A Study Comparing the Effects of Trimbow to Fostair in COPD

NCT03842904 | Completed Phase 4

• 2 other identifiers: MEU 17/3612018-003113-17
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 1

Brief Summary

A randomised, open label 2-way cross-over study to compare the effects of inhaled Beclometasone/Formoterol/Glycopyrronium (TRIMBOW) pMDI to Beclometasone/Formoterol (FOSTAIR) pMDI on hyperinflation and expiratory flow limitation in moderate to severe chronic obstructive pulmonary disease (COPD).

Conditions

Chronic Obstructive Pulmonary Disease (COPD)

Outcome Measures

Primary Outcomes (2)

• Forced Expired Volume in 1 second (FEV1), L.

  To compare the effect of Trimbow and Fostair on FEV1 \[(forced expiratory volume in 1 sec - changes from pre-dose day 1)\].

  Pre-dose Day 1 and Day 5 (treatment period 1 & 2 - pre-dose, 30 minutes, 1, 2, 4, 6, 8, 10 and 12 hours post dose)

• Residual Volume (RV), L.

  To compare the effect of Trimbow and Fostair on RV \[(residual volume) - changes from pre-dose day 1)\].

  Pre-dose Day 1 and Day 5 (treatment period 1 & 2 - pre-dose, 1, 2, 4, 8 and 12 hours post dose)

Secondary Outcomes (15)

• Peripheral Respiratory Resistance (R5-R20), kPa/L/s.

  Pre-dose Day 1 and Day 5 (treatment period 1 & 2 - pre-dose, 30 mins, 1, 2, 4, 6, 8, 10 & 12 hrs post dose)

• Expiratory Flow Limitation (Delta X5), kPa/L/s.

  Pre-dose Day 1 and Day 5 (treatment period 1 & 2 - pre-dose, 30 mins, 1, 2, 4, 6, 8, 10 & 12 hrs post dose)

• Forced Vital Capacity (FVC), L

  Baseline, Pre-dose Day 1 and Day 5 (treatment period 1 & 2 - pre-dose, 30 mins, 1, 2, 4, 6, 8, 10 & 12 hrs post dose)

• Forced Expiratory Flow between 25-75% of FVC (FEF25-75%), L/s

  Baseline, Pre-dose Day 1 and Day 5 (treatment period 1 & 2 - pre-dose, 30 mins, 1, 2, 4, 6, 8, 10 & 12 hrs post dose)

• Resistance at 5Hz (R5), kPa/L/s

  Baseline, Pre-dose Day 1 and Day 5 (treatment period 1 & 2 - pre-dose, 30 mins, 1, 2, 4, 6, 8, 10 & 12 hrs post dose)

Other Outcomes (1)

• Frequency of AEs reported

  From consent through study completion (study duration is approx. 5-10 weeks)

Study Arms (2)

Trimbow pMDI

EXPERIMENTAL

Trimbow 87 micrograms/5 micrograms/9 micrograms pressurised inhalation solution.

Drug: Trimbow pMDI

Fostair pMDI

ACTIVE COMPARATOR

Fostair 100/6 micrograms per actuation pressurised inhalation solution.

Drug: Fostair pMDI

Interventions

Trimbow pMDI DRUG

Clinical Trial of an Investigational Medicinal Product (CTIMP)

Trimbow pMDI

Fostair pMDI DRUG

Clinical Trial of an Investigational Medicinal Product (CTIMP)

Fostair pMDI

Eligibility Criteria

• Age: 40 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and female adults aged 40 to 75 years with written informed consent obtained prior to any study-related procedure.
• COPD diagnosis: Subjects with a diagnosis of moderate to severe COPD according to the GOLD 2018 COPD recommendations, with symptoms compatible with COPD for at least 1 year prior to screening.
• Clinically stable COPD in the 6 weeks prior to screening and during the run-in period prior to randomisation.
• Body mass index (BMI) in the range of 18.0 to 33.0 kg/m2 and with a minimum weight of 50 kg at screening.
• Current smokers or ex-smokers with a smoking history of at least 10 pack years \[pack-years = (number of cigarettes per day x number of years)/20\].
• A post-bronchodilator FEV1 ≥ 30 % and ≤ 70% of the predicted normal value and a post-bronchodilator FEV1/FVC ratio \< 0.7 at screening.
• Evidence of pre-bronchodilator hyperinflation (RV\>120% predicted) at screening (V1) and baseline (V2).
• Subject is willing and, in the opinion of the Investigator, able to change current COPD therapy as required by the protocol.
• Subject is treated with double or triple therapy for at least 1 month prior to screening visit with either:
• Inhaled corticosteroids/long-acting β2-agonist, combination treatment (fixed and/or free)
• Inhaled corticosteroids and long-acting muscarinic antagonist
• inhaled corticosteroids/long-acting β2-agonist/long-acting muscarinic antagonist, combination treatment (fixed and/or free) In addition to the above subjects may be currently taking inhaled short acting β2-agonists and/or inhaled short acting anticholinergics.
• A cooperative attitude and ability to be trained to correctly use the pMDI inhaler.
• Compliance with inhaled Beclometasone run-in medication of between 80 to 120% at Visit 2 (baseline visit) and Visit 3 (Treatment Period 1, Day 1)

You may not qualify if:

• Inability to comply with study procedures, required restrictions, study treatment intake or any other reason that the Investigator considers makes the patient unsuitable to participate.
• COPD exacerbation requiring oral steroids and/or antibiotics, in the 8 weeks prior to screening or prior to randomisation.
• Use of antibiotics for a respiratory tract infection in the 8 weeks prior to screening or prior to randomisation.
• Inability to perform technically acceptable impulse oscillometry, whole body plethysmography or spirometry at screening, (V1) or baseline (V2).
• Pregnant, lactating or breastfeeding women at screening, baseline or prior to randomisation. Positive urine pregnancy test at screening, baseline or prior to randomisation.
• A history of one or more hospitalisations for COPD in the 12 months prior to screening or prior to randomisation.
• Requires oxygen therapy, even on an occasional basis.
• Known respiratory disorders other than COPD which may impact the efficacy or the safety of the study drug according to investigator's judgement. This can include but is not limited to known alpha-1 antitrypsin deficiency, active tuberculosis, lung cancer and bronchial carcinoma, bronchiectasis, sarcoidosis, lung fibrosis, pulmonary hypertension and interstitial lung disease.
• An abnormal and clinically significant 12-lead ECG which may impact the safety of the patient according to investigator's judgement.
• N.B: Subject whose electrocardiogram (ECG) (12 lead) shows QTcF\>450 males or QTcF\> 470 ms for females at screening are not eligible.
• Medical diagnosis of narrow-angle glaucoma, prostatic hypertrophy or bladder neck obstruction that in the opinion of the investigator would prevent use of anticholinergic agents.
• History of hypersensitivity to anticholinergics, β2-agonist, corticosteroids or any of the excipients contained in any of the formulations used in the trial which may raise contra-indications or impact the efficacy of the study drug according to the investigator's judgement.
• Clinically significant laboratory abnormalities at screening indicating a significant or unstable concomitant disease which may impact the efficacy of the study drug or the safety of the patient, according to investigator's judgement.
• Subjects with a history of chronic uncontrolled disease including, but not limited to, endocrine, active hyperthyroidism, neurological, hepatic, gastrointestinal, renal, haematological, urological, immunological, or ophthalmic diseases that the Investigator believes are clinically significant.
• Uncontrolled cardiovascular disease: arrhythmias, angina, recent or suspected myocardial infarction, congestive heart failure, a history of unstable, or uncontrolled hypertension, or has been diagnosed with hypertension in the 3 months prior to screening or randomisation.

Sponsors & Collaborators

• Medicines Evaluation Unit Ltd: lead
• Chiesi UK: collaborator

Study Sites (1)

The Medicines Evaluation Unit (MEU)

Manchester, M23 9QZ, United Kingdom

Location

Related Publications (1)

• Dean J, Panainte C, Khan N, Singh D. The TRIFLOW study: a randomised, cross-over study evaluating the effects of extrafine beclometasone/formoterol/glycopyrronium on gas trapping in COPD. Respir Res. 2020 Dec 9;21(1):323. doi: 10.1186/s12931-020-01589-5.

  PMID: 33298062 DERIVED

Related Links

• Research facility website

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Condition Hierarchy (Ancestors)

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

Study Officials

• David Rogers

  Medicines Evaluation Unit Ltd

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This is a phase IV, open-label, randomised, single centre, 2-way crossover study.

Study Record Dates

• First Submitted: February 11, 2019
• First Posted: February 15, 2019
• Study Start: December 13, 2018
• Primary Completion: July 30, 2019
• Study Completion: August 6, 2019
• Last Updated: January 27, 2020

Record last verified: 2020-01

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)