search
Back to results

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

Primary Purpose

Chronic Obstructive Pulmonary Disease (COPD)

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Indacaterol
Tiotropium
Placebo
Sponsored by
Novartis
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Chronic Obstructive Pulmonary Disease (COPD) focused on measuring Chronic obstructive pulmonary disease, indacaterol, tiotropium, placebo controlled

Eligibility Criteria

40 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Novartis Investigative site
  • Novartis Investigator Site
  • Novartis Investigator Site
  • Novartis Investigator Site
  • Novartis Investigator site
  • Novartis Investigator Site
  • Novartis Investigator Site
  • Novartis Investigator Site
  • Novartis Investigator Site
  • Novartis Investigator Site
  • Novartis Investigator Site
  • Novartis Investigator Site
  • Novartis Investigator Site
  • Novartis Investigator Site
  • Novartis Investigator Site
  • Novartis Investigative site
  • Novartis Investigative Site
  • Novartis Investigator Site
  • Novartis Investigative Site
  • Novartis Investigator Site

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Experimental

Arm Label

Sequence 1: Placebo,Tiotropium, Indacaterol 150 μg

Sequence 2: Indacaterol 300 μg, Indacaterol 150 μg, Tiotropium

Sequence 3: Indacaterol 150 μg, Indacaterol 300 μg, Placebo

Sequence 4: Tiotropium, Placebo, Indacaterol 300 μg

Arm Description

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.

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.

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.

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.

Outcomes

Primary Outcome Measures

24-hour Post-dose Trough Forced Expiratory Volume in 1 Second (FEV1) After 14 Days of Treatment
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
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.

Full Information

First Posted
February 1, 2008
Last Updated
July 22, 2011
Sponsor
Novartis
search

1. Study Identification

Unique Protocol Identification Number
NCT00615459
Brief Title
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
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
Study Type
Interventional

2. Study Status

Record Verification Date
July 2011
Overall Recruitment Status
Completed
Study Start Date
February 2008 (undefined)
Primary Completion Date
December 2008 (Actual)
Study Completion Date
December 2008 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
Novartis

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Obstructive Pulmonary Disease (COPD)
Keywords
Chronic obstructive pulmonary disease, indacaterol, tiotropium, placebo controlled

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Crossover Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
169 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Sequence 1: Placebo,Tiotropium, Indacaterol 150 μg
Arm Type
Experimental
Arm Description
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.
Arm Title
Sequence 2: Indacaterol 300 μg, Indacaterol 150 μg, Tiotropium
Arm Type
Experimental
Arm Description
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.
Arm Title
Sequence 3: Indacaterol 150 μg, Indacaterol 300 μg, Placebo
Arm Type
Experimental
Arm Description
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.
Arm Title
Sequence 4: Tiotropium, Placebo, Indacaterol 300 μg
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Indacaterol
Intervention Description
Indacaterol 150 μg or 300 μg, delivered via SDDPI
Intervention Type
Drug
Intervention Name(s)
Tiotropium
Intervention Description
Tiotropium 18 μg once daily delivered via inhalation device
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
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®)
Primary Outcome Measure Information:
Title
24-hour Post-dose Trough Forced Expiratory Volume in 1 Second (FEV1) After 14 Days of Treatment
Description
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.
Time Frame
23 hours 10 minutes and 23 hours 45 minutes post-dose on Day 15 of each treatment period
Secondary Outcome Measure Information:
Title
Peak FEV1 During 4 Hours Post Morning Dose on Day 1
Description
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.
Time Frame
Day 1 (from 0 to 4 hours post morning dose)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
40 Years
Accepts Healthy Volunteers
No
Eligibility 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: Smoking history of at least 10 pack years (current or previous smokers) 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% 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharma
Organizational Affiliation
Novartis Pharmaceuticals
Official's Role
Study Chair
Facility Information:
Facility Name
Novartis Investigative site
City
Camperdown
Country
Australia
Facility Name
Novartis Investigator Site
City
Gauting
Country
Germany
Facility Name
Novartis Investigator Site
City
Grosshansdorf
Country
Germany
Facility Name
Novartis Investigator Site
City
Mainz
Country
Germany
Facility Name
Novartis Investigator site
City
Marburg
Country
Germany
Facility Name
Novartis Investigator Site
City
Wiesbaden
Country
Germany
Facility Name
Novartis Investigator Site
City
Almelo
Country
Netherlands
Facility Name
Novartis Investigator Site
City
Breda
Country
Netherlands
Facility Name
Novartis Investigator Site
City
Eindhoven
Country
Netherlands
Facility Name
Novartis Investigator Site
City
Harderwijk
Country
Netherlands
Facility Name
Novartis Investigator Site
City
Helmond
Country
Netherlands
Facility Name
Novartis Investigator Site
City
Wellington
Country
New Zealand
Facility Name
Novartis Investigator Site
City
Katowice
Country
Poland
Facility Name
Novartis Investigator Site
City
Warsaw
Country
Poland
Facility Name
Novartis Investigator Site
City
Durban
Country
South Africa
Facility Name
Novartis Investigative site
City
Alicante
Country
Spain
Facility Name
Novartis Investigative Site
City
Cacenes
Country
Spain
Facility Name
Novartis Investigator Site
City
La Coruna
Country
Spain
Facility Name
Novartis Investigative Site
City
Madrid
Country
Spain
Facility Name
Novartis Investigator Site
City
Orense
Country
Spain

12. IPD Sharing Statement

Citations:
PubMed Identifier
20920365
Citation
Vogelmeier C, Ramos-Barbon D, Jack D, Piggott S, Owen R, Higgins M, Kramer B; INTIME study investigators (INdacaterol & TIotropium: Measuring Efficacy). Indacaterol provides 24-hour bronchodilation in COPD: a placebo-controlled blinded comparison with tiotropium. Respir Res. 2010 Oct 5;11(1):135. doi: 10.1186/1465-9921-11-135.
Results Reference
derived

Learn more about this trial

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

We'll reach out to this number within 24 hrs