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)

NCT00558285 | Completed Phase 2 Results

• 1 other identifier: CQVA149A2203
• Study Type: interventional
• Target: 257
• Locations: 8 countries
• Sites: 40

Brief Summary

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.

Conditions

Chronic Obstructive Pulmonary Disease (COPD)

Keywords

COPD; Chronic Obstructive Pulmonary Disease; Indacaterol; QVA149

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Mean 24 Hour Heart Rate at Day 14

  Heart rate was assessed by Holter monitoring and was measured over a 24 hour period at day 14. Heart rate was defined as the average value over the 24 hour monitoring period. The baseline measurement was the average heart rate taken from the 24 hour Holter monitoring period performed at screening or the last 24-hour period before taking the first dose of study drug. Least square means are based on the analysis of covariance: 24 hours mean heart rate = center + treatment + baseline value + Forced Expiratory Volume in one second (FEV1) before inhalation of salbutamol/albuterol + FEV1 30 min post salbutamol/albuterol + error.

  Baseline, Day 14

Secondary Outcomes (6)

• Change From Baseline in Mean 24 Hour Heart Rate at Day 1

  Baseline, Day 1

• Trough Forced Expiratory Volume in 1 Second (FEV1) at Day 1 and Day 14

  Day 1, Day 14

• Trough Forced Vital Capacity (FVC) at Day 1 and Day 14

  Day 1 and Day 14

• Change From Baseline in QTc (Fridericia's Formula) at Day 1

  Baseline, Day 1

• Change From Baseline in QTc (Fridericia's Formula) at Day 7

  Baseline, Day 7

Study Arms (5)

indacaterol/glycopyrrolate 600/100 μg

EXPERIMENTAL

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.

Drug: indacaterol/glycopyrrolate

indacaterol/glycopyrrolate 300/100 μg

EXPERIMENTAL

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.

Drug: indacaterol/glycopyrrolate; Drug: placebo

indacaterol/glycopyrrolate 150/100 μg

EXPERIMENTAL

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.

Drug: indacaterol/glycopyrrolate; Drug: glycopyrrolate

indacaterol 300 μg

ACTIVE COMPARATOR

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.

Drug: indacaterol; Drug: placebo

placebo

PLACEBO COMPARATOR

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.

Drug: placebo

Interventions

indacaterol/glycopyrrolate DRUG

Inhalation capsule delivered via a single dose dry powder inhaler in the morning for 14 days.

Also known as: QVA149

indacaterol/glycopyrrolate 150/100 μg; indacaterol/glycopyrrolate 300/100 μg; indacaterol/glycopyrrolate 600/100 μg

indacaterol DRUG

Inhalation capsule delivered via a single dose dry powder inhaler in the morning for 14 days.

Also known as: QAB149

indacaterol 300 μg

glycopyrrolate DRUG

Inhalation capsule delivered via a single dose dry powder inhaler in the morning for 14 days.

indacaterol/glycopyrrolate 150/100 μg

placebo DRUG

Inhalation capsule delivered via a single dose dry powder inhaler in the morning for 14 days.

indacaterol 300 μg; indacaterol/glycopyrrolate 300/100 μg; placebo

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Novartis: lead

Study Sites (40)

Novartis Investigator Site

Adelaide, Australia

Location

Novartis Investigator Site

Clayton, Australia

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Daw Park, Australia

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Heidelberg, Australia

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Nedlands, Australia

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Brussels, Belgium

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Jambes, Belgium

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Jette, Belgium

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Liège, Belgium

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Ostend, Belgium

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Mississauga, Canada

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Newmarket, Canada

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Ottawa, Canada

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Pointe-Claire, Canada

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Québec, Canada

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Sainte-Foy, Canada

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Ambroise, France

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Lille, France

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Marseille, France

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Martigues, France

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Nantes, France

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Nice, France

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Perpignan, France

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Berlin, Germany

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Dortmund, Germany

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Erfurt, Germany

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Hanover, Germany

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Mainz, Germany

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Marburg, Germany

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Florence, Italy

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Modena, Italy

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Trieste, Italy

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Badalona, Spain

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Barakaldo, Spain

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Cáceres, Spain

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Centelles, Spain

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Mataró, Spain

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Valencia, Spain

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Istanbul, Turkey (Türkiye)

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Novartis Investigator Site

Izmir, Turkey (Türkiye)

Location

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Interventions

indacaterol; Glycopyrrolate; indacaterol-glycopyrronium combination

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Quaternary Ammonium Compounds; Amines; Organic Chemicals; Onium Compounds; Pyrrolidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

862-778-8300

Study Officials

• Novartis Pharma AG

  Novartis Pharmaceuticals

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 12, 2007
• First Posted: November 14, 2007
• Study Start: November 1, 2007
• Primary Completion: July 1, 2008
• Study Completion: July 1, 2008
• Last Updated: November 30, 2012
• Results First Posted: November 22, 2012

Record last verified: 2012-11

Locations

FR (7); TU (2); DE (6); BE (5); CA (6); ES (6); AU (5); IT (3)