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

History of Changes

Tracking Information

First Received Date ^ICMJE

November 12, 2007

Last Updated Date

November 28, 2012

Start Date ^ICMJE

November 2007

Primary Completion Date

July 2008 (final data collection date for primary outcome measure)

Current Primary Outcome Measures ^ICMJE

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.

Original Primary Outcome Measures ^ICMJE

To assess the effect of 14 days treatment with QVA149 600µg/100µg, QVA 300µg/100µg, QVA149 150µg/100µg on change in mean 24h heart rate compared to placebo delivered by a Single Dose Dry Powder Inhaler (SDDPI [ Time Frame: 14 days ]

Change History

Complete list of historical versions of study NCT00558285 on ClinicalTrials.gov Archive Site

Current Secondary Outcome Measures ^ICMJE

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.

Original Secondary Outcome Measures ^ICMJE

Change in mean 24h heart rate after 1 & 14 days (D) treatment with QVA v. QAB (also QVA v placebo at 1D). Change in QTc on D 1,7, 14. 24 h Holter assessments on D1, D14. QVA v. placebo & QAB for FEV1 and FVC at all timepoints. [ Time Frame: varies, 1-14 days (details above) ]

Current Other Outcome Measures ^ICMJE

Not Provided

Original Other Outcome Measures ^ICMJE

Not Provided

Descriptive Information

Brief Title ^ICMJE

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 ^ICMJE

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)

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.

Detailed Description

Not Provided

Study Type ^ICMJE

Interventional

Study Phase

Phase 2

Study Design ^ICMJE

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment

Condition ^ICMJE

Chronic Obstructive Pulmonary Disease (COPD)

Intervention ^ICMJE

Drug: indacaterol/glycopyrrolate
Inhalation capsule delivered via a single dose dry powder inhaler in the morning for 14 days.

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

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

Study Arm (s)

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.

Intervention: Drug: indacaterol/glycopyrrolate
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.
Interventions:
- Drug: indacaterol/glycopyrrolate
- Drug: placebo
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.
Interventions:
- Drug: indacaterol/glycopyrrolate
- Drug: glycopyrrolate
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.
Interventions:
- Drug: indacaterol
- Drug: placebo
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.

Intervention: Drug: placebo

Publications *

Not Provided

* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.

Recruitment Information

Recruitment Status ^ICMJE

Completed

Enrollment ^ICMJE

257

Completion Date

July 2008

Primary Completion Date

July 2008 (final data collection date for primary outcome measure)

Eligibility Criteria ^ICMJE

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

Gender

Both

Ages

40 Years and older

Accepts Healthy Volunteers

Contacts ^ICMJE

Contact information is only displayed when the study is recruiting subjects

Location Countries ^ICMJE

Australia, Belgium, Canada, France, Germany, Italy, Spain, Turkey

Administrative Information

NCT Number ^ICMJE

NCT00558285

Other Study ID Numbers ^ICMJE

CQVA149A2203

Has Data Monitoring Committee

Not Provided

Responsible Party

Novartis

Study Sponsor ^ICMJE

Novartis

Collaborators ^ICMJE

Not Provided

Investigators ^ICMJE

Study Chair:

Novartis Pharma AG

Novartis Pharmaceuticals

Information Provided By

Novartis

Verification Date

November 2012

^ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

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