A Study Comparing Efficacy, Safety and Tolerability of the Fixed Dose Triple Combination CHF 5993 With the Fixed Dose Dual Combination CHF 1535 in Subjects With COPD

COPD Clinical Trial

— TRITON  

Official title:

A Phase III, 52-week, Multinational, Multicenter, Randomized, Double-blind, 2-arm Parallel Group Study Comparing Efficacy, Safety and Tolerability of the Fixed Dose Triple Combination of Beclomethasone Dipropionate Plus Formoterol Fumarate Plus Glycopyrronium Bromide (CHF 5993) With the Fixed Dose Dual Combination of Beclomethasone Dipropionate Plus Formoterol Fumarate (CHF 1535), Both Administered Via pMDI in Subjects With Chronic Obstructive Pulmonary Disease (COPD)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04320342
• Other study ID #: CLI-05993AA3-06
• Secondary ID: 2020-002389-16
• Status: Recruiting
• Phase: Phase 3
• Start date: April 28, 2022
• Est. completion date: December 2024

Study information

• Verified date: April 2024
• Source: Chiesi Farmaceutici S.p.A.
• Contact: Chiesi Clinical Trial Info
• Phone: +39 0521 2791
• Email: clinicaltrials_info[@]chiesi.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to compare CHF 5993 with CHF 1535 in improving lung function, reducing moderate and severe COPD exacerbations, and other clinical efficacy and safety outcomes in the target subject population.

Description:

This is a phase III, multinational, multicenter, randomized, double-blind active controlled 2-arm parallel group study to compare efficacy, safety, and tolerability of CHF 5993 pMDI with CHF 1535 pMDI with respect to lung function, incidence of moderate and severe COPD exacerbations, and other clinical efficacy and safety outcomes. After screening, eligible subjects will enter 2-week run-in period using their regular COPD maintenance therapies after which they will be randomized to one of 2 study treatment groups. Following randomization, subjects will be assessed after 4 weeks then at 6-week intervals thereafter for a period of 52 weeks. A follow-up safety phone call will be performed a week after the last clinic visit. A subset of subjects consenting to participate in the pharmacokinetic substudy will undergo additional assessments (totaling 3 visits) during the scheduled study visits. During the study, daily symptoms, rescue medication use and compliance with the study drug will be recorded via a subject electronic diary. Subject concomitant medications, adverse events, and healthcare resource utilization will be assessed and recorded throughout the study. At intermittent study visits, subjects will undergo vital signs examinations including weight, spirometry measurements, and 12-lead ECG. Symptoms and COPD health status will be assessed through disease specific questionnaires. Routine hematology, blood chemistry, and serum pregnancy testing will be performed before enrollment and at end of study.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 2934
• Est. completion date: December 2024
• Est. primary completion date: December 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years and older

Eligibility

Inclusion Criteria:

• Signed and dated written informed consent must be obtained prior to initiating any study-related procedures
• Outpatient
• Male or female subjects aged =40 years
• Female subjects:

1. WOCBP fulfilling one of the following criteria: i. WOCBP with fertile male partners: they and/or their partner must be willing to use a highly effective birth control method from the signing of the informed consent form and until the follow-up contact or ii. WOCBP with non-fertile male partners (contraception is not required in this case).

2. Female subjects of non-childbearing potential defined as physiologically incapable of becoming pregnant (i.e. post-menopausal or permanently sterile as per definitions given in Appendix 5). Tubal ligation or partial surgical interventions are not acceptable. If indicated, as per investigator's request, post-menopausal status may be confirmed by follicle-stimulating hormone levels (according to local laboratory ranges)

• COPD diagnosis for at least 12 months before the screening visit in accordance with the definition by the GOLD 2020 Report
• Current or ex-smokers who quit smoking at least 6 months prior to screening with a smoking history of at least 10 pack-years [pack-years = (number of cigarettes per day x number of years)/20]
• COPD Assessment Test (CAT) score =10
• A pre- and post-bronchodilator FEV1/FVC ratio <0.70 at screening
• A post-bronchodilator FEV1 <50% predicted normal at screening and a documented history of =1 moderate or severe COPD exacerbation in the previous 12 months OR a post-bronchodilator FEV1 =50% and <80% of predicted normal at screening and a documented history of =2 moderate COPD exacerbations or =1 severe COPD exacerbation in the previous 12 months
• Subjects receiving daily inhaled maintenance therapy for their COPD, at a stable dose for at least 3 months prior to the screening and randomization visits
• Documentation (including imagery and report) of chest x-ray (CXR) or CT scan performed within 6 months prior to the screening visit, without evidence of significant abnormalities (other than those related to the presence of COPD).
• A cooperative attitude and ability to demonstrate correct use of the pMDI inhalers and eDiary.

Exclusion Criteria:

• Female subjects who are pregnant (as evident by a positive urine hCG or serum ß-hCG test) or lactating
• Subjects using the following medications prior to the screening visit and during the

run-in period:

1. Systemic/oral/parenteral corticosteroids in the prior 4 weeks

2. Use of antibiotics for a lower respiratory tract infection (e.g. pneumonia) or COPD exacerbation in the prior 4 weeks

3. Any long-term chronic maintenance use of antibiotic treatment in the prior 4 weeks

4. Oral xanthine derivatives (e.g. theophylline) in the prior 7 days

• A moderate or severe COPD exacerbation or a respiratory tract infection (e.g., pneumonia) that has not resolved =14 days prior to the screening visit or during the run-in period
• Current treatment with non-cardioselective ß-blockers
• Requirement of long term (> 15 hours daily) oxygen therapy
• Known respiratory disorders other than COPD which may impact the efficacy of the study drug according to investigator's judgement.
• Lung transplant surgery or lung volume reduction surgery (subjects with lung volume reduction surgery are excluded if the procedure was performed within 1 year before the Screening visit)
• Medical diagnosis of narrow-angle glaucoma, prostatic hypertrophy or bladder neck obstruction that, in the opinion of the investigator, would prevent use of anticholinergic agents
• History of hypersensitivity to M3 receptor antagonists, ß2 agonists, corticosteroids or any of the excipients contained in any of the study drugs used in the trial which may raise contra-indications or impact the efficacy of the study drug according to the investigator's judgement
• Subject has severe, acute or uncontrolled cardiovascular condition (such as but not limited to unstable ischemic heart disease, NYHA Class IV, left ventricular failure, acute myocardial infarction or unstable angina) in the last 6 months
• An abnormal and clinically significant 12-lead ECG at either the screening or randomization visit. This is characterized as but not limited to any of the following

findings:

1. Atrial fibrillation (AF) with rapid ventricular response > 120 bpm

2. Ventricular tachycardias (sustained, non-sustained [>3 up to 30 sec])

3. Evidence of Mobitz Type II second degree or third-degree atrioventricular block

4. Prolonged QTcF (>450ms for males, or >470ms for females). This criterion is not applicable for subjects with a pacemaker or permanent AF.

• Clinically significant laboratory abnormalities indicating a significant or unstable concomitant disease which may impact the efficacy or the safety of the study drug according to investigator's judgement
• Unstable or uncontrolled concurrent disease which may impact the efficacy or safety of the study drug or the subject's participation in the study according to investigator's judgment
• Malignancy that has not been in complete remission for at least 1 year or any untreated localized carcinomas
• History of alcohol abuse and/or substance/drug abuse within 12 months prior to the screening visit
• Receipt of any other investigational drug within 1 month or 5 half-lives (whichever is greater) prior to the screening visit or have been previously randomized in this trial, or are currently participating in another clinical trial
• Currently in the acute phase of a pulmonary rehabilitation program within 4 weeks before the screening visit or planning to enroll in the acute phase of such a program during the study. Subjects who are in the maintenance phase of a pulmonary rehabilitation program are not excluded
• Mentally or legally incapacitated, or subjects incarcerated as a result of an official or judicial order
• Major surgery in the 3 months prior to the screening visit or have a planned surgery during the trial
• Non-satisfactory compliance with the eDiary (<65% or >135%) during the run-in period
• Subjects requiring the use of spacer device or nebulizer for administration of maintenance COPD therapies.
• Veins unsuitable for repeat venipuncture
• Blood donation or blood loss (=450mL) in the 4 weeks before randomization

Related Conditions & MeSH terms

• COPD
• COPD Exacerbation
• Pulmonary Disease, Chronic Obstructive

Intervention

Drug:
• Beclomethasone Dipropionate
Available in pressurized inhalation solution BDP/FF/GB 100/6/12.5µg and BDP/FF 100/6µg
• Glycopyrronium Bromide
Available in pressurized inhalation solution BDP/FF/GB 100/6/12.5µg
• Formoterol Fumarate
Available in pressurized inhalation solution BDP/FF/GB 100/6/12.5µg and BDP/FF 100/6µg

Locations

Country	Name	City	State
Argentina	Chiesi Clinical Trial Site 032125	Buenos Aires
Argentina	Chiesi Clinical Trial Site 032130	Buenos Aires
Argentina	Chiesi Clinical Trial Site 032133	Buenos Aires
Argentina	Chiesi Clinical Trial Site 032103	Ciudad Autonoma de Buenos Aire
Argentina	Chiesi Clinical Trial Site 032107	Ciudad Autonoma de Buenos Aire	Buenos Aires
Argentina	Chiesi Clinical Trial Site 032109	Ciudad Autonoma de Buenos Aire
Argentina	Chiesi Clinical Trial Site 032112	Ciudad Autonoma de Buenos Aire	Buenos Aires
Argentina	Chiesi Clinical Trial Site 032113	Ciudad Autonoma de Buenos Aire	Buenos Aires
Argentina	Chiesi Clinical Trial Site 032115	Ciudad Autonoma de Buenos Aire	Buenos Aires
Argentina	Chiesi Clinical Trial Site 032121	Ciudad Autonoma de Buenos Aire	Buenos Aires
Argentina	Chiesi Clinical Trial Site 032120	Concepción Del Uruguay	Entre Rios
Argentina	Chiesi Clinical Trial Site 032111	Córdoba	Cordoba
Argentina	Chiesi Clinical Trial Site 032122	Córdoba
Argentina	Chiesi Clinical Trial Site 032110	Florencio Varela	Buenos Aires
Argentina	Chiesi Clinical Trial Site 032108	La Plata	Buenos Aires
Argentina	Chiesi Clinical Trial Site 032131	Lobos
Argentina	Chiesi Clinical Trial Site 032114	Mar Del Plata	Buenos Aires
Argentina	Chiesi Clinical Trial Site 032118	Mar Del Plata	Buenos Aires
Argentina	Chiesi Clinical Trial Site 032119	Mar Del Plata
Argentina	Chiesi Clinical Trial Site 032105	Mendoza
Argentina	Chiesi Clinical Trial Site 032126	Mendoza
Argentina	Chiesi Clinical Trial Site 032129	Mendoza
Argentina	Chiesi Clinical Trial Site 032102	Monte Grande	Buenos Aires
Argentina	Chiesi Clinical Trial Site 032123	Paraná
Argentina	Chiesi Clinical Trial Site 032106	Quilmes	Buenos Aires
Argentina	Chiesi Clinical Trial Site 032101	Rosario	Santa Fe
Argentina	Chiesi Clinical Trial Site 032128	Rosario
Argentina	Chiesi Clinical Trial Site 032132	Rosario	Santa Fe
Argentina	Chiesi Clinical Trial Site 032116	San Fernando	Buenos Aires
Argentina	Chiesi Clinical Trial Site 032134	San Miguel De Tucumán
Argentina	Chiesi Clinical Trial Site 032136	San Miguel De Tucumán
Argentina	Chiesi Clinical Trial Site 032127	San Rafael
Argentina	Chiesi Clinical Trial Site 032124	Santa Fe
Argentina	Chiesi Clinical Trial Site 032117	Tucumán	Tucuman
Argentina	Chiesi Clinical Trial Site 032100	Vicente López	Buenos Aires
Bulgaria	Chiesi Clinical Trial Site 100125	Gabrovo
Bulgaria	Chiesi Clinical Trial Site 100109	Haskovo
Bulgaria	Chiesi Clinical Trial Site 100129	Kozloduy
Bulgaria	Chiesi Clinical Trial Site 100111	Lovech
Bulgaria	Chiesi Clinical Trial Site 100115	Montana
Bulgaria	Chiesi Clinical Trial Site 100101	Pleven
Bulgaria	Chiesi Clinical Trial Site 100132	Pleven
Bulgaria	Chiesi Clinical Trial Site 100102	Plovdiv
Bulgaria	Chiesi Clinical Trial Site 100126	Plovdiv
Bulgaria	Chiesi Clinical Trial Site 100131	Plovdiv
Bulgaria	Chiesi Clinical Trial Site 100128	Razgrad
Bulgaria	Chiesi Clinical Trial Site 100104	Ruse
Bulgaria	Chiesi Clinical Trial Site 100113	Ruse
Bulgaria	Chiesi Clinical Trial Site 100100	Sofia
Bulgaria	Chiesi Clinical Trial Site 100110	Sofia
Bulgaria	Chiesi Clinical Trial Site 100112	Sofia
Bulgaria	Chiesi Clinical Trial Site 100116	Sofia
Bulgaria	Chiesi Clinical Trial Site 100117	Sofia
Bulgaria	Chiesi Clinical Trial Site 100118	Sofia
Bulgaria	Chiesi Clinical Trial Site 100119	Sofia
Bulgaria	Chiesi Clinical Trial Site 100121	Sofia
Bulgaria	Chiesi Clinical Trial Site 100123	Sofia
Bulgaria	Chiesi Clinical Trial Site 100124	Sofia
Bulgaria	Chiesi Clinical Trial Site 100127	Sofia
Bulgaria	Chiesi Clinical Trial Site 100103	Stara Zagora
Bulgaria	Chiesi Clinical Trial Site 100107	Stara Zagora
Bulgaria	Chiesi Clinical Trial Site 100130	Varna
Bulgaria	Chiesi Clinical Trial Site 100122	Veliko Tarnovo
Bulgaria	Chiesi Clinical Trial Site 100106	Vidin
Bulgaria	Chiesi Clinical Trial Site 100114	Vidin
Canada	Chiesi Clinical Trial Site 124102	Burlington	Ontario
Canada	Chiesi Clinical Trial Site 124103	Edmonton	Alberta
Canada	Chiesi Clinical Trial Site 124105	Sherwood Park	Alberta
Canada	Chiesi Clinical Trial Site 124104	Sudbury	Ontario
Canada	Chiesi Clinical Trial Site 124106	Trois-Rivières	Quebec
Canada	Chiesi Clinical Trial Site 124100	Windsor	Ontario
Czechia	Chiesi Clinical Trial Site 203101	Brandýs Nad Labem
Czechia	Chiesi Clinical Trial Site 203107	Jindrichuv Hradec
Czechia	Chiesi Clinical Trial Site 203109	Miroslav
Czechia	Chiesi Clinical Trial Site 203114	Praha
Czechia	Chiesi Clinical Trial Site 203115	Praha
Czechia	Chiesi Clinical Trial Site 203116	Praha
Czechia	Chiesi Clinical Trial Site 203112	Rokycany
Czechia	Chiesi Clinical Trial Site 203108	Strakonice
Czechia	Chiesi Clinical Trial Site 203105	Tábor
Czechia	Chiesi Clinical Trial Site 203104	Teplice
Czechia	Chiesi Clinical Trial Site 203110	Varnsdorf
Hungary	Chiesi Clinical Trial Site 348107	Balassagyarmat	Nograd
Hungary	Chiesi Clinical Trial Site 348124	Csorna	GS
Hungary	Chiesi Clinical Trial Site 348118	Debrecen
Hungary	Chiesi Clinical Trial Site 348120	Gödöllo	Pest
Hungary	Chiesi Clinical Trial Site 348112	Hajdúnánás
Hungary	Chiesi Clinical Trial Site 348116	Hatvan
Hungary	Chiesi Clinical Trial Site 348121	Komló	BA
Hungary	Chiesi Clinical Trial Site 348103	Monor
Hungary	Chiesi Clinical Trial Site 348104	Nyiregyhaza	Szabolcs-Szatmar-Bereg
Hungary	Chiesi Clinical Trial Site 348109	Nyiregyhaza	Szabolcs-Szatmár-Bereg
Hungary	Chiesi Clinical Trial Site 348122	Pécs	BA
Hungary	Chiesi Clinical Trial Site 348125	Sellye
Hungary	Chiesi Clinical Trial Site 348108	Szarvas	Bekes
Hungary	Chiesi Clinical Trial Site 348126	Szolnok	JN
Hungary	Chiesi Clinical Trial Site 348105	Szombathely	Vas
Mexico	Chiesi Clinical Trial Site 484105	Chihuahua
Mexico	Chiesi Clinical Trial Site 484109	Chihuahua
Mexico	Chiesi Clinical Trial Site 484116	Chihuahua
Mexico	Chiesi Clinical Trial Site 484103	Cuauhtémoc	Cdmx
Mexico	Chiesi Clinical Trial Site 484100	Guadalajara	Jalisco
Mexico	Chiesi Clinical Trial Site 484102	Guadalajara	Jalisco
Mexico	Chiesi Clinical Trial Site 484104	Guadalajara	Jalisco
Mexico	Chiesi Clinical Trial Site 484106	Guadalajara	Jalisco
Mexico	Chiesi Clinical Trial Site 484112	Guadalajara	Jalisco
Mexico	Chiesi Clinical Trial Site 484113	Guadalajara	Jalisco
Mexico	Chiesi Clinical Trial Site 484115	Guadalupe	Jalisco
Mexico	Chiesi Clinical Trial Site 484101	Monterrey	Nuevo Leon
Mexico	Chiesi Clinical Trial Site 484111	Monterrey	Nuevo Leon
Mexico	Chiesi Clinical Trial Site 484107	Morelia	Michoacan
Mexico	Chiesi Clinical Trial Site 484110	Tijuana	Baja California
Mexico	Chiesi Clinical Trial Site 484108	Tlalpan
Poland	Chiesi Clinical Trial Site 616119	Bialystok
Poland	Chiesi Clinical Trial Site 616125	Bialystok
Poland	Chiesi Clinical Trial Site 616100	Gizycko
Poland	Chiesi Clinical Trial Site 616113	Grudziadz
Poland	Chiesi Clinical Trial Site 616116	Katowice
Poland	Chiesi Clinical Trial Site 616106	Kraków
Poland	Chiesi Clinical Trial Site 616109	Kraków
Poland	Chiesi Clinical Trial Site 616118	Kraków
Poland	Chiesi Clinical Trial Site 616122	Kraków
Poland	Chiesi Clinical Trial Site 616103	Lódz
Poland	Chiesi Clinical Trial Site 616128	Olsztyn
Poland	Chiesi Clinical Trial Site 616105	Ostróda
Poland	Chiesi Clinical Trial Site 616117	Ostrowiec
Poland	Chiesi Clinical Trial Site 616107	Poznan
Poland	Chiesi Clinical Trial Site 616110	Poznan
Poland	Chiesi Clinical Trial Site 616123	Poznan
Poland	Chiesi Clinical Trial Site 616108	Rzeszów
Poland	Chiesi Clinical Trial Site 616114	Skierniewice
Poland	Chiesi Clinical Trial Site 616120	Skorzewo
Poland	Chiesi Clinical Trial Site 616102	Sosnowiec
Poland	Chiesi Clinical Trial Site 616111	Tarnów
Poland	Chiesi Clinical Trial Site 616115	Torun
Poland	Chiesi Clinical Trial Site 616127	Warszawa
Poland	Chiesi Clinical Trial Site 616104	Wroclaw
Poland	Chiesi Clinical Trial Site 616112	Wroclaw
Poland	Chiesi Clinical Trial Site 616126	Wroclaw
Poland	Chiesi Clinical Trial Site 616101	Zawadzkie
Puerto Rico	Chiesi Clinical Trial Site 840393	Guaynabo
Romania	Chiesi Clinical Trial Site 642109	Bacau
Romania	Chiesi Clinical Trial Site 642106	Bragadiru
Romania	Chiesi Clinical Trial Site 642107	Bragadiru	Ilfov
Romania	Chiesi Clinical Trial Site 642117	Brasov
Romania	Chiesi Clinical Trial Site 642103	Bucharest
Romania	Chiesi Clinical Trial Site 642113	Bucharest
Romania	Chiesi Clinical Trial Site 642108	Bucuresti
Romania	Chiesi Clinical Trial Site 642115	Caracal
Romania	Chiesi Clinical Trial Site 642104	Cluj-Napoca	Cluj
Romania	Chiesi Clinical Trial Site 642111	Cluj-Napoca
Romania	Chiesi Clinical Trial Site 642105	Constanta
Romania	Chiesi Clinical Trial Site 642110	Craiova
Romania	Chiesi Clinical Trial Site 642118	Craiova
Romania	Chiesi Clinical Trial Site 642120	Deva	Hunedoara
Romania	Chiesi Clinical Trial Site 642101	Iasi
Romania	Chiesi Clinical Trial Site 642102	Oradea	Bihor
Romania	Chiesi Clinical Trial Site 642114	Re?ca
Romania	Chiesi Clinical Trial Site 642112	Satu Mare
Romania	Chiesi Clinical Trial Site 642116	Timisoara
Romania	Chiesi Clinical Trial Site 642119	Timisoara	Timis
United States	Chiesi Clinical Trial Site 840223	Adairsville	Georgia
United States	Chiesi Clinical Trial Site 840116	Altamonte Springs	Florida
United States	Chiesi Clinical Trial Site 840222	Anderson	South Carolina
United States	Chiesi Clinical Trial Site 840268	Aventura	Florida
United States	Chiesi Clinical Trial Site 840101	Baytown	Texas
United States	Chiesi Clinical Trial Site 840300	Beaver	Pennsylvania
United States	Chiesi Clinical Trial Site 840297	Berlin	New Jersey
United States	Chiesi Clinical Trial Site 840330	Binghamton	New York
United States	Chiesi Clinical Trial Site 840350	Birmingham	Alabama
United States	Chiesi Clinical Trial Site 840114	Boerne	Texas
United States	Chiesi Clinical Trial Site 840229	Boulder	Colorado
United States	Chiesi Clinical Trial Site 840192	Brandon	Florida
United States	Chiesi Clinical Trial Site 840128	Bronx	New York
United States	Chiesi Clinical Trial Site 840397	Brooklyn	New York
United States	Chiesi Clinical Trial Site 840310	Brooksville	Florida
United States	Chiesi Clinical Trial Site 840254	Buffalo	New York
United States	Chiesi Clinical Trial Site 840307	Buffalo	New York
United States	Chiesi Clinical Trial Site 840158	Charlotte	North Carolina
United States	Chiesi Clinical Trial Site 840215	Charlotte	North Carolina
United States	Chiesi Clinical Trial Site 840366	Charlotte	North Carolina
United States	Chiesi Clinical Trial Site 840305	Chattanooga	Tennessee
United States	Chiesi Clinical Trial Site 840278	Chesterfield	Missouri
United States	Chiesi Clinical Trial Site 840321	Chicago	Illinois
United States	Chiesi Clinical Trial Site 840365	Chicago Ridge	Illinois
United States	Chiesi Clinical Trial Site 840240	Chiefland	Florida
United States	Chiesi Clinical Trial Site 840104	Cincinnati	Ohio
United States	Chiesi Clinical Trial Site 840357	Cincinnati	Ohio
United States	Chiesi Clinical Trial Site 840153	Clearwater	Florida
United States	Chiesi Clinical Trial Site 840337	Colchester	Vermont
United States	Chiesi Clinical Trial Site 840130	Columbia	South Carolina
United States	Chiesi Clinical Trial Site 840155	Columbia	Missouri
United States	Chiesi Clinical Trial Site 840334	Columbia	South Carolina
United States	Chiesi Clinical Trial Site 840124	Columbus	Ohio
United States	Chiesi Clinical Trial Site 840218	Columbus	Georgia
United States	Chiesi Clinical Trial Site 840272	Coral Gables	Florida
United States	Chiesi Clinical Trial Site 840304	Coral Gables	Florida
United States	Chiesi Clinical Trial Site 840318	Council Bluffs	Iowa
United States	Chiesi Clinical Trial Site 840207	Crowley	Louisiana
United States	Chiesi Clinical Trial Site 840332	Cumberland	Rhode Island
United States	Chiesi Clinical Trial Site 840311	Cutler Bay	Florida
United States	Chiesi Clinical Trial Site 840335	Cutler Bay	Florida
United States	Chiesi Clinical Trial Site 840146	Cypress	Texas
United States	Chiesi Clinical Trial Site 840141	Daytona Beach	Florida
United States	Chiesi Clinical Trial Site 840325	Dearborn	Michigan
United States	Chiesi Clinical Trial Site 840400	Dearborn	Michigan
United States	Chiesi Clinical Trial Site 840133	DeLand	Florida
United States	Chiesi Clinical Trial Site 840269	Doral	Florida
United States	Chiesi Clinical Trial Site 840186	Dothan	Alabama
United States	Chiesi Clinical Trial Site 840308	DuBois	Pennsylvania
United States	Chiesi Clinical Trial Site 840209	Escondido	California
United States	Chiesi Clinical Trial Site 840214	Fall River	Massachusetts
United States	Chiesi Clinical Trial Site 840183	Farmington Hills	Michigan
United States	Chiesi Clinical Trial Site 840340	Flint	Michigan
United States	Chiesi Clinical Trial Site 840401	Flint	Michigan
United States	Chiesi Clinical Trial Site 840368	Flushing	New York
United States	Chiesi Clinical Trial Site 840258	Foley	Alabama
United States	Chiesi Clinical Trial Site 840211	Fort Mill	South Carolina
United States	Chiesi Clinical Trial Site 840144	Fountain Valley	California
United States	Chiesi Clinical Trial Site 840351	Franklin	Tennessee
United States	Chiesi Clinical Trial Site 840182	Gaffney	South Carolina
United States	Chiesi Clinical Trial Site 840111	Greenville	South Carolina
United States	Chiesi Clinical Trial Site 840163	Hialeah	Florida
United States	Chiesi Clinical Trial Site 840165	Hialeah	Florida
United States	Chiesi Clinical Trial Site 840184	Hialeah	Florida
United States	Chiesi Clinical Trial Site 840238	Hialeah	Florida
United States	Chiesi Clinical Trial Site 840241	Hialeah	Florida
United States	Chiesi Clinical Trial Site 840253	Hialeah	Florida
United States	Chiesi Clinical Trial Site 840265	Hialeah	Florida
United States	Chiesi Clinical Trial Site 840267	Hialeah	Florida
United States	Chiesi Clinical Trial Site 840303	Hialeah	Florida
United States	Chiesi Clinical Trial Site 840354	Hialeah	Florida
United States	Chiesi Clinical Trial Site 840256	Hialeah Gardens	Florida
United States	Chiesi Clinical Trial Site 840224	Houston	Texas
United States	Chiesi Clinical Trial Site 840284	Houston	Texas
United States	Chiesi Clinical Trial Site 840389	Houston	Texas
United States	Chiesi Clinical Trial Site 840236	Huntersville	North Carolina
United States	Chiesi Clinical Trial Site 840279	Jasper	Alabama
United States	Chiesi Clinical Trial Site 840156	Jenkintown	Pennsylvania
United States	Chiesi Clinical Trial Site 840306	Johnson City	Tennessee
United States	Chiesi Clinical Trial Site 840102	Katy	Texas
United States	Chiesi Clinical Trial Site 840274	Katy	Texas
United States	Chiesi Clinical Trial Site 840302	Kettering	Ohio
United States	Chiesi Clinical Trial Site 840200	Kissimmee	Florida
United States	Chiesi Clinical Trial Site 840171	Knoxville	Tennessee
United States	Chiesi Clinical Trial Site 840232	Lakeland	Florida
United States	Chiesi Clinical Trial Site 840160	Lampasas	Texas
United States	Chiesi Clinical Trial Site 840213	Las Vegas	Nevada
United States	Chiesi Clinical Trial Site 840285	Las Vegas	Nevada
United States	Chiesi Clinical Trial Site 840299	Las Vegas	Nevada
United States	Chiesi Clinical Trial Site 840227	Lawrenceville	Georgia
United States	Chiesi Clinical Trial Site 840390	Lawrenceville	Georgia
United States	Chiesi Clinical Trial Site 840113	Leesburg	Florida
United States	Chiesi Clinical Trial Site 840281	Lincoln	Nebraska
United States	Chiesi Clinical Trial Site 840358	Lomita	California
United States	Chiesi Clinical Trial Site 840264	Manassas	Virginia
United States	Chiesi Clinical Trial Site 840386	Mauldin	South Carolina
United States	Chiesi Clinical Trial Site 840233	Maumee	Ohio
United States	Chiesi Clinical Trial Site 840119	McKinney	Texas
United States	Chiesi Clinical Trial Site 840203	Medford	Oregon
United States	Chiesi Clinical Trial Site 840122	Miami	Florida
United States	Chiesi Clinical Trial Site 840137	Miami	Florida
United States	Chiesi Clinical Trial Site 840148	Miami	Florida
United States	Chiesi Clinical Trial Site 840162	Miami	Florida
United States	Chiesi Clinical Trial Site 840166	Miami	Florida
United States	Chiesi Clinical Trial Site 840175	Miami	Florida
United States	Chiesi Clinical Trial Site 840178	Miami	Florida
United States	Chiesi Clinical Trial Site 840180	Miami	Florida
United States	Chiesi Clinical Trial Site 840193	Miami	Florida
United States	Chiesi Clinical Trial Site 840202	Miami	Florida
United States	Chiesi Clinical Trial Site 840205	Miami	Florida
United States	Chiesi Clinical Trial Site 840235	Miami	Florida
United States	Chiesi Clinical Trial Site 840237	Miami	Florida
United States	Chiesi Clinical Trial Site 840239	Miami	Florida
United States	Chiesi Clinical Trial Site 840243	Miami	Florida
United States	Chiesi Clinical Trial Site 840244	Miami	Florida
United States	Chiesi Clinical Trial Site 840247	Miami	Florida
United States	Chiesi Clinical Trial Site 840257	Miami	Florida
United States	Chiesi Clinical Trial Site 840261	Miami	Florida
United States	Chiesi Clinical Trial Site 840262	Miami	Florida
United States	Chiesi Clinical Trial Site 840275	Miami	Florida
United States	Chiesi Clinical Trial Site 840280	Miami	Florida
United States	Chiesi Clinical Trial Site 840289	Miami	Florida
United States	Chiesi Clinical Trial Site 840292	Miami	Florida
United States	Chiesi Clinical Trial Site 840312	Miami	Florida
United States	Chiesi Clinical Trial Site 840326	Miami	Florida
United States	Chiesi Clinical Trial Site 840341	Miami	Florida
United States	Chiesi Clinical Trial Site 840346	Miami	Florida
United States	Chiesi Clinical Trial Site 840347	Miami	Florida
United States	Chiesi Clinical Trial Site 840352	Miami	Florida
United States	Chiesi Clinical Trial Site 840355	Miami	Florida
United States	Chiesi Clinical Trial Site 840360	Miami	Florida
United States	Chiesi Clinical Trial Site 840367	Miami	Florida
United States	Chiesi Clinical Trial Site 840370	Miami	Florida
United States	Chiesi Clinical Trial Site 840372	Miami	Florida
United States	Chiesi Clinical Trial Site 840377	Miami	Florida
United States	Chiesi Clinical Trial Site 840380	Miami	Florida
United States	Chiesi Clinical Trial Site 840381	Miami	Florida
United States	Chiesi Clinical Trial Site 840382	Miami	Florida
United States	Chiesi Clinical Trial Site 840387	Miami	Florida
United States	Chiesi Clinical Trial Site 840388	Miami	Florida
United States	Chiesi Clinical Trial Site 840392	Miami	Florida
United States	Chiesi Clinical Trial Site 840319	Miami Beach	Florida
United States	Chiesi Clinical Trial Site 840288	Miami Lakes	Florida
United States	Chiesi Clinical Trial Site 840328	Miami Lakes	Florida
United States	Chiesi Clinical Trial Site 840353	Miami Lakes	Florida
United States	Chiesi Clinical Trial Site 840378	Miami Lakes	Florida
United States	Chiesi Clinical Trial Site 840385	Miami Lakes	Florida
United States	Chiesi Clinical Trial Site 840167	Middleburg Heights	Ohio
United States	Chiesi Clinical Trial Site 840273	Missoula	Montana
United States	Chiesi Clinical Trial Site 840259	Monroe	North Carolina
United States	Chiesi Clinical Trial Site 840206	Montgomery	Alabama
United States	Chiesi Clinical Trial Site 840201	Morgantown	West Virginia
United States	Chiesi Clinical Trial Site 840140	Mount Dora	Florida
United States	Chiesi Clinical Trial Site 840249	Muscle Shoals	Alabama
United States	Chiesi Clinical Trial Site 840322	New Bedford	Massachusetts
United States	Chiesi Clinical Trial Site 840194	New Bern	North Carolina
United States	Chiesi Clinical Trial Site 840263	New Port Richey	Florida
United States	Chiesi Clinical Trial Site 840362	New Windsor	New York
United States	Chiesi Clinical Trial Site 840173	Newport Beach	California
United States	Chiesi Clinical Trial site 840250	North Dartmouth	Massachusetts
United States	Chiesi Clinical Trial Site 840132	North Miami	Florida
United States	Chiesi Clinical Trial Site 840161	North Miami Beach	Florida
United States	Chiesi Clinical Trial Site 840176	North Richland Hills	Texas
United States	Chiesi Clinical Trial Site 840208	Northridge	California
United States	Chiesi Clinical Trial Site 840277	Northridge	California
United States	Chiesi Clinical Trial Site 840399	Norwalk	Connecticut
United States	Chiesi Clinical Trial Site 840345	Novi	Michigan
United States	Chiesi Clinical Trial Site 840329	Omaha	Nebraska
United States	Chiesi Clinical Trial Site 840110	Orlando	Florida
United States	Chiesi Clinical Trial Site 840125	Orlando	Florida
United States	Chiesi Clinical Trial Site 840255	Orlando	Florida
United States	Chiesi Clinical Trial Site 840121	Palmetto Bay	Florida
United States	Chiesi Clinical Trial Site 840283	Pearland	Texas
United States	Chiesi Clinical Trial Site 840196	Pembroke Pines	Florida
United States	Chiesi Clinical Trial Site 840198	Pembroke Pines	Florida
United States	Chiesi Clinical Trial Site 840402	Peoria	Arizona
United States	Chiesi Clinical Trial Site 840190	Phoenix	Arizona
United States	Chiesi Clinical Trial Site 840327	Pittsburgh	Pennsylvania
United States	Chiesi Clinical Trial Site 840363	Plantation	Florida
United States	Chiesi Clinical Trial Site 840371	Plantation	Florida
United States	Chiesi Clinical Trial Site 840252	Pompano Beach	Florida
United States	Chiesi Clinical Trial Site 840105	Port Charlotte	Florida
United States	Chiesi Clinical Trial Site 840338	Portsmouth	New Hampshire
United States	Chiesi Clinical Trial Site 840344	Potsdam	New York
United States	Chiesi Clinical Trial Site 840120	Raleigh	North Carolina
United States	Chiesi Clinical Trial Site 840398	Rapid City	South Dakota
United States	Chiesi Clinical Trial Site 840364	Redding	California
United States	Chiesi Clinical Trial Site 840342	Renton	Washington
United States	Chiesi Clinical Trial Site 840159	Richmond	Virginia
United States	Chiesi Clinical Trial Site 840316	Richmond Heights	Missouri
United States	Chiesi Clinical Trial Site 840138	Rincon	Georgia
United States	Chiesi Clinical Trial Site 840100	Rock Hill	South Carolina
United States	Chiesi Clinical Trial Site 840112	Rocky Mount	North Carolina
United States	Chiesi Clinical Trial Site 840226	Sacramento	California
United States	Chiesi Clinical Trial Site 840150	Saint Charles	Missouri
United States	Chiesi Clinical Trial Site 840123	Saint Louis	Missouri
United States	Chiesi Clinical Trial Site 840142	Saint Louis	Missouri
United States	Chiesi Clinical Trial Site 840282	Saint Louis	Missouri
United States	Chiesi Clinical Trial Site 840290	Saint Petersburg	Florida
United States	Chiesi Clinical Trial Site 840291	Saint Petersburg	Florida
United States	Chiesi Clinical Trial Site 840191	San Antonio	Texas
United States	Chiesi Clinical Trial Site 840293	San Antonio	Texas
United States	Chiesi Clinical Trial Site 840320	San Antonio	Texas
United States	Chiesi Clinical Trial Site 840107	San Diego	California
United States	Chiesi Clinical Trial Site 840373	Santa Ana	California
United States	Chiesi Clinical Trial Site 840294	Sarasota	Florida
United States	Chiesi Clinical Trial Site 840135	Shelby	North Carolina
United States	Chiesi Clinical Trial Site 840231	Sherman	Texas
United States	Chiesi Clinical Trial Site 840396	Sherman	Texas
United States	Chiesi Clinical Trial Site 840287	Southfield	Michigan
United States	Chiesi Clinical Trial Site 840375	Spartanburg	South Carolina
United States	Chiesi Clinical Trial Site 840394	Splendora	Texas
United States	Chiesi Clinical Trial Site 840221	Sugar Land	Texas
United States	Chiesi Clinical Trial Site 840131	Tampa	Florida
United States	Chiesi Clinical Trial Site 840309	Tampa	Florida
United States	Chiesi Clinical Trial Site 840313	Tampa	Florida
United States	Chiesi Clinical Trial Site 840324	Tampa	Florida
United States	Chiesi Clinical Trial Site 840356	Tampa	Florida
United States	Chiesi Clinical Trial Site 840379	Tampa	Florida
United States	Chiesi Clinical Trial Site 840210	The Villages	Florida
United States	Chiesi Clinical Trial Site 840157	Toledo	Ohio
United States	Chiesi Clinical Trial Site 840139	Tomball	Texas
United States	Chiesi Clinical Trial Site 840314	Tomball	Texas
United States	Chiesi Clinical Trial Site 840333	Toms River	New Jersey
United States	Chiesi Clinical Trial Site 840349	Tucson	Arizona
United States	Chiesi Clinical Trial Site 840271	Tullahoma	Tennessee
United States	Chiesi Clinical Trial Site 840106	Union	South Carolina
United States	Chiesi Clinical Trial Site 840383	Union City	Georgia
United States	Chiesi Clinical Trial Site 840164	Upland	California
United States	Chiesi Clinical Trial Site 840108	Valparaiso	Indiana
United States	Chiesi Clinical Trial Site 840154	Vancouver	Washington
United States	Chiesi Clinical Trial Site 840295	West Columbia	South Carolina
United States	Chiesi Clinical Trial Site 840174	West Covina	California
United States	Chiesi Clinical Trial Site 840199	Westminster	Maryland
United States	Chiesi Clinical Trial Site 840189	Wilmington	North Carolina
United States	Chiesi Clinical Trial Site 840129	Winter Park	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Chiesi Farmaceutici S.p.A.

Countries where clinical trial is conducted

United States,  Argentina,  Bulgaria,  Canada,  Czechia,  Hungary,  Mexico,  Poland,  Puerto Rico,  Romania, 

References & Publications (33)

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Hanania NA, Crater GD, Morris AN, Emmett AH, O'Dell DM, Niewoehner DE. Benefits of adding fluticasone propionate/salmeterol to tiotropium in moderate to severe COPD. Respir Med. 2012 Jan;106(1):91-101. doi: 10.1016/j.rmed.2011.09.002. Epub 2011 Oct 29. — View Citation

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Jones PW, Gelhorn H, Wilson H, Karlsson N, Menjoge S, Mullerova H, Rennard SI, Tal-Singer R, Merrill D, Tabberer M. Responder Analyses for Treatment Effects in COPD Using the St George's Respiratory Questionnaire. Chronic Obstr Pulm Dis. 2017 Mar 2;4(2):124-131. doi: 10.15326/jcopdf.4.2.2017.0130. — View Citation

Jones PW, Harding G, Berry P, Wiklund I, Chen WH, Kline Leidy N. Development and first validation of the COPD Assessment Test. Eur Respir J. 2009 Sep;34(3):648-54. doi: 10.1183/09031936.00102509. — View Citation

Jones PW, Tabberer M, Chen WH. Creating scenarios of the impact of COPD and their relationship to COPD Assessment Test (CAT) scores. BMC Pulm Med. 2011 Aug 11;11:42. doi: 10.1186/1471-2466-11-42. — View Citation

Jones PW. St. George's Respiratory Questionnaire: MCID. COPD. 2005 Mar;2(1):75-9. doi: 10.1081/copd-200050513. — View Citation

Jung KS, Park HY, Park SY, Kim SK, Kim YK, Shim JJ, Moon HS, Lee KH, Yoo JH, Lee SD; Korean Academy of Tuberculosis and Respiratory Diseases study group; Korea Chronic Obstructive Pulmonary Disease study group. Comparison of tiotropium plus fluticasone propionate/salmeterol with tiotropium in COPD: a randomized controlled study. Respir Med. 2012 Mar;106(3):382-9. doi: 10.1016/j.rmed.2011.09.004. Epub 2011 Oct 4. — View Citation

Kon SS, Canavan JL, Jones SE, Nolan CM, Clark AL, Dickson MJ, Haselden BM, Polkey MI, Man WD. Minimum clinically important difference for the COPD Assessment Test: a prospective analysis. Lancet Respir Med. 2014 Mar;2(3):195-203. doi: 10.1016/S2213-2600(14)70001-3. Epub 2014 Feb 4. — View Citation

Lane DC, Stemkowski S, Stanford RH, Tao Z. Initiation of Triple Therapy with Multiple Inhalers in Chronic Obstructive Pulmonary Disease: An Analysis of Treatment Patterns from a U.S. Retrospective Database Study. J Manag Care Spec Pharm. 2018 Nov;24(11):1165-1172. doi: 10.18553/jmcp.2018.24.11.1165. — View Citation

Lipson DA, Barnacle H, Birk R, Brealey N, Locantore N, Lomas DA, Ludwig-Sengpiel A, Mohindra R, Tabberer M, Zhu CQ, Pascoe SJ. FULFIL Trial: Once-Daily Triple Therapy for Patients with Chronic Obstructive Pulmonary Disease. Am J Respir Crit Care Med. 2017 Aug 15;196(4):438-446. doi: 10.1164/rccm.201703-0449OC. — View Citation

Lipson DA, Barnhart F, Brealey N, Brooks J, Criner GJ, Day NC, Dransfield MT, Halpin DMG, Han MK, Jones CE, Kilbride S, Lange P, Lomas DA, Martinez FJ, Singh D, Tabberer M, Wise RA, Pascoe SJ; IMPACT Investigators. Once-Daily Single-Inhaler Triple versus Dual Therapy in Patients with COPD. N Engl J Med. 2018 May 3;378(18):1671-1680. doi: 10.1056/NEJMoa1713901. Epub 2018 Apr 18. — View Citation

Lopez AD, Shibuya K, Rao C, Mathers CD, Hansell AL, Held LS, Schmid V, Buist S. Chronic obstructive pulmonary disease: current burden and future projections. Eur Respir J. 2006 Feb;27(2):397-412. doi: 10.1183/09031936.06.00025805. No abstract available. — View Citation

Lozano R, Naghavi M, Foreman K, Lim S, Shibuya K, Aboyans V, Abraham J, Adair T, Aggarwal R, Ahn SY, Alvarado M, Anderson HR, Anderson LM, Andrews KG, Atkinson C, Baddour LM, Barker-Collo S, Bartels DH, Bell ML, Benjamin EJ, Bennett D, Bhalla K, Bikbov B, Bin Abdulhak A, Birbeck G, Blyth F, Bolliger I, Boufous S, Bucello C, Burch M, Burney P, Carapetis J, Chen H, Chou D, Chugh SS, Coffeng LE, Colan SD, Colquhoun S, Colson KE, Condon J, Connor MD, Cooper LT, Corriere M, Cortinovis M, de Vaccaro KC, Couser W, Cowie BC, Criqui MH, Cross M, Dabhadkar KC, Dahodwala N, De Leo D, Degenhardt L, Delossantos A, Denenberg J, Des Jarlais DC, Dharmaratne SD, Dorsey ER, Driscoll T, Duber H, Ebel B, Erwin PJ, Espindola P, Ezzati M, Feigin V, Flaxman AD, Forouzanfar MH, Fowkes FG, Franklin R, Fransen M, Freeman MK, Gabriel SE, Gakidou E, Gaspari F, Gillum RF, Gonzalez-Medina D, Halasa YA, Haring D, Harrison JE, Havmoeller R, Hay RJ, Hoen B, Hotez PJ, Hoy D, Jacobsen KH, James SL, Jasrasaria R, Jayaraman S, Johns N, Karthikeyan G, Kassebaum N, Keren A, Khoo JP, Knowlton LM, Kobusingye O, Koranteng A, Krishnamurthi R, Lipnick M, Lipshultz SE, Ohno SL, Mabweijano J, MacIntyre MF, Mallinger L, March L, Marks GB, Marks R, Matsumori A, Matzopoulos R, Mayosi BM, McAnulty JH, McDermott MM, McGrath J, Mensah GA, Merriman TR, Michaud C, Miller M, Miller TR, Mock C, Mocumbi AO, Mokdad AA, Moran A, Mulholland K, Nair MN, Naldi L, Narayan KM, Nasseri K, Norman P, O'Donnell M, Omer SB, Ortblad K, Osborne R, Ozgediz D, Pahari B, Pandian JD, Rivero AP, Padilla RP, Perez-Ruiz F, Perico N, Phillips D, Pierce K, Pope CA 3rd, Porrini E, Pourmalek F, Raju M, Ranganathan D, Rehm JT, Rein DB, Remuzzi G, Rivara FP, Roberts T, De Leon FR, Rosenfeld LC, Rushton L, Sacco RL, Salomon JA, Sampson U, Sanman E, Schwebel DC, Segui-Gomez M, Shepard DS, Singh D, Singleton J, Sliwa K, Smith E, Steer A, Taylor JA, Thomas B, Tleyjeh IM, Towbin JA, Truelsen T, Undurraga EA, Venketasubramanian N, Vijayakumar L, Vos T, Wagner GR, Wang M, Wang W, Watt K, Weinstock MA, Weintraub R, Wilkinson JD, Woolf AD, Wulf S, Yeh PH, Yip P, Zabetian A, Zheng ZJ, Lopez AD, Murray CJ, AlMazroa MA, Memish ZA. Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet. 2012 Dec 15;380(9859):2095-128. doi: 10.1016/S0140-6736(12)61728-0. Erratum In: Lancet. 2013 Feb 23;381(9867):628. AlMazroa, Mohammad A [added]; Memish, Ziad A [added]. — View Citation

Mathers CD, Loncar D. Projections of global mortality and burden of disease from 2002 to 2030. PLoS Med. 2006 Nov;3(11):e442. doi: 10.1371/journal.pmed.0030442. — View Citation

Miller MR, Hankinson J, Brusasco V, Burgos F, Casaburi R, Coates A, Crapo R, Enright P, van der Grinten CP, Gustafsson P, Jensen R, Johnson DC, MacIntyre N, McKay R, Navajas D, Pedersen OF, Pellegrino R, Viegi G, Wanger J; ATS/ERS Task Force. Standardisation of spirometry. Eur Respir J. 2005 Aug;26(2):319-38. doi: 10.1183/09031936.05.00034805. No abstract available. — View Citation

Miller MR, Hankinson J, Brusasco V, Burgos F, Casaburi R, Coates A, Enright P, van der Grinten C, Gustafsson P, Jensen R, Macintyre N, McKay RT, Pedersen OF, Pellegrino R, Viegi G, Wanger J. Standardisation of lung function testing: the authors' replies to readers' comments. Eur Respir J. 2010 Dec;36(6):1496-8. doi: 10.1183/09031936.00130010. No abstract available. — View Citation

Montes de Oca M, Perez-Padilla R, Talamo C, Halbert RJ, Moreno D, Lopez MV, Muino A, Jose Roberto BJ, Valdivia G, Pertuze J, Ana Maria BM; PLATINO Team. Acute bronchodilator responsiveness in subjects with and without airflow obstruction in five Latin American cities: the PLATINO study. Pulm Pharmacol Ther. 2010 Feb;23(1):29-35. doi: 10.1016/j.pupt.2009.09.005. Epub 2009 Oct 8. — View Citation

Mullerova H, Dransfield MT, Thomashow B, Jones PW, Rennard S, Karlsson N, Fageras M, Metzdorf N, Petruzzelli S, Rommes J, Sciurba FC, Tabberer M, Merrill D, Tal-Singer R. Clinical Development and Research Applications of the Chronic Obstructive Pulmonary Disease Assessment Test. Am J Respir Crit Care Med. 2020 May 1;201(9):1058-1067. doi: 10.1164/rccm.201907-1369PP. No abstract available. — View Citation

Papi A, Vestbo J, Fabbri L, Corradi M, Prunier H, Cohuet G, Guasconi A, Montagna I, Vezzoli S, Petruzzelli S, Scuri M, Roche N, Singh D. Extrafine inhaled triple therapy versus dual bronchodilator therapy in chronic obstructive pulmonary disease (TRIBUTE): a double-blind, parallel group, randomised controlled trial. Lancet. 2018 Mar 17;391(10125):1076-1084. doi: 10.1016/S0140-6736(18)30206-X. Epub 2018 Feb 9. Erratum In: Lancet. 2018 Feb 26;: — View Citation

Quanjer PH, Stanojevic S, Cole TJ, Baur X, Hall GL, Culver BH, Enright PL, Hankinson JL, Ip MS, Zheng J, Stocks J; ERS Global Lung Function Initiative. Multi-ethnic reference values for spirometry for the 3-95-yr age range: the global lung function 2012 equations. Eur Respir J. 2012 Dec;40(6):1324-43. doi: 10.1183/09031936.00080312. Epub 2012 Jun 27. — View Citation

Roger JH, Bratton DJ, Mayer B, Abellan JJ, Keene ON. Treatment policy estimands for recurrent event data using data collected after cessation of randomised treatment. Pharm Stat. 2019 Jan;18(1):85-95. doi: 10.1002/pst.1910. Epub 2018 Nov 8. — View Citation

Roland NJ, Bhalla RK, Earis J. The local side effects of inhaled corticosteroids: current understanding and review of the literature. Chest. 2004 Jul;126(1):213-9. doi: 10.1378/chest.126.1.213. — View Citation

Seemungal TA, Donaldson GC, Paul EA, Bestall JC, Jeffries DJ, Wedzicha JA. Effect of exacerbation on quality of life in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 1998 May;157(5 Pt 1):1418-22. doi: 10.1164/ajrccm.157.5.9709032. — View Citation

Singh 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. — View Citation

Vestbo J, Papi A, Corradi M, Blazhko V, Montagna I, Francisco C, Cohuet G, Vezzoli S, Scuri M, Singh D. Single inhaler extrafine triple therapy versus long-acting muscarinic antagonist therapy for chronic obstructive pulmonary disease (TRINITY): a double-blind, parallel group, randomised controlled trial. Lancet. 2017 May 13;389(10082):1919-1929. doi: 10.1016/S0140-6736(17)30188-5. Epub 2017 Apr 3. — View Citation

Wedzicha JA, Singh D, Vestbo J, Paggiaro PL, Jones PW, Bonnet-Gonod F, Cohuet G, Corradi M, Vezzoli S, Petruzzelli S, Agusti A; FORWARD Investigators. Extrafine beclomethasone/formoterol in severe COPD patients with history of exacerbations. Respir Med. 2014 Aug;108(8):1153-62. doi: 10.1016/j.rmed.2014.05.013. Epub 2014 Jun 6. Erratum In: Respir Med. 2015 Mar;109(3):434-5. — View Citation

Welte T, Miravitlles M, Hernandez P, Eriksson G, Peterson S, Polanowski T, Kessler R. Efficacy and tolerability of budesonide/formoterol added to tiotropium in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2009 Oct 15;180(8):741-50. doi: 10.1164/rccm.200904-0492OC. Epub 2009 Jul 30. — View Citation

* Note: There are 33 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from baseline in pre-dose morning Forced Expiratory Volume in the 1st second (FEV1) at Week 28		Week 28
Secondary	Change from baseline in 2-hour post-dose morning FEV1 at Week 28		Week 28
Secondary	Rate of moderate and severe COPD exacerbations over 52 weeks of treatment	Annualized rate of moderate and severe COPD exacerbations as observed during the 52-week study treatment period.	52-week treatment period
Secondary	Change from baseline in pre-dose morning FEV1 at designated clinic visits		Week 4, Week 10, Week 40, & Week 52
Secondary	Change from baseline in 2-hour post-dose morning FEV1 designated clinic visits		Day 1, Week 4, Week 10, Week 40, & Week 52
Secondary	Change from pre-dose to 2-hour post-dose morning FEV1 at designated clinic visits		Day 1, Week 4, Week 10, Week 28, Week 40, & Week 52
Secondary	FEV1 response (change from baseline in pre-dose morning FEV1 =100ml) at designated clinic visits		Day 1, Week 4, Week 10, Week 28, Week 40, & Week 52
Secondary	Time to first moderate or severe COPD exacerbation		52-week treatment period
Secondary	Rate of severe COPD exacerbations over 52 weeks of treatment	Annualized rate of severe COPD exacerbations as observed during 52-week treatment period	52-week treatment period
Secondary	Time to first severe COPD exacerbation		52-week treatment period
Secondary	Saint George's Respiratory Questionnaire (SGRQ) response (a decrease from baseline in total score =4) at designated clinic visits		Week 4, Week 10, Week 28, Week 40, & Week 52
Secondary	Change from baseline in the SGRQ total score and domain scores at each designated clinic visit		Week 4, Week 10, Week 28, Week 40, & Week 52
Secondary	Change from baseline to each inter-visit period in the percentage of days without intake of rescue medication	Change from baseline (defined as the 2-week run-in period prior to randomization) to each inter-visit period (defined as the period of time between designated clinic visits) in percentage of days without rescue medication	Day 1-Week 4, Week 4-Week 10, Week 10-Week 28, Week 28-Week 40, Week 40-Week 52
Secondary	Change from baseline to each inter-visit period in the average use of rescue medication (number of puffs/day)	Change from baseline (defined as the 2-week run-in period prior to randomization) in the average number of puffs per day of rescue medication for each inter-visit period (defined as the period of time between designated clinic visits).	Day 1-Week 4, Week 4-Week 10, Week 10-Week 28, Week 28-Week 40, Week 40-Week 52
Secondary	Change from baseline in pre-dose morning Forced Vital Capacity (FVC) at designated clinic visits		Week 4, Week 10, Week 28, Week 40, & Week 52
Secondary	Change from baseline in 2-hour post-dose morning FVC at designated clinic visits	Change from baseline (defined as the pre-dose value on Day 1) in 2-hour post-dose morning FVC at designated clinic visits	Day 1, Week 4, Week 10, Week 28, Week 40, & Week 52
Secondary	Change from pre-dose to 2-hour post-dose morning FVC at designated clinic visits		Day 1, Week 4, Week 10, Week 28, Week 40, & Week 52
Secondary	Change from baseline to each inter-visit period in the average E-RS total score and domain scores	Change from baseline (defined as the 2-week run-in period prior to randomization) in the average E-RS total score and E-RS domain scores for the period of time between designated clinic visits.	Day 1-Week 4, Week 4-Week 10, Week 10-Week 28, Week 28-Week 40, Week 40-Week 52
Secondary	Change from baseline in COPD Assessment Test (CAT) score at designated clinic visit	The CAT is composed of 8 questions to measure the impact of COPD on daily life, which are scored from 0 to 5 with higher scores reflecting greater impact.	Week 4, Week 10, Week 28, Week 40, & Week 52
Secondary	CAT response (decrease from baseline =2 points) at designated clinic visits		Week 4, Week 10, Week 28, Week 40, & Week 52
Secondary	Modified Medical Research Council (mMRC) dyspnea scale at designated clinic visits	Descriptive statistics of the mMRC dyspnea scale score at designated clinic visits. The mMRC dyspnea scale is graded from 0 to 4, with higher grades reflecting greater severity.	Day 1, Week 4, Week 10, Week 28, Week 40, & Week 52
Secondary	Change from baseline in health-related quality of life (decrease from baseline in total SGRQ score =4) over 52 weeks of treatment.		52-week treatment period

External Links

•   COPD Assessment Test (CAT)
•   Global Initiative for Chronic Obstructive Lung Disease: Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease (2020 Report)
•   ICH E9 (R1) addendum on estimands and sensitivity analysis in clinical trials to the guideline on statistical principles for clinical trials
•   Measuring shortness of breath (dyspnea) in COPD.