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Phase 3 Completed N=10,355 Randomized Double-blind Treatment

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)

Pulmonary Disease, Chronic Obstructive
Source: ClinicalTrials.gov NCT02164513 ↗
Enrolled (actual)
10,355
Serious AEs
21.4%
Results posted
Oct 2018
Primary outcomePrimary: Annual Rate of On-treatment Moderate/Severe Exacerbations Comparing FF/UMEC/VI With UMEC/VI and FF/VI — 0.91; 1.07; 1.21 Exacerbations per participant per year — p=<0.001
◆ Published Evidence
Established
21citations · ~7 / year
Estimating individual treatment effects on COPD exacerbations by causal machine learning on randomised controlled trials.
Thorax · 2023 · Open access · Likely link

Summary

The study evaluates the efficacy of fluticasone furoate/umeclidinium bromide/vilanterol (FF/UMEC/VI) to reduce the annual rate of moderate and severe exacerbations compared with dual therapy of FF/VI or UMEC/VI in subjects with COPD. Published studies which assessed the use of an 'open' triple therapy (use of Inhaled Corticosteroid [ICS]/ Long-acting Muscarinic Receptor Antagonists [LAMA])/ Long Acting Beta-Agonist [LABA] delivered via multiple inhalers) in moderate-severe COPD patients, reported improvements in lung function, Health Related Quality of Life (HRQoL), hospitalization rates and rescue medication use, compared to dual therapy (ICS/LABA) or LAMA alone. These studies have also shown similar safety profile with dual or monotherapy doses for periods of up to one year. Given the clinical experience with FF, UMEC and VI, and that the associated risks with these compounds are anticipated from their known pharmacology, the potential benefit of a new therapy option in patients with moderate to severe COPD supports the further development of the closed triple combination (delivered via one inhaler). In the current study subjects meeting all inclusion/exclusion criteria will complete 2-week run-in period; 52 week treatment period and a 1-week safety follow-up period. Eligible subjects will be randomized to one of the following double-blind treatment groups FF/UMEC/VI 100 micrograms (mcg)/62.5 mcg/25 mcg once daily (QD), FF/VI 100 mcg/25 mcg QD, or UMEC/VI 62.5 mcg/25 mcg QD

Linked Publications (5)

  • Estimating individual treatment effects on COPD exacerbations by causal machine learning on randomised controlled trials.
    Thorax · 2023 · 21 citations · Open access · Likely link
  • Association between Increased Risk of Pneumonia with ICS in COPD: A Continuous Variable Analysis of Patient Factors from the IMPACT Study.
    Pulmonary therapy · 2024 · 6 citations · Open access · Likely link
  • The long-term clinical and economic benefits of treating advanced COPD patients with single-inhaler triple therapy in Quebec, Canada - The IMPACT trial.
    Respiratory medicine · 2024 · 2 citations · Open access · Likely link
  • Impact of Increased Use of Single-Inhaler Triple Therapies on COPD Exacerbation Rates, Mortality, and Total Costs: PROMETHEUS France.
    International journal of chronic obstructive pulmonary disease · 2025 · 1 citation · Open access · Likely link
  • Classification and regression trees to identify COPD subgroups in clinical trial populations: insights from the IMPACT trial.
    BMC pulmonary medicine · 2026 · 0 citations · Open access · Likely link

Outcome Measures

OutcomeResultp-value
PRIMARY
Annual Rate of On-treatment Moderate/Severe Exacerbations Comparing FF/UMEC/VI With UMEC/VI and FF/VI
0.91; 1.07; 1.21 <0.001 sig
SECONDARY
Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1), at Week 52 Comparing FF/UMEC/VI With FF/VI
0.094; -0.003 <0.001 sig
SECONDARY
Change From Baseline in St. George's Respiratory Questionnaire for (SGRQ) Total Score at Week 52 Comparing FF/UMEC/VI With FF/VI
-5.5; -3.7 <0.001 sig
SECONDARY
Time to First On-treatment Moderate/Severe Exacerbation Comparing FF/UMEC/VI With FF/VI and With UMEC/VI
112; 81; 73; NA; NA; 306 <0.001 sig
SECONDARY
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
0.95; 1.39 <0.001 sig
SECONDARY
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
107; 55; NA; 253 <0.001 sig
SECONDARY
Annual Rate of On-treatment Severe Exacerbations Comparing FF/UMEC/VI With FF/VI and With UMEC/VI
0.13; 0.15; 0.19 0.064

Eligibility 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 = 1 moderate or severe COPD exacerbation in the previous 12 months OR a post-bronchodilator 50% = 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) 1.5 x ULN is acceptable if bilirubin is fractionated and direct bilirubin 120 beats per minute); sustained or nonsustained ventricular tachycardia (VT); Second degree heart block Mobitz type II and third degree heart block (unless pacemaker or defibrillator had
View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT02164513) and the linked publication. Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.

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