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Completed

NCT Number: NCT01222533

Tiotropium Respimat Pharmacokinetic Study in 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.

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Key information

Conditions

Pulmonary Disease, Chronic Obstructive Chronic Disease Disease Attributes Lung Diseases Lung Diseases, Obstructive Pathologic Processes Pathological Conditions, Signs and Symptoms Respiratory Tract Diseases

Age range

40 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

205.458.32003 Boehringer Ingelheim Investigational Site, Genk, Belgium

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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.
  • Relatively stable, moderate to very severe Chronic Obstructive Pulmonary Disease (COPD)
  • Current or ex-smokers (smoking history of at least 10 pack years)
  • Able to perform lung function tests
  • Able to use study inhalers

Exclusion criteria

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

Treatment and study plan

Tiotropium medium

Drug

Tiotropium inhalation solution medium dose

Tiotropium low

Drug

Tiotropium inhalation solution low dose

Tiotropium high

Drug

Tiotropium inhalation solution high dose

Tiotropium 18mcg

Drug

Tiotropium inhalation powder 18mcg

Tiotropium placebo

Drug

Placebo inhalation solution

Primary outcomes

  1. 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.

    Cmax,ss is the maximum measured concentration of tiotropium in plasma at steady-state.

  2. 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.

    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.

Secondary outcomes

  1. Trough Forced Expiratory Volume in One Second (FEV1) at the End of Each Treatment Period

    Time frame: 4 weeks

    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.

  2. FEV1 Area Under the Curve 0 to 6 Hours (AUC0-6h) at the End of Each Treatment Period

    Time frame: 4 weeks

    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.

  3. FEV1 Area Under the Curve 0 to 3 Hours (AUC0-3h) at the End of Each Treatment Period

    Time frame: 4 weeks

    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.

  4. Trough Forced Vital Capacity (FVC) at the End of Each Treatment Period

    Time frame: 4 weeks

    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.

  5. FVC AUC0-6h at the End of Each Treatment Period

    Time frame: 4 weeks

    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.

  6. FVC AUC0-3h at the End of Each Treatment Period

    Time frame: 4 weeks

    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.

  7. FEV1 at Each Planned Time at the End of Each Treatment Period

    Time frame: 4 weeks

    Means are adjusted for period, planned time, period*planned time, patient*planned time and patient*treatment*planned time.

  8. FVC at Each Planned Time at the End of Each Treatment Period

    Time frame: 4 weeks

    Means are adjusted for period, planned time, period*planned time, patient*planned time and patient*treatment*planned time.

  9. 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.

    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.

  10. 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.

    Tmax,ss is the time from dosing to the maximum concentration of tiotropium in plasma-venous blood at steady-state.

  11. 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.

    Total quantity of the analyte that is excreted in urine over the time interval 0 to 6 hours at steady state.

  12. 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)

    Cpre,ss is the measured concentration of tiotropium in plasma before dosing at steady-state.

  13. 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.

    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.

  14. 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.

    Cmin,ss is the minimum measured concentration of tiotropium in plasma at steady-state.

Other outcomes

  1. Maximum Heart Rate (HR)

    Time frame: 6.5 hours (including pre dose)

    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.

  2. Mean Heart Rate (HR)

    Time frame: 6.5 hours (including pre dose)

    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.

  3. SVPB Total

    Time frame: 6.5 hours (including pre dose)

    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.

  4. SVPB Runs

    Time frame: 6.5 hours (including pre dose)

    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.

  5. SVPB Pairs

    Time frame: 6.5 hours (including pre dose)

    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.

  6. SVPB Singles

    Time frame: 6.5 hours (including pre dose)

    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.

  7. VPB Total

    Time frame: 6.5 hours (including pre dose)

    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.

  8. VPB Runs

    Time frame: 6.5 hours (including pre dose)

    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.

  9. VPB Pairs

    Time frame: 6.5 hours (including pre dose)

    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.

  10. VPB Singles

    Time frame: 6.5 hours (including pre dose)

    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.

Sponsors and collaborators

Lead sponsor

Boehringer Ingelheim

Industry

Registry information

Official study 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)

Important dates

Study start
2010
Primary completion
2011
First posted
Oct 18, 2010
Registry last updated
May 16, 2014

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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