A 24-week Arterial Stiffness Study With Fluticasone Furoa... | NCT01336608

NCT01336608

Status Module

Sponsor/Collaborators Module

Oversight Module

No data available

No data is available for this block.

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Fluticasone Furoate/Vilanterol	Experimental	Inhaled corticosteroid/long acting beta-agonist	Drug: Fluticasone Furoate/Vilanterol
vilanterol	Experimental	Inhaled long acting beta-agonist	Drug: Vilanterol
placebo	Placebo Comparator	Placebo	Drug: Placebo

Name	Type	Description	Arm Group Labels	Other Names
Fluticasone Furoate/Vilanterol	Drug	Inhaled corticosteroid/long acting beta-agonist	Fluticasone Furoate/Vilanterol

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Mean Change From Baseline (BL) in Aortic Pulse Wave Velocity (aPWV) at the End of the 24-week Treatment Period (Day 168)	PWV is defined as the speed of travel of the pressure pulse along an arterial segment and can be obtained for any arterial segment accessible to palpation. aPWV is measured with tonometers positioned transcutaneously at the base of the common carotid artery and over the femoral artery. PWV increases with arterial stiffness and is defined by the Moens-Korteweg equation: PWV=square root of (Eh/2ρR), where E is Young's modulus of the arterial wall, h is the wall thickness, R is the arterial radius at the end of diastole, and ρ is the blood density. Change from BL was calculated as the Day 168 value minus the BL value. The analysis was performed using a repeated measures model with covariates of treatment, visit, age, gender, smoking history, history of exacerbation strata, geographical region, BL aPWV and interaction terms of BL by visit and treatment by visit.	BL to Day 168

Secondary Outcomes

Measure	Description	Time Frame
Change From BL in Clinic Visit Trough (Pre-bronchodilator and Pre-dose) FEV1 at Day 168	Pulmonary function was measured by forced expiratory volume in one second (FEV1), defined as the maximal amount of air that can be forcefully exhaled from the lungs in one second. Trough FEV1 measurements were taken electronically by spirometry at Screening, Days 1, 28, 84, 126, and 168. BL FEV1 was defined as the mean of the assessments made 30 minutes pre-dose and 5 minutes pre-dose on Treatment Day 1. Trough FEV1 was defined as the mean of the FEV1 values obtained 24 hours after previous morning's dosing. Change from BL was calculated as the average at each visit minus the BL value. Analysis was preformed using a repeated measures model with covariates of visit, treatment, history of exacerbation strata, geographical region, BL FEV1 and interaction terms of BL by visit and treatment by visit.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

COPD diagnosis defined by ATS/ERS
Former or current smoker
A measured aortic pulse wave velocity = or > 11.0 m/s at Screening

Exclusion Criteria:

Pregnancy
A current diagnosis of asthma
alpha1-antitrypsin deficiency as the underlying cause of COPD
subjects with other and active respiratory disorders
A cardiovascular event occurred in the 6 months prior to Visit 1
Current severe heart failure (New York Heart Association Class IV) and have a known ejection fraction of < 30 %
Clinical significant and uncontrolled hypertension
Abnormal and clinical significant 12-lead ECG findings at Visit 1
Have lung volume reduction or lung transplantation within 12 months prior to Visit 1
Poorly controlled COPD: Acute worsening of COPD that is managed by subject with antibiotics or corticosteroids, or requires treatment prescribed by a physician in the 6 weeks prior to Visit 1; or subject needs to be hospitalised due to poorly controlled COPD within 12 weeks prior to Visit 1
Lower respiratory tract infection that required use of antibiotics within 6 weeks prior to Visit 1
Participate in the acute phase of a pulmonary rehabilitation within 4 weeks prior to Visit 1 or who will enter the acute phase of pulmonary rehabilitation during the study.
Other diseases or abnormalities in the opinion of the investigator would put safety of the subject at risk through participation; or would affect the safety or efficacy analysis if the disease/condition exacerbated during the study.
subjects with carcinoma has not been in complete remission for at least 5 years. Carcinoma in site of the cervix, squamous cell carcinoma and basal cell carcinoma of the skin would not be excluded if the subject has been considered cured within 5 years since diagnosis.
subjects with a history of hypersensitivity to any of the study medications or components of the inhalation powder.
subjects with a known or suspected history of alcohol or drug abuse within the last 2 years prior to Screening
subjects are medically unable to withhold albuterol or ipratropium for 4 hours prior to spirometry testing at each study visit
subjects are medically unable to stop the 'excluded medications' listed in the protocol
subjects started, discontinued certain medications listed in the protocol or have not been on a stable dose in the past three months prior to Screening, or are not anticipated to remain on a stable dose during the study treatment period.
Long term oxygen therapy requiring >12 hour per day or a flow rate > 2 L/min
A body mass index = or >35 kg/m2
Fasting lipid level LDL>3.3 mmol/L, total cholesterol >5.2 mmol/L, and triglycerides > 2.24mmol/L
Non-compliance
Questionable validity of consent
Prior use of study medication or other investigational drugs.
Affiliation with investigator site

Contacts/Locations Module

Name	Affiliation	Role
GSK Clinical Trials	GlaxoSmithKline	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
GSK Investigational Site		Birmingham	Alabama	35294	United States
GSK Investigational Site

References Module

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
113108	Individual Participant Data Set	View IPD

IPD Sharing Statement Module

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Placebo-Run-in	Participants received placebo once daily (QD) in the morning for 2 weeks. In addition, participants were provided an inhaled short-acting beta2-receptor agonist (SABA), albuterol (salbutamol) (metered dose inhaler [MDI] or nebules), to be used as a rescue medication for relief of chronic obstructive pulmonary disease (COPD) symptoms during the Run-in and Treatment Periods.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

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No data is available for this block.

Derived Section

Miscellaneous Info Module

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

Intervention Browse Module

Masking Info

FG000559 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects

Type of Units Analyzed

Arm/Group Information

ID	Title	Description
BG000	Placebo QD	Participants received placebo QD in the morning via a DPI for 24 weeks. In addition, participants were provided an inhaled SABA, albuterol (salbutamol) , to be used as a rescue medication for relief of COPD symptoms during the Run-in and Treatment Periods.
BG001	VI 25 µg QD	Participants received VI 25 µg inhalation QD in the morning via a DPI for 24 weeks. In addition, participants were provided an inhaled SABA, albuterol (salbutamol), to be used as a rescue medication for relief of COPD symptoms during the Run-in and Treatment Periods.
BG002	FF/VI 100/25 µg QD	Participants received FF/VI 100/25 µg inhalation QD in the morning via a DPI for 24 weeks. In addition, participants were provided an inhaled SABA, albuterol (salbutamol) to be used as a rescue medication for relief of COPD symptoms during the Run-in and Treatment Periods.
BG003	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

Years

Title

Denominators

Categories

Title	Measurements
	BG00068.2± 8.10 BG00168.7± 7.69 BG00268.5± 8.01 BG003

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG00022 BG00136 BG002

Race/Ethnicity, Customized

Number

Participants

Title

Denominators

Categories

African American/African Heritage

Title	Measurements
	BG0007 BG0014 BG002

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

Mean Change From Baseline (BL) in Aortic Pulse Wave Velocity (aPWV) at the End of the 24-week Treatment Period (Day 168)

PWV is defined as the speed of travel of the pressure pulse along an arterial segment and can be obtained for any arterial segment accessible to palpation. aPWV is measured with tonometers positioned transcutaneously at the base of the common carotid artery and over the femoral artery. PWV increases with arterial stiffness and is defined by the Moens-Korteweg equation: PWV=square root of (Eh/2ρR), where E is Young's modulus of the arterial wall, h is the wall thickness, R is the arterial radius at the end of diastole, and ρ is the blood density. Change from BL was calculated as the Day 168 value minus the BL value. The analysis was performed using a repeated measures model with covariates of treatment, visit, age, gender, smoking history, history of exacerbation strata, geographical region, BL aPWV and interaction terms of BL by visit and treatment by visit.

ITT Population: all randomized par. who received at least one dose of study medication. Number of par. presented represent those with data available at the time point being presented; however, all par. in the ITT population without missing covariate information and with at least one post BL measurement are included in the analysis.

Posted

Least Squares Mean

Standard Error

meters per second (m/sec)

BL to Day 168

ID	Title	Description
OG000	Placebo QD	Participants received placebo QD in the morning via a DPI for 24 weeks. In addition, participants were provided an inhaled SABA, albuterol (salbutamol) , to be used as a rescue medication for relief of COPD symptoms during the Run-in and Treatment Periods.
OG001	VI 25 µg QD	Participants received VI 25 µg inhalation QD in the morning via a DPI for 24 weeks. In addition, participants were provided an inhaled SABA, albuterol (salbutamol), to be used as a rescue medication for relief of COPD symptoms during the Run-in and Treatment Periods.
OG002	FF/VI 100/25 µg QD	Participants received FF/VI 100/25 µg inhalation QD in the morning via a DPI for 24 weeks. In addition, participants were provided an inhaled SABA, albuterol (salbutamol) to be used as a rescue medication for relief of COPD symptoms during the Run-in and Treatment Periods.

Units	Counts
Participants	OG00085 OG001117 OG002103

Title

Denominators

Categories

Title	Measurements
	OG000-1.97± 0.279 OG001-1.95± 0.241 OG002-1.75± 0.256

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		Mixed Models Analysis	Restricted maximum likelihood (REML)-based repeated measures approach (MMRM)	0.969		Least Squares Mean Difference	0.01			2-Sided	95	-0.71	0.74					Superiority or Other
OG000 OG002		Mixed Models Analysis

Secondary

Change From BL in Clinic Visit Trough (Pre-bronchodilator and Pre-dose) FEV1 at Day 168

Pulmonary function was measured by forced expiratory volume in one second (FEV1), defined as the maximal amount of air that can be forcefully exhaled from the lungs in one second. Trough FEV1 measurements were taken electronically by spirometry at Screening, Days 1, 28, 84, 126, and 168. BL FEV1 was defined as the mean of the assessments made 30 minutes pre-dose and 5 minutes pre-dose on Treatment Day 1. Trough FEV1 was defined as the mean of the FEV1 values obtained 24 hours after previous morning's dosing. Change from BL was calculated as the average at each visit minus the BL value. Analysis was preformed using a repeated measures model with covariates of visit, treatment, history of exacerbation strata, geographical region, BL FEV1 and interaction terms of BL by visit and treatment by visit.

ITT Population. Number of par. presented represent those with data available at the time point being presented; however, all par. in the ITT population without missing covariate information and with at least one post BL measurement are included in the analysis.

Posted

Least Squares Mean

Standard Error

Liters (L)

BL to Day 168

ID	Title	Description
OG000	Placebo QD	Participants received placebo QD in the morning via a DPI for 24 weeks. In addition, participants were provided an inhaled SABA, albuterol (salbutamol) , to be used as a rescue medication for relief of COPD symptoms during the Run-in and Treatment Periods.
OG001	VI 25 µg QD

Secondary

Mean Number of Occasions Rescue Medication [Albuterol (Salbutamol)] Used During a 24-hour Period Averaged Over the Entire 24-week Treatment Period

Participants were given daily record cards for daily completion from BL (Week -1) through Week 24 (Visit 6) each morning and prior to taking study medication (i.e., single-blind and double-blind study medication) supplemental medication (albuterol [salbutamol] if received) and ipratropium bromide (if received). Participants recorded number of occasions supplemental albuterol/salbutamol (MDI and/or nebules) used over the previous 24 hours and any medical problems that they had experienced and any medication used to treat these medical problems over the previous 24 hours. Analysis was performed using an analysis of covarience (ANCOVA) model with covariates of treatment, BL mean of occasions of rescue medication use (Week -1), history of exacerbation, and geographical region.

ITT Population: all randomized participants who received at least one dose of study medication. Only those participants with at least 1 on treatment rescue medication measurement during the treatment period and without missing covariate information were analyzed.

Posted

Least Squares Mean

Standard Error

Occasions per 24 hours

BL (Week -1), Week 1 to Week 24

ID	Title	Description
OG000	Placebo QD	Participants received placebo QD in the morning via a DPI for 24 weeks. In addition, participants were provided an inhaled SABA, albuterol (salbutamol) , to be used as a rescue medication for relief of COPD symptoms during the Run-in and Treatment Periods.
OG001

Arm/Groups

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Placebo QD	Participants received placebo QD in the morning via a DPI for 24 weeks. In addition, participants were provided an inhaled SABA, albuterol (salbutamol) , to be used as a rescue medication for relief of COPD symptoms during the Run-in and Treatment Periods.	5	145	24	145
EG001	VI 25 µg QD	Participants received VI 25 µg inhalation QD in the morning via a DPI for 24 weeks. In addition, participants were provided an inhaled SABA, albuterol (salbutamol), to be used as a rescue medication for relief of COPD symptoms during the Run-in and Treatment Periods.	12	158	27	158
EG002	FF/VI 100/25 µg QD	Participants received FF/VI 100/25 µg inhalation QD in the morning via a DPI for 24 weeks. In addition, participants were provided an inhaled SABA, albuterol (salbutamol) to be used as a rescue medication for relief of COPD symptoms during the Run-in and Treatment Periods.	9	141	34	141

Serious Adverse Events

Term	Organ System	Statistical Information
Angina pectoris	Cardiac disorders	EG0001 affected145 at risk EG0010 affected158 at risk EG0020 affected141 at risk
Angina unstable	Cardiac disorders	EG0001 affected145 at risk EG0010 affected158 at risk EG0020 affected141 at risk
Cardio-respiratory arrest	Cardiac disorders	EG0000 affected145 at risk EG0011 affected158 at risk EG0020 affected141 at risk
Faecaloma	Gastrointestinal disorders	EG0000 affected145 at risk EG0010 affected158 at risk EG0021 affected141 at risk
Inguinal hernia	Gastrointestinal disorders	EG0001 affected145 at risk EG0010 affected158 at risk EG0020 affected141 at risk
Infective exacerbation of chronic obstructive airways diseas	Infections and infestations	EG0000 affected145 at risk EG0011 affected158 at risk EG0020 affected141 at risk
Pneumonia	Infections and infestations	EG0002 affected145 at risk EG0011 affected158 at risk EG0022 affected141 at risk
Pulmonary tuberculosis	Infections and infestations	EG0000 affected145 at risk EG0011 affected158 at risk EG0020 affected141 at risk
Pyelonephritis	Infections and infestations	EG0000 affected145 at risk EG0010 affected158 at risk EG0021 affected141 at risk
Septic shock	Infections and infestations	EG0000 affected145 at risk EG0011 affected158 at risk EG0020 affected141 at risk
Facial bones fracture	Injury, poisoning and procedural complications	EG0000 affected145 at risk EG0011 affected158 at risk EG0020 affected141 at risk
Fibula fracture	Injury, poisoning and procedural complications	EG0000 affected145 at risk EG0010 affected158 at risk EG0021 affected141 at risk
Hip fracture	Injury, poisoning and procedural complications	EG0000 affected145 at risk EG0010 affected158 at risk EG0021 affected141 at risk
Tibia fracture	Injury, poisoning and procedural complications	EG0000 affected145 at risk EG0010 affected158 at risk EG0021 affected141 at risk
Hepatic enzyme increased	Investigations	EG0000 affected145 at risk EG0010 affected158 at risk EG0021 affected141 at risk
Hypokalaemia	Metabolism and nutrition disorders	EG0000 affected145 at risk EG0011 affected158 at risk EG0020 affected141 at risk
Type 2 diabetes mellitus	Metabolism and nutrition disorders	EG0000 affected145 at risk EG0011 affected158 at risk EG0020 affected141 at risk
Adenocarcinoma of colon	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	EG0000 affected145 at risk EG0011 affected158 at risk EG0020 affected141 at risk
Colorectal cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	EG0000 affected145 at risk EG0010 affected158 at risk EG0021 affected141 at risk
Lung neoplasm malignant	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	EG0001 affected145 at risk EG0010 affected158 at risk EG0020 affected141 at risk
Prostate cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	EG0000 affected145 at risk EG0010 affected158 at risk EG0021 affected141 at risk
Cerebrovascular accident	Nervous system disorders	EG0000 affected145 at risk EG0011 affected158 at risk EG0020 affected141 at risk
Renal failure acute	Renal and urinary disorders	EG0000 affected145 at risk EG0011 affected158 at risk EG0020 affected141 at risk
Benign prostatic hyperplasia	Reproductive system and breast disorders	EG0000 affected145 at risk EG0011 affected158 at risk EG0020 affected141 at risk
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	EG0001 affected145 at risk EG0015 affected158 at risk EG0022 affected141 at risk

Other Adverse Events

Term	Organ System	Statistical Information
Nasopharyngitis	Infections and infestations	EG0005 affected145 at risk EG00112 affected158 at risk EG0029 affected141 at risk
Oral candidiasis	Infections and infestations	EG0001 affected145 at risk EG0012 affected158 at risk EG0029 affected141 at risk
Upper respiratory tract infection	Infections and infestations	EG0006 affected145 at risk EG0014 affected158 at risk EG0022 affected141 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	EG0004 affected145 at risk EG0011 affected158 at risk EG0025 affected141 at risk
Back pain	Musculoskeletal and connective tissue disorders	EG0005 affected145 at risk EG0015 affected158 at risk EG0024 affected141 at risk
Headache	Nervous system disorders	EG0005 affected145 at risk EG0019 affected158 at risk EG0028 affected141 at risk
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	EG0001 affected145 at risk EG0012 affected158 at risk EG0026 affected141 at risk

ID	Term
D029424	Pulmonary Disease, Chronic Obstructive

Ancestor Terms

ID	Term
D008173	Lung Diseases, Obstructive
D008171	Lung Diseases
D012140	Respiratory Tract Diseases
D002908	Chronic Disease
D020969	Disease Attributes
D010335	Pathologic Processes
D013568	Pathological Conditions, Signs and Symptoms

ID	Term
C523187	fluticasone furoate
C550468	vilanterol

Par. were considered to have completed the TP if they attended Visit 6 (Week 24).

Par. completed study if attended Wk 24, had 1-wk follow-up contact and no early withdrawal.