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

NCT00615459 | Completed Phase 3 Results

• 1 other identifier: CQAB149B2331
• Study Type: interventional
• Target: 169
• Locations: 7 countries
• Sites: 20

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.

Conditions

Chronic Obstructive Pulmonary Disease (COPD)

Keywords

Chronic obstructive pulmonary disease, indacaterol, tiotropium, placebo controlled

Outcome Measures

Primary Outcomes (1)

• 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.

  23 hours 10 minutes and 23 hours 45 minutes post-dose on Day 15 of each treatment period

Secondary Outcomes (1)

• Peak FEV1 During 4 Hours Post Morning Dose on Day 1

  Day 1 (from 0 to 4 hours post morning dose)

Study Arms (4)

Sequence 1: Placebo,Tiotropium, Indacaterol 150 μg

EXPERIMENTAL

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; Drug: Tiotropium; Drug: Placebo

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

EXPERIMENTAL

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; Drug: Tiotropium

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

EXPERIMENTAL

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; Drug: Placebo

Sequence 4: Tiotropium, Placebo, Indacaterol 300 μg

EXPERIMENTAL

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; Drug: Tiotropium; Drug: Placebo

Interventions

Indacaterol DRUG

Indacaterol 150 μg or 300 μg, delivered via SDDPI

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

Tiotropium DRUG

Tiotropium 18 μg once daily delivered via inhalation device

Sequence 1: Placebo,Tiotropium, Indacaterol 150 μg; Sequence 2: Indacaterol 300 μg, Indacaterol 150 μg, Tiotropium; Sequence 4: Tiotropium, Placebo, Indacaterol 300 μg

Placebo DRUG

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®)

Sequence 1: Placebo,Tiotropium, Indacaterol 150 μg; Sequence 3: Indacaterol 150 μg, Indacaterol 300 μg, Placebo; Sequence 4: Tiotropium, Placebo, Indacaterol 300 μg

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
• 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%

You may not qualify if:

• 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

Sponsors & Collaborators

• Novartis: lead

Study Sites (20)

Novartis Investigative site

Camperdown, Australia

Location

Novartis Investigator Site

Gauting, Germany

Location

Novartis Investigator Site

Großhansdorf, Germany

Location

Novartis Investigator Site

Mainz, Germany

Location

Novartis Investigator site

Marburg, Germany

Location

Novartis Investigator Site

Wiesbaden, Germany

Location

Novartis Investigator Site

Almelo, Netherlands

Location

Novartis Investigator Site

Breda, Netherlands

Location

Novartis Investigator Site

Eindhoven, Netherlands

Location

Novartis Investigator Site

Harderwijk, Netherlands

Location

Novartis Investigator Site

Helmond, Netherlands

Location

Novartis Investigator Site

Wellington, New Zealand

Location

Novartis Investigator Site

Katowice, Poland

Location

Novartis Investigator Site

Warsaw, Poland

Location

Novartis Investigator Site

Durban, South Africa

Location

Novartis Investigator Site

A Coruña, Spain

Location

Novartis Investigative site

Alicante, Spain

Location

Novartis Investigative Site

Cacenes, Spain

Location

Novartis Investigative Site

Madrid, Spain

Location

Novartis Investigator Site

Ourense, Spain

Location

Related Publications (1)

• 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.

  PMID: 20920365 DERIVED

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Interventions

indacaterol; Tiotropium Bromide

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)

Scopolamine Derivatives; Tropanes; Azabicyclo Compounds; Aza Compounds; Organic Chemicals; Alkaloids; Heterocyclic Compounds; Bridged Bicyclo Compounds, Heterocyclic; Heterocyclic Compounds, Bridged-Ring

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

862-778-8300

Study Officials

• Novartis Pharma

  Novartis Pharmaceuticals

  STUDY CHAIR

Publication Agreements

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

Study Design

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

Study Record Dates

• First Submitted: February 1, 2008
• First Posted: February 14, 2008
• Study Start: February 1, 2008
• Primary Completion: December 1, 2008
• Study Completion: December 1, 2008
• Last Updated: August 17, 2011
• Results First Posted: August 17, 2011

Record last verified: 2011-07

Locations

ES (5); ZA (1); DE (5); NL (5); NZ (1); AU (1); PL (2)