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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01609478
First received: April 23, 2012
Last updated: August 12, 2013
Last verified: August 2013
  Purpose

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.


Condition Intervention Phase
Asthma
Drug: indacaterol
Drug: placebo
Drug: mometasone furoate
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Trough Forced Expiratory Volume in one second (FEV1) [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    Spirometry is conducted according to the global standard. Trough FEV1 is defined as the average of the 23 hour 10 minute and 23 hour 45 minute post dose FEV1 readings.


Secondary Outcome Measures:
  • Asthma Control Questionnaire 5 (ACQ-5) [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]

    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).


  • Trough FEV1 [ Time Frame: 2 weeks, 4 weeks, 8 weeks ] [ Designated as safety issue: No ]
    Spirometry is conducted according to the global standard. Trough FEV1 is defined as the average of the 50 minute and 15 minute pre dose FEV1 readings for 4 weeks and as the average of the 23 hour 10 minute and 23 hour 45 minute post dose FEV1 readings for 2weeks and 8weeks.

  • Forced vital capacity (FVC) at each timepoint [ Time Frame: Day 1, Day 2, Day 14, Day 15, Day 29, Day 57, Day 84, Day 85 ] [ Designated as safety issue: No ]
    Spirometry is conducted according to the global standard. FVC is measured at pre-dose and post dose up to 6 hour on Day 1, Day 14 and Day 84, at post dose 23 hour 10 minute and 23 hour 45 minutes on Day 2, Day 15 and Day 85, and at pre-dose 50 min and 15 min on Day 29 and Day 57.

  • FEV1/FVC at each timepoint [ Time Frame: Day 1, Day 2, Day 14, Day 15, Day 29, Day 57, Day 84, Day 85 ] [ Designated as safety issue: No ]
    Spirometry is conducted according to the global standard. FVC is measured at pre-dose and post dose up to 6 hour on Day 1, Day 14 and Day 84, at post dose 23 hour 10 minute and 23 hour 45 minutes on Day 2, Day 15 and Day 85, and at pre-dose 50 min and 15 min on Day 29 and Day 57.

  • Standardized FEV1 AUC(5 min - 4 h), (5 min - 1 h) and (1 h - 4 h) [ Time Frame: Day 1, 2 Weeks, 12 Weeks ] [ Designated as safety issue: No ]
    Spirometry is conducted according to the global standard. FEV1 AUC(5 min - 4 h), (5 min - 1 h) and (1 h - 4 h) are measured at Day 1 and 2 Weeks and 12 Weeks and defined as average of FEV1 at specified timepoints above.

  • Peak FEV1 [ Time Frame: Day 1, 2 Weeks, 12 Weeks ] [ Designated as safety issue: No ]
    Spirometry is conducted according to the global standard. Peak FEV1 is defined as the maximum FEV1 during the first 4 h post morning dosing at Day 1, 2Weeks and 12 Weeks.

  • Asthma Control Questionnaire 5 (ACQ-5) [ Time Frame: 4 Weeks, 8 Weeks ] [ Designated as safety issue: No ]

    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).


  • Morning and evening peak expiratory flow rate (PEFR) [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    PEFR is measured with portable spirometer by participants every morning and evening at home.

  • The usage of rescue medication (short acting β2-agonist) [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    Participants record the number of puffs of rescue medication taken in the previous 12 hours in the morning and evening.

  • Asthma Quality of Life Questionnaire (AQLQ(S)) [ Time Frame: 4 Weeks, 12 Weeks ] [ Designated as safety issue: No ]
    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.

  • Adverse events, laboratory analysis, vital signs and ECG [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]
    Adverse event, laboratory tests (haematology, clinical chemistry and urinalysis), vital signs (i.e. blood pressure, pulse rate), and ECG (e.g. quantitative assessments - heart rate, QTc, PRS, PR intervals).

  • Plasma Indacaterol concentrations [ Time Frame: Day 1, Day 14 ] [ Designated as safety issue: Yes ]
    Indacaterol concentrations will be measured from pre-dose to 23h25min post -dose on Day 1 and Day 14.

  • Time to first asthma exacerbation (mild, moderate, severe, moderate or severe and any) during the 12 week treatment period [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    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.

  • The annual rate of asthma exacerbations (mild, moderate, severe, moderate or severe and any) [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    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.

  • Duration of asthma exacerbations (mild, moderate, severe, moderate or severe and any) [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    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.

  • The percentage of patients with at least one asthma exacerbation (mild, moderate, severe, moderate or severe and any) [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    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.

  • Time to permanent study discontinuation due to asthma exacerbation [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    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.

  • The percentage of patients who permanently discontinued study due to asthma exacerbation [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    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.

  • Total amounts (in doses) of systemic corticosteroids used to treat asthma exacerbations. [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    Total amounts (in doses) of systemic corticosteroids used to treat asthma exacerbations. 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.


Enrollment: 330
Study Start Date: August 2012
Study Completion Date: July 2013
Primary Completion Date: July 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: indacaterol acetate 75 µg

indacaterol acetate 75 µg od delivered via Concept 1 inhaler

Background therapy: mometasone furoate 200 mcg od

Drug: indacaterol
indacaterol acetate 150 µg indacaterol delivered via Concept 1 inhaler
Drug: mometasone furoate
via Twisthaler inhaler
Experimental: indacaterol acetate 150 µg

indacaterol acetate 150 µg od delivered via Concept 1 inhaler

Background therapy: mometasone furoate 200 mcg od

Drug: indacaterol
indacaterol acetate 150 µg indacaterol delivered via Concept 1 inhaler
Drug: mometasone furoate
via Twisthaler inhaler
Placebo Comparator: placebo

placebo delivered via Concept 1 inhaler

Background therapy: mometasone furoate 200 mcg od

Drug: placebo
placebo delivered via Concept 1 inhaler
Drug: mometasone furoate
via Twisthaler inhaler

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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

  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01609478

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Locations
Bulgaria
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Lovech, Bulgaria, 5500
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Pleven, Bulgaria, 5800
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Plovdiv, Bulgaria, 4002
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Ruse, Bulgaria, 7002
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Sofia, Bulgaria, 1431
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Sofia, Bulgaria, 1463
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Sofia, Bulgaria, 1233
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Sofia, Bulgaria, 1000
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Varna, Bulgaria, 9020
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Varna, Bulgaria, 9000
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Veliko Tarnovo, Bulgaria, 5000
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Downsview, Ontario, Canada, M3N 2Z9
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Grimsby, Ontario, Canada, L3M 1P3
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Montreal, Quebec, Canada, H4J 1C5
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Ste-Foy, Quebec, Canada, G1W 4R4
Germany
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Bad Woerishofen, Germany, 86825
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Bonn, Germany, 53123
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Dortmund, Germany, 44263
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Gifu, Japan, 502-8558
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Rotterdam, Netherlands, 3045 PM
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Sittard-Geleen, Netherlands, 6162 BG
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Bialystok, Poland, 15-461
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Bienkowka, Poland, 34-212
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Bydgoszcz, Poland, 85-046
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Gdansk, Poland, 80-958
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Lodz, Poland, 90-242
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Znin, Poland, 88-400
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Banska Bystrica, Slovak Republic, Slovakia, 975 17
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Bardejov, Slovak Republic, Slovakia, 085 01
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Levice, Slovak republic, Slovakia, 934 01
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Dunajska Streda, Slovakia, 929 01
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Komarno, Slovakia, 945 01
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Kosice, Slovakia, 040 01
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Liptovsky Hradok, Slovakia, 033 01
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Liptovsky Mikulas, Slovakia, 031 23
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Nove Zamky, Slovakia, 940 01
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Rimavska Sobota, Slovakia, 979 01
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Spisská Nová Ves, Slovakia, 052 01
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Topolcany, Slovakia, 955 01
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Vysne Hagy, Slovakia, 5984
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Zvolen, Slovakia, 960 01
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01609478     History of Changes
Other Study ID Numbers: CQMF149E2203, 2012-000520-18
Study First Received: April 23, 2012
Last Updated: August 12, 2013
Health Authority: United States: Food and Drug Administration
Canada: Health Canada
Germany: Federal Institute for Drugs and Medical Devices
Japan: Pharmaceuticals and Medical Devices Agency
Latvia: State Agency of Medicines
Netherlands: Medicines Evaluation Board (MEB)
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Slovakia: State Institute for Drug Control
Bulgaria: Bulgarian Drug Agency
Korea: Food and Drug Administration

Keywords provided by Novartis:
asthma

Additional relevant MeSH terms:
Asthma
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Mometasone furoate
Anti-Allergic Agents
Therapeutic Uses
Pharmacologic Actions
Anti-Inflammatory Agents

ClinicalTrials.gov processed this record on April 22, 2014