A Dose Ranging Trial of 4 Doses of Indacaterol Delivered Via TWISTHALER® Device in Adult and Adolescent Patients With Persistent Asthma

NCT00545272 | Completed Phase 2 Results

• 2 other identifiers: CQMF149A22012007-003191-19
• Study Type: interventional
• Target: 392
• Locations: 10 countries
• Sites: 60

Brief Summary

This study will evaluate the dose response relationship among four doses of indacaterol as well as placebo delivered via the TWISTHALER® device.

Conditions

Asthma

Keywords

QMF; indacaterol; Twisthaler®

Outcome Measures

Primary Outcomes (1)

• The Mean Change From 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 baseline to 24 hour post dose trough FEV1 after 14 days of treatment was analyzed using Analysis of Covariance (ANCOVA) adjusting for treatment and region with baseline FEV1 as a covariate.

  Baseline (prior to first dose) and Day 15 (24 hours after last dose)

Secondary Outcomes (6)

• Standardized Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve (AUC) Between Baseline (Predose) and 4 Hours Post-dose

  Day 14, pre-dose, 5, 20 and 30 minutes, 1, 2, 3, and 4 hours post-dose.

• The Mean Change From Baseline to 24 Hour Post-dose (Trough) Forced Expiratory Volume in 1 Second (FEV1) on Day 1

  Day 1 Baseline (prior to first dose) and 24 hours post-dose.

• Standardized Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve (AUC) Between Baseline (Predose) and 4 Hours Post-dose on Day 1

  Day 1, pre-dose, 5, 20 and 30 minutes, 1, 2, 3, and 4 hours post-dose.

• Time to Peak Forced Expiratory Volume in 1 Second (FEV1) on Day 1 and Day 14

  Day 1 and Day 14 measured pre-dose and up to 4 hours post-dose

• Change From Baseline in Morning and Evening Peak Expiratory Flow

  Baseline (recorded during the screening period) and Days 1-14 (treatment period)

Study Arms (6)

indacaterol 62.5 μg

EXPERIMENTAL

Indacaterol 62.5 μg delivered by the TWISTHALER® device once a day and placebo to formoterol (placebo AEROLIZER® device) twice a day for 14 days. All participants were supplied with salbutamol/albuterol to use throughout the study as rescue medication.

Drug: indacaterol; Drug: placebo to formoterol; Drug: short acting β2-agonist

indacaterol 125 μg

EXPERIMENTAL

Indacaterol 125 μg delivered by the TWISTHALER® device once a day and placebo to formoterol (placebo AEROLIZER® device) twice a day for 14 days. All participants were supplied with salbutamol/albuterol to use throughout the study as rescue medication.

Drug: indacaterol; Drug: placebo to formoterol; Drug: short acting β2-agonist

indacaterol 250 μg

EXPERIMENTAL

Indacaterol 250 μg delivered by the TWISTHALER® device once a day and placebo to formoterol (placebo AEROLIZER® device) twice a day for 14 days. All participants were supplied with salbutamol/albuterol to use throughout the study as rescue medication.

Drug: indacaterol; Drug: placebo to formoterol; Drug: short acting β2-agonist

indacaterol 500 μg

EXPERIMENTAL

Indacaterol 500 μg delivered by the TWISTHALER® device once a day and placebo to formoterol (placebo AEROLIZER® device) twice a day for 14 days. All participants were supplied with salbutamol/albuterol to use throughout the study as rescue medication.

Drug: indacaterol; Drug: placebo to formoterol; Drug: short acting β2-agonist

formoterol

ACTIVE COMPARATOR

Formoterol 12 μg delivered by the AEROLIZER® device twice a day and placebo to indacaterol (placebo TWISTHALER® device) once a day for 14 days. All participants were supplied with salbutamol/albuterol to use throughout the study as rescue medication.

Drug: formoterol; Drug: placebo to indacaterol; Drug: short acting β2-agonist

placebo

PLACEBO COMPARATOR

Placebo to indacaterol (placebo TWISTHALER® device) once a day and placebo to formoterol (placebo AEROLIZER® device) twice a day for 14 days. All participants were supplied with salbutamol/albuterol to use throughout the study as rescue medication.

Drug: placebo to indacaterol; Drug: placebo to formoterol; Drug: short acting β2-agonist

Interventions

indacaterol DRUG

Indacaterol delivered by multiple dose dry powder inhaler (TWISTHALER® device).

indacaterol 125 μg; indacaterol 250 μg; indacaterol 500 μg; indacaterol 62.5 μg

formoterol DRUG

Formoterol delivered by oral inhalation via AEROLIZER® inhalation device.

formoterol

placebo to indacaterol DRUG

Placebo TWISTHALER® device

formoterol; placebo

placebo to formoterol DRUG

Placebo AEROLIZER® device

indacaterol 125 μg; indacaterol 250 μg; indacaterol 500 μg; indacaterol 62.5 μg; placebo

short acting β2-agonist DRUG

100 μg/ 90 μg salbutamol/albuterol Metered Dose Inhaler (MDI) or equivalent dose of Dry Powder Inhaler (DPI).

formoterol; indacaterol 125 μg; indacaterol 250 μg; indacaterol 500 μg; indacaterol 62.5 μg; placebo

Eligibility Criteria

• Age: 12 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and female adult and adolescent patients aged 12-75 years inclusive (or ≥18-75 years depending upon regulatory and/or Institutional Review Board (IRB)/Independent Ethics Committee (IEC)/Research Ethics Board (REB) approval), who have signed an Informed Consent Form prior to initiation of any study-related procedure, including any adjustments to asthma medication prior to Visit 1. Patients below the legal age of consent are required to have the Informed Consent Form signed by the patient's parent / guardian.
• Patients with 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 package leaflet, in a stable regimen for the month prior to Visit 1.
• Patients with a Forced Expiratory Volume in one second (FEV1) at Visit 1 of ≥50% of the predicted normal value for the patient. This criterion for FEV1 will have to be demonstrated after a washout period of at least 6 hours during which no short acting β2-agonist has been inhaled, and a minimum of 48 hours for a long acting β2-agonist.
• Patients who demonstrate an increase of ≥12% and ≥200 mL in FEV1 over their pre-bronchodilator value within 30 minutes after inhaling a total of 200 µg/180 µg of salbutamol/albuterol Metered Dose Inhaler (MDI) (or equivalent dose of Dry Powder Inhaler \[DPI\]) (the reversibility test). Reversibility will have to be demonstrated after an appropriate washout period of at least 6 hrs prior to the evaluation for a short-acting β2-agonist. The administration of salbutamol/albuterol for the reversibility test is to be within 30 minutes after pre bronchodilator spirometry. Reversibility has to be demonstrated at Visit 1 or between Visits 1 and 2, in order for patients to be included in the trial.

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 with Chronic Obstructive Pulmonary Disease (COPD), or current smokers, or patients who have used tobacco products within the 6 month period prior to Visit 1, or who have a smoking history of greater than 10 pack years.
• Patients:
• who's asthma is likely to deteriorate during the study (including seasonal allergy),
• hospitalized for an acute asthma attack/asthma exacerbation within 6 months prior to Visit 1,
• who have had an emergency room visit for an asthma attack/asthma exacerbation within 6 weeks prior to Visit 1
• who have had a respiratory tract infection or emergency room treatment for an asthma attack/asthma exacerbation within 4 weeks prior to Visit 1
• Patients who require the use of ≥8 inhalations per day of short acting B2-agonist (100 µg/ 90 µg salbutamol/albuterol MDI or equivalent dose of DPI) on any 2 consecutive days from Screening to Randomization.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead
• Schering-Plough: collaborator

Study Sites (60)

Novartis Investigator Site

Aalst, Belgium

Location

Novartis Investigator Site

Halen, Belgium

Location

Novartis Investigator Site

Oostham, Belgium

Location

Novartis Investigator site

Veurne, Belgium

Location

Novartis Investigator Site

Boskovice, Czechia

Location

Novartis Investigator Site

Brno, Czechia

Location

Novartis Investigator site

Břeclav, Czechia

Location

Novartis Investigator Site

Liberec, Czechia

Location

Novartis Investigator Site

Most, Czechia

Location

Novartis Investigator Site

Tábor, Czechia

Location

Novartis Investigator Site

Aalen, Germany

Location

Novartis Investigator Site

Berlin, Germany

Location

Novartis Investigator Site

Braunschweig, Germany

Location

Novartis Investigator Site

Deggendorf, Germany

Location

Novartis Investigator Site

Fürstenwalde, Germany

Location

Novartis Investigator Site

Leipzig, Germany

Location

novartis Investigator site

München, Germany

Location

Novartis investigator site

Balassagyarmat, Hungary

Location

Novartis Investigator Site

Érd, Hungary

Location

Novartis Investigator site

Füzesabony, Hungary

Location

Novartis Investigator Site

Gyonggyos, Hungary

Location

Novartis Investigator Site

Mosdoz, Hungary

Location

Novartis Investigator Site

Pest, Hungary

Location

Novartis Investigator Site

Siófok, Hungary

Location

Novartis Investigator Site

Százhalombatta, Hungary

Location

Novartis Investigator Site

Afula, Israel

Location

Novartis Investigator Site

Ashkelon, Israel

Location

Novartis Investigator Site

Beersheba, Israel

Location

Novartis investigator site

Haifa, Israel

Location

Novartis investigator site

Jerusalem, Israel

Location

Novartis Investigator Site

Petah Tikva, Israel

Location

Novartis Investigator Site

Rehovot, Israel

Location

Novartis Investigator Site

Tel Aviv, Israel

Location

Novartis Investigator Site

Tel-Hashorner, Israel

Location

Novartis Investigator Site

Zrifin, Israel

Location

Novartis Investigator Site

Bialystok, Poland

Location

Novartis investigator site

Bydgoszcz, Poland

Location

Novartis Investigator Site

Lodz, Poland

Location

Novartis Investigator site

Lubin, Poland

Location

Novartis Investigator Site

Tarnów, Poland

Location

Novartis Investigator Site

Moscow, Russia

Location

Novartis Investigator Site

Saint Petersburg, Russia

Location

Novartis Investigator Site

Smolensk, Russia

Location

Novartis investigator site

Tomsk, Russia

Location

Novartis Investigator Site

Bloernfontain, South Africa

Location

Novartis Investigator Site

Cape Town, South Africa

Location

Novartis Investigator Site

Johannesburg, South Africa

Location

Novartis Investigator Site

Krugersdorp, South Africa

Location

Novartis Investigator Site

Les Marais, South Africa

Location

Novartis Investigator Site

Pretoria, South Africa

Location

Novartis Investigator Site

Roodepoort, South Africa

Location

Novartis Investigator Site

Themba, South Africa

Location

Novartis Investigator Site

Madrid, Spain

Location

Novartis Investigator Site

Pozuelo de Alacron, Spain

Location

Novartis Investigator Site

Valencia, Spain

Location

Novartis Investigator Site

Downpatrick, United Kingdom

Location

Novartis Investigator Site

Glasgow, United Kingdom

Location

Novartis Investigator Site

London, United Kingdom

Location

Novartis Investigator Site

Southampton, United Kingdom

Location

Novartis Investigator Site

Watford, United Kingdom

Location

MeSH Terms

Conditions

Asthma

Interventions

indacaterol; Formoterol Fumarate

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines

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: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 16, 2007
• First Posted: October 17, 2007
• Study Start: October 1, 2007
• Primary Completion: April 1, 2008
• Study Completion: April 1, 2008
• Last Updated: January 18, 2013
• Results First Posted: January 18, 2013

Record last verified: 2012-11

Locations

PL (5); ZA (8); GB (5); RU (4); CZ (6); BE (4); HU (8); IL (10); DE (7); ES (3)