Safety and Tolerability of QVA149 (Indacaterol/Glycopyrrolate) Compared to Placebo and to Indacaterol in Patients With Moderate to Severe Stable Chronic Obstructive Pulmonary Disease (COPD)

Novartis

Status and phase: Completed; Phase 2

Conditions: Chronic Obstructive Pulmonary Disease (COPD)

Treatments: Drug: indacaterol; Drug: placebo; Drug: indacaterol/glycopyrrolate; Drug: glycopyrrolate

Study type: Interventional

Funder types: Industry

Identifiers

NCT00558285

CQVA149A2203

Details and patient eligibility

About

An investigational inhalation product (QVA149) for the treatment of patients with Chronic Obstructive Pulmonary Disease (COPD) is being developed. This 14 day study will investigate the effect on heart rate and cardiovascular effects to ensure the product is safe.

Enrollment: 257 patients

Sex: All

Ages: 40+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Consented male or female adults aged ≥40 years
• Moderate to severe stable Chronic Obstructive Pulmonary Disease (COPD) according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) Guidelines (2006)
• Patients who have smoking history of at least 10 pack years
• Patients with a post-bronchodilator Forced Expiratory Volume in one second (FEV1) ≥30% and <80% of the predicted normal and post-bronchodilator FEV1/Forced vital capacity (FVC) <0.70 at Visit 1 and Visit 3

Exclusion criteria

• Pregnant or nursing (lactating) women
• Patients requiring long term oxygen therapy (> 15 hours 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 screening (Visit 1) or during the screening period
• Patients who had a respiratory tract infection within 6 weeks of Visit 1 or at screening
• Concomitant pulmonary disease, pulmonary tuberculosis (TB) (unless chest x-ray confirms no longer active) or clinically significant bronchiectasis
• Any history of asthma
• Patients who have clinically relevant lab abnormalities / conditions such as (but not limited to) long term prednisone therapy, unstable ischemic heart disease, left ventricular failure, history of myocardial infarction, arrhythmia (excluding stable atrial fibrillation [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
• Patients with a history of cardiac failure, life threatening arrhythmias (screening Holter) and acute ischemic changes (screening ECG)
• Patients with a history of long QT syndrome or whose QTc (Fridericia method) interval measured at screening (Visit 1) is prolonged (>450 ms for males or >470 for females)
• History of malignancy of any organ system, treated or untreated within the past 5 years
• Uncontrolled Type I / Type II Diabetes or blood glucose outside the normal range or Hemoglobin A1C (HbA1c) >8.0% of total hemoglobin measured at Visit 1

Other protocol-defined inclusion/exclusion criteria may apply

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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257 participants in 5 patient groups, including a placebo group

indacaterol/glycopyrrolate 600/100 μg

Experimental group

Description:

Two capsules indacaterol/glycopyrrolate 300/50 μg delivered via a single dose dry powder inhaler in the morning for 14 days. The use of salbutamol/albuterol as rescue medication was permitted throughout the study.

Treatment:

Drug: indacaterol/glycopyrrolate

indacaterol/glycopyrrolate 300/100 μg

Experimental group

Description:

One capsule indacaterol/glycopyrrolate 300/100 μg and one placebo capsule delivered via a single dose dry powder inhaler in the morning for 14 days. The use of salbutamol/albuterol as rescue medication was permitted throughout the study.

Treatment:

Drug: indacaterol/glycopyrrolate

Drug: placebo

indacaterol/glycopyrrolate 150/100 μg

Experimental group

Description:

One capsule indacaterol/glycopyrrolate 150/50 μg and one capsule 50 μg glycopyrrolate delivered via a single dose dry powder inhaler in the morning for 14 days. The use of salbutamol/albuterol as rescue medication was permitted throughout the study.

Treatment:

Drug: indacaterol/glycopyrrolate

Drug: glycopyrrolate

indacaterol 300 μg

Active Comparator group

Description:

One capsule indacaterol 300 μg and one placebo capsule delivered via s single dose dry powder inhaler in the morning for 14 days. The use of salbutamol/albuterol as rescue medication was permitted throughout the study.

Treatment:

Drug: placebo

Drug: indacaterol

placebo

Placebo Comparator group

Description:

Two placebo capsules delivered via a single dose dry powder inhaler in the morning for 14 days. The use of salbutamol/albuterol as rescue medication was permitted throughout the study.

Treatment:

Drug: placebo