title "Ataluren in patients with nonsense mutation Duchenne muscular dystrophy (ACT DMD): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial" @default.
• W2735778907 cites W10680619 @default.
• W2735778907 cites W1496452409 @default.
• W2735778907 cites W1508659364 @default.
• W2735778907 cites W1524530894 @default.
• W2735778907 cites W1913640993 @default.
• W2735778907 cites W1951817210 @default.
• W2735778907 cites W1966981537 @default.
• W2735778907 cites W1972813632 @default.
• W2735778907 cites W1975417324 @default.
• W2735778907 cites W1984486655 @default.
• W2735778907 cites W2002936663 @default.
• W2735778907 cites W2005330089 @default.
• W2735778907 cites W2018490414 @default.
• W2735778907 cites W2031257767 @default.
• W2735778907 cites W2035041709 @default.
• W2735778907 cites W2037559753 @default.
• W2735778907 cites W2065376245 @default.
• W2735778907 cites W2080417224 @default.
• W2735778907 cites W2085811948 @default.
• W2735778907 cites W2114534925 @default.

• next