search
Back to results

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)

Primary Purpose

Chronic Obstructive Pulmonary Disease (COPD)

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
indacaterol/glycopyrrolate
indacaterol
glycopyrrolate
placebo
Sponsored by
Novartis
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Chronic Obstructive Pulmonary Disease (COPD) focused on measuring COPD, Chronic Obstructive Pulmonary Disease, Indacaterol, QVA149

Eligibility Criteria

40 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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  • Concomitant pulmonary disease, pulmonary tuberculosis (TB) (unless chest x-ray confirms no longer active) or clinically significant bronchiectasis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

Sites / Locations

  • Novartis Investigator Site
  • Novartis Investigator Site
  • Novartis Investigator Site
  • Novartis Investigator site
  • Novartis Investigator Site
  • Novartis Investigator Site
  • Novartis Investigator Site
  • Novartis Investigator Site
  • Novartis Investigator site
  • Novartis Investigator Site
  • Novartis Investigator Site
  • Novartis Investigator Site
  • Novartis Investigator Site
  • Novartis Investigator Site
  • Novartis Investigator Site
  • Novartis Investigator Site
  • Novartis Investigator Site
  • Novartis Investigator Site
  • Novartis Investigator Site
  • Novartis investigator site
  • Novartis Investigator Site
  • Novartis Investigator site
  • Novartis Investigator Site
  • Novartis Investigator Site
  • Novartis Investigator Site
  • Novartis Investigator Site
  • Novartis Investigator Site
  • Novartis Investigator Site
  • Novartis Investigator Site
  • Novartis Investigator Site
  • Novartis Investigator site
  • Novartis Investigator Site
  • Novartis Investigator Site
  • Novartis Investigator Site
  • Novartis Investigator Site
  • Novartis Investigator Site
  • Novartis Investigator Site
  • Novartis Investigator Site
  • Novartis Investigator Site
  • Novartis Investigator Site

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Experimental

Experimental

Experimental

Active Comparator

Placebo Comparator

Arm Label

indacaterol/glycopyrrolate 600/100 μg

indacaterol/glycopyrrolate 300/100 μg

indacaterol/glycopyrrolate 150/100 μg

indacaterol 300 μg

placebo

Arm 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.

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.

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.

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.

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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

Full Information

First Posted
November 12, 2007
Last Updated
November 28, 2012
Sponsor
Novartis
search

1. Study Identification

Unique Protocol Identification Number
NCT00558285
Brief Title
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)
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)
Study Type
Interventional

2. Study Status

Record Verification Date
November 2012
Overall Recruitment Status
Completed
Study Start Date
November 2007 (undefined)
Primary Completion Date
July 2008 (Actual)
Study Completion Date
July 2008 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis

4. Oversight

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Obstructive Pulmonary Disease (COPD)
Keywords
COPD, Chronic Obstructive Pulmonary Disease, Indacaterol, QVA149

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
257 (Actual)

8. Arms, Groups, and Interventions

Arm Title
indacaterol/glycopyrrolate 600/100 μg
Arm Type
Experimental
Arm 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.
Arm Title
indacaterol/glycopyrrolate 300/100 μg
Arm Type
Experimental
Arm 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.
Arm Title
indacaterol/glycopyrrolate 150/100 μg
Arm Type
Experimental
Arm 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.
Arm Title
indacaterol 300 μg
Arm Type
Active Comparator
Arm 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.
Arm Title
placebo
Arm Type
Placebo Comparator
Arm 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.
Intervention Type
Drug
Intervention Name(s)
indacaterol/glycopyrrolate
Other Intervention Name(s)
QVA149
Intervention Description
Inhalation capsule delivered via a single dose dry powder inhaler in the morning for 14 days.
Intervention Type
Drug
Intervention Name(s)
indacaterol
Other Intervention Name(s)
QAB149
Intervention Description
Inhalation capsule delivered via a single dose dry powder inhaler in the morning for 14 days.
Intervention Type
Drug
Intervention Name(s)
glycopyrrolate
Intervention Description
Inhalation capsule delivered via a single dose dry powder inhaler in the morning for 14 days.
Intervention Type
Drug
Intervention Name(s)
placebo
Intervention Description
Inhalation capsule delivered via a single dose dry powder inhaler in the morning for 14 days.
Primary Outcome Measure Information:
Title
Change From Baseline in Mean 24 Hour Heart Rate at Day 14
Description
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.
Time Frame
Baseline, Day 14
Secondary Outcome Measure Information:
Title
Change From Baseline in Mean 24 Hour Heart Rate at Day 1
Description
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.
Time Frame
Baseline, Day 1
Title
Trough Forced Expiratory Volume in 1 Second (FEV1) at Day 1 and Day 14
Description
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.
Time Frame
Day 1, Day 14
Title
Trough Forced Vital Capacity (FVC) at Day 1 and Day 14
Description
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.
Time Frame
Day 1 and Day 14
Title
Change From Baseline in QTc (Fridericia's Formula) at Day 1
Description
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.
Time Frame
Baseline, Day 1
Title
Change From Baseline in QTc (Fridericia's Formula) at Day 7
Description
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.
Time Frame
Baseline, Day 7
Title
Change From Baseline in QTc (Fridericia's Formula) at Day 14
Description
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.
Time Frame
Baseline, Day 14

10. Eligibility

Sex
All
Minimum Age & Unit of Time
40 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharma AG
Organizational Affiliation
Novartis Pharmaceuticals
Official's Role
Study Chair
Facility Information:
Facility Name
Novartis Investigator Site
City
Adelaide
Country
Australia
Facility Name
Novartis Investigator Site
City
Clayton
Country
Australia
Facility Name
Novartis Investigator Site
City
Daw Park
Country
Australia
Facility Name
Novartis Investigator site
City
Heidelberg
Country
Australia
Facility Name
Novartis Investigator Site
City
Nedlands
Country
Australia
Facility Name
Novartis Investigator Site
City
Brussels
Country
Belgium
Facility Name
Novartis Investigator Site
City
Jambes
Country
Belgium
Facility Name
Novartis Investigator Site
City
Jette
Country
Belgium
Facility Name
Novartis Investigator site
City
Liege
Country
Belgium
Facility Name
Novartis Investigator Site
City
Oostende
Country
Belgium
Facility Name
Novartis Investigator Site
City
Mississauga
Country
Canada
Facility Name
Novartis Investigator Site
City
Newmarket
Country
Canada
Facility Name
Novartis Investigator Site
City
Ottawa
Country
Canada
Facility Name
Novartis Investigator Site
City
Pointe-Claire
Country
Canada
Facility Name
Novartis Investigator Site
City
Quebec
Country
Canada
Facility Name
Novartis Investigator Site
City
Sainte-Foy
Country
Canada
Facility Name
Novartis Investigator Site
City
Ambroise
Country
France
Facility Name
Novartis Investigator Site
City
Lille
Country
France
Facility Name
Novartis Investigator Site
City
Marseille
Country
France
Facility Name
Novartis investigator site
City
Martigues
Country
France
Facility Name
Novartis Investigator Site
City
Nantes
Country
France
Facility Name
Novartis Investigator site
City
Nice
Country
France
Facility Name
Novartis Investigator Site
City
Perpignan
Country
France
Facility Name
Novartis Investigator Site
City
Berlin
Country
Germany
Facility Name
Novartis Investigator Site
City
Dortmund
Country
Germany
Facility Name
Novartis Investigator Site
City
Erfurt
Country
Germany
Facility Name
Novartis Investigator Site
City
Hannover
Country
Germany
Facility Name
Novartis Investigator Site
City
Mainz
Country
Germany
Facility Name
Novartis Investigator Site
City
Marburg
Country
Germany
Facility Name
Novartis Investigator Site
City
Firenze
Country
Italy
Facility Name
Novartis Investigator site
City
Modena
Country
Italy
Facility Name
Novartis Investigator Site
City
Trieste
Country
Italy
Facility Name
Novartis Investigator Site
City
Badalona
Country
Spain
Facility Name
Novartis Investigator Site
City
Baracaldo
Country
Spain
Facility Name
Novartis Investigator Site
City
Caceres
Country
Spain
Facility Name
Novartis Investigator Site
City
Centelles
Country
Spain
Facility Name
Novartis Investigator Site
City
Mataro
Country
Spain
Facility Name
Novartis Investigator Site
City
Valencia
Country
Spain
Facility Name
Novartis Investigator Site
City
Istanbul
Country
Turkey
Facility Name
Novartis Investigator Site
City
Izmir
Country
Turkey

12. IPD Sharing Statement

Learn more about this trial

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)

We'll reach out to this number within 24 hrs