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

NCT00531050 | Completed Phase 2 Results

• 1 other identifier: CQAB149B2217
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Chronic Obstructive Pulmonary Disease

Keywords

COPD; cycle ergometry; exercise testing; spirometry; cardiovascular; salbutamol; indacaterol; chronic obstructive pulmonary disease

Outcome Measures

Primary Outcomes (4)

• 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)

• 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

• 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

• 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

Secondary Outcomes (2)

• Change in Heart Rate During Exercise in Part 1

  1.5 hour post dose to max heart rate during exercise

• Trough Forced Expiratory Volume in 1 Second (FEV1) During Part 1 and Part 2

  23 hours 30 minutes and 24 hours post-dose at Day 1

Study Arms (6)

Part 1: Sequence A, Part 2: Sequence A

EXPERIMENTAL

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; Drug: Placebo; Drug: Salmeterol

Part 1 : Sequence B, Part 2: Sequence B

EXPERIMENTAL

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; Drug: Placebo; Drug: Salmeterol

Part 1: Sequence C, Part 2: Sequence C

EXPERIMENTAL

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; Drug: Placebo; Drug: Salmeterol

Part 1; Sequence D, Part 2: Sequence D

EXPERIMENTAL

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; Drug: Placebo; Drug: Salmeterol

Part 1: Sequence E, Part 2: Sequence E

EXPERIMENTAL

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; Drug: Placebo; Drug: Salmeterol

Part 1: Sequence F, Part 2: Sequence F

EXPERIMENTAL

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; Drug: Placebo; Drug: Salmeterol

Interventions

Indacaterol DRUG

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).

Part 1 : Sequence B, Part 2: Sequence B; Part 1: Sequence A, Part 2: Sequence A; Part 1: Sequence C, Part 2: Sequence C; Part 1: Sequence E, Part 2: Sequence E; Part 1: Sequence F, Part 2: Sequence F; Part 1; Sequence D, Part 2: Sequence D

Placebo DRUG

Single dose indacaterol matching placebo via Concept 1 device

Part 1 : Sequence B, Part 2: Sequence B; Part 1: Sequence A, Part 2: Sequence A; Part 1: Sequence C, Part 2: Sequence C; Part 1: Sequence E, Part 2: Sequence E; Part 1: Sequence F, Part 2: Sequence F; Part 1; Sequence D, Part 2: Sequence D

Salmeterol DRUG

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.

Part 1 : Sequence B, Part 2: Sequence B; Part 1: Sequence A, Part 2: Sequence A; Part 1: Sequence C, Part 2: Sequence C; Part 1: Sequence E, Part 2: Sequence E; Part 1: Sequence F, Part 2: Sequence F; Part 1; Sequence D, Part 2: Sequence D

Eligibility Criteria

• Age: 40 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Novartis: lead

Study Sites (1)

Novartis Investigative site

Antwerp, Belgium

Location

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Interventions

indacaterol; Salmeterol Xinafoate

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Albuterol; Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines; Phenethylamines; Ethylamines

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

862-778-8300

Study Officials

• Novartis

  Investigative site

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 17, 2007
• First Posted: September 18, 2007
• Study Start: August 1, 2007
• Primary Completion: June 1, 2008
• Study Completion: June 1, 2008
• Last Updated: May 23, 2012
• Results First Posted: May 23, 2012

Record last verified: 2012-04

Locations

BE (1)