Back to resultsInvestigation of the 24 Hour Forced Expiratory Flow in 1 Second (FEV1) Profile of a Single Dose of Indacaterol/Mometasone Delivered Via the TWISTHALER® Device in Adult Patients With Persistent Asthma
Primary Purpose
Asthma
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
fluticasone propionate/salmeterol
indacaterol maleate / mometasone furoate
placebo to indacaterol/mometasone
placebo to fluticasone propionate/salmeterol
Sponsored by
About this trial
This is an interventional treatment trial for Asthma focused on measuring Asthma, QMF, Indacaterol, Mometasone
Eligibility Criteria
Inclusion Criteria:
- Male and female adult patients aged 18-75 years (inclusive), who have signed an Informed Consent Form prior to initiation of any study-related procedure,
Patients with persistent asthma, diagnosed according to Global Initiative for Asthma (GINA) guidelines (National Institute of Health, National Heart, Lung and Blood Institute, 2006) and who additionally meet the following criteria:
- Patients receiving daily treatment with inhaled corticosteroid up to the maximum dose per day indicated in the product label, in a stable regimen for the month prior to Visit 1.
- Patients with an FEV1 at Visit 1 ≥50% of predicted normal.
- Patients who demonstrate an increase of ≥ 12% and ≥ 200 mL in FEV1 over their pre-bronchodilator.
Exclusion Criteria:
- Pregnant women, nursing mothers, or females of childbearing potential, regardless of whether or not sexually active, if they are not using a reliable form of contraception.
- Patients who have used tobacco products within the 6 months period prior to Visit 1, or who have a smoking history of greater than 10 pack years.
- Patients diagnosed with Chronic Obstructive Pulmonary disease (COPD) as defined by the GOLD guidelines (Global Initiative for Chronic Obstructive Lung Disease 2006).
- Patients with seasonal allergy whose asthma is likely to deteriorate during the study period.
- Patients who have had an acute asthma attack/exacerbation requiring hospitalization in the 6 months prior to Visit 1.
- Patients who have had an acute asthma attack / exacerbation requiring an emergency room visit within 6 weeks prior to Visit 1 or at any time between Visit 1 and Visit 2.
- Patients who have had a respiratory tract infection within 4 weeks prior to Visit 1 or at any time between Visit 1 and Visit 2.
- Patients with a history of long QT interval syndrome or whose QT interval corrected for heart rate (QTc) interval (Bazett's) measured at Visit 1 or Visit 2 is prolonged: > 450 ms (males) or > 470 ms (females).
- Other clinically significant conditions which may interfere with the study conduct or patient safety as specified in the protocol.
Other protocol-defined inclusion/exclusion criteria may apply.
Sites / Locations
- Novartis Investigator Site
- Novartis Investigator site
- Novartis Investigator Site
- Novartis Investigator Site
- Novartis Investigator Site
- Novartis Investigator Site
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Experimental
Arm Label
Ind/M - FP/Salm - Pbo
FP/Salm - Pbo - Ind/M
Pbo - Ind/M - FP/Salm
Arm Description
In Treatment Period 1 (Days 1 & 2) participants received indacaterol/mometasone (Ind/M) 500/400 μg via the TWISTHALER device (2 inhalations of 250/200 μg) in the evening and placebo to fluticasone/salmeterol via multi-dose dry powder inhaler (MDDPI), one inhalation in the evening and one inhalation the following morning. In Treatment Period 2 (Days 8 & 9) participants received 2 inhalations of placebo to indacaterol/mometasone via the TWISTHALER device in the evening and fluticasone/salmeterol (FP/Salm) 250/50 μg via MDDPI, one inhalation in the evening and one inhalation the following morning. In Treatment Period 3 (Days 15 & 16) participants received 2 inhalations of placebo (Pbo) to indacaterol/mometasone via the TWISTHALER device in the evening and placebo to fluticasone/salmeterol via MDDPI, one inhalation in the evening and one inhalation the following morning. Each treatment period was separated by a 6-day washout period.
In Treatment Period 1 (Days 1 & 2) participants received 2 inhalations of placebo to indacaterol/mometasone via the TWISTHALER device in the evening and fluticasone/salmeterol (FP/Salm) 250/50 μg via MDDPI, one inhalation in the evening and one inhalation the following morning. In Treatment Period 2 (Days 8 & 9) participants received 2 inhalations of placebo to indacaterol/mometasone via the TWISTHALER device in the evening and placebo to fluticasone/salmeterol via MDDPI, one inhalation in the evening and one inhalation the following morning. In Treatment Period 3 (Days 15 & 16) participants received indacaterol/mometasone (Ind/M) 500/400 μg via the TWISTHALER device (2 inhalations of 250/200 μg) in the evening and placebo to fluticasone/salmeterol via MDDPI, one inhalation in the evening and one inhalation the following morning. Each treatment period was separated by a 6-day washout period.
In Treatment Period 1 (Days 1 & 2) participants received 2 inhalations of placebo (Pbo) to indacaterol/mometasone via the TWISTHALER device in the evening and placebo to fluticasone/salmeterol via MDDPI, one inhalation in the evening and one inhalation the following morning. In Treatment Period 2 (Days 8 & 9) participants received indacaterol/mometasone (Ind/M) 500/400 μg via the TWISTHALER device (2 inhalations of 250/200 μg) in the evening and placebo to fluticasone/salmeterol via MDDPI, one inhalation in the evening and one inhalation the following morning. In Treatment Period 3 (Days 15 & 16) participants received 2 inhalations of placebo to indacaterol/mometasone via the TWISTHALER device in the evening and fluticasone/salmeterol (FP/Salm) 250/50 μg via MDDPI, one inhalation in the evening and one inhalation the following morning. Each treatment period was separated by a 6-day washout period.
Outcomes
Primary Outcome Measures
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 analyzed using Analysis of Covariance (ANCOVA) adjusting for treatment, period, sequence and center with period baseline as a covariate and patient nested within sequence as a random effect.
Secondary Outcome Measures
Forced Expiratory Volume in 1 Second (FEV1) at Single Time Points
FEV1 is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation. FEV1 was analyzed using Analysis of Covariance (ANCOVA) adjusting for treatment, period, sequence and center with period baseline as a covariate and patient nested within sequence as a random effect.
Forced Expiratory Volume in 1 Second (FEV1) Standardized Area Under the Curve (AUC) Between Baseline (Pre-dose) and 24 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. FEV1 was measured pre-dose and up to 24 hours post-dose. The FEV1 standardized area under the curve (AUC) was analyzed for four time intervals:
Baseline (pre-dose) to 4 hours (hr) post-dosing;
Baseline (pre-dose) to 23 hours, 45 minutes (min) post-dosing;
11 hours, 10 minutes to 12 hours, 30 minutes post-dosing;
11 hours, 10 minutes to 23 hours, 45 minutes post-dosing.
AUC for FEV1 was analyzed using Analysis of Covariance adjusting for treatment, period, sequence and center with period baseline as a covariate and patient nested within sequence as a random effect.
Time to Peak 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. Time to peak FEV1 is calculated in minutes from the time of inhalation of study drug to the time of the peak FEV1 during the first 4 hours post-dose.
Time to peak FEV1 is based on log-transformed analysis of variance adjusted for treatment, period, sequence and center, with patient nested within sequence as a random effect. Geometric Mean was obtained by taking anti-logs of the adjusted means from the model and standard error was calculated using the delta method.
Forced Vital Capacity (FVC) at Single Time Points
Vital capacity is the amount of air which can be forcibly exhaled from the lungs after taking the deepest breath possible.
FVC was analyzed using ANCOVA adjusting for treatment, period, sequence and center with period baseline as a covariate and patient nested within sequence as a random effect.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00557440
Brief Title
Investigation of the 24 Hour Forced Expiratory Flow in 1 Second (FEV1) Profile of a Single Dose of Indacaterol/Mometasone Delivered Via the TWISTHALER® Device in Adult Patients With Persistent Asthma
Official Title
A Multi-center, Randomized, Double-blind, Double Dummy, Placebo and Active Controlled Crossover Study, to Investigate the 24 Hour FEV1 Profile of a Single Dose of QMF TWISTHALER Device in Adult Patients With Persistent Asthma
Study Type
Interventional
2. Study Status
Record Verification Date
April 2009
Overall Recruitment Status
Completed
Study Start Date
November 2007 (undefined)
Primary Completion Date
April 2008 (Actual)
Study Completion Date
April 2008 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis
4. Oversight
5. Study Description
Brief Summary
This study is designed to provide data about the 24 hours FEV1 profile, safety and tolerability of indacaterol/mometasone TWISTHALER device compared to placebo and using fluticasone/salmeterol as an active control.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Asthma
Keywords
Asthma, QMF, Indacaterol, Mometasone
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
37 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Ind/M - FP/Salm - Pbo
Arm Type
Experimental
Arm Description
In Treatment Period 1 (Days 1 & 2) participants received indacaterol/mometasone (Ind/M) 500/400 μg via the TWISTHALER device (2 inhalations of 250/200 μg) in the evening and placebo to fluticasone/salmeterol via multi-dose dry powder inhaler (MDDPI), one inhalation in the evening and one inhalation the following morning.
In Treatment Period 2 (Days 8 & 9) participants received 2 inhalations of placebo to indacaterol/mometasone via the TWISTHALER device in the evening and fluticasone/salmeterol (FP/Salm) 250/50 μg via MDDPI, one inhalation in the evening and one inhalation the following morning.
In Treatment Period 3 (Days 15 & 16) participants received 2 inhalations of placebo (Pbo) to indacaterol/mometasone via the TWISTHALER device in the evening and placebo to fluticasone/salmeterol via MDDPI, one inhalation in the evening and one inhalation the following morning.
Each treatment period was separated by a 6-day washout period.
Arm Title
FP/Salm - Pbo - Ind/M
Arm Type
Experimental
Arm Description
In Treatment Period 1 (Days 1 & 2) participants received 2 inhalations of placebo to indacaterol/mometasone via the TWISTHALER device in the evening and fluticasone/salmeterol (FP/Salm) 250/50 μg via MDDPI, one inhalation in the evening and one inhalation the following morning.
In Treatment Period 2 (Days 8 & 9) participants received 2 inhalations of placebo to indacaterol/mometasone via the TWISTHALER device in the evening and placebo to fluticasone/salmeterol via MDDPI, one inhalation in the evening and one inhalation the following morning.
In Treatment Period 3 (Days 15 & 16) participants received indacaterol/mometasone (Ind/M) 500/400 μg via the TWISTHALER device (2 inhalations of 250/200 μg) in the evening and placebo to fluticasone/salmeterol via MDDPI, one inhalation in the evening and one inhalation the following morning.
Each treatment period was separated by a 6-day washout period.
Arm Title
Pbo - Ind/M - FP/Salm
Arm Type
Experimental
Arm Description
In Treatment Period 1 (Days 1 & 2) participants received 2 inhalations of placebo (Pbo) to indacaterol/mometasone via the TWISTHALER device in the evening and placebo to fluticasone/salmeterol via MDDPI, one inhalation in the evening and one inhalation the following morning.
In Treatment Period 2 (Days 8 & 9) participants received indacaterol/mometasone (Ind/M) 500/400 μg via the TWISTHALER device (2 inhalations of 250/200 μg) in the evening and placebo to fluticasone/salmeterol via MDDPI, one inhalation in the evening and one inhalation the following morning.
In Treatment Period 3 (Days 15 & 16) participants received 2 inhalations of placebo to indacaterol/mometasone via the TWISTHALER device in the evening and fluticasone/salmeterol (FP/Salm) 250/50 μg via MDDPI, one inhalation in the evening and one inhalation the following morning.
Each treatment period was separated by a 6-day washout period.
Intervention Type
Drug
Intervention Name(s)
fluticasone propionate/salmeterol
Other Intervention Name(s)
Advair®, Seretide®
Intervention Description
Fluticasone propionate/salmeterol 250/50 μg twice daily delivered via MDDPI.
Intervention Type
Drug
Intervention Name(s)
indacaterol maleate / mometasone furoate
Other Intervention Name(s)
QMF149
Intervention Description
Indacaterol maleate / mometasone furoate 500/400 μg once daily delivered via the TWISTHALER device.
Intervention Type
Drug
Intervention Name(s)
placebo to indacaterol/mometasone
Intervention Description
Placebo to indacaterol maleate/mometasone furoate delivered via the TWISTHALER device.
Intervention Type
Drug
Intervention Name(s)
placebo to fluticasone propionate/salmeterol
Intervention Description
Placebo to fluticasone propionate / salmeterol delivered via MDDPI.
Primary Outcome Measure Information:
Title
Change From Period Baseline to 24 Hour Post-dose (Trough) Forced Expiratory Volume in 1 Second (FEV1)
Description
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 analyzed using Analysis of Covariance (ANCOVA) adjusting for treatment, period, sequence and center with period baseline as a covariate and patient nested within sequence as a random effect.
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).
Secondary Outcome Measure Information:
Title
Forced Expiratory Volume in 1 Second (FEV1) at Single Time Points
Description
FEV1 is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation. FEV1 was analyzed using Analysis of Covariance (ANCOVA) adjusting for treatment, period, sequence and center with period baseline as a covariate and patient nested within sequence as a random effect.
Time Frame
5, 30 minutes, 1, 2, 3, 4 hours, 11 hours 10 minutes, 11 hours 45 minutes, 12 hours 30 minutes, 14, 16, 18, 20, 22 hours, 23 hours 10 minutes, and 23 hours 45 minutes post-dosing.
Title
Forced Expiratory Volume in 1 Second (FEV1) Standardized Area Under the Curve (AUC) Between Baseline (Pre-dose) and 24 Hours Post-dose
Description
FEV1 is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation. FEV1 was measured pre-dose and up to 24 hours post-dose. The FEV1 standardized area under the curve (AUC) was analyzed for four time intervals:
Baseline (pre-dose) to 4 hours (hr) post-dosing;
Baseline (pre-dose) to 23 hours, 45 minutes (min) post-dosing;
11 hours, 10 minutes to 12 hours, 30 minutes post-dosing;
11 hours, 10 minutes to 23 hours, 45 minutes post-dosing.
AUC for FEV1 was analyzed using Analysis of Covariance adjusting for treatment, period, sequence and center with period baseline as a covariate and patient nested within sequence as a random effect.
Time Frame
Pre-dose, 5, 30 minutes, 1, 2, 3, 4 hours, 11 hours 10 minutes, 11 hours 45 minutes, 12 hours 30 minutes, 14, 16, 18, 20, 22 hours, 23 hours 10 minutes, and 23 hours 45 minutes post-dosing.
Title
Time to Peak Forced Expiratory Volume in 1 Second (FEV1)
Description
FEV1 is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation. Time to peak FEV1 is calculated in minutes from the time of inhalation of study drug to the time of the peak FEV1 during the first 4 hours post-dose.
Time to peak FEV1 is based on log-transformed analysis of variance adjusted for treatment, period, sequence and center, with patient nested within sequence as a random effect. Geometric Mean was obtained by taking anti-logs of the adjusted means from the model and standard error was calculated using the delta method.
Time Frame
Up to 4 hours post-dose
Title
Forced Vital Capacity (FVC) at Single Time Points
Description
Vital capacity is the amount of air which can be forcibly exhaled from the lungs after taking the deepest breath possible.
FVC was analyzed using ANCOVA adjusting for treatment, period, sequence and center with period baseline as a covariate and patient nested within sequence as a random effect.
Time Frame
5, 30 minutes, 1, 2, 3, 4 hours, 11 hours 10 minutes, 11 hours 45 minutes, 12 hours 30 minutes, 14, 16, 18, 20, 22 hours, 23 hours 10 minutes, and 23 hours 45 minutes post-dosing.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Male and female adult patients aged 18-75 years (inclusive), who have signed an Informed Consent Form prior to initiation of any study-related procedure,
Patients with persistent asthma, diagnosed according to Global Initiative for Asthma (GINA) guidelines (National Institute of Health, National Heart, Lung and Blood Institute, 2006) and who additionally meet the following criteria:
Patients receiving daily treatment with inhaled corticosteroid up to the maximum dose per day indicated in the product label, in a stable regimen for the month prior to Visit 1.
Patients with an FEV1 at Visit 1 ≥50% of predicted normal.
Patients who demonstrate an increase of ≥ 12% and ≥ 200 mL in FEV1 over their pre-bronchodilator.
Exclusion Criteria:
Pregnant women, nursing mothers, or females of childbearing potential, regardless of whether or not sexually active, if they are not using a reliable form of contraception.
Patients who have used tobacco products within the 6 months period prior to Visit 1, or who have a smoking history of greater than 10 pack years.
Patients diagnosed with Chronic Obstructive Pulmonary disease (COPD) as defined by the GOLD guidelines (Global Initiative for Chronic Obstructive Lung Disease 2006).
Patients with seasonal allergy whose asthma is likely to deteriorate during the study period.
Patients who have had an acute asthma attack/exacerbation requiring hospitalization in the 6 months prior to Visit 1.
Patients who have had an acute asthma attack / exacerbation requiring an emergency room visit within 6 weeks prior to Visit 1 or at any time between Visit 1 and Visit 2.
Patients who have had a respiratory tract infection within 4 weeks prior to Visit 1 or at any time between Visit 1 and Visit 2.
Patients with a history of long QT interval syndrome or whose QT interval corrected for heart rate (QTc) interval (Bazett's) measured at Visit 1 or Visit 2 is prolonged: > 450 ms (males) or > 470 ms (females).
Other clinically significant conditions which may interfere with the study conduct or patient safety as specified in the protocol.
Other protocol-defined inclusion/exclusion criteria may apply.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharma
Organizational Affiliation
Novartis Pharmaceuticals
Official's Role
Study Chair
Facility Information:
Facility Name
Novartis Investigator Site
City
Aalst
Country
Belgium
Facility Name
Novartis Investigator site
City
Ghent
Country
Belgium
Facility Name
Novartis Investigator Site
City
Berlin
Country
Germany
Facility Name
Novartis Investigator Site
City
Hannover
Country
Germany
Facility Name
Novartis Investigator Site
City
Landsberg
Country
Germany
Facility Name
Novartis Investigator Site
City
Rostock
Country
Germany
12. IPD Sharing Statement
Learn more about this trial
Investigation of the 24 Hour Forced Expiratory Flow in 1 Second (FEV1) Profile of a Single Dose of Indacaterol/Mometasone Delivered Via the TWISTHALER® Device in Adult Patients With Persistent Asthma
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