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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis
ClinicalTrials.gov Identifier:
NCT00557440
First received: November 12, 2007
Last updated: February 15, 2013
Last verified: April 2009
  Purpose

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.


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

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

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 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 [ 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. ] [ 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. 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 [ 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. ] [ 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. 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) [ Time Frame: Up to 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. 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 [ 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. ] [ 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.

    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.



Enrollment: 37
Study Start Date: November 2007
Study Completion Date: April 2008
Primary Completion Date: April 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Ind/M - FP/Salm - Pbo

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.

Drug: fluticasone propionate/salmeterol
Fluticasone propionate/salmeterol 250/50 μg twice daily delivered via MDDPI.
Other Names:
  • Advair®
  • Seretide®
Drug: indacaterol maleate / mometasone furoate
Indacaterol maleate / mometasone furoate 500/400 μg once daily delivered via the TWISTHALER device.
Other Name: QMF149
Drug: placebo to indacaterol/mometasone
Placebo to indacaterol maleate/mometasone furoate delivered via the TWISTHALER device.
Drug: placebo to fluticasone propionate/salmeterol
Placebo to fluticasone propionate / salmeterol delivered via MDDPI.
Experimental: FP/Salm - Pbo - Ind/M

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.

Drug: fluticasone propionate/salmeterol
Fluticasone propionate/salmeterol 250/50 μg twice daily delivered via MDDPI.
Other Names:
  • Advair®
  • Seretide®
Drug: indacaterol maleate / mometasone furoate
Indacaterol maleate / mometasone furoate 500/400 μg once daily delivered via the TWISTHALER device.
Other Name: QMF149
Drug: placebo to indacaterol/mometasone
Placebo to indacaterol maleate/mometasone furoate delivered via the TWISTHALER device.
Drug: placebo to fluticasone propionate/salmeterol
Placebo to fluticasone propionate / salmeterol delivered via MDDPI.
Experimental: Pbo - Ind/M - FP/Salm

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.

Drug: fluticasone propionate/salmeterol
Fluticasone propionate/salmeterol 250/50 μg twice daily delivered via MDDPI.
Other Names:
  • Advair®
  • Seretide®
Drug: indacaterol maleate / mometasone furoate
Indacaterol maleate / mometasone furoate 500/400 μg once daily delivered via the TWISTHALER device.
Other Name: QMF149
Drug: placebo to indacaterol/mometasone
Placebo to indacaterol maleate/mometasone furoate delivered via the TWISTHALER device.
Drug: placebo to fluticasone propionate/salmeterol
Placebo to fluticasone propionate / salmeterol delivered via MDDPI.

  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 (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.

  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: NCT00557440

Locations
Belgium
Novartis Investigator Site
Aalst, Belgium
Novartis Investigator site
Ghent, Belgium
Germany
Novartis Investigator Site
Berlin, Germany
Novartis Investigator Site
Hannover, Germany
Novartis Investigator Site
Landsberg, Germany
Novartis Investigator Site
Rostock, Germany
Sponsors and Collaborators
Novartis
Investigators
Study Chair: Novartis Pharma Novartis Pharmaceuticals
  More Information

No publications provided

Responsible Party: Novartis
ClinicalTrials.gov Identifier: NCT00557440     History of Changes
Other Study ID Numbers: CQMF149A2202
Study First Received: November 12, 2007
Results First Received: February 15, 2013
Last Updated: February 15, 2013
Health Authority: Belgium: Federal Agency for Medicinal Products and Health Products
Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by Novartis:
Asthma
QMF
Indacaterol
Mometasone

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
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
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Reproductive Control Agents
Respiratory System Agents

ClinicalTrials.gov processed this record on October 20, 2014