Chronic Obstructive Pulmonary Disease (COPD)Phase 3TRILOGYNCT01917331
Efficacy of Fixed Combination of Beclometasone + Formoterol + Glycopyrrolate Versus Foster® in COPD
A Phase 3 study testing Beclometasone/Formoterol/Glycopyrrolate and Beclometasone/Formoterol in people with Chronic Obstructive Pulmonary Disease (COPD), run by Chiesi Farmaceutici S.p.A. at 1 site in Hungary.
Trial summary
Randomized,double-blind,multicenter,multinational,parallel-group,Phase III study to demonstrate the superiority of the triple fixed combination of beclometasone + formoterol + glycopyrrolate (BDP/FF/GB) administered via pressurised metered dose inhaler (pMDI) over the equivalent dose of Foster® (beclometasone… Read more about this study
- Who is it for?
- Ages 40 years and older
- Conditions the study is for
- Chronic Obstructive Pulmonary Disease (COPD)
- What is being tested?
- Beclometasone/Formoterol/Glycopyrrolate and Beclometasone/Formoterol
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,368 participants
- Where
- 1 siteHungary
- Study dates
- 21 Mar 2014to 14 Jan 2016
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female adults aged ≥ 40 years with a diagnosis of COPD
- Current smokers or ex-smokers
- A post-bronchodilator Forced Expiratory Volume in the 1st Second (FEV1) < 50% of the predicted normal value and a post- bronchodilator FEV1/ Forced Vital Capacity (FVC) < 0.7
- At least one exacerbation in the 12 months preceding the screening visit
Who cannot join
- Pregnant or lactating women
- Diagnosis of asthma or history of allergic rhinitis or atopy
- Patients treated with non-cardioselective β-blockers in the month preceding the screening visit
- Patients treated for exacerbations in the 4 weeks prior to screening visit
- Patients treated with long-acting antihistamines unless taken at stable regimen at least 2 months prior to screening and to be maintained constant during the study or if taken as PRN
- Patients requiring long term (at least 12 hours daily) oxygen therapy for chronic hypoxemia
- Known respiratory disorders other than COPD
- Patients who have clinically significant cardiovascular condition
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase 3 Randomised Double Blind Randomised Parallel Multinational Trial Comparing a Fixed Combination of Beclometasone + Formoterol + Glycopyrrolate to Foster® in Patients With Chronic Obstructive Pulmonary Disease
Randomized,double-blind,multicenter,multinational,parallel-group,Phase III study to demonstrate the superiority of the triple fixed combination of beclometasone + formoterol + glycopyrrolate (BDP/FF/GB) administered via pressurised metered dose inhaler (pMDI) over the equivalent dose of Foster® (beclometasone dipropionate (BDP) / formoterol fumarate (FF), in patients diagnosed with chronic obstructive pulmonary disease (COPD) after 52 weeks of treatment.
Read the detailed description
This 52-week randomised 2 parallel groups study evaluated the superiority of fixed triple therapy with Inhaled Corticosteroid (ICS) / Long-Acting β2-Agonist (LABA) / Long-Acting Muscarinic Antagonist (LAMA) compared with ICS/LABA in patients with severe to very severe diagnosed of COPD.
Patients' eligibility was checked during the screening visit including the review of medical history, spirometry assessments, routine labs, physical examination, 12-lead electrocardiogram (ECG), vital signs measurement, prior to entering a 2-week open-label run-in period with BDP/FF to establish a baseline.
After the run-in period, eligible patients were randomised, to either fixed triple therapy BDP/FF/GB or BDP/FF treatment group. During the 52-week treatment period, patients who completed the study did have 5 subsequent visits post randomisation scheduled respectively after 4, 12, 26, 40, and 52 weeks of treatment. During these visits, pre-dose and post-dose spirometry, 12-lead ECG, vital signs, and dyspnoea assessments were performed. Rescue medication use, compliance with the treatment, and EXACT-PRO questionnaire [EXAcerbations of Chronic Obstructive Pulmonary Disease Tool (EXACT): a patient-reported outcome (PRO)] were recorded daily (via an electronic diary) during the run-in and randomised treatment periods.
For pharmacovigilance purposes, adverse events (AE) were recorded from the time of patient informed consent signature until subject's study participation ended (Week 52 or early discontinuation).
- Being tested
- Beclometasone/Formoterol/Glycopyrrolate, Beclometasone/Formoterol
- Keywords
- spirometry, severe COPD, lung disease, fixed combination treatment, COPD, Chronic Obstructive Pulmonary Disease
- Medical subject headings
- Pulmonary Disease, Chronic Obstructive, Lung Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Beclometasone/Formoterol/GlycopyrrolateDrug
Also called BDP/FF/GB or CHF 5993 pMDI 100/6/12.5 µg
Active drug tested
Beclometasone/FormoterolDrug
Also called Foster® or CHF 1535 pMDI 100/6 µg
Active comparator
| Study group | Role | What they receive |
|---|---|---|
| Beclometasone/Formoterol/Glycopyrrolate | Experimental | CHF 5993 pMDI 100/6/12.5 µg 2 inhalations bid Receives: Drug: Beclometasone/Formoterol/Glycopyrrolate |
| Beclometasone/Formoterol | Active comparator | Foster® 100/6 µg 2 inhalations bid Receives: Drug: Beclometasone/Formoterol |
What is being measured
The primary outcome is the main question the study is designed to answer.
1_Change From Baseline in Pre-dose Morning Forced Expiratory Volume in the 1st Second (FEV1) -- at Week 26
Changes from baseline in pre-dose morning FEV1 to visit at Week 26.
FEV1=Forced expiratory volume in the 1st second. It is the volume of air that can be forced out in one second after taking a deep breath.
Measured: Baseline (Week 0), Week 26.
2_Change From Baseline in 2-hour Post-dose FEV1 -- at Week 26
Change from baseline in 2-hour post-dose FEV1, at Week 26.
FEV1=Forced expiratory volume in the 1st second. It is the volume of air that can be forced out in one second after taking a deep breath.
Measured: Baseline (Week 0) to 2-hour post-dose at Week 26.
3_Transition Dyspnoea Index (TDI) Focal Score -- at Week 26
Transition Dyspnoea Index (TDI) focal score is a symptom-based variable tool, used to assess breathlessness and the impact of intervention. BDI/TDI is a clinical rating method based on a validated tool that measures the impact of dyspnoea based on 3 domains: functional impairment, magnitude of task, and magnitude of effort. BDI focal score is the baseline value from which TDI focal score is assessed.
BDI scores range from 0 (very severe impairment) to 4 (no impairment) for each domain with the baseline focal score consisting of the sum of each domain (i.e. from 0 to 12). Change from baseline in dyspnoea severity was measured using the TDI. TDI score ranges from -3 (major deterioration) to +3 (major improvement) for each domain, with the TDI focal score consisting of the sum of each domain (i.e. from -9 to +9). A higher total score indicates improvement, while a lower or negative score indicates worsening symptoms.
BDI=Baseline Dyspnoea Index TDI=Transition Dyspnoea Index
Measured: Baseline (Week 0), Week 26.
Secondary outcomes (16)
4_Change From Baseline in Pre-dose Morning FEV1 -- at All the Other Clinic Visits
Change from baseline in pre-dose morning FEV1, at all the other clinic visits.
Please note: results at visit Week 26, are presented as the primary outcome measure #1 for this study.
FEV1=Forced expiratory volume in the 1st second. It is the volume of air that can be forced out in one second after taking a deep breath.
Measured: Baseline (Week 0), Week 4. 12, 40, 52.
5_Change From Baseline to the Average in Pre-dose Morning FEV1 -- Over the Treatment Period
Changes from baseline for the average in pre-dose morning FEV1 over the treatment period.
FEV1=Forced expiratory volume in the 1st second. It is the volume of air that can be forced out in one second after taking a deep breath.
Measured: Baseline (Week 0), Week 4, 12, 26, 40, 52.
6_Number of Participants Defined as Responders Wrt. to FEV1 -- Change From Baseline in Pre-dose Morning FEV1 ≥100 mL -- at Week 26 and Week 52
Number of participants defined as responders wrt. to FEV1 -- at Week 26 and Week 52.
FEV1 response was defined as a change from baseline in pre-dose morning FEV1 of ≥100 mL. If the change from baseline was <100 mL, the patient was classified as a non-responder in terms of FEV1. Subjects with missing pre-dose morning FEV1 value at the pre-specified tested time points were also classified as non-responders.
FEV1=Forced expiratory volume in the 1st second. It is the volume of air that can be forced out in one second after taking a deep breath.
Measured: Baseline (Week 0), Week 26, Week 52.
7_Change From Baseline in 2-hour Post-dose of FEV1 -- at All the Other Clinic Visits
Change from baseline in 2-hour post-dose of FEV1, at all the other clinic visits.
Please note: a) results at visit Week 26, are presented as the primary outcome measure #2 for this study; b) for Week 0, the measurement shown in the results table below was made 2 h after the baseline measurement i.e. pre-treatment at study baseline.
FEV1=Forced expiratory volume in the 1st second. It is the volume of air that can be forced out in one second after taking a deep breath.
Measured: Baseline (Week 0), Week 4, 12, 40, 52.
8_Change From Pre-dose to 2-hour Post-dose FEV1 -- at All Study Visits
Change from pre-dose to 2-hour post-dose value of FEV1, at study visits on Week 4, 12, 26, 40, and 52.
FEV1=Forced expiratory volume in the 1st second. It is the volume of air that can be forced out in one second after taking a deep breath.
Measured: Week 4, 12, 26, 40, 52.
9_Transition Dyspnoea Index (TDI) Focal Score -- at All Study Visits
TDI focal score is a symptom-based tool, used to assess breathlessness and the impact of intervention.
BDI/TDI is a clinical rating method based on a validated tool that measures the impact of dyspnoea on 3 domains: functional impairment, magnitude of task, and magnitude of effort.
TDI tool and its scoring system are defined in the outcome measure #3 of this PRS study entry.
Please note: Results at Week 26, are presented as the primary outcome measure #3 for this PRS study entry.
BDI=Baseline Dyspnoea Index TDI=Transition Dyspnoea Index
Measured: Baseline (Week 0), Week 4, 12, 40, 52.
10_Number of Participants With Transition Dyspnoea Index (TDI) Response (Focal Score ≥1) -- at Week 26 and Week 52
Number of participants with transition dyspnoea index (TDI) response (focal score ≥1) -- at Week 26 and Week 52.
TDI tool and its scoring system are defined in the outcome measure #3 of this PRS study entry.
TDI response was defined as a TDI focal score of ≥1. If the TDI focal score was <1, the patient was classified as a non-responder in terms of TDI. Patients with missing TDI focal score at the pre-specified tested time points were also classified as non-responders.
Measured: Week 26, Week 52.
11a_Change From Baseline in Saint George's Respiratory Questionnaire (SGRQ) -- at All Study Visits: Total Score
Change from baseline in Saint George's respiratory questionnaire (SGRQ) Total score.
SGRQ is a 76-item questionnaire developed to measure health in chronic airflow limitation. SGRQ consists of scores from three component that are used to calculate the total score: Symptoms, Activity, and Impacts on daily life. SGRQ questionnaire was completed by the patient at all study visits (Week 0 baseline, and Week 4, 12, 26, 40, 52).
The Total score range is from 0 to 100 (0=Best, 100=Worst); lower scores correspond to better health.
SGRQ questionnaire was completed by the patient at all study visits (Week 0 baseline, 4, 12, 26, 40, 52).
Measured: Baseline (Week 0), Week 4, 12, 26, 40, 52.
11b_Change From Baseline in Saint George's Respiratory Questionnaire (SGRQ) -- at All Study Visits: Symptoms Score
Change from baseline in Saint George's respiratory questionnaire (SGRQ) -- Symptoms Score.
SGRQ is a questionnaire developed to measure health in chronic airflow limitation.
SGRQ questionnaire was completed by the patient at all study visits (Week 0 baseline, 4, 12, 26, 40, 52).
Result show the Saint George's Respiratory Questionnaire (SGRQ) as change from baseline for the domain Symptoms.
The Symptoms score is calculated on a scale of 0 to 100. A score of 0 indicates no impairment (best health); a score of 100 indicates the worst possible health status.
Measured: Baseline (Week 0), Week 4, 12, 26, 40, 52.
11c_Change From Baseline in Saint George's Respiratory Questionnaire (SGRQ) -- at All Study Visits: Impacts Score
Saint George's respiratory questionnaire (SGRQ) -- Impacts Score.
SGRQ is a questionnaire developed to measure health in chronic airflow limitation.
SGRQ questionnaire was completed by the patient at all study visits (Week 0 baseline, 4, 12, 26, 40, 52).
Result show the Saint George's Respiratory Questionnaire (SGRQ) as change from baseline for the domain Impacts.
The Impact score is calculated on a scale of 0 to 100. A score of 0 indicates no impairment (best health); a score of 100 indicates the worst possible health status.
Measured: Baseline (Week 0), Week 4, 12, 26, 40, 52.
11d_Change From Baseline in Saint George's Respiratory Questionnaire (SGRQ) -- at All Study Visits: Activity Score
Saint George's respiratory questionnaire (SGRQ) -- Activity score.
SGRQ is a questionnaire developed to measure health in chronic airflow limitation.
SGRQ questionnaire was completed by the patient at all study visits (Week 0 baseline, 4, 12, 26, 40, 52).
Result show the Saint George's Respiratory Questionnaire (SGRQ) as change from baseline for the domain Activity.
The Activity score is calculated on a scale of 0 to 100. A score of 0 indicates no impairment (best health); a score of 100 indicates the worst possible health status.
Measured: Baseline (Week 0), Week 4, 12, 26, 40, 52.
12_Number of Participants With Saint George's Respiratory Questionnaire (SGRQ) Response (Change From Baseline in Total Score ≤-4) -- at Week 26 and Week 52
Number of participants with Saint George's Respiratory Questionnaire (SGRQ) response, defined as a change from baseline in SGRQ total score ≤ -4, at Week 26 and Week 52.
If the change from baseline was > -4, the patient was assessed as a non-responder in terms of SGRQ.
Patients with missing change from baseline at the pre-specified tested time points were also classified as non-responders.
Results shown represent the number of responder participants in terms of SGRQ, for the comparison of CHF 5993 pMDI versus CHF 1535 pMDI.
Measured: Baseline (Week 0), Week 26, Week 52.
13a_Change From Baseline for Percentage of Days Without Intake of Rescue Medication -- Over Entire Treatment Period (52 Weeks of Treatment)
Days WITHOUT intake of rescue medication.
Change from baseline to each inter-visit period and for the entire treatment period (Week 1-52) in the percentage of days without intake of rescue medication.
Measured: Baseline (Week 0) to Week 4, 12, 26, 40, 52.
13b_Change From Baseline for the Average Use of Rescue Medication -- Over Entire Treatment Period (52 Weeks of Treatment)
Average use of rescue medication, over the entire treatment period (52 Weeks of treatment).
Change from baseline to each inter-visit period and for the entire treatment period (Week 1-52) in the average use of rescue medication (number of puffs/day).
Measured: Baseline (Week 0) to Week 4, 12, 26, 40, 52.
14_Rate of Moderate and Severe Chronic Obstructive Pulmonary Disease (COPD) Exacerbation Rate -- Over Entire Treatment Period (52 Weeks of Treatment)
Rate of moderate AND severe COPD exacerbations over the entire treatment period of treatment (52 weeks).
COPD=Chronic obstructive pulmonary disease
Measured: Baseline (Week 0) to Week 52 (entire treatment period).
15_First Occurrence of All Moderate or Severe Chronic Obstructive Pulmonary Disease (COPD) Exacerbation
First occurrence of at least 1 moderate OR severe COPD exacerbation.
First occurrence was analysed by Cox regression as time to first exacerbation and reported as hazard ratio.
COPD=Chronic obstructive pulmonary disease
Measured: Baseline (Week 0), Week 52.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Aug 2013 (estimated)
- Study start21 Mar 2014
- Primary completion14 Jan 2016
- Study completion14 Jan 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Chronic Obstructive Pulmonary Disease (COPD)Studies of the same condition, open and under way.
- More trials run by Chiesi Farmaceutici S.p.A.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 1,368 participants (actual)
Sponsor and investigators
- Lead sponsor
- Chiesi Farmaceutici S.p.A.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Dave SINGH, MD, Principal investigator, University Hospital of South Manchester, MANCHESTER M23 9 QZ, UK
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01917331
- Sponsor's protocol ID
- CCD-1207-PR-0091
- Other IDs
- 2013-001057-27
- Acronym
- TRILOGY
- Status last verified
- Jun 2026
- First submitted
- 5 Aug 2013
- Last updated
- 20 Jul 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- Yes: Chiesi clinical data sharing scope, process and data access criteria is available on the Chiesi Group website.
Publications
Vanfleteren L, Fabbri LM, Papi A, Petruzzelli S, Celli B. Triple therapy (ICS/LABA/LAMA) in COPD: time for a reappraisal. Int J Chron Obstruct Pulmon Dis. 2018 Dec 12;13:3971-3981. doi: 10.2147/COPD.S185975. eCollection 2018.
PubMed 30587953Singh D, Fabbri LM, Vezzoli S, Petruzzelli S, Papi A. Extrafine triple therapy delays COPD clinically important deterioration vs ICS/LABA, LAMA, or LABA/LAMA. Int J Chron Obstruct Pulmon Dis. 2019 Feb 28;14:531-546. doi: 10.2147/COPD.S196383. eCollection 2019.
PubMed 30880943Singh D, Fabbri LM, Corradi M, Georges G, Guasconi A, Vezzoli S, Petruzzelli S, Papi A. Extrafine triple therapy in patients with symptomatic COPD and history of one moderate exacerbation. Eur Respir J. 2019 May 18;53(5):1900235. doi: 10.1183/13993003.00235-2019. Print 2019 May.
PubMed 30792343Singh D, Papi A, Corradi M, Pavlisova I, Montagna I, Francisco C, Cohuet G, Vezzoli S, Scuri M, Vestbo J. Single inhaler triple therapy versus inhaled corticosteroid plus long-acting beta2-agonist therapy for chronic obstructive pulmonary disease (TRILOGY): a double-blind, parallel group, randomised controlled trial. Lancet. 2016 Sep 3;388(10048):963-73. doi: 10.1016/S0140-6736(16)31354-X. Epub 2016 Sep 1.
PubMed 27598678