Chronic obstructive pulmonary disease (COPD) MedDRA version: 20.0 Level: LLT Classification code 10010952 Term: COPD System Organ Class: 100000004855
Conditions
Interventions
Trade Name: Trimbow 87 micrograms/5 micrograms/9 micrograms pressurised inhalation, solution
Product Name: Trimbow 87 micrograms/5 micrograms/9 micrograms pressurised inhalation, solut
Sponsors
The Medicines Evaluation Unit (MEU) Ltd. (Investigator led study)
Eligibility
Sex/Gender
All
Inclusion criteria
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 35.0 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 = 80% of the predicted normal value and a post-bronchodilator FEV1/FVC ratio 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: a.Inhaled corticosteroids/long-acting ß2-agonist, combination treatment (fixed and/or free) b.Inhaled corticosteroids and long-acting muscarinic antagonist c.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). Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 14 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 10
Exclusion criteria
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 1) To compare the effect of Trimbow and Fostair on FEV1 [(forced expiratory volume in 1 second – changes from pre-dose day 1)]. 2) To compare the effect of Trimbow and Fostair on RV [(residual volume) – changes from pre-dose day 1)]. ; Secondary Objective: Secondary: 1) To compare the effect of Trimbow and Fostair on peripheral airway resistance (R5-R20) and expiratory flow limitation (?X5) - changes from pre-dose day 1. 2) To compare the effect of Trimbow and Fostair on other measures of Impulse Oscillometry (IOS), Body plethysmography and Spirometry (FVC; FEF25-75%; R5; X5; Fres; AX; TLC; FRC; IC; SGaw; Raw) - changes from pre-dose day 1. 3) To evaluate the effect of Trimbow compared to Baseline (Visit 2) on measures of IOS, Body plethysmography and Spirometry (FEV1, FVC; FEF25-75%; R5; X5; RV; Fres; AX; TLC; FRC; IC; SGaw; Raw). 4) To evaluate the effect of Fostair compared to Baseline (Visit 2) on measures of IOS, Body plethysmography and Spirometry (FEV1, FVC; FEF25-75%; R5; X5; RV; Fres; AX; TLC; FRC; IC; SGaw; Raw). Other: To assess the safety and tolerability of the study treatment, as frequency of adverse events (AEs) reported. ; Primary end point(s): Primary efficacy variables: •Forced Expired Volume in 1 second (FEV1), L •Residual Volume (RV), L The primary endpoint will be the area under the FEV1 curve in the 12 hours after treatment on day 5 of each treatment period (AUC0-12). ; Timepoint(s) of evaluation of this end point: Objective 1) FEV1 = Spirometry perfromed pre-dose, 30 minutes, 1, 2, 4, 6, 8, 10 and 12 hours post dose on Day 5 (Treatment Period 1 & 2). Objective 2) Residual Volume = Whole body plethysmography performed pre-dose, 1, 2, 4, 8 and 12 hours post dose on Day 5 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary efficacy variables: •Forced Vital Capacity (FVC), L •Forced Expiratory Flow between 25-75% of FVC (FEF25-75%), L/s •Resistance at 5Hz (R5), kPa/L/s •Peripheral Respiratory Resistance (R5-R20), kPa/L/s •Reactance at 5Hz (X5), kPa/L/s •Expiratory Flow Limitation (Delta X5), kPa/L/s •Resonance Frequency (Fres), Hz •Reactance Area (AX), kPa/L •Total Lung Capacity (TLC), L •Functional Residual Capacity (FRC), L •Inspiratory Capacity (IC), L •Specific Airway Conductance (SGaw), L/s/kPa/L •Airway Resistance (Raw), kPa/L/s Safety variables: •Adverse Events (AEs) and Adverse Drug Reactions (ADRs) ; Timepoint(s) of evaluation of this end point: Objective 1) R5-R20 & Delta X5 = IOS performed pre-dose, 30 mins, 1, 2, 4, 6, 8, 10 & 12 hrs post dose on Day 5 (both TPs). Objective 2) FVC, FEF25-75%, R5, X5, Fres, AX, TLC, FRC, IC, SGaw, Raw = IOS, Spirometry & plethysmography performed pre-dose, 30 mins, 1, 2, 4, 6, 8, 10 & 12 hrs post dose on Day 5 (both TPs). Objectives 3 & 4) FEV1, FVC, FEF25-75%, R5, X5, RV, Fres, AX, TLC, FRC, IC, SGaw, Raw = IOS, Spirometry & plethysmography performed pre-dose on Day 1 and pre-dose, 30 mins, 1, 2, 4, 6, 8, 10 & 12 hrs post dose on Day 5 (both TPs). Other Objective) AEs & ADRs = throughout the study from signing consent. | — |
Countries
United Kingdom
Contacts
Public ContactPaul Strelow
The Medicines Evaluation Unit (MEU) Ltd. (Investigator led study)
Outcome results
None listed