PMID- 22419863
OWN - NLM
STAT- MEDLINE
DCOM- 20120625
LR  - 20211021
IS  - 1178-2005 (Electronic)
IS  - 1176-9106 (Print)
IS  - 1176-9106 (Linking)
VI  - 7
DP  - 2012
TI  - Safety and efficacy of dual therapy with GSK233705 and salmeterol versus 
      monotherapy with salmeterol, tiotropium, or placebo in a crossover pilot study in 
      partially reversible COPD patients.
PG  - 153-64
LID - 10.2147/COPD.S26100 [doi]
AB  - BACKGROUND: GSK233705 is an inhaled, long-acting muscarinic antagonist in 
      development for the treatment of chronic obstructive pulmonary disease (COPD). 
      This study was performed to see if the addition of GSK233705 to salmeterol would 
      provide greater bronchodilation than salmeterol or tiotropium alone in COPD. 
      METHODS: In an incomplete-block, three-period, crossover design, dually 
      responsive patients received three of the following five treatments: GSK233705 20 
      mug plus salmeterol 50 mug twice-daily; GSK233705 50 mug plus salmeterol 50 mug 
      twice-daily; salmeterol 50 mug or placebo, each twice-daily; and tiotropium 18 mug 
      or placebo once-daily for 7 days. Each treatment period was separated by a 14-day 
      washout. The primary efficacy endpoint was morning (trough) forced expiratory 
      volume in 1 second (FEV(1)) on Day 8, following 7 days of treatment. Secondary 
      endpoints included pulmonary function, plethysmography, pharmacokinetics of 
      GSK233705 and salmeterol, adverse events (AEs), electrocardiograms (ECGs), vital 
      signs, and laboratory parameters. RESULTS: A total of 47 patients were 
      randomized. The mean % predicted normal postbronchodilator FEV(1) was 55% at 
      screening. Compared with placebo (n = 24), the adjusted mean change from baseline 
      in trough FEV(1) on Day 8 was 215 mL higher with GSK233705 20 mug + salmeterol (n 
      = 23) and 203 mL higher with GSK233705 50 mug + salmeterol (n = 27), whereas with 
      salmeterol (n = 27) and tiotropium (n = 28) the changes were 101 mL and 118 mL 
      higher, respectively. The primary efficacy results were supported by the results 
      from the other secondary lung function assessments. AEs were reported by similar 
      proportions of patients across the treatment groups, with headache the most 
      frequently reported treatment-related AE reported by one subject receiving each 
      of GSK233705 20 mug + salmeterol, tiotropium, and placebo. No significant 
      differences were seen in vital signs, ECGs, or laboratory parameters between the 
      groups. CONCLUSION: The addition of GSK233705 to salmeterol in partially 
      reversible COPD patients resulted in greater bronchodilation than salmeterol or 
      tiotropium alone and was well tolerated.
FAU - Beier, Jutta
AU  - Beier J
AD  - INSAF Respiratory Research Institute, Germany. j.beier@insaf-wi.de
FAU - van Noord, Jan
AU  - van Noord J
FAU - Deans, Amanda
AU  - Deans A
FAU - Brooks, Jean
AU  - Brooks J
FAU - Maden, Claire
AU  - Maden C
FAU - Baggen, Suus
AU  - Baggen S
FAU - Mehta, Rashmi
AU  - Mehta R
FAU - Cahn, Anthony
AU  - Cahn A
LA  - eng
SI  - ClinicalTrials.gov/NCT00422604
PT  - Comparative Study
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20120305
PL  - New Zealand
TA  - Int J Chron Obstruct Pulmon Dis
JT  - International journal of chronic obstructive pulmonary disease
JID - 101273481
RN  - 0 (Adrenergic beta-2 Receptor Agonists)
RN  - 0 (Bronchodilator Agents)
RN  - 0 (Muscarinic Antagonists)
RN  - 0 (Placebos)
RN  - 0 (Scopolamine Derivatives)
RN  - 6EW8Q962A5 (Salmeterol Xinafoate)
RN  - QF8SVZ843E (Albuterol)
RN  - XX112XZP0J (Tiotropium Bromide)
SB  - IM
MH  - Administration, Inhalation
MH  - Adrenergic beta-2 Receptor Agonists/administration & dosage/adverse 
      effects/pharmacokinetics/*therapeutic use
MH  - Aged
MH  - Albuterol/administration & dosage/adverse effects/*analogs & 
      derivatives/pharmacokinetics/therapeutic use
MH  - Bronchodilator Agents/administration & dosage/adverse 
      effects/pharmacokinetics/*therapeutic use
MH  - Cross-Over Studies
MH  - Drug Administration Schedule
MH  - Drug Therapy, Combination
MH  - Electrocardiography
MH  - Europe
MH  - Female
MH  - Forced Expiratory Volume
MH  - Humans
MH  - Lung/*drug effects/physiopathology
MH  - Male
MH  - Middle Aged
MH  - Muscarinic Antagonists/administration & dosage/adverse 
      effects/pharmacokinetics/*therapeutic use
MH  - Pilot Projects
MH  - Placebos
MH  - Plethysmography
MH  - Pulmonary Disease, Chronic Obstructive/diagnosis/*drug therapy/physiopathology
MH  - Salmeterol Xinafoate
MH  - Scopolamine Derivatives/administration & dosage/adverse 
      effects/pharmacokinetics/*therapeutic use
MH  - Spirometry
MH  - Time Factors
MH  - Tiotropium Bromide
MH  - Treatment Outcome
MH  - Vital Signs
PMC - PMC3299545
OTO - NOTNLM
OT  - COPD
OT  - LABA
OT  - LAMA
OT  - bronchodilation
OT  - dual therapy
EDAT- 2012/03/16 06:00
MHDA- 2012/06/26 06:00
PMCR- 2012/03/05
CRDT- 2012/03/16 06:00
PHST- 2012/03/16 06:00 [entrez]
PHST- 2012/03/16 06:00 [pubmed]
PHST- 2012/06/26 06:00 [medline]
PHST- 2012/03/05 00:00 [pmc-release]
AID - copd-7-153 [pii]
AID - 10.2147/COPD.S26100 [doi]
PST - ppublish
SO  - Int J Chron Obstruct Pulmon Dis. 2012;7:153-64. doi: 10.2147/COPD.S26100. Epub 
      2012 Mar 5.