Study B2C112060: A Study of the Efficacy and Safety of Vilanterol Inhalation Powder in Adults and Adolescents With Persistent Asthma

A Randomized, Double-blind, Double-dummy, Parallel-group, Placebo Controlled (on Inhaled Corticosteroid Medication), Multicenter Study to Evaluate the Efficacy and Safety of Vilanterol Inhalation Powder (GW642444) and Salmeterol, Compared With Placebo in the Treatment of Persistent Asthma in Adults and Adolescents Uncontrolled on Inhaled Corticosteroids

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01181895

Enrollment

348

Registered

2010-08-13

Start date

2010-09-01

Completion date

2011-08-26

Last updated

2017-11-08

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Asthma

Keywords

asthma

Brief summary

The objective of this study is to evaluate the efficacy and safety of vilanterol inhalation powder administered once daily in the evening in adolescent and adult subjects 12 years of age and older with persistent asthma over a 12-week treatment period.

Interventions

DRUGVilanterol

Vilanterol inhalation powder inhaled orally once daily for 12 weeks

DRUGSalmeterol Inhalation Powder

Salmeterol inhalation powder inhaled orally twice daily for 12 weeks

DRUGPlacebo Inhalation Powder NDPI

Placebo inhalation powder inhaled orally via Novel Dry Powder Inhaler

DRUGPlacebo Inhalation Powder Diskus

Placebo inhalation powder inhaled orally twice daily for 12 weeks

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

DOUBLE (Subject, Investigator)

Eligibility

Sex/Gender

ALL

Age

12 Years to No maximum

Healthy volunteers

Inclusion criteria

* Outpatient at least 12 years of age * Both genders; females of childbearing potential must be willing to use birth control method * Clinical diagnosis of asthma for ≥12 weeks * Best pre-bronchodilator FEV1 of 40%-90% predicted * Reversibility of FEV1 of at least 12% and 200mls * Current asthma therapy that include an inhaled corticosteroid for at least 12 weeks prior to 1st visit * Ability to use replace current short-acting rescue treatment with albuterol and ability to withhold albuterol use for at least 6 hours prior to study visits

Exclusion criteria

* History of life-threatening asthma * Respiratory infection within last 4 weeks leading to change in asthma management * Asthma exacerbation within last 3 months * Concurrent respiratory disease or other disease that would confound study participation or affect subject safety * Allergies to study drugs, study drugs' excipients, or medications related to study drugs * Taking another investigational medication or medication prohibited for use during the study. * Previous participation in a vilanterol (GW642444) study

Design outcomes

Primary

Measure	Time frame	Description
Change From Baseline in Weighted-mean 24-hour Serial Forced Expiratory Volume in One Second (FEV1) at Week 12	Baseline and Week 12	FEV1 is a measure of lung function and is defined as the volume of air that can be forcefully exhaled in one second. The weighted mean is calculated from the pre-dose FEV1 and post-dose FEV1 measurements at 5, 15, and 30 minutes (min) and at 1, 2, 3, 4, 11, 12, 12.5, 13, 14, 16, 20, 23, and 24 hours, respectively, at Week 12. The Baseline value was the Day 1 pre-dose FEV1 measurement. Change from Baseline is calculated as the weighted mean 0-24 hour FEV1 (Liters) at Week 12 minus the Baseline value. Analysis was performed using analysis of covariance (ANCOVA) with covariates of Baseline FEV1, region, sex, age, and treatment.

Secondary

Measure	Time frame	Description
Change From Baseline in the Percentage of Symptom-free 24-hour (hr) Periods During the 12-week Treatment Period	Baseline and Weeks 1-12	Participants who were symptom free for 24-hour periods during the12-week treatment period were assessed. The Baseline value was derived from the last 7 days of the daily diary prior to the randomization of the participant (including the day of randomization). Change from Baseline is calculated as the value at Weeks 1-12 minus the value at Baseline. Analysis was performed using ANCOVA with covariates of Baseline, region, sex, age, and treatment.
Change From Baseline in Individual Serial FEV1 Assessments at the End of the 12-week Treatment Period, Including the 12-hour and 24-hour Time Points	Baseline and Week 12	FEV1 is a measure of lung function and is defined as the volume of air that can be forcefully exhaled in one second. The individual serial FEV1 is calculated from the pre-dose FEV1 and post-dose FEV1 measurements at 5, 15, 30, and 60 minutes (min) and 2, 3, 5, 11, 12, 12.5, 13, 14, 16, 20, 23, and 24 hours, relatively, on Treatment Day 84 (Week 12). The Baseline value was the Day 1 pre-dose FEV1 measurement. Change from Baseline was calculated as the value of the individual serial FEV1 taken at Week 12 minus the Baseline value. Analysis was performed using ANCOVA with covariates of Baseline FEV1, region, sex, age, and treatment. Analysis was performed separately for each planned time point.
Change From Baseline in Daily Trough (Pre-dose and Pre-rescue Bronchodilator) PM (Evening) Peak Expiratory Flow (PEF) Averaged Over the 12-week Treatment Period	Baseline and Weeks 1-12	PEF is defined as the maximum airflow during a forced expiration beginning with the lungs fully inflated. Trough PEF is the PEF measured approximately 24 hours after the last administration of study drug. The Baseline value is the average value of the last 7 days of daily PM PEF prior to randomization. Change from Baseline in trough PM PEF was calculated as the averaged value of all daily PM PEF for Week 1 to Week 12 minus the value at Baseline. Analysis was performed using ANCOVA with covariates of Baseline, region, sex, age, and treatment.
Change From Baseline in the Percentage of Rescue-free 24-hour (hr) Periods During the 12-week Treatment Period	Baseline and Weeks 1-12	The time span during which the participants did not have to take any rescue bronchodilator (medication intended to relieve symptoms immediately) was considered to be a rescue-free period. The Baseline value was derived from the last 7 days of the daily diary prior to the randomization of the participant (including the day of randomization). Change from Baseline is calculated as the value at Weeks 1-12 minus the value at Baseline. Analysis was performed using ANCOVA with covariates of Baseline, region, sex, age, and treatment.
Number of Participants With the Indicated Time to an Increase of >=12% and >=200 Milliliters (mL) Above Baseline in FEV1 on Day 1 and Day 84 (0-2 Hours)	Day 1 and Week 12	The number of participants with a \>=12% and \>=200 mL increase from Baseline in FEV1 (the maximal amount of air that can be forcefully exhaled in one second) was evaluated on Day 1 and Week 12 for the time to a \>=12% increase from Baseline (at the 5 minutes (min), 15 min, 30 min, 1hour (hr), and 2 hr nominal time points. Participants who did not achieve a \>=12% and \>=200 mL increase from Baseline in FEV1 over this time period were considered censored.
Number of Participants With the Indicated Global Assessment of Change Questionnaire Responses at the End of Week 4 and Week 12	Week 4 and Week 12	At the end of Week 4 and Week 12, the Global Assessment of Change Questionnaire, which assesses changes in asthma symptoms and rescue medication use, was completed by participants using the following scale: asthma symptom (AS) change: much better, somewhat better, a little better, the same, a little worse, somewhat worse, much worse; rescue medication use (RMU): much less often , somewhat less often , a little less often , the same , a little more often , somewhat more often , much more often.
Change From Baseline in Daily AM (Morning) PEF Averaged Over the 12-week Treatment Period	Baseline and Weeks 1-12	PEF is defined as the maximum airflow during a forced expiration beginning with the lungs fully inflated. Trough PEF is the PEF measured approximately 24 hours after the last administration of study drug. The Baseline value is the average value of the last 7 days of daily AM PEF prior to randomization. Change from Baseline in trough AM PEF was calculated as the averaged value of all daily AM PEF for Weeks 1 to Week 12 minus the value at Baseline. Analysis was performed using ANCOVA with covariates of Baseline, region, sex, age, and treatment.

Countries

Germany, Peru, Poland, Ukraine, United States

Participant flow

Recruitment details

347 participants (par.) were randomized to treatment; all 347 were included in the Intent-to-Treat (ITT) Population. One par. was not randomized but received treatment in error. This par. was not included in the ITT Population and is thus not captured in the Participant Flow module. This par. is categorized as being enrolled in the study (n=348).

Pre-assignment details

Participants (par.) meeting eligibility criteria at the Screening visit completed a 28-day Run-in Period for Baseline, safety evaluations, and measures of asthma status. Par. were then randomized to an 8-week Treatment Period. A total of 583 par. were screened, and 347 were randomized, of which 298 received at least one dose of study treatment.

Participants by arm

Arm	Count
Placebo Participants received placebo once daily (OD) in the evening from the dry powder inhaler (DPI) and placebo twice daily (BID) from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) for 12 weeks. In addition, participants were provided supplemental albuterol/salbutamol inhalation aerosol to be used as needed throughout the study.	116
Vilanteral 25 µg OD Participants received Vilanterol (VI) 25 micrograms (µg) OD in the evening from the DPI and placebo BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) for 12 weeks. In addition, participants were provided supplemental albuterol/salbutamol aerosol to be used as needed throughout the study.	115
Salmeterol 50 µg BID Participants received Salmeterol 50 µg BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) plus placebo OD in the evening from the DPI for 12 weeks. In addition, participants were provided supplemental albuterol/salbutamol aerosol to be used as needed throughout the study.	116
Total	347

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002
Overall Study	Adverse Event	3	1	1
Overall Study	Investigator Discretion	1	2	1
Overall Study	Lack of Efficacy	8	9	9
Overall Study	Lost to Follow-up	0	1	2
Overall Study	Protocol Violation	2	1	0
Overall Study	Withdrawal by Subject	3	0	5

Baseline characteristics

Characteristic	Placebo	Vilanteral 25 µg OD	Salmeterol 50 µg BID	Total
Age, Continuous	41.7 Years STANDARD_DEVIATION 16.64	41.0 Years STANDARD_DEVIATION 17.81	41.1 Years STANDARD_DEVIATION 16.84	41.3 Years STANDARD_DEVIATION 17.06
Race/Ethnicity, Customized African American/African Heritage	11 Participants	5 Participants	6 Participants	22 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	37 Participants	44 Participants	41 Participants	122 Participants
Race/Ethnicity, Customized Japanese/East Asian Heritage	0 Participants	0 Participants	1 Participants	1 Participants
Race/Ethnicity, Customized White	68 Participants	66 Participants	68 Participants	202 Participants
Sex: Female, Male Female	59 Participants	68 Participants	77 Participants	204 Participants
Sex: Female, Male Male	57 Participants	47 Participants	39 Participants	143 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk
deaths Total, all-cause mortality	— / —	— / —	— / —
other Total, other adverse events	26 / 116	26 / 115	21 / 116
serious Total, serious adverse events	1 / 116	1 / 115	0 / 116

Outcome results

Primary

Change From Baseline in Weighted-mean 24-hour Serial Forced Expiratory Volume in One Second (FEV1) at Week 12

FEV1 is a measure of lung function and is defined as the volume of air that can be forcefully exhaled in one second. The weighted mean is calculated from the pre-dose FEV1 and post-dose FEV1 measurements at 5, 15, and 30 minutes (min) and at 1, 2, 3, 4, 11, 12, 12.5, 13, 14, 16, 20, 23, and 24 hours, respectively, at Week 12. The Baseline value was the Day 1 pre-dose FEV1 measurement. Change from Baseline is calculated as the weighted mean 0-24 hour FEV1 (Liters) at Week 12 minus the Baseline value. Analysis was performed using analysis of covariance (ANCOVA) with covariates of Baseline FEV1, region, sex, age, and treatment.

Time frame: Baseline and Week 12

Population: Intent-to-Treat (ITT) Population: all participants randomized to treatment who received at least one dose of study medication. Only those participants available at the indicated time point were assessed.

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
Placebo	Change From Baseline in Weighted-mean 24-hour Serial Forced Expiratory Volume in One Second (FEV1) at Week 12	0.289 Liters	Standard Error 0.0429
Vilanteral 25 µg OD	Change From Baseline in Weighted-mean 24-hour Serial Forced Expiratory Volume in One Second (FEV1) at Week 12	0.359 Liters	Standard Error 0.0416
Salmeterol 50 µg BID	Change From Baseline in Weighted-mean 24-hour Serial Forced Expiratory Volume in One Second (FEV1) at Week 12	0.283 Liters	Standard Error 0.0419

p-value: 0.24495% CI: [-0.048, 0.188]ANCOVA

p-value: 0.92695% CI: [-0.124, 0.113]ANCOVA

Secondary

Change From Baseline in Daily AM (Morning) PEF Averaged Over the 12-week Treatment Period

PEF is defined as the maximum airflow during a forced expiration beginning with the lungs fully inflated. Trough PEF is the PEF measured approximately 24 hours after the last administration of study drug. The Baseline value is the average value of the last 7 days of daily AM PEF prior to randomization. Change from Baseline in trough AM PEF was calculated as the averaged value of all daily AM PEF for Weeks 1 to Week 12 minus the value at Baseline. Analysis was performed using ANCOVA with covariates of Baseline, region, sex, age, and treatment.

Time frame: Baseline and Weeks 1-12