A Dose Ranging Trial of 4 Doses of Indacaterol Delivered Via the TWISTHALER® Device in Patients With Chronic Obstructive Pulmonary Disease (COPD)

This study has been completed.
Sponsor:
Collaborator:
Schering-Plough
Information provided by (Responsible Party):
Novartis
ClinicalTrials.gov Identifier:
NCT00557466
First received: November 13, 2007
Last updated: December 12, 2012
Last verified: November 2012
  Purpose

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


Condition Intervention Phase
COPD
Drug: indacaterol
Drug: formoterol
Drug: placebo to indacaterol
Drug: placebo to formoterol
Drug: short acting β2- agonist
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Multi-center, Parallel Group, Double Blind, Placebo and Formoterol Controlled 14 Day Dose Ranging Trial of 4 Doses of Indacaterol Delivered Via TWISTHALER® Device in Patients With COPD

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • The Mean Change From Baseline to 24 Hour Post-dose (Trough) Forced Expiratory Volume in 1 Second (FEV1) [ Time Frame: Baseline (prior to first dose) and Day 15 (24 hours after last 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. 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.


Secondary Outcome Measures:
  • Standardized Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve (AUC) Between Baseline (Predose) and 4 Hours Post-dose [ Time Frame: Day 14, pre-dose and at 5, 20, 30 minutes and 1, 2, 3, and 4 hours post-dose. ] [ Designated as safety issue: No ]
    FEV1 was measured on Day 14 pre-dose and up to 4 hours post-dose. The Area Under the Curve (AUC) for FEV1 was analyzed using Analysis of Covariance adjusting for treatment and region with baseline FEV1 as a covariate.

  • The Mean Change From Baseline to 24 Hour Post-dose (Trough) Forced Expiratory Volume in 1 Second (FEV1) on Day 1 [ Time Frame: Day 1 Baseline (prior to first dose) and 24 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. Change from baseline to 24 hour post dose trough FEV1 after 1 day of treatment was analyzed using Analysis of Covariance (ANCOVA) adjusting for treatment and region with baseline FEV1 as a covariate.

  • Standardized Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve (AUC) Between Baseline (Predose) and 4 Hours Post-dose on Day 1 [ Time Frame: Day 1; pre-dose and at 5, 20, 30 minutes and 1, 2, 3, and 4 hours post-dose. ] [ Designated as safety issue: No ]
    FEV1 was measured on Day 1 pre-dose and up to 4 hours post-dose. The Area Under the Curve (AUC) for FEV1 was analyzed using Analysis of Covariance adjusting for treatment and region with baseline FEV1 as a covariate.

  • Time to Peak Forced Expiratory Volume in 1 Second (FEV1) on Day 1 and Day 14 [ Time Frame: Day 1 and Day 14 measured pre-dose and 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, which is taken as the maximum FEV1 recorded post-dose.

  • Change From Baseline in Morning and Evening Peak Expiratory Flow [ Time Frame: Baseline (recorded during the screening period) and Days 1-14 (treatment period). ] [ Designated as safety issue: No ]
    The Peak Expiratory Flow (PEF) rate is the maximal rate that a person can exhale during a short maximal expiratory effort after fully inhaling. Participants measured their PEF using a peak flow meter prior to taking study medication and recorded measurements in a diary every morning and evening during the study. Change from baseline is the difference between the mean baseline PEF recorded during the screening period until the first day of treatment, and the overall mean PEF from Days 1 to 14.

  • Number of Participants Using Rescue Medication [ Time Frame: Over 14 days ] [ Designated as safety issue: No ]
    Participants recorded the use of rescue medications (salbutamol/albuterol) for treatment of asthma symptoms twice a day in a diary during the 14 days of the treatment period.


Enrollment: 568
Study Start Date: October 2007
Study Completion Date: May 2008
Primary Completion Date: May 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: indacaterol 62.5 μg
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
Indacaterol delivered by multiple dose dry powder inhaler (TWISTHALER® device).
Drug: placebo to formoterol
Placebo AEROLIZER® device
Drug: short acting β2- agonist
100 μg / 90 μg salbutamol/albuterol Metered Dose Inhaler (MDI) or equivalent dose of Dry Powder Inhaler (DPI).
Experimental: indacaterol 125 μg
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
Indacaterol delivered by multiple dose dry powder inhaler (TWISTHALER® device).
Drug: placebo to formoterol
Placebo AEROLIZER® device
Drug: short acting β2- agonist
100 μg / 90 μg salbutamol/albuterol Metered Dose Inhaler (MDI) or equivalent dose of Dry Powder Inhaler (DPI).
Experimental: Indacaterol 250 μg
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
Indacaterol delivered by multiple dose dry powder inhaler (TWISTHALER® device).
Drug: placebo to formoterol
Placebo AEROLIZER® device
Drug: short acting β2- agonist
100 μg / 90 μg salbutamol/albuterol Metered Dose Inhaler (MDI) or equivalent dose of Dry Powder Inhaler (DPI).
Experimental: indacaterol 500 μg
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
Indacaterol delivered by multiple dose dry powder inhaler (TWISTHALER® device).
Drug: placebo to formoterol
Placebo AEROLIZER® device
Drug: short acting β2- agonist
100 μg / 90 μg salbutamol/albuterol Metered Dose Inhaler (MDI) or equivalent dose of Dry Powder Inhaler (DPI).
Active Comparator: formoterol
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
Formoterol delivered by oral inhalation via AEROLIZER® inhalation device.
Drug: placebo to indacaterol
Placebo TWISTHALER® device
Drug: short acting β2- agonist
100 μg / 90 μg salbutamol/albuterol Metered Dose Inhaler (MDI) or equivalent dose of Dry Powder Inhaler (DPI).
Placebo Comparator: placebo
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
Placebo TWISTHALER® device
Drug: placebo to formoterol
Placebo AEROLIZER® device
Drug: short acting β2- agonist
100 μg / 90 μg salbutamol/albuterol Metered Dose Inhaler (MDI) or equivalent dose of Dry Powder Inhaler (DPI).

  Eligibility

Ages Eligible for Study:   40 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male and female adults aged ≥ 40 years, who have signed an Informed Consent Form prior to initiation of any study-related procedure (which include any adjustment to their current COPD treatment)
  • Cooperative outpatients with a diagnosis of COPD (moderate to severe as classified by the Global Initiative for Obstructive Lung Disease (GOLD) Guidelines, 2006) and:

    • Smoking history of at least 10 pack years
    • Post-bronchodilator Forced Expiratory Volume in one second (FEV1) < 80% and ≥30% of the predicted normal value.
    • Post-bronchodilator FEV1/Forced vital capacity (FVC) < 70%

Exclusion Criteria:

  • Pregnant women, nursing mothers, or females of childbearing potential, regardless of whether or not sexually active, if they are not using acceptable methods of contraception.
  • Patients who have been hospitalized for an exacerbation of their airways disease within 6 weeks prior to Visit 1 or between Visit 1 and Visit 2.
  • Patients with a history of asthma.
  • Patients with an acute respiratory tract infection within 4 weeks prior to Visit 1, will be not allowed to enter the study.
  • 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: NCT00557466

  Show 77 Study Locations
Sponsors and Collaborators
Novartis
Schering-Plough
Investigators
Study Chair: Novartis Pharma AG Novartis Pharmaceuticals
  More Information

No publications provided

Responsible Party: Novartis
ClinicalTrials.gov Identifier: NCT00557466     History of Changes
Other Study ID Numbers: CQMF149B2201
Study First Received: November 13, 2007
Results First Received: November 12, 2012
Last Updated: December 12, 2012
Health Authority: Belgium: Federal Agency for Medicinal Products and Health Products
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Federal Institute for Drugs and Medical Devices
Hungary: National Institute of Pharmacy
Ireland: Irish Medicines Board
Italy: The Italian Medicines Agency
Latvia: State Agency of Medicines
Lithuania: State Medicine Control Agency - Ministry of Health
Norway: Norwegian Medicines Agency
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Romania: National Medicines Agency
South Africa: Medicines Control Council
Sweden: Medical Products Agency
Turkey: Ministry of Health
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica
Chile: Comisión Nacional de Investigación Científica y Tecnológica
Peru: Ministry of Health

Keywords provided by Novartis:
QMF
indacaterol
TWISTHALER® device

Additional relevant MeSH terms:
Lung Diseases, Obstructive
Pulmonary Disease, Chronic Obstructive
Lung Diseases
Respiratory Tract Diseases
Formoterol
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Asthmatic Agents
Respiratory System Agents
Therapeutic Uses
Adrenergic beta-2 Receptor Agonists
Adrenergic beta-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 18, 2014