BACKGROUND: @entity935 agonists (DAs) are a first-line therapy for moderate-to-severe @entity4531 ( @entity4531 ), but these treatments may lead to complications, such as augmentation and @entity23 , requiring switching to another therapeutic class. Here we assess efficacy and tolerability of @entity2682 enacarbil (GEn) in adults with moderate-to-severe primary @entity4531 , with or without prior DA exposure. METHODS: Data from 3 trials were pooled. @entity1 were identified as DA-naive or DA-exposed, based on prior treatment with @entity25049 , @entity399 , @entity26742 , or @entity4088 , and the @entity935 precursor @entity3034 . Details on prior treatment duration and dose were unavailable. @entity1 with a history of augmentation were excluded. Within DA-naive/DA-exposed @entity1 we investigated the co-primary end points from the pivotal trials: mean change from baseline to week 12 in International @entity4531 (IRLS) Rating Scale total score and proportion of responders ("much"/"very much" improved) on the investigator-rated Clinical Global Impression-Improvement (CGI-I) scale. Safety was also assessed. RESULTS: 671 @entity1 were randomized (DA-naive: placebo, n   =   194; GEn 600  mg, n   =   131; GEn 1200  mg, n   =   214; DA-exposed: placebo, n   =   50; GEn 600  mg, n   =   30; GEn 1200  mg, n   =   52). Across treatment arms, no significant differences between DA-naive and DA-exposed subgroups in IRLS Rating Scale total score change from baseline at any visit were seen, except week 1 in the placebo group (-6.1 DA-naive vs -3.4 DA-exposed, P   =   .020). No significant differences in the odds of CGI-I response at week 12 between DA-naive vs DA-exposed @entity1 in any treatment group were seen; however, with placebo there was a nonsignificant trend toward fewer responders among DA-exposed (34.0%) vs DA-naive (44.3%) @entity1 . Both GEn doses significantly improved the IRLS Rating Scale total score change from baseline and CGI-I response vs placebo, regardless of prior DA exposure. The most common treatment-emergent adverse events were @entity1296 and @entity2147 . CONCLUSIONS: Prior DA exposure had no significant effect on efficacy or tolerability of GEn (600 or 1200  mg) in this pooled analysis of adults with moderate-to-severe primary @entity4531 . These data support the use of GEn in DA-exposed and DA-naive @entity1 . TRIAL REGISTRATION: ClinicalTrials.gov NCT00298623, NCT00365352, and NCT01332305.

Effect of prior exposure to @entity935 agonists on treatment with @entity2682 enacarbil in adults with moderate-to-severe primary XXXX : pooled analyses from 3 randomized trials.

@entity1 :: ('9606', 'Species') :: ['Patients', 'patients'] @entity3034 :: ('MESH:D007980', 'Chemical') :: ['levodopa'] @entity26742 :: ('MESH:C047508', 'Chemical') :: ['rotigotine'] @entity25049 :: ('MESH:C046649', 'Chemical') :: ['ropinirole'] @entity2682 :: ('MESH:C040029', 'Chemical') :: ['gabapentin'] @entity935 :: ('MESH:D004298', 'Chemical') :: ['dopamine', 'Dopamine'] @entity2147 :: ('MESH:D006970', 'Disease') :: ['somnolence'] @entity4088 :: ('MESH:D010479', 'Chemical') :: ['pergolide mesylate'] @entity23 :: ('MESH:D007174', 'Disease') :: ['impulse control disorders'] @entity4531 :: ('MESH:D012148', 'Disease') :: ['restless legs syndrome', 'RLS'] @entity1296 :: ('MESH:D004244', 'Disease') :: ['dizziness'] @entity399 :: ('MESH:C061333', 'Chemical') :: ['pramipexole']
@entity4531 :: (MESH:D012148,Disease) :: ['restless legs syndrome']
