Clinical trial NCT01696071: 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
Official title: A Randomised, Double- Blind, 2 Way Cross-over Study to Determine 24-hour FEV1-time Profile of Inhaled Tiotropium, Delivered Via the Respimat Inhaler, After 4 Weeks of Once Daily [5 mcg in the Evening (2 Actuations of 2.5 mcg)] or Twice Daily [2.5 mcg in the Morning and Evening (2 Actuations of 1.25 mcg)] Administration in Patients With Moderate Persistent Asthma.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Asthma
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
Collaborators: name: Pfizer
First posted: 2012-09-28
Enrollment: 98
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Forced Expiratory Volume in One Second (FEV1) Area Under the Curve From 0 - 24h (AUC 0-24) Response.
timeFrame: Baseline FEV1 taken at visit 2 prior to the first evening dose of randomised study medication. Then, 10 minutes (min) prior to dose to 30 min,1 hour (h),2h,3h,4h,11h50min,12h30min,13h,14h,15h,16h,18h,20h,22h and 23h,23h50min relative to dose after 4 weeks
Secondary outcomes:
measure: FEV1 AUC0-12h Response
timeFrame: Baseline FEV1 taken at visit 2 prior to the first evening dose of randomised study medication. Then, 10 minutes(min) prior to dose to 30min,1hour(h),2h,3h,4h,11h50min,12h30min,13h,14h,15h,16h,18h,20h,22h and 23h,23h50min relative to dose after 4 weeks
measure: FEV1 AUC12-24h Response
timeFrame: Baseline FEV1 taken at visit 2 prior to the first evening dose of randomised study medication. Then, 10 minutes(min) prior to dose to 30min,1hour(h),2h,3h,4h,11h50min,12h30min,13h,14h,15h,16h,18h,20h,22h and 23h,23h50min relative to dose after 4 weeks
measure: Peak FEV1 Response.
timeFrame: 10 minutes (min) prior to dose to 30 min,1 hour (h),2h,3h,4h,11h50min,12h30min,13h,14h,15h,16h,18h,20h,22h and 23h,23h50min relative to dose after 4 weeks.
measure: Trough FEV1 (L) Response.
timeFrame: 10 minutes (min) prior to dose after 4 weeks
measure: Forced Vital Capacity (FVC) AUC0-24h Response
timeFrame: Baseline taken at visit 2 prior to the first evening dose of randomised study medication. Then, 10 minutes(min) prior to dose to 30min,1hour(h),2h,3h,4h,11h50min,12h30min,13h,14h,15h,16h,18h,20h,22h and 23h,23h50min relative to dose after 4 weeks
measure: FVC AUC0-12h Response
timeFrame: Baseline taken at visit 2 prior to the first evening dose of randomised study medication. Then, 10 minutes(min) prior to dose to 30min,1hour(h),2h,3h,4h,11h50min,12h30min,13h,14h,15h,16h,18h,20h,22h and 23h,23h50min relative to dose after 4 weeks
measure: FVC AUC12-24h Response
timeFrame: Baseline taken at visit 2 prior to the first evening dose of randomised study medication. Then, 10 minutes(min) prior to dose to 30min,1hour(h),2h,3h,4h,11h50min,12h30min,13h,14h,15h,16h,18h,20h,22h and 23h,23h50min relative to dose after 4 weeks
measure: Peak FVC Response
timeFrame: Baseline taken at visit 2 prior to the first evening dose of randomised study medication. Then, 10 minutes(min) prior to dose to 30min,1hour(h),2h,3h,4h,11h50min,12h30min,13h,14h,15h,16h,18h,20h,22h and 23h,23h50min relative to dose after 4 weeks
measure: Trough FVC Responses
timeFrame: Baseline taken at visit 2 prior to the first evening dose of randomised study medication. Then, 10 minutes(min) prior to dose after 4 weeks
measure: Peak Expiratory Flow (PEF) AUC0-24h Response
timeFrame: Baseline taken at visit 2 prior to the first evening dose of randomised study medication. Then, 10 minutes(min) prior to dose to 30min,1hour(h),2h,3h,4h,11h50min,12h30min,13h,14h,15h,16h,18h,20h,22h and 23h,23h50min relative to dose after 4 weeks
Other outcomes:
Locations:
city: Grieskirchen
country: Austria
facility: 205.441.43004 Boehringer Ingelheim Investigational Site
city: Linz
country: Austria
facility: 205.441.43003 Boehringer Ingelheim Investigational Site
city: Thalheim bei Wels
country: Austria
facility: 205.441.43001 Boehringer Ingelheim Investigational Site
city: Wels
country: Austria
facility: 205.441.43002 Boehringer Ingelheim Investigational Site
city: Berlin
country: Germany
facility: 205.441.49015 Boehringer Ingelheim Investigational Site
city: Frankfurt
country: Germany
facility: 205.441.49003 Boehringer Ingelheim Investigational Site
city: Frankfurt
country: Germany
facility: 205.441.49014 Boehringer Ingelheim Investigational Site
city: Großhansdorf
country: Germany
facility: 205.441.49007 Boehringer Ingelheim Investigational Site
city: Hannover
country: Germany
facility: 205.441.49005 Boehringer Ingelheim Investigational Site
city: Leipzig
country: Germany
facility: 205.441.49004 Boehringer Ingelheim Investigational Site
city: Lübeck
country: Germany
facility: 205.441.49010 Boehringer Ingelheim Investigational Site
city: Mannheim
country: Germany
facility: 205.441.49013 Boehringer Ingelheim Investigational Site
city: Neu-Isenburg
country: Germany
facility: 205.441.49001 Boehringer Ingelheim Investigational Site
city: Wiesbaden
country: Germany
facility: 205.441.49002 Boehringer Ingelheim Investigational Site
city: Wiesloch
country: Germany
facility: 205.441.49011 Boehringer Ingelheim Investigational Site
city: Cegled
country: Hungary
facility: 205.441.36003 Boehringer Ingelheim Investigational Site
city: Godollo
country: Hungary
facility: 205.441.36002 Boehringer Ingelheim Investigational Site
city: Pecs
country: Hungary
facility: 205.441.36001 Boehringer Ingelheim Investigational Site
city: Szazhalombatta
country: Hungary
facility: 205.441.36005 Boehringer Ingelheim Investigational Site
city: Szigetszentmiklos
country: Hungary
facility: 205.441.36004 Boehringer Ingelheim Investigational Site
city: Golnik
country: Slovenia
facility: 205.441.38601 Boehringer Ingelheim Investigational Site
city: Kamnik
country: Slovenia
facility: 205.441.38602 Boehringer Ingelheim Investigational Site
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References: