Study Evaluating the Effect of Fluticasone Furoate/ Vilanterol (FF/VI) Inhalation Powder Compared With Vilanterol (VI) Inhalation Powder on Bone Mineral Density (BMD) in Subjects With Chronic Obstructive Pulmonary Disease (COPD).

NCT01957150 | Completed Phase 4 Results

• 2 other identifiers: 1029722012-004801-28
• Study Type: interventional
• Target: 283
• Locations: 5 countries
• Sites: 45

Brief Summary

This is a multi-center, randomized, double-blind, parallel-group study. The FF/VI inhalation powder once daily and VI inhalation powder once daily will be evaluated in subjects with COPD over 156 weeks. The primary objective of this study is to evaluate the effect of the inhaled corticosteroid FF on bone mineral density assessed at the total hip by comparing FF/VI treatment with VI treatment in subjects with moderate COPD.

Conditions

Pulmonary Disease, Chronic Obstructive

Outcome Measures

Primary Outcomes (1)

• Percentage Change From Baseline in Bone Mineral Density (BMD) Measured at Total Hip

  BMD analysis performed on log (BMD ratio to baseline) using a repeated measures model with covariates of treatment group, age, gender, baseline BMI, visit, log baseline BMD, log baseline BMD by visit and treatment group by visit interactions. These estimates were then converted into annual changes and averaged to calculate the overall treatment estimates and difference which were used for testing non-inferiority. The analysis shown is for the "While on Treatment" estimand of the difference in percentage change from baseline per annum between FF/VI ± BMD medication/SCS (systemic corticosteroids) and VI ± BMD medication/SCS. Baseline is defined as the measurement performed at Visit 1. Percentage change is calculated as (BMD value post-Baseline divided by Baseline value) -1 multiplied by 100.

  Baseline (Visit 1) and 26, 52, 78, 104, 130 and 156 Weeks

Secondary Outcomes (5)

• Percentage Change From Baseline in BMD Measurements at Total Hip by Gender (Male Participants)

  Baseline (Visit 1) and 26, 52, 78, 104, 130 and 156 Weeks

• Percentage Change From Baseline in BMD Measurements at Total Hip by Gender (Female Participants)

  Baseline (Visit 1) and 26, 52, 78, 104, 130 and 156 Weeks

• Percentage Change From Baseline in BMD Measurements at Lumbar Spine (L1 to L4) by Gender (Male Participants)

  Baseline (Visit 1) and 26, 52, 78, 104, 130 and 156 Weeks

• Percentage Change From Baseline in BMD Measurements at Lumbar Spine (L1 to L4) by Gender (Female Participants)

  Baseline (Visit 1) and 26, 52, 78, 104, 130 and 156 Weeks

• Percentage Change From Baseline in BMD Measurements at Lumbar Spine (L1 to L4)

  Baseline (Visit 1) and 26, 52, 78, 104, 130 and 156 Weeks

Study Arms (2)

Fluticasone Furoate/Vilanterol 100/25 micrograms (mcg) QD

EXPERIMENTAL

Subjects will self administer FF/VI 100/25 mcg inhalation powder once daily for 156 weeks via the NDPI.

Drug: Fluticasone Furoate/Vilanterol

Vilanterol 25 mcg QD

EXPERIMENTAL

Subjects will self administer VI 25 mcg inhalation powder once daily for 156 weeks via the NDPI.

Drug: Vilanterol

Interventions

Fluticasone Furoate/Vilanterol DRUG

Dry white powder containing 100 mcg of Fluticasone Furoate blended with lactose per blister was administered by NDPI. Dry white powder containing 25 mcg of Vilanterol micronised drug (as the 'M' salt triphenylacetate) blended with lactose and magnesium stearate per blister was administered by NDPI.

Fluticasone Furoate/Vilanterol 100/25 micrograms (mcg) QD

Vilanterol DRUG

Dry white powder containing 25 mcg of Vilanterol micronised drug (as the 'M' salt triphenylacetate) blended with lactose and magnesium stearate per blister was administered by NDPI.

Vilanterol 25 mcg QD

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Informed consent: Subjects must give their signed and dated written informed consent to participate.
• Gender: Male or female subjects. Female subjects must be post-menopausal or using a highly effective method for avoidance of pregnancy. The decision to include or exclude women of childbearing potential may be made at the discretion of the investigator in accordance with local practice in relation to adequate contraception.
• Age: \>= 40 years of age at Screening (Visit 1)
• COPD diagnosis: Subjects with a clinical history of COPD in accordance with the following definition by the American Thoracic Society/European Respiratory Society: COPD is a preventable and treatable disease characterized by airflow limitation that is not fully reversible. The airflow limitation is usually progressive and is associated with an abnormal inflammatory response of the lungs to noxious particles or gases, primarily caused by cigarette smoking. Although COPD affects the lungs, it also produces significant systemic consequences.
• Tobacco use: Subjects with a current or prior history of \>=10 pack-years of cigarette smoking at screening (Visit 1). Former smokers are defined as those who have stopped smoking for at least 6 months prior to Visit 1. Number of pack years = (number of cigarettes per day/20) x number of years smoked Note: Pipe and/or cigar use cannot be used to calculate pack year history.
• Severity of Disease: Subject with a measured post-albuterol/salbutamol Forced expiratory volume (FEV1)/forced vital capacity (FVC) ratio of \<0.70 at Screening (Visit 1). Subjects with a measured post-albuterol/salbutamol 50% \<=FEV1 \<=70% of predicted normal values calculated using National Health and Nutrition Examination Survey (NHANES III) reference equations at Screening (Visit 1).
• Native Hip: Have at least one evaluable native hip.

You may not qualify if:

• Pregnancy: Women who are pregnant or lactating or are planning on becoming pregnant during the study.
• Asthma: Subjects with a current diagnosis of asthma. (Subjects with a prior history of asthma are eligible if they have a current diagnosis of COPD).
• Alpha1-antitrypsin deficiency: Subjects with alpha-1 antitrypsin deficiency as the underlying cause of COPD.
• Other respiratory disorders: Subjects with tuberculosis, lung cancer, bronchiectasis, sarcoidosis, lung fibrosis, pulmonary hypertension, interstitial lung diseases or other active pulmonary diseases.
• Lung resection or transplantation: Subjects with lung volume reduction surgery within the 12 months prior to Screening Visit 1 or having had a lung transplant.
• Chest X-ray: Subjects with a chest X-ray (or Computer Axial Tomography (CT) scan) that revealed evidence of clinically significant abnormalities not believed to be due to the presence of COPD. A chest X-ray should be taken at Screening Visit 1 if a chest X-ray or CT scan is not available within 12 months prior to Visit 1.
• Poorly controlled COPD: Subjects with poorly controlled COPD, defined as the occurrence of the following in the 12 weeks prior to Screening Visit 1: Acute worsening of COPD that is managed by the subject with corticosteroids or antibiotics or that requires treatment prescribed by a physician or requires hospitalization.
• Moderate or severe COPD exacerbation or lower respiratory tract infection: Subjects with 2 or more moderate or severe COPD exacerbations and/or a lower respiratory tract infection (including pneumonia) within the 12 months prior to Screening Visit 1 or experience a moderate or severe COPD exacerbation and/or a lower respiratory infection (including pneumonia) during the Run-In period. NOTE: A moderate COPD exacerbation is defined as requiring systemic corticosteroids and/or antibiotics. A severe COPD exacerbation is defined as requiring hospitalization.
• Abnormal clinically significant laboratory finding: Subjects who have an abnormal, clinically significant finding in any liver chemistry, biochemical, or haematology tests at Screening Visit 1 or upon repeat prior to randomization.
• Abnormal and clinically significant 12-lead Electrocardiogram (ECG): Subjects who have an abnormal, clinically significant ECG finding at Screening Visit 1.
• Non-Compliance during Run-In Period: Failure to demonstrate adequate compliance with run-in medication (\< 80% compliant), the ability to withhold COPD medications, and to keep clinic visit appointments.
• Bone disorders/conditions: Subjects with historical or current evidence of bone cancer, severe scoliosis, rheumatoid arthritis, metabolic bone diseases (other than osteoporosis) including hyper-or hypo-parathyroidism, Paget's disease of bone, osteomalacia, or osteogenesis imperfecta. Removal of vertebrae between L1 and L4 of the lumbar spine and/or presence of metal implants or devices, such as plates, rods, or screws in the lumbar spine and/or hip.
• Immobility: Wheel chair bound or paraplegic.
• Low vitamin D: Previously known low-serum 25-hydroxy vitamin D concentration (less than 10ng \[25nmoles\] per liter).
• Other diseases/abnormalities: Serious, uncontrolled disease (including serious psychological disorders) likely to interfere with the study within the 3-year study.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (45)

GSK Investigational Site

Jasper, Alabama, 35501, United States

Location

GSK Investigational Site

Phoenix, Arizona, 85006, United States

Location

GSK Investigational Site

Fort Lauderdale, Florida, 33316, United States

Location

GSK Investigational Site

Lawrenceville, Georgia, 30046, United States

Location

GSK Investigational Site

Minneapolis, Minnesota, 55402, United States

Location

GSK Investigational Site

Plymouth, Minnesota, 55441, United States

Location

GSK Investigational Site

Bellevue, Nebraska, 68123-4303, United States

Location

GSK Investigational Site

Wilmington, North Carolina, 28401, United States

Location

GSK Investigational Site

Medford, Oregon, 97504, United States

Location

GSK Investigational Site

Erie, Pennsylvania, 16508, United States

Location

GSK Investigational Site

Charleston, South Carolina, 29406-7108, United States

Location

GSK Investigational Site

Old Point Station, South Carolina, 29707, United States

Location

GSK Investigational Site

Spartanburg, South Carolina, 29303, United States

Location

GSK Investigational Site

Chattanooga, Tennessee, 37404, United States

Location

GSK Investigational Site

Knoxville, Tennessee, 37919, United States

Location

GSK Investigational Site

San Antonio, Texas, 78229, United States

Location

GSK Investigational Site

Spokane Valley, Washington, 99216, United States

Location

GSK Investigational Site

Sherwood Park, Alberta, T8H 0N2, Canada

Location

GSK Investigational Site

Winnipeg, Manitoba, R2H 2A6, Canada

Location

GSK Investigational Site

Toronto, Ontario, M5T 3A9, Canada

Location

GSK Investigational Site

Québec, Quebec, G1V 4G5, Canada

Location

GSK Investigational Site

Saint-Charles-Borromée, Quebec, J6E 2B4, Canada

Location

GSK Investigational Site

Frankfurt am Main, Hesse, 60596, Germany

Location

GSK Investigational Site

Neu-Isenburg, Hesse, 63263, Germany

Location

GSK Investigational Site

Cologne, North Rhine-Westphalia, 51069, Germany

Location

GSK Investigational Site

Koblenz, Rhineland-Palatinate, 56068, Germany

Location

GSK Investigational Site

Berlin, 10787, Germany

Location

GSK Investigational Site

Berlin, 12157, Germany

Location

GSK Investigational Site

Hamburg, 22143, Germany

Location

GSK Investigational Site

Alkmaar, 1815 JD, Netherlands

Location

GSK Investigational Site

Beek, 6191 JW, Netherlands

Location

GSK Investigational Site

Ede, 6716 RP, Netherlands

Location

GSK Investigational Site

Eindhoven, 5623 EJ, Netherlands

Location

GSK Investigational Site

Hengelo, 7555 DL, Netherlands

Location

GSK Investigational Site

Hoorn, 1624 NP, Netherlands

Location

GSK Investigational Site

Losser, 7581 BV, Netherlands

Location

GSK Investigational Site

Voerendaal, 6367 TM, Netherlands

Location

GSK Investigational Site

Barcelona, Catalonia, 08017, Spain

Location

GSK Investigational Site

Alicante, 03004, Spain

Location

GSK Investigational Site

Barcelona, 08025, Spain

Location

GSK Investigational Site

L'Hospitalet de Llobregat, 08907, Spain

Location

GSK Investigational Site

Mérida (Badajoz), 06800, Spain

Location

GSK Investigational Site

Ponferrada (León), 24411, Spain

Location

GSK Investigational Site

Pozuelo de Alarcón/Madrid, 28223, Spain

Location

GSK Investigational Site

Salamanca, 37007, Spain

Location

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Interventions

fluticasone furoate; vilanterol

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

GSKClinicalSupportHD@gsk.com

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 4, 2013
• First Posted: October 8, 2013
• Study Start: January 28, 2014
• Primary Completion: March 26, 2018
• Study Completion: March 26, 2018
• Last Updated: April 10, 2019
• Results First Posted: April 10, 2019

Record last verified: 2019-03

Locations

DE (7); US (17); NL (8); ES (8); CA (5)