Clinical trial NCT01584505: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD)
Keywords: COPD
Lead sponsor: Chiesi Farmaceutici S.p.A.
Sponsor class: INDUSTRY
First posted: 2012-04-25
Enrollment: 191
Sex: ALL
Minimum age (years): 40
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Cardiac Safety Study

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.

Eligibility criteria: 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

Primary outcomes:
measure: Change from baseline in average 24-hour heart rate at Final visit
timeFrame: Day 14 of study treatment
Secondary outcomes:
measure: Heart Rate and ECG parameters variation
timeFrame: Day 1 and Day 14 of Study Treatment
Other outcomes:
Locations:
city: Sofia
country: Bulgaria
facility: Hospital "Lozenets"
city: Berlin
country: Germany
facility: Praxis Dr. Kampschulte
city: Budapest
country: Hungary
facility: Fővárosi Önkormányzat Szent János Kórháza és Észak-budai Egyesített Kórházai Tüdőgondozó Szakrendelő
city: Białystok
country: Poland
facility: ISPL Centrum Medyczne Robert M. Mróz
city: Moscow
country: Russian Federation
facility: State Budgetary Healthcare Institution of Moscow city
city: Manchester
country: United Kingdom
facility: Medicines Evaluation Unit, Langley Building
Study officials:
affiliation: Arzt für Innere Medizin und Pneumologie, Berlin, Germany
name: Hans-Jörg Kampschulte, MD
role: PRINCIPAL_INVESTIGATOR
References: