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

Asthma Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00557440
• Other study ID #: CQMF149A2202
• Status: Completed
• Phase: Phase 2
• First received: November 12, 2007
• Last updated: February 15, 2013
• Start date: November 2007
• Est. completion date: April 2008

Study information

• Verified date: April 2009
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: Belgium: Federal Agency for Medicinal Products and Health ProductsGermany: Federal Institute for Drugs and Medical Devices
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 37
• 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 (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.

Study Design

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

Related Conditions & MeSH terms

• Asthma

Intervention

Drug:
• fluticasone propionate/salmeterol
Fluticasone propionate/salmeterol 250/50 µg twice daily delivered via MDDPI.
• indacaterol maleate / mometasone furoate
Indacaterol maleate / mometasone furoate 500/400 µg once daily delivered via the TWISTHALER device.
• placebo to indacaterol/mometasone
Placebo to indacaterol maleate/mometasone furoate delivered via the TWISTHALER device.
• placebo to fluticasone propionate/salmeterol
Placebo to fluticasone propionate / salmeterol delivered via MDDPI.

Locations

Country	Name	City	State
Belgium	Novartis Investigator Site	Aalst
Belgium	Novartis Investigator site	Ghent
Germany	Novartis Investigator Site	Berlin
Germany	Novartis Investigator Site	Hannover
Germany	Novartis Investigator Site	Landsberg
Germany	Novartis Investigator Site	Rostock

Sponsors (1)

Lead Sponsor	Collaborator
Novartis

Countries where clinical trial is conducted

Belgium,  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 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.	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	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.	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.	No
Secondary	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.	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.	No
Secondary	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.	Up to 4 hours post-dose	No
Secondary	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.	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.	No