FORSYYN: Foster® pMDI (CHF 1535) Versus Symbicort® Turbohaler in COPD Patient

Sponsor

Chiesi Farmaceutici S.p.A. (Industry)

Overall Status

Completed

CT.gov ID

NCT03888131

Collaborator

(none)

750

Enrollment

Locations

Arms

45.2

Actual Duration (Months)

14.2

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of the study is to demonstrate the non-inferiority of CHF1535 pMDI versus Symbicort® Turbohaler® in terms of lung function parameters and patients reported outcomes and to assess its safety and tolerability.

Condition or Disease	Intervention/Treatment	Phase
Chronic Obstructive Pulmonary Disease	Drug: CHF 1535 100/6 µg pMDI plus Symbicort® Turbohaler® Placebo Drug: Symbicort® Turbohaler® plus CHF 1535 pMDI Placebo	Phase 3

Study Design

Study Type:

Interventional

Actual Enrollment :

750 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

Official Title:

A 24-week, Double Blind, Double Dummy, Randomized, Multicentre, 2-arm Parallel Group, Active Controlled Clinical Trial of Fixed Combination of Beclometasone Dipropionate Plus Formoterol Fumarate Administered Via pMDI (CHF 1535) Versus the Fixed Combination of Budesonide Plus Formoterol Fumarate (Symbicort® Turbohaler®) in Patients With Chronic Obstructive Pulmonary Disease

Actual Study Start Date :

Jul 30, 2018

Actual Primary Completion Date :

May 6, 2022

Actual Study Completion Date :

May 6, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: CHF 1535 100/6 µg pMDI 2 inhalations BID Total Daily Dose = 400/24µg	Drug: CHF 1535 100/6 µg pMDI plus Symbicort® Turbohaler® Placebo Fixed combination of beclometasone dipropionate 100 µg plus formoterol fumarate 6 µg (BDP/FF)
Active Comparator: Symbicort® Turbohaler® 2 inhalations BID Total Daily Dose = 640/18µg	Drug: Symbicort® Turbohaler® plus CHF 1535 pMDI Placebo Fixed combination of 160 µg budesonide + 4.5 µg formoterol fumarate (BUD/FF)

Arm

Intervention/Treatment

Experimental: CHF 1535 100/6 µg pMDI

2 inhalations BID Total Daily Dose = 400/24µg

Drug: CHF 1535 100/6 µg pMDI plus Symbicort® Turbohaler® Placebo

Fixed combination of beclometasone dipropionate 100 µg plus formoterol fumarate 6 µg (BDP/FF)

Active Comparator: Symbicort® Turbohaler®

2 inhalations BID Total Daily Dose = 640/18µg

Drug: Symbicort® Turbohaler® plus CHF 1535 pMDI Placebo

Fixed combination of 160 µg budesonide + 4.5 µg formoterol fumarate (BUD/FF)

Outcome Measures

Primary Outcome Measures

Demonstration of the non-inferiority of CHF 1535 pMDI versus Symbicort® Turbohaler® in terms of pulmonary function [At week 24]
Change from baseline in pre-dose morning First Expiratory Volume in 1 second (FEV1) in patients with Chronic Obstructive Pulmonary Disease (COPD)

Secondary Outcome Measures

Effect of CHF 1535 on change from baseline pre-dose morning FEV1 [At week 4, week 12, week 18 and week 24]
FEV1 is the volume of air that can be forced out in one second after taking a deep breath. FEV1 will be measured via spirometer.
Effect of CHF 1535 on chnage from Baseline in pre-dose morning Force Vital Capacity (FVC) [At week 4, week 12, week 18 and week 24]
FVC is the volume of air expired after a maximum inspiration. FVC will be measured via spirometer.
Effect of CHF 1535 on change from baseline in the St. George's Respiratory Questionnaire (SGRQ) total scores and domains [At week 12, week 24]
The SGRQ is a well-established, self-completed tool to measure impact on overall health, daily life and perceived well-being in patients with obstructive airways disease. Score range from 0 to 100 with higher scores indicating more limitations.
Effect of CHF 1535 on change from baseline in COPD Assessment Test (CAT) [Over 28 weeks]
CAT is an easy questionnaire self-administered by patients. It was specifically designed to measure candidate items regarding daily symptoms, activity limitations and other manifestations of the COPD. It will be filled in at all clinical visits.
Effect of CHF 1535 on the rate of COPD exacerbations [Over 24 weeks of treatment]
The number of moderate and severe COPD exacerbations during the treatment period will be collected and analyzed. Moderate exacerbations require treatment with systemic corticosteroids and/or antibiotics Severe exacerbations require hospitalisation or result in death
Number of patients with Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) [Over 29 weeks (from Visit 0 to Visit 6)]
An AE is "any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment". A SAE is defined as any untoward medical occurrence or effect that, at any dose may result in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment.
Assessment of blood pressure [Over 28 weeks (from Visit 1 to Visit 6)]
Systolic and diastolic blood pressure will be measured at all clinical visits from Visit 1 after 10 minutes in seated resting position.
Number of subjects with abnormal Electrocardiogram (ECG) findings [At screening visit and week 24]
Twelve-lead ECG measurements will be obtained after the subject laid in a resting position for 10 minutes. ECG will be recorded in triplicate and evaluated at Visit 1 and Visit 6.
Number of subjects with abnormal Haematology parameters [At screening visit and week 24]
The following Haematology parameters will be assessed by a central laboratory: Red blood cells count (RBC), white blood cells count (WBC) and differential, total haemoglobin (Hb), hematocrit (Hct), platelets count (PLT).
Number of subjects with abnormal Blood Chemistry parameters [At screening visit and week 24]
The following Blood Chemistry parameters will be assessed by a central laboratory: creatinine, BUN, fasting serum glucose, aspartate aminotransferase (AST), alanine aminotransferase (ALT), Gamma-glutamyl transpeptidase (γ-GT), total bilirubin, alkaline phosphatase, sodium, potassium, calcium, and chloride electrolytes (Na, K, Ca, Cl), albumin.

Eligibility Criteria

Criteria

Ages Eligible for Study:

40 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Adults aged ≥ 40 years, Chinese ethnicity
Patients with COPD diagnosed at least 12 months before the screening visit.
A smoking history of at least 10 pack years
Post-bronchodilator FEV1 < 50% of the predicted normal value
Post-bronchodilator FEV1/FVC ratio < 0.7
One exacerbation in the 12 months prior the screening visit

Exclusion Criteria:

Patients requiring OCS/antibiotics/PDE inhibitors in the 4 weeks prior to screening
COPD exacerbation requiring OCS/antibiotics or hospitalization during the run-in period
Known respiratory disorders other than COPD
Diagnosis of asthma

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Site 15604 - Anhui Provincial Hospital	Hefei	Anhui	China	230001
2	Site 15635 - The Second Hospital of Anhui Medical Hospital	Hefei	Anhui	China	231200
3	Site 15613 - Beijing Friendship Hospital, Capital Medical University	Beijing	Beijing	China	100050
4	Site 15611 - Xuanwu Hospital Capital Medical University	Beijing	Beijing	China	100053
5	Site 15640 - Peking University Shougang Hospital	Beijing	Beijing	China	100144
6	Site 15626 - Peking University Third Hospital	Beijing	Beijing	China	100191
7	Site 15612 - Beijing Tong Ren Hospital, Capital Medical University	Beijing	Beijing	China	100730
8	Site 15634 - Chongqing General Hospital	Chongqing	Chongqing	China	400013
9	Site 15616 - Chongqing Red Cross Hospital, People's Hospital of Jiangbei District	Chongqing	Chongqing	China	400020
10	Site 15636 - Fujian Province Hospital	Fuzhou	Fujian	China	350001
11	Site 15650 - The First Hospital of Lanzhou University	Lanzhou	Gansu	China	730000
12	Site 15630 - Dongguan People's Hospital	Dongguan	Guangdong	China	523059
13	Site 15607 - The First People's Hospital of Shunde	Foshan	Guangdong	China	528300
14	Site 15619 - The Third Affiliated Hospital of Southern Medical University	Guangzhou	Guangdong	China	510000
15	Site 15608 - The First Affiliated Hospital Sun Yat-sen University	Guangzhou	Guangdong	China	510030
16	Site 15646 - The Second Affiliated Hospital of Guangzhou Medical University	Guangzhou	Guangdong	China	510260
17	Site 15651 - The Second Xiangya Hospital of Central South University	Guangzhou	Guangdong	China	510260
18	Site 15614 - Guangzhou Panyu central hospital	Guangzhou	Guangdong	China	511400
19	Site 15618 - Affiliated Hospital of Guangdong Medical University	Zhanjiang	Guangdong	China	524000
20	Site 15656 - The People's Hospital of Guangxi Zhuang Autonomous Region	Nanning	Guangxi	China	530021
21	Site 15637 - Affiliated Hospital of Zunyi Medical College	Zunyi	Guizhou	China	563099
22	Site 15623 - Haikou People's Hospital	Haikou	Hainan	China	570208
23	Site 15645 - Hainan General Hospital	Haikou	Hainan	China	570311
24	Site 15654 - Henan Provincial People's Hospital	Zhengzhou	Henan	China	450003
25	Site 15617 - Henan Provincial Chest Hospital	Zhengzhou	Henan	China	450008
26	Site 15622 - The Third Hospital of Changsha	Changsha	Hunan	China	410015
27	Site 15647 - The Second hospital. University of South China	Hengyang	Hunan	China	421001
28	Site 15653 - Xiangtan Central Hospital	Xiangtan	Hunan	China	411100
29	Site 15603 - The Affiliated Hospital of Inner Mongolia Medical University	Hohhot	Inner Mongolia	China	010050
30	Site 15657 - Zhong Da Hospital, Southeast University	Nanjing	Jiangsu	China	210009
31	Site 15627 - Nanjing Medical University Affiliated 2nd Hospital	Nanjing	Jiangsu	China	210011
32	Site 15621 - Wuxi People's Hospital	Wuxi	Jiangsu	China	241023
33	Site 15632 - Xuzhou Central Hospital	Xuzhou	Jiangsu	China	221009
34	Site 15659 - Jiangxi Provincial People's Hospital	Nanchang	Jiangxi	China	330006
35	Site 15658 - Jilin Province People's Hospital	Changchun	Jilin	China	130021
36	Site 15643 - No.2 Hospital Affiliated to Jilin University	Changchun	Jilin	China	130041
37	Site 15648 - Dalian Municipal Central Hospital Affiliated of Dalian Medical University	Dalian	Liaoning	China	116033
38	Site 15644 - Jinan Central Hospital	Jinan	Shandong	China	250013
39	Site 15629 - Shanghai East Hospital	Shanghai	Shanghai	China	2000120
40	Site 15628 - Shanghai Xuhui Center Hospital	Shanghai	Shanghai	China	200031
41	Site 15601 - Huadong Hospital Afflilliated to Fudan University	Shanghai	Shanghai	China	200040
42	Site 15631 - Shanghai Yangpu District Centre Hospital	Shanghai	Shanghai	China	200090
43	Site 15610 - Tong Ren Hospital Shanghai Jiaotong University School of Medicine	Shanghai	Shanghai	China	200336
44	Site 15606 - Shanghai Pulmonary Hospital	Shanghai	Shanghai	China	200433
45	Site 15625 - Central Hospital of Shanghai Minhang District	Shanghai	Shanghai	China	201199
46	Site 15638 - Second Hospital of Shanxi Medical	Taiyuan	Shanxi	China	0300001
47	Site 15649 - The 1st Affiliated Hospital of Shanxi Medical University	Taiyuan	Shanxi	China	030001
48	Site 15605 - West China Hospital, Sichuan University	Chengdu	Sichuan	China	610041
49	Site 15609 - Tianjin First Center Hospital	Tianjin	Tianjin	China	300192
50	Site 15633 - Tianjin Haihe Hospital	Tianjin	Tianjin	China	300350
51	Site 15602 - Hangzhou First People's Hospital	Hangzhou	Zhejiang	China	310006
52	Site 15642 - Taizhou Hospital of Zhejiang Province	Taizhou	Zhejiang	China	317000
53	Site 15639 -The second Affiliated Hospital of Wenzhou Medical College	Wenzhou	Zhejiang	China	325027