Clinical study to assess the effect of QVA149 on cardiac functions in COPD patients

• Register: EUCTR
• Last refreshed on: 22 January 2018
• Main ID: EUCTR2014-004680-21-DE
• Date of registration: 26/02/2015
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharma GmbH
• Public title: Clinical study to assess the effect of QVA149 on cardiac functions in COPD patients
• Scientific title: A randomized, double-blinded, single-center, placebo controlled, cross-over study to assess the effect of QVA149 (indacaterol maleate / glycopyrronium bromide) on cardiac function in patients with chronic obstructive pulmonary disease (COPD)
• Date of first enrolment: 23/04/2015
• Target sample size: 62
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-004680-21
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: no; Cross over: yes; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): yes

Countries of recruitment

Germany

Contacts

• Name: Medizinischer Infoservice
• Affiliation: Novartis Pharma GmbH

• Name: Medizinischer Infoservice
• Affiliation: Novartis Pharma GmbH

Key inclusion & exclusion criteria

Inclusion criteria:
1. Written informed consent must be obtained before any assessment is performed.
2. Male or female subjects, aged = 40 years, giving written Informed Consent and who are willing and capable to comply with all study procedures.
3. Patients with stable COPD according to the current GOLD guidelines (GOLD 2014).
4. Patients with airflow limitation indicated by a post-bronchodilator FEV1 <80% of the predicted normal value and a post-bronchodilator FEV1/FC<0.7 at Visit 3. Post-bronchodilator refers to within 10-15 min after inhalation of 400 µg (4x100 µg) of salbutamol.
5. Current or ex-smokers who have a smoking history of at least 10 pack years. (Ten pack-years are defined as 20 cigarettes a day for 10 years, or 10 cigarettes a day for 20 years etc.)
6. Hyperinflated patients with RVol>135% predicted as measured at Visit 3, before intake of salbutamol.

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 20
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 42

Exclusion criteria:
1. Pat. with conditions contraindicated for treatment with, or having a history of reactions/hypersensitivity to any of the following inhaled drugs, drugs of a similar class or any component thereof
• anticholinergics
• long and short acting beta-2 agonists
• sympathomimetic amines
• lactose or any of the other excipients
2. Pat. with a history of long QT syndrome or whose QTcF (Fredericia method) measured at Visit 3 is prolonged (>450 ms for males and >470 ms for females). These patients should not be re-screened.
3. Pat. who have a clinically significant abnormality on the ECG at Visit 3, who in the judgment of the investigator would be at potential risk if enrolled into the study. These patients should not be re-screened.
4. Pat. who have clinically significant cardiovascular abnormalities, which could interfere with the assessment of the study treatment
5. Pat. with a known history or current atrial fibrillation to be confirmed by ECG at Visit 3.
6. Pat. with pacemaker or bypass.
7. Pat. with a mean sitting systolic blood pressure >160 mmHg and/or mean sitting diastolic blood pressure >90 mmHg at Visit 3. These pats. will be permitted to be rescreened after having achieved controlled disease status following initiation or intensification of antihypertensive therapy. Re-screening can start at Visit 2, 4 weeks after change of antihypertensive medication.
8. Past or present disease, which as judged by the investigator, may affect the outcome of this study. These diseases include, but are not limited to history of hepatic disease, renal disease, hematological disease, neurological and psychiatric disease, endocrine disease or pulmonary disease other than COPD (including but not confined to tuberculosis, bronchiectasis, cystic fibrosis, pulmonary hypertension, sarcoidosis, interstitial lung disease or lung fibrosis).
9. History of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases.
10. Pat. with narrow-angle glaucoma, symptomatic benign prostatic hyperplasia or bladder-neck obstruction or severe renal impairment (GFR<30 mL/min/1.73 m2) including those with end-stage renal disease requiring dialysis or urinary retention. Benign Prostatic Hyperplasia (BPH) patients who are stable on treatment can be considered.
11. Pat. with Type I or uncontrolled Type II diabetes.
12. Pat. with active/ clinical history of asthma.
13. Pat. unable to undergo MRI scans, including claustrophobia or presence of any metal objects within the patient, preventing from MRI scan. A separate MRI patient informed consent form including MRI safety will be signed by the patient before each MRI exam.
14. History of lower respiratory tract infection within four weeks prior to Visit 2 and between Visit 2 and Visit 4. These patients will not be eligible, but will be permitted to be re-screened 4 weeks after the resolution of the respiratory tract infection and can re-start at Visit 2.
15. History of one COPD exacerbation that required treatment with antibiotics, systemic steroids or hospitalization within 3 months prior to Visit 2.
16. More than one COPD exacerbation that required treatment with antibiotics, systemic steroids or hospitalization within 6 months prior Visit 2.
17. Pat. who develop a COPD exacerbation between Visit 2 and Visit 4 will not be eligible but will be permitted to be

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

Health Condition(s) or Problem(s) studied

chronic obstructive pulmonary disease (COPD)
MedDRA version: 19.0 Level: LLT Classification code 10010952 Term: COPD System Organ Class: 100000004855

Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]

Intervention(s)

Trade Name: Ultibro Breezhaler
Product Code: QVA149
Pharmaceutical Form: Inhalation powder, hard capsule
INN or Proposed INN: Indacaterol maleate
CAS Number: 753498-25-8
Current Sponsor code: QAB149
Other descriptive name: INDACATEROL MALEATE
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 110-
INN or Proposed INN: GLYCOPYRRONIUM BROMIDE
CAS Number: 596-51-0
Current Sponsor code: NVA237
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 50-
Pharmaceutical form of the placebo: Inhalation powder, hard capsule
Route of administration of the placebo: Inhalation use

Primary Outcome(s)

Primary end point(s): The primary efficacy variable is the left ventricular enddiastolic volume assessed by MRI after 2 weeks of treatment.

Main Objective: To determine the effect of once-daily QVA149 (110/50 µg o.d.) compared with placebo on left ventricular enddiastolic volume as measured by MRI after 2 weeks of treatment in hyperinflated COPD patients.

Secondary Objective: • To evaluate the effects of QVA149 compared to placebo on lung function parameters after 14 days of treatment, as measured by:
o Forced spirometry (75 min post-dose)
- FEV1 and FVC
o Bodyplethysmography (60 min post-dose):
- inspiratory capacity (IC)
- total lung capacity (TLC)
- residual volume (RVol)
- specific airway resistance (sRaw)
- functional residual capacity (FRC)

To evaluate the effects of QVA149 compared to placebo on cardiac parameters, as measured by MRI after 14 days of treatment:
o right and left ventricular ejection fraction
o right and left ventricular endsystolic volumes
o right ventricular enddiastolic volume
o cardiac output

Timepoint(s) of evaluation of this end point: 14 days

Secondary Outcome(s)

Secondary end point(s): All secondary endpoints (lung function- and other cardiac function parameters) will be analyzed analogous to the primary endpoint. Exploratory endpoints and Qol-measurements will be analyzed descriptively.

Timepoint(s) of evaluation of this end point: 14 days

Secondary ID(s)

CQVA149ADE05

Source(s) of Monetary Support

Novartis Pharma GmbH