CLI-01535AC1-03_Foster1
Research type
Research Study
Full title
Comparison of two formulations of beclometasone/formoterol pMDI on respiratory system impedance using impulse oscillometry in asthmatic patients.
IRAS ID
249813
Contact name
Brian Lipworth
Contact email
Sponsor organisation
CHIESI FARMACEUTICI S.p.A
Eudract number
2018-000353-50
Duration of Study in the UK
1 years, 6 months, 0 days
Research summary
Research Summary
The aim of this study is to compare two different products containing both a steroid, namely Beclometasone dipropionate (BDP) 100g/actuation, and a long acting-bronchodilator (reliever), namely Formoterol fumarate (FF) 6 g/actuation in asthmatic patients.
The first product is a commonly prescribed, asthma inhaler named Fostair® (also called CHF 1535) 100/6 µg/actuation. The second product is a new CHF 1535 100/6 µg pMDI HFA formulation developed by Chiesi named “alternative product”. This “alternative product” is an improved formulation, with exactly the same strength and dose of medication delivered by the current commercially available Fostair inhaler.
The effects of the two medications will be assessed using breathing tests, asthma control questionnaires, and blood tests.
The main objective of the study is to evaluate the impact of these two different inhalers on a specific type of breathing test called impulse oscillometry (a gentle breathing test) and on a specific blood test called a pharmacokinetic profile (a blood test looking at what the body does to the drug).
Approximately 24 asthmatic patients will be selected to be administered the two different treatments according to a random sequence established in advance.
Potential patients may be recruited from both primary and secondary care, as well as a Scottish Centre for Respiratory Research (SCRR) database of volunteers who have agreed to be contacted with regard to participating in departmental clinical research.
In total each patient will spend 2 to 10 weeks in the adaptation period to adapt the treatment received to study needs. Then, each patient will receive both possible treatments during 2 different treatment periods of 3 – 4 weeks. The two treatment periods will be separated by a wash-out period during which no tested product will be administered. In total, each patient will remain in the study for 11 to 24 weeks.Summary of Results
The primary aim of the study was to evaluate the effect of two formulations of CHF 1535 100/6 µg pressurised metered-dose inhaler (pMDI) on area under the curve of reactance (AX) 0-60 min post-investigational medicinal product (IMP) administration in asthmatic patients.
Study CLI-01535AC1-03 started enrolment on 14 March 2019 and was put on hold in March 2020 due to the coronavirus disease 2019 (COVID-19) pandemic outbreak. Due to the pandemic, the study was not enrolling for 15 months and due to the projected prolonged timelines, in July 2021 Chiesi decided to early terminate the study. Although the study was terminated prematurely, the methodology below is described as it was planned per protocol.
This clinical study was a Phase IIa study, with a single-centre, randomised, double-blind, multiple-dose, 2-way cross-over design. Each treatment period was 3 to 4 weeks long and each patient was to take 2 puffs in the morning and 2 puffs in the evening of CHF 1535 100/6 µg commercial formulation or alternative product (AP), according to the randomisation list.
In order to obtain 22 evaluable patients, approximately 24 asthmatic patients were planned to be randomised to be administered the two different treatments established according to the randomisation list. In total, 13 patients were allocated to one of the two treatment sequences, of whom 6 patients to treatment sequence T-R and 7 patients to treatment sequence R-T. Nine (69.2%) of the randomised patients completed the study. One (7.7%) patient discontinued due to an adverse event (AE) and 3 (23.1%) patients discontinued due to the coronavirus outbreak.Efficacy and Pharmacokinetic Results: since the study was terminated prematurely, efficacy and pharmacokinetic variables were not analysed and therefore not described in this Clinical Study Report.
Safety Results:
One (7.7%) patient experienced TEAEs leading to study discontinuation. This patient was reported with the moderate, not-related TEAEs viral upper respiratory tract infection and asthma (reported term: asthma exacerbation) reported in the wash-out period between Treatment Period 1 and 2. Overall, 27 TEAEs were reported in 9 (69.2%) patients, i.e., 7 (63.6%) patients reported a TEAE after inhalation of CHF 1535 100/6 µg AP pMDI HFA and 6 (54.5%) patients after inhalation of CHF 1535 100/6 µg pMDI HFA. By preferred term, the most frequently reported TEAEs were headache (in 3 patients overall), viral upper respiratory tract infection (in 3 patients overall), and nausea (in 2 patients overall). Other TEAEs were reported in at most 1 patient overall. No deaths or other serious AEs were reported during the study. All TEAEs were mild or moderate in intensity.
Overall, 3 TEAEs in 1 patient were considered to be treatment related by the Investigator: dyspepsia, nausea, and oropharyngeal pain in 1 patient after inhalation of CHF 1535 100/6 µg AP pMDI HFA. All 3 ADRs were mild in intensity and were considered resolved before the end of the patient’s study participation.
All 13 patients used rescue medication (salbutamol) during the study. No post-baseline abnormalities in lung function were reported. Based on assessment by the Investigator, PEF remained stable for all patients. No laboratory-related, vital sign-related, ECG-related, lung function-related, and physical examination-related TEAEs were reported.
Conclusion: Study CLI-01535AC1-03 started enrolment on 14 March 2019 and was put on hold in March 2020 due to the COVID-19 pandemic outbreak. Due to the pandemic, the study was not enrolling for 15 months and due to the projected prolonged timelines, in July 2021 Chiesi decided to early terminate the study. In conclusion, based on the collected data, CHF 1535 100/6 µg AP pMDI HFA and CHF 1535 100/6 µg pMDI HFA were safe and well tolerated.REC name
East of Scotland Research Ethics Service REC 2
REC reference
18/ES/0089
Date of REC Opinion
12 Sep 2018
REC opinion
Further Information Favourable Opinion