A Study Comparing the Efficacy, Safety and Tolerability of Fixed Dose Combination (FDC) of FF/UMEC/VI With the FDC of FF/VI and UMEC/VI; Administered Once-daily Via a Dry Powder Inhaler (DPI) in Subjects With Chronic Obstructive Pulmonary Disease (COPD)

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT02164513
• Date of registration: 12/06/2014
• Prospective Registration: Yes
• Primary sponsor: GlaxoSmithKline
• Public title: A Study Comparing the Efficacy, Safety and Tolerability of Fixed Dose Combination (FDC) of FF/UMEC/VI With the FDC of FF/VI and UMEC/VI; Administered Once-daily Via a Dry Powder Inhaler (DPI) in Subjects With Chronic Obstructive Pulmonary Disease (COPD)
• Scientific title: A Phase III, 52 Week, Randomized, Double-blind, 3-arm Parallel Group Study, Comparing the Efficacy, Safety and Tolerability of the Fixed Dose Triple Combination FF/UMEC/VI With the Fixed Dose Dual Combinations of FF/VI and UMEC/VI, All Administered Once-daily in the Morning Via a Dry Powder Inhaler in Subjects With Chronic Obstructive Pulmonary Disease
• Date of first enrolment: June 30, 2014
• Target sample size: 10355
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02164513
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Double (Participant, Investigator).
• Phase: Phase 3

Countries of recruitment

Argentina, Australia, Austria, Belgium, Brazil, Canada, Chile, China, Colombia, Croatia, Czech Republic, Czechia, Denmark, Finland, France, Germany, Hong Kong, Israel, Japan, Korea, Republic of, Netherlands, New Zealand, Norway, Peru, Philippines, Poland, Puerto Rico, Romania, Russian Federation, Singapore, South Africa, Spain, Sweden, Thailand, Turkey, Ukraine, United Kingdom, United States, Vietnam

Contacts

• Name: GSK Clinical Trials
• Affiliation: GlaxoSmithKline

Key inclusion & exclusion criteria

Inclusion Criteria:

- Informed Consent: A signed and dated written informed consent prior to study
participation

- Type of subject: Outpatient

- Age: Subjects 40 years of age or older at Visit 1

- Gender: Male or female subjects. 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 for greater than 1 year with an appropriate clinical profile, e.g. age
appropriate, > 45 years, in the absence of hormone replacement therapy OR 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 safety follow-up contact): Abstinence;
Oral Contraceptive, either combined or progestogen alone; Injectable progestogen;
Implants of levonorgestrel; Estrogenic vaginal ring; Percutaneous contraceptive
patches; Intrauterine device (IUD) or intrauterine system (IUS); Male partner
sterilization (vasectomy with documentation of azoospermia) prior to the female
subject's entry into the study, and this male is the sole partner for that subject.
For this definition, "documented" refers to the outcome of the
investigator's/designee's medical examination of the subject or review of the
subject's medical history for study eligibility, as obtained via a verbal interview
with the subject or from the subject's medical records. Double barrier method: condom
and an occlusive cap (diaphragm or cervical/vault caps) with a vaginal spermicidal
agent (foam/gel/film/cream/suppository)

- COPD Diagnosis: An established clinical history of COPD in accordance with the
definition by the American Thoracic Society/European Respiratory Society

- Smoking History: Current or former cigarette smokers with a history of cigarette
smoking of >=10 pack-years at screening (visit 1) [number of pack years = (number of
cigarettes per day / 20) x number of years smoked (e.g., 20 cigarettes per day for 10
years, or 10 cigarettes per day for 20 years)]. Previous smokers are defined as those
who have stopped smoking for at least 6 months prior to Visit 1. Note: Pipe and/or
cigar use cannot be used to calculate pack-year history

- Severity of COPD symptoms: A score of >=10 on the COPD Assessment Test (CAT) at
screening

- Severity of COPD Disease: A post-albuterol/salbutamol FEV1/ Forced Vital Capacity
(FVC) ratio of <0.70 at Screening

- Existing COPD maintenance treatment: Subject must be receiving daily maintenance
treatment for their COPD for at least 3 months prior to Screening. Note: Subjects
receiving only Pro re nata (PRN) COPD medications are not eligible

- History of Exacerbations: Subjects must demonstrate: a post-bronchodilator FEV1 <50%
predicted normal and a documented history of >= 1 moderate or severe COPD exacerbation
in the previous 12 months OR a post-bronchodilator 50% <=FEV1 < 80% predicted normal
and a documented history of >= 2 moderate exacerbations or a documented history of >=1
severe COPD exacerbation (hospitalized) in the previous 12 months. Note: Percent
predicted will be calculated using the European Respiratory Society Global Lung
Function Initiative reference equations. Note: A documented history of a COPD
exacerbation (e.g., medical record verification) is a medical record of worsening COPD
symptoms that required systemic/oral corticosteroids and/or antibiotics (for a
moderate exacerbation) or hospitalization (for a severe exacerbation). Prior use of
antibiotics alone does not qualify as an exacerbation history unless the use was
associated with treatment of worsening symptoms of COPD, such as increased dyspnea,
sputum volume, or sputum purulence (color). Subject verbal reports are not acceptable

- Liver function tests: alanine aminotransferase (ALT) <2x upper limit of normal (ULN);
alkaline phosphatase <=1.5xULN; bilirubin <=1.5xULN (isolated bilirubin >1.5 x ULN is
acceptable if bilirubin is fractionated and direct bilirubin <35%)

- French subjects: In France, a subject will be eligible for inclusion in this study
only if either affiliated to or a beneficiary of a social security category

Exclusion Criteria:

- 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 Alpha1-antitrypsin deficiency as the
underlying cause of COPD

- Other respiratory disorders: Subjects with active tuberculosis, lung cancer,
significant 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

- Risk Factors for Pneumonia: immune suppression (e.g. human immunodeficiency virus
[HIV], Lupus) or other risk factors for pneumonia (e.g. neurological disorders
affecting control of the upper airway, such as Parkinson's Disease, Myasthenia
Gravis). Patients at potentially high risk (e.g. very low BMI, severely malnourished,
or very low FEV1) will only be included at the discretion of the Investigator

- Pneumonia and/or moderate or severe COPD exacerbation that has not resolved at least
14 days prior to Screening and at least 30 days following the last dose of
oral/systemic corticosteroids (if applicable). In addition, any subject that
experiences pneumonia and/or moderate or severe COPD exacerbation during the run-in
period will be excluded

- Other Respiratory tract infections that have not resolved at least 7 days prior to
screening

- Abnormal Chest x-ray(CXR): Chest x-ray (posteroanterior and lateral) reveals evidence
of pneumonia or a clinically significant abnormality not believed to be due to the
presence of COPD, or another condition that would hinder the ability to detect an
infiltrate on CXR (e.g. significant cardiomegaly, pleural effusion or scarring). All
subjects


Age minimum: 40 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Pulmonary Disease, Chronic Obstructive

Intervention(s)

Drug: umeclidinium bromide (UMEC)

Drug: fluticasone furoate (FF)

Drug: vilanterol (VI)

Primary Outcome(s)

Annual Rate of On-treatment Moderate/Severe Exacerbations Comparing FF/UMEC/VI With UMEC/VI and FF/VI [Time Frame: Up to Week 52]

Secondary Outcome(s)

Time to First On-treatment Moderate/Severe Exacerbation Comparing FF/UMEC/VI With FF/VI and With UMEC/VI [Time Frame: Up to Week 52]

Annual Rate of On-treatment Moderate/Severe Exacerbations Comparing FF/UMEC/VI With UMEC/VI in the Subset of Participants With a Blood Eosinophil Count >=150 Cells Per Microliter [Time Frame: Up to Week 52]

Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1), at Week 52 Comparing FF/UMEC/VI With FF/VI [Time Frame: Baseline and Week 52]

Annual Rate of On-treatment Severe Exacerbations Comparing FF/UMEC/VI With FF/VI and With UMEC/VI [Time Frame: Up to Week 52]

Change From Baseline in St. George's Respiratory Questionnaire for (SGRQ) Total Score at Week 52 Comparing FF/UMEC/VI With FF/VI [Time Frame: Baseline and Week 52]

Time to First On-treatment Moderate/Severe Exacerbation Comparing FF/UMEC/VI With UMEC/VI in the Subset of Particpants With a Blood Eosinophil Count >=150 Cells Per Microliter at Baseline [Time Frame: Up to Week 52]

Secondary ID(s)

116855

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 10/10/2018
• URL: https://clinicaltrials.gov/ct2/show/results/NCT02164513