Efficacy and Safety Comparison of Steroid or Placebo in Combination With Salmeterol and Tiotropium in COPD

A Randomised, Phase II, Double-Blind, Double-Dummy, Four-period Crossover Efficacy and Safety Comparison of 4-Week Treatment Periods of Blinded Fluticasone (500 mcg Bid, MDI), Ciclesonide (400 mcg qd, MDI), Ciclesonide (800 mcg qd, MDI) or Placebo in Free Combination With Open-Label Tiotropium (18 mcg qd, HandiHaler) and Salmeterol (50 mcg Bid, Diskus) in Patients With COPD.

This efficacy and safety study compares four different combinations of blinded inhaled steroid treatments on top of open-label tiotropium and salmeterol in patients with chronic obstructive pulmonary disease (COPD). The primary objective is the effect on lung function parameters.

Study Overview

• Status: Completed
• Conditions: Pulmonary Disease, Chronic Obstructive
• Intervention / Treatment: Drug: Tiotropium; Drug: Salmeterol; Drug: Fluticasone; Drug: Ciclesonide low; Drug: Ciclesonide high; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 103
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Genk, Belgium
    • 1249.1.32003 Boehringer Ingelheim Investigational Site
  • Gent, Belgium
    • 1249.1.32001 Boehringer Ingelheim Investigational Site
  • Hasselt, Belgium
    • 1249.1.32002 Boehringer Ingelheim Investigational Site
  • Oostende, Belgium
    • 1249.1.32004 Boehringer Ingelheim Investigational Site
• Denmark
  • Aarhus C, Denmark
    • 1249.1.45001 Boehringer Ingelheim Investigational Site
• Germany
  • Großhansdorf, Germany
    • 1249.1.49001 Boehringer Ingelheim Investigational Site
  • Mannheim, Germany
    • 1249.1.49002 Boehringer Ingelheim Investigational Site
  • Weinheim, Germany
    • 1249.1.49003 Boehringer Ingelheim Investigational Site
• Netherlands
  • Eindhoven, Netherlands
    • 1249.1.31002 Boehringer Ingelheim Investigational Site
  • Harderwijk, Netherlands
    • 1249.1.31003 Boehringer Ingelheim Investigational Site
  • Heerlen, Netherlands
    • 1249.1.31001 Boehringer Ingelheim Investigational Site
  • Veldhoven, Netherlands
    • 1249.1.31004 Boehringer Ingelheim Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Relatively stable, moderate to severe COPD
• Male or female patients 40 years of age or older.
• Current or ex-smokers with a smoking history of more than 10 pack years

Exclusion Criteria:

• Other significant disease that can influence the study results or be a safety risk for the patient
• Other medication that can influence the study results
• Hypersensitivity to the study medication
• Patients with unstable COPD

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Tiotropium; Oral inhalation by HandiHaler® device; Drug: Salmeterol; Oral inhalation from Diskus®; Drug: Placebo; Oral inhalation from MDI
Experimental: Tiotropium+salmeterol+fluticasone	Drug: Tiotropium; Oral inhalation by HandiHaler® device; Drug: Salmeterol; Oral inhalation from Diskus®; Drug: Fluticasone; Oral inhalation from metered dose inhaler (MDI)
Experimental: Tiotropium+salmeterol+ciclesonide low	Drug: Tiotropium; Oral inhalation by HandiHaler® device; Drug: Salmeterol; Oral inhalation from Diskus®; Drug: Ciclesonide low; Oral inhalation from MDI
Experimental: Tiotropium+salmeterol+ciclesonide high	Drug: Tiotropium; Oral inhalation by HandiHaler® device; Drug: Salmeterol; Oral inhalation from Diskus®; Drug: Ciclesonide high; Oral inhalation from MDI

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Trough FEV1 response at the end of each 4 week period of randomised treatment	4 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Trough forced vital capacity (FVC) response after 4 weeks of each blinded treatment	after 4 weeks of each blinded treatment
All adverse events	24 weeks
Pulse rate and blood pressure (seated)	24 weeks
FEV1 and FVC morning peak response	day 1 and day 28 of each blinded treatment
FEV1 and FVC evening peak response	day 1 and day 28 of each blinded treatment
FEV1 AUC (0-3h), after 4 weeks of each blinded treatment	after 4 weeks of each blinded treatment
FEV1 AUC (12-15h) after 4 weeks of each blinded treatment	after 4 weeks of each blinded treatment
FVC AUC (0-3h) after 4 weeks of each blinded treatment	after 4 weeks of each blinded treatment
FVC AUC (12-15h) after 4 weeks of each blinded treatment	after 4 weeks of each blinded treatment
Trough and peak inspiratory capacity (IC) and vital capacity (VC) response in the morning of day 1 and at day 28 of each treatment period	day 1 and day 28 of each blinded treatment
Weekly mean pre-dose morning and evening peak expiratory flow (PEF)	28 weeks
Weekly mean number of occasions of rescue therapy used per day	28 weeks
Mahler Dyspnea Indices (TDI) collected at the end of each treatment period and each wash-out period	28 weeks
Fractional exhaled nitric oxide after 4 weeks of each blinded treatment	after 4 weeks of each blinded treatment

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Study record dates

Study Major Dates

• Study Start: October 1, 2007
• Primary Completion (Actual): September 1, 2008

Study Registration Dates

• First Submitted: September 25, 2007
• First Submitted That Met QC Criteria: September 25, 2007
• First Posted (Estimate): September 26, 2007

Study Record Updates

• Last Update Posted (Estimate): May 30, 2014
• Last Update Submitted That Met QC Criteria: May 22, 2014
• Last Verified: May 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Parasympatholytics; Autonomic Agents; Peripheral Nervous System Agents; Cholinergic Antagonists; Cholinergic Agents; Anti-Inflammatory Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Adrenergic Agonists; Dermatologic Agents; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Anti-Allergic Agents; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Fluticasone; Salmeterol Xinafoate; Ciclesonide; Tiotropium Bromide
• Other Study ID Numbers: 1249.1; Eudract2007-003169-42