***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: BACKGROUND Ivacaftor has been shown to be a safe , effective treatment for cystic fibrosis in patients aged 6 years or older with a CFTR gating mutation . We aim ed to assess the safety , pharmacokinetics , and pharmacodynamics of ivacaftor in children aged 2 - 5 years . METHODS In the two-part KIWI study , we enrolled children aged 2 - 5 years weighing 8 kg or more with a confirmed diagnosis of cystic fibrosis and a CFTR gating mutation on at least one allele from 15 hospitals in the USA , UK , and Canada . Participants received oral ivacaftor 50 mg ( if bodyweight < 14 kg ) or 75 mg ( if bodyweight ≥14 kg ) every 12 h for 4 days in part A ( to establish the short-term safety of doses for subsequent assessment in part B ) , and then for 24 weeks in part B ( to assess safety and longer-term pharmacodynamics ) . Children could participate in both or just one part of the study . Primary outcomes were pharmacokinetics and safety , analysed in all patients who received at least one dose of ivacaftor . Secondary outcomes were absolute change from baseline in sweat chloride concentrations and bodyweight , body-mass index ( BMI ) , and height Z scores , and pharmacokinetic parameter estimation of ivacaftor  . This study is registered with Clinical Trials.gov , number NCT01705145 . FINDINGS Between Jan 8 , 2013 , and March 1 , 2013 , nine patients were enrolled onto part A of the study , all of whom completed the 4 day treatment period , and eight of whom took part in part B. Between June 28 , 2013 , and Sept 26 , 2013 , 34 patients were enrolled in part B , 33 of whom completed the 24 week treatment period . All patients received at least one dose of ivacaftor . Results of ivacaftor pharmacokinetics suggested that exposure was similar to that reported in adults ( median Cmin were 536 ng/mL for the 50 mg dose ; 580 ng/mL for the 75 mg dose ; median ivacaftor  AUC values were 9840 ng × h/mL and 10 200 ng × h/mL , respectively ) . Common adverse events in part B included cough ( in 19 [ 56 % ] of 34 patients ) and vomiting ( in ten [ 29 % ] ) . Five ( 15 % ) patients had liver function test ( LFT ) results that were more than eight times higher than the upper limit of normal , four of whom had study drug interrupted , and one of whom had study drug discontinued . Six ( 18 % ) of 34 patients had seven serious adverse events ; a raised concentration of transaminases was the only serious adverse event regarded as related to ivacaftor and the only adverse event that result ed in study treatment discontinuation . At week 24 , in patients for whom we had data , sweat chloride had changed from baseline by a mean of -46·9 mmol/L ( SD 26·2 , p<0·0001 ) , weight Z score by 0·2 ( 0·3 ; p<0·0001 ) , BMI Z score by 0·4 ( 0·4 , p<0·0001 ) , and height Z score by -0·01 ( 0·3 ; p=0·84 ) . INTERPRETATION Ivacaftor at doses of 50 mg and 75 mg seems to be safe  in children aged 2 - 5 years with cystic fibrosis with a gating mutation followed up for 24 weeks , although the frequency of elevated LFTs suggests that monitoring should be frequent in young children , particularly those with a history of elevated LFTs . Results of an ongoing extension study assessing durability of these effects and longer-term safety are warranted . FUNDING Vertex Pharmaceuticals Incorporated BACKGROUND We examined data from a Phase 2 trial { NCT00457821 } of ivacaftor , a CFTR potentiator , in cystic fibrosis ( CF ) patients with aG551D mutation to evaluate st and ardized approaches to sweat chloride measurement and to explore the use of sweat chloride and nasal potential difference ( NPD ) to estimate CFTR activity . METHODS Sweat chloride and NPD were secondary endpoints in this placebo-controlled , multicenter trial . St and ardization of sweat collection , processing , and analysis was employed for the first time . Sweat chloride and chloride ion transport ( NPD ) were integrated into a model of CFTR activity . RESULTS Within-patient sweat chloride determinations showed sufficient precision to detect differences between dose-groups and assess ivacaftor treatment effects . Analysis of changes in sweat chloride and NPD demonstrated that patients treated with ivacaftor achieved CFTR activity equivalent to approximately 35%–40 % of normal . CONCLUSIONS Sweat chloride is useful in multicenter trials as a biomarker of CFTR activity and to test the effect of CFTR potentiators Background Cystic fibrosis ( CF ) is an inherited , rare autosomal recessive disease that results in chronically debilitating morbidities and high premature mortality . We evaluated how ivacaftor treatment affected CF symptoms , functioning , and well-being , as measured by the Cystic Fibrosis Question naire-Revised ( CFQ-R ) , a widely-used patient-reported outcome ( PRO ) measure . Methods STRIVE , a double-blind , placebo-controlled r and omized trial , evaluated ivacaftor ( 150 mg ) in CF patients aged 12 + with the G551D-CFTR mutation for 48 weeks . Treatment effect analysis used a mixed-effects repeated measures model . Treatment benefit analyses applied the cumulative distribution function and a categorical analysis of change scores ( “ improvement , ” “ no change , ” or “ decline ” ) . Content-based interpretation examined treatment effect on specific item responses . Results Data from 152 patients with a baseline CFQ-R assessment were analyzed . The treatment effect analysis favored treatment with ivacaftor over placebo on the Body Image , Eating , Health Perceptions , Physical Functioning , Respiratory , Social Functioning , Treatment Burden , and Vitality scales . Findings were supported by the analysis of categorical change . On all CFQ-R scales , the percentage of patients who improved was greater for ivacaftor . In the content-based analysis , the treatment benefit was characterized by better scores across a broad range of domains . Conclusions Results illustrate broad benefits of ivacaftor treatment across many domains : respiratory symptoms , physical and social functioning , health perceptions , and vitality , as measured by the CFQ-R. The breadth of improvements reflects the systemic mechanism of action of ivacaftor compared to other therapies . Findings support the patient-reported value of ivacaftor treatment in this patient population .Trial Registration Clinical Trials.gov BACKGROUND Increasing the activity of defective cystic fibrosis transmembrane conductance regulator ( CFTR ) protein is a potential treatment for cystic fibrosis . METHODS We conducted a r and omized , double-blind , placebo-controlled trial to evaluate ivacaftor ( VX-770 ) , a CFTR potentiator , in subjects 12 years of age or older with cystic fibrosis and at least one G551D-CFTR mutation . Subjects were r and omly assigned to receive 150 mg of ivacaftor every 12 hours ( 84 subjects , of whom 83 received at least one dose ) or placebo ( 83 , of whom 78 received at least one dose ) for 48 weeks . The primary end point was the estimated mean change from baseline through week 24 in the percent of predicted forced expiratory volume in 1 second ( FEV(1 ) ) . RESULTS The change from baseline through week 24 in the percent of predicted FEV(1 ) was greater by 10.6 percentage points in the ivacaftor group than in the placebo group ( P<0.001 ) . Effects on pulmonary function were noted by 2 weeks , and a significant treatment effect was maintained through week 48 . Subjects receiving ivacaftor were 55 % less likely to have a pulmonary exacerbation than were patients receiving placebo , through week 48 ( P<0.001 ) . In addition , through week 48 , subjects in the ivacaftor group scored 8.6 points higher than did subjects in the placebo group on the respiratory-symptoms domain of the Cystic Fibrosis Question naire-revised instrument ( a 100-point scale , with higher numbers indicating a lower effect of symptoms on the patient 's quality of life ) ( P<0.001 ) . By 48 weeks , patients treated with ivacaftor had gained , on average , 2.7 kg more weight than had patients receiving placebo ( P<0.001 ) . The change from baseline through week 48 in the concentration of sweat chloride , a measure of CFTR activity , with ivacaftor as compared with placebo was -48.1 mmol per liter ( P<0.001 ) . The incidence of adverse events was similar with ivacaftor and placebo , with a lower proportion of serious adverse events with ivacaftor than with placebo ( 24 % vs. 42 % ) . CONCLUSIONS Ivacaftor was associated with improvements in lung function at 2 weeks that were sustained through 48 weeks . Substantial improvements were also observed in the risk of pulmonary exacerbations , patient-reported respiratory symptoms , weight , and concentration of sweat chloride . ( Funded by Vertex Pharmaceuticals and others ; VX08 - 770 - 102 Clinical Trials.gov number , NCT00909532 . ) Background The analysis aim ed to examine the impact of pulmonary exacerbations ( PEs ) and lung function on generic measures of HRQL in patients with cystic fibrosis ( CF ) using trial-based data . Methods In a 48-week r and omized , placebo-controlled study of  ivacaftor in patients ≥12 years with CF and a G551D-CFTR mutation the relationship between PEs , PE-related hospitalizations and percent predicted forced expiratory volume in one second ( ppFEV1 ) with EQ-5D measures ( index and visual analog scale [ VAS ] ) was examined in post-hoc analyses . Multivariate mixed-effects models were employed to describe the association of PEs , PE-related hospitalizations , and ppFEV1 on EQ-5D measures . Results One hundred sixty one patients ( age : mean 25.5 [ SD 9.5 ] years ; baseline ppFEV1 : 63.6 [ 16.4 ] ) contributed 1,214 observations ( ppFEV1 : no lung dysfunction [ n = 157 ] , mild [ n = 419 ] , moderate [ n = 572 ] , severe [ n = 66 ] ) . Problems were most frequently reported on pain/discomfort , anxiety/depression , and usual activities EQ-5D items . The mean ( SE ) EQ-5D index nominally decreased ( worsened ) with worsening severity of lung dysfunction ( P = 0.070 ) : 0.931 ( 0.023 ) ; mild : 0.923 ( 0.021 ) ; moderate : 0.904 ( 0.018 ) ; severe : 0.870 ( 0.020 ) . 146 PEs were experienced by 72 patients , including 52 PEs ( 35.6 % ) that required hospitalization . Mean EQ-5D index and VAS scores were lowest ( worst ) within 1 week ( before or after PE start ) for PEs requiring hospitalization . Pulmonary exacerbations , PE-related hospitalizations , and ppFEV1 were significant predictors of EQ-5D index and VAS . Conclusions In a clinical study of patients with CF ( ≥12 years of age and a G551D-CFTR mutation ) , PEs , primarily those requiring hospitalization , were associated with low EQ-5D index and VAS scores . The impact of ppFEV1 was relatively smaller . Reducing PEs , in particular those requiring hospitalization , would likely improve HRQL among these patients .Trial registration Clinical Trials.gov , NCT00909532 ; URL : clinical trials.gov , May 26 , CPX ( 8-cyclopentyl-1,3-dipropylxanthine ) is a novel compound currently under development as a potential treatment for cystic fibrosis ( CF ) . The drug has been shown to increase chloride efflux and CFTR trafficking in vitro in CF airway cells . This phase I multicenter , single-dose , placebo-controlled trial was performed at four institutions . Thirty-seven subjects homozygous for the Delta F(508 ) allele were studied in an escalating dose protocol of seven single-dose cohorts ( 1 , 3 , 10 , 30 , 100 , 300 , and 1,000 mg ) to evaluate the safety , pharmacokinetics , and efficacy of CPX .  Efficacy was determined using nasal transepithelial potential difference and sweat chloride measurements prior to dosing and at 1 , 2 , and 4 hr postdose . The incidence of adverse events in the treatment group was similar to that with placebo , indicating safety of the single doses studied . One serious adverse event ( an acute pulmonary exacerbation ) occurred 13 days after dosing , and was not considered related to the study drug . The maximal plasma CPX concentration and total amount of CPX absorbed appeared to be linearly related to dose , but was highly variable throughout the 
    Output:
    
Both G551D phase 3 trials ( n = 219 ) demonstrated a clinical ly relevant impact of the potentiator ivacaftor on outcomes at 24 and 48 weeks , providing evidence for the use of this treatment in adults and children ( over six years of age ) with cystic fibrosis and the G551D mutation ( class III ) .