Efficacy and Safety Study in Subjects With Asthma

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Asthma

Intervention / Treatment
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* Drug: Dose 4 QD
* Drug: Dose 3 QD
* Drug: placebo
* Drug: Dose 2 QD
* Drug: Dose 1 BD


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: C/E/A/B/D<br>GW642444 Dose 2 QD/GW642444 Dose 4 QD/placebo/GW642444 Dose 1 BD/GW642444 Dose 3 QD | Drug: Dose 2 QD<br>* QD once daily<br>|
| Experimental: D/C/E/A/B<br>GW642444 Dose 3 QD/GW642444 Dose 2 QD/GW642444 Dose 4 QD/placebo/GW642444 Dose 1 BD | Drug: Dose 3 QD<br>* QD once daily<br>|
| Experimental: A/B/C/D/E<br>placebo/GW642444 Dose 1 BD/GW642444 Dose 2 QD/GW642444 Dose 3 QD/GW642444 Dose 4 QD | Drug: placebo<br>* placebo<br>|
| Experimental: B/A/D/E/C<br>GW642444 Dose 1 BD/placebo/GW642444 Dose 3 QD/GW642444 Dose 4 QD/GW642444 Dose 2 QD | Drug: Dose 1 BD<br>* BD twice daily<br>|
| Experimental: E/D/B/C/A<br>GW642444 Dose 4 QD/GW642444 Dose 3 QD/GW642444 Dose 1 BD/GW642444 Dose 2 QD/placebo | Drug: Dose 4 QD<br>* QD once daily<br>|

What is the study measuring?
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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) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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GW642444, once daily dosing, asthma, efficacy, safety, FEV1