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

NCT00557440 | Completed Phase 2 Results

• 1 other identifier: CQMF149A2202
• Study Type: interventional
• Target: 37
• Locations: 2 countries
• Sites: 6

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.

Conditions

Asthma

Keywords

Asthma; QMF; Indacaterol; Mometasone

Outcome Measures

Primary Outcomes (1)

• 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).

Secondary Outcomes (4)

• Forced Expiratory Volume in 1 Second (FEV1) at Single Time Points

  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.

• Forced Expiratory Volume in 1 Second (FEV1) Standardized Area Under the Curve (AUC) Between Baseline (Pre-dose) and 24 Hours Post-dose

  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.

• Time to Peak Forced Expiratory Volume in 1 Second (FEV1)

  Up to 4 hours post-dose

• Forced Vital Capacity (FVC) at Single Time Points

  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.

Study Arms (3)

Ind/M - FP/Salm - Pbo

EXPERIMENTAL

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; Drug: indacaterol maleate / mometasone furoate; Drug: placebo to indacaterol/mometasone; Drug: placebo to fluticasone propionate/salmeterol

FP/Salm - Pbo - Ind/M

EXPERIMENTAL

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; Drug: indacaterol maleate / mometasone furoate; Drug: placebo to indacaterol/mometasone; Drug: placebo to fluticasone propionate/salmeterol

Pbo - Ind/M - FP/Salm

EXPERIMENTAL

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; Drug: indacaterol maleate / mometasone furoate; Drug: placebo to indacaterol/mometasone; Drug: placebo to fluticasone propionate/salmeterol

Interventions

fluticasone propionate/salmeterol DRUG

Fluticasone propionate/salmeterol 250/50 μg twice daily delivered via MDDPI.

Also known as: Advair®, Seretide®

FP/Salm - Pbo - Ind/M; Ind/M - FP/Salm - Pbo; Pbo - Ind/M - FP/Salm

indacaterol maleate / mometasone furoate DRUG

Indacaterol maleate / mometasone furoate 500/400 μg once daily delivered via the TWISTHALER device.

Also known as: QMF149

FP/Salm - Pbo - Ind/M; Ind/M - FP/Salm - Pbo; Pbo - Ind/M - FP/Salm

placebo to indacaterol/mometasone DRUG

Placebo to indacaterol maleate/mometasone furoate delivered via the TWISTHALER device.

FP/Salm - Pbo - Ind/M; Ind/M - FP/Salm - Pbo; Pbo - Ind/M - FP/Salm

placebo to fluticasone propionate/salmeterol DRUG

Placebo to fluticasone propionate / salmeterol delivered via MDDPI.

FP/Salm - Pbo - Ind/M; Ind/M - FP/Salm - Pbo; Pbo - Ind/M - FP/Salm

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Novartis: lead

Study Sites (6)

Novartis Investigator Site

Aalst, Belgium

Location

Novartis Investigator site

Ghent, Belgium

Location

Novartis Investigator Site

Berlin, Germany

Location

Novartis Investigator Site

Hanover, Germany

Location

Novartis Investigator Site

Landsberg, Germany

Location

Novartis Investigator Site

Rostock, Germany

Location

MeSH Terms

Conditions

Asthma

Interventions

Fluticasone-Salmeterol Drug Combination; Mometasone Furoate; QMF149; Salmeterol Xinafoate

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Intervention Hierarchy (Ancestors)

Albuterol; Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines; Phenethylamines; Ethylamines; Fluticasone; Androstadienes; Androstenes; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Drug Combinations; Pharmaceutical Preparations; Pregnadienediols; Pregnadienes; Pregnanes

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

862-778-8300

Study Officials

• Novartis Pharma

  Novartis Pharmaceuticals

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 12, 2007
• First Posted: November 14, 2007
• Study Start: November 1, 2007
• Primary Completion: April 1, 2008
• Study Completion: April 1, 2008
• Last Updated: March 21, 2013
• Results First Posted: March 21, 2013

Record last verified: 2009-04

Locations

BE (2); DE (4)