Comparison of Two Daily Dose Regimens of Tiotropium 5 µg Once Daily and Tiotropium 2.5 µg Twice Daily for 4 Weeks on Top of Maintenance Therapy With Inhaled Corticosteroid Controller Medication

NCT ID: NCT01696071

Last Updated: 2014-08-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 98 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-09-30
• Study Completion Date: 2013-06-30

Brief Summary

Determine the 24-hour FEV1-profile of tiotropium solution for inhalation after 4 weeks treatment periods of 5 mcg tiotropium administered once daily in the evening and 2.5 mcg tiotropium administered twice daily (morning and evening). In addition compare the 24 hours pharmacokinetic profile of 5 mcg tiotropium administered once daily and 2.5mcg tiotropium administered twice daily in pharmacokinetic sub-investigation.

Conditions

Asthma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Treatment A

2 puffs of daily dose (5 mcg) in the evening and 2 puffs of matching placebo in the morning via Respimat inhaler

Group Type: EXPERIMENTAL

Tiotropium 5 mcg qd

Intervention Type: DRUG

2 puffs (2.5 mcg each) in the evening 5 mcg in total and 2 puffs of matching placebo in the morning

Treatment B

2 puffs of half daily dose (2.5 mcg) twice daily, in the evening and in the morning via Respimat inhaler

Group Type: EXPERIMENTAL

Tiotropium 2.5 mcg bid

Intervention Type: DRUG

2 puffs (1.25 mcg each) twice daily, in the evening and in the morning, 5 mcg in total

Interventions

Tiotropium 5 mcg qd

2 puffs (2.5 mcg each) in the evening 5 mcg in total and 2 puffs of matching placebo in the morning

Intervention Type: DRUG

Tiotropium 2.5 mcg bid

2 puffs (1.25 mcg each) twice daily, in the evening and in the morning, 5 mcg in total

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. All patients must sign and date an Informed Consent Form consistent with ICH-GCP guidelines and local legislation prior to participation in the trial.

2. Male or female patients aged at least 18 years at Visit 0 but not more than 75 years at Visit 0.

3. All patients must have at least a 3 months history of asthma at the time of enrolment (signing ICF) into the trial. The initial diagnosis of asthma must have been made before the patient's age of 40.

4. All patients must have a pre-bronchodilator FEV1 = 60% predicted and = 90% of predicted normal at Visit 1.Variation of absolute pre-bronchodilator FEV1 values at Visit 1 and Visit 2 must be within ± 30%.

5. Patient's diagnosis of asthma has to be confirmed at Visit 1 with bronchodilator reversibility (ie 10 minutes prior to and 15-30 minutes after inhalation of 400 µg salbutamol) defined as an FEV1 increase of = 12% and = 200 mL.

6. All patients must have a diagnosis of moderate persistent asthma and must be symptomatic despite their current maintenance treatment with medium doses of ICS.

7. All patients must be symptomatic at Visit 1and Visit 2 as defined by an ACQ mean score of = 1.5.

8. All patients must have maintenance treatment with stable medium daily dose of ICS for at least 4 weeks prior to Visit 1.

9. 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 at Visit 0.

10. Patients must be able to use the Respimat inhaler correctly.

11. Patients must be able to perform all trial related procedures including technically acceptable pulmonary function tests and use of the AM3 (e-diary) compliance of at least 80% is required.

12. 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).

Exclusion Criteria

1. 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.

2. Patients with a clinically relevant abnormal screening hematology or blood chemistry at Visit 1 if the abnormality defines a significant disease as defined in exclusion criterion no. 1.

3. Patients requiring more than 12 puffs of rescue medication (salbutamol MDI) per 24 hours for more than 2 consecutive days between Visit 1 and Visit 2 (screening period).

4. Patients with a recent history (ie six months or less) of Acute Coronary Syndrome (STEMI, non-STEMI, Unstable Angina Pectoris) prior to Visit 1 (screening).

5. Patients who have been hospitalised for cardiac failure during the past year prior to Visit 1 (screening).

6. Patients with any unstable or life-threatening cardiac arrhythmia or cardiac arrhythmia requiring intervention or a change in drug therapy within the past year prior to Visit 1 (screening).

7. Patients with lung diseases other than asthma (eg COPD).

8. Patients with known active tuberculosis.

9. Patients with malignancy for which the patient has undergone resection, radiation therapy or chemotherapy within the last five years prior to Visit 1 (screening). Patients with treated basal cell carcinoma are allowed.

10. Patients who have undergone thoracotomy with pulmonary resection. Patients with a history of thoracotomy for other reasons should be evaluated as per exclusion criterion no. 1.

11. Patients with significant alcohol or drug abuse on Investigator's assessment within the past two years prior to Visit 1 (screening).

12. Patients who are currently in a pulmonary rehabilitation program or have completed a pulmonary rehabilitation program in the 6 weeks prior to Visit 1 (screening).

13. Patients with known hypersensitivity to anticholinergic drugs, BAC, EDTA or any other components of the study medication delivery systems.

14. Pregnant or nursing women, including female patients with positive ß-HCG test at Visit 1.

15. Female patients of child-bearing potential not using highly effective method of birth control. As defined in ICH (M3) [R09-1400], note 3, highly effective methods of birth control are defined as those, alone or in combination, that result in a low failure rate (ie less than 1% per year) when used consistently and correctly, such as implants, injectables, combined oral contraceptives, some intrauterine devices (IUDs), sexual abstinence or vasectomised partner. Barrier contraceptives (eg male condom or diaphragm) are acceptable if used in combination with spermicides (eg foam, gel).

Female patients will be considered to be of childbearing potential unless surgically sterilised by hysterectomy or bilateral tubal ligation/salpingectomy, or post-menopausal for at least two years.

16. Patients who have been treated with restricted medication prior to Visit 1 and/or during the screening period.

17. Patients with any asthma exacerbation or any respiratory tract infection in the four weeks prior to Visit 1 or during the screening period.

Visit 1 and/or Visit 2 should be postponed in case of an asthma exacerbation or respiratory tract infection. Refer to Section 6.1 for information on re-scheduling of visits.

18. Patients who are currently participating in another trial or who have been participating in another trial within one month prior to Visit 0, and patients who have previously been randomised in this trial.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Pfizer

INDUSTRY

Sponsor Role: collaborator

Boehringer Ingelheim

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Boehringer Ingelheim

Role: STUDY_CHAIR

Boehringer Ingelheim

Locations

205.441.43004 Boehringer Ingelheim Investigational Site

Grieskirchen, , Austria

205.441.43003 Boehringer Ingelheim Investigational Site

Linz, , Austria

205.441.43001 Boehringer Ingelheim Investigational Site

Thalheim bei Wels, , Austria

205.441.43002 Boehringer Ingelheim Investigational Site

Wels, , Austria

205.441.49015 Boehringer Ingelheim Investigational Site

Berlin, , Germany

205.441.49003 Boehringer Ingelheim Investigational Site

Frankfurt, , Germany

205.441.49014 Boehringer Ingelheim Investigational Site

Frankfurt, , Germany

205.441.49007 Boehringer Ingelheim Investigational Site

Großhansdorf, , Germany

205.441.49005 Boehringer Ingelheim Investigational Site

Hanover, , Germany

205.441.49004 Boehringer Ingelheim Investigational Site

Leipzig, , Germany

205.441.49010 Boehringer Ingelheim Investigational Site

Lübeck, , Germany

205.441.49013 Boehringer Ingelheim Investigational Site

Mannheim, , Germany

205.441.49001 Boehringer Ingelheim Investigational Site

Neu-Isenburg, , Germany

205.441.49002 Boehringer Ingelheim Investigational Site

Wiesbaden, , Germany

205.441.49011 Boehringer Ingelheim Investigational Site

Wiesloch, , Germany

205.441.36003 Boehringer Ingelheim Investigational Site

Cegléd, , Hungary

205.441.36002 Boehringer Ingelheim Investigational Site

Gödöllő, , Hungary

205.441.36001 Boehringer Ingelheim Investigational Site

Pécs, , Hungary

205.441.36005 Boehringer Ingelheim Investigational Site

Százhalombatta, , Hungary

205.441.36004 Boehringer Ingelheim Investigational Site

Szigetszentmiklós, , Hungary

205.441.38601 Boehringer Ingelheim Investigational Site

Golnik, , Slovenia

205.441.38602 Boehringer Ingelheim Investigational Site

Kamnik, , Slovenia

Countries

Austria; Germany; Hungary; Slovenia

Other Identifiers

2012-001873-10

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

205.441

Identifier Type: -

Identifier Source: org_study_id