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)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis
ClinicalTrials.gov Identifier:
NCT00558285
First received: November 12, 2007
Last updated: November 28, 2012
Last verified: November 2012
  Purpose

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.


Condition Intervention Phase
Chronic Obstructive Pulmonary Disease (COPD)
Drug: indacaterol/glycopyrrolate
Drug: indacaterol
Drug: glycopyrrolate
Drug: placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official 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)

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Change From Baseline in Mean 24 Hour Heart Rate at Day 14 [ Time Frame: Baseline, Day 14 ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Change From Baseline in Mean 24 Hour Heart Rate at Day 1 [ Time Frame: Baseline, Day 1 ] [ Designated as safety issue: No ]
    Heart rate was assessed by Holter monitoring and was measured over a 24 hour period at day 1. 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 squares 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 after inhalation of salbutamol/albuterol + error.

  • Trough Forced Expiratory Volume in 1 Second (FEV1) at Day 1 and Day 14 [ Time Frame: Day 1, Day 14 ] [ Designated as safety issue: No ]
    Spirometry testing was performed in accordance with American Thoracic Society standards. Trough FEV1 was defined as the mean of two measurements at 23 hours 15 minutes and 23 hour 45 minutes post dosing. Baseline is defined as the mean of the two values taken at 45 minutes and 15 minutes prior to dosing at day 1. Least square means are based on the analysis of covariance: response variable=center + treatment + baseline value + Forced Expiratory Volume in one second (FEV1) before inhalation of salbutamol/albuterol + FEV1 30 minutes post inhalation of salbutamol/albuterol.

  • Trough Forced Vital Capacity (FVC) at Day 1 and Day 14 [ Time Frame: Day 1 and Day 14 ] [ Designated as safety issue: No ]
    Spirometry testing was performed in accordance with American Thoracic Society standards. Trough FVC was defined as the mean of two measurements at 23 hours 15 minutes and the 23 hours 45 minutes post dosing. Baseline was defined as the mean of the two values taken at 45 minutes and 15 minutes prior to dosing at day 1. Analysis of covariance: FVC parameter = center + treatment + baseline FVC + FEV1 before inhalation of salbutamol/albuterol + FEV1 30 min after inhalation of salbutamol/albuterol + error.

  • Change From Baseline in QTc (Fridericia's Formula) at Day 1 [ Time Frame: Baseline, Day 1 ] [ Designated as safety issue: No ]
    The change from baseline in QTc at 30 minutes, 4 hours and 23 hours 45 minutes post dose on day 1. QT calculated (QTc) was calculated from the QT interval and RR (in seconds) using Fridericia's formula: QTc = QT / 3√ RR. Least square means are based on the analysis of covariance: response variable = center + treatment + baseline value + FEV1 before inhalation of salbutamol/albuterol + FEV1 30 min post inhalation of salbutamol/albuterol.

  • Change From Baseline in QTc (Fridericia's Formula) at Day 7 [ Time Frame: Baseline, Day 7 ] [ Designated as safety issue: No ]
    The change from baseline in QTc at 30 minutes and 2 hours post dose on day 7. QT calculated (QTc) was calculated from the QT interval and RR (in seconds) using Fridericia's formula: QTc = QT / 3√ RR. Least square means are based on the analysis of covariance: response variable = center + treatment + baseline value + FEV1 before inhalation of salbutamol/albuterol + FEV1 30 min post inhalation of salbutamol/albuterol.

  • Change From Baseline in QTc (Fridericia's Formula) at Day 14 [ Time Frame: Baseline, Day 14 ] [ Designated as safety issue: No ]
    The change from baseline in QTc at 30 minutes, 4 hours and 23 hours 45 minutes post dose on day 14. QT calculated (QTc) was calculated from the QT interval and RR (in seconds) using Fridericia's formula: QTc = QT / 3√ RR. Least square means are based on the analysis of covariance: response variable = center + treatment + baseline value + FEV1 before inhalation of salbutamol/albuterol + FEV1 30 minutes post inhalation of salbutamol/albuterol.


Enrollment: 257
Study Start Date: November 2007
Study Completion Date: July 2008
Primary Completion Date: July 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: indacaterol/glycopyrrolate 600/100 μg

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
Inhalation capsule delivered via a single dose dry powder inhaler in the morning for 14 days.
Other Name: QVA149
Experimental: indacaterol/glycopyrrolate 300/100 μg

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
Inhalation capsule delivered via a single dose dry powder inhaler in the morning for 14 days.
Other Name: QVA149
Drug: placebo
Inhalation capsule delivered via a single dose dry powder inhaler in the morning for 14 days.
Experimental: indacaterol/glycopyrrolate 150/100 μg

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
Inhalation capsule delivered via a single dose dry powder inhaler in the morning for 14 days.
Other Name: QVA149
Drug: glycopyrrolate
Inhalation capsule delivered via a single dose dry powder inhaler in the morning for 14 days.
Active Comparator: indacaterol 300 μg

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
Inhalation capsule delivered via a single dose dry powder inhaler in the morning for 14 days.
Other Name: QAB149
Drug: placebo
Inhalation capsule delivered via a single dose dry powder inhaler in the morning for 14 days.
Placebo Comparator: placebo

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

  Eligibility

Ages Eligible for Study:   40 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00558285

  Show 40 Study Locations
Sponsors and Collaborators
Novartis
Investigators
Study Chair: Novartis Pharma AG Novartis Pharmaceuticals
  More Information

No publications provided

Responsible Party: Novartis
ClinicalTrials.gov Identifier: NCT00558285     History of Changes
Other Study ID Numbers: CQVA149A2203
Study First Received: November 12, 2007
Results First Received: October 23, 2012
Last Updated: November 28, 2012
Health Authority: Australia: Department of Health and Ageing Therapeutic Goods Administration
Belgium: Federal Agency for Medicinal Products and Health Products
Canada: Health Canada
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Federal Institute for Drugs and Medical Devices
Italy: The Italian Medicines Agency
Spain: Spanish Agency of Medicines
Turkey: Ministry of Health

Keywords provided by Novartis:
COPD
Chronic Obstructive Pulmonary Disease
Indacaterol
QVA149

Additional relevant MeSH terms:
Lung Diseases
Respiration Disorders
Pulmonary Disease, Chronic Obstructive
Lung Diseases, Obstructive
Respiratory Tract Diseases
Glycopyrrolate
Adjuvants, Anesthesia
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Muscarinic Antagonists
Cholinergic Antagonists
Cholinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 28, 2014