A Study Comparing the Effects of Trimbow to Fostair in COPD

Chronic Obstructive Pulmonary Disease (COPD) Clinical Trial

— TRIFLOW  

Official title:

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03842904
• Other study ID #: MEU 17/361
• Secondary ID: 2018-003113-17
• Status: Completed
• Phase: Phase 4
• Start date: December 13, 2018
• Est. completion date: August 6, 2019

Study information

• Verified date: January 2020
• Source: Medicines Evaluation Unit Ltd
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Description:

This study will investigate the contributions of extra-fine glycopyrronium and formoterol (within triple therapy) to improvements in small airway function in COPD patients. This will be achieved by recruiting patients with hyperinflation, and measuring improvements in hyperinflation and expiratory flow limitation as measurements of small airway disease.

This study will help understand the mechanisms of action of the bronchodilators within BDP/FF/GB, and potentially encourage treatment of small airway disease in COPD with extra-fine bronchodilator treatments. This trial will be conducted in compliance with the Declaration of Helsinki (1964 and amendments) current Good Clinical Practices and all other applicable laws and regulations.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 23
• Est. completion date: August 6, 2019
• Est. primary completion date: July 30, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 75 Years

Eligibility

Inclusion Criteria:

1. Male and female adults aged 40 to 75 years with written informed consent obtained prior to any study-related procedure.

2. 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.

3. Clinically stable COPD in the 6 weeks prior to screening and during the run-in period prior to randomisation.

4. 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.

5. 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].

6. A post-bronchodilator FEV1 = 30 % and = 70% of the predicted normal value and a post-bronchodilator FEV1/FVC ratio < 0.7 at screening.

7. Evidence of pre-bronchodilator hyperinflation (RV>120% predicted) at screening (V1) and baseline (V2).

8. Subject is willing and, in the opinion of the Investigator, able to change current COPD therapy as required by the protocol.

9. Subject is treated with double or triple therapy for at least 1 month prior to screening visit with either:

1. Inhaled corticosteroids/long-acting ß2-agonist, combination treatment (fixed and/or free)

2. Inhaled corticosteroids and long-acting muscarinic antagonist

3. inhaled corticosteroids/long-acting ß2-agonist/long-acting muscarinic antagonist, combination treatment (fixed and/or free) In addition to the above subjects may be currently taking inhaled short acting ß2-agonists and/or inhaled short acting anticholinergics.

10. A cooperative attitude and ability to be trained to correctly use the pMDI inhaler.

11. 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)

Exclusion Criteria:

1. 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.

2. COPD exacerbation requiring oral steroids and/or antibiotics, in the 8 weeks prior to screening or prior to randomisation.

3. Use of antibiotics for a respiratory tract infection in the 8 weeks prior to screening or prior to randomisation.

4. Inability to perform technically acceptable impulse oscillometry, whole body plethysmography or spirometry at screening, (V1) or baseline (V2).

5. Pregnant, lactating or breastfeeding women at screening, baseline or prior to randomisation. Positive urine pregnancy test at screening, baseline or prior to randomisation.

6. A history of one or more hospitalisations for COPD in the 12 months prior to screening or prior to randomisation.

7. Requires oxygen therapy, even on an occasional basis.

8. 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.

9. 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.

10. 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.

11. History of hypersensitivity to anticholinergics, ß2-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.

12. 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.

13. 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.

14. 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.

15. History of alcohol abuse and/or substance/drug abuse within 2 years prior to screening visit.

16. Has had major surgery, (requiring general anaesthesia) in the 8 weeks prior to screening or prior to randomisation, or has planned surgery through the end of the study.

17. Previous lung resection or lung reduction surgery.

18. Participation in another clinical trial and received investigational drug within 30 days (or 5 half-lives whichever is longer). N.B.: For biologic products with slow elimination a washout of at least 6 months needs to be met prior to screening visit.

Related Conditions & MeSH terms

• Chronic Obstructive Pulmonary Disease (COPD)
• Lung Diseases
• Lung Diseases, Obstructive
• Pulmonary Disease, Chronic Obstructive

Intervention

Drug:
• Trimbow pMDI
Clinical Trial of an Investigational Medicinal Product (CTIMP)
• Fostair pMDI
Clinical Trial of an Investigational Medicinal Product (CTIMP)

Locations

Country	Name	City	State
United Kingdom	The Medicines Evaluation Unit (MEU)	Manchester

Sponsors (2)

Lead Sponsor	Collaborator
Medicines Evaluation Unit Ltd	Chiesi UK

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Frequency of AEs reported	To assess the safety and tolerability of the study treatment, as frequency of AEs reported.	From consent through study completion (study duration is approx. 5-10 weeks)
Primary	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)
Primary	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	Peripheral Respiratory Resistance (R5-R20), kPa/L/s.	Impulse Oscillometry measurement	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)
Secondary	Expiratory Flow Limitation (Delta X5), kPa/L/s.	Impulse Oscillometry measurement	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)
Secondary	Forced Vital Capacity (FVC), L	Spirometry measurement	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)
Secondary	Forced Expiratory Flow between 25-75% of FVC (FEF25-75%), L/s	Spirometry measurement	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)
Secondary	Resistance at 5Hz (R5), kPa/L/s	Impulse Oscillometry measurement	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)
Secondary	Reactance at 5Hz (X5), kPa/L/s	Impulse Oscillometry measurement	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)
Secondary	Resonance Frequency (Fres), Hz	Impulse Oscillometry measurement	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)
Secondary	Reactance Area (AX), kPa/L	Impulse Oscillometry measurement	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)
Secondary	Total Lung Capacity (TLC), L	Plethysmography measurement	Baseline, Pre-dose Day 1 and Day 5 (treatment period 1 & 2 - pre-dose, 1, 2, 4, 8 & 12 hrs post dose)
Secondary	Functional Residual Capacity (FRC), L	Plethysmography measurement	Baseline, Pre-dose Day 1 and Day 5 (treatment period 1 & 2 - pre-dose, 1, 2, 4, 8 & 12 hrs post dose)
Secondary	Inspiratory Capacity (IC), L	Plethysmography measurement	Baseline, Pre-dose Day 1 and Day 5 (treatment period 1 & 2 - pre-dose, 1, 2, 4, 8 & 12 hrs post dose)
Secondary	Specific Airway Conductance (SGaw), L/s/kPa/L	Plethysmography measurement	Baseline, Pre-dose Day 1 and Day 5 (treatment period 1 & 2 - pre-dose, 1, 2, 4, 8 & 12 hrs post dose)
Secondary	Airway Resistance (Raw), kPa/L/s	Plethysmography measurement	Baseline, Pre-dose Day 1 and Day 5 (treatment period 1 & 2 - pre-dose, 1, 2, 4, 8 & 12 hrs post dose)
Secondary	Forced Expired Volume in 1 second (FEV1), L.	Spirometry measurement	Baseline and Day 5 (treatment period 1 & 2 - pre-dose, 30 mins, 1, 2, 4, 6, 8, 10 & 12 hrs post dose)
Secondary	Residual Volume (RV), L.	Plethysmography measurement	Baseline and Day 5 (treatment period 1 & 2 - pre-dose, 1, 2, 4, 8 & 12 hrs post dose)

External Links

•   Research facility website