A Comparison Study Between the Fixed Dose Triple Combination of Fluticasone Furoate/ Umeclidinium/ Vilanterol Trifenatate (FF/UMEC/VI) With Budesonide/Formoterol in Subjects With Chronic Obstructive Pulmonary Disease (COPD)

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT02345161
• Date of registration: 19/01/2015
• Prospective Registration: Yes
• Primary sponsor: GlaxoSmithKline
• Public title: A Comparison Study Between the Fixed Dose Triple Combination of Fluticasone Furoate/ Umeclidinium/ Vilanterol Trifenatate (FF/UMEC/VI) With Budesonide/Formoterol in Subjects With Chronic Obstructive Pulmonary Disease (COPD)
• Scientific title: A Phase III, 24 Week, Randomized, Double Blind, Double Dummy, Parallel Group Study (With an Extension to 52 Weeks in a Subset of Subjects) Comparing the Efficacy, Safety and Tolerability of the Fixed Dose Triple Combination FF/UMEC/VI Administered Once Daily in the Morning Via a Dry Powder Inhaler With Budesonide/Formoterol 400mcg/12mcg Administered Twice-Daily Via a Reservoir Inhaler in Subjects With Chronic Obstructive Pulmonary Disease
• Date of first enrolment: January 23, 2015
• Target sample size: 1811
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02345161
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Double (Participant, Investigator).
• Phase: Phase 3

Countries of recruitment

Bulgaria, China, Czech Republic, Czechia, Estonia, Germany, Greece, Hungary, Italy, Korea, Republic of, Mexico, Poland, Romania, Russian Federation, Slovakia, Ukraine

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 Screening (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 (Visit 1).

- Severity of Disease: Subjects must demonstrate at Screening: FEV1 <50% predicted normal OR a post-bronchodilator FEV1 <80% predicted normal and a
documented history of >=2 moderate exacerbations or one severe (hospitalized)
exacerbation in the previous 12 months. Subjects must also have a measured post
albuterol/salbutamol FEV1/FVC ratio of <0.70 at screening. 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 dyspnoea, sputum volume, or
sputum purulence (colour). Subject verbal reports are not acceptable.

- 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 as required (PRN) COPD medications are not eligible.

- 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%).

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). Subjects at potentially high risk (e.g. very low Body mass index [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.

- Respiratory tract infection that has 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 will have a CXR at Screening Visit 1) (or historical radiograph or Computed
Tomography [CT] scan obtained within 3 months prior to screening) that will be
over-read by a central vendor. Note: Subjects who have experienced pneumonia and/or
moderate or severe COPD exacerbation wit


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

Health Condition(s) or Problem(s) studied

Pulmonary Disease, Chronic Obstructive

Intervention(s)

Drug: Albuterol/salbutamol

Drug: Placebo to match FF/UMEC/VI

Drug: Budesonide/Formoterol

Drug: Triple FF/UMEC/VI

Drug: Placebo to match Budesonide/Formoterol combination

Primary Outcome(s)

Change From Baseline in St George's Respiratory Questionnaire-COPD; SGRQ Total Score for COPD Participants at Week 52 [Time Frame: Baseline to Week 52]

Change From Baseline in St George's Respiratory Questionnaire-Chronic Obstructive Pulmonary Disease (COPD; SGRQ) Total Score for COPD Participants at Week 24 [Time Frame: Baseline to Week 24]

Change From Baseline in Trough Forced Expiratory Volume in One Second (FEV1) at Week 52 [Time Frame: Baseline to Week 52]

Change From Baseline in Trough Forced Expiratory Volume in One Second (FEV1) at Week 24 [Time Frame: Baseline to Week 24]

Secondary Outcome(s)

Change From Baseline in Albumin and Protein at Week 24 [Time Frame: Baseline and Week 24]

Change From Baseline in Erythrocytes at Week 52 [Time Frame: Baseline and Week 52]

Change From Baseline in Albumin and Protein at Week 52 [Time Frame: Baseline and Week 52]

Change From Baseline in ALT, AST, GGT, ALP, and Creatine Kinase at Week 52 [Time Frame: Baseline and Week 52]

Change From Baseline in Heart Rate at Week 52 [Time Frame: Baseline and Week 52]

Mean Annual On-treatment Moderate and/or Severe COPD Exacerbations up to Week 52 [Time Frame: Up to Week 52]

Number of Participants With at Least One On-treatment Bone Fracture Incident in the Extension Part of the Study [Time Frame: Up to Week 52]

Change From Baseline in Basophils, Eosinophils, Monocytes, Neutrophils, Leukocytes, Lymphocytes, and Platelets at Week 24 [Time Frame: Baseline and Week 24]

Change From Baseline in QT Interval Corrected for Heart Rate According to Bazett's Formula (QTcB) at Week 24 [Time Frame: Baseline and Week 24]

Change From Baseline in Bilirubin, Creatinine, and Urate at Week 52 [Time Frame: Baseline and Week 52]

Change From Baseline in Glucose, Calcium, Carbon Dioxide (CO2), Chloride, Phosphate, Potassium, Sodium, and Urea at Week 24 [Time Frame: Baseline and Week 24]

Change From Baseline in Systolic and Diastolic Blood Pressures (BP) at Week 52 [Time Frame: Baseline and Week 52]

Daily Activity Question Percentage of Days Reporting a Score of 2 up to Week 24 [Time Frame: Up to Week 24]

Number of Participants With Any On-treatment AE/SAEs in the Extension Part of the Study [Time Frame: Up to Week 52]

Change From Baseline in Hematocrit at Week 24 [Time Frame: Baseline and Week 24]

Change From Baseline in Pulse Rate at Week 52 [Time Frame: Baseline and Week 52]

Number of Participants With an On-treatment Penumonia Event in the Treatment Period [Time Frame: Up to Week 24]

Number of Participants With at Least One On-treatment Bone Fracture Incident in the Treatment Period [Time Frame: Up to Week 24]

Number of Participants Reporting an AESI of Oropharyngeal Origin in the Extension Part of the Study [Time Frame: Up to Week 52]

Transitional Dyspnea Index (TDI) Focal Score Expressed as Least Square Mean at Week 24 [Time Frame: Week 24]

Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean Exacerbations of Chronic Pulmonary Disease Tool (EXACT)-RS Scores up to Week 24 [Time Frame: Baseline to Week 24]

Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean EXACT-RS Scores up to Week 52 [Time Frame: Baseline to Week 52]

Change From Baseline in Erythrocytes at Week 24 [Time Frame: Baseline and Week 24]

Daily Activity Question Percentage of Days Reporting a Score of 2 up to Week 52 [Time Frame: Up to Week 52]

Number of Participants With an On-treatment Penumonia Event in the Extension Part of the Study [Time Frame: Up to Week 52]

Number of Participants With Any On-treatment Adverse Event (AE) and Serious Adverse Event (SAE) in the Treatment Period [Time Frame: Up to Week 24]

Transitional Dyspnea Index (TDI) Focal Score Expressed as Least Square Mean at Week 52 [Time Frame: Week 52]

Change From Baseline in Corrected QT Interval Using Fridericia's Correction (QTcF) and PR Interval at Week 24 [Time Frame: Baseline and Week 24]

Change From Baseline in Hematocrit at Week 52 [Time Frame: Baseline and Week 52]

Change From Baseline in Hemoglobin at Week 24 [Time Frame: Baseline and Week 24]

Change From Baseline in Hemoglobin at Week 52 [Time Frame: Baseline and Week 52]

Change From Baseline in Systolic and Diastolic Blood Pressures (BP) at Week 24 [Time Frame: Baseline and Week 24]

Number of Participants Reporting an Adverse Event of Special Interest (AESI) of Oropharyngeal Origin in the Treatment Period [Time Frame: Up to Week 24]

Change From Baseline in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Gamma Glutamyl Aminotransferase (GGT), Alkaline Phosphatase (ALP), and Creatine Kinase at Week 24 [Time Frame: Baseline and Week 24]

Change From Baseline in Basophils, Eosinophils, Monocytes, Neutrophils, Leukocytes, Lymphocytes, and Platelets at Week 52 [Time Frame: Baseline and Week 52]

Number of Participants With Any Abnormal Holter Electrocardiogram (ECG) Finding at Week 24 [Time Frame: Up to Week 24]

Change From Baseline in QTcF and PR Interval at Week 52 [Time Frame: Baseline and Week 52]

Number of Participants With Any On-treatment Cardiovascular (CV) Events (Including Supraventricular Arrhythmia and Non Fatal Myocardial Infarction) in the Treatment Period [Time Frame: Up to Week 24]

Change From Baseline in Bilirubin, Creatinine, and Urate at Week 24 [Time Frame: Baseline and Week 24]

Change From Baseline in Glucose, Calcium, CO2, Chloride, Magnesium, Phosphate, Potassium, Sodium, and Urea at Week 52 [Time Frame: Baseline and Week 52]

Change From Baseline in Heart Rate at Week 24 [Time Frame: Baseline and Week 24]

Change From Baseline in Pulse Rate at Week 24 [Time Frame: Baseline and Week 24]

Change From Baseline in QTcB at Week 52 [Time Frame: Baseline and Week 52]

Mean Annual On-treatment Moderate and/or Severe COPD Exacerbations up to Week 24 [Time Frame: Up to Week 24]

Number of Participants With Any On-treatment CV Events (Including Supraventricular Arrhythmia and Non Fatal Myocardial Infarction) in the Extension Part of the Study [Time Frame: Up to Week 52]

Secondary ID(s)

116853

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 13/07/2018
• URL: https://clinicaltrials.gov/ct2/show/results/NCT02345161