Phase II Study to Evaluate the Cardiac Safety of 2 Doses of CHF5993 Both Combined With CHF1535 BID Versus CHF1535 BID in Patients With Moderate to Severe COPD (CARSAF)

Randomized, Double-Blind, Active Controlled, 3-Arm Parallel Group, Multi-National, Multi-Centre Study To Evaluate The Cardiac Safety Of Two Doses Of CHF5993 BID Delivered Via HFA PMDI Both Combined With CHF1535 BID Delivered Via HFA PMDI Versus CHF1535 BID Delivered Via HFA PMDI In Patients With Moderate To Severe COPD

Cardiac Safety Study

Study Overview

• Status: Completed
• Conditions: Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD)
• Intervention / Treatment: Drug: CHF1535 + CHF5992 dose 1 BID; Drug: CHF1535 + CHF5992 dose2 BID; Drug: CHF1535 daily dose

Detailed Description

The purpose of this study is to demonstrate equivalence between CHF1535 plus CHF5992 (two different dosages) over CHF1535 alone in change from baseline in average 24-hour heart rate, as primary end point, and other ECG parameters.

• Study Type: Interventional
• Enrollment (Actual): 191
• Phase: Phase 2

Contacts and Locations

Study Locations

• Bulgaria
  • Sofia, Bulgaria, 1407
    • Hospital "Lozenets"
• Germany
  • Berlin, Germany, D-12165
    • Praxis Dr. Kampschulte
• Hungary
  • Budapest, Hungary, 1122
    • Fővárosi Önkormányzat Szent János Kórháza és Észak-budai Egyesített Kórházai Tüdőgondozó Szakrendelő
• Poland
  • Białystok, Poland, 15-003
    • ISPL Centrum Medyczne Robert M. Mróz
• Russian Federation
  • Moscow, Russian Federation, 127018
    • State Budgetary Healthcare Institution of Moscow City
• United Kingdom
  • Manchester, United Kingdom, M23 9QZ
    • Medicines Evaluation Unit, Langley Building

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male and female adults ≥ 40years and ≤ 80years old
2. Male subjects: they and/or their partner must be willing to use an approved method of contraception 1) from the time of dose administration and until 30 days after the last dose of study. Subjects must not donate sperm for 30 days after the last dose of study drug
3. Written informed consent obtained by the patient prior to any study related procedures

4. Outpatient with diagnosis of COPD (defined in GOLD guidelines, up to date 2010) at least in the 6 months before the screening visit, including:

   • Smoking history of at least 10 pack years defined as [(number of cigarettes smoked per day) x (number of years of smoking)]/20; both current and ex smokers are eligible. For patients who are in smoking cessation therapy this must be completed at least 1 week before study enrollment
   • Regular use of bronchodilators (e.g. β2-agonist or/and anticholinergics) in the previous 2 months at Visit 0
   • Post-bronchodilator FEV1 ≥ 30% and ≤ 60% of the predicted normal value
   • Post-bronchodilator FEV1/FVC ≤ 0.70

Exclusion Criteria:

1. Pregnant or lactating women or all women physiologically capable of becoming pregnant UNLESS they meet the following definition of postmenopausal: 12 months of natural (spontaneous) amenorrhea or 6 months of spontaneous amenorrhea with already documented serum FSH level > 40mlU/mL or are using one of the following acceptable methods of contraception

   • Surgical sterilization (e.g. bilateral tubal ligation, hysterectomy)
   • Hormonal contraception (implantable, patch, oral)
   • Double-barrier methods (any double combination of: IUD, male or female condom with spermicidal gel, diaphragm, sponge, cervical cap) Reliable contraception should be maintained throughout the study and for 30 days after study drug discontinuation
2. Current diagnosis of asthma or other respiratory disorders (other than COPD) which may interfere with data interpretation according to the investigator's opinion
3. Hospitalization due to COPD exacerbation in the three months prior to screening and during run-in period or COPD exacerbation requiring systemic steroids and or antibiotics in the 6 weeks prior to screening and during run-in period. COPD exacerbation will be defined according to the following criteria: a sustained worsening of the patient condition (dyspnoea, cough and/or sputum production/purulence), from the stable state and beyond normal day-to-day variations, that is acute in onset and necessitates a change in regular medication that includes prescription of oral corticosteroids and/or antibiotics, or need for hospitalization.
4. Patient with COPD who requires regular long term use of oxygen therapy
5. Patient who requires chronic mechanical ventilation for COPD
6. Patient treated regularly with oral or parenteral corticosteroids for their COPD
7. Change of COPD regular medication in the 4 weeks prior to enrollment
8. Unstable CV diseases
9. Known abnormality of any cardiac valve

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CHF5993 HFA pMDI dose 1, BID	Drug: CHF1535 + CHF5992 dose 1 BID; CHF1535 + CHF5992 dose 1 BID for 14 days
Experimental: CHF5993 HFA pMDI dose 2, BID	Drug: CHF1535 + CHF5992 dose2 BID; CHF1535 + CHF5992 dose 2 BID for 14 days
Active Comparator: CHF1535 HFA pMDI + Placebo; CHF1535 HFA pMDI BID plus placebo BID	Drug: CHF1535 daily dose; CHF1535 daily dose for 14 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in average 24-hour heart rate at Final visit	To assess the effect on change from baseline in average 24h Heart Rate at Day 14 of study treatment	Day 14 of study treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Heart Rate and ECG parameters variation	Pre and post-dose	Day 1 and Day 14 of Study Treatment

Collaborators and Investigators

• Sponsor: Chiesi Farmaceutici S.p.A.
• Investigators: Principal Investigator: Hans-Jörg Kampschulte, MD, Arzt für Innere Medizin und Pneumologie, Berlin, Germany

Publications and helpful links

Helpful Links

• Study Record on EU Clinical Trials Register including results
• CSR Synopsis available in the CHIESI Clinical Study Register

Study record dates

Study Major Dates

• Study Start: April 1, 2012
• Primary Completion (Actual): September 1, 2012
• Study Completion (Actual): January 1, 2013

Study Registration Dates

• First Submitted: April 23, 2012
• First Submitted That Met QC Criteria: April 24, 2012
• First Posted (Estimate): April 25, 2012

Study Record Updates

• Last Update Posted (Actual): October 29, 2021
• Last Update Submitted That Met QC Criteria: October 28, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Keywords: COPD
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive
• Other Study ID Numbers: CCD-1107-PR-0067; 2011-004759-37 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes

IPD Plan Description

Chiesi commits to sharing with qualified scientific and medical Researchers, conducting legitimate research, Patient-level Data, Study-level Data, the Clinical Protocol and the full CSR, providing access to clinical trial information consistently with the principle of safeguarding commercially confidential information and patient privacy. Any shared Patient-level Data is anonymized to protect personally identifiable information.

Chiesi access criteria and complete process for clinical data sharing is available on the Chiesi Group website.

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