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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT00558285




Registration number
NCT00558285
Ethics application status
Date submitted
12/11/2007
Date registered
14/11/2007
Date last updated
30/11/2012

Titles & IDs
Public 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)
Scientific 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)
Secondary ID [1] 0 0
CQVA149A2203
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic Obstructive Pulmonary Disease (COPD) 0 0
Condition category
Condition code
Respiratory 0 0 0 0
Chronic obstructive pulmonary disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - indacaterol/glycopyrrolate
Treatment: Drugs - indacaterol
Treatment: Drugs - glycopyrrolate
Treatment: Drugs - placebo

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.

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.

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.

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.

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.


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

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

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

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

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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.
Timepoint [1] 0 0
Baseline, Day 14
Secondary outcome [1] 0 0
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.
Timepoint [1] 0 0
Baseline, Day 1
Secondary outcome [2] 0 0
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.
Timepoint [2] 0 0
Day 1, Day 14
Secondary outcome [3] 0 0
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.
Timepoint [3] 0 0
Day 1 and Day 14
Secondary outcome [4] 0 0
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.
Timepoint [4] 0 0
Baseline, Day 1
Secondary outcome [5] 0 0
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.
Timepoint [5] 0 0
Baseline, Day 7
Secondary outcome [6] 0 0
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.
Timepoint [6] 0 0
Baseline, Day 14

Eligibility
Key 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
Minimum age
40 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Novartis Investigator Site - Adelaide
Recruitment hospital [2] 0 0
Novartis Investigator Site - Clayton
Recruitment hospital [3] 0 0
Novartis Investigator Site - Daw Park
Recruitment hospital [4] 0 0
Novartis Investigator site - Heidelberg
Recruitment hospital [5] 0 0
Novartis Investigator Site - Nedlands
Recruitment postcode(s) [1] 0 0
- Adelaide
Recruitment postcode(s) [2] 0 0
- Clayton
Recruitment postcode(s) [3] 0 0
- Daw Park
Recruitment postcode(s) [4] 0 0
- Heidelberg
Recruitment postcode(s) [5] 0 0
- Nedlands
Recruitment outside Australia
Country [1] 0 0
Belgium
State/province [1] 0 0
Brussels
Country [2] 0 0
Belgium
State/province [2] 0 0
Jambes
Country [3] 0 0
Belgium
State/province [3] 0 0
Jette
Country [4] 0 0
Belgium
State/province [4] 0 0
Liege
Country [5] 0 0
Belgium
State/province [5] 0 0
Oostende
Country [6] 0 0
Canada
State/province [6] 0 0
Mississauga
Country [7] 0 0
Canada
State/province [7] 0 0
Newmarket
Country [8] 0 0
Canada
State/province [8] 0 0
Ottawa
Country [9] 0 0
Canada
State/province [9] 0 0
Pointe-Claire
Country [10] 0 0
Canada
State/province [10] 0 0
Quebec
Country [11] 0 0
Canada
State/province [11] 0 0
Sainte-Foy
Country [12] 0 0
France
State/province [12] 0 0
Ambroise
Country [13] 0 0
France
State/province [13] 0 0
Lille
Country [14] 0 0
France
State/province [14] 0 0
Marseille
Country [15] 0 0
France
State/province [15] 0 0
Martigues
Country [16] 0 0
France
State/province [16] 0 0
Nantes
Country [17] 0 0
France
State/province [17] 0 0
Nice
Country [18] 0 0
France
State/province [18] 0 0
Perpignan
Country [19] 0 0
Germany
State/province [19] 0 0
Berlin
Country [20] 0 0
Germany
State/province [20] 0 0
Dortmund
Country [21] 0 0
Germany
State/province [21] 0 0
Erfurt
Country [22] 0 0
Germany
State/province [22] 0 0
Hannover
Country [23] 0 0
Germany
State/province [23] 0 0
Mainz
Country [24] 0 0
Germany
State/province [24] 0 0
Marburg
Country [25] 0 0
Italy
State/province [25] 0 0
Firenze
Country [26] 0 0
Italy
State/province [26] 0 0
Modena
Country [27] 0 0
Italy
State/province [27] 0 0
Trieste
Country [28] 0 0
Spain
State/province [28] 0 0
Badalona
Country [29] 0 0
Spain
State/province [29] 0 0
Baracaldo
Country [30] 0 0
Spain
State/province [30] 0 0
Caceres
Country [31] 0 0
Spain
State/province [31] 0 0
Centelles
Country [32] 0 0
Spain
State/province [32] 0 0
Mataro
Country [33] 0 0
Spain
State/province [33] 0 0
Valencia
Country [34] 0 0
Turkey
State/province [34] 0 0
Istanbul
Country [35] 0 0
Turkey
State/province [35] 0 0
Izmir

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Novartis
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT00558285
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Novartis Pharma AG
Address 0 0
Novartis Pharmaceuticals
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications