Randomised, Double- Blind, Cross-over Efficacy and Safety Comparison of Three Different Doses of Tiotropium Administered Once Daily Versus Placebo in Patients With Moderate Persistent Asthma.

NCT01233284 | Completed Phase 2 Results

• 2 other identifiers: 205.3802010-018471-26
• Study Type: interventional
• Target: 149
• Locations: 3 countries
• Sites: 19

Brief Summary

Rationale for the current trial is to evaluate the efficacy and safety of three doses (1.25 µg, 2.5 µg and 5.0 µg ex mouthpiece) of tiotropium inhalation solution in patients with moderate persistent asthma who are still symptomatic despite regular maintenance therapy with inhaled corticosteroids (ICS). The data collected in the present trial will provide useful information to health care providers and patients regarding the efficacy and safety of a once daily inhalation of three different doses of tiotropium solution delivered by the Respimat® inhaler in addition to inhaled corticosteroids in the treatment of not fully controlled moderate asthma in comparison to placebo. The Pharmacokinetics (PK) of tiotropium is well established in COPD patients. However, there is currently no PK data available for the 3 doses of tiotropium being tested in this trial in patients with moderate persistent asthma. Tiotropium is a once daily drug. Hence, the rationale for blood and urine sampling for PK analysis over 24 hours in a subset of patients is to confirm the PK of the 3 doses in moderate asthma patients. Rationale for the 24-hour pulmonary function test sub-investigation is to demonstrate that a once daily dosing of tiotropium inhalation solution is effective and safe in the treatment of moderate persistent asthma.

Conditions

Asthma

Outcome Measures

Primary Outcomes (1)

• Forced Expiratory Volume in One Second (FEV1) Peak Within 0-3 Hours Post-dose Response

  Mixed model repeated measurement (MMRM) results. Response was defined as change from baseline at the end of of each 4-week treatment period. Means are adjusted for treatment, period, patient and study baseline.

  10 minutes (min) before drug administration and 30 min, 1h, 2h, 3h after drug administration

Secondary Outcomes (17)

• Trough FEV1 Response

  Baseline and 4 weeks

• FEV1 Area Under the Curve 0-3 Hours (AUC0-3h) Response

  10 minutes (min) before drug administration and 30 min, 1h, 2h, 3h after drug administration

• Forced Vital Capacity (FVC) Peak Within 0-3 Hours Post-dose Response

  10 minutes (min) before drug administration and 30 min, 1h, 2h, 3h after drug administration

• Trough FVC Response

  Baseline and 4 weeks

• FVC AUC0-3h Response

  10 minutes (min) before drug administration and 30 min, 1h, 2h, 3h after drug administration

Study Arms (4)

tiotropium low dose once daily

EXPERIMENTAL

once daily, delivered by the Respimat® inhaler

Drug: tiotropium bromide 1.25µg once daily

tiotropium medium dose once daily

EXPERIMENTAL

once daily, delivered by the Respimat® inhaler

Drug: tiotropium bromide 2.5µg once daily

tiotropium high dose once daily

EXPERIMENTAL

once daily, delivered by the Respimat® inhaler

Drug: tiotropium bromide high dose once daily

Placebo once daily

PLACEBO COMPARATOR

once daily, delivered by the Respimat® inhaler

Drug: Tiotropium matching Placebo once daily

Interventions

tiotropium bromide 2.5µg once daily DRUG

Efficacy and safety comparison of 3 doses of inhaled tiotropium (1.25µg, 2.5µg and 5µg) versus placebo

tiotropium medium dose once daily

Tiotropium matching Placebo once daily DRUG

Efficacy and safety comparison of 3 doses of inhaled tiotropium (1.25µg, 2.5µg and 5µg) versus placebo

Placebo once daily

tiotropium bromide high dose once daily DRUG

Efficacy and safety comparison of 3 doses of inhaled tiotropium (1.25µg, 2.5µg and 5µg) versus placebo

tiotropium high dose once daily

tiotropium bromide 1.25µg once daily DRUG

IMP

tiotropium low dose once daily

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• All patients must sign and date an Informed Consent Form consistent with the Harmonised Tripartite Guideline for Good Clinical Practice (ICH-GCP) and local legislation prior to participation in the trial (i.e. prior to any trial procedures, including any pre-trial washout of medications and medication restrictions for pulmonary function test at Visit 1).
• Male or female patients aged between 18 and 75 years (at date of informed consent).
• The initial diagnosis of asthma must have been made before the patient's age of 40.
• The diagnosis of asthma has to be confirmed at Visit 1 with a bronchodilator reversibility (15 to 30 minutes after 4 puffs of 100 µg salbutamol) resulting in a Forced Expiratory Volume in one second (FEV1) increase of = 12% and = 200mL.
• All patients must have been on maintenance treatment with a medium, stable dose of inhaled corticosteroids (alone or in a fixed combination with a long acting or short acting beta agonist \[LABA or SABA\]) for at least 4 weeks prior to Visit 1.
• All patients must be symptomatic at Visit 1 (screening) and prior to randomisation at Visit 2 as defined by an Asthma Control Questionnaire (ACQ) mean score of = 1.5.
• All patients must have a pre-bronchodilator FEV1 = 60% and = 90% of predicted normal at Visit 1. Predicted normal values will be calculated according to the European Community for Steel and Coal (ECSC).
• Variation of absolute FEV1 values of Visit 1 (pre-bronchodilator) as compared to Visit 2 (pre-dose) must be within ± 30%.
• Patients must be never-smokers or ex-smokers who stopped smoking at least one year prior to enrolment (Visit 0) and who have a smoking history of less than 10 pack years.
• Patients must be able to use the Respimat® inhaler correctly.
• Patients must be able to perform all trial related procedures including technically acceptable pulmonary function tests and use of electronic diary/peak flow meter (diary compliance of at least 80% is required).

You may not qualify if:

• Patients with a significant disease other than asthma.
• Patients with a recent history (i.e. six months or less) of myocardial infarction.
• Patients who have been hospitalised for cardiac failure during the past year.
• Patients with any unstable or life-threatening cardiac arrhythmia or cardiac arrhythmia requiring intervention or a change in drug therapy within the past year.
• Patients with lung diseases other than asthma.
• Patients with known active tuberculosis.
• Patients with malignancy for which the patient has undergone resection, radiation therapy or chemotherapy within the last five years.
• Patients with known moderate to severe renal impairment.
• Patients with known narrow angle glaucoma or any other disease where anticholinergic treatment is contraindicated.
• Patients with significant symptomatic prostatic hyperplasia or bladder-neck obstruction. Patients whose symptoms are controlled on treatment may be included.
• Patients with significant alcohol or drug abuse within the past two years (to the discretion of the investigator).
• Patients who are currently in a pulmonary rehabilitation program or have completed pulmonary rehabilitation program in the 6 weeks prior to Visit 1 (screening) or who will start a rehabilitation program during the study.
• Patients with known hypersensitivity to anticholinergic drugs, Benzalkonium chloride (BAC), Ethylenediaminetetraacetate (EDTA) or any other components of the study medication delivery system (Respimat®/ tiotropium inhalation solution).
• Pregnant or nursing woman.
• Women of childbearing potential not using a highly effective method of birth control.

Sponsors & Collaborators

• Boehringer Ingelheim: lead
• Pfizer: collaborator

Study Sites (19)

205.380.43002 Boehringer Ingelheim Investigational Site

Hallein, Austria

Location

205.380.43004 Boehringer Ingelheim Investigational Site

Linz, Austria

Location

205.380.43005 Boehringer Ingelheim Investigational Site

Neumarkt am Wallersee, Austria

Location

205.380.43001 Boehringer Ingelheim Investigational Site

Schlüsslberg, Austria

Location

205.380.43003 Boehringer Ingelheim Investigational Site

Thalheim bei Wels, Austria

Location

205.380.49006 Boehringer Ingelheim Investigational Site

Berlin, Germany

Location

205.380.49010 Boehringer Ingelheim Investigational Site

Berlin, Germany

Location

205.380.49003 Boehringer Ingelheim Investigational Site

Frankfurt, Germany

Location

205.380.49004 Boehringer Ingelheim Investigational Site

Hamburg, Germany

Location

205.380.49007 Boehringer Ingelheim Investigational Site

Hanover, Germany

Location

205.380.49009 Boehringer Ingelheim Investigational Site

Mainz, Germany

Location

205.380.49008 Boehringer Ingelheim Investigational Site

Schwerin, Germany

Location

205.380.49001 Boehringer Ingelheim Investigational Site

Wiesbaden, Germany

Location

205.380.49005 Boehringer Ingelheim Investigational Site

Wiesloch, Germany

Location

205.380.38005 Boehringer Ingelheim Investigational Site

Ivano-Frankivsk, Ukraine

Location

205.380.38003 Boehringer Ingelheim Investigational Site

Kharkiv, Ukraine

Location

205.380.38004 Boehringer Ingelheim Investigational Site

Kharkiv, Ukraine

Location

205.380.38001 Boehringer Ingelheim Investigational Site

Kiev, Ukraine

Location

205.380.38002 Boehringer Ingelheim Investigational Site

Kiev, Ukraine

Location

Related Publications (1)

• Beeh KM, Moroni-Zentgraf P, Ablinger O, Hollaenderova Z, Unseld A, Engel M, Korn S. Tiotropium Respimat(R) in asthma: a double-blind, randomised, dose-ranging study in adult patients with moderate asthma. Respir Res. 2014 Jun 3;15(1):61. doi: 10.1186/1465-9921-15-61.

  PMID: 24890738 DERIVED

MeSH Terms

Conditions

Asthma

Interventions

Tiotropium Bromide

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

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: Boehringer Ingelheim Call Center
• Organization: Boehringer Ingelheim Pharmaceuticals

clintriage.rdg@boehringer-ingelheim.com

1-800-243-0127

Study Officials

• Boehringer Ingelheim

  Boehringer Ingelheim

  STUDY CHAIR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 2, 2010
• First Posted: November 3, 2010
• Study Start: November 1, 2010
• Primary Completion: January 1, 2012
• Last Updated: December 24, 2013
• Results First Posted: January 21, 2013

Record last verified: 2013-09

Locations

AU (5); UA (5); DE (9)