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

Asthma Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00556673
• Other study ID #: CQMF149A2204
• Secondary ID: 2007-002360-10
• Status: Completed
• Phase: Phase 2
• First received: November 9, 2007
• Last updated: March 11, 2013
• Start date: October 2007
• Est. completion date: April 2008

Study information

• Verified date: March 2013
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)Germany: Federal Institute for Drugs and Medical Devices
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 31
• Est. completion date: April 2008
• Est. primary completion date: April 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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 ß2-agonist had been inhaled, and a minimum of 48 hours for a long acting ß2-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 ß2-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.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Asthma

Intervention

Drug:
• indacaterol maleate/mometasone furoate
Indacaterol maleate 250 µg / mometasone furoate 200 µg delivered via the Twisthaler device.
• placebo to indacaterol maleate/mometasone furoate
Placebo to indacaterol maleate/mometasone furoate delivered via the Twisthaler device.
• fluticasone proprionate / salmeterol xinafoate
Fluticasone proprionate 250 µg / salmeterol xinafoate 50 µg delivered via the Accuhaler® device.

Locations

Country	Name	City	State
France	Novartis Investigator Site	Poitiers
Germany	Novartis Investigator Site	Berlin

Sponsors (2)

Lead Sponsor	Collaborator
Novartis	Merck Sharp & Dohme Corp.

Countries where clinical trial is conducted

France,  Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Period Baseline to 24 Hour Post-dose (Trough) Forced Expiratory Volume in 1 Second (FEV1)	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.	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).	No
Secondary	Change From Baseline in Peak Forced Expiratory Volume in One Second (FEV1)	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.	Days 1, 8 and 15, pre-dose (Baseline) and 5, 15, and 30 minutes, 1, 2, 3, and 4 hours post-dose.	No
Secondary	Change From Period Baseline in Trough Percent Predicted Forced Expiratory Volume in 1 Second (FEV1)	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.	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).	No
Secondary	Change From Period Baseline in Peak Percent Predicted Forced Expiratory Volume in 1 Second (FEV1)	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.	Days 1, 8 and 15, pre-dose (Baseline) and 5, 15, and 30 minutes, 1, 2, 3, and 4 hours post-dose.	No
Secondary	Change From Period Baseline in Trough Forced Vital Capacity (FVC)	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.	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).	No
Secondary	Change From Period Baseline in Peak Forced Vital Capacity (FVC)	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.	Days 1, 8 and 15, pre-dose (Baseline) and 5, 15, and 30 minutes, 1, 2, 3, and 4 hours post-dose.	No
Secondary	Change From Period Baseline in Trough FEV1/FVC Ratio	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.	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).	No
Secondary	Change From Period Baseline in Peak FEV1/FVC Ratio	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.	Days 1, 8 and 15, pre-dose (Baseline) and 5, 15, and 30 minutes, 1, 2, 3, and 4 hours post-dose.	No
Secondary	Area Under the Concentration-time Curve From Time 0 to 12 Hours Post-dose for Mometasone Furoate		Samples were taken pre-dose and at 15 and 30 minutes and 1, 2, 4, and 12 hours post-dose.	No
Secondary	Area Under the Concentration-time Curve From Time 0 to 24 Hours Post-dose for Mometasone Furoate		Samples were taken pre-dose and at 15 and 30 minutes and 1, 2, 4, 12 and 24 hours post-dose.	No
Secondary	Area Under the Concentration-time Curve From Time 0 to 24 Hours Post-dose for Indacaterol		Samples were taken pre-dose and at 15 and 30 minutes and 1, 2, 4, 12 and 24 hours post-dose.	No
Secondary	Maximum (Peak) Plasma Concentration (Cmax) of Mometasone Furoate		Samples were taken pre-dose and at 15 and 30 minutes and 1, 2, 4, 12 and 24 hours post-dose.	No
Secondary	Maximum (Peak) Plasma Concentration (Cmax) of Indacaterol		Samples were taken pre-dose and at 15 and 30 minutes and 1, 2, 4, 12 and 24 hours post-dose.	No
Secondary	Time to Reach Peak or Maximum Concentration Following Drug Administration for Mometasone Furoate		Samples were taken pre-dose and at 15 and 30 minutes and 1, 2, 4, 12 and 24 hours post-dose.	No
Secondary	Time to Reach Peak or Maximum Concentration Following Drug Administration for Indacaterol		Samples were taken pre-dose and at 15 and 30 minutes and 1, 2, 4, 12 and 24 hours post-dose.	No