Study Evaluating the 24-Hour Pulmonary Function Profile of Fluticasone Furoate (FF) /GW642444 (Vilanterol) (VI) Inhalation Powder 100/25mcg Once Daily Compared With Fluticasone Propionate/Salmeterol Inhalation Powder 250/50mcg Twice Daily in Subjects With Chronic Obstructive Pulmonary Disease (COPD)

• Sponsor: GlaxoSmithKline (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01323621
• Collaborator: (none)
• Enrollment: 512
• Locations: 51
• Arms: 2
• Duration (Months): 10.3
• Patients Per Site: 10
• Patients Per Site Per Month: 1

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the 24-hour spirometry effect (FEV1) of FF/VI 100/25mcg once daily compared with Fluticasone Propionate/Salmeterol 250/50mcg twice daily over a 12-week treatment period in subjects with COPD.

Condition or Disease	Intervention/Treatment	Phase
Pulmonary Disease, Chronic Obstructive	Drug: Fluticasone Furoate 100mcg/ GW642444 (vilanterol) 25mcg; Drug: Fluticasone Propionate 250mcg / salmeterol 50mcg; Drug: Double-dummy placebo; Drug: Salbutamol as needed	Phase 3

Detailed Description

This is a randomized, double-blind, double-dummy, multi-centre parallel group study. Subjects who meet the eligibility criteria at Screening and meet the randomization criteria at the end of a 2-week Run-In period will enter a 12-week treatment period. There will be a 7-day Follow-up period after the treatment period.

Study Design

• Study Type: Interventional
• Actual Enrollment: 512 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A 12-week Study to Evaluate the 24-hour Pulmonary Function Profile of Fluticasone Furoate/Vilanterol (FF/VI) Inhalation Powder 100/25 mcg Once Daily Compared With Fluticasone Propionate/Salmeterol Inhalation Powder 250/50 mcg Twice Daily in Subjects With Chronic Obstructive Pulmonary Disease (COPD)
• Study Start Date: Mar 18, 2011
• Actual Primary Completion Date: Jan 1, 2012
• Actual Study Completion Date: Jan 24, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Fluticasone Furoate / GW642444 (vilanterol) Inhaled Corticosteroid (ICS)/ Long acting Beta Agonist (LABA)	Drug: Fluticasone Furoate 100mcg/ GW642444 (vilanterol) 25mcg; inhalation powder; Drug: Double-dummy placebo; inhalation powder; Drug: Salbutamol as needed; inhalation powder
Active Comparator: Fluticasone Propionate / salmeterol Inhaled Corticosteroid (ICS)/ Long acting Beta Agonist (LABA)	Drug: Fluticasone Propionate 250mcg / salmeterol 50mcg; inhalation powder; Drug: Double-dummy placebo; inhalation powder; Drug: Salbutamol as needed; inhalation powder

Outcome Measures

Primary Outcome Measures

1. Change From Baseline Trough in 24-Hour Weighted Mean FEV1 on Treatment Day 84 [Baseline (Day 1) and Day 84]

   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. The weighted mean was calculated from the pre-dose FEV1 and the post-dose FEV1 measurements at 5, 15, 30, and 60 minutes (min) and 2, 4, 6, 8, 12, 13, 14, 16, 20, and 24 hours post-dose on Treatment Day 84. Baseline trough FEV1 was calculated as the mean of the two assessments made 30 and 5 minutes pre-dose on Treatment Day 1. Change from Baseline was calculated as the average of the Day 84 values minus the Baseline value. Analysis of covariance (ANCOVA) was conducted with covariates for country, smoking status, reversibility, and Baseline FEV1.

Secondary Outcome Measures

1. Time to Onset on Treatment Day 1 [Baseline and Day 1]

   Time to onset on Treatment Day 1 is defined as the time to an increase of 100 milliliters (mL) from Baseline in FEV1. Time to onset was calculated over 0 to 4 hours (5 min, 15 min, 30 min, 60 min, 120 min, and 240 min) post-dose.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 40 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Signed and dated written informed consent

• Male or females ≥ 40 years of age

• Established clinical history of COPD by ATS/ERS definition

• Females are eligible to enter and participate if of non-childbearing potential, or if of child bearing potential, has a negative serum pregnancy test at screening, and agrees to one of the acceptable contraceptive methods listed in protocol, used consistently and correctly

• Former or current smoker > 10 pack years

• Post-albuterol spirometry criteria: FEV1/FVC ratio ≤ 0.70 and FEV1 ≤ 70% of predicted normal (NHANES III)

Exclusion Criteria:

• Current diagnosis of asthma

• Subjects with other respiratory disorders including active tuberculosis, α1-antitrypsin deficiency, lung cancer, bronchiectasis, sarcoidosis, lung fibrosis, pulmonary hypertension, interstitial lung diseases or other active pulmonary diseases

• Lung volume reduction surgery within previous 12 months

• Clinically significant abnormalities not due to COPD by chest x-ray

• Hospitalized for poorly controlled COPD within 12 weeks of Screening

• Poorly controlled COPD 6 weeks prior to Screening, defined as acute worsening of COPD that is managed by the subject with corticosteroids or antibiotics or that requires treatment prescribed by a physician

• Lower respiratory infection requiring antibiotics 6 weeks prior to Screening

• Uncontrolled or clinically significant (in opinion of PI) cardiovascular, hypertension, neurological, psychiatric, renal, hepatic, immunological, endocrine, peptic ulcer disease, or hematological abnormalities

• Carcinoma not in complete remission for at least 5 years

• Subjects with history of hypersensitivity to study medications (e.g., beta-agonists, corticosteroid) or components of inhalation powder (e.g., lactose, magnesium stearate)

• Subjects with history of severe milk protein allergy that, in opinion of study physician, contraindicates subject's participation

• Known/suspected history of alcohol or drug abuse in the last 2 years

• Women who are pregnant or lactating or plan to become pregnant

• Subjects medically unable to withhold albuterol and/or ipratropium 4 hours prior to spirometry testing at each study visit

• Use of certain medications such as bronchodilators and corticosteroids for the protocol-specific times prior to Visit 1 (the Investigator will discuss the specific medications)

• Long Term Oxygen Therapy (LTOT) or nocturnal oxygen therapy >12 hours a day

• Participation in the acute phase of a pulmonary rehabilitation program within 4 weeks prior to Screening or during the study

• Non-compliance or inability to comply with study procedures or scheduled visits

• Affiliation with investigator site

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Jasper	Alabama	United States	35501
2	GSK Investigational Site	Riverside	California	United States	92506
3	GSK Investigational Site	DeLand	Florida	United States	32720
4	GSK Investigational Site	Coeur d'Alene	Idaho	United States	83814
5	GSK Investigational Site	Minneapolis	Minnesota	United States	55402
6	GSK Investigational Site	Cincinnati	Ohio	United States	45231
7	GSK Investigational Site	Oklahoma City	Oklahoma	United States	73103
8	GSK Investigational Site	Medford	Oregon	United States	97504
9	GSK Investigational Site	Gaffney	South Carolina	United States	29340
10	GSK Investigational Site	Orangeburg	South Carolina	United States	29118
11	GSK Investigational Site	Seneca	South Carolina	United States	29678
12	GSK Investigational Site	Spartanburg	South Carolina	United States	29303
13	GSK Investigational Site	Boerne	Texas	United States	78006
14	GSK Investigational Site	Luebeck	Schleswig-Holstein	Germany	23552
15	GSK Investigational Site	Napoli	Campania	Italy	80131
16	GSK Investigational Site	San Felice A Cancello Caserta	Campania	Italy	81027
17	GSK Investigational Site	Telese Terme (BN)	Campania	Italy	82037
18	GSK Investigational Site	Parma	Emilia-Romagna	Italy	43100
19	GSK Investigational Site	Roma	Lazio	Italy	00185
20	GSK Investigational Site	Rozzano (MI)	Lombardia	Italy	20089
21	GSK Investigational Site	Torrette (AN)	Marche	Italy	60126
22	GSK Investigational Site	Cagliari	Sardegna	Italy	09126
23	GSK Investigational Site	Palermo	Sicilia	Italy	90146
24	GSK Investigational Site	Firenze	Toscana	Italy	50134
25	GSK Investigational Site	Padova	Veneto	Italy	35128
26	GSK Investigational Site	Benoni	Gauteng	South Africa	1501
27	GSK Investigational Site	Bellville		South Africa	7531
28	GSK Investigational Site	Bloemfontein		South Africa	9301
29	GSK Investigational Site	Cape Town		South Africa	7572
30	GSK Investigational Site	George		South Africa	6529
31	GSK Investigational Site	Port Elizabeth		South Africa	6045
32	GSK Investigational Site	Reiger Park		South Africa	1459
33	GSK Investigational Site	Somerset West		South Africa	7130
34	GSK Investigational Site	Thabazimbi		South Africa	0380
35	GSK Investigational Site	Witbank		South Africa	1034
36	GSK Investigational Site	Alicante		Spain	03114
37	GSK Investigational Site	Córdoba		Spain	14004
38	GSK Investigational Site	Lugo		Spain	27003
39	GSK Investigational Site	Mérida (Badajoz)		Spain	06800
40	GSK Investigational Site	Ponferrada (León)		Spain	24411
41	GSK Investigational Site	Valladolid		Spain	47005
42	GSK Investigational Site	Cherkassy		Ukraine	18009
43	GSK Investigational Site	Donetsk		Ukraine	83099
44	GSK Investigational Site	Kharkiv		Ukraine	61002
45	GSK Investigational Site	Kharkiv		Ukraine	61035
46	GSK Investigational Site	Kiev		Ukraine	03680
47	GSK Investigational Site	Kyiv		Ukraine	03038
48	GSK Investigational Site	Kyiv		Ukraine	03049
49	GSK Investigational Site	Kyiv		Ukraine	04107
50	GSK Investigational Site	Mykolayiv		Ukraine	54003
51	GSK Investigational Site	Vinnytsia		Ukraine	21018

Sponsors and Collaborators

• GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

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

Publications

None provided.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT01323621
• Other Study ID Numbers: 112352
• First Posted: Mar 25, 2011
• Last Update Posted: Feb 15, 2018
• Last Verified: Jan 1, 2018

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Additional relevant MeSH terms: Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Respiratory Aspiration; Fluticasone; Xhance; Albuterol; Salmeterol Xinafoate

Study Results

Participant Flow

Pre-assignment Detail	At Visit 1, eligible participants entered a 2-week, single blind (placebo) Run-In Period to obtain Baseline assessments of albuterol (salbutamol) use and to evaluate adherence with study treatment and procedures, diary card completion, and assessment of disease stability. At Visit 2, participants were randomized to a 12-week Treatment Period.

Arm/Group Title	Placebo + Salbutamol	FSC 250/50 µg BID	FF/VI 100/25 µg QD
Arm/Group Description	Participants were instructed to take single-blind placebo (ACCUHALER/DISKUS and Novel Dry Powder Inhaler [NDPI]): one inhalation each morning from each device, and one inhalation from the ACCUHALER/DISKUS in the evening. In addition, all participants received supplemental albuterol (salbutamol) (metered dose inhaler [MDI] and/or nebules) to be used on an as-needed basis. Ipratropium bromide alone was permitted, provided that the participant was on a stable dose from Visit 1 (Screening) and remained on the stable dose throughout the study; however, Ipratropium must have been withheld for 4 hours prior to and during each clinic visit.	Participants received a Fluticasone Propionate and Salmeterol (FSC) 250/50 microgram (µg) inhalation (available as a combination dry inhalation powder of Fluticasone 250 µg and Salmeterol 50 µg in a single strip) twice daily (BID) (morning and evening) from the ACCUHALER/DISKUS and placebo once daily (QD) in the morning from the NDPI over the course of 12 weeks.	Participants received a Fluticasone Furoate /Vilanterol (FF/VI) 100/25 µg inhalation (available as a dry inhalation powder in two separate strips of FF 100 µg and VI 25 µg) QD in the morning from the NDPI and placebo BID (morning and evening) from the ACCUHALER/DISKUS over the course of 12 weeks.
Period Title: 2-week, Single-blind Run In Period
STARTED	739	0	0
COMPLETED	511	0	0
NOT COMPLETED	228	0	0
Period Title: 2-week, Single-blind Run In Period
STARTED	0	252	259
COMPLETED	0	237	239
NOT COMPLETED	0	15	20

Baseline Characteristics

Arm/Group Title	FSC 250/50 µg BID	FF/VI 100/25 µg QD	Total
Arm/Group Description	Participants received a Fluticasone Propionate and Salmeterol (FSC) 250/50 microgram (µg) inhalation (available as a combination dry inhalation powder of Fluticasone 250 µg and Salmeterol 50 µg in a single strip) twice daily (BID) (morning and evening) from the ACCUHALER/DISKUS and placebo once daily (QD) in the morning from the NDPI over the course of 12 weeks.	Participants received a Fluticasone Furoate /Vilanterol (FF/VI) 100/25 µg inhalation (available as a dry inhalation powder in two separate strips of FF 100 µg and VI 25 µg) QD in the morning from the NDPI and placebo BID (morning and evening) from the ACCUHALER/DISKUS over the course of 12 weeks.	Total of all reporting groups
Overall Participants	252	259	511
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	61.7 (9.05)	61.6 (9.59)	61.6 (9.32)
Sex: Female, Male (Count of Participants)
Female	85 33.7%	78 30.1%	163 31.9%
Male	167 66.3%	181 69.9%	348 68.1%
Race/Ethnicity, Customized (participants) [Number]
White - White/Caucasian/European Heritage	238 94.4%	241 93.1%	479 93.7%
African American/African Heritage	14 5.6%	17 6.6%	31 6.1%
White - Arabic/North African Heritage	0 0%	1 0.4%	1 0.2%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline Trough in 24-Hour Weighted Mean FEV1 on Treatment Day 84
Description	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. The weighted mean was calculated from the pre-dose FEV1 and the post-dose FEV1 measurements at 5, 15, 30, and 60 minutes (min) and 2, 4, 6, 8, 12, 13, 14, 16, 20, and 24 hours post-dose on Treatment Day 84. Baseline trough FEV1 was calculated as the mean of the two assessments made 30 and 5 minutes pre-dose on Treatment Day 1. Change from Baseline was calculated as the average of the Day 84 values minus the Baseline value. Analysis of covariance (ANCOVA) was conducted with covariates for country, smoking status, reversibility, and Baseline FEV1.
Time Frame	Baseline (Day 1) and Day 84

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	FSC 250/50 µg BID	FF/VI 100/25 µg QD
Arm/Group Description	Participants received a Fluticasone Propionate and Salmeterol (FSC) 250/50 microgram (µg) inhalation (available as a combination dry inhalation powder of Fluticasone 250 µg and Salmeterol 50 µg in a single strip) twice daily (BID) (morning and evening) from the ACCUHALER/DISKUS and placebo once daily (QD) in the morning from the NDPI over the course of 12 weeks.	Participants received a Fluticasone Furoate /Vilanterol (FF/VI) 100/25 µg inhalation (available as a dry inhalation powder in two separate strips of FF 100 µg and VI 25 µg) QD in the morning from the NDPI and placebo BID (morning and evening) from the ACCUHALER/DISKUS over the course of 12 weeks.
Measure Participants	217	219
Least Squares Mean (Standard Error) [Liters]	0.114 (0.0183)	0.142 (0.0182)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	FSC 250/50 µg BID, FF/VI 100/25 µg QD
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.267
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least squares mean difference
	Estimated Value	0.029
	Confidence Interval	() 95%; -0.022 to 0.080
	Parameter Dispersion	Type: Value:
	Estimation Comments	ANCOVA analysis was conducted with covariates for country, smoking status, reversibility, and Baseline FEV1.

2. Secondary Outcome

Title	Time to Onset on Treatment Day 1
Description	Time to onset on Treatment Day 1 is defined as the time to an increase of 100 milliliters (mL) from Baseline in FEV1. Time to onset was calculated over 0 to 4 hours (5 min, 15 min, 30 min, 60 min, 120 min, and 240 min) post-dose.
Time Frame	Baseline and Day 1

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	FSC 250/50 µg BID	FF/VI 100/25 µg QD
Arm/Group Description	Participants received a Fluticasone Propionate and Salmeterol (FSC) 250/50 microgram (µg) inhalation (available as a combination dry inhalation powder of Fluticasone 250 µg and Salmeterol 50 µg in a single strip) twice daily (BID) (morning and evening) from the ACCUHALER/DISKUS and placebo once daily (QD) in the morning from the NDPI over the course of 12 weeks.	Participants received a Fluticasone Furoate /Vilanterol (FF/VI) 100/25 µg inhalation (available as a dry inhalation powder in two separate strips of FF 100 µg and VI 25 µg) QD in the morning from the NDPI and placebo BID (morning and evening) from the ACCUHALER/DISKUS over the course of 12 weeks.
Measure Participants	251	258
Median (Full Range) [Minutes]	30	16

Adverse Events

Arm/Group Title	FSC 250/50 µg BID		FF/VI 100/25 µg QD
Arm/Group Description	Participants received a Fluticasone Propionate and Salmeterol (FSC) 250/50 microgram (µg) inhalation (available as a combination dry inhalation powder of Fluticasone 250 µg and Salmeterol 50 µg in a single strip) twice daily (BID) (morning and evening) from the ACCUHALER/DISKUS and placebo once daily (QD) in the morning from the NDPI over the course of 12 weeks.		Participants received a Fluticasone Furoate /Vilanterol (FF/VI) 100/25 µg inhalation (available as a dry inhalation powder in two separate strips of FF 100 µg and VI 25 µg) QD in the morning from the NDPI and placebo BID (morning and evening) from the ACCUHALER/DISKUS over the course of 12 weeks.
All Cause Mortality
	FSC 250/50 µg BID		FF/VI 100/25 µg QD
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	FSC 250/50 µg BID		FF/VI 100/25 µg QD
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/252 (1.2%)		5/259 (1.9%)
Cardiac disorders
Cardiac failure	0/252 (0%)		1/259 (0.4%)
Myocardial infarction	0/252 (0%)		1/259 (0.4%)
Infections and infestations
Infective tenosynovitis	0/252 (0%)		1/259 (0.4%)
Injury, poisoning and procedural complications
Comminuted fracture	1/252 (0.4%)		0/259 (0%)
Wrist fracture	1/252 (0.4%)		0/259 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lung adenocarcinoma metastatic	0/252 (0%)		1/259 (0.4%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure	0/252 (0%)		1/259 (0.4%)
Bronchitis chronic	0/252 (0%)		1/259 (0.4%)
Chronic obstructive pulmonary disease	0/252 (0%)		1/259 (0.4%)
Pulmonary embolism	1/252 (0.4%)		0/259 (0%)
Respiratory failure	0/252 (0%)		1/259 (0.4%)
Other (Not Including Serious) Adverse Events
	FSC 250/50 µg BID		FF/VI 100/25 µg QD
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	10/252 (4%)		12/259 (4.6%)
Nervous system disorders
Headache	10/252 (4%)		12/259 (4.6%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.