Fluticasone Propionate/Salmeterol Combination 250/50 DISKUS in the Exercise Endurance Time in Patients With Chronic Obstructive Pulmonary Disease

NCT01124422 | Completed Phase 4 Results

• 1 other identifier: 113877
• Study Type: interventional
• Target: 255
• Locations: 2 countries
• Sites: 27

Brief Summary

The objective of this study is to demonstrate that, when added to tiotropium (TIO), fluticasone propionate/salmeterol combination (FSC) DISKUS 250/50 significantly increases exercise endurance time (EET) in the endurance shuttle walk test (ESWT), compared to TIO alone. Male and female subjects at least 40 years of age with a diagnosis of Chronic Obstructive Pulmonary Disease (COPD) are eligible. Subjects will be screened and consented at or during a 6-week (wk) period prior to visit (V)1. The 4-wk run-in period begins immediately after V1, when subjects receive open-label TIO plus as-needed relief inhaler (identical formulations called albuterol in the US and salbutamol in Canada). At V2, subjects will perform an incremental shuttle walk test (ISWT) to establish their maximal walk response. The first ESWT will occur at V3. Subjects must demonstrate an EET of ≤20 min that is reproducible (EET from V3 and V4 varying by ≤2 min). Eligible subjects are then randomized at V5 to either FSC 250/50mcg DISKUS twice daily plus open label TIO 18 mcg daily, or placebo DISKUS twice daily plus open label TIO 18 mcg daily for the 4-wk treatment period. The last study visit is V6. The primary efficacy measure is the difference between the EET at V6 (wk-8) vs. V4 (wk-3; the last ESWT done before randomized study drug is given). Secondary efficacy measures include V6 vs. V4 comparisons in exercise dyspnea scale (EDS), exercise inspiratory capacity (EIC) and cardio-respiratory measurements (CRM), and V6 vs. V5 comparisons in dyspnea related to activities of daily living (baseline dyspnea index and transition dyspnea index interviewer-administered \[BDI-TDI\]) and quality of life (Chronic Respiratory Disease Questionnaire Self-administered Standardized \[CRQ-SAS\]). The safety measure will be an assessment of adverse events. We will also attempt to validate prospectively the minimal clinically-important difference (MCID) for a change in the EET through correlation with dyspnea and quality of life results.

Conditions

Pulmonary Disease, Chronic Obstructive

Keywords

endurance shuttle walk test; chronic obstructive pulmonary disease; fluticasone propionate; dyspnea; exercise endurance time; tiotropium; salmeterol; exercise inspiratory capacity; quality of life

Outcome Measures

Primary Outcomes (1)

• Mean Change in Exercise Endurance Time (EET) From Baseline (Week 3) to Week 8

  EET is defined as the time taken by a participant to exert himself during an exercise. EET was calculated based on the Endurance Shuttle Walk test (ESWT). The ESWT is a standardized, externally controlled, constant-paced field test for the assessment of endurance capacity in participants with chronic lung disease. Change from Baseline in EET was calculated as the value at Week 8 minus the value at Baseline.

  Baseline (Week 3) and Week 8

Secondary Outcomes (18)

• Mean Change in Scores on the Exercise Dyspnea Scale (EDS) From Baseline (Week 3) to Week 8

  Baseline (Week 3) and Week 8

• Mean Change in EDS at Isotime From Baseline (Week 3) to Week 8

  Baseline (Week 3) and Week 8

• Mean Change in Pre-dose and Post-dose Resting Inspiratory Capacity (IC) From Baseline (Week 4) to Week 8

  Baseline (Week 4) and Week 8

• Mean Change in Exercise Inspiratory Capacity (EIC) at the End of Exercise From Baseline (Week 3) to Week 8

  Baseline (Week 3) and Week 8

• Mean Change in Flow of Oxygen (V'O2) Per Time Slope During the Course of the ESWT From Baseline (Week 3) to Week 8

  Baseline (Week 3) and Week 8

Study Arms (2)

fluticasone propionate/salmeterol DISKUS 250/50 + tiotropium

EXPERIMENTAL

This is the active DISKUS (that is, containing fluticasone propionate/salmeterol combination) + open-label tiotropium

Drug: fluticasone propionate/salmeterol inhalation powder DISKUS 250/50; Drug: tiotropium bromide inhalation powder HandiHaler

placebo DISKUS + tiotropium

PLACEBO COMPARATOR

This is the DISKUS and excipient minus the active ingredient (which is fluticasone propionate/salmeterol combination) + open-label tiotropium

Drug: tiotropium bromide inhalation powder HandiHaler

Interventions

fluticasone propionate/salmeterol inhalation powder DISKUS 250/50 DRUG

Experimental comparator consisting of inhaled corticosteroid plus long-acting beta agonist combination also known as ADVAIR DISKUS

fluticasone propionate/salmeterol DISKUS 250/50 + tiotropium

tiotropium bromide inhalation powder HandiHaler DRUG

Open-label drug also known as Spiriva HandiHaler

fluticasone propionate/salmeterol DISKUS 250/50 + tiotropium; placebo DISKUS + tiotropium

Eligibility Criteria

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

You may qualify if:

• Subjects eligible for enrolment in the study must meet all of the following criteria at V1.
• Consent: A signed and dated written informed consent must be obtained from the subject and/or subject's legally acceptable representative prior to study participation.
• Age: at least 40 yr of age
• Sex: Male or Female
• Females are eligible to participate only if they are currently not pregnant and not lactating. In addition, female subjects should not be enrolled if they plan to become pregnant during the time of study participation. A female is otherwise eligible to enter and participate in the study if she is of:
• non-child bearing potential (i.e., physiologically incapable of becoming pregnant, including any female who is post-menopausal); or,
• child-bearing potential, has a negative pregnancy test (urine) at screening, and is committed to the consistent and correct use of an acceptable method of birth control, starting at V2, throughout the clinical trial, and for a period after the trial to account for elimination of the drug (minimum of six days), as defined by at least one of the following:
• use of implants of levonorgestrel or etonogestrel
• percutaneous contraceptive patches
• use of injectable progestogen
• use of oral contraceptive (either combined estrogen/progestin or progestin only)
• use of any intrauterine device (IUD) with published data showing that the highest expected failure rate is less than 1% per yr
• male partner is sterile (vasectomy with documentation of azoospermia; note that a verbal report of azoospermia is acceptable) and is the sole sexual partner for that female subject prior to the female subject's entry into the study
• double-barrier method; condom or occlusive cap (diaphragm or cervical/vault caps) plus spermicide
• abstinence: if not sexually active, must commit to complete abstinence from intercourse

You may not qualify if:

• Subjects meeting any of the following criteria at V1 must not be enrolled in the study:
• Asthma: A current diagnosis of asthma.
• Other Respiratory Disorders: Subject had lung resection surgery (e.g., lung volume reduction surgery or lobectomy) within 1 yr of V1 or has a significant respiratory disorder other than COPD (e.g., lung cancer, sarcoidosis, active tuberculosis, bronchiectasis, pulmonary fibrosis, sleep apnea, cystic fibrosis, or alpha-1-antitrypsin deficiency) that, in the opinion of the investigator, would put the safety of the subject at risk through study participation, or which would affect the efficacy analysis if the disease/condition exacerbated during the study.
• Acute Exacerbation of COPD: active disease within the past 6 wk. For the purpose of this study, an acute exacerbation of COPD will be identified using the following criteria \[Anthonisen, 1987; Burge, 2003; Anzueto, 2009\]: either
• worsening of two or more of the following "major" symptoms for at least two consecutive days:
• dyspnea
• sputum volume
• sputum purulence or
• worsening of any one major symptom together with any one of the following "minor" symptoms for at least two consecutive days:
• sore throat
• nasal discharge or nasal congestion
• fever without other cause
• increased cough or wheeze.
• Pulmonary Rehabilitation: Participation in the early, active phase of a Pulmonary Rehabilitation Program. For the purpose of this study, the "early, active" phase of pulmonary rehabilitation consists of sessions, scheduled on a regular and frequent basis (generally more than bi-weekly and for a total duration of at least 4 wk), held at an institution or at home, that include exercise training among interventions such as education and psychosocial support. Not included as the "early, active" phase of pulmonary rehabilitation are reinforcement or maintenance sessions that follow an "early, active" phase with interactions that are less frequent and less intense but may be scheduled for a longer total duration such as 6 months to 1 yr.
• Lead ECG: Potential subjects are excluded if they have a functioning cardiac pacemaker. Otherwise, the investigator will determine the clinical significance of any ECG abnormality, and whether it precludes the potential subject from entering the study.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (27)

GSK Investigational Site

Birmingham, Alabama, 35294, United States

Location

GSK Investigational Site

Phoenix, Arizona, 85006, United States

Location

GSK Investigational Site

Torrance, California, 90505, United States

Location

GSK Investigational Site

Fort Collins, Colorado, 80528, United States

Location

GSK Investigational Site

Hartford, Connecticut, 06105, United States

Location

GSK Investigational Site

Saint Charles, Missouri, 63301, United States

Location

GSK Investigational Site

Omaha, Nebraska, 68131, United States

Location

GSK Investigational Site

Lebanon, New Hampshire, 03756, United States

Location

GSK Investigational Site

Albany, New York, 12205, United States

Location

GSK Investigational Site

Easley, South Carolina, 29640, United States

Location

GSK Investigational Site

Gaffney, South Carolina, 29340, United States

Location

GSK Investigational Site

Greenville, South Carolina, 29615, United States

Location

GSK Investigational Site

Spartanburg, South Carolina, 29303, United States

Location

GSK Investigational Site

Union, South Carolina, 29379, United States

Location

GSK Investigational Site

Houston, Texas, 77030, United States

Location

GSK Investigational Site

The Woodlands, Texas, 77380, United States

Location

GSK Investigational Site

Webster, Texas, 77598, United States

Location

GSK Investigational Site

Richmond, Virginia, 23229, United States

Location

GSK Investigational Site

Calgary, Alberta, T2N 4Z6, Canada

Location

GSK Investigational Site

Vancouver, British Columbia, V5Z 1M9, Canada

Location

GSK Investigational Site

Halifax, Nova Scotia, B3H 3A7, Canada

Location

GSK Investigational Site

Hamilton, Ontario, L9H 7S4, Canada

Location

GSK Investigational Site

Kingston, Ontario, K7L 2V7, Canada

Location

GSK Investigational Site

Toronto, Ontario, M5T 3A9, Canada

Location

GSK Investigational Site

Montreal, Quebec, H4J 1C5, Canada

Location

GSK Investigational Site

Québec, Quebec, G1V 4G5, Canada

Location

GSK Investigational Site

Saskatoon, Saskatchewan, S7N 0W8, Canada

Location

Related Publications (2)

• Maltais F, Mahler DA, Pepin V, Nadreau E, Crater GD, Morris AN, Emmett AH, Ferro TJ. Effect of fluticasone propionate/salmeterol plus tiotropium versus tiotropium on walking endurance in COPD. Eur Respir J. 2013 Aug;42(2):539-41. doi: 10.1183/09031936.00074113. No abstract available.

  PMID: 23904549 BACKGROUND

• Borel B, Pepin V, Mahler DA, Nadreau E, Maltais F. Prospective validation of the endurance shuttle walking test in the context of bronchodilation in COPD. Eur Respir J. 2014 Nov;44(5):1166-76. doi: 10.1183/09031936.00024314. Epub 2014 Sep 3.

  PMID: 25186261 DERIVED

Related Links

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

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive; Dyspnea

Interventions

Fluticasone

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Androstadienes; Androstenes; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

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: May 13, 2010
• First Posted: May 17, 2010
• Study Start: July 19, 2010
• Primary Completion: May 1, 2011
• Study Completion: May 2, 2011
• Last Updated: November 8, 2017
• Results First Posted: December 21, 2011

Record last verified: 2017-10

Data Sharing

• IPD Sharing: Will share

Locations

US (18); CA (9)