A Study to Evaluate the Efficacy, Safety, Tolerability, Pharmacokinetic (PK), and Pharmacodynamic (PD) Profiles of 3 Doses of Fluticasone Furoate (FF)/GW642444 Inhalation Powder at the End of a 28-day Treatment Period in Subjects With Chronic Obstructive Pulmonary Disease (COPD) Compared to Placebo

NCT01072149 | Completed Phase 3 Results

• 1 other identifier: 110946
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 8

Brief Summary

The Purpose of this study is to evaluate the 24-hour spirometry effect Forced Expiratory Volume in One second (FEV1) of 3 doses of Fluticasone Furoate (FF)/GW642444 Inhalation Powder at the end of a 28-day treatment period in subjects with Chronic Obstructive Pulmonary Disease (COPD) compared with placebo. Other objectives are to assess additional efficacy, plus the safety, pharmcodynamics and tolerability of concurrent treatment with Fluticasone Furoate (FF) plus GW642444 when administered at three dose levels for 28 days in subjects with COPD and to assess the steady-state pharmacokinetic profile of Fluticasone Furoatee (FF) and GW642444 at the end of each treatment period.

Conditions

Pulmonary Disease, Chronic Obstructive

Keywords

COPD; Safety; FEV1; Efficacy

Outcome Measures

Primary Outcomes (1)

• Time-adjusted Area Under the Curve (AUC) (i.e., Weighted Mean) for 24-hour Serial Forced Expiratory Volume in One Second (FEV1) at the End of Each 28-day Treatment Period

  FEV1 is defined as the amount of air that can be forcibly exhaled from the lungs in the first second of a forced exhalation. The weighted mean was calculated from pre-dose FEV1 (calculated as the mean of the -30 and -5 minute measurements) and post-dose FEV1 after 5, 15, 30, and 60 minutes and after 2, 4, 6, 8, 12, 16, 20, 22, 23, and 24 hours. Data are provided as the Least Squares Mean of the weighted mean for all three treatment periods. Analysis was performed using a mixed effects model with covariates of period treatment group, period Baseline, mean Baseline (defined as the mean of all available period Baseline FEV1 values), and period as fixed effects and participant as a random effect.

  Pre-dose and the end of each 28-day treatment period (up to 19 weeks)

Secondary Outcomes (2)

• Change From Period Baseline in Clinic Visit Trough FEV1 at the End of Each 28-day Treatment Period

  From Baseline to the end of each 28-day treatment period (up to 19 weeks)

• Change From Period Baseline in 25-hour Serial FEV1 at the End of Each 28 Day-treatment Period

  Baseline; pre-dose; 5 minutes, 15 minutes, 30 minutes, 60 minutes, and 2, 4, 6, 8, 12, 16, 20, 22, 23, 24, and 25 hours post-dose on Day 28 and Day 29 of each 28-day treatment period (up to 19 weeks)

Study Arms (4)

50mcg Fluticasone Furoate (FF)/25mcg GW642444

EXPERIMENTAL

Inhaled Corticosteroid (ICS)/ Long Acting Beta Agonist(LABA)

Drug: Fluticasone Furoate (FF)/GW642444 Inhalation Powder

100mcg Fluticasone Furoate (FF)/25mcg GW642444

EXPERIMENTAL

Inhaled Corticosteroid (ICS)/ Long Acting Beta Agonist(LABA)

Drug: Fluticasone Furoate (FF)/GW642444 Inhalation Powder

200mcg Fluticasone Furoate (FF)/25mcg GW642444

EXPERIMENTAL

Inhaled Corticosteroid (ICS)/ Long Acting Beta Agonist(LABA)

Drug: Fluticasone Furoate (FF)/GW642444 Inhalation Powder

placebo

PLACEBO COMPARATOR

placebo

Device: placebo

Interventions

Fluticasone Furoate (FF)/GW642444 Inhalation Powder DRUG

Inhaled Corticosteroid (ICS)/ Long Acting Beta Agonist(LABA) for COPD

100mcg Fluticasone Furoate (FF)/25mcg GW642444; 200mcg Fluticasone Furoate (FF)/25mcg GW642444; 50mcg Fluticasone Furoate (FF)/25mcg GW642444

placebo DEVICE

placebo

placebo

Eligibility Criteria

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

You may qualify if:

• Outpatient/Inpatient; Male or female subjects
• Subjects must give their signed and dated written informed consent to participate.
• A female is 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 surgically sterile). Surgically sterile females are defined as those with a documented hysterectomy and/or bilateral oophorectomy or tubal ligation. Post-menopausal females are defined as being amenorrhoeic, \> 45 years, in the absence of hormone replacement therapy. However in questionable cases, a blood sample with FSH \>40MIU/ml and estradiol \< 40pg/ml (\<140 pmol/L) is confirmatory.
• Child bearing potential, has a negative pregnancy test at screening, and agrees to one of the following acceptable contraceptive methods used consistently and correctly (i.e. in accordance with the approved product label and the instructions of the physician for the duration of the study - screening to follow-up contact):
• Complete abstinence from intercourse from screening until the follow-up contact; or
• Male partner is sterile (vasectomy with documentation of azoospermia) prior to female subject entry into the study, and this male partner is the sole partner for that subject; or
• Implants of levonorgestral inserted for at least 1 month prior to the study medication administration but not beyond the third successive year following insertion; or
• Injectable progestogen administered for at least 1 month prior to study medication administration; or
• Oral contraceptive (combined or progestogen only) administered for at least one monthly cycle prior to study medication administration; or
• Double barrier method: condom or occlusive cap (diaphragm or cervical/vault caps) plus spermicidal agent (foam/gel/film/cream/suppository); or
• An intrauterine device (IUD), inserted by a qualified physician, with published data showing that the highest expected failure rate is less than 1% per year; or
• Estrogenic vaginal ring; or
• Percutaneous contraceptive patches.
• 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 \[Celli, 2004\]: 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.

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)
• α1-antitrypsin deficiency: Subjects with α-1 antitrypsin deficiency as the underlying cause of COPD
• Other respiratory disorders: Subjects with active tuberculosis, lung cancer, bronchiectasis, sarcoidosis, lung fibrosis, pulmonary hypertension, interstitial lung diseases or other active pulmonary diseases
• Lung resection: Subjects with lung volume reduction surgery within the 12 months prior to Screening
• Chest X-ray (or CT scan): Subjects with a chest X-ray (or CT scan) thats reveals evidence of clinically significant abnormalities not believed to be due to the presence of COPD. A chest X-ray must be taken at Screening if a chest X-ray or CT scan is not available within 6 months prior to Screening (Visit 1)
• Hospitalization: Subjects who are hospitilized due to poorly controlled COPD with 12 weeks of Screening (Visit 1)
• Poorly controlled COPD: Subjects with poorly controlled COPD defined as the occurrence of any of the following in the 6 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
• Lower respiratory tract infection: Subjects with lower respiratory tract infection that require the use of antibiotics within 6 weeks prior to Screening (Visit 1)
• Other diseases/abnormalities: Subjects with historical or current evidence of clinically significant cardiovascular (i.e., pacemaker), neurological, psychiatric, renal, hepatic, immunological, endocrine (including uncontrolled diabetes or thyroid disease) or haematological abnormalities that are uncontrolled. Significant is defined as any disease that, in the opinion of the investigator, would put the safety of the subject at risk through participation, or which would affect the efficacy or safety analysis if the disease/condition exacerbated during the study.
• Peptic Ulcer disease: Subjects with clinically significant peptic ulcer disease that is uncontrolled.
• Hypertension: Subjects with clinically significant hypertension that is uncontrolled
• Cancer: Subjects with carcinoma that has not been in complete remission for at least 5 years. Carcinoma in situ 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.
• Drug/food allergy: Subjects with a history of hypersensitivity to any of the study medications (e.g. beta-agonists, corticosteroid) or components of the inhalation powder (e.g. lactose, magnesium stearate). In addition, patients with a history of severe milk protein allergy that, in the opinion of the study physician, contraindicates the subject's participation will also be excluded.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (8)

GSK Investigational Site

DeLand, Florida, 32720, United States

Location

GSK Investigational Site

Orlando, Florida, 32822, United States

Location

GSK Investigational Site

Madisonville, Kentucky, 42431, United States

Location

GSK Investigational Site

Columbus, Ohio, 43215, United States

Location

GSK Investigational Site

Greenville, South Carolina, 29615, United States

Location

GSK Investigational Site

Orangeburg, South Carolina, 29118, United States

Location

GSK Investigational Site

Spartanburg, South Carolina, 29303, United States

Location

GSK Investigational Site

Union, South Carolina, 29379, United States

Location

Related Publications (1)

• Boscia JA, Pudi KK, Zvarich MT, Sanford L, Siederer SK, Crim C. Effect of once-daily fluticasone furoate/vilanterol on 24-hour pulmonary function in patients with chronic obstructive pulmonary disease: a randomized, three-way, incomplete block, crossover study. Clin Ther. 2012 Aug;34(8):1655-66.e5. doi: 10.1016/j.clinthera.2012.06.005. Epub 2012 Jul 11.

  PMID: 22789766 BACKGROUND

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

Interventions

fluticasone furoate

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

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 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 12, 2010
• First Posted: February 19, 2010
• Study Start: January 1, 2010
• Primary Completion: July 1, 2010
• Study Completion: July 1, 2010
• Last Updated: November 9, 2017
• Results First Posted: December 25, 2013

Record last verified: 2017-10

Data Sharing

• IPD Sharing: Will share

Locations

US (8)