Efficacy, Safety, Tolerability, and Pharmacokinetics of Indacaterol Salts in Patients With Asthma

Novartis

Status and phase: Completed; Phase 2

Conditions: Asthma

Treatments: Drug: Indacaterol maleate 400 μg; Drug: Indacaterol xinafoate 400 μg; Drug: Indacaterol acetate 400 μg; Drug: Placebo to indacaterol

Study type: Interventional

Funder types: Industry

Identifiers

NCT00927901

2009-010589-46 (EudraCT Number)

CQAB149D2301

Details and patient eligibility

About

This study assessed the efficacy, safety, and pharmacokinetics of indacaterol salts (maleate, xinafoate and acetate) in patients with asthma.

Enrollment: 30 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Non-smoker male and female adult patients aged 18-75 years inclusive, who have signed an informed consent form prior to initiation of any study-related procedure, including any adjustments to asthma medication prior to screening.
• Patients with asthma, receiving daily treatment with inhaled corticosteroid.
• Patients with a forced expiratory volume in 1 second (FEV1) during screening of ≥ 50% of the predicted normal value for the patient.
• Body mass index (BMI) must be within the range 18-32 kg/m^2 (inclusive).
• Able to communicate well with the investigator and comply with the requirements of the study.

Exclusion criteria

• A urine cotinine level greater than the local laboratory lowest level of quantification (LOQ of 500 ng/ml or lower).
• Patients who have had a severe asthma attack/exacerbation requiring hospitalization in the 6 months prior to screening.
• Patients who have had an emergency room visit for an asthma attack/exacerbation within 6 weeks prior to screening or any time between screening and pre-dose on day 1 of the study.
• Patients who have had a respiratory tract infection within 4 weeks prior to screening or any time between screening and pre-dose on day 1 of the study.
• Patients who require the use of ≥ 8 inhalations per day of the short-acting β2-agonist salbutamol/albuterol (100 μg/90 μg salbutamol/albuterol metered dose inhaler [MDI] or equivalent dose of a dry-powder inhaler [DPI]) on any 2 consecutive days from screening to randomization.
• Patients diagnosed with chronic obstructive pulmonary disease (COPD) as defined by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines (2008).
• Participation in any clinical investigation within 4 weeks prior to dosing or longer if required by local regulation. Previous participation in a study with either the investigational or comparator drugs does not exclude a patient from participation in this study.
• Significant illness.
• History of being immunocompromised, including a positive human immunodeficiency virus (HIV) test result (ELISA and Western blot).
• A positive hepatitis B surface antigen (HBsAg) or hepatitis C test result.
• Patients who are considered vulnerable as per ICH GCP guidelines.
• Patients with a history of hypersensitivity to indacaterol or to similar drugs including untoward reactions to sympathomimetic amines or inhaled medication or any component thereof.
• Treatments for asthma and allied conditions:
• The following treatments should not be used unless they have been stabilized prior to screening: antihistamines, inhaled nasal cromolyn, inhaled nasal corticosteroids, and maintenance immunotherapy.

Other protocol-defined inclusion/exclusion criteria applied to the study.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Quadruple Blind

---

30 participants in 4 patient groups

Indacaterol (ind) maleate-placebo-ind xinafoate-ind acetate

Experimental group

Description:

In treatment period 1, patients received indacaterol maleate 400 μg; in treatment period 2, patients received placebo to indacaterol; in treatment period 3, patients received indacaterol xinafoate 400 μg; and in treatment period 4, patients received indacaterol acetate 400 μg. Patients received each treatment once daily for 7 days via the Concept1 single-dose dry-powder inhaler. There was a washout period of at least 7 days between each treatment period. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.

Treatment:

Drug: Indacaterol xinafoate 400 μg

Drug: Indacaterol acetate 400 μg

Drug: Placebo to indacaterol

Drug: Indacaterol maleate 400 μg

Indacaterol (ind) xinafoate-ind maleate-ind acetate-placebo

Experimental group

Description:

In treatment period 1, patients received indacaterol xinafoate 400 μg; in treatment period 2, patients received indacaterol maleate 400 μg; in treatment period 3, patients received indacaterol acetate 400 μg; and in treatment period 4, patients received placebo to indacaterol 400 μg. Patients received each treatment once daily for 7 days via the Concept1 single-dose dry-powder inhaler. There was a washout period of at least 7 days between each treatment period. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.

Treatment:

Drug: Indacaterol xinafoate 400 μg

Drug: Indacaterol acetate 400 μg

Drug: Placebo to indacaterol

Drug: Indacaterol maleate 400 μg

Indacaterol (ind) acetate-ind xinafoate-placebo-ind maleate

Experimental group

Description:

In treatment period 1, patients received indacaterol acetate 400 μg; in treatment period 2, patients received indacaterol xinafoate 400 μg; in treatment period 3, patients received placebo to indacaterol; and in treatment period 4, patients received indacaterol maleate 400 μg. Patients received each treatment once daily for 7 days via the Concept1 single-dose dry-powder inhaler. There was a washout period of at least 7 days between each treatment period. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.

Treatment:

Drug: Indacaterol xinafoate 400 μg

Drug: Indacaterol acetate 400 μg

Drug: Placebo to indacaterol

Drug: Indacaterol maleate 400 μg

Placebo-indacaterol (ind) acetate-ind maleate-ind xinafoate

Experimental group

Description:

In treatment period 1, patients received placebo to indacaterol; in treatment period 2, patients received indacaterol acetate 400 μg; in treatment period 3, patients received indacaterol maleate 400 μg; and in treatment period 4, patients received indacaterol xinafoate 400 μg. Patients received each treatment once daily for 7 days via the Concept1 single-dose dry-powder inhaler. There was a washout period of at least 7 days between each treatment period. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.

Treatment:

Drug: Indacaterol xinafoate 400 μg

Drug: Indacaterol acetate 400 μg

Drug: Placebo to indacaterol

Drug: Indacaterol maleate 400 μg