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

NCT00927901 | Completed Phase 2 Results

• 2 other identifiers: CQAB149D23012009-010589-46
• Study Type: interventional
• Target: 30
• Locations: 3 countries
• Sites: 3

Brief Summary

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

Conditions

Asthma

Keywords

QAB149; asthma; indacaterol salts (acetate, maleate, and xinafoate); orally inhaled indacaterol salts; persistent asthma

Outcome Measures

Primary Outcomes (1)

• 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)

Secondary Outcomes (5)

• Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1) 24 Hours Post-dose on Day 1

  Baseline to Day 1

• Time to Peak Forced Expiratory Volume in 1 Second (FEV1) on Day 1 and Day 7

  Day 1 and Day 7

• Percentage of Patients Using Rescue Medication During Each 7 Day Treatment Period

  Baseline to the end of each treatment period (Day 7)

• Indacaterol Exposure (AUC[0-24 Hours]) at the End of Each 7 Day Treatment Period

  End of each treatment period (Day 7)

• Indacaterol Exposure (Cmax) at the End of Each 7 Day Treatment Period

  End of each treatment period (Day 7)

Study Arms (4)

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

EXPERIMENTAL

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.

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

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

EXPERIMENTAL

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.

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

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

EXPERIMENTAL

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.

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

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

EXPERIMENTAL

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.

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

Interventions

Indacaterol maleate 400 μg DRUG

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 (ind) acetate-ind xinafoate-placebo-ind maleate; Indacaterol (ind) maleate-placebo-ind xinafoate-ind acetate; Indacaterol (ind) xinafoate-ind maleate-ind acetate-placebo; Placebo-indacaterol (ind) acetate-ind maleate-ind xinafoate

Indacaterol acetate 400 μg DRUG

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 (ind) acetate-ind xinafoate-placebo-ind maleate; Indacaterol (ind) maleate-placebo-ind xinafoate-ind acetate; Indacaterol (ind) xinafoate-ind maleate-ind acetate-placebo; Placebo-indacaterol (ind) acetate-ind maleate-ind xinafoate

Indacaterol xinafoate 400 μg DRUG

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.

Indacaterol (ind) acetate-ind xinafoate-placebo-ind maleate; Indacaterol (ind) maleate-placebo-ind xinafoate-ind acetate; Indacaterol (ind) xinafoate-ind maleate-ind acetate-placebo; Placebo-indacaterol (ind) acetate-ind maleate-ind xinafoate

Placebo to indacaterol DRUG

Placebo to indacaterol was provided in powder filled capsules with the Concept1 single-dose dry-powder inhaler.

Indacaterol (ind) acetate-ind xinafoate-placebo-ind maleate; Indacaterol (ind) maleate-placebo-ind xinafoate-ind acetate; Indacaterol (ind) xinafoate-ind maleate-ind acetate-placebo; Placebo-indacaterol (ind) acetate-ind maleate-ind xinafoate

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (3)

Novartis Investigative Site

Poitiers, France

Location

Novartis Investigative Site

Wiesbaden, Germany

Location

Novartis Investigative Site

Verona, Italy

Location

MeSH Terms

Conditions

Asthma

Interventions

indacaterol

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

862 778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

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

Study Design

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

Study Record Dates

• First Submitted: June 24, 2009
• First Posted: June 25, 2009
• Study Start: June 1, 2009
• Primary Completion: November 1, 2009
• Study Completion: November 1, 2009
• Last Updated: September 9, 2013
• Results First Posted: August 30, 2011

Record last verified: 2013-08

Locations

IT (1); DE (1); FR (1)