Study of Fluticasone/Formoterol/Glycopyrronium for the Treatment Chronic Obstructive Pulmonary Disease (TRIPLAR) (TRIPLAR)

Randomized, Open-label, Parallel, Active-controlled, Multicenter Study of Efficacy and Safety of Fixed-dose Combination of Fluticasone /Formoterol /Glycopyrronium for the Treatment of Patients With Chronic Obstructive Pulmonary Disease

Several studies have demonstrated the benefits of the LAMA (Long-Acting Muscarinic Antagonists) + LABA (Long-Acting Beta-Agonists) + IC (inhaled corticosteroids) combination in the treatment of chronic obstructive pulmonary disease (COPD). The use of the triple combination in patients with severe airflow obstruction and a history of flares has been associated with improved lung function, improved patient-reported endpoints and prevention of flares, when compared to LABA, LABA + LAMA and LABA + IC. Furthermore, when compared to dual therapies LABA + IC and LABA + LAMA, triple therapy has been able to reduce all-cause deaths among chronic obstructive pulmonary disease (COPD) patients.

Previously published studies have demonstrated that the triple combination of Fluticasone 250 mcg/Formoterol 12 mcg/Glycopyrronium 12.5 mcg was able to improve lung function in chronic obstructive pulmonary disease (COPD) patients with a history of flares. There was also a significant improvement in the mMRC (modified-Medical Research Council) which began in the 2nd week of treatment and continued up to week 12. The association was considered safe and well tolerated, with only mild to moderate adverse events recorded in approximately 25% of the subjects treated in the study.

Furthermore, bioavailability studies performed with the components of the combination proposed as experimental drug - Fluticasone/Formoterol/Glycopyrronium - indicated that there is no pharmacokinetic interaction between the 3 active ingredients when they were administered concomitantly to healthy individuals under fasting conditions.

Study Overview

• Status: Not yet recruiting
• Conditions: Chronic Obstructive Pulmonary Disease
• Intervention / Treatment: Drug: Fluticasone 250mcg/Formoterol 12mcg/Glycopyrronium 25mcg; Drug: Comparator - Trimbow®

Detailed Description

This is a phase 3 non-inferiority, randomized, open-label study with active control to compare the efficacy and safety of a fixed-dose triple combination to another triple combination with already established efficacy in subjects with symptomatic chronic obstructive pulmonary disease (COPD).

This study will be conducted in two stages. Study Step 1 The primary assessment of non-inferiority will be performed after 12 weeks of treatment by assessing FEV1 (Forced expiratory volume in the first second) in relation to baseline.

Study Step 2 In a second step, it will be assessed whether the benefits of the new triple combination on respiratory symptoms and health-related quality of life are sustained in the long term and to determine the annual rate of flares in 52 weeks of treatment.

The study will comprise a screening phase, consisting of a screening and run-in visit lasting up to 14 days, and a treatment phase in which, after collecting baseline data (which includes assessment of FEV1 (Forced expiratory volume in the first second) and quality of life through a questionnaire), participants will be randomized and begin their respective treatments.

Visits during Step 1 of treatment will be performed at weeks 4 and 12. The week 12 visit will be the primary endpoint visit.

After 12 weeks, Step 2 of the study will begin with all participants who completed Step 1 and who agreed to remain in the study to receive Eurofarma's experimental drug for up to 52 weeks. Visits during this step will be performed at weeks 24, 36 and 52 to assess safety, quality of life, lung function and flare rate (exploratory endpoints).

• Study Type: Interventional
• Enrollment (Estimated): 986
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Edilene Macedo; Phone Number: +551150908600; Email: edilene.macedo@eurofarma.com
• Study Contact Backup: Name: Gleyce Pinto; Phone Number: +551150908600; Email: gleyce.lima@eurofarma.com

Study Locations

• Brazil
  • Padrão
    • São Paulo, Padrão, Brazil, 06696-000
      • Eurofarma Laboratorios S.A
      • Contact: Edilene Macedo; Phone Number: +551150908600; Email: edilene.macedo@eurofarma.com
      • Contact: Gleyce Pinto; Phone Number: +551150908600; Email: gleyce.lima@eurofarma.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Participants of both sexes who meet all of the following criteria will be included in the study:

  1. Signed Informed Consent Form (ICF).
  2. Male or female aged 40 or over.
  3. Medical diagnosis of chronic obstructive pulmonary disease (COPD) documented by post-bronchodilator FEV1/FVC (Forced Expiratory Volume in the 1st second/ Forced Vital Capacity) ratio < 0.7 (Previous examination report or examination performed at the screening visit).

Exclusion Criteria:

• Participants who meet any of the following criteria will be excluded from the study:

  1. Pregnant or lactating women.
  2. Current diagnosis of asthma without current diagnosis of chronic obstructive pulmonary disease (COPD). Observation: Subjects with a prior history of asthma are eligible if they have a current diagnosis of chronic obstructive pulmonary disease (COPD).
  3. Other respiratory disorders other than chronic obstructive pulmonary disease (COPD) (for example, but not restricted to: active tuberculosis, sarcoidosis, pulmonary fibrosis, pulmonary hypertension).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Fluticasone Propionate 250 mcg/Formoterol Fumarate dihydrate 12 mcg/Glycopyrronium Bromide 25 mcg; Fluticasone Propionate 250 mcg/Formoterol Fumarate dihydrate 12 mcg/Glycopyrronium Bromide 25 mcg in the pharmaceutical form of hard capsule with powder for inhalation - 1 capsule per inhalation twice a day	Drug: Fluticasone 250mcg/Formoterol 12mcg/Glycopyrronium 25mcg; Participants randomized to this group will receive 1 capsule per inhalation twice a day; Other Names: Fluticasone Propionate 250 mcg/Formoterol Fumarate dihydrate 12 mcg/Glycopyrronium Bromide 25 mcg
Active Comparator: Trimbow® (Beclomethasone 100 mcg/Formoterol 6 mcg/Glycopyrronium 12.5 mcg); Beclomethasone Dipropionate 100 mcg/Formoterol Fumarate dihydrate 6 mcg/Glycopyrronium Bromide 12.5 mcg in pharmaceutical form aerosol solution in pressurized metered dose device (pMDI) for inhalation (Trimbow® - Chiesi Farmacêutica Ltda.) - 2 triggering twice a day	Drug: Comparator - Trimbow®; Participants randomized to this group will receive 2 triggering twice a day; Other Names: Trimbow® - Beclomethasone Dipropionate 100 mcg/Formoterol Fumarate dihydrate 6 mcg/Glycopyrronium Bromide 12.5 mcg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change to morning pre-dose FEV1	Change to morning pre-dose FEV1 at week 12 relative to baseline Forced expiratory volume in the first (FEV1).	week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change to SGRQ (Saint George's Respiratory Questionnaire)	Change to SGRQ (Saint George's Respiratory Questionnaire) total score at week 12 compared to baseline	week 12
Change to the COPD (chronic obstructive pulmonary disease )	Change to the COPD (chronic obstructive pulmonary disease ) Assessment Test (CAT - questionnaire to measure the impact of COPD on a person's life) in weeks 4 and 12 in relation to baseline	weeks 4 and 12

Collaborators and Investigators

• Sponsor: Eurofarma Laboratorios S.A.

Study record dates

Study Major Dates

• Study Start (Estimated): February 28, 2026
• Primary Completion (Estimated): November 30, 2027
• Study Completion (Estimated): July 30, 2028

Study Registration Dates

• First Submitted: January 3, 2024
• First Submitted That Met QC Criteria: January 29, 2024
• First Posted (Estimated): January 31, 2024

Study Record Updates

• Last Update Posted (Estimated): January 31, 2024
• Last Update Submitted That Met QC Criteria: January 29, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Disease Attributes; Chronic Disease; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Muscarinic Antagonists; Cholinergic Antagonists; Cholinergic Agents; Anti-Inflammatory Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Adrenergic Agonists; Dermatologic Agents; Adjuvants, Anesthesia; Anticonvulsants; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Anti-Allergic Agents; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Fluticasone; Xhance; Beclomethasone; Glycopyrrolate; Bromides; Formoterol Fumarate
• Other Study ID Numbers: EF183

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No