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

NCT00669617 | Completed Phase 3 Results

• 2 other identifiers: CQAB149B2307EUDRACT: 2007-006189-14
• Study Type: interventional
• Target: 89
• Locations: 4 countries
• Sites: 17

Brief Summary

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

Conditions

Chronic Obstructive Pulmonary Disease

Keywords

chronic obstructive pulmonary disease; COPD; indacaterol; adults

Outcome Measures

Primary Outcomes (1)

• Forced Expiratory Volume in 1 Second (FEV1) at 5 Minutes Post-dose

  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.

  Five Minutes Post Dose

Study Arms (5)

Ind 150μg, Salm/flut, Ind 300μg, Placebo, Salbut

EXPERIMENTAL

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; Drug: Salmeterol/fluticasone (50/500 μg); Drug: Salbutamol (200 µg); Drug: Placebo to Indacaterol; Drug: Placebo to Salmeterol/fluticasone; Drug: Placebo to salbutamol

Ind 300μg, Ind 150μg, Salbut, Salm/flut, Placebo

EXPERIMENTAL

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; Drug: Salmeterol/fluticasone (50/500 μg); Drug: Salbutamol (200 µg); Drug: Placebo to Indacaterol; Drug: Placebo to Salmeterol/fluticasone; Drug: Placebo to salbutamol

Salm/flut, Placebo, Ind 150μg, Salbut, Ind 300μg

EXPERIMENTAL

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; Drug: Salmeterol/fluticasone (50/500 μg); Drug: Salbutamol (200 µg); Drug: Placebo to Indacaterol; Drug: Placebo to Salmeterol/fluticasone; Drug: Placebo to salbutamol

Salbut, Ind 300μg, Placebo, Ind 150μg, Salm/flut

EXPERIMENTAL

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; Drug: Salmeterol/fluticasone (50/500 μg); Drug: Salbutamol (200 µg); Drug: Placebo to Indacaterol; Drug: Placebo to Salmeterol/fluticasone; Drug: Placebo to salbutamol

Placebo, Salbut, Salm/flut , Ind 300μg, Ind 150μg

EXPERIMENTAL

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; Drug: Salmeterol/fluticasone (50/500 μg); Drug: Salbutamol (200 µg); Drug: Placebo to Indacaterol; Drug: Placebo to Salmeterol/fluticasone; Drug: Placebo to salbutamol

Interventions

Indacaterol DRUG

Indacaterol 150 and 300 μg, delivered via single-dose dry-powder inhaler (SDDPI)

Also known as: Arcapta, Neohaler

Ind 150μg, Salm/flut, Ind 300μg, Placebo, Salbut; Ind 300μg, Ind 150μg, Salbut, Salm/flut, Placebo; Placebo, Salbut, Salm/flut , Ind 300μg, Ind 150μg; Salbut, Ind 300μg, Placebo, Ind 150μg, Salm/flut; Salm/flut, Placebo, Ind 150μg, Salbut, Ind 300μg

Salmeterol/fluticasone (50/500 μg) DRUG

Salmeterol/fluticasone 50/500 μg fixed-dose combination delivered via manufacturer's proprietary Multi-Dose Dry-Powder Inhaler (MDDPI).

Ind 150μg, Salm/flut, Ind 300μg, Placebo, Salbut; Ind 300μg, Ind 150μg, Salbut, Salm/flut, Placebo; Placebo, Salbut, Salm/flut , Ind 300μg, Ind 150μg; Salbut, Ind 300μg, Placebo, Ind 150μg, Salm/flut; Salm/flut, Placebo, Ind 150μg, Salbut, Ind 300μg

Salbutamol (200 µg) DRUG

Salbutamol 200 μg delivered via manufacturer's proprietary Multi-Dose Dry-Powder Inhaler (MDDPI).

Ind 150μg, Salm/flut, Ind 300μg, Placebo, Salbut; Ind 300μg, Ind 150μg, Salbut, Salm/flut, Placebo; Placebo, Salbut, Salm/flut , Ind 300μg, Ind 150μg; Salbut, Ind 300μg, Placebo, Ind 150μg, Salm/flut; Salm/flut, Placebo, Ind 150μg, Salbut, Ind 300μg

Placebo to Indacaterol DRUG

Placebo to indacaterol delivered via SDDPI

Ind 150μg, Salm/flut, Ind 300μg, Placebo, Salbut; Ind 300μg, Ind 150μg, Salbut, Salm/flut, Placebo; Placebo, Salbut, Salm/flut , Ind 300μg, Ind 150μg; Salbut, Ind 300μg, Placebo, Ind 150μg, Salm/flut; Salm/flut, Placebo, Ind 150μg, Salbut, Ind 300μg

Placebo to Salmeterol/fluticasone DRUG

Placebo to salmeterol/fluticasone delivered via MDDPI

Ind 150μg, Salm/flut, Ind 300μg, Placebo, Salbut; Ind 300μg, Ind 150μg, Salbut, Salm/flut, Placebo; Placebo, Salbut, Salm/flut , Ind 300μg, Ind 150μg; Salbut, Ind 300μg, Placebo, Ind 150μg, Salm/flut; Salm/flut, Placebo, Ind 150μg, Salbut, Ind 300μg

Placebo to salbutamol DRUG

Placebo to salbutamol delivered via MDDPI

Ind 150μg, Salm/flut, Ind 300μg, Placebo, Salbut; Ind 300μg, Ind 150μg, Salbut, Salm/flut, Placebo; Placebo, Salbut, Salm/flut , Ind 300μg, Ind 150μg; Salbut, Ind 300μg, Placebo, Ind 150μg, Salm/flut; Salm/flut, Placebo, Ind 150μg, Salbut, Ind 300μg

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Novartis: lead

Study Sites (17)

Novartis Investigative Site

Tamarac, Florida, 33321, United States

Location

Novartis Investigator Site

Lafayette, Louisiana, 70503, United States

Location

Novartis Investigative Site

Saint Charles, Missouri, 63301-2847, United States

Location

Novartis Investigative site

Shelby, North Carolina, 28150, United States

Location

Novartis Investigative Site

Beaver, Pennsylvania, 15009, United States

Location

Novartis Investigative Site

Antwerp, Belgium

Location

Novartis Investigative Site

Berlin, Germany

Location

Novartis Investigator Site

Borstel, Germany

Location

Novartis Investigative site

Dortmund, Germany

Location

Novartis Investigative site

Hamburg, Germany

Location

Novartis Investigative site

Hanover, Germany

Location

Novartis Investigative site

Mainz, Germany

Location

Novartis Investigator Site

Potsdam, Germany

Location

Novartis Investigative site

Wiesbaden, Germany

Location

Novartis Investigative site

Debrecen, Hungary

Location

Novartis Investigative site

Deszk, Hungary

Location

Novartis Investigative Site

Nyíregyháza, Hungary

Location

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Interventions

indacaterol; Salmeterol Xinafoate; Fluticasone; Albuterol

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines; Phenethylamines; Ethylamines; Androstadienes; Androstenes; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

862-778-8300

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: April 28, 2008
• First Posted: April 30, 2008
• Study Start: April 1, 2008
• Primary Completion: August 1, 2008
• Study Completion: August 1, 2008
• Last Updated: September 12, 2011
• Results First Posted: August 17, 2011

Record last verified: 2011-09

Locations

DE (8); BE (1); US (5); HU (3)