Tiotropium Respimat Pharmacokinetic Study in COPD

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT01222533
First received: October 15, 2010
Last updated: May 7, 2014
Last verified: August 2013

October 15, 2010
May 7, 2014
October 2010
November 2011   (final data collection date for primary outcome measure)
  • Maximum Plasma Concentration at Steady-state (Cmax,ss) [ Time Frame: 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. ] [ Designated as safety issue: No ]
    Cmax,ss is the maximum measured concentration of tiotropium in plasma at steady-state.
  • Area Under the Curve 0 to 6 Hours at Steady-state (AUC0-6h,ss) [ Time Frame: 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. ] [ Designated as safety issue: No ]
    AUC0-6h,ss is the area under the concentration time curve of tiotropium in plasma over the time interval 0 to 6 hours post-dose at steady-state. AUC0-6h,ss was calculated using the linear up/log down algorithm.
  • Cmax ss (maximum concentration) at end of each treatment period [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
  • AUC0-6 ss (area under the concentration time curve) at end of each treatment period. [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
  • Trough forced expiratory volume in one second (FEV1) at end of each treatment period [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01222533 on ClinicalTrials.gov Archive Site
  • Trough Forced Expiratory Volume in One Second (FEV1) at the End of Each Treatment Period [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
    Defined as FEV1 measured just prior to the last administration of the morning dose of the randomised treatment. Means are adjusted for sequence, patients within sequences, period and treatment.
  • FEV1 Area Under the Curve 0 to 6 Hours (AUC0-6h) at the End of Each Treatment Period [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
    FEV1 AUC0-6h calculated from zero time to 6 hours using the trapezoidal rule divided by 6 hours. Trough FEV1 will be assigned to zero time. Means are adjusted for sequence, patients within sequences, period and treatment.
  • FEV1 Area Under the Curve 0 to 3 Hours (AUC0-3h) at the End of Each Treatment Period [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
    FEV1 AUC0-3h calculated from zero time to 3 hours using the trapezoidal rule divided by 3 hours. Trough FEV1 will be assigned to zero time. Means are adjusted for sequence, patients within sequences, period and treatment.
  • Trough Forced Vital Capacity (FVC) at the End of Each Treatment Period [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
    Defined as the pre-dose FVC measured just prior to the last administration of the morning dose of the randomised treatment. Means are adjusted for sequence, patients within sequences, period and treatment.
  • FVC AUC0-6h at the End of Each Treatment Period [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
    FVC AUC0-6h calculated from zero time to 6 hours using the trapezoidal rule divided by 6 hours. Trough FVC will be assigned to zero time. Means are adjusted for sequence, patients within sequences, period and treatment.
  • FVC AUC0-3h at the End of Each Treatment Period [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
    FVC AUC0-3h calculated from zero time to 3 hours using the trapezoidal rule divided by 3 hours. Trough FVC will be assigned to zero time. Means are adjusted for sequence, patients within sequences, period and treatment.
  • FEV1 at Each Planned Time at the End of Each Treatment Period [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
    Means are adjusted for period, planned time, period*planned time, patient*planned time and patient*treatment*planned time.
  • FVC at Each Planned Time at the End of Each Treatment Period [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
    Means are adjusted for period, planned time, period*planned time, patient*planned time and patient*treatment*planned time.
  • Area Under the Curve 0 to 1 Hour at Steady-state (AUC0-1h,ss) [ Time Frame: 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. ] [ Designated as safety issue: No ]
    AUC0-1h,ss is the area under the concentration time curve of tiotropium in plasma over the time interval 0 to 1 hour post-dose at steady-state. AUC0-1h,ss was calculated using the linear up/log down algorithm.
  • Time to Maximum Plasma Concentration at Steady-state (Tmax,ss) [ Time Frame: 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. ] [ Designated as safety issue: No ]
    Tmax,ss is the time from dosing to the maximum concentration of tiotropium in plasma-venous blood at steady-state.
  • Amount of Drug Eliminated in Urine at Steady-state (Ae0-6h,ss) [ Time Frame: 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. ] [ Designated as safety issue: No ]
    Total quantity of the analyte that is excreted in urine over the time interval 0 to 6 hours at steady state.
  • Pre-dose Plasma Concentration at Steady-state (Cpre,ss) [ Time Frame: 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) ] [ Designated as safety issue: No ]
    Cpre,ss is the measured concentration of tiotropium in plasma before dosing at steady-state.
  • Renal Clearance at Steady-state (CL R,0-6h,ss) [ Time Frame: Based on blood and urine sampling for PK assessments done at 4 weeks over 6 h post dosing. ] [ Designated as safety issue: No ]
    Renal clearance of the drug over the time interval 0 to 6 hours at steady-state. CL R,0-6h,ss was calculated as the quotient of Ae0-6h,ss and AUC0-6h,ss.
  • Minimum Plasma Concentration at Steady-state (Cmin,ss) [ Time Frame: 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. ] [ Designated as safety issue: No ]
    Cmin,ss is the minimum measured concentration of tiotropium in plasma at steady-state.
  • Trough forced vital capacity (FVC) at end of each treatment period [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
  • FEV1 AUC (area under the curve) and FVC AUC at end of each treatment period [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
  • AUCt1-t2,ss (Area under the concentation time curve) over time interval t1-t2. AUC0-tz ss (Area under the concentration curve) [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
  • tmax ss (time from dosing to the maximum concentration) t1/2 ss (terminal half life) [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
  • MRTih ss (mean residence time) [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
  • Vz /F ss, (apparent volume of distribution) Aet1-t2 ss (amount of drug eliminated in urine) [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
  • fet1-t2 ss (fraction of drug eliminated in urine) CLR, t1-t2, ss (renal clearance of the drug) [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
  • Cpre, ss (pre-dose concentration) Cmin, ss (minimum concentration) [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
  • Terminal rate constant in plasma at steady state [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
  • All adverse events; ECG monitoring [ Time Frame: 20 weeks ] [ Designated as safety issue: No ]
  • Maximum Heart Rate (HR) [ Time Frame: 6.5 hours (including pre dose) ] [ Designated as safety issue: No ]
    Maximum HR evaluated over the entire 6.5 h Holter monitoring period. The arrhythmia variables were pre-specified for day 29 and analysed post-hoc for day 26. The lines "Day 29 1st h" and "Day 26 1st h" are related to the interval 0 h to 1 h, i.e. the first hour after dosing.
  • Mean Heart Rate (HR) [ Time Frame: 6.5 hours (including pre dose) ] [ Designated as safety issue: No ]
    Mean HR evaluated over the entire 6.5 h Holter monitoring period. The arrhythmia variables were pre-specified for day 29 and analysed post-hoc for day 26. The lines "Day 29 1st h" and "Day 26 1st h" are related to the interval 0 h to 1 h, i.e. the first hour after dosing.
  • SVPB Total [ Time Frame: 6.5 hours (including pre dose) ] [ Designated as safety issue: No ]
    The outcome measure describes the number of patients with a Supraventricular Premature Beat (SVPB) event evaluated over the entire 6.5 h Holter monitoring period. The arrhythmia variables were pre-specified for day 29 and analysed post-hoc for day 26. The lines "Day 29 1st h" and "Day 26 1st h" are related to the interval 0 h to 1 h, i.e. the first hour after dosing.
  • SVPB Runs [ Time Frame: 6.5 hours (including pre dose) ] [ Designated as safety issue: No ]
    The outcome measure describes the number of patients with a Supraventricular Premature Beat (SVPB) run evaluated over the entire 6.5 h Holter monitoring period. Runs were defined as at least 3 premature beats in a row. The arrhythmia variables were pre-specified for day 29 and analysed post-hoc for day 26. The lines "Day 29 1st h" and "Day 26 1st h" are related to the interval 0 h to 1 h, i.e. the first hour after dosing.
  • SVPB Pairs [ Time Frame: 6.5 hours (including pre dose) ] [ Designated as safety issue: No ]
    The outcome measure describes the number of patients with a Supraventricular Premature Beat (SVPB) pair evaluated over the entire 6.5 h Holter monitoring period. Pairs were defined as 2 consecutive premature beats in a row. The arrhythmia variables were pre-specified for day 29 and analysed post-hoc for day 26. The lines "Day 29 1st h" and "Day 26 1st h" are related to the interval 0 h to 1 h, i.e. the first hour after dosing.
  • SVPB Singles [ Time Frame: 6.5 hours (including pre dose) ] [ Designated as safety issue: No ]
    The outcome measure describes the number of patients with a Supraventricular Premature Beat (SVPB) single evaluated over the entire 6.5 h Holter monitoring period. The arrhythmia variables were pre-specified for day 29 and analysed post-hoc for day 26. The lines "Day 29 1st h" and "Day 26 1st h" are related to the interval 0 h to 1 h, i.e. the first hour after dosing.
  • VPB Total [ Time Frame: 6.5 hours (including pre dose) ] [ Designated as safety issue: No ]
    The outcome measure describes the number of patients with a Ventricular Premature Beat (VPB) event evaluated over the entire 6.5 h Holter monitoring period. The arrhythmia variables were pre-specified for day 29 and analysed post-hoc for day 26. The lines "Day 29 1st h" and "Day 26 1st h" are related to the interval 0 h to 1 h, i.e. the first hour after dosing.
  • VPB Runs [ Time Frame: 6.5 hours (including pre dose) ] [ Designated as safety issue: No ]
    The outcome measure describes the number of patients with a Ventricular Premature Beat (VPB) run evaluated over the entire 6.5 h Holter monitoring period. Runs were defined as at least 3 premature beats in a row. The arrhythmia variables were pre-specified for day 29 and analysed post-hoc for day 26. The lines "Day 29 1st h" and "Day 26 1st h" are related to the interval 0 h to 1 h, i.e. the first hour after dosing.
  • VPB Pairs [ Time Frame: 6.5 hours (including pre dose) ] [ Designated as safety issue: No ]
    The outcome measure describes the number of patients with a Ventricular Premature Beat (VPB) pair evaluated over the entire 6.5 h Holter monitoring period. Pairs were defined as 2 consecutive premature beats in a row. The arrhythmia variables were pre-specified for day 29 and analysed post-hoc for day 26. The lines "Day 29 1st h" and "Day 26 1st h" are related to the interval 0 h to 1 h, i.e. the first hour after dosing.
  • VPB Singles [ Time Frame: 6.5 hours (including pre dose) ] [ Designated as safety issue: No ]
    The outcome measure describes the number of patients with a Ventricular Premature Beat (VPB) single evaluated over the entire 6.5 h Holter monitoring period. The arrhythmia variables were pre-specified for day 29 and analysed post-hoc for day 26. The lines "Day 29 1st h" and "Day 26 1st h" are related to the interval 0 h to 1 h, i.e. the first hour after dosing.
Not Provided
 
Tiotropium Respimat Pharmacokinetic Study in COPD
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)

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.

Not Provided
Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Crossover Assignment
Masking: Double-Blind
Primary Purpose: Treatment
Pulmonary Disease, Chronic Obstructive
  • Drug: Tiotropium medium
    Tiotropium inhalation solution medium dose
  • Drug: Tiotropium low
    Tiotropium inhalation solution low dose
  • Drug: Tiotropium high
    Tiotropium inhalation solution high dose
  • Drug: Tiotropium 18mcg
    Tiotropium inhalation powder 18mcg
  • Drug: Tiotropium placebo
    Placebo inhalation solution
  • Experimental: Tiotropium low
    Tiotropium inhalation solution low dose
    Intervention: Drug: Tiotropium low
  • Experimental: Tiotropium medium
    Tiotropium inhalation solution medium dose
    Intervention: Drug: Tiotropium medium
  • Experimental: Tiotropium high
    Tiotropium inhalation solution high dose
    Intervention: Drug: Tiotropium high
  • Active Comparator: Tiotropium 18mcg
    Tiotropium inhalation powder 18mcg
    Intervention: Drug: Tiotropium 18mcg
  • Placebo Comparator: Tiotropium placebo
    Placebo inhalation solution
    Intervention: Drug: Tiotropium placebo
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
154
Not Provided
November 2011   (final data collection date for primary outcome measure)

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)

Both
40 Years and older
No
Contact information is only displayed when the study is recruiting subjects
Belgium,   Denmark,   Finland,   Germany,   Netherlands
 
NCT01222533
205.458, 2009-016251-21
Not Provided
Boehringer Ingelheim
Boehringer Ingelheim
Not Provided
Study Chair: Boehringer Ingelheim Boehringer Ingelheim
Boehringer Ingelheim
August 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP