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

• ClinicalTrials.gov Identifier: NCT00556673
• Recruitment Status: Completed
• First Posted: November 12, 2007
• Results First Posted: April 22, 2013
• Last Update Posted: April 22, 2013
• Sponsor: Novartis
• Collaborator: Merck Sharp & Dohme Corp.
• Information provided by (Responsible Party): Novartis

Study Description

Brief Summary:

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 or disease	Intervention/treatment	Phase
Asthma	Drug: indacaterol maleate/mometasone furoate; Drug: placebo to indacaterol maleate/mometasone furoate; Drug: fluticasone proprionate / salmeterol xinafoate	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 31 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Quadruple (Participant, Care Provider, 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
• Study Start Date: October 2007
• Actual Primary Completion Date: April 2008
• Actual Study Completion Date: April 2008

Arms and Interventions

Arm	Intervention/treatment
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®

Outcome Measures

Primary Outcome Measures :

1. 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). ]
   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 :

1. 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. ]
   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.
2. 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). ]
   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.
3. 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. ]
   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.
4. 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). ]
   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.
5. 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. ]
   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.
6. 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). ]
   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.
7. 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. ]
   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.
8. 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. ]
9. 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. ]
10. 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. ]
11. 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. ]
12. 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. ]
13. 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. ]
14. 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. ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• 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

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

• Responsible Party: Novartis
• ClinicalTrials.gov Identifier: NCT00556673
• Other Study ID Numbers: CQMF149A2204; 2007-002360-10 ( EudraCT Number )
• First Posted: November 12, 2007
• Results First Posted: April 22, 2013
• Last Update Posted: April 22, 2013
• Last Verified: March 2013

Keywords provided by Novartis:

Asthma, QMF149, fixed combination of indacaterol and mometasone furoate

Additional relevant MeSH terms:

Asthma; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Fluticasone; Mometasone Furoate; Salmeterol Xinafoate; Maleic acid; Anti-Inflammatory Agents; Bronchodilator Agents; Autonomic Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Anti-Asthmatic Agents; Respiratory System Agents; Dermatologic Agents; Anti-Allergic Agents; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Adrenergic Agonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors