PMID- 24793536
OWN - NLM
STAT- MEDLINE
DCOM- 20160330
LR  - 20181202
IS  - 1879-114X (Electronic)
IS  - 0149-2918 (Linking)
VI  - 36
IP  - 6
DP  - 2014 Jun 1
TI  - Tolerability of fluticasone furoate/vilanterol combination therapy in children 
      aged 5 to 11 years with persistent asthma.
PG  - 928-939.e1
LID - S0149-2918(14)00182-9 [pii]
LID - 10.1016/j.clinthera.2014.03.014 [doi]
AB  - BACKGROUND: Asthma is a chronic disease afflicting millions of children 
      worldwide. Short-acting beta2-agonist reliever medications and inhaled 
      corticosteroid (ICS) maintenance therapies are effective treatments; however, 
      many children remain uncontrolled with short-acting beta2-agonist and ICS treatment, 
      in which case guidelines recommend adding a long-acting beta2-agonist. OBJECTIVE: We 
      sought to investigate the safety profile, tolerability, and pharmacokinetic (PK) 
      and pharmacodynamic (PD) properties of the long-acting beta2-agonist vilanterol (VI) 
      combined with the ICS fluticasone furoate (FF) administered via the ELLIPTA dry 
      powder inhaler (GlaxoSmithKline, London, United Kingdom) in children aged 5 to 11 
      years with persistent asthma. METHODS: In this randomized, double-blind, 
      repeated-dose, 2-way crossover study, data from 8- to 11-year-old children with 
      asthma were reviewed before those from 5- to 7-year-old children with asthma. 
      Patients received once-daily FF/VI, 100/25 microg, or FF, 100 microg, in the morning for 
      14 days, followed by a >/=7-day washout period before switching to the other 
      treatment for 14 days; the study duration was </=11 weeks. Primary end points were 
      adverse events (AEs), clinical laboratory measurements, peak expiratory flow, 
      maximum heart rate, blood pressure, and electrocardiographic parameters. 
      Secondary end points comprised PK (AUC0-4, Cmax) and PD (serum potassium [0-4 
      hours], serum cortisol [0-12 hours], and glucose [0-4 hours]) parameters on day 
      14. RESULTS: Twenty-six children were randomized (58% boys; mean age, 8.1 years). 
      No clinically significant changes in the primary end points were observed. Five 
      patients reported 4 and 2 AEs with FF/VI and FF therapy, respectively. After 
      FF/VI or FF treatment, the geometric mean ratios (90% CIs) for FF AUC0-4 (1.02 
      [0.86-1.22]) and FF Cmax (0.98 [0.65-1.48]) were similar. For serum glucose (0-4 
      hours) concentration, a difference of 0.50 mM (95% CI, 0.19-0.82 mM) was observed 
      for FF/VI versus FF; no differences were observed for other PD parameters. No AEs 
      were judged to be serious or treatment related. The PK profile of FF did not seem 
      to be altered by VI and was not affected by age or sex. The significance of an 
      increased serum glucose level is difficult to judge as measurements were taken 
      from nonfasted patients. Results can be compared only with active treatment, and 
      the ability to generalize is limited by the small number of patients in this 
      single-center study. CONCLUSIONS: Once-daily repeated dosing of FF/VI, 100/25 microg, 
      using the ELLIPTA dry powder inhaler was as well tolerated as FF, 100 microg, in this 
      small, selected population of 5- to 11-year-old, mostly white/caucasian children 
      with persistent asthma.
CI  - Copyright (c) 2014 The Authors. Published by EM Inc USA.. All rights reserved.
FAU - Oliver, Amanda
AU  - Oliver A
AD  - GlaxoSmithKline, Uxbridge, United Kingdom. Electronic address: 
      Amanda.j.oliver@gsk.com.
FAU - VanBuren, Sandi
AU  - VanBuren S
AD  - GlaxoSmithKline, King of Prussia, Pennsylvania.
FAU - Allen, Ann
AU  - Allen A
AD  - GlaxoSmithKline, Stevenage, United Kingdom.
FAU - Hamilton, Melanie
AU  - Hamilton M
AD  - GlaxoSmithKline, Ware, United Kingdom.
FAU - Tombs, Lee
AU  - Tombs L
AD  - Synergy, Slough, United Kingdom.
FAU - Inamdar, Amir
AU  - Inamdar A
AD  - GlaxoSmithKline, Uxbridge, United Kingdom.
FAU - Kempsford, Rodger
AU  - Kempsford R
AD  - GlaxoSmithKline, Stevenage, United Kingdom.
LA  - eng
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20140430
PL  - United States
TA  - Clin Ther
JT  - Clinical therapeutics
JID - 7706726
RN  - 0 (Adrenergic beta-2 Receptor Agonists)
RN  - 0 (Androstadienes)
RN  - 0 (Benzyl Alcohols)
RN  - 0 (Chlorobenzenes)
RN  - 0 (Drug Combinations)
RN  - 0 (Glucocorticoids)
RN  - 028LZY775B (vilanterol)
RN  - JS86977WNV (fluticasone furoate)
SB  - IM
MH  - Administration, Inhalation
MH  - Adrenergic beta-2 Receptor Agonists/*administration & dosage
MH  - Androstadienes/*administration & dosage
MH  - Asthma/*drug therapy
MH  - Benzyl Alcohols/*administration & dosage
MH  - Child
MH  - Chlorobenzenes/*administration & dosage
MH  - Chronic Disease
MH  - Cross-Over Studies
MH  - Double-Blind Method
MH  - Drug Combinations
MH  - Dry Powder Inhalers
MH  - Female
MH  - Glucocorticoids/administration & dosage
MH  - Humans
MH  - Male
MH  - Treatment Outcome
OTO - NOTNLM
OT  - ICS
OT  - LABA
OT  - pediatric
OT  - pharmacodynamics
OT  - pharmacokinetics
OT  - tolerability
EDAT- 2014/05/06 06:00
MHDA- 2016/03/31 06:00
CRDT- 2014/05/06 06:00
PHST- 2013/11/21 00:00 [received]
PHST- 2014/02/21 00:00 [revised]
PHST- 2014/03/25 00:00 [accepted]
PHST- 2014/05/06 06:00 [entrez]
PHST- 2014/05/06 06:00 [pubmed]
PHST- 2016/03/31 06:00 [medline]
AID - S0149-2918(14)00182-9 [pii]
AID - 10.1016/j.clinthera.2014.03.014 [doi]
PST - ppublish
SO  - Clin Ther. 2014 Jun 1;36(6):928-939.e1. doi: 10.1016/j.clinthera.2014.03.014. 
      Epub 2014 Apr 30.