A Comparative Study Between Fluticasone Furoate/Umeclidinium/Vilanterol (FF/UMEC/VI) Single Inhaler Triple Therapy Versus Tiotropium Monotherapy in Subjects With Chronic Obstructive Pulmonary Disease (COPD)

NCT03474081 | Completed Phase 4 Results FDA Drug FDA Device

• 2 other identifiers: 2076262017-001190-16
• Study Type: interventional
• Target: 800
• Locations: 3 countries
• Sites: 72

Brief Summary

COPD is a progressive disease characterized by increasing obstruction to airflow and the progressive development of respiratory symptoms including chronic cough, increased sputum production, dyspnea and wheezing. Once-daily triple therapy of an Inhaled Corticosteroid/ Long-acting Muscarinic Receptor Antagonists/ Long Acting Beta-Agonist (ICS/LAMA/LABA) that is combination of FF/UMEC/VI in a single device is being developed with the aim of providing a new treatment option for the management of advanced COPD. The primary purpose of this study is to evaluate lung function and health related quality of life (HRQoL) after 84 days of treatment with a single inhaler triple therapy combination of FF/ UMEC/VI once daily via the ELLIPTA® dry powder inhaler (DPI) compared with tiotropium once daily via HANDIHALER®, in subjects with COPD. Subjects will be randomized 1:1 to receive FF/UMEC/VI or tiotropium in the morning for 84 days. Subjects will also receive albuterol/salbutamol as a rescue therapy throughout the study. Approximately 848 subjects with advanced COPD will be enrolled in the study. The total study duration will be approximately 17 weeks including, 4-week run-in period, 12-week treatment period and a 1-week follow-up period. ELLIPTA is a registered trademark of GlaxoSmithKline (GSK) group of companies. HANDIHALER and RESPIMAT are registered trademarks of Boeringher Ingelheim.

Conditions

Pulmonary Disease, Chronic Obstructive

Keywords

Umeclidinium; Lung function; RESPIMAT; Chronic obstructive pulmonary disease; Triple Therapy; Vilanterol; HANDIHALER; Tiotropium; Fluticasone furoate

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1) on Day 85

  FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second. Trough FEV1 on Day 85 was defined as the mean of the two planned spirometry FEV1 measurements. Change from Baseline in trough FEV1 on Day 85 was calculated by subtracting Baseline FEV1 value from the trough FEV1 value on Day 85. Baseline FEV1 was defined as the mean of the two assessments made at 30 and 5 minutes pre-dose on Day 1.

  Baseline (Day 1 [Pre-dose at 30 minutes and 5 minutes]) and Day 85

Secondary Outcomes (5)

• Change From Baseline in Trough FEV1 on Day 28

  Baseline (Day 1 [Pre-dose at 30 minutes and 5 minutes]) and Day 28

• Change From Baseline in Trough FEV1 on Day 84

  Baseline (Day 1 [Pre-dose at 30 minutes and 5 minutes]) and Day 84

• Number of Participants With Non-serious Adverse Events (Non-SAEs) and Serious Adverse Events (SAEs)

  Up to Day 95

• Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)

  Baseline (Day 1, Pre-dose) and Day 84

• Change From Baseline in Pulse Rate

  Baseline (Day 1, Pre-dose) and Day 84

Study Arms (2)

Subjects receiving FF/UMEC/VI + Placebo to match tiotropium

EXPERIMENTAL

Eligible subjects will receive FF/UMEC/VI at a dose of 100/62.5/25 microgram (mcg) administered once daily in the morning via ELLIPTA along with placebo to match tiotropium administered once daily in the morning via HANDIHALER. Subjects will self-administer 4 puffs of rescue medication (Albuterol/salbutamol) via metered dose inhaler (MDI).

Drug: FF/UMEC/VI; Drug: Albuterol/salbutamol; Drug: Placebo to match tiotropium; Device: ELLIPTA inhaler; Device: HANDIHALER; Device: MDI

Subjects receiving Tiotropium + Placebo to match FF/UMEC/VI

EXPERIMENTAL

Eligible subjects will receive Tiotropium at a dose of 18 mcg administered once daily in the morning via HANDIHALER along with placebo to match FF/UMEC/VI administered once daily in the morning via ELLIPTA. Subjects will self-administer 4 puffs of rescue medication (Albuterol/salbutamol) via MDI.

Drug: Tiotropium; Drug: Albuterol/salbutamol; Drug: Placebo to match FF/UMEC/VI; Device: ELLIPTA inhaler; Device: HANDIHALER; Device: MDI

Interventions

FF/UMEC/VI DRUG

A single inhaler triple therapy of FF/UMEC/VI will be provided via ELLIPTA DPI. FF/UMEC/VI will be available as dry white powder with dosing strengths of 100/25/62.5 mcg per blister.

Subjects receiving FF/UMEC/VI + Placebo to match tiotropium

Tiotropium DRUG

Tiotropium will be provided as a hard gelatin capsule for oral inhalation containing 18 mcg tiotropium bromide blended with lactose, administered via HANDIHALER DPI.

Subjects receiving Tiotropium + Placebo to match FF/UMEC/VI

Albuterol/salbutamol DRUG

Albuterol/salbutamol will be provided as an inhalation via MDI with a spacer or nebules and will be given as a rescue medication throughout the study.

Subjects receiving FF/UMEC/VI + Placebo to match tiotropium; Subjects receiving Tiotropium + Placebo to match FF/UMEC/VI

Placebo to match FF/UMEC/VI DRUG

Placebo matching FF/UMEC/VI will be available as a dry white powder of lactose or magnesium stearate, administered via ELLIPTA DPI.

Subjects receiving Tiotropium + Placebo to match FF/UMEC/VI

Placebo to match tiotropium DRUG

Placebo will be given as hard gelatin capsule for oral inhalation containing lactose, administered via HANDIHALER DPI.

Subjects receiving FF/UMEC/VI + Placebo to match tiotropium

ELLIPTA inhaler DEVICE

ELLIPTA DPI will contain two individual blister strips with 30 blisters per strip. FF/UMEC/VI and placebo to match FF/UMEC/VI will be administered to the subjects using ELLIPTA DPI.

Subjects receiving FF/UMEC/VI + Placebo to match tiotropium; Subjects receiving Tiotropium + Placebo to match FF/UMEC/VI

HANDIHALER DEVICE

Tiotropium and placebo to match tiotropium will be administered to the subjects using HANDIHALER DPI.

Subjects receiving FF/UMEC/VI + Placebo to match tiotropium; Subjects receiving Tiotropium + Placebo to match FF/UMEC/VI

MDI DEVICE

Albuterol/salbutamol will be provided as a rescue medication throughout the study using MDI.

Subjects receiving FF/UMEC/VI + Placebo to match tiotropium; Subjects receiving Tiotropium + Placebo to match FF/UMEC/VI

Eligibility Criteria

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

You may qualify if:

• Subjects capable of giving signed informed consent.
• Outpatients will be included in the study.
• Subjects 40 years of age or older at Screening (Visit 1).
• Male or female subjects will be included; a female subject is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies: not a woman of childbearing potential (WOCBP) or a WOCBP who agrees to follow the contraceptive guidance during the treatment period and until the safety follow-up contact after the last dose of study treatment.
• An established clinical history of COPD in accordance with the definition by the American Thoracic Society/European Respiratory Society.
• 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 \[example given {e.g.}, 20 cigarettes per day for 10 years, or 10 cigarettes per day for 20 years\]). Previous smokers are defined as those who have stopped smoking for at least 6 months prior to Visit 1.
• A score of \>=10 on the COPD Assessment Test (CAT) at Screening (Visit 1).
• Subjects must demonstrate at Screening: A post-bronchodilator FEV1 \<50 percent predicted normal or a post-bronchodilator FEV1 \<80 percent 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/forced vital capacity (FVC) ratio of \<0.70 at screening.
• Subjects must have been receiving daily maintenance treatment with tiotropium alone (via the HANDIHALER or RESPIMAT®) for their COPD for at least 3 months prior to Screening.

You may not qualify if:

• Women who are pregnant or lactating or are planning on becoming pregnant during the study.
• Subjects with a current diagnosis of asthma. (Subjects with a prior history of asthma are eligible if they have a current diagnosis of COPD).
• Subjects with alpha1-antitrypsin deficiency as the underlying cause of COPD.
• Subjects with active tuberculosis, lung cancer, and clinically significant: bronchiectasis, sarcoidosis, lung fibrosis, pulmonary hypertension, interstitial lung disease or other active pulmonary diseases.
• Subjects who have undergone lung volume reduction surgery within the 12 months prior to Screening.
• Immune suppression (e.g. advanced human immunodeficiency virus \[HIV\] with high viral load and low cluster of differentiation 4 \[CD4\] count, lupus on immunosuppressant's) that in the opinion of the investigator would increase risk of pneumonia 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 for pneumonia (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).
• Respiratory tract infection that has not resolved at least 7 days prior to Screening.
• 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 chest x-ray (e.g. significant cardiomegaly, pleural effusion or scarring). All subjects will have a chest x-ray at Screening Visit 1 (or historical radiograph or computerized tomography \[CT\] scan obtained within 3 months prior to screening). For sites in Germany: If a chest x-ray (or CT scan) within 3 months prior to Screening (Visit 1) is not available, approval to conduct a diagnostic chest x-ray will need to be obtained from the Federal Office for Radiation Protection (BfS).
• Subjects with historical or current evidence of clinically significant cardiovascular, neurological, psychiatric, renal, hepatic, immunological, gastrointestinal, urogenital, nervous system, musculoskeletal, skin, sensory, endocrine (including uncontrolled diabetes or thyroid disease) or hematological 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.
• Alanine Transaminase (ALT) \>2x Upper Limit of Normal (ULN); and bilirubin \>1.5x ULN (isolated bilirubin \>1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin \<35 percent). Current active liver or biliary disease (with the exception of Gilbert's syndrome or asymptomatic gallstones or otherwise stable chronic liver disease per investigator assessment). Chronic stable hepatitis B and C (e.g., presence of hepatitis B surface antigen \[HBsAg\] or positive hepatitis C antibody test result at screening or within 3 months prior to first dose of study treatment) are acceptable if subject otherwise meets entry criteria.
• Subjects with any of the following at Screening (Visit 1): myocardial infarction or unstable angina in the last 6 months; unstable or life threatening cardiac arrhythmia requiring intervention in the last 3 months; New York Heart Association (NYHA) Class IV Heart failure.
• Abnormal and clinically significant 12-lead electrocardiogram (ECG) finding at Visit 1. The Investigator will determine the clinical significance of each abnormal ECG finding in relation to the Subject's medical history and exclude subjects who would be at undue risk by participating in the trial. An abnormal and clinically significant finding that would preclude a subject from entering the trial is defined as a 12-lead ECG tracing that is interpreted at, but not limited to, any of the following: atrial fibrillation (AF) with rapid ventricular rate \>120 beats per minute (BPM); sustained and non-sustained ventricular tachycardia (VT); second degree heart block Mobitz type II and third degree heart block (unless pacemaker or defibrillator had been inserted); QT interval corrected for heart rate (QTc) \>=500 millisecond (msec) in subjects with QRS \<120 msec and QTc \>=530 msec in subjects with QRS \>=120 msec.
• A history of allergy or hypersensitivity to any corticosteroid, anticholinergic/muscarinic receptor antagonist, beta2-agonist, lactose/milk protein or magnesium stearate or a medical condition such as narrow-angle glaucoma, prostatic hypertrophy or bladder neck obstruction that, in the opinion of the Investigator, contraindicates study participation.
• Subjects with carcinoma that has not been in complete remission for at least 3 years. Subjects who have had carcinoma in situ of the cervix, squamous cell carcinoma and basal cell carcinoma of the skin would not be excluded based on the 3 year waiting period if the subject has been considered cured by treatment.

Sponsors & Collaborators

• GlaxoSmithKline: lead
• Parexel: collaborator

Study Sites (72)

GSK Investigational Site

Andalusia, Alabama, 36420, United States

Location

GSK Investigational Site

Huntington Beach, California, 92647, United States

Location

GSK Investigational Site

Sacramento, California, 95821, United States

Location

GSK Investigational Site

Simi Valley, California, 93065, United States

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GSK Investigational Site

Colorado Springs, Colorado, 80907, United States

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GSK Investigational Site

Daytona Beach, Florida, 32117, United States

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GSK Investigational Site

Kissimmee, Florida, 34741, United States

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GSK Investigational Site

Miami, Florida, 33126, United States

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GSK Investigational Site

Miami, Florida, 33134, United States

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GSK Investigational Site

Miami Lakes, Florida, 33014, United States

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GSK Investigational Site

Orlando, Florida, 32825, United States

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GSK Investigational Site

Ormond Beach, Florida, 32174, United States

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GSK Investigational Site

Panama City, Florida, 32405, United States

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GSK Investigational Site

Nampa, Idaho, 83687, United States

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GSK Investigational Site

Oxon Hill, Maryland, 20745, United States

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GSK Investigational Site

Edina, Minnesota, 55435, United States

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GSK Investigational Site

Minneapolis, Minnesota, 55407, United States

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GSK Investigational Site

Bronxville, New York, 10708, United States

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GSK Investigational Site

Fayetteville, New York, 13066, United States

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GSK Investigational Site

Gastonia, North Carolina, 28054, United States

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GSK Investigational Site

Cincinnati, Ohio, 45242, United States

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GSK Investigational Site

Dublin, Ohio, 43016, United States

Location

GSK Investigational Site

DuBois, Pennsylvania, 15801, United States

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GSK Investigational Site

Anderson, South Carolina, 29621, United States

Location

GSK Investigational Site

Gaffney, South Carolina, 29340, United States

Location

GSK Investigational Site

Greer, South Carolina, 29650, United States

Location

GSK Investigational Site

Little River, South Carolina, 029566, United States

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GSK Investigational Site

Pelzer, South Carolina, 29669, United States

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GSK Investigational Site

Seneca, South Carolina, 29678, United States

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GSK Investigational Site

Spartanburg, South Carolina, 29303, United States

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GSK Investigational Site

Corsicana, Texas, 75110, United States

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GSK Investigational Site

Huntsville, Texas, 77340, United States

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GSK Investigational Site

Salt Lake City, Utah, 84102, United States

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GSK Investigational Site

Bialystok, 15-003, Poland

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GSK Investigational Site

Bialystok, 15-044, Poland

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GSK Investigational Site

Bielsko-Biala, 43-300, Poland

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GSK Investigational Site

Bydgoszcz, 85-796, Poland

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GSK Investigational Site

Bydgoszcz, 85-863, Poland

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GSK Investigational Site

Chojnice, 89-600, Poland

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GSK Investigational Site

Grudziądz, 86-300, Poland

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GSK Investigational Site

Kielce, 25-751, Poland

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GSK Investigational Site

Krakow, 30-033, Poland

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GSK Investigational Site

Krakow, 31-209, Poland

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GSK Investigational Site

Lublin, 20-412, Poland

Location

GSK Investigational Site

Nowa Sól, 67-100, Poland

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GSK Investigational Site

Ostrowiec Świętokrzyski, 27-400, Poland

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GSK Investigational Site

Ostróda, 14-100, Poland

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GSK Investigational Site

Piaseczno, 05-500, Poland

Location

GSK Investigational Site

Proszowice, 32-100, Poland

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GSK Investigational Site

Siedlce, 08-110, Poland

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GSK Investigational Site

Skierniewice, 96-100, Poland

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GSK Investigational Site

Sopot, 81-741, Poland

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GSK Investigational Site

Swidnica, 58-100, Poland

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GSK Investigational Site

Szczecin, 71-124, Poland

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GSK Investigational Site

Torun, 87-100, Poland

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GSK Investigational Site

Warsaw, 02-777, Poland

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GSK Investigational Site

Zamość, 22-400, Poland

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GSK Investigational Site

Zawadzkie, 47-120, Poland

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GSK Investigational Site

Ivanovo, 153005, Russia

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GSK Investigational Site

Moscow, 111539, Russia

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GSK Investigational Site

Moscow, 115 280, Russia

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GSK Investigational Site

Moscow, 115682, Russia

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GSK Investigational Site

Novosibirsk, 630008, Russia

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GSK Investigational Site

Novosibirsk, 630087, Russia

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GSK Investigational Site

Saint Petersburg, 196084, Russia

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GSK Investigational Site

Saint Petersburg, 197022, Russia

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GSK Investigational Site

Saint Petersburg, 198260, Russia

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GSK Investigational Site

Saint Petersburg, 199106, Russia

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GSK Investigational Site

Saratov, 410028, Russia

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GSK Investigational Site

Ulyanovsk, 432063, Russia

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GSK Investigational Site

Voronezh, 394066, Russia

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GSK Investigational Site

Yekaterinburg, 620109, Russia

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Related Publications (1)

• Bansal S, Anderson M, Anzueto A, Brown N, Compton C, Corbridge TC, Erb D, Harvey C, Kaisermann MC, Kaye M, Lipson DA, Martin N, Zhu CQ, Papi A. Single-inhaler fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) triple therapy versus tiotropium monotherapy in patients with COPD. NPJ Prim Care Respir Med. 2021 May 25;31(1):29. doi: 10.1038/s41533-021-00241-z.

  PMID: 34035312 BACKGROUND

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Interventions

Tiotropium Bromide; Albuterol

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Scopolamine Derivatives; Tropanes; Azabicyclo Compounds; Aza Compounds; Organic Chemicals; Alkaloids; Heterocyclic Compounds; Bridged Bicyclo Compounds, Heterocyclic; Heterocyclic Compounds, Bridged-Ring; Ethanolamines; Amino Alcohols; Alcohols; Amines; Phenethylamines; Ethylamines

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
• Masking Details: This will be a double blind study. Subjects and investigator will be masked.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Subjects will be randomized 1:1 to receive either FF/UMEC/VI via ELLIPTA DPI along with placebo to match tiotropium or tiotropium via HANDIHALER along with placebo to match FF/UMEC/VI in the morning for 84 days.

Study Record Dates

• First Submitted: March 15, 2018
• First Posted: March 22, 2018
• Study Start: March 29, 2018
• Primary Completion: July 17, 2019
• Study Completion: July 17, 2019
• Last Updated: July 15, 2021
• Results First Posted: April 24, 2020

Record last verified: 2021-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: IPD is available via the Clinical Study Data Request site (copy the URL below to your browser)
• Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.

Locations

RU (14); US (33); PL (25)