Efficacy and Safety Study in Subjects With Asthma

A Multi-center, Randomized, Double-blind, Placebo-controlled, Five Period Cross-over Study to Evaluate the Efficacy and Safety of Selected Doses and Dose Intervals of GW642444 Administered Via a Novel Dry Powder Inhaler (NDPI) in Subjects ≥18 Years of Age With Persistent Asthma

The study is a multi-center, double-blind, placebo-controlled, cross-over study to evaluate the efficacy and safety of selected doses and dose intervals of the novel long acting beta agonist (LABA), GW642444 in asthmatic subjects ≥18 years of age who are currently receiving inhaled corticosteroid treatment.

Study Overview

• Status: Completed
• Conditions: Asthma
• Intervention / Treatment: Drug: placebo; Drug: Dose 2 QD; Drug: Dose 3 QD; Drug: Dose 1 BD; Drug: Dose 4 QD

Detailed Description

The study will be a five-period cross-over study with each 7 day treatment period separated by a 7 day wash-out period. The study will enroll asthmatic subjects ≥18 years of age who are currently receiving inhaled corticosteroid treatment with an FEV1 of between 40-85% of predicted normal and with airway reversibility as demonstrated by an increase in FEV1 of ≥12% and ≥200ml .

Efficacy assessments include 24-hour serial lung function testing. Safety assessments include incidence of adverse events and measurement of vital signs.

• Study Type: Interventional
• Enrollment (Actual): 75
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Cypress, California, United States, 90630
      • GSK Investigational Site
    • Huntington Beach, California, United States, 92647
      • GSK Investigational Site
  • Maryland
    • Bethesda, Maryland, United States, 20814
      • GSK Investigational Site
  • Missouri
    • Rolla, Missouri, United States, 65401
      • GSK Investigational Site
  • North Carolina
    • Raleigh, North Carolina, United States, 27607
      • GSK Investigational Site
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73103
      • GSK Investigational Site
  • Oregon
    • Medford, Oregon, United States, 97504
      • GSK Investigational Site
  • South Carolina
    • Orangeburg, South Carolina, United States, 29118
      • GSK Investigational Site
  • Texas
    • Boerne, Texas, United States, 78006
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Outpatient
• ≥18 years of age at Visit 1
• Male or Eligible Female
• Diagnosis of asthma at least 12 weeks prior to Visit 1
• Disease reversibility
• Current anti-asthma therapy
• Appropriately signed and dated informed consent has been obtained
• Able to comply with all the study requirements

Exclusion Criteria:

• History of Life-Threatening Asthma
• No use of systemic corticosteroids for any indication within 8 weeks prior to Visit
• No concurrent diseases/abnormalities that would put the safety of the subject at risk through study participation
• Drug Allergy to β2 agonist or sympathomimetic drugs, or known or suspected sensitivity to lactose or magnesium stearate
• History of severe milk protein allergy
• Non-compliance with study medication and other study-related requirements
• No use of inhaled tobacco products within the past three months or historical use of 10 pack years or more
• Administration of prohibited medications and non-drug therapies and corresponding timeframes as outlined in the protocol

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: C/E/A/B/D; GW642444 Dose 2 QD/GW642444 Dose 4 QD/placebo/GW642444 Dose 1 BD/GW642444 Dose 3 QD	Drug: Dose 2 QD; QD once daily
Experimental: D/C/E/A/B; GW642444 Dose 3 QD/GW642444 Dose 2 QD/GW642444 Dose 4 QD/placebo/GW642444 Dose 1 BD	Drug: Dose 3 QD; QD once daily
Experimental: A/B/C/D/E; placebo/GW642444 Dose 1 BD/GW642444 Dose 2 QD/GW642444 Dose 3 QD/GW642444 Dose 4 QD	Drug: placebo; placebo
Experimental: B/A/D/E/C; GW642444 Dose 1 BD/placebo/GW642444 Dose 3 QD/GW642444 Dose 4 QD/GW642444 Dose 2 QD	Drug: Dose 1 BD; BD twice daily
Experimental: E/D/B/C/A; GW642444 Dose 4 QD/GW642444 Dose 3 QD/GW642444 Dose 1 BD/GW642444 Dose 2 QD/placebo	Drug: Dose 4 QD; QD once daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Trough (Pre-bronchodilator and Pre-dose) FEV1 on Day 7 of the Treatment Period	Pulmonary function was measured by forced expiratory volume in one second (FEV1), defined as the maximal amount of air that can be forcefully exhaled in one second. Trough FEV1 is defined as the mean of the FEV1 values obtained at the last two scheduled time points at the Day 7 clinic visit (i.e., 11 and 12 hours after the morning dose, or 23 and 24 hours after the evening dose). Change from Baseline was calculated as the Day 7 value minus the Baseline value. Analysis was performed using a mixed model analysis of covariance (ANCOVA) with fixed effects of treatment, period, sex, and age. Participants is fitted as a random effect, and the period Baseline measurement is included as part of a bivariate response. The model for the period Baseline value is not affected by treatment group.	Baseline and Day 7 of the treatment period (up to Study Day 63)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Weighted Mean 24-hour FEV1 on Day 7 of the Treatment Period	Pulmonary function was measured by FEV1, defined as the maximal amount of air that can be forcefully exhaled in one second. Weighted mean was derived by calculating the average area under curve, and then dividing by the relevant time interval. 24-hour serial measurements of FEV1 were performed on Day 7 of each of the 5 treatment periods (Visits 3, 5, 7, 9, and 11). Measurements were taken at pre-dose; 30 and 60 minutes; and 3, 5, 11, 12, 12.5, 13, 15, 17, 23, and 24 hours post-dose. Visits 3, 5, 7, 9, and 11 were overnight visits. Change from Baseline was calculated as the Day 7 value minus the Baseline value. Analysis was performed using a mixed effects analysis of covariance (ANCOVA) model, with fixed effects for treatment, period, sex, and age. Participant was fitted as a random effect, and the period Baseline FEV1 measurement was included as part of a bivariate response. The model for the period Baseline value is not affected by treatment group.	Baseline and Day 7 of the treatment period (up to Study Day 63)

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

General Publications

• Sterling R, Lim J, Frith L, Snowise NG, Jacques L, Haumann B. Efficacy and optimal dosing interval of the long-acting beta(2) agonist, vilanterol, in persistent asthma: a randomised trial. Respir Med. 2012 Aug;106(8):1110-5. doi: 10.1016/j.rmed.2012.03.007. Epub 2012 Apr 19.

Helpful Links

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

Study record dates

Study Major Dates

• Study Start: September 1, 2009
• Primary Completion (Actual): January 1, 2010
• Study Completion (Actual): January 1, 2010

Study Registration Dates

• First Submitted: September 17, 2009
• First Submitted That Met QC Criteria: September 17, 2009
• First Posted (Estimate): September 18, 2009

Study Record Updates

• Last Update Posted (Estimate): January 30, 2017
• Last Update Submitted That Met QC Criteria: December 1, 2016
• Last Verified: December 1, 2016

More Information

Terms related to this study

• Keywords: safety; asthma; efficacy; GW642444; FEV1; once daily dosing
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma
• Other Study ID Numbers: 113310

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

Study Data/Documents

1. Individual Participant Data Set
   Information identifier: 113310
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
2. Statistical Analysis Plan
   Information identifier: 113310
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
3. Annotated Case Report Form
   Information identifier: 113310
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
4. Clinical Study Report
   Information identifier: 113310
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
5. Dataset Specification
   Information identifier: 113310
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
6. Informed Consent Form
   Information identifier: 113310
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
7. Study Protocol
   Information identifier: 113310
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register