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

Novartis

Status and phase: Completed; Phase 2

Conditions: Chronic Obstructive Pulmonary Disease

Treatments: Drug: Placebo; Drug: Indacaterol; Drug: Salmeterol

Study type: Interventional

Funder types: Industry

Identifiers

NCT00531050

CQAB149B2217

Details and patient eligibility

About

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.

Enrollment: 27 patients

Sex: All

Ages: 40 to 75 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Double Blind

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27 participants in 6 patient groups

Part 1: Sequence A, Part 2: Sequence A

Experimental group

Description:

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.

Treatment:

Drug: Salmeterol

Drug: Placebo

Drug: Indacaterol

Part 1 : Sequence B, Part 2: Sequence B

Experimental group

Description:

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.

Treatment:

Drug: Salmeterol

Drug: Placebo

Drug: Indacaterol

Part 1: Sequence C, Part 2: Sequence C

Experimental group

Description:

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.

Treatment:

Drug: Salmeterol

Drug: Placebo

Drug: Indacaterol

Part 1; Sequence D, Part 2: Sequence D

Experimental group

Description:

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.

Treatment:

Drug: Salmeterol

Drug: Placebo

Drug: Indacaterol

Part 1: Sequence E, Part 2: Sequence E

Experimental group

Description:

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.

Treatment:

Drug: Salmeterol

Drug: Placebo

Drug: Indacaterol

Part 1: Sequence F, Part 2: Sequence F

Experimental group

Description:

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.

Treatment:

Drug: Salmeterol

Drug: Placebo

Drug: Indacaterol