Clinical trial NCT01222533: Tiotropium Respimat Pharmacokinetic Study in COPD
Official title: A Multicenter, Randomised, Placebo- and Active-controlled, 5 Way, Crossover Trial to Characterise the Pharmacokinetics and Evaluate the Bronchodilator Efficacy and Safety of Once-daily Tiotropium Delivered (Double-blind) From the Respimat Inhaler as Solution for Inhalation (1.25, 2.5, 5 mcg or Placebo) and as Inhalation Powder (18mcg) From the HandiHaler (Open Label) After 4 Week-treatment Periods in Patients With Chronic Obstructive Pulmonary Disease (COPD)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Pulmonary Disease, Chronic Obstructive
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2010-10-18
Enrollment: 154
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: The purpose of this study is compare the effect of different doses of tiotropium delivered by the HandiHaler and Respimat device on lung function. Additionally, the study will investigate the pharmacokinetic profile of these different doses. Studying the pharmacokinetic profile shows what happens to the medication in the body over a period of hours and provides information on potential effects of the medication.


Eligibility criteria: Inclusion criteria:

1. All patient must sign an informed consent consistent with IInternational Conference on Harmonisation- Good Clinical Practice (ICH-GCP) guidelines and local legislation prior to any study-related procedures, including medication washout and restrictions.
2. Relatively stable, moderate to very severe Chronic Obstructive Pulmonary Disease (COPD)
3. Current or ex-smokers (smoking history of at least 10 pack years)
4. Able to perform lung function tests
5. Able to use study inhalers

Exclusion criteria:

1. Significant diseases other than COPD
2. Recent myocardial infarction, unstable or life-threatening cardiac arrhythmia, hospitalisation for cardiac failure.
3. Malignancy requiring resection, radiation therapy or chemotherapy within the last 5 years
4. History of asthma, life-threatening pulmonary obstruction, cystic fibrosis or clinically evident bronchiectasis 5 Active tuberculosis

6. History of alcohol or drug abuse 7. Pulmonary resection 8. Recent completion of a pulmonary rehabilitation program or current participation which will not be continued 9. Daytime oxygen therapy for more than 1 hour per day. 10. Use of other investigational drugs, restrictions on the use of some respiratory medications during the study period.

11. Current participation in another clinical trial 12. Pregnant or nursing women 13. Women of childbearing potential not using a highly effective method of contraception (e.g: implants, injectable, oral contraceptives)

Primary outcomes:
measure: Maximum Plasma Concentration at Steady-state (Cmax,ss)
timeFrame: Based on blood sampling for PK assessments done at 4 weeks at the following time points: 5 minutes (min) before study drug (baseline) and at 2 min , 5 min, 7 min, 9 min, 12 min, 15 min, 20 min, 30 min, 40 min, 1 hour (h), 2 h, 4 h and 6 h post dosing.
measure: Area Under the Curve 0 to 6 Hours at Steady-state (AUC0-6h,ss)
timeFrame: Based on blood sampling for PK assessments done at 4 weeks at the following time points: 5 minutes (min) before study drug (baseline) and at 2 min , 5 min, 7 min, 9 min, 12 min, 15 min, 20 min, 30 min, 40 min, 1 hour (h), 2 h, 4 h and 6 h post dosing.
Secondary outcomes:
measure: Trough Forced Expiratory Volume in One Second (FEV1) at the End of Each Treatment Period
timeFrame: 4 weeks
measure: FEV1 Area Under the Curve 0 to 6 Hours (AUC0-6h) at the End of Each Treatment Period
timeFrame: 4 weeks
measure: FEV1 Area Under the Curve 0 to 3 Hours (AUC0-3h) at the End of Each Treatment Period
timeFrame: 4 weeks
measure: Trough Forced Vital Capacity (FVC) at the End of Each Treatment Period
timeFrame: 4 weeks
measure: FVC AUC0-6h at the End of Each Treatment Period
timeFrame: 4 weeks
measure: FVC AUC0-3h at the End of Each Treatment Period
timeFrame: 4 weeks
measure: FEV1 at Each Planned Time at the End of Each Treatment Period
timeFrame: 4 weeks
measure: FVC at Each Planned Time at the End of Each Treatment Period
timeFrame: 4 weeks
measure: Area Under the Curve 0 to 1 Hour at Steady-state (AUC0-1h,ss)
timeFrame: Based on blood sampling for PK assessments done at 4 weeks at the following time points: 5 minutes (min) before study drug (baseline) and at 2 min , 5 min, 7 min, 9 min, 12 min, 15 min, 20 min, 30 min, 40 min, 1 hour (h), 2 h, 4 h and 6 h post dosing.
measure: Time to Maximum Plasma Concentration at Steady-state (Tmax,ss)
timeFrame: Based on blood sampling for PK assessments done at 4 weeks at the following time points: 5 min before first dosing of study drug (baseline) and at 2 min , 5 min, 7 min, 9 min, 12 min, 15 min, 20 min, 30 min, 40 min, 1 h, 2 h, 4 h and 6 h post dosing.
measure: Amount of Drug Eliminated in Urine at Steady-state (Ae0-6h,ss)
timeFrame: Based on urine sampling for PK assessments done at 4 weeks in the following intervals: -1 to 0 hour (h), 0 to 2 h and 2 to 6 h post-dosing.
measure: Pre-dose Plasma Concentration at Steady-state (Cpre,ss)
timeFrame: Based on blood sampling for PK assessments done at 4 weeks at the following time point: 5 minutes (min) before first dosing of study drug (baseline)
measure: Renal Clearance at Steady-state (CL R,0-6h,ss)
timeFrame: Based on blood and urine sampling for PK assessments done at 4 weeks over 6 h post dosing.
measure: Minimum Plasma Concentration at Steady-state (Cmin,ss)
timeFrame: Based on blood sampling for PK assessments done at 4 weeks at the following time points: 5 min before first dosing of study drug (baseline) and at 2 min , 5 min, 7 min, 9 min, 12 min, 15 min, 20 min, 30 min, 40 min, 1 h, 2 h, 4 h and 6 h post dosing.
Other outcomes:
measure: Maximum Heart Rate (HR)
timeFrame: 6.5 hours (including pre dose)
measure: Mean Heart Rate (HR)
timeFrame: 6.5 hours (including pre dose)
measure: SVPB Total
timeFrame: 6.5 hours (including pre dose)
measure: SVPB Runs
timeFrame: 6.5 hours (including pre dose)
measure: SVPB Pairs
timeFrame: 6.5 hours (including pre dose)
measure: SVPB Singles
timeFrame: 6.5 hours (including pre dose)
measure: VPB Total
timeFrame: 6.5 hours (including pre dose)
measure: VPB Runs
timeFrame: 6.5 hours (including pre dose)
measure: VPB Pairs
timeFrame: 6.5 hours (including pre dose)
measure: VPB Singles
timeFrame: 6.5 hours (including pre dose)
Locations:
city: Genk
country: Belgium
facility: 205.458.32003 Boehringer Ingelheim Investigational Site
city: Gent
country: Belgium
facility: 205.458.32001 Boehringer Ingelheim Investigational Site
city: Hasselt
country: Belgium
facility: 205.458.32002 Boehringer Ingelheim Investigational Site
city: Copenhagen K
country: Denmark
facility: 205.458.45001 Boehringer Ingelheim Investigational Site
city: København NV
country: Denmark
facility: 205.458.45003 Boehringer Ingelheim Investigational Site
city: Odense C
country: Denmark
facility: 205.458.45002 Boehringer Ingelheim Investigational Site
city: Helsinki
country: Finland
facility: 205.458.35801 Boehringer Ingelheim Investigational Site
city: Tampere
country: Finland
facility: 205.458.35802 Boehringer Ingelheim Investigational Site
city: Hannover
country: Germany
facility: 205.458.49001 Boehringer Ingelheim Investigational Site
city: Heerlen
country: Netherlands
facility: 205.458.31001 Atrium Medisch Centrum Parkstad
city: Winschoten
country: Netherlands
facility: 205.458.31002 Ommelander ziekenhuis groep, locatie Lucas
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References:
citation: Hohlfeld JM, Furtwaengler A, Konen-Bergmann M, Wallenstein G, Walter B, Bateman ED. Cardiac safety of tiotropium in patients with COPD: a combined analysis of Holter-ECG data from four randomised clinical trials. Int J Clin Pract. 2015 Jan;69(1):72-80. doi: 10.1111/ijcp.12596. Epub 2014 Dec 11.
citation: Hohlfeld JM, Sharma A, van Noord JA, Cornelissen PJ, Derom E, Towse L, Peterkin V, Disse B. Pharmacokinetics and pharmacodynamics of tiotropium solution and tiotropium powder in chronic obstructive pulmonary disease. J Clin Pharmacol. 2014 Apr;54(4):405-14. doi: 10.1002/jcph.215. Epub 2013 Nov 27.