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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis
ClinicalTrials.gov Identifier:
NCT00531050
First received: September 17, 2007
Last updated: April 23, 2012
Last verified: April 2012
History of Changes
  Purpose

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.


Condition Intervention Phase
Chronic Obstructive Pulmonary Disease
 Drug: Indacaterol
Drug: Placebo
Drug: Salmeterol
 Phase 2

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

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Novartis:

Primary Outcome Measures:
  • Percentage of Participants With Maximum Heart Rate Increase During Exercise in Part 1 of the Study [ Time Frame: 24-hours post-dose on Day 1 (of each treatment) ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants With Maximum Heart Rate Increase During Salbutamol Administration in Part 2 of the Study [ Time Frame: 24 hours post dose on Day 1 ] [ Designated as safety issue: No ]

    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

  • Maximum Heart Rate During Exercise in Part 1 [ Time Frame: 2 hour post-dose on Day 1 ] [ Designated as safety issue: No ]
    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.

  • Maximum Heart Rate (HR) During Salbutamol Administration in Part 2 [ Time Frame: 24 hours post dose on Day 1 ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Change in Heart Rate During Exercise in Part 1 [ Time Frame: 1.5 hour post dose to max heart rate during exercise ] [ Designated as safety issue: No ]

    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.


  • Trough Forced Expiratory Volume in 1 Second (FEV1) During Part 1 and Part 2 [ Time Frame: 23 hours 30 minutes and 24 hours post-dose at Day 1 ] [ Designated as safety issue: No ]
    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.


Enrollment: 27
Study Start Date: August 2007
Study Completion Date: June 2008
Primary Completion Date: June 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Part 1: Sequence A, Part 2: Sequence A

Part 1: Sequence 'A' consisted of - Period 1, patient received a single inhaled dose of indacaterol 300μg capsule via the Concept1 inhaler device. Period 2, patient received single dose of salmeterol 50μg via Diskus dry powder inhaler (DPI). Period 3, patient received single dose of indacaterol matching placebo via the Concept1 inhaler device.

Part 2: Sequence 'A' consisted of - Period 1, patients received a morning single inhalational dose of indacaterol 300μg and an evening single inhalation dose of indacaterol matching placebo via the Concept1 inhaler device. Period 2, patients received morning and evening single inhalational dose of salmeterol 50μg via Diskus DPI. Period 3, patients received single inhalation dose of indacaterol matching placebo in morning and evening via Concept1 device. In Part 2 of the study, at 20 minutes following each dose, patients received three doses of nebulized salbutamol 2.5 mg at 20 minute intervals.

 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).
Drug: Placebo
Single dose indacaterol matching placebo via Concept 1 device
Drug: 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.
Experimental: Part 1 : Sequence B, Part 2: Sequence B

Part 1: Sequence 'B' consisted of - Period 1, patient received a single inhaled dose of indacaterol 300μg capsule administered via the Concept1 inhaler device. Period 2, patient received single dose of indacaterol matching placebo via the Concept1 inhaler device. Period 3, patient received single dose of salmeterol 50μg via Diskus DPI.

Part 2: Sequence 'B' consisted of - Period 1, patients received a morning single inhalational dose of indacaterol 300μg and an evening single inhalation dose of indacaterol matching placebo via the Concept1 inhaler device. Period 2, patients received single inhalation dose of indacaterol matching placebo in morning and evening via Concept1 device. Period 3, patients received morning and evening single inhalational dose of salmeterol 50μg via Diskus DPI. In Part 2 of the study, at 20 minutes following each dose, patients received three doses of nebulized salbutamol 2.5 mg at 20 minute intervals.

 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).
Drug: Placebo
Single dose indacaterol matching placebo via Concept 1 device
Drug: 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.
Experimental: Part 1: Sequence C, Part 2: Sequence C

Part 1: Sequence 'C' consisted of - Period 1, patient received single dose of indacaterol matching placebo via the Concept1 inhaler device. Period 2, patient received single dose of salmeterol 50μg via Diskus DPI. Period 3, patient received a single inhaled dose of indacaterol 300μg capsule administered via the Concept1 inhaler device.

Part 2: Sequence 'C' consisted of - Period 1, patients received single inhalation dose of indacaterol matching placebo in morning and evening via Concept1 device. Period 2, patients received morning and evening single inhalational dose of salmeterol 50μg via Diskus DPI. Period 3, patients received a morning single inhalational dose of indacaterol 300μg and an evening single inhalation dose of indacaterol matching placebo via the Concept1 inhaler device . In Part 2 of the study, at 20 minutes following each dose, patients received three doses of nebulized salbutamol 2.5 mg at 20 minute intervals.

 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).
Drug: Placebo
Single dose indacaterol matching placebo via Concept 1 device
Drug: 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.
Experimental: Part 1; Sequence D, Part 2: Sequence D

Part 1: Sequence 'D' consisted of - Period 1, patient received single dose of indacaterol matching placebo via the Concept1 inhaler device. Period 2, patient received a single inhaled dose of indacaterol 300μg capsule administered via the Concept1 inhaler device. Period 3, patient received single dose of salmeterol 50μg via Diskus DPI.

Part 2: Sequence 'D' consisted of - Period 1, patients received single inhalation dose of indacaterol matching placebo in morning and evening via Concept1 device. Period 2, patients received a morning single inhalational dose of indacaterol 300μg and an evening single inhalation dose of indacaterol matching placebo via the Concept1 inhaler device. Period 3, patients received morning and evening single inhalational dose of salmeterol 50μg via Diskus DPI. In Part 2 of the study, at 20 minutes following each dose, patients received three doses of nebulized salbutamol 2.5 mg at 20 minute intervals.

 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).
Drug: Placebo
Single dose indacaterol matching placebo via Concept 1 device
Drug: 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.
Experimental: Part 1: Sequence E, Part 2: Sequence E

Part 1: Sequence 'E' consisted of - Period 1, patient received single dose of salmeterol 50μg via Diskus DPI. Period 2, patient received a single inhaled dose of indacaterol 300μg capsule administered via the Concept1 inhaler device. Period 3, patient received single dose of indacaterol matching placebo via the Concept1 inhaler device.

Part 2: Sequence 'E' consisted of - Period 1, patients received morning and evening single inhalational dose of salmeterol 50μg via Diskus DPI. Period 2, patients received a morning single inhalational dose of indacaterol 300μg and an evening single inhalation dose of indacaterol matching placebo via the Concept1 inhaler device. Period 3, patients received single inhalation dose of indacaterol matching placebo in morning and evening via Concept1 device. In Part 2 of the study, at 20 minutes following each dose, patients received three doses of nebulized salbutamol 2.5 mg at 20 minute intervals.

 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).
Drug: Placebo
Single dose indacaterol matching placebo via Concept 1 device
Drug: 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.
Experimental: Part 1: Sequence F, Part 2: Sequence F

Part 1: Sequence 'F' consisted of - Period 1, patient received single dose of salmeterol 50μg via Diskus DPI. Period 2, patient received single dose of indacaterol matching placebo via the Concept1 inhaler device. Period 3, patient received a single inhaled dose of indacaterol 300μg capsule administered via the Concept1 inhaler device.

Part 2: Sequence 'F' consisted of - Period 1, patients received morning and evening single inhalational dose of salmeterol 50μg via Diskus DPI. Period 2, patients received single inhalation dose of indacaterol matching placebo in morning and evening via Concept1 device. Period 3, patients received a morning single inhalational dose of indacaterol 300μg and an evening single inhalation dose of indacaterol matching placebo via the Concept1 inhaler device. In Part 2 of the study, at 20 minutes following each dose, patients received three doses of nebulized salbutamol 2.5 mg at 20 minute intervals.

 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).
Drug: Placebo
Single dose indacaterol matching placebo via Concept 1 device
Drug: 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.

  Eligibility

Ages Eligible for Study:   40 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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

  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00531050

Locations
Belgium
Novartis Investigative site
Antwerp, Belgium
Sponsors and Collaborators
Novartis
Investigators
Principal Investigator: Novartis Investigative site
  More Information

No publications provided

Responsible Party: Novartis
ClinicalTrials.gov Identifier: NCT00531050     History of Changes
Other Study ID Numbers: CQAB149B2217
Study First Received: September 17, 2007
Results First Received: July 29, 2011
Last Updated: April 23, 2012
Health Authority: Belgium: Federal Agency for Medicinal Products and Health Products

Keywords provided by Novartis:
COPD
cycle ergometry
exercise testing
spirometry
 cardiovascular
salbutamol
indacaterol
chronic obstructive pulmonary disease

Additional relevant MeSH terms:
Lung Diseases
Respiration Disorders
Pulmonary Disease, Chronic Obstructive
Lung Diseases, Obstructive
Respiratory Tract Diseases
Albuterol
Salmeterol
Tocolytic Agents
Reproductive Control Agents
Physiological Effects of Drugs
Pharmacologic Actions
Therapeutic Uses
 Adrenergic beta-2 Receptor Agonists
Adrenergic beta-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Anti-Asthmatic Agents
Respiratory System Agents

ClinicalTrials.gov processed this record on May 19, 2013