Efficacy, Safety and Pharmacokinetics of Indacaterol Acetate in Patients With Persistent Asthma

Study Overview
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Brief Summary
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To provide the efficacy, safety and pharmacokinetics of indacaterol acetate in patients with persistent asthma to support dose selection of indacaterol in fixed dose combination QMF149.

Official Title
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A Multicenter, Randomized, Double-blind, Placebo-controlled, 12-week Treatment, Parallel-group Study to Assess the Efficacy, Safety and Pharmacokinetics of Indacaterol Acetate (75 and 150 µg o.d.) in Patients With Persistent Asthma

Conditions
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Asthma

Intervention / Treatment
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* Drug: indacaterol
* Drug: placebo
* Drug: mometasone furoate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with persistent asthma, diagnosed according to GINA 2010 guideline and who additionally meet the following criteria: Patients who are receiving ICS treatment in a stable regimen for ≥ 4 weeks Patients with a pre-bronchodilator FEV1 value of ≥ 40% and ≤ 80% of predicted normal value Patients who demonstrate an increase of >= 12% and 200 mL in FEV1 ACQ-5 score ≥ 1.5 Exclusion Criteria: Patients who are current smokers or have a smoking history of greater than 10 pack years (defined as the number of packs of 20 cigarettes smoked per day multiplied by number of years the patient smoked). Patients with chronic lung disease, including COPD, pulmonary tuberculosis, bronchiectasis, sarcoidosis, interstitial lung disease and cystic fibrosis. Patients with any chronic conditions affecting the respiratory tract (e.g., chronic sinusitis) which in the opinion of the investigator may interfere with the study evaluation or optimal participation in the study. Other protocol-defined inclusion/exclusion criteria may apply

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: indacaterol acetate 75 µg<br>indacaterol acetate 75 µg od delivered via Concept 1 inhaler Background therapy: mometasone furoate 200 mcg od | Drug: indacaterol<br>* indacaterol acetate 75 µg or indacaterol acetate 150 µg delivered via Concept 1 inhaler<br>Drug: mometasone furoate<br>* via Twisthaler inhaler<br>|
| Experimental: indacaterol acetate 150 µg<br>indacaterol acetate 150 µg od delivered via Concept 1 inhaler Background therapy: mometasone furoate 200 mcg od | Drug: indacaterol<br>* indacaterol acetate 75 µg or indacaterol acetate 150 µg delivered via Concept 1 inhaler<br>Drug: mometasone furoate<br>* via Twisthaler inhaler<br>|
| Placebo Comparator: placebo<br>placebo delivered via Concept 1 inhaler Background therapy: mometasone furoate 200 mcg od | Drug: placebo<br>* placebo delivered via Concept 1 inhaler<br>Drug: mometasone furoate<br>* via Twisthaler inhaler<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Trough Forced Expiratory Volume in One Second (FEV1) After 12 Weeks (Day 85) | Forced Expiratory Volume in 1 second (FEV1) was measured via 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 after 12 weeks (Day 85) | after 12 weeks (Day 85) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Asthma Control Questionnaire 5 (ACQ-5) After 12 Weeks (Day 85) | The Asthma Control Questionnaire (ACQ-5) is a validated questionnaire consisting of 5 items for the assessment of asthma symptom which are night symptom, morning symptom, limitation for the activities, shortness of breath, and wheeze. The ACQ-5 score is the mean of the 5 questions and therefore between 0 (totally controlled) and 6 (severely uncontrolled). A negative change in score indicates improvement in symptoms. MIXED model: Change from baseline in ACQ-5 = treatment + gender + baseline ACQ-5 score + age + level of asthma control + region + center (region) + error. Center is included as a random effect nested within region. | aftert 12 weeks (Day 85) | 
| Trough Forced Expiratory Volume in One Second (FEV1) After 2 Weeks (Day 15), 4 Weeks (Day 29), and 8 Weeks (Day 57) of Treatment. | Forced Expiratory Volume in 1 second (FEV1) was measured via 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 after 2 weeks (Day 15), 4 weeks (Day 29), and 8 weeks (Day 57) of treatment. | Day 15, Day 29 and Day 57 | 
| Forced Vital Capacity (FVC) on Day 1, Day 2, Day 14, Day 15, Day 84, Day 85 at All Time Points | Forced Vital Capacity (FVC) was measured via spirometry conducted according to internationally accepted standards. FVC is measured on Day 1, Day 2, Day 14, Day 15, Day 84, Day 85 at all time points | Day 1, Day 2, Day 14, Day 15, Day 84, Day 85 | 
| Forced Expiratory Volume in One Second (FEV1)/ Forced Vital Capacity (FVC) on Day 1, Day 2, Day 14, Day 15, Day 84, Day 85 | Forced Expiratory Volume in 1 second (FEV1)/Forced Vital Capacity (FVC) was measured via spirometry conducted according to internationally accepted standards. | Day 1, Day 2, Day 14, Day 15, Day 84, Day 85 | 
| Forced Expiratory Flow (FEF 25-75% )on Day 1, Day 2, Day 14, Day 15, Day 84, Day 85 | Forced Expiratory Flow (FEF 25-75%) was measured via spirometry conducted according to internationally accepted standards. | Day 1, Day 2, Day 14, Day 15, Day 84, Day 85 | 
| Standardized Forced Expiratory Volume in One Second (FEV1) Area Under the Curve (AUC) at (5 Min - 4 h), (5 Min - 1 h) (1 h - 4 h) Measured on Day 1, 2 Weeks (Day 14)&12 Weeks (Day 84) | Forced Expiratory Volume in 1 second (FEV1)/Area Under the Curve(AUC) was measured via spirometry conducted according to internationally accepted standards.FEV1 AUC(5 min - 4 h), (5 min - 1 h) and (1 h - 4 h) are measured at Day 1, 2 Weeks (Day 14) and 12 Weeks (Day84) and defined as average of FEV1 at specified timepoints above. | Day 1, 2 Weeks, 12 Weeks | 
| Peak Forced Expiratory Volume in 1 Second (FEV1) at Day 1, 2 Weeks (Day 14), 12 Weeks (Day 84) | Peak Forced Expiratory Volume in 1 second (FEV1) was measured via spirometry conducted according to internationally accepted standards. Peak FEV1 is defined as the maximum FEV1 during the first 4 h post morning dosing at Day 1, 2Weeks and 12 Weeks. | Day 1, 2 weeks (Day 14), 12 weeks (Day 84) | 
| Asthma Control Questionnaire 5 (ACQ-5) After 4 Weeks (Day 29) and After 8 Weeks (Day 57) of Treatment | The ACQ-5 is a validated questionnaire consisting of 5 items for the assessment of asthma symptom which are night symptom, morning symptom, limitation for the activities, shortness of breath, and wheeze. Each item is graded on a scale of 0-6 and the questions are equally weighted. The ACQ-5 score is the mean of the 5 questions and therefore between 0 (totally controlled) and 6 (severely uncontrolled). | after 4 weeks (Day 29) and after 8 weeks (Day 57) | 
| Morning and Evening Peak Expiratory Flow Rate (PEFR) Over 12 Weeks of Treatment. This is LS Mean of the Treatment Period. | PEFR is measured with portable spirometer by participants every morning and evening at home. | baseline, 4weeks, 8 weeks and 12 weeks | 
| The Usage of Rescue Medication (Short Acting β2-agonist) Over 12 Weeks of Treatment | Participants record the number of puffs of rescue medication taken in the previous 12 hours in the morning and nighttime. | 12 weeks | 
| Asthma Quality of Life Questionnaire (AQLQ(S)) After 4 Weeks (Day 29) and 12 Weeks (Day 85) of Treatment | The AQLQ is a 32-item disease specific questionnaire designed to measure functional impairments in asthma. Patients are asked to score each item on a 7-point scale based on the experience of last 2 weeks. The overall AQLQ score is the mean response to all 32 questions. Therefore, the possible highest score (better) would be 7 and the lowest (worse) would be 1. Changes in scores of 0.5 to 1.0 are considered clinically meaningful; 1.0 to 1.5 as moderate and > 1.5 as marked clinically important differences for any individual domain or for the overall summary score. | 4 Weeks, 12 Weeks | 
| Time to First Asthma Exacerbation (Mild, Moderate, Severe, Moderate or Severe and Any) Over the 12 Week Treatment Period | Duration of treatment until first asthma exacerbation by severity of exacerbation. A severe asthma exacerbation is systemic corticosteroids (SCS) use ≥3 days and hospitalization or emergency department visit (greater than 24 h) or death due to asthma. A moderate asthma exacerbation is SCS use ≥3 days either as an outpatient or in emergency department visits (less than or equal to 24 h). Worsening of asthma not requiring more than 3 days of SCS or hospitalization/emergency room will be considered mild asthma exacerbations. | 12 weeks | 
| The Annual Rate of Asthma Exacerbations (Mild, Moderate, Severe, Moderate or Severe and Any) Over the 12 Week Treatment Period | Annual incidence rate of asthma exacerbation by severity of exacerbation. The number of asthma exacerbation is used to calculate annual incidence rate. A severe asthma exacerbation is SCS use ≥3 days and hospitalization or emergency department visit (greater than 24 h) or death due to asthma. A moderate asthma exacerbation is SCS use ≥3 days either as an outpatient or in emergency department visits (less than or equal to 24 h). Worsening of asthma not requiring more than 3 days of SCS or hospitalization/emergency room will be considered mild asthma exacerbations. Number of the asthma exacerbation will be analyzed by the negative binomial regression including treatment, history of asthma exacerbation in the 12 months prior to screening and region as factors and FEV1 prior to inhalation and FEV1 30 min post inhalation of salbutamol/albuterol (components of SABA reversibility) as covariates. The estimates are obtained from the model and so we cannot specify a formula. | 12 weeks | 
| Duration of Asthma Exacerbations (Mild, Moderate, Severe, Moderate or Severe and Any) Over the 12 Week Treatment Period | Duration of asthma exacerbations by severity of exacerbation. A severe asthma exacerbation is SCS use ≥3 days and hospitalization or emergency department visit (greater than 24 h) or death due to asthma. A moderate asthma exacerbation is SCS use ≥3 days either as an outpatient or in emergency department visits (less than or equal to 24 h). Worsening of asthma not requiring more than 3 days of SCS or hospitalization/emergency room will be considered mild asthma exacerbations. | 12 weeks | 
| The Percentage of Patients With at Least One Asthma Exacerbation (Mild, Moderate, Severe, Moderate or Severe and Any) Over the 12 Week Treatment Period | The percentage of patients with at least one asthma exacerbation by severity of exacerbation. A severe asthma exacerbation is SCS use ≥3 days and hospitalization or emergency department visit (greater than 24 h) or death due to asthma. A moderate asthma exacerbation is SCS use ≥3 days either as an outpatient or in emergency department visits (less than or equal to 24 h). Worsening of asthma not requiring more than 3 days of SCS or hospitalization/emergency room will be considered mild asthma exacerbations. | 12 weeks | 
| Time to Permanent Study Discontinuation Due to Asthma Exacerbation Over the 12 Week Treatment Period | Time to permanent study discontinuation due to asthma exacerbation. A severe asthma exacerbation is SCS use ≥3 days and hospitalization or emergency department visit (greater than 24 h) or death due to asthma. A moderate asthma exacerbation is SCS use ≥3 days either as an outpatient or in emergency department visits (less than or equal to 24 h). Worsening of asthma not requiring more than 3 days of SCS or hospitalization/emergency room will be considered mild asthma exacerbations. | 12 weeks | 
| The Percentage of Patients Who Permanently Discontinued Study Due to Asthma Exacerbation Over the 12 Week Treatment Period | The percentage of patients who permanently discontinued study due to asthma exacerbation. A severe asthma exacerbation is SCS use ≥3 days and hospitalization or emergency department visit (greater than 24 h) or death due to asthma. A moderate asthma exacerbation is SCS use ≥3 days either as an outpatient or in emergency department visits (less than or equal to 24 h). Worsening of asthma not requiring more than 3 days of SCS or hospitalization/emergency room will be considered mild asthma exacerbations. | 12 weeks | 
| Total Amounts (in Doses) of Systemic Corticosteroids Used to Treat Asthma Exacerbations Over the 12 Week Treatment Period | Total amounts (in doses) of systemic corticosteroids (SCS) used to treat asthma exacerbations.SCS includes Intramuscular (IM), Intravenous (IV) and Oral. A severe asthma exacerbation is SCS use ≥3 days and hospitalization or emergency department visit (greater than 24 h) or death due to asthma. A moderate asthma exacerbation is SCS use ≥3 days either as an outpatient or in emergency department visits (less than or equal to 24 h). Worsening of asthma not requiring more than 3 days of SCS or hospitalization/emergency room will be considered mild asthma exacerbations. | 12 weeks | 
| Plasma Indacaterol Concentrations at Day 1 and Day 14 | Maximum plasma concentration after drug administration (Cmax) was measured for indacaterol acetate 75 µg and indacaterol acetate 150 µg for Pharmacokinetic (PK) Subgroup | Day 1 and Day 14 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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asthma