Triple in Asthma Dose Finding

NCT02127866 | Completed Phase 2 Results

• 2 other identifiers: CCD-1206-PR-00882013-003043-36
• Study Type: interventional
• Target: 211
• Locations: 6 countries
• Sites: 44

Brief 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.

Conditions

Asthma

Keywords

Asthma, anticholinergics; CHF5259 pMDI; glycopirrolate; Asthma, Foster; Asthma, ICS plus LABA

Outcome Measures

Primary Outcomes (1)

• FEV1 AUC0-12h Normalised by Time on Day 42

  FEV1 = Forced expiratory volume in the first second. AUC0-12h = area under the curve between the time 0 and 12 hours. Post-dose FEV1 on Day 42 of each treatment period was recorded at 15'; 30'; 45'; 1h; 2h; 3h, 4h,6h,8h, 11h30 and 12h post-study drug intake. The baseline FEV1 was the average FEV1 recorded on Day 1 at 45 and 10 minutes prior to study intake.

  Day 42

Secondary Outcomes (28)

• Change From Baseline in Peak FEV1 on Day 42

  Day 42

• FEV1 AUC0-3h Normalised by Time on Day 1

  Day 1

• FEV1 AUC0-3h Normalised by Time on Day 42

  Day 42

• Change From Baseline in FEV1 Pre-dose on Day 14

  Day 14

• Change From Baseline in FEV1 Pre-dose on Day 42

  Day 42

Study Arms (4)

Sequence A-C-B

EXPERIMENTAL

Each subject was allocated to 3 out of the 4 possible treatments performed in sequence during a cross over design (incomplete block). Treatment A (CHF 5259 12.5 μg + Foster 100/6 μg): total daily dose of GB 25 μg + BDP 400 μg/FF 24 μg; patients followed a schedule of one puff of CHF 5259 12.5 μg BID, one puff of CHF 5259 placebo BID, two puffs of Foster 100/6 μg BID. Treatment C (CHF 5259 25 μg + Foster 100/6 μg): total daily dose of GB 100 μg + BDP 400 μg/FF 24 μg; Patients followed a schedule of two puffs of CHF 5259 25 μg BID and two puffs of Foster 100/6 μg BID. Treatment B (CHF 5259 25 μg + Foster 100/6 μg): total daily dose of GB 50 μg + BDP 400 μg/FF 24 μg; patients followed a schedule of one puff of CHF 5259 25 μg BID, one puff of CHF 5259 placebo BID, two puffs of Foster 100/6 μg BID.

Drug: CHF 5259 plus Foster 100/6 µg; Drug: Foster 100/6 µg (four puffs BID)

Sequence B-D-C

EXPERIMENTAL

Each subject was allocated to 3 out of the 4 possible treatments performed in sequence during a cross over design (incomplete block). Treatment B (CHF 5259 25 μg + Foster 100/6 μg): total daily dose of GB 50 μg + BDP 400 μg/FF 24 μg; patients followed a schedule of one puff of CHF 5259 25 μg BID, one puff of CHF 5259 placebo BID, two puffs of Foster 100/6 μg BID. 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. Treatment C (CHF 5259 25 μg + Foster 100/6 μg): total daily dose of GB 100 μg + BDP 400 μg/FF 24 μg; Patients followed a schedule of two puffs of CHF 5259 25 μg BID and two puffs of Foster 100/6 μg BID.

Drug: CHF 5259 plus Foster 100/6 µg; Drug: Foster 100/6 µg (four puffs BID)

Sequence C-A-D

EXPERIMENTAL

Each subject was allocated to 3 out of the 4 possible treatments performed in sequence during a cross over design (incomplete block). Treatment C (CHF 5259 25 μg + Foster 100/6 μg): total daily dose of GB 100 μg + BDP 400 μg/FF 24 μg; Patients followed a schedule of two puffs of CHF 5259 25 μg BID and two puffs of Foster 100/6 μg BID. Treatment A (CHF 5259 12.5 μg + Foster 100/6 μg): total daily dose of GB 25 μg + BDP 400 μg/FF 24 μg; patients followed a schedule of one puff of CHF 5259 12.5 μg BID, one puff of CHF 5259 placebo BID, two puffs of Foster 100/6 μg BID. 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.

Drug: CHF 5259 plus Foster 100/6 µg; Drug: Foster 100/6 µg (four puffs BID)

Sequence B-D-A

EXPERIMENTAL

Each subject was allocated to 3 out of the 4 possible treatments performed in sequence during a cross over design (incomplete block). Treatment B (CHF 5259 25 μg + Foster 100/6 μg): total daily dose of GB 50 μg + BDP 400 μg/FF 24 μg; patients followed a schedule of one puff of CHF 5259 25 μg BID, one puff of CHF 5259 placebo BID, two puffs of Foster 100/6 μg BID. 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. Treatment A (CHF 5259 12.5 μg + Foster 100/6 μg): total daily dose of GB 25 μg + BDP 400 μg/FF 24 μg; patients followed a schedule of one puff of CHF 5259 12.5 μg BID, one puff of CHF 5259 placebo BID, two puffs of Foster 100/6 μg BID.

Drug: CHF 5259 plus Foster 100/6 µg; Drug: Foster 100/6 µg (four puffs BID)

Interventions

CHF 5259 plus Foster 100/6 µg DRUG

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.

Also known as: glycopyrrolate + beclometasone/formoterol

Sequence A-C-B; Sequence B-D-A; Sequence B-D-C; Sequence C-A-D

Foster 100/6 µg (four puffs BID) DRUG

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.

Also known as: beclometasone dipropionate/formoterol

Sequence A-C-B; Sequence B-D-A; Sequence B-D-C; Sequence C-A-D

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient's written informed consent obtained prior to any study-related procedures;
• Male or female patients aged ≥18;
• Patients with uncontrolled asthma on medium doses of ICS+LABA (\>500-1000 μg daily dose BDP non-extrafine or equivalent plus formoterol 24 μg or salmeterol 100 μg) at a stable dose for at least 4 weeks prior to Screening; Drug\* Medium daily dose BDP non-extrafine \>500 - 1000 μg BDP extrafine \>250 - 500 μg Budesonide \>400 - 800 μg Ciclesonide \>160 - 320 μg Fluticasone \>250 - 500 μg Mometasone ≥400 μg - \< 800 μg
• \*In this table (adapted from GINA 2012) the recommendations for doses of inhaled glucocorticosteroids are given as "μg/day budesonide or equivalent"
• Patients with a pre-bronchodilator FEV1 ≥40% and \<80% of their predicted normal value, after appropriate wash-out from bronchodilators, at Screening and at the end of the run-in period;
• Patients with a positive response to the reversibility test at Screening within 30 minutes after administration of 400 μg of salbutamol pMDI, defined as ΔFEV1 ≥12% and ≥200 mL over Baseline; Note: In case the reversibility threshold is not met, the test can be performed once before randomisation.
• Patients with uncontrolled asthma evidenced by a score at the Asthma Control Questionnaire® (ACQ) ≥1.5 (criterion must be met at Screening and at the end of the run-in period);
• Patients with a co-operative attitude and ability to be trained to correctly use the pMDI.

You may not qualify if:

• Patients were not enrolled if one or more of the following criteria were present:
• Inability to carry out pulmonary lung function testing, to comply with study procedures or with study treatment intake;
• History of near fatal asthma or of a past hospitalisation for asthma in intensive care unit or of frequent exacerbations which, in the judgement of the Investigator, may have placed the patient at undue risk;
• Hospitalisation, emergency room admission or use of systemic corticosteroids for asthma exacerbation in the 4 weeks prior to Screening visit and during the run-in period;
• Lower respiratory tract infection in the 4 weeks before the Screening visit or during the run-in period;
• Patients who were in therapy for gastroesophageal reflux disease (GERD) and/or patients with a medical history of GERD that led to asthma symptoms;
• Patients with a seasonal worsening of asthma and who were not able to complete the study outside the relevant allergen season;
• History of cystic fibrosis, bronchiectasis or alpha-1 antitrypsin deficiency, or any other significant lung disease which may have interfered with data evaluation;
• Patients who suffered from COPD as defined by the current Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines;
• Current smokers or ex-smokers with total cumulative exposure equal or more than 10 pack-years and /or having stopped smoking one year or less prior to Screening visit;
• Any change in dose, schedule, formulation of ICS + LABAs in the 4 weeks prior to Screening visit;
• Patients used to be or treated with inhaled long-acting antimuscarinic drugs;
• Patients treated with anti-IgE antibodies;
• Pregnant or lactating women and all women physiologically capable of becoming pregnant (i.e. women of childbearing potential) UNLESS were using one or more of the following reliable methods of contraception:
• Placement of an intra uterine device (IUD) or intra uterine system (IUS);

Sponsors & Collaborators

• Chiesi Farmaceutici S.p.A.: lead

Study Sites (44)

Chiesi Clinical Trial Site 0105

Dupnitsa, 2600, Bulgaria

Location

Chiesi Clinical Trial Site 0101

Rousse, 7002, Bulgaria

Location

Chiesi Clinical Trial Site 0106

Sevlievo, 5400, Bulgaria

Location

Chiesi Clinical Trial Site 0107

Sofia, 1233, Bulgaria

Location

Chiesi Clinical Trial Site 0108

Sofia, 1336, Bulgaria

Location

Chiesi Clinical Trial Site 0102

Sofia, 1407, Bulgaria

Location

Chiesi Clinical Trial Site 0110

Sofia, 1431, Bulgaria

Location

Chiesi Clinical Trial Site 0109

Sofia, 1432, Bulgaria

Location

Chiesi Clinical Trial Site 0103

Stara Zagora, 6003, Bulgaria

Location

Chiesi Clinical Trial Site 0104

Troyan Municipality, 5600, Bulgaria

Location

Chiesi Clinical Trial Site 0208

Berlin, 10787, Germany

Location

Chiesi Clinical Trial Site 0207

Berlin, 12165, Germany

Location

Chiesi Clinical Trial Site 0206

Großhansdorf, 22927, Germany

Location

Chiesi Clinical Trial Site 0201

Leipzig, 04357, Germany

Location

Chiesi Clinical Trial Site 0203

Lübeck, 23552, Germany

Location

Chiesi Clinical Trial Site 0202

Magdeburg, 39112, Germany

Location

Chiesi Clinical Trial Site 0204

Radebeul, 01445, Germany

Location

Chiesi Clinical Trial Site 0210

Witten, 58452, Germany

Location

Chiesi Clinical Trial Site 0307

Balassagyarmat, 2660, Hungary

Location

Chiesi Clinical Trial Site 0302

Budapest, 1122, Hungary

Location

Chiesi Clinical Trial Site 0304

Deszk, 6772, Hungary

Location

Chiesi Clinical Trial Site 0305

Gödöllő, 2100, Hungary

Location

Chiesi Clinical Trial Site 0303

Komárom, 2900, Hungary

Location

Chiesi Clinical Trial Site 0301

Siófok, 8600, Hungary

Location

Chiesi Clinical Trial Site 0306

Szarvas, 5540, Hungary

Location

Chiesi Clinical Trial Site 0403

Brescia, 25123, Italy

Location

Chiesi Clinical Trial Site 0402

Parma, 43125, Italy

Location

Chiesi Clinical Trial Site 0401

Pisa, 56124, Italy

Location

Chiesi Clinical Trial Site 0408

Trieste, 34149, Italy

Location

Chiesi Clinical Trial Site 0404

Verona, 37134, Italy

Location

Chiesi Clinical Trial Site 0510

Bialystok, 15-430, Poland

Location

Chiesi Clinical Trial Site 0507

Gdansk, 80-847, Poland

Location

Chiesi Clinical Trial Site 0502

Giżycko, 11-500, Poland

Location

Chiesi Clinical Trial Site 0511

Krakow, 31-637, Poland

Location

Chiesi Clinical Trial Site 0505

Lodz, 90-141, Poland

Location

Chiesi Clinical Trial Site 0509

Lodz, 90-153, Poland

Location

Chiesi Clinical Trial Site 0512

Lublin, 20-718, Poland

Location

Chiesi Clinical Trial Site 0503

Ostróda, 14-100, Poland

Location

Chiesi Clinical Trial Site 0501

Oświęcim, 32-600, Poland

Location

Chiesi Clinical Trial Site 0506

Proszowice, 32-100, Poland

Location

Chiesi Clinical Trial Site 0508

Rzeszów, 35-241, Poland

Location

Chiesi Clinical Trial Site 0504

Wroclaw, 51-162, Poland

Location

Chiesi Clinical Trial Site 0602

London, W1G 8HU, United Kingdom

Location

Chiesi Clinical Trial Site 0601

Manchester, M23 9QZ, United Kingdom

Location

Related Links

• Study Record on EU Clinical Trials Register including results

MeSH Terms

Conditions

Asthma

Interventions

Foster Home Care; Glycopyrrolate; Beclomethasone; Formoterol Fumarate

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Intervention Hierarchy (Ancestors)

Patient Care; Therapeutics; Community Health Services; Health Services; Health Care Facilities Workforce and Services; Quaternary Ammonium Compounds; Amines; Organic Chemicals; Onium Compounds; Pyrrolidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Chlorinated; Ethanolamines; Amino Alcohols; Alcohols

Results Point of Contact

• Title: Clinical Trial INFO
• Organization: Chiesi Farmaceutici S.p.A.

clinicaltrials_info@chiesi.com

+39 0521 2791

Study Officials

• Dave Singh, MD

  University Hospital of South Manchester, MANCHESTER M23 9 QZ, UK

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 9, 2014
• First Posted: May 1, 2014
• Study Start: April 11, 2014
• Primary Completion: March 8, 2015
• Study Completion: March 8, 2015
• Last Updated: April 14, 2026
• Results First Posted: April 14, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Access Criteria: Chiesi access criteria and complete process for clinical data sharing is available on the Chiesi Group website.

Locations

BU (10); GB (2); HU (7); IT (5); PL (12); DE (8)