Noninferiority of beclometasone dipropionate/formoterol fumarate/glycopyrronium bromide versus beclometasone dipropionate/formoterol fumarate in asthma

The primary objective is to demonstrate noninferiority of asthma control with Trimbow® 87/5/9 pMDI compared with Foster® 200/6 pMDI, based on the change in Asthma Control Questionnaire-5 score from baseline to Month 12. This endpoint is clinically relevant because it directly evaluates long-term control of disease symptoms. The secondary objectives are to assess long-term safety and tolerability, and to evaluate effects on other lung function parameters, asthma exacerbations, participants’ health status, and other clinical outcome measures.

The trial enrolled 38 participants with asthma, including male and female adults aged 18 years and older. The population consisted of individuals with a physician-confirmed diagnosis of asthma and generally stable background treatment, with at least 3 months of regular ICS/LABA therapy before randomisation. Participants had poor asthma control at randomisation, defined by an ACQ-5 score of at least 1.5 and at least one exacerbation in the previous year. Selection was based on written informed consent and the ability to comply with study requirements, including use of the patient app and completion of electronic patient-reported outcomes. Women with childbearing potential and their fertile male partners were required to use a highly effective contraceptive method. Participants with asthma and no clinically relevant concurrent chronic obstructive pulmonary disease diagnosis could be included, and those on maintenance and reliever therapy were eligible if the ICS dose did not exceed 400 µg/day of beclometasone or equivalent.

This is a phase IV, randomized, open-label, controlled, two-arm, parallel-group, prospective study in asthma. The trial compares Trimbow 87/5/9 pMDI with Foster 200/6 pMDI over an overall treatment period of 12 months. The study begins with a screening visit, at which eligibility is confirmed and baseline assessments are performed before randomization. After randomization, participants receive the assigned inhaled treatment and attend scheduled follow-up visits during the treatment period for efficacy and safety assessments, including questionnaire-based outcomes, lung function measures, and exacerbation monitoring. The final end-of-study visit occurs at Month 12 and is used to assess the primary endpoint and complete study evaluations. Participant involvement is expected to last approximately 12 months from randomization. Early termination may occur if informed consent is withdrawn, eligibility criteria are no longer met, or discontinuation is required for safety or other protocol-defined reasons.

The experimental treatment was Trimbow 87 micrograms/5 micrograms/9 micrograms pressurised inhalation, solution. It contained beclometasone dipropionate, glycopyrronium bromide, and formoterol fumarate dihydrate. The pharmaceutical form was pressurised inhalation solution, and the route of administration was inhalation. The stated dose was 400.00 µg microgram(s).

The comparator treatment was Fostair 200 microgram/6 microgram per actuation pressurised inhalation solution. It contained formoterol fumarate dihydrate and beclometasone dipropionate anhydrous. The pharmaceutical form was pressurised inhalation solution, and the route of administration was inhalation. The stated dose was 800.00 µg microgram(s).

The study was a randomized, open-label, two-arm, parallel-group trial. No additional information on dosing frequency, administration schedule, or participant compliance monitoring was provided.

Efficacy will be assessed by change from baseline in Asthma Control Questionnaire-5 (ACQ-5) at Visit 7, corresponding to Month 12, for the primary comparison between treatment groups. Secondary efficacy assessments will include change from baseline in ACQ-5 at all applicable visits, rates of severe asthma exacerbations and moderate/severe asthma exacerbations during the 12-month treatment period, including analyses at 6 and 12 months, time to first severe asthma exacerbation, and time to first moderate/severe asthma exacerbation. Additional efficacy measures will include speed of change questionnaire results at each applicable study visit, change from baseline in eosinophils value, number of days and total dose with oral systemic corticosteroids during the 12-month treatment period, change from baseline in the Test of the Adherence to Inhalers questionnaire, change from baseline in spirometry parameters and oscillometry parameters at each applicable on-site visit, change from baseline in the EuroQol 5-Dimension 5-Level questionnaire (EQ-5D-5L), and change from baseline in the chronic airways assessment test questionnaire at each applicable visit. The percentage of study participants with asthma remission, including partial and complete remission, will also be assessed at 6 and 12 months. Complete clinical asthma remission is defined by no systemic corticosteroid intake at the timepoint, no severe asthma exacerbation before the timepoint, ACQ-5 ≤1.5 at the timepoint, and change from baseline in predose forced expiratory volume in 1 second of at least 0 mL. Partial clinical asthma remission is defined by no systemic corticosteroid intake at the timepoint and fulfilment of two of the other three criteria.