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

Asthma Clinical Trial

Official title:

A Multi-centre, Randomized, Double-blind, Placebo-controlled, Multiple-dose, 4-way Crossover Study to Evaluate the Efficacy, Safety, Tolerability, and Pharmacokinetics of Orally Inhaled Indacaterol Salts (Maleate, Xinafoate, and Acetate) in Patients With Persistent Asthma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00927901
• Other study ID #: CQAB149D2301
• Secondary ID: 2009-010589-46
• Status: Completed
• Phase: Phase 2
• First received: June 24, 2009
• Last updated: August 26, 2013
• Start date: June 2009
• Est. completion date: November 2009

Study information

• Verified date: August 2013
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical DevicesItaly: Ethics CommitteeFrance: French Health Products Safety Agency (AFSSAPS)
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: November 2009
• Est. primary completion date: November 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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 ß2-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.

Study Design

Allocation: Randomized, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Asthma

Intervention

Drug:
• Indacaterol maleate 400 µg
Indacaterol maleate 400 µg was provided in powder filled capsules with the Concept1 single-dose dry-powder inhaler. The dose refers to 400 µg of free base indacaterol.
• Indacaterol acetate 400 µg
Indacaterol acetate 400 µg was provided in powder filled capsules with the Concept1 single-dose dry-powder inhaler. The dose refers to 400 µg of free base indacaterol.
• Indacaterol xinafoate 400 µg
Indacaterol xinafoate 400 µg was provided in powder filled capsules with the Concept1 single-dose dry-powder inhaler. The dose refers to 400 µg of free base indacaterol.
• Placebo to indacaterol
Placebo to indacaterol was provided in powder filled capsules with the Concept1 single-dose dry-powder inhaler.

Locations

Country	Name	City	State
France	Novartis Investigative Site	Poitiers
Germany	Novartis Investigative Site	Wiesbaden
Italy	Novartis Investigative Site	Verona

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

France,  Germany,  Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1) 24 Hours Post-dose at the End of Each Treatment Period (Day 7)	FEV1 was measured with spirometry conducted according to internationally accepted standards. Trough FEV1 was defined as the average of measurements made 23 hours 10 minutes and 23 hours 45 minutes post-dose at Baseline and at the end of each treatment period. The analysis included period baseline FEV1 as covariate.	Baseline to the end of each treatment period (Day 7)	No
Secondary	Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1) 24 Hours Post-dose on Day 1	FEV1 was measured with spirometry conducted according to internationally accepted standards. Trough FEV1 was defined as the average of measurements made 23 hours 10 minutes and 23 hours 45 minutes post-dose at Baseline and on Day 1. The analysis included period baseline FEV1 as covariate.	Baseline to Day 1	No
Secondary	Time to Peak Forced Expiratory Volume in 1 Second (FEV1) on Day 1 and Day 7	FEV1 was measured with spirometry conducted according to internationally accepted standards at 5, 15, and 30 minutes; 1 hour, 1 hour 30 minutes; and 2, 4, and 12 hours post-dose on Day 1 and Day 7.	Day 1 and Day 7	No
Secondary	Percentage of Patients Using Rescue Medication During Each 7 Day Treatment Period	Patients recorded use of rescue medication (salbutamol/albuterol multi-dose inhaler) as the number of puffs taken in respective preceding 12 hours morning and evening in a diary. Patient with any use of rescue medication (any number of puffs > 0) was included to calculate endpoint.	Baseline to the end of each treatment period (Day 7)	No
Secondary	Indacaterol Exposure (AUC[0-24 Hours]) at the End of Each 7 Day Treatment Period	Venous blood samples for pharmacokinetic evaluation were collected at 15 and 30 minutes; and 1, 2, 4, 12, and 24 hours post-dose at the end of each 7 day treatment period and were analyzed using a LC-MS/MS assay. Area under the concentration-time curve up to 24 hours (AUC[0-24 hours]) was calculated from concentration-time data and recorded sampling times using non-compartmental methods.	End of each treatment period (Day 7)	No
Secondary	Indacaterol Exposure (Cmax) at the End of Each 7 Day Treatment Period	Venous blood samples for pharmacokinetic evaluation were collected at 15 and 30 minutes; and 1, 2, 4, 12, and 24 hours post-dose at the end of each 7 day treatment period and were analyzed using a LC-MS/MS assay. Maximum (peak) plasma drug concentration after drug administration (Cmax) was calculated from concentration-time data and recorded sampling times using non-compartmental methods.	End of each treatment period (Day 7)	No