Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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.
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.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| C/E/A/B/D | Experimental | GW642444 Dose 2 QD/GW642444 Dose 4 QD/placebo/GW642444 Dose 1 BD/GW642444 Dose 3 QD |
|
| D/C/E/A/B | Experimental | GW642444 Dose 3 QD/GW642444 Dose 2 QD/GW642444 Dose 4 QD/placebo/GW642444 Dose 1 BD |
|
| A/B/C/D/E | Experimental | placebo/GW642444 Dose 1 BD/GW642444 Dose 2 QD/GW642444 Dose 3 QD/GW642444 Dose 4 QD |
|
| B/A/D/E/C | Experimental | GW642444 Dose 1 BD/placebo/GW642444 Dose 3 QD/GW642444 Dose 4 QD/GW642444 Dose 2 QD |
|
| E/D/B/C/A | Experimental | GW642444 Dose 4 QD/GW642444 Dose 3 QD/GW642444 Dose 1 BD/GW642444 Dose 2 QD/placebo |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Dose 4 QD | Drug | QD once daily |
| |
| Dose 3 QD |
| 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) |
| 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. |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| GSK Clinical Trials | GlaxoSmithKline | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| GSK Investigational Site | Cypress | California | 90630 | United States | ||
| GSK Investigational Site |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 22520084 | Background | 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. |
| Label | URL |
|---|---|
| Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research. | View source |
| ID | Type | URL | Comment |
|---|---|---|---|
| 113310 | Individual Participant Data Set | View IPD |
Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
Not provided
Not provided
Not provided
Not provided
The study was a multi-centre, double-blind, placebo-controlled, five-period cross-over study. Following the 7(+7)-day RIP, eligible participants were randomized to 1 of 5 sequences of GW642444 at doses of 6.25 micrograms (µg) once daily (QD), 6.25 µg twice daily, 12.5 µg QD, 25 µg QD, and placebo.
Participants (par,) who met all inclusion criteria at screening entered a 7-day Run-in Period (RIP). Par. were instructed to administer albuterol inhalation aerosol as needed and to continue their inhaled corticosteroid at a stable dose throughout the study. Par. who met randomization criteria at the end of the RIP entered Treatment Period 1.
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Sequence 1: 6.25 µg BID, Pbo, 12.5 µg QD, 25 µg QD, 6.25 µg QD | Participants received GW642444 6.25 micrograms (µg) twice a day (BID), placebo (pbo), GW642444 12.5 µg once a day (QD) in the evening, GW642444 25 µg QD in the evening, and GW642444 6.25 µg QD in the evening in Treatment Periods 1, 2, 3, 4, and 5 respectively. Participants received all treatments from a Dry Powder Inhaler (DPI) for 7 days. The treatments were administered approximately 12 hours apart. All participants took blinded treatment (active or placebo) every 12 hours, and therefore followed a 12-hour dosing interval. The five treatment periods were separated by a washout period of at least 7 days. |
| FG001 | Sequence 2: Pbo, 6.25 µg BID, 6.25 µg QD, 12.5 µg QD, 25 µg QD | Participants received placebo, GW642444 6.25 µg BID, GW642444 6.25 µg QD in the evening, GW642444 12.5 µg QD in the evening, and GW642444 25 µg QD in the evening and in Treatment Periods 1, 2, 3, 4, and 5 respectively. Participants received all treatments from a DPI for 7 days. The treatments were administered approximately 12 hours apart. All participants took blinded treatment (active or placebo) every 12 hours, and therefore followed a 12-hour dosing interval. The five treatment periods were separated by a washout period of at least 7 days. |
| FG002 | Sequence 3: 6.25 µg QD, 25 µg QD, Pbo, 6.25 µg BID, 12.5 µg QD | Participants received GW642444 6.25 µg QD in the evening, GW642444 25 µg QD in the evening, placebo, GW642444 6.25 µg BID, and GW642444 12.5 µg QD in the evening in Treatment Periods 1, 2, 3, 4, and 5 respectively. Participants received all treatments from a DPI for 7 days. The treatments were administered approximately 12 hours apart. All participants took blinded treatment (active or placebo) every 12 hours, and therefore followed a 12-hour dosing interval. The five treatment periods were separated by a washout period of at least 7 days. |
| FG003 | Sequence 4: 12.5 µg QD, 6.25 µg QD, 25 µg QD, Pbo, 6.25 µg BID | Participants received GW642444 12.5 µg QD in the evening, GW642444 6.25 µg QD in the evening, GW642444 25 µg QD in the evening, placebo, and GW642444 6.25 µg BID and in Treatment Periods 1, 2, 3, 4, and 5 respectively. Participants received all treatments from a DPI for 7 days. The treatments were administered approximately 12 hours apart. All participants took blinded treatment (active or placebo) every 12 hours, and therefore followed a 12-hour dosing interval. The five treatment periods were separated by a washout period of at least 7 days. |
| FG004 | Sequence 5: 25 µg QD, 12.5 µg QD, 6.25 µg BID, 6.25 µg QD, Pbo | Participants received GW642444 25 µg QD in the evening, GW642444 12.5 µg QD in the evening, GW642444 6.25 µg BID, GW642444 6.25 µg QD in the evening, and placebo in Treatment Periods 1, 2, 3, 4, and 5 respectively. Participants received all treatments from a DPI for 7 days. The treatments were administered approximately 12 hours apart. All participants took blinded treatment (active or placebo) every 12 hours, and therefore followed a 12-hour dosing interval. The five treatment periods were separated by a washout period of at least 7 days. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 7-day Treatment Period 1 |
|
| ||||||||||||||||||
| 7-day Washout Period 1 |
| |||||||||||||||||||
| 7-day Treatment Period 2 |
| |||||||||||||||||||
| 7-day Washout Period 2 |
| |||||||||||||||||||
| 7-day Treatment Period 3 |
| |||||||||||||||||||
| 7-day Washout Period 3 |
| |||||||||||||||||||
| 7-day Treatment Period 4 |
| |||||||||||||||||||
| 7-day Washout Period 4 |
| |||||||||||||||||||
| 7-day Treatment Period 5 |
|
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | PB, GW642444 6.25 µg QD, 6.25 µg BID, 12.5 µg QD, and 25 µg QD | All participants received one of the following five treatments in one of the five Treatment Periods from two DPI dispensed on Day 1of each of the five 7-day treatment periods: Placebo (PB), GW642444 6.25 µg once daily (QD) in the evening, GW642444 6.25 µg twice daily (BID), GW642444 12.5 µg QD in the evening, and GW642444 25 µg QD in the evening. Participants received their first evening medication dose in the clinic on Day 1 of each of the five treatment periods. The treatments were administered in the morning (AM) and in the evening (PM), approximately 12 hours apart. All participants took blinded treatment (active or placebo) every 12 hours, and therefore followed a 12-hour dosing interval. The five treatment periods were separated by a 7-day washout period. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Intent-to Treat (ITT) Population: all participants randomized to treatment who received at least one dose of trial medication. Randomized participants were assumed to have received trial medication unless definitive evidence to the contrary existed. Only participants available at the indicated time point were analyzed. | Posted | Least Squares Mean | Standard Error | Liters | Baseline and Day 7 of the treatment period (up to Study Day 63) |
Serious adverse events (SAEs) and non-serious AEs were collected from randomization until follow-up (up to Day 70).
SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication. Randomized participants were assumed to have received trial medication unless definitive
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Placebo | Participants received 2 placebo actuations per day during one of the five 7-day Treatment Periods. Participants received treatment in the morning (AM) and evening (PM), approximately 12 hours apart, from two seperate DPIs starting with their first dose on the evening of Day 1. Each treatment period was followed by a 7-day washout period. |
Not provided
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Upper respiratory tract information | Infections and infestations | MedDRA | Systematic Assessment |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| GSK Response Center | GlaxoSmithKline | 866-435-7343 |
Not provided
| ID | Term |
|---|---|
| D001249 | Asthma |
| ID | Term |
|---|---|
| D001982 | Bronchial Diseases |
| D012140 | Respiratory Tract Diseases |
| D008173 | Lung Diseases, Obstructive |
| D008171 | Lung Diseases |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Drug |
QD once daily |
|
| placebo | Drug | placebo |
|
| Dose 2 QD | Drug | QD once daily |
|
| Dose 1 BD | Drug | BD twice daily |
|
| Baseline and Day 7 of the treatment period (up to Study Day 63) |
| Huntington Beach |
| California |
| 92647 |
| United States |
| GSK Investigational Site | Bethesda | Maryland | 20814 | United States |
| GSK Investigational Site | Rolla | Missouri | 65401 | United States |
| GSK Investigational Site | Raleigh | North Carolina | 27607 | United States |
| GSK Investigational Site | Oklahoma City | Oklahoma | 73103 | United States |
| GSK Investigational Site | Medford | Oregon | 97504 | United States |
| GSK Investigational Site | Orangeburg | South Carolina | 29118 | United States |
| GSK Investigational Site | Boerne | Texas | 78006 | United States |
For additional information about this study please refer to the GSK Clinical Study Register |
| 113310 | Statistical Analysis Plan | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| 113310 | Annotated Case Report Form | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| 113310 | Clinical Study Report | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| 113310 | Dataset Specification | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| 113310 | Informed Consent Form | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| 113310 | Study Protocol | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| COMPLETED |
|
| NOT COMPLETED |
|
| COMPLETED |
|
| NOT COMPLETED |
|
| COMPLETED |
|
| NOT COMPLETED |
|
| COMPLETED |
|
| NOT COMPLETED |
|
|
| COMPLETED |
|
| NOT COMPLETED |
|
| COMPLETED |
|
| NOT COMPLETED |
|
| COMPLETED |
|
| NOT COMPLETED |
|
| COMPLETED |
|
| NOT COMPLETED |
|
| Years |
|
| Gender | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Number | participants |
|
| ID | Title | Description |
|---|---|---|
| OG000 | Placebo | Participants received 2 placebo actuations per day during one of the five 7-day Treatment Periods. Participants received treatment in the morning (AM) and evening (PM), approximately 12 hours apart, from two seperate DPIs starting with their first dose on the evening of Day 1. Each treatment period was followed by a 7-day washout period. |
| OG001 | GW642444 6.25 µg QD | Participants received 2 actuations per day (AM and PM) during one of the five 7-day Treatment Periods from two seperate DPIs starting with their first dose on the evening of Day 1. Participants received one actuation of GW642444 6.25 µg and another actuation of placebo. The treatments were administered approximately 12 hours apart. All participants took blinded treatment (active or placebo) every 12 hours, and therefore followed a 12-hour dosing interval. Each treatment period was followed by a 7-day washout period. |
| OG002 | GW642444 6.25 µg BID | Participants received 2 actuations per day for during one of the five 7-day Treatment Periods from two separate DPIs starting with their first dose on the evening of Day 1. Participants received one actuation of GW642444 6.25 µg in the morning and a second actuation in the evening. The treatments were administered approximately 12 hours apart. All participants took blinded treatment every 12 hours, and therefore followed a 12-hour dosing interval. Each treatment period was followed by a 7-day washout period. |
| OG003 | GW642444 12.5 µg QD | Participants received 2 actuations per day (AM and PM) during one of the five 7-day Treatment Periods from two seperate DPIs starting with their first dose on the evening of Day 1. Participants received one actuation of GW642444 12.5 µg and another actuation of placebo. The treatments were administered approximately 12 hours apart. All participants took blinded treatment (active or placebo) every 12 hours, and therefore followed a 12-hour dosing interval. Each treatment period was followed by a 7-day washout period. |
| OG004 | GW642444 25 µg QD | Participants received 2 actuations per day (AM and PM) during one of the five 7-day Treatment Periods from two seperate DPIs starting with their first dose on the evening of Day 1. Participants received one actuation of GW642444 25 µg and another actuation of placebo. The treatments were administered approximately 12 hours apart. All participants took blinded treatment (active or placebo) every 12 hours, and therefore followed a 12-hour dosing interval. Each treatment period was followed by a 7-day washout period. |
|
|
|
| Secondary | 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. | ITT Population. Only those participants available at the indicated time points were analyzed. | Posted | Least Squares Mean | Standard Error | Liters | Baseline and Day 7 of the treatment period (up to Study Day 63) |
|
|
|
| 0 |
| 74 |
| 1 |
| 74 |
| EG001 | GW642444 6.25 µg QD | Participants received 2 actuations per day (AM and PM) during one of the five 7-day Treatment Periods from two seperate DPIs starting with their first dose on the evening of Day 1. Participants received one actuation of GW642444 6.25 µg and another actuation of placebo. The treatments were administered approximately 12 hours apart. All participants took blinded treatment (active or placebo) every 12 hours, and therefore followed a 12-hour dosing interval. Each treatment period was followed by a 7-day washout period. | 0 | 73 | 0 | 73 |
| EG002 | GW642444 6.25 µg BID | Participants received 2 actuations per day for during one of the five 7-day Treatment Periods from two separate DPIs starting with their first dose on the evening of Day 1. Participants received one actuation of GW642444 6.25 µg in the morning and a second actuation in the evening. The treatments were administered approximately 12 hours apart. All participants took blinded treatment every 12 hours, and therefore followed a 12-hour dosing interval. Each treatment period was followed by a 7-day washout period. | 0 | 74 | 3 | 74 |
| EG003 | GW642444 12.5 µg QD | Participants received 2 actuations per day (AM and PM) during one of the five 7-day Treatment Periods from two seperate DPIs starting with their first dose on the evening of Day 1. Participants received one actuation of GW642444 12.5 µg and another actuation of placebo. The treatments were administered approximately 12 hours apart. All participants took blinded treatment (active or placebo) every 12 hours, and therefore followed a 12-hour dosing interval. Each treatment period was followed by a 7-day washout period. | 0 | 73 | 0 | 73 |
| EG004 | GW642444 25 µg QD | Participants received 2 actuations per day (AM and PM) during one of the five 7-day Treatment Periods from two seperate DPIs starting with their first dose on the evening of Day 1. Participants received one actuation of GW642444 25 µg and another actuation of placebo. The treatments were administered approximately 12 hours apart. All participants took blinded treatment (active or placebo) every 12 hours, and therefore followed a 12-hour dosing interval. Each treatment period was followed by a 7-day washout period. | 0 | 73 | 3 | 73 |
| Road traffic accident | Injury, poisoning and procedural complications | MedDRA | Systematic Assessment |
|
GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
| D012130 |
| Respiratory Hypersensitivity |
| D006969 | Hypersensitivity, Immediate |
| D006967 | Hypersensitivity |
| D007154 | Immune System Diseases |