A Randomised, Double- Blind, Placebo Controlled, Cross-over Efficacy and Safety Comparison of Tiotropium 5 µg Once Daily and Tiotropium 2.5 µg Twice Daily for Four Weeks in Patients With Moderate Persistent Asthma

NCT01152450 | Completed Phase 2 Results

• 2 other identifiers: 205.4202009-018006-21
• Study Type: interventional
• Target: 94
• Locations: 5 countries
• Sites: 15

Brief Summary

Rationale for the current trial is to demonstrate 24 hour bronchodilator efficacy and safety of tiotropium 5 µg administered once daily (in the evening) which is regarded beneficial for the compliance and convenience of the patient in comparison to placebo. Further the rationale is to evaluate efficacy and safety of tiotropium 2.5 µg administered twice daily delivered by the Respimat® inhaler in comparison to placebo and tiotropium 5 µg administered once daily (in the evening) delivered by the Respimat® inhaler in patients with moderate persistent asthma. Rationale for the pharmacokinetic subinvestigation is to evaluate the 24 hours exposure to tiotropium in patients with moderate persistent asthma when administered 5 µg tiotropium once daily (in the evening) or 2.5 µg tiotropium twice daily.

Conditions

Asthma

Outcome Measures

Primary Outcomes (1)

• Forced Expiratory Volume in One Second (FEV1) Area Under the Curve 0-24 Hours (AUC0-24h) Response

  Mixed Model Repeated Measure (MMRM) results. Response was defined as change from baseline. Means are adjusted for treatment, period, patient and study baseline. Measurements performed in relation to evening dosing. AUC0-24h calculated using the trapezoidal rule divided by the observation time (24 hours) to report in litres.

  10 minutes (min) prior to first dose (baseline) and -10 min, 30 min, 60 min, 2 hours (h) , 3 h, 4 h , 11 h 50 min, 12 h 30 min, 13 h, 14 h, 15 h, 16 h, 18 h, 20 h, 22 h, 23 h, and 23 h 50 min related to evening dose at week 4

Secondary Outcomes (20)

• Mean Pre-dose Morning Peak Expiratory Flow (PEF a.m.) Response During the Last Week on Treatment

  Baseline and during week 4 of each treatment period

• Mean Pre-dose Evening Peak Expiratory Flow (PEF p.m.) Response During the Last Week on Treatment

  Baseline and during week 4 of each treatment period

• FEV1 Area Under the Curve 0-12 Hours (AUC0-12h) Response

  10 min prior to first dose (baseline) and -10 min, 30 min, 60 min, 2 h, 3 h, 4 h and 11 h 50 min related to evening dose at week 4

• FEV1 Area Under the Curve 12-24 Hours (AUC12-24h) Response

  10 min prior to first dose (baseline) and 11 h 50 min, 12 h 30 min, 13 h, 14 h, 15 h, 16 h, 18 h, 20 h, 22 h, 23 h, and 23 h 50 min related to evening dose at week 4

• Peak FEV1 Within 24 Hours Post-dose Response

  Baseline and 4 weeks

Study Arms (3)

Tiotropium daily dose q.d.

EXPERIMENTAL

two actuations delivered via Respimat® inhaler

Drug: Tiotropium 5 µg q.d.

Tiotropium half daily dose b.i.d.

EXPERIMENTAL

two actuations delivered via Respimat® inhaler

Drug: Tiotropium 2.5 µg b.i.d

Placebo

PLACEBO COMPARATOR

N/A (two actuations of placebo) delivered via Respimat® inhaler

Drug: Placebo

Interventions

Tiotropium 2.5 µg b.i.d DRUG

2.5 µg (two actuations of 1.25 µg) delivered via Respimat® inhaler

Tiotropium half daily dose b.i.d.

Placebo DRUG

N/A (two actuations of placebo) delivered via Respimat® inhaler

Placebo

Tiotropium 5 µg q.d. DRUG

5 µg (two actuations of 2.5 µg) delivered via Respimat® inhaler

Tiotropium daily dose q.d.

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 International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use Good Clinical Practice ( ICH-GCP) guidelines 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 at least 18 years but not more than 75 years.
• All patients must have at least a 3 months history of asthma at the time of enrolment into the trial. The diagnosis of asthma has to be confirmed at Visit 1 with a bronchodilator reversibility resulting in a Forced Expiratory Volume in 1 Second (FEV1) increase of equal above 12% and equal above 200mL.
• The initial diagnosis of asthma must have been made before the patient's age of 40.
• All patients must have a diagnosis of moderate persistent asthma and must be symptomatic despite their current maintenance treatment with medium doses of inhaled corticosteroids.
• 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 Betaadrenergic (LABA) or Short Acting Betaadrenergic (SABA)) for at least 4 weeks prior to Visit 1.
• All patients must be symptomatic at Visit 1 (screening) and Visit 2 as defined by an Asthma Control Questionnaire (ACQ) Score
• All patients must have a pre-bronchodilator FEV1 above equal 60% predicted and below equal 90% of predicted normal at Visit 1. Predicted normal values will be calculated according to the European Coal and Steel Community Guidelines (ECSC).
• All patients must have an increase in FEV1 of equal above 12% and equal above 200 mL 15 minutes after 400 µg salbutamol at Visit 1.
• 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 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 the e-Diary/peak flow meter.
• Patients taking a chronic pulmonary medication allowed by the study protocol must be willing to continue this therapy for the entire duration of the study (exception: times of acute disease deterioration).

You may not qualify if:

• Patients with a significant disease other than asthma.A significant disease is defined as a disease which, in the opinion of the investigator, may (i) put the patient at risk because of participation in the trial, or (ii) influence the results of the trial, or (iii) cause concern regarding the patient's ability to participate in the trial.
• 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 (e.g. Chronic Obstructive Lung Disease (COPD)).
• 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 treated basal cell carcinoma are allowed.
• Patients who have undergone thoracotomy with pulmonary resection.
• Patients with significant alcohol or drug abuse within the past two years.
• Patients who are currently in a pulmonary rehabilitation program or have completed a pulmonary rehabilitation program in the 6 weeks prior to V 1.
• Patients with known hypersensitivity to anticholinergic drugs, Benzalconiumchloride (BAC), Ethylenediaminetetraacetate (EDTA) or any other components of the study medication delivery systems.
• Pregnant or nursing women.
• Women of childbearing potential not using a highly effective method of birth control.
• Patients who have been treated with beta-blocker medication within four weeks prior to Visit 1 or during the screening period. Topical cardio-selective beta-blocker eye medications for non-arrow angle glaucoma are allowed.
• Patients who have been treated with the long-acting anticholinergic tiotropium (Spiriva®) within four weeks prior to Visit 1 or during the screening period.

Sponsors & Collaborators

• Boehringer Ingelheim: lead
• Pfizer: collaborator

Study Sites (15)

205.420.43002 Boehringer Ingelheim Investigational Site

Linz, Austria

Location

205.420.43004 Boehringer Ingelheim Investigational Site

Schlüsslberg, Austria

Location

205.420.43003 Boehringer Ingelheim Investigational Site

Thalheim bei Wels, Austria

Location

205.420.43001 Boehringer Ingelheim Investigational Site

Wels, Austria

Location

205.420.42002 Boehringer Ingelheim Investigational Site

Brno, Czechia

Location

205.420.42001 Boehringer Ingelheim Investigational Site

Kyjov, Czechia

Location

205.420.37201 Boehringer Ingelheim Investigational Site

Kohtla-Järve, Estonia

Location

205.420.37202 Boehringer Ingelheim Investigational Site

Tallinn, Estonia

Location

205.420.49002 Boehringer Ingelheim Investigational Site

Großhansdorf, Germany

Location

205.420.49004 Boehringer Ingelheim Investigational Site

Hanover, Germany

Location

205.420.49001 Boehringer Ingelheim Investigational Site

Mannheim, Germany

Location

205.420.49003 Boehringer Ingelheim Investigational Site

Schwerin, Germany

Location

205.420.37102 Boehringer Ingelheim Investigational Site

Daugavpils, Latvia

Location

205.420.37101 Boehringer Ingelheim Investigational Site

Riga, Latvia

Location

205.420.37103 Boehringer Ingelheim Investigational Site

Riga, Latvia

Location

Related Publications (1)

• Timmer W, Moroni-Zentgraf P, Cornelissen P, Unseld A, Pizzichini E, Buhl R. Once-daily tiotropium Respimat((R)) 5 mug is an efficacious 24-h bronchodilator in adults with symptomatic asthma. Respir Med. 2015 Mar;109(3):329-38. doi: 10.1016/j.rmed.2014.12.005. Epub 2014 Dec 27.

  PMID: 25661281 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: June 28, 2010
• First Posted: June 29, 2010
• Study Start: July 1, 2010
• Primary Completion: August 1, 2011
• Last Updated: December 19, 2024
• Results First Posted: October 30, 2012

Record last verified: 2024-12

Locations

AU (4); ES (2); DE (4); CZ (2); LA (3)