A randomized, double blind, placebo controlled, multicenter study to determine the effect of QVA149 on mean 24-hours heart rate in patients with Chronic Obstructive Pulmonary Disease (COPD) - ND

• Register: EUCTR
• Last refreshed on: 12 June 2012
• Main ID: EUCTR2007-003670-25-IT
• Date of registration: 15/10/2007
• Prospective Registration: No
• Primary sponsor: NOVARTIS FARMA
• Public title: A randomized, double blind, placebo controlled, multicenter study to determine the effect of QVA149 on mean 24-hours heart rate in patients with Chronic Obstructive Pulmonary Disease (COPD) - ND
• Scientific title: A randomized, double blind, placebo controlled, multicenter study to determine the effect of QVA149 on mean 24-hours heart rate in patients with Chronic Obstructive Pulmonary Disease (COPD) - ND
• Date of first enrolment: 03/10/2007
• Target sample size: 250
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2007-003670-25
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: yes Other: no

Countries of recruitment

France, Germany, Italy, Spain

Key inclusion & exclusion criteria

Inclusion criteria:
1. Male or female adults aged ≥40 years, who have signed an Informed Consent Form prior to initiation of any study-related procedure. 2. Patients with moderate to severe stable COPD according to the GOLD Guidelines (2006) (see Appendix 3). 3. Patients who have smoking history of at least 10 pack years. 4. Patients with a post-bronchodilator FEV1 ≥30% and < 80% of the predicted normal and post-bronchodilator FEV1/FVC <0.70 at Visit 1 and Visit 3.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive urine pregnancy test. 2. Women of child-bearing potential (WOCBP), defined as all women physiologically capable of becoming pregnant, including women whose career, lifestyle, or sexual orientation precludes intercourse with a male partner and women whose partners have been sterilized by vasectomy or other means, UNLESS they meet the following definition of post-menopausal: 12 months of natural (spontaneous) amenorrhea or 6 months of spontaneous amenorrhea with serum FSH levels >40 mIU/mL, OR are using one or more 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) (if accepted by local regulatory authority and ethical committee) Reliable contraception should be maintained throughout the study and for 7 days after study drug discontinuation. 3. Patients requiring long term oxygen therapy (> 15 hr a day) on a daily basis for chronic hypoxemia, or who have been hospitalized or visited an emergency room for a COPD exacerbation in the 6 weeks prior to Visit 1 or during the screening period (up to Visit 4). 4. Patients who have had a respiratory tract infection within 6 weeks prior to Visit 1. Patients who develop a respiratory tract infection during the screening period must discontinue from the trial, but will be permitted to re-enroll at a later date (at least 6 weeks after the resolution of the respiratory tract infection). 5. Patients with concomitant pulmonary disease, pulmonary tuberculosis (unless confirmed by chest x-ray to be no longer active) or clinically significant bronchiectasis. 6. Patients with any history of asthma 7. Patients with blood eosinophil count > 400/mm3 8. Patients who, in the judgment of the investigator or the responsible Novartis personnel, have a clinically relevant laboratory abnormality or a clinically significant condition such as (but not limited to) unstable ischemic heart disease, left ventricular failure, long term prednisone therapy, history of myocardial infarction, arrhythmia (excluding stable AF), uncontrolled hypertension, narrow-angle glaucoma, symptomatic prostatic hyperplasia or bladder-neck obstruction or moderate to severe renal impairment, uncontrolled hypo- and hyperthyroidism, hypokalemia, hyperadrenergic state or any condition which might compromise patient safety or compliance, interfere with evaluation, or preclude completion of the study. 9. Patients with a history of episodes of cardiac failure, life threatening arrhythmias as seen during screening Holter monitoring and evidence of acute ischemic changes during the screening ECGs 10. Patients with uncontrolled diabetes Type I or diabetes Type II including patients with a history of blood glucose levels consistently outside the normal range or HbA1c > 8.0% of total Hb measured at Visit 1. 11. History of malignancy of any organ system (including lung cancer), treated or untreated, within the past 5 years whether or not there is evidence of local recurrence or metastases, with the exception of localized basal cell carcinoma of the skin. 12. Patients who are contraindicated for or who have shown an

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Chronic obstructive Pulmonary Disease (COPD)
MedDRA version: 9.1 Level: LLT Classification code 10061877 Term: Obstructive airways disorder

Intervention(s)

Product Name: indacaterol maleate
Product Code: QAB149
Pharmaceutical Form: Inhalation powder
INN or Proposed INN: indacaterol maleate
Concentration unit: µg/l microgram(s)/litre
Concentration type: equal
Concentration number: 300-
Pharmaceutical form of the placebo: Inhalation powder
Route of administration of the placebo: Inhalation use

Product Name: Indacaterol maleate/Glycopyrronium bromide
Product Code: QVA149
Pharmaceutical Form: Inhalation powder
INN or Proposed INN: Indacaterol maleate/Glycopyrronium bromide
Concentration unit: µg/l microgram(s)/litre
Concentration type: equal
Concentration number: 600-
Pharmaceutical form of the placebo: Inhalation powder
Route of administration of the placebo: Inhalation use

Product Name: indacaterol maleate/Glycopyrronium bromide
Product Code: QVA149
Pharmaceutical Form: Inhalation powder
INN or Proposed INN: Indacaterol maleate/Glycopyrronium bromide
Concentration unit: µg/l microgram(s)/litre
Concentration type: equal
Concentration number: 300-
Pharmaceutical form of the placebo: Inhalation powder
Route of administration of the placebo: Inhalation use

Product Name: indacaterol maleate/Glycopyrronium bromide
Product Code: QVA149
Pharmaceutical Form: Inhalation powder
INN or Proposed INN: Indacaterol maleate/Glycopyrronium bromide
Concentration unit: µg/l microgram(s)/litre
Concentration type: equal
Concentration number: 150-
Pharmaceutical form of the placebo: Inhalation powder
Route of administration of the placebo: Inhalation use

Primary Outcome(s)

Primary end point(s): To assess the effect of 14 days treatment with QVA 149 600/100 microgrami, QVA 149 300/100 microgrami, QVA 149 150/100 microgrami on change in mean 24-h heart rate (ventricular rate) compared to placebo delivered by the Single Dose Dry Powder Inhaler (SDDPI) Concept 1 once a day in patients with moderate to severe stable Chronic Obstructive Pulomonary Disease (COPD).

Main Objective: To assess the effect of 14 days treatment with QVA149 600µg/100µg, QVA149 300µg/100µg, QVA149 150µg/100µg on change in mean 24-h heart rate (ventricular rate) compared to placebo delivered by the Single Dose Dry Powder Inhaler (SDDPI) Concept 1 once a day in patients with moderate to severe stable Chronic Obstructive Pulmonary Disease (COPD).

Secondary Objective: To evaluate the effect of 14 days treatment with QVA149 600µg/100µg, 300µg/100µg and 150µg/100µg on change in mean 24-h heart rate (ventricular rate) compared to QAB149 300µg. To evaluate the effect of QVA149 600µg/100µg, 300µg/100µg, 150µg/100µg compared to placebo and QAB149 300µg on: Change in QTc at all time points assessed via ECGs on day 1, day 7 and day 14 (although all time points will be assessed, the main focus will be change in QTc at 30min, 4 h and 23h 45min post dose) 24 hour Holter assessments on day 1 and day 14 in terms of Change in heart rate at 30min, 4 h and 23h 45min hours post dose Number of Ventricular ectopic events including Singular premature ventricular contraction (PVC) Couplets, defined as two PVCs preceded and followed by regular beats Non-sustained Ventricular tachycardia (defined as three or more PVC?s and not meeting the definition of sustained ventricular tachycardia) pls see protocol

Secondary ID(s)

2007-003670-25-FR

CQVA149A2203