Bronchodilatory Efficacy of a Single Dose QMF149 (Indacaterol Maleate/Mometasone Furoate) Via the Twisthaler® Device in Adult Patients With Asthma

This study has been completed.
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Novartis
ClinicalTrials.gov Identifier:
NCT00556673
First received: November 9, 2007
Last updated: March 11, 2013
Last verified: March 2013
  Purpose

This study is designed to evaluate the bronchodilatory efficacy of indacaterol maleate 500 μg/mometasone furoate 400 μg via the Twisthaler® device in adult patients with persistent asthma.


Condition Intervention Phase
Asthma
Drug: indacaterol maleate/mometasone furoate
Drug: placebo to indacaterol maleate/mometasone furoate
Drug: fluticasone proprionate / salmeterol xinafoate
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: An Exploratory, Multi-centre, Double-blind, Placebocontrolled Crossover Study, to Investigate the Bronchodilatory Efficacy of a Single Dose of Indacaterol in Fixed Combination With Mometasone Furoate Delivered Via a MDDPI (Twisthaler®) in Adult Patients With Persistent Asthma Using Open Label Seretide® Accuhaler® (50/250 Mcg b.i.d.) as an Active Control

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Change From Period Baseline to 24 Hour Post-dose (Trough) Forced Expiratory Volume in 1 Second (FEV1) [ Time Frame: Pre-dose for each Treatment Period (Days 1, 8 and 15) and 24-hours post-dose for each Treatment Period (Days 2, 9 and 16). ] [ Designated as safety issue: No ]
    FEV1 is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation. Change from the period baseline to 24 hour post dose trough FEV1 after 1 day of treatment was modeled using a linear mixed effect model fitting treatment, sequence and period as fixed factors, patient within sequence as a random factor and pre-dose FEV1 as covariate.


Secondary Outcome Measures:
  • Change From Baseline in Peak Forced Expiratory Volume in One Second (FEV1) [ Time Frame: Days 1, 8 and 15, pre-dose (Baseline) and 5, 15, and 30 minutes, 1, 2, 3, and 4 hours post-dose. ] [ Designated as safety issue: No ]
    FEV1 is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation. Peak FEV1 is defined as the peak FEV1 between 0 and 4 hours post-dose. The change from baseline in peak FEV1 was modeled using a linear mixed effect model fitting treatment, sequence and period as fixed factors, patient within sequence as a random factor and pre-dose FEV1 as covariate.

  • Change From Period Baseline in Trough Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) [ Time Frame: Pre-dose for each Treatment Period (Days 1, 8 and 15) and 24-hours post-dose for each Treatment Period (Days 2, 9 and 16). ] [ Designated as safety issue: No ]
    Trough FEV1 was measured 24 hours post-dose. The FEV1 percent predicted expresses FEV1 as a percentage of the "predicted values" for participants of similar characteristics (height, age, sex, and sometimes race and weight). A positive change from baseline in FEV1 % predicted indicates improvement in lung function. Change from baseline in trough FEV1 % predicted was modeled using a linear mixed effect model fitting treatment, sequence and period as fixed factors, patient within sequence as a random factor and pre-dose value as covariate.

  • Change From Period Baseline in Peak Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) [ Time Frame: Days 1, 8 and 15, pre-dose (Baseline) and 5, 15, and 30 minutes, 1, 2, 3, and 4 hours post-dose. ] [ Designated as safety issue: No ]
    Peak FEV1 was defined as the peak FEV1 up to 4 hours post-dose. The FEV1 percent predicted expresses FEV1 as a percentage of the "predicted values" for participants of similar characteristics (height, age, sex, and sometimes race and weight). A positive change from baseline in FEV1 % predicted indicates improvement in lung function. Change from baseline in peak FEV1 % predicted was modeled using a linear mixed effect model fitting treatment, sequence and period as fixed factors, patient within sequence as a random factor and pre-dose value as covariate.

  • Change From Period Baseline in Trough Forced Vital Capacity (FVC) [ Time Frame: Pre-dose for each Treatment Period (Days 1, 8 and 15) and 24-hours post-dose for each Treatment Period (Days 2, 9 and 16). ] [ Designated as safety issue: No ]
    Vital capacity is the amount of air which can be forcibly exhaled from the lungs after taking the deepest breath possible. Trough FVC was measured 24 hours post-dose. Change form baseline in trough FVC was modeled using a linear mixed effect model fitting treatment, sequence and period as fixed factors, patient within sequence as a random factor and pre-dose value as covariate.

  • Change From Period Baseline in Peak Forced Vital Capacity (FVC) [ Time Frame: Days 1, 8 and 15, pre-dose (Baseline) and 5, 15, and 30 minutes, 1, 2, 3, and 4 hours post-dose. ] [ Designated as safety issue: No ]
    Vital capacity is the amount of air which can be forcibly exhaled from the lungs after taking the deepest breath possible. Peak FVC was measured up to 4 hours post-dose. Change from baseline in peak FVC was modeled using a linear mixed effect model fitting treatment, sequence and period as fixed factors, patient within sequence as a random factor and pre-dose value as covariate.

  • Change From Period Baseline in Trough FEV1/FVC Ratio [ Time Frame: Pre-dose for each Treatment Period (Days 1, 8 and 15) and 24-hours post-dose for each Treatment Period (Days 2, 9 and 16). ] [ Designated as safety issue: No ]
    The forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) ratio represents the proportion of a person's vital capacity that they are able to expire in the first second of an expiration. Trough FEV1/FVC was calculated from measurements taken 24 hours post-dose. Change from baseline in trough FEV1/FVC ratio was modeled using a linear mixed effect model fitting treatment, sequence and period as fixed factors, patient within sequence as a random factor and pre-dose value as covariate.

  • Change From Period Baseline in Peak FEV1/FVC Ratio [ Time Frame: Days 1, 8 and 15, pre-dose (Baseline) and 5, 15, and 30 minutes, 1, 2, 3, and 4 hours post-dose. ] [ Designated as safety issue: No ]
    The forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) ratio represents the proportion of a person's vital capacity that they are able to expire in the first second of an expiration. Peak FEV1/FVC was calculated from spirometry measurements taken up to 4 hours post-dose. Change from baseline in peak FEV1/FVC ratio was modeled using a linear mixed effect model fitting treatment, sequence and period as fixed factors, patient within sequence as a random factor and pre-dose value as covariate.

  • Area Under the Concentration-time Curve From Time 0 to 12 Hours Post-dose for Mometasone Furoate [ Time Frame: Samples were taken pre-dose and at 15 and 30 minutes and 1, 2, 4, and 12 hours post-dose. ] [ Designated as safety issue: No ]
  • Area Under the Concentration-time Curve From Time 0 to 24 Hours Post-dose for Mometasone Furoate [ Time Frame: Samples were taken pre-dose and at 15 and 30 minutes and 1, 2, 4, 12 and 24 hours post-dose. ] [ Designated as safety issue: No ]
  • Area Under the Concentration-time Curve From Time 0 to 24 Hours Post-dose for Indacaterol [ Time Frame: Samples were taken pre-dose and at 15 and 30 minutes and 1, 2, 4, 12 and 24 hours post-dose. ] [ Designated as safety issue: No ]
  • Maximum (Peak) Plasma Concentration (Cmax) of Mometasone Furoate [ Time Frame: Samples were taken pre-dose and at 15 and 30 minutes and 1, 2, 4, 12 and 24 hours post-dose. ] [ Designated as safety issue: No ]
  • Maximum (Peak) Plasma Concentration (Cmax) of Indacaterol [ Time Frame: Samples were taken pre-dose and at 15 and 30 minutes and 1, 2, 4, 12 and 24 hours post-dose. ] [ Designated as safety issue: No ]
  • Time to Reach Peak or Maximum Concentration Following Drug Administration for Mometasone Furoate [ Time Frame: Samples were taken pre-dose and at 15 and 30 minutes and 1, 2, 4, 12 and 24 hours post-dose. ] [ Designated as safety issue: No ]
  • Time to Reach Peak or Maximum Concentration Following Drug Administration for Indacaterol [ Time Frame: Samples were taken pre-dose and at 15 and 30 minutes and 1, 2, 4, 12 and 24 hours post-dose. ] [ Designated as safety issue: No ]

Enrollment: 31
Study Start Date: October 2007
Study Completion Date: April 2008
Primary Completion Date: April 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Indacaterol/mometasone - Placebo
In Treatment Period 1 (Day 1) participants received 2 inhalations of indacaterol maleate 250 μg / mometasone furoate 200 μg once a day in the morning via the Twisthaler device. In Treatment Period 2 (Day 8) participants received 2 inhalations of placebo via the Twisthaler device once a day in the morning. In Treatment Period 3 (Day 15) participants received fluticasone proprionate 250 μg / salmeterol xinafoate 50 μg twice a day delivered via dry-powder inhaler. Each treatment period was separated by a minimum washout period of 7 days.
Drug: indacaterol maleate/mometasone furoate
Indacaterol maleate 250 μg / mometasone furoate 200 μg delivered via the Twisthaler device.
Other Name: QMF149
Drug: placebo to indacaterol maleate/mometasone furoate
Placebo to indacaterol maleate/mometasone furoate delivered via the Twisthaler device.
Drug: fluticasone proprionate / salmeterol xinafoate
Fluticasone proprionate 250 μg / salmeterol xinafoate 50 μg delivered via the Accuhaler® device.
Other Name: Seretide® Accuhaler®
Experimental: Placebo - indacaterol/mometasone
In Treatment Period 1 (Day 1) participants received 2 inhalations of placebo in the morning via the Twistheler device. In Treatment Period 2 (Day 8) participants received 2 inhalations of indacaterol maleate 250 μg / mometasone furoate 200 μg via the Twisthaler device in the morning. In Treatment Period 3 (Day 15) participants received fluticasone proprionate 250 μg / salmeterol xinafoate 50 μg twice a day delivered via dry-powder inhaler. Each treatment period was separated by a minimum washout period of 7 days.
Drug: indacaterol maleate/mometasone furoate
Indacaterol maleate 250 μg / mometasone furoate 200 μg delivered via the Twisthaler device.
Other Name: QMF149
Drug: placebo to indacaterol maleate/mometasone furoate
Placebo to indacaterol maleate/mometasone furoate delivered via the Twisthaler device.
Drug: fluticasone proprionate / salmeterol xinafoate
Fluticasone proprionate 250 μg / salmeterol xinafoate 50 μg delivered via the Accuhaler® device.
Other Name: Seretide® Accuhaler®

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male and female adult patients aged 18-75 years with persistent asthma
  • Patients with persistent asthma, diagnosed according to the Global Initiative for Asthma guidelines (GINA) and who additionally met the following criteria:

    1. Patients receiving daily treatment with inhaled corticosteroid up to the maximum dose per day indicated in the package leaflet, in a stable regimen for the month prior to Visit 1.
    2. Patients with a forced expiratory volume in 1 second (FEV1) at Visit 1 of ≥ 50% of the predicted normal value. This criterion for FEV1 had to be demonstrated after a washout period of at least 6 hours during which no short acting β2-agonist had been inhaled, and a minimum of 48 hours for a long acting β2-agonist.
    3. Patients who demonstrated an increase of ≥12% and ≥200 mL in FEV1 over their pre-bronchodilator value 30 minutes after inhaling a total of 200 μg of salbutamol (or albuterol) via metered dose inhaler (MDI) (the reversibility test). Reversibility had to be demonstrated after an appropriate washout period of at least 6 hrs prior to the evaluation for a shortacting β2-agonist. The administration of salbutamol (or albuterol) for the reversibility test was to be within 30 minutes after pre-bronchodilator spirometry. Reversibility had to be demonstrated at Visit 1 or between Visits 1 and 2, in order for patients to be included in the trial.
    4. For each patient, the smaller value of the Visit 1 FEV1 or the Visit 2 FEV1 pre-dose value had to be at least 85% of the larger value.
  • Body mass index (BMI) between 18 and 32 kg/m^2 and weight >50 kg.
  • patients using local contraception

Exclusion Criteria:

  • Pregnant or nursing women
  • Recent use of tobacco or history of smoking > 10 pack years
  • Patients diagnosed with chronic obstructive pulmonary disease (COPD)
  • Patients with recent experience of severe asthma attack/exacerbation within 6-months of study start
  • Patients with frequent rescue medication (>8 puffs/day for two consecutive days)
  • Clinically relevant laboratory abnormality or a clinically significant condition
  • Active cancer or a history of cancer with less than 5 years disease free survival time
  • History of long QT syndrome or with long QTc interval prior to dosing
  • History of hypersensitivity to the study drugs or to drugs with similar chemical structures
  • Use of certain medications
  • Use of other investigational drugs
  • A positive Hepatitis B surface antigen (HBsAg) or Hepatitis C test result
  • History of immunodeficiency diseases, including a positive human immumodeficiency virus (HIV) test result.
  • History of drug or alcohol abuse or evidence of such abuse

Other protocol-defined inclusion/exclusion criteria may apply.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00556673

Locations
France
Novartis Investigator Site
Poitiers, France, 86000
Germany
Novartis Investigator Site
Berlin, Germany, 14050
Sponsors and Collaborators
Novartis
Merck Sharp & Dohme Corp.
Investigators
Principal Investigator: Novartis Novartis investigator site
  More Information

No publications provided

Responsible Party: Novartis
ClinicalTrials.gov Identifier: NCT00556673     History of Changes
Other Study ID Numbers: CQMF149A2204, 2007-002360-10
Study First Received: November 9, 2007
Results First Received: March 11, 2013
Last Updated: March 11, 2013
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by Novartis:
Asthma, QMF149, fixed combination of indacaterol and mometasone furoate

Additional relevant MeSH terms:
Asthma
Bronchial Diseases
Hypersensitivity
Hypersensitivity, Immediate
Immune System Diseases
Lung Diseases
Lung Diseases, Obstructive
Respiratory Hypersensitivity
Respiratory Tract Diseases
Albuterol
Fluticasone
Maleic acid
Mometasone furoate
Salmeterol
Adrenergic Agents
Adrenergic Agonists
Adrenergic beta-2 Receptor Agonists
Adrenergic beta-Agonists
Anti-Allergic Agents
Anti-Asthmatic Agents
Anti-Inflammatory Agents
Autonomic Agents
Bronchodilator Agents
Dermatologic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 22, 2014