Safety of Exercise and High-dose Salbutamol in Patients With Chronic Obstructive Pulmonary Disease (COPD) Receiving Therapeutic Doses of Indacaterol (QAB 149) and Salmeterol

Chronic Obstructive Pulmonary Disease Clinical Trial

Official title:

A Double-blind, Randomized, Cross-over, Placebo-controlled, 2-part Study to Compare the Effect of Exercise and High-dose Salbutamol on Maximal Heart-rate in Patients With COPD Following Therapeutic Doses of Inhaled QAB149 and Salmeterol

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00531050
• Other study ID #: CQAB149B2217
• Status: Completed
• Phase: Phase 2
• First received: September 17, 2007
• Last updated: April 23, 2012
• Start date: August 2007
• Est. completion date: June 2008

Study information

• Verified date: April 2012
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: Belgium: Federal Agency for Medicinal Products and Health Products
• Study type: Interventional

Clinical Trial Summary

This study investigated the effect of exercise and high-dose salbutamol on the maximum heart rate in patients with chronic obstructive pulmonary disease (COPD) receiving therapeutic doses of indacaterol, salmeterol and placebo.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 27
• Est. completion date: June 2008
• Est. primary completion date: June 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 40 Years to 75 Years

Eligibility

Inclusion Criteria:

• Patients between 40 and 75 years of age diagnosed with chronic obstructive pulmonary disease (COPD). Female patients must be surgically sterilized, postmenopausal or using a double-barrier method of contraception.

• Body mass index (BMI) must be within the range of 18 to 32.

Exclusion Criteria:

• Participation in any clinical investigation with experimental drug therapy within four weeks prior to dosing or longer as required by local regulation.

• Donation or loss of 400 mL or more of blood within two months prior to dosing.

• Significant illness (other than respiratory) within two weeks prior to dosing.

• A past medical history of, or a family history (grandparents, parents and siblings) of a prolonged QT-interval syndrome or a prolonged QT-interval at screening.

• Any clinically significant medical abnormalities (excluding COPD) limiting ability to perform standardized exercise protocol on cycle ergometer will exclude the patient. For example, arthritis.

• History of clinically significant drug allergy or history of atopic allergy (asthma, urticaria, eczematous dermatitis).

• A known hypersensitivity to the study drug or drugs similar to the study drug.

• History of immunocompromise, including a positive HIV, Hepatitis B or C test result.

• History of drug or alcohol abuse within the 12 months prior to dosing

• Any conditions that in the opinion of the investigator may compromise patient safety, interfere with evaluations, or preclude the completion of the trial.

Other protocol-defined inclusion/exclusion criteria may apply

Study Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chronic Obstructive Pulmonary Disease
• Lung Diseases
• Lung Diseases, Obstructive
• Pulmonary Disease, Chronic Obstructive

Intervention

Drug:
• Indacaterol
Single dose of indacaterol 300µg capsule via Concept 1 inhaler device at approximately the same time in the morning (i.e. between 8am and 9am).
• Placebo
Single dose indacaterol matching placebo via Concept 1 device
• Salmeterol
Single dose salmeterol 50µg via the Diskus dry powder inhaler (DPI) in part 1 of the study. Morning single inhalational dose and an evening single inhalation dose of salmeterol 50µg via the Diskus DPI in part 2 of the study.

Locations

Country	Name	City	State
Belgium	Novartis Investigative site	Antwerp

Sponsors (1)

Lead Sponsor	Collaborator
Novartis

Country where clinical trial is conducted

Belgium, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With Maximum Heart Rate Increase During Exercise in Part 1 of the Study	The percentage of patients with an increase of more than 10 beats per minute (bpm) in their heart rate following treatment with indacaterol and salmeterol compared to treatment with placebo was determined.	24-hours post-dose on Day 1 (of each treatment)	No
Primary	Percentage of Participants With Maximum Heart Rate Increase During Salbutamol Administration in Part 2 of the Study	The percentage of patients with an increase of >= 10 beats per minute (bpm) in their heart rate (HR) following treatment with indacaterol and salmeterol compared to treatment with placebo over 24 hours in Part 2 was determined.; 0-12 hours: post first dose measurements up to second dose; 12-24 hours: post second dose measurement up to and including the 24 hour measurement; 0-24 hours: all post dose measurements up to and including the 24 hour measurement	24 hours post dose on Day 1	No
Primary	Maximum Heart Rate During Exercise in Part 1	Maximum heart rate was generally taken from the continuous ECG monitoring. Analysis based on mixed effects analysis using model with treatment and period as fixed effects and subject as random effect.	2 hour post-dose on Day 1	No
Primary	Maximum Heart Rate (HR) During Salbutamol Administration in Part 2	Maximum HR (0-12 hours): maximum (max) of post dose measurement up to second administration. Maximum HR (12-24 hours): max of the post second administration of salbutamol measurements. Maximum HR (0-24 hours): max of all post dose measurements up to and including the 24 hour measurement. Mixed effects analysis model used period baseline HR as the covariate. The maximum HR for 0-24 hours (h) is the maximum of the maximum HR for the two 12h periods and thus the average (LS means) of the maximum HRs for 0-24h will be equal to or greater than the average of the maximum for the two periods.	24 hours post dose on Day 1	No
Secondary	Change in Heart Rate During Exercise in Part 1	Change in heart rate is calculated from the 1.5 hour post dose to the maximum heart rate during exercise.; Analysis of covariance included treatment and period as fixed effects, subject as random effect and 1.5 hour pre-exercise/post dose heart rate as a covariate.	1.5 hour post dose to max heart rate during exercise	No
Secondary	Trough Forced Expiratory Volume in 1 Second (FEV1) During Part 1 and Part 2	FEV1 was measured with spirometry conducted according to internationally accepted standards. Trough FEV1 was defined as the mean of the 23 hours 30 minutes and 24 hours post morning dose FEV1 measurements. Analysis of covariance included pre-dose FEV1 as covariate.	23 hours 30 minutes and 24 hours post-dose at Day 1	No