Active Controlled Trial of CHF5993 Pressurized Metered-dose Inhaler ( pMDI) vs Symbicort®Turbuhaler® in Patients With Chronic Obstructive Pulmonary Disease ( COPD) (TRIVERSYTI)

A 24-week, Double Blind, Double Dummy, Randomized, Multinational, Multicentre, 2-arm Parallel Group,Active Controlled Clinical Trial of Fixed Combination of Beclometasone Dipropionate Plus Formoterol Fumarate Plus Glycopyrronium Bromide Administered Via pMDI (CHF 5993) Versus the Fixed Combination of Budesonide Plus Formoterol Fumarate (Symbicort® Turbuhaler®) in Patients With Chronic Obstructive Pulmonary Disease

The purpose of this study is to demonstrate the superiority of CHF 5993 pMDI (fixed combination of extrafine beclometasone dipropionate plus formoterol fumarate plus glycopyrronium bromide) over Symbicort® Turbuhaler® in terms of pulmonary function, as well as to assess its safety.

Study Overview

• Status: Completed
• Conditions: COPD (Chronic Obstructive Pulmonary Disease)
• Intervention / Treatment: Drug: CHF 5993 100/6/12.5 µg; Drug: 160 µg budesonide + 4.5 µg formoterol fumarate

• Study Type: Interventional
• Enrollment (Actual): 990
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100000
      • Chiesi clinical Trial Site 156031
    • Beijing, Beijing, China, 100020
      • Chiesi Clinical Trial Site 156026
    • Beijing, Beijing, China, 100029
      • Chiesi clinical Trial Site 156017
    • Beijing, Beijing, China, 100144
      • Chiesi Clinical Trial Site 156012
  • Chongqing
    • Chongqing, Chongqing, China, 400000
      • Chiesi Clinical Trial Site 156045
  • Fujian
    • Fuzhou, Fujian, China, 350005
      • Chiesi Clinical Trial Site 156002
  • Guangdong
    • Foshan, Guangdong, China, 528000
      • Chiesi clinical Trial Site 156024
    • Guangzhou, Guangdong, China, 510000
      • Chiesi Clinical Trial Site 156048
    • Guangzhou, Guangdong, China, 510080
      • Chiesi Clinical Trial Site 156013
    • Guanzhou, Guangdong, China, 510120
      • The First Affiliated Hospital of Guangzhou Medical University site 156001
    • Zhanjiang, Guangdong, China, 524000
      • Chiesi Clinical Trial Site 156008
  • Guangxi
    • Nanning, Guangxi, China, 530021
      • Chiesi Clinical Trial site 156003
  • Hainan
    • Haikou, Hainan, China, 570100
      • Chiesi clinical Trial Site 156020
  • Hebei
    • Shijiangzhuang, Hebei, China, 050000
      • Chiesi Clinical Trial Site 156044
  • Hunan
    • Changsha, Hunan, China, 410000
      • Chiesi Clinical Trial Site 156040
    • Changsha, Hunan, China, 410011
      • Chiesi Clinical Trial Site 156040
  • Inner Mongolia
    • Baotou, Inner Mongolia, China, 014000
      • Chiesi Clinical Trial Site 156043
    • Baotou, Inner Mongolia, China, 014010
      • Chiesi Clinical Trial Site 156015
  • Jiangsu
    • Huai'an, Jiangsu, China, 223300
      • Chiesi Clinical Trial Site 156004
    • Jiangyin, Jiangsu, China, 320281
      • Chiesi clinical Trial Site 156033
    • Nanjing, Jiangsu, China, 210006
      • Chiesi clinical Trial Site 156022
    • Suzhou, Jiangsu, China, 215000
      • Chiesi Clinical Trial Site 156049
  • Jiangxi
    • Jiujiang, Jiangxi, China, 332000
      • Chiesi Clinical Trial Site 156047
    • Nanchang, Jiangxi, China, 330000
      • Chiesi Clinical Trial Site 156041
    • Nanchang, Jiangxi, China, 330006
      • Chiesi clinical Trial Site 156028
    • Pingxiang, Jiangxi, China, 337000
      • Chiesi Clinical Trial Site 156042
  • Jilin
    • Changchun, Jilin, China, 130000
      • Chiesi clinical Trial Site 156023
    • Changchun, Jilin, China, 130000
      • Chiesi Clinical Trial Site 156036
    • Changchun, Jilin, China, 130021
      • Chiesi clinical Trial Site 156019
  • Liaoning
    • Shenyang, Liaoning, China, 110004
      • Chiesi Clinical Trial Site 156007
  • Ningxia
    • YinChuan, Ningxia, China, 750000
      • Chiesi clinical Trial Site 156025
  • Shanghai
    • Shanghai, Shanghai, China, 200025
      • Chiesi Clinical Trial Site 156014
    • Shanghai, Shanghai, China, 200031
      • Chiesi clinical Trial Site 156037
    • Shanghai, Shanghai, China, 200072
      • Chiesi Clinical Trial Site 156005
    • Shanghai, Shanghai, China, 200433
      • Chiesi Clinical Trial Site 156006
    • Shanghai, Shanghai, China, 200433
      • Chiesi Clinical Trial Site 156011
    • Shanghai, Shanghai, China, 210009
      • Chiesi Clinical Trial Site 156038
  • Shanxi
    • Taiyuan, Shanxi, China, 030001
      • Chiesi Clinical Trial Site 156039
  • Sichuan
    • Chengdu, Sichuan, China, 610000
      • Chiesi clinical Trial Site 156035
    • Chengdu, Sichuan, China, 610041
      • Chiesi Clinical Trial Site 156010
    • Chongqing, Sichuan, China, 400000
      • Chiesi clinical Trial Site 156032
  • Tianjin
    • Tianjin, Tianjin, China, 300052
      • Chiesi clinical Trial Site 156034
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310014
      • Chiesi clinical Trial Site 156018
    • Linhai, Zhejiang, China, 317000
      • Chiesi Clinical Trial Site 156046
• Korea, Republic of
  • Seoul, Korea, Republic of, 04401
    • Chiesi Clinical Trial Site 410011
  • Seoul, Korea, Republic of, 2559
    • Chiesi Clinical Trial Site 410013
  • Seoul, Korea, Republic of, 5030
    • Chiesi Clinical Trial Site 410014
  • Gang'weondo
    • Chuncheon, Gang'weondo, Korea, Republic of, 24289
      • Chiesi Clinical Trial Site 410003
  • Gyeonggido
    • Bucheon, Gyeonggido, Korea, Republic of, 420-717
      • Chiesi Clinical Trial Site 410001
    • Bucheon-si, Gyeonggido, Korea, Republic of, 14584
      • Chiesi Clinical Trial Site 410012
    • Goyang-si, Gyeonggido, Korea, Republic of, 10380
      • Chiesi Clinical Trial Site 410002
  • Jeonrabugdo
    • Jeonju, Jeonrabugdo, Korea, Republic of, 54907
      • Chiesi Clinical Trial Site 410005
  • Seoul Teugbyeols
    • Gyeonggi-do, Seoul Teugbyeols, Korea, Republic of, 135-720
      • Chiesi Clinical Trial Site 410009
  • Seoul Teugbyeolsi
    • Seoul, Seoul Teugbyeolsi, Korea, Republic of, 07345
      • Chiesi Clinical Trial Site 410008
    • Seoul, Seoul Teugbyeolsi, Korea, Republic of, 07985
      • Chiesi Clinical Trial Site 410007
    • Seoul, Seoul Teugbyeolsi, Korea, Republic of, 100-032
      • Chiesi Clinical Trial Site 410004
    • Seoul, Seoul Teugbyeolsi, Korea, Republic of, 136-705
      • Chiesi Clinical Trial Site 410006
  • Ulsan
    • Daegu, Ulsan, Korea, Republic of, 705-703
      • Chiesi Clinical Trial Site 410010
• Taiwan
  • Changhua, Taiwan, 500
    • Chiesi Clinical Trial Site 158010
  • Kaohsiung, Taiwan, 824
    • Chiesi Clinical Trial Site 158006
  • Taichung, Taiwan
    • Chiesi Clinical Trial Site 158008
  • Taipei, Taiwan, 11217
    • Chiesi Clinical Trial Site 158005
  • Taipei, Taiwan, 220
    • Chiesi Clinical Trial Site 158011
  • Keelung Municipality
    • Keelung, Keelung Municipality, Taiwan, 204
      • Chiesi Clinical Trial Site 158001
  • Penghu
    • Kaohsiung, Penghu, Taiwan, 83301
      • Chiesi Clinical Trial Site 158004
  • Taiwan Province
    • Changhua, Taiwan Province, Taiwan, 500
      • Chiesi Clinical Trial Site 158010
  • Yunlin
    • Douliu, Yunlin, Taiwan, 64041
      • Chiesi Clinical Trial Site 158003

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or Female adults aged > 40 years with a diagnosis of COPD
• Current smokers or ex-smokers
• A post-bronchodilator FEV1 < 50% of the predicted normal value and a post-bronchodilator FEV1/FVC ratio < 0.7 at least 10-15 minutes after 4 puffs (4 x 100 µg) of salbutamol pMDI
• At least one exacerbation in the 12 months preceding the screening visit

Exclusion Criteria:

• Pregnant or lactating women
• Diagnosis of asthma, history of allergic rhinitis or atopy
• Patients treated for exacerbations in the 4 weeks prior to screening visit
• Patients treated with non-cardioselective ß-blockers in the month preceding the 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 Pro Re Nata
• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CHF 5993 100/6/12.5 µg; Fixed combination of extrafine beclometasone dipropionate 100 µg plus formoterol fumarate 6 µg plus glycopyrronium bromide 12.5 µg / metered dose (BDP/FF/GB) (Beclometasone dipropionate / Formoterol Fumarate / glycoppyronium Bromide)	Drug: CHF 5993 100/6/12.5 µg; Fixed combination of extrafine beclometasone dipropionate 100 µg plus formoterol fumarate 6 µg plus glycopyrronium bromide 12.5 µg / metered dose
Active Comparator: Symbicort Turbuhaler 160/4.5 µg; Fixed combination of 160 µg budesonide + 4.5 µg formoterol fumarate (160µg + 4.5 µg expresses the delivered dose; 200 µg + 6 µg expresses the metered dose) ( BUD/FF) (Budesonide/Formoterol Fumarate)	Drug: 160 µg budesonide + 4.5 µg formoterol fumarate; Fixed combination of budesonide 160 µg plus formoterol fumarate 4.5 µg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from Baseline in pre-dose FEV1(Forced Expiratory Volume within the first second) at week 24	Change from Baseline in pre-dose FEV1(Forced Expiratory Volume within the first second) at week 24	Baseline to Week 24
Change from Baseline in 2-hour post-dose FEV1 at week 24	Change from Baseline in 2-hour post-dose FEV1 at week 24	Baseline to Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from Baseline in pre-dose morning FEV1 and 2-hour post-dose morning FEV1 at week 24	Change from Baseline in pre-dose morning FEV1 and 2-hour post-dose	Baseline to Week 24
Time to First COPD exacerbation	Time to First COPD exacerbation	Baseline to week 24
Rate of COPD exacerbations	Rate of COPD exacerbations	Baseline to week 24
Change in COPD Assessment Test (CAT)	Change in COPD Assessment Test (CAT)	At all visits (from baseline to Week 24)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Events and Adverse Drug reactions	Adverse Events and Adverse Drug reactions	Screening up to week 24

Collaborators and Investigators

• Sponsor: Chiesi Farmaceutici S.p.A.
• Investigators: Principal Investigator: Jinping Zheng, The First Affiliated Hospital of Guangzhou Medical University

Publications and helpful links

General Publications

• Zheng J, Baldi S, Zhao L, Li H, Lee KH, Singh D, Papi A, Grapin F, Guasconi A, Georges G. Efficacy and safety of single-inhaler extrafine triple therapy versus inhaled corticosteroid plus long-acting beta2 agonist in eastern Asian patients with COPD: the TRIVERSYTI randomised controlled trial. Respir Res. 2021 Mar 23;22(1):90. doi: 10.1186/s12931-021-01683-2.

Study record dates

Study Major Dates

• Study Start (Actual): December 14, 2016
• Primary Completion (Actual): May 26, 2020
• Study Completion (Actual): May 26, 2020

Study Registration Dates

• First Submitted: January 25, 2017
• First Submitted That Met QC Criteria: June 22, 2017
• First Posted (Actual): June 23, 2017

Study Record Updates

• Last Update Posted (Actual): April 1, 2021
• Last Update Submitted That Met QC Criteria: March 30, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Keywords: COPD; Triple Combination; Anticholinergics
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Adrenergic Agonists; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Budesonide; Formoterol Fumarate
• Other Study ID Numbers: CCD-5993AA1-14; China (Other Identifier: China: Food and Drug Administration); Taiwan (Other Identifier: Taiwan : Food and Drug Administration); South Korea (Other Identifier: Ministry of Food and Drugs Safety)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No