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)

Chronic Obstructive Pulmonary Disease (COPD) Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00558285
• Other study ID #: CQVA149A2203
• Status: Completed
• Phase: Phase 2
• First received: November 12, 2007
• Last updated: November 28, 2012
• Start date: November 2007
• Est. completion date: July 2008

Study information

• Verified date: November 2012
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: Australia: Department of Health and Ageing Therapeutic Goods AdministrationBelgium: Federal Agency for Medicinal Products and Health ProductsCanada: Health CanadaFrance: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)Germany: Federal Institute for Drugs and Medical DevicesItaly: The Italian Medicines AgencySpain: Spanish Agency of MedicinesTurkey: Ministry of Health
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 257
• Est. completion date: July 2008
• Est. primary completion date: July 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 40 Years and older

Eligibility

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

Study Design

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

Related Conditions & MeSH terms

• Chronic Obstructive Pulmonary Disease (COPD)
• Lung Diseases
• Lung Diseases, Obstructive
• Pulmonary Disease, Chronic Obstructive

Intervention

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

Locations

Country	Name	City	State
Australia	Novartis Investigator Site	Adelaide
Australia	Novartis Investigator Site	Clayton
Australia	Novartis Investigator Site	Daw Park
Australia	Novartis Investigator site	Heidelberg
Australia	Novartis Investigator Site	Nedlands
Belgium	Novartis Investigator Site	Brussels
Belgium	Novartis Investigator Site	Jambes
Belgium	Novartis Investigator Site	Jette
Belgium	Novartis Investigator site	Liege
Belgium	Novartis Investigator Site	Oostende
Canada	Novartis Investigator Site	Mississauga
Canada	Novartis Investigator Site	Newmarket
Canada	Novartis Investigator Site	Ottawa
Canada	Novartis Investigator Site	Pointe-Claire
Canada	Novartis Investigator Site	Quebec
Canada	Novartis Investigator Site	Sainte-Foy
France	Novartis Investigator Site	Ambroise
France	Novartis Investigator Site	Lille
France	Novartis Investigator Site	Marseille
France	Novartis investigator site	Martigues
France	Novartis Investigator Site	Nantes
France	Novartis Investigator site	Nice
France	Novartis Investigator Site	Perpignan
Germany	Novartis Investigator Site	Berlin
Germany	Novartis Investigator Site	Dortmund
Germany	Novartis Investigator Site	Erfurt
Germany	Novartis Investigator Site	Hannover
Germany	Novartis Investigator Site	Mainz
Germany	Novartis Investigator Site	Marburg
Italy	Novartis Investigator Site	Firenze
Italy	Novartis Investigator site	Modena
Italy	Novartis Investigator Site	Trieste
Spain	Novartis Investigator Site	Badalona
Spain	Novartis Investigator Site	Baracaldo
Spain	Novartis Investigator Site	Caceres
Spain	Novartis Investigator Site	Centelles
Spain	Novartis Investigator Site	Mataro
Spain	Novartis Investigator Site	Valencia
Turkey	Novartis Investigator Site	Istanbul
Turkey	Novartis Investigator Site	Izmir

Sponsors (1)

Lead Sponsor	Collaborator
Novartis

Countries where clinical trial is conducted

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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.	Baseline, Day 1	No
Secondary	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.	Day 1, Day 14	No
Secondary	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.	Day 1 and Day 14	No
Secondary	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 / 3v 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.	Baseline, Day 1	No
Secondary	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 / 3v 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.	Baseline, Day 7	No
Secondary	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 / 3v 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.	Baseline, Day 14	No