A Crossover Study to Determine the Effect on Lung Function of Indacaterol in Patients With Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD), Using Tiotropium as an Active Control

This study has been completed.
Sponsor:
Information provided by:
Novartis
ClinicalTrials.gov Identifier:
NCT00615459
First received: February 1, 2008
Last updated: July 22, 2011
Last verified: July 2011
  Purpose

The study compared the 24-hour spirometry profile of indacaterol with that of placebo and with tiotropium as an active control in patients with chronic obstructive pulmonary disease.


Condition Intervention Phase
Chronic Obstructive Pulmonary Disease (COPD)
Drug: Indacaterol
Drug: Tiotropium
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Phase III, Randomized, Double-blind, Double-dummy, Placebo-controlled, Multicenter, 3-period Incomplete Block, Multidose Crossover Study to Determine the Effect on Lung Function of Indacaterol (150 and 300 μg o.d.) in Patients With Moderate to Severe COPD, Using Tiotropium (18 μg o.d.) as an Active Control

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • 24-hour Post-dose Trough Forced Expiratory Volume in 1 Second (FEV1) After 14 Days of Treatment [ Time Frame: 23 hours 10 minutes and 23 hours 45 minutes post-dose on Day 15 of each treatment period ] [ Designated as safety issue: No ]
    FEV1 was measured with spirometry conducted according to internationally accepted standards. Trough FEV1 was defined as the mean of FEV1 measurements at 23 h 10 min and 23 h 45 min post Day 14 dose measured on the morning of Day 15 in each treatment period. The model used for analysis contained the (period) baseline FEV1 as covariate. The (period) baseline FEV1 was defined as the value measured before the study drug administration in that treatment period.


Secondary Outcome Measures:
  • Peak FEV1 During 4 Hours Post Morning Dose on Day 1 [ Time Frame: Day 1 (from 0 to 4 hours post morning dose) ] [ Designated as safety issue: No ]
    FEV1 was measured with spirometry conducted according to internationally accepted standards. The peak effect on Day 1 was defined as the maximum FEV1 during the first 4 hour on that day. FEV1 measurements taken within 6 hour of rescue use were set to missing before the peak FEV1 (0-4 hour) was calculated. The model used for analysis contained the (period) baseline FEV1 as covariate. The (period) baseline FEV1 was defined as the value measured before the study drug administration in that treatment period.


Enrollment: 169
Study Start Date: February 2008
Study Completion Date: December 2008
Primary Completion Date: December 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Sequence 1: Placebo,Tiotropium, Indacaterol 150 μg
In period I, placebo to indacaterol (150 or 300 μg) delivered via SDDPI. The placebo for blinding tiotropium was delivered via the tiotropium inhalation device. In period II, tiotropium (18 μg) once daily delivered via inhalation device and matching placebo to indacaterol delivered once daily via single dose dry powder inhaler (SDDPI). In period III, indacaterol 150 μg once daily delivered via SDDPI and placebo to tiotropium was delivered once daily via the tiotropium inhalation device. Daily inhaled corticosteroid (ICS) monotherapy (where applicable) was provided to remain stable throughout study. The Short acting (beta) β2-agonist (SABA) was available for rescue use throughout the study.
Drug: Indacaterol
Indacaterol 150 μg or 300 μg, delivered via SDDPI
Drug: Tiotropium
Tiotropium 18 μg once daily delivered via inhalation device
Drug: Placebo
Placebo to indacaterol (150 or 300 μg) delivered via SDDPI. The placebo for blinding tiotropium was delivered via the tiotropium manufacturer's proprietary inhalation device (HandiHaler®)
Experimental: Sequence 2: Indacaterol 300 μg, Indacaterol 150 μg, Tiotropium
In period I,indacaterol 300 μg once daily delivered via single dose dry powder inhaler (SDDPI)and matching placebo to tiotropium delivered once daily via tiotropium inhalation device. In period II, indacaterol 150 μg once daily delivered via SDDPI and matching placebo to tiotropium delivered once daily via tiotropium inhalation device. In period III, tiotropium (18 μg) once daily delivered via inhalation device and matching placebo to indacaterol delivered once daily via SDDPI. Daily ICS monotherapy (where applicable) was provided to remain stable throughout study. The SABA was available for rescue use throughout the study.
Drug: Indacaterol
Indacaterol 150 μg or 300 μg, delivered via SDDPI
Drug: Tiotropium
Tiotropium 18 μg once daily delivered via inhalation device
Experimental: Sequence 3: Indacaterol 150 μg, Indacaterol 300 μg, Placebo
In period I, indacaterol 150 μg once daily delivered via SDDPI and matching placebo to tiotropium delivered once daily via tiotropium inhalation device. In period II, indacaterol 300 μg once daily delivered via SDDPI and matching placebo to tiotropium delivered once daily via tiotropium inhalation device. In period III, placebo to indacaterol (150 or 300 μg) delivered via SDDPI. The placebo for blinding tiotropium was delivered via the tiotropium inhalation device. Daily ICS monotherapy (where applicable) was provided to remain stable throughout study. The SABA was available for rescue use throughout the study.
Drug: Indacaterol
Indacaterol 150 μg or 300 μg, delivered via SDDPI
Drug: Placebo
Placebo to indacaterol (150 or 300 μg) delivered via SDDPI. The placebo for blinding tiotropium was delivered via the tiotropium manufacturer's proprietary inhalation device (HandiHaler®)
Experimental: Sequence 4: Tiotropium, Placebo, Indacaterol 300 μg
In period I, tiotropium (18 μg) once daily delivered via inhalation device and matching placebo to indacaterol delivered once daily via SDDPI. In period II, placebo to indacaterol (150 or 300 μg) delivered via SDDPI. The placebo for blinding tiotropium was delivered via the tiotropium inhalation device. In period III, indacaterol 300 μg once daily delivered via SDDPI and matching placebo to tiotropium delivered once daily via tiotropium inhalation device. Daily ICS monotherapy (where applicable) was provided to remain stable throughout study. The SABA was available for rescue use throughout the study.
Drug: Indacaterol
Indacaterol 150 μg or 300 μg, delivered via SDDPI
Drug: Tiotropium
Tiotropium 18 μg once daily delivered via inhalation device
Drug: Placebo
Placebo to indacaterol (150 or 300 μg) delivered via SDDPI. The placebo for blinding tiotropium was delivered via the tiotropium manufacturer's proprietary inhalation device (HandiHaler®)

  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 out patients with a diagnosis of chronic obstructive pulmonary disease (COPD) (moderate to severe as classified by the Global initiative for chronic obstructive lung disease (GOLD) Guidelines, 2006) and:

    1. Smoking history of at least 10 pack years (current or previous smokers)
    2. Post-bronchodilator forced expiratory volume in 1 second (FEV1) < 80% and ≥30% of the predicted normal value.
    3. Post-bronchodilator FEV1/Forced vital capacity (FVC) < 70%

Exclusion Criteria:

  • 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 for chronic hypoxemia
  • Patients who have had a respiratory tract infection within 6 weeks prior to Visit
  • Patients with concomitant pulmonary disease
  • Patients with a history of asthma
  • Patients with diabetes Type I or uncontrolled diabetes Type II
  • Any patient with lung cancer or a history of lung cancer
  • 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 (Bazett's) measured at Visit 1 or randomization is prolonged
  • Patients who have been vaccinated with live attenuated vaccines within 30 days prior to screening or during the run-in period.
  • Patients unable to successfully use a dry powder inhaler device, MDI or perform spirometry measurements

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: NCT00615459

Locations
Australia
Novartis Investigative site
Camperdown, Australia
Germany
Novartis Investigator Site
Gauting, Germany
Novartis Investigator Site
Grosshansdorf, Germany
Novartis Investigator Site
Mainz, Germany
Novartis Investigator site
Marburg, Germany
Novartis Investigator Site
Wiesbaden, Germany
Netherlands
Novartis Investigator Site
Almelo, Netherlands
Novartis Investigator Site
Breda, Netherlands
Novartis Investigator Site
Eindhoven, Netherlands
Novartis Investigator Site
Harderwijk, Netherlands
Novartis Investigator Site
Helmond, Netherlands
New Zealand
Novartis Investigator Site
Wellington, New Zealand
Poland
Novartis Investigator Site
Katowice, Poland
Novartis Investigator Site
Warsaw, Poland
South Africa
Novartis Investigator Site
Durban, South Africa
Spain
Novartis Investigative site
Alicante, Spain
Novartis Investigative Site
Cacenes, Spain
Novartis Investigator Site
La Coruna, Spain
Novartis Investigative Site
Madrid, Spain
Novartis Investigator Site
Orense, Spain
Sponsors and Collaborators
Novartis
Investigators
Study Chair: Novartis Pharma 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: NCT00615459     History of Changes
Other Study ID Numbers: CQAB149B2331
Study First Received: February 1, 2008
Results First Received: July 22, 2011
Last Updated: July 22, 2011
Health Authority: Australia: National Health and Medical Research Council
Germany: Federal Institute for Drugs and Medical Devices
Netherlands: Medicines Evaluation Board (MEB)
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
South Africa: Department of Health
Spain: Spanish Agency of Medicines

Keywords provided by Novartis:
Chronic obstructive pulmonary disease, indacaterol, tiotropium, placebo controlled

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

ClinicalTrials.gov processed this record on July 24, 2014