NCT02127866

Triple in Asthma Dose Finding

A MULTICENTRE, RANDOMISED, DOUBLE-BLIND, ACTIVE-CONTROLLED, 3-WAY CROSS-OVER STUDY TO EVALUATE THE EFFICACY AND SAFETY OF A FREE COMBINATION OF 3 DOSES OF CHF 5259 (GLYCOPYRROLATE) PLUS FOSTER® 100/6 µg (FIXED COMBINATION OF BECLOMETHASONE DIPROPIONATE PLUS FORMOTEROL) IN A METERED DOSE INHALER FOR THE TREATMENT OF PATIENTS WITH UNCONTROLLED ASTHMA UNDER MEDIUM DOSES OF INHALED CORTICOSTEROIDS PLUS LONG-ACTING β2-AGONISTS.

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 211 (actual)
• Sponsor: Chiesi Farmaceutici S.p.A. · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Primary objective The primary objective was to evaluate the efficacy of a free combination of CHF 5259 at 3 dose levels plus Foster® 100/6 μg in a pMDI by comparison with Foster® 100/6 μg in terms of forced expiratory volume in the first second (FEV1) area under the curve between time 0 and 12 hours (AUC0-12h) normalised by time on Day 42. Key secondary objective The key secondary objective was to evaluate the efficacy of the free combination CHF 5259 plus Foster® 100/6 μg by comparison with Foster® 100/6 μg in terms of peak FEV1 on Day 42. Secondary objectives The secondary objectives were: * To evaluate the effect of the free combination of CHF 5259 plus Foster® 100/6 μg on other lung function parameters and on clinical outcome measures; * To assess the safety and the tolerability of the study treatments.

Detailed description

This was a dose-finding, phase II, multicentre, randomised, double-blind, active-controlled, 3-way cross-over of 6 weeks, balanced incomplete block and multiple dose study. Since each patient serves as his/her own control, the cross-over design reduces the effect of potentially confounding variables and allows for greater statistical power with fewer subjects. This study was designed to evaluate the efficacy of a free combination of CHF 5259 at 3 dose levels (25 μg, 50 μg or 100 μg daily) plus Foster vs. Foster alone, administered via pMDI over a 6-week treatment period in patients with uncontrolled asthma. A total of 220 patients were targeted for randomisation to ensure that a minimum of 164 completed the study (assuming an estimated non-evaluable rate of 25%). There were 4 treatments, but as it was a cross-over incomplete block design, each patient took only 3 treatments out of 4, according to the randomisation list of sequences: A-C-B; B-D-C; C-A-D and D-B-A. . The four treatments were: * Treatment A = CHF 5259 (GB 25 μg/day) plus Foster (BDP 400/FF 24 μg/day); * Treatment B = CHF 5259 (GB 50 μg/day) plus Foster (BDP 400/FF 24 μg/day); * Treatment C = CHF 5259 (GB 100 μg/day) plus Foster (BDP 400/FF 24 μg/day); * Treatment D = Foster (BDP 400/FF 24 μg/day) alone. Foster was used during the study as the control despite an indication in "patients not adequately controlled with inhaled corticosteroids and 'as needed' inhaled rapid-acting β2-agonist" (and not in patients with uncontrolled asthma). No risks for the patients were foreseen owing to the short study duration (6 weeks), the possibility of using salbutamol as rescue medication and the close medical monitoring during the entire study period. The Foster dose (400/24 μg daily) for the run-in and wash-out periods was selected as this is a standard dosing regimen marketed for the use of Foster in the treatment of asthma. This study comprised a total of 11 visits and a follow-up phone call: * A Pre-Screening visit (Visit 0 \[V0\]), carried out in order to fully explain the study to potential patients, to obtain their written informed consent and to instruct them on Screening visit procedures (such as fasting and medication restrictions). This visit occurred one week maximum prior to the Screening visit.A Screening visit (V1), carried out to establish the eligibility of patients for inclusion in the study and to instruct them on study procedures (such as fasting, medication restrictions, recognition of asthma exacerbations and use of the pMDI device, of the e-diary and of the e-peakflow meter). This visit was followed by a 2-week (±2 days) open-label run-in period on Foster. A 2-week run-in period on Foster prior to randomisation was deemed sufficient to standardise the patient population on the same concomitant treatment without leading to a deterioration of the disease. * An investigational phase, which lasted approximately 21 weeks and comprised 3 treatment periods (Period \[P\] 1, P2 and P3) of 6 weeks each (±2 days) separated by an open-label wash-out period of 1 week on Foster. Each 6-week treatment period allowed for adequate assessment of efficacy variables. Each treatment period comprised 3 visits (Day \[D\] 1, Day 14 and Day 42) during which efficacy and safety assessments were performed. Patients were also re-instructed on study procedures. Patients underwent the following visits: * A Randomisation visit at Visit P1D1 (V2); * Eight subsequent visits: Day 1 of the second and third treatment period (day of the first dosing): Visit P2D1 (V5) and Visit P3D1 (V8); Day 14 of each treatment period: Visit P1D14 (V3), Visit P2D14 (V6) and Visit P3D14 (V9); Day 42 of each treatment period (day of last dosing): Visit P1D42 (V4), Visit P2D42 (V7) and Visit P3D42 (V10). These visits were followed by a 1-week wash-out period with Foster. • A safety follow-up phone call was made one week after Visit P3D42 (V10) (or 1 week after the last dose intake and/or last visit in case of premature discontinuation of the patient) to check any unresolved or new adverse events (AEs)/serious adverse events (SAEs).

Conditions

• Asthma

Interventions

Type	Name	Description
DRUG	CHF 5259 plus Foster 100/6 µg	Comparison of different doses of CHF 5259 (on top of Foster 100/6 µg) versus Foster 100/6 µg over a treatment period of 6 weeks. Each subject was allocated to 3 out of the 4 possible treatments performed in sequence during a cross over design (incomplete block). All treatment medications were administered via pMDI. During each treatment period, treatment was administered as four puffs BID (morning and evening) approximately at the same time of the day.
DRUG	Foster 100/6 µg (four puffs BID)	Active comparator Treatment D = Foster 400 μg/24 μg (daily dose): patients followed a schedule of two puffs of CHF 5259 placebo BID and two puffs of Foster 100/6 μg BID. All treatment medications were administered via pMDI. During each of the 3 treatment periods, treatment was administered as four puffs BID (morning and evening) approximately at the same time of the day.

Timeline

• Start date: 2014-04-11
• Primary completion: 2015-03-08
• Completion: 2015-03-08
• First posted: 2014-05-01
• Last updated: 2026-04-14
• Results posted: 2026-04-14

Locations

44 sites across 6 countries: Bulgaria, Germany, Hungary, Italy, Poland, United Kingdom