26 Week Efficacy, Safety and Tolerability Study of Indacaterol in Patients With Chronic Obstructive Pulmonary Disease (COPD)

This study has been completed.
Sponsor:
Information provided by:
Novartis
ClinicalTrials.gov Identifier:
NCT00463567
First received: April 19, 2007
Last updated: July 22, 2011
Last verified: July 2011
  Purpose

Stage 1 of the study is designed to provide data about the risk-benefit of 4 dose regimens of indacaterol (75, 150, 300 & 600 µg o.d.) in order to select two doses to carry forward into study Stage 2. Study Stage 2 will provide pivotal confirmation of efficacy, safety, and tolerability of the selected indacaterol doses in patients with COPD


Condition Intervention Phase
Pulmonary Disease, Chronic Obstructive
COPD
Lung Diseases, Obstructive
Drug: Indacaterol
Drug: Formoterol (12 µg b.i.d.)
Drug: Tiotropium (18 µg o.d.)
Drug: Placebo to Indacaterol
Drug: Placebo to Formoterol
Phase 2
Phase 3

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 26-week Treatment, Multicenter, Randomized, Double Blind, Double Dummy, Placebo-controlled, Adaptive, Seamless, Parallel-group Study to Assess the Efficacy, Safety and Tolerability of Two Doses of Indacaterol (Selected From 75, 150, 300 & 600 µg o.d.) in Patients With Chronic Obstructive Pulmonary Disease Using Blinded Formoterol (12 µg b.i.d.) and Open Label Tiotropium (18 µg o.d.) as Active Controls

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Trough Forced Expiratory Volume in 1 Second (FEV1) Assessed by Spirometry 24 Hour Post Dose After 12 Weeks of Treatment [ Time Frame: after 12 weeks of treatment ] [ Designated as safety issue: No ]
    FEV1 was measured with spirometry conducted according to internationally accepted standards. Trough FEV1 was defined as the average of the 23 h 10 min and the 23 h 45 min post dose values. Mixed model used baseline FEV1, FEV1 prior to and 30 minutes post inhalation of salbutamol/albuterol, and FEV1 prior to and 1 hour post inhalation of ipratropium as covariates.


Secondary Outcome Measures:
  • The Percentage of "Days of Poor Control" Reported Over the 26 Week Treatment Period [ Time Frame: up to 26 weeks ] [ Designated as safety issue: No ]
    A Chronic Obstructive Pulmonary Disease (COPD) "day of poor control" was defined as any day in the participant's diary with a score ≥2 (moderate or severe) for at least 2 of 5 symptoms (cough, wheeze, production of sputum, color of sputum, breathlessness). Score for each symptom ranges from 0-3; a higher number indicates a more severe symptom. The model contained baseline percentage of "days of poor control" as well as FEV1 reversibility components as covariates.


Enrollment: 2059
Study Start Date: April 2007
Study Completion Date: August 2008
Primary Completion Date: August 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Indacaterol 150 µg (Continued Into Stage 2)

In the morning, Indacaterol 150 µg once daily orally inhaled via a single dose dry powder inhaler (SDDPI) + Placebo to Indacaterol delivered via SDDPI + Placebo to Formoterol delivered via Aerolizer. In the evening, Placebo to Formoterol delivered via Aerolizer. Participated in the 2 week Stage 1 and continued treatment up to 26 weeks in Stage 2. Placebo to Formoterol inhalation in the morning and in the evening was discontinued after Stage 1.

Daily Inhaled Corticosteroid (ICS) monotherapy (if applicable) was to remain stable and Salbutamol/albuterol was available for rescue use throughout study.

Drug: Indacaterol
In the morning, Indacaterol once daily (o.d.) orally inhaled via a single dose dry powder inhaler (SDDPI).
Drug: Placebo to Indacaterol
In the morning, Placebo to Indacaterol once daily (o.d.) orally inhaled via a single dose dry powder inhaler (SDDPI).
Drug: Placebo to Formoterol
In the morning and in the evening, placebo to formoterol delivered via Aerolizer.
Experimental: Indacaterol 300 µg (Continued Into Stage 2)

In the morning, Indacaterol 300 µg once daily orally inhaled via a SDDPI + Placebo to Indacaterol delivered via SDDPI + Placebo to Formoterol delivered via Aerolizer. In evening, Placebo to Formoterol delivered via Aerolizer. Participated in the 2 week Stage 1 and continued treatment up to 26 weeks in Stage 2. Placebo to Formoterol inhalation in the morning and in the evening was discontinued after Stage 1.

Daily ICS monotherapy (if applicable) was to remain stable and Salbutamol/albuterol was available for rescue use throughout study.

Drug: Indacaterol
In the morning, Indacaterol once daily (o.d.) orally inhaled via a single dose dry powder inhaler (SDDPI).
Drug: Placebo to Indacaterol
In the morning, Placebo to Indacaterol once daily (o.d.) orally inhaled via a single dose dry powder inhaler (SDDPI).
Drug: Placebo to Formoterol
In the morning and in the evening, placebo to formoterol delivered via Aerolizer.
Active Comparator: Tiotropium 18 µg (Continued Into Stage 2)

Tiotropium 18 µg dry powder capsules delivered (open label) via manufacturer's proprietary SDDPI, (Handihaler®). Participated in the 2 week Stage 1 and continued treatment up to 26 weeks in Stage 2.

Daily ICS monotherapy (if applicable) was to remain stable and Salbutamol/albuterol was available for rescue use throughout study.

Drug: Tiotropium (18 µg o.d.)
Tiotropium 18 µg once daily (o.d.) dry powder capsules delivered via a SDDPI.
Placebo Comparator: Placebo (Continued Into Stage 2)

In the morning, Placebo to Indacaterol delivered via two SDDPI devices + Placebo to Formoterol delivered via Aerolizer. In the evening, Placebo to Formoterol delivered via Aerolizer. Participated in the 2 week Stage 1 and continued treatment up to 26 weeks in Stage 2. Placebo to Formoterol inhalation in the morning and in the evening was discontinued after Stage 1.

Daily ICS monotherapy (if applicable) was to remain stable and Salbutamol/albuterol was available for rescue use throughout study.

Drug: Placebo to Indacaterol
In the morning, Placebo to Indacaterol once daily (o.d.) orally inhaled via a single dose dry powder inhaler (SDDPI).
Drug: Placebo to Formoterol
In the morning and in the evening, placebo to formoterol delivered via Aerolizer.
Experimental: Indacaterol 75 µg (Not Continued into Stage 2)

In the morning, Indacaterol 75 µg once daily orally inhaled via a SDDPI + Placebo to Indacaterol delivered via SDDPI + Placebo to Formoterol delivered via Aerolizer. In the evening, Placebo to Formoterol delivered via Aerolizer. Participated in the 2 week Stage 1 but did not continue to Stage 2.

Daily ICS monotherapy (if applicable) was to remain stable and Salbutamol/albuterol was available for rescue use throughout study.

Drug: Indacaterol
In the morning, Indacaterol once daily (o.d.) orally inhaled via a single dose dry powder inhaler (SDDPI).
Drug: Placebo to Indacaterol
In the morning, Placebo to Indacaterol once daily (o.d.) orally inhaled via a single dose dry powder inhaler (SDDPI).
Drug: Placebo to Formoterol
In the morning and in the evening, placebo to formoterol delivered via Aerolizer.
Experimental: Indacaterol 600 µg (Not Continued Into Stage 2)

In the morning, 2 capsules of Indacaterol 300 µg once daily orally inhaled via two SDDPI devices + Placebo to Formoterol delivered via Aerolizer. In the evening, Placebo to Formoterol delivered via Aerolizer. Participated in the 2 week Stage 1 but did not continue to Stage 2.

Daily ICS monotherapy (if applicable) was to remain stable and Salbutamol/albuterol was available for rescue use throughout study.

Drug: Indacaterol
In the morning, Indacaterol once daily (o.d.) orally inhaled via a single dose dry powder inhaler (SDDPI).
Drug: Placebo to Formoterol
In the morning and in the evening, placebo to formoterol delivered via Aerolizer.
Active Comparator: Formoterol 12 µg (Not Continued Into Stage 2)

In the morning, Placebo to Indacaterol delivered via two SDDPI devices + Formoterol 12 µg delivered via Aerolizer. In evening, Formoterol 12 µg delivered via Aerolizer. Participated in the 2 week Stage 1 but did not continue to Stage 2.

Daily ICS monotherapy (if applicable) was to remain stable and Salbutamol/albuterol was available for rescue use throughout study.

Drug: Formoterol (12 µg b.i.d.)
Formoterol 12 µg twice daily (b.i.d.) in the morning and in the evening via an aerolizer.
Drug: Placebo to Indacaterol
In the morning, Placebo to Indacaterol once daily (o.d.) orally inhaled via a single dose dry powder inhaler (SDDPI).

  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
  • Co-operative outpatients with a diagnosis of COPD (moderate to severe as classified by the Global Initiative for Chronic Obstructive Pulmonary Disease (GOLD) Guidelines, 2005) and:

    • Smoking history of at least 20 pack years
    • Post-bronchodilator FEV1 < 80% and ≥ 30% of the predicted normal value.
    • Post-bronchodilator FEV1/FVC < 70% (Post refers to within 30 min of inhalation of 400 µg of salbutamol)

Exclusion Criteria:

  • Pregnant or lactating females
  • Patients who have been hospitalized for a COPD exacerbation in the 6 weeks prior to Visit 1 or during the run-in period
  • Patients requiring long term oxygen therapy (> 15 h a day)
  • Patients who have had a respiratory tract infection 6 weeks prior to V1 (with further criteria)
  • Patients with concomitant pulmonary disease, pulmonary tuberculosis, or clinically significant bronchiectasis
  • Patients with a history of asthma (with further criteria)
  • Patients with Type I or uncontrolled Type II diabetes
  • Patients with contraindications for tiotropium
  • Patients who have clinically relevant laboratory abnormalities or a clinically significant abnormality
  • Any patient with active cancer or a history of cancer with less than 5 years disease free survival time
  • Patients with a history of long QT syndrome or whose QTc interval is prolonged
  • Patients with a hypersensitivity to any of the study drugs or drugs with similar chemical structures
  • Patients who have had treatment with the investigational drug (with further criteria)
  • Patients who have had live attenuated vaccinations within 30 days prior to visit 1, or during run-in period
  • Patients with known history of non compliance to medication
  • Patients unable to satisfactorily use a dry powder inhaler device or perform spirometry measurements

Other protocol-defined inclusion/exclusion criteria may apply

  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00463567

  Show 345 Study Locations
Sponsors and Collaborators
Novartis
Investigators
Study Chair: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided by Novartis

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: external affairs, Novartis
ClinicalTrials.gov Identifier: NCT00463567     History of Changes
Other Study ID Numbers: CQAB149B2335S
Study First Received: April 19, 2007
Results First Received: July 22, 2011
Last Updated: July 22, 2011
Health Authority: Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica
Germany: Federal Institute for Drugs and Medical Devices
Spain: Spanish Agency of Medicines
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Canada: Health Canada
Italy: Direzione Generale di Sanità Veterinaria e degli Alimenti
Korea: Food and Drug Administration
United States: Food and Drug Administration
Taiwan: Department of Health
India: Institutional Review Board
Sweden: Medical Products Agency
Turkey: Ministry of Health
Venezuela: Intituto Nacional de Higiene Rafael Rangel

Keywords provided by Novartis:
indacaterol
long acting beta-2 agonist

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

ClinicalTrials.gov processed this record on April 22, 2014