Study to Determine the Onset of Action of Indacaterol in Patients With Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD) - Full Text View

Sponsor:	Novartis
Information provided by:	Novartis
ClinicalTrials.gov Identifier:	NCT00669617

Purpose

This study will evaluate the onset of action of indacaterol (150 and 300 µg) as compared to placebo, salbutamol 200 µg and salmeterol/fluticasone 50/500 µg

Condition	Intervention	Phase
Chronic Obstructive Pulmonary Disease	Drug: Indacaterol Drug: Salmeterol/fluticasone (50/500 μg) Drug: Salbutamol (200 µg) Drug: Placebo to Indacaterol Drug: Placebo to Salmeterol/fluticasone Drug: Placebo to salbutamol	Phase III

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Crossover Assignment Masking: Double Blind (Subject, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	A Phase III, Randomized, Double-blind, Triple-dummy, Placebo Controlled, Multicenter, 5-period, Single-dose Complete Block Crossover Study to Determine the Onset of Action of Indacaterol (150 and 300 μg) in Patients With Moderate to Severe COPD Using Salbutamol (200 μg) and Salmeterol/Fluticasone (50/500 μg) as Active Controls

Resource links provided by NLM:

MedlinePlus related topics: COPD (Chronic Obstructive Pulmonary Disease)

Drug Information available for: Albuterol Levalbuterol hydrochloride Albuterol sulfate Fluticasone propionate Salmeterol Fluticasone Salmeterol xinafoate Indacaterol Levalbuterol tartrate

U.S. FDA Resources

Further study details as provided by Novartis:

Primary Outcome Measures:

Forced Expiratory Volume in 1 Second (FEV1) at 5 Minutes Post-dose [ Time Frame: Five Minutes Post Dose ] [ Designated as safety issue: No ]
FEV1 was measured at 5 minutes after dosing with spirometry conducted according to internationally accepted standards. The time of dosing was defined as the time corresponding to the use of the first inhaler device. The primary variable was analyzed using a mixed model containing the period baseline FEV1 as covariate. The period baseline FEV1 was the average of the FEV1 value measured in the clinic at 50 and 15 min prior to the study drug administration in that period.

Enrollment:	89
Study Start Date:	April 2008
Study Completion Date:	August 2008
Primary Completion Date:	August 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Ind 150μg, Salm/flut, Ind 300μg, Placebo, Salbut Participants received a single dose of each treatment from Period I - V in the following order, separated by a washout period of 4-7 days: Indacaterol 150 μg (Ind 150μg), Salmeterol/fluticasone 50/500 μg (Salm/flut), Indacaterol 300 μg (Ind 300μg), Placebo, Salbutamol 200 μg (Salbut). At each treatment visit, participants received the specified treatment and 2 placebo inhalations (one inhalation from the SDDPI, and one inhalation from each of the two MDDPIs) to maintain blinding. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.	Drug: Indacaterol Indacaterol 150 and 300 μg, delivered via single-dose dry-powder inhaler (SDDPI) Other Names: Arcapta Neohaler Drug: Salmeterol/fluticasone (50/500 μg) Salmeterol/fluticasone 50/500 μg fixed-dose combination delivered via manufacturer's proprietary Multi-Dose Dry-Powder Inhaler (MDDPI). Drug: Salbutamol (200 µg) Salbutamol 200 μg delivered via manufacturer's proprietary Multi-Dose Dry-Powder Inhaler (MDDPI). Drug: Placebo to Indacaterol Placebo to indacaterol delivered via SDDPI Drug: Placebo to Salmeterol/fluticasone Placebo to salmeterol/fluticasone delivered via MDDPI Drug: Placebo to salbutamol Placebo to salbutamol delivered via MDDPI
Experimental: Ind 300μg, Ind 150μg, Salbut, Salm/flut, Placebo Participants received a single dose of each treatment from Period I - V in the following order, separated by a washout period of 4-7 days: Indacaterol 300 μg (Ind 300μg), Indacaterol 150 μg (Ind 150μg), Salbutamol 200 μg (Salbut), Salmeterol/fluticasone 50/500 μg (Salm/flut), Placebo. At each treatment visit, participants received the specified treatment and 2 placebo inhalations (one inhalation from the SDDPI, and one inhalation from each of the two MDDPIs) to maintain blinding. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.	Drug: Indacaterol Indacaterol 150 and 300 μg, delivered via single-dose dry-powder inhaler (SDDPI) Other Names: Arcapta Neohaler Drug: Salmeterol/fluticasone (50/500 μg) Salmeterol/fluticasone 50/500 μg fixed-dose combination delivered via manufacturer's proprietary Multi-Dose Dry-Powder Inhaler (MDDPI). Drug: Salbutamol (200 µg) Salbutamol 200 μg delivered via manufacturer's proprietary Multi-Dose Dry-Powder Inhaler (MDDPI). Drug: Placebo to Indacaterol Placebo to indacaterol delivered via SDDPI Drug: Placebo to Salmeterol/fluticasone Placebo to salmeterol/fluticasone delivered via MDDPI Drug: Placebo to salbutamol Placebo to salbutamol delivered via MDDPI
Experimental: Salm/flut, Placebo, Ind 150μg, Salbut, Ind 300μg Participants received a single dose of each treatment from Period I - V in the following order, separated by a washout period of 4-7 days: Salmeterol/fluticasone 50/500 μg (Salm/flut), Placebo, Indacaterol 150 μg (Ind 150μg), Salbutamol 200 μg (Salbut), Indacaterol 300 μg (Ind 300μg). At each treatment visit, participants received the specified treatment and 2 placebo inhalations (one inhalation from the SDDPI, and one inhalation from each of the two MDDPIs) to maintain blinding. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.	Drug: Indacaterol Indacaterol 150 and 300 μg, delivered via single-dose dry-powder inhaler (SDDPI) Other Names: Arcapta Neohaler Drug: Salmeterol/fluticasone (50/500 μg) Salmeterol/fluticasone 50/500 μg fixed-dose combination delivered via manufacturer's proprietary Multi-Dose Dry-Powder Inhaler (MDDPI). Drug: Salbutamol (200 µg) Salbutamol 200 μg delivered via manufacturer's proprietary Multi-Dose Dry-Powder Inhaler (MDDPI). Drug: Placebo to Indacaterol Placebo to indacaterol delivered via SDDPI Drug: Placebo to Salmeterol/fluticasone Placebo to salmeterol/fluticasone delivered via MDDPI Drug: Placebo to salbutamol Placebo to salbutamol delivered via MDDPI
Experimental: Salbut, Ind 300μg, Placebo, Ind 150μg, Salm/flut Participants received a single dose of each treatment from Period I - V in the following order, separated by a washout period of 4-7 days: Salbutamol 200 μg (Salbut), Indacaterol 300 μg (Ind 300μg), Placebo, Indacaterol 150 μg (Ind 150μg), Salmeterol/fluticasone 50/500 μg (Salm/flut). At each treatment visit, participants received the specified treatment and 2 placebo inhalations (one inhalation from the SDDPI, and one inhalation from each of the two MDDPIs) to maintain blinding. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.	Drug: Indacaterol Indacaterol 150 and 300 μg, delivered via single-dose dry-powder inhaler (SDDPI) Other Names: Arcapta Neohaler Drug: Salmeterol/fluticasone (50/500 μg) Salmeterol/fluticasone 50/500 μg fixed-dose combination delivered via manufacturer's proprietary Multi-Dose Dry-Powder Inhaler (MDDPI). Drug: Salbutamol (200 µg) Salbutamol 200 μg delivered via manufacturer's proprietary Multi-Dose Dry-Powder Inhaler (MDDPI). Drug: Placebo to Indacaterol Placebo to indacaterol delivered via SDDPI Drug: Placebo to Salmeterol/fluticasone Placebo to salmeterol/fluticasone delivered via MDDPI Drug: Placebo to salbutamol Placebo to salbutamol delivered via MDDPI
Experimental: Placebo, Salbut, Salm/flut , Ind 300μg, Ind 150μg Participants received a single dose of each treatment from Period I - V in the following order, separated by a washout period of 4-7 days: Placebo, Salbutamol 200 μg (Salbut), Salmeterol/fluticasone 50/500 μg (Salm/flut), Indacaterol 300 μg (Ind 300μg), Indacaterol 150 μg (Ind 150μg). At each treatment visit, participants received the specified treatment and 2 placebo inhalations (one inhalation from the SDDPI, and one inhalation from each of the two MDDPIs) to maintain blinding. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.	Drug: Indacaterol Indacaterol 150 and 300 μg, delivered via single-dose dry-powder inhaler (SDDPI) Other Names: Arcapta Neohaler Drug: Salmeterol/fluticasone (50/500 μg) Salmeterol/fluticasone 50/500 μg fixed-dose combination delivered via manufacturer's proprietary Multi-Dose Dry-Powder Inhaler (MDDPI). Drug: Salbutamol (200 µg) Salbutamol 200 μg delivered via manufacturer's proprietary Multi-Dose Dry-Powder Inhaler (MDDPI). Drug: Placebo to Indacaterol Placebo to indacaterol delivered via SDDPI Drug: Placebo to Salmeterol/fluticasone Placebo to salmeterol/fluticasone delivered via MDDPI Drug: Placebo to salbutamol Placebo to salbutamol delivered via MDDPI

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
Patients with a diagnosis of Chronic Obstructive Pulmonary Disease (COPD) (moderate-to-severe as classified by the GOLD Guidelines, 2006) and:
- Smoking history of at least 20 pack years
- Post-bronchodilator Forced Expiratory Volume in 1 Second (FEV1) <80% and ≥30% of the predicted normal value.
- Post-bronchodilator FEV1/Forced Vital Capacity (FVC) < 70%, where FVC is forced vital capacity ('Post-' refers to 15-30 minutes after inhalation of 400 μg of salbutamol at Visit 2)

Exclusion Criteria:

Pregnant / nursing women or women of child-bearing potential
Long term oxygen therapy (more than 15 hours per day) on a daily basis for chronic hypoxemia
Patients hospitalized for COPD exacerbation in 6 weeks prior to Visit 2 and up to Visit 3
Respiratory tract infection within 6 weeks prior to Visit 2 and up to Visit 3
Concomitant pulmonary disease, pulmonary tuberculosis (unless chest x-ray confirms no longer active) or clinically significant bronchiectasis
Any history of asthma, including: blood eosinophil count >400/mm3; onset of asthma symptoms prior to age 40 years
History of long QT syndrome or whose QTc (Bazett's) measured at Visit 2 or Visit 3 is prolonged (>450ms for males or >470ms for females)
Clinically relevant lab abnormalities / conditions such as (but not limited to) unstable ischemic heart disease, arrhythmia (excluding stable AF), uncontrolled hypertension, uncontrolled hypo- and hyperthyroidism, hypokalemia, hyperadrenergic state or any condition which in the investigator's opinion might compromise patient safety or compliance, interfere with evaluation, or preclude completion of the study
Uncontrolled Type I / Type II Diabetes or blood glucose outside normal or HbA1c >8.0% of total hemoglobin measured at Visit 2
Any patient with lung cancer or any active cancer or a history of cancer with less than 5 years disease-free survival time
History of hypersensitivity to any of the study drugs
Irregular day/night, waking/sleeping cycles e.g. shift workers
Live attenuated vaccinations within 30 days prior to Visit 2
Investigational drug within 30 days prior to Visit 2
Known history of non-compliance or not able to use devices or perform spirometry

Other protocol-defined inclusion/exclusion criteria may apply

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00669617

Locations

United States, Florida
Novartis Investigative Site
Tamarac, Florida, United States, 33321
United States, Louisiana
Novartis Investigator Site
Lafayette, Louisiana, United States, 70503
United States, Missouri
Novartis Investigative Site
St Charles, Missouri, United States, 63301-2847
United States, North Carolina
Novartis Investigative site
Shelby, North Carolina, United States, 28150
United States, Pennsylvania
Novartis Investigative Site
Beaver, Pennsylvania, United States, 15009
Belgium
Novartis Investigative Site
Antwerpen, Belgium
Germany
Novartis Investigative Site
Berlin, Germany
Novartis Investigator Site
Borstel, Germany
Novartis Investigative site
Dortmund, Germany
Novartis Investigative site
Hamburg, Germany
Novartis Investigative site
Hannover, Germany
Novartis Investigative site
Mainz, Germany
Novartis Investigator Site
Potsdam, Germany
Novartis Investigative site
Wiesbaden, Germany
Hungary
Novartis Investigative site
Debrecen, Hungary
Novartis Investigative site
Deszk, Hungary
Novartis Investigative Site
Nyiregyhaza, Hungary

Sponsors and Collaborators

Novartis

More Information

No publications provided

Responsible Party:	External Affairs, Novartis
ClinicalTrials.gov Identifier:	NCT00669617 History of Changes
Other Study ID Numbers:	CQAB149B2307, EUDRACT: 2007-006189-14
Study First Received:	April 28, 2008
Results First Received:	July 22, 2011
Last Updated:	September 7, 2011
Health Authority:	Germany: Federal Institute for Drugs and Medical Devices; Hungary: National Institute of Pharmacy; United States: Food and Drug Administration

Keywords provided by Novartis:

chronic obstructive pulmonary disease
COPD
indacaterol
adults

Additional relevant MeSH terms:

Lung Diseases
Respiration Disorders
Pulmonary Disease, Chronic Obstructive
Lung Diseases, Obstructive
Respiratory Tract Diseases
Albuterol
Salmeterol
Fluticasone
Tocolytic Agents
Reproductive Control Agents
Physiological Effects of Drugs
Pharmacologic Actions
Therapeutic Uses
Adrenergic beta-2 Receptor Agonists

Adrenergic beta-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Anti-Asthmatic Agents
Respiratory System Agents
Dermatologic Agents
Anti-Allergic Agents
Anti-Inflammatory Agents

ClinicalTrials.gov processed this record on February 12, 2012