Pharmacokinetic Study in Elderly Patients With Chronic Obstructive Bronchitis (COPD)
Primary Purpose
Pulmonary Disease, Chronic Obstructive
Status
Completed
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
Tiotropium inhalation capsules for oral inhalation
Sponsored by
About this trial
This is an interventional treatment trial for Pulmonary Disease, Chronic Obstructive
Eligibility Criteria
Inclusion Criteria:
All patients were required to have a diagnosis of COPD and to meet the following spirometric criteria:
- Relatively stable, moderate to severe airway obstruction with an FEV1 ≤ 65% of predicted normal and FEV1/FVC ≤ 70%
Patients were required to have normal renal clearance. Renal clearance will be evaluated by the determination of creatinine clearance. To qualify for this trial, the patient's measured creatinine clearance was required to be within 20% of the calculated creatinine clearance, as given by the following equations:
- Males: Calculated Creatinine Clearance (ml/min) = [140 - Age (yrs)] x weight(kg) / 72 x serum creatinine (mg/dL)
- Females: Calculated Creatinine Clearance (ml/min) = [140 - Age (yrs)] x weight (kg) / 85 x serum creatinine (mg/dL)
- Both male or female patients were eligible. Twelve patients ≥ 70 years old and twelve patients ≤ 50 years
- Patients were required to have a smoking history of more than ten pack-years, where a pack-year was defined as the equivalent of smoking one pack of cigarettes per day for a year
- Patients must be able to perform all specified procedures and maintain records during the study period as required in the protocol
- Patients were required to be able to inhale medication from the HandiHaler®
- Patients were required to sign an Informed Consent Form prior to participation in the trial, including any necessary prior to pre-study washout of their usual pulmonary medications
Exclusion Criteria:
- Patients with significant diseases other than COPD were excluded from participation in the trial. A significant disease was defined as a disease which in the opinion of the investigator may either have put the patient at risk because of participation in the trial or a disease which may have influenced the results of the trial or the patient's ability to participate in the trial;
- Patients with clinically significant abnormal baseline haematology, blood chemistry or urinalysis, if the abnormality defined a disease listed as an exclusion criterion;
- Patients with alanine transaminase (ALT/SGOT) > 80 IU/L or aspartate transaminase (AST/SGPT) > 80 IU/L, or bilirubin > 2.0 mg/dL or creatinine > 2.0 mg/dL were excluded from participation in the trial, regardless of the patient's clinical condition. Repeat laboratory evaluations were not conducted in these patients;
- Patients with a recent history (i.e., one year or less) of myocardial infarction (MI);
- Patients with a recent history (i.e., three years or less) of heart failure or patients with any cardiac arrhythmia requiring drug therapy;
- Patients with regular use of daytime oxygen therapy;
- Patients with known active tuberculosis;
- Patients with a history of cancer within the last five years. However, patients with treated basal cell carcinoma are allowed to participate;
- Patients with a history of life-threatening pulmonary obstruction, or a history of cystic fibrosis or bronchiectasis;
- Patients who had undergone thoracotomy with pulmonary resection. Patients with a history of a thoracotomy for other reasons were evaluated as per exclusion criterion # 1;
- Patients who had developed an upper respiratory tract infection in six weeks prior to the Screening Visit (Visit 1) or during the baseline period;
- Patients with known hypersensitivity to anticholinergic drugs, lactose or any other components of the inhalation capsule delivery system;
- Patients with known symptomatic prostatic hypertrophy or bladder neck obstruction;
- Patients with known narrow-angle glaucoma;
- Patients treated with cromolyn sodium or nedocromil sodium;
- Patients treated with antihistamines (H1 receptor antagonists);
- Patients using oral corticosteroid medication at unstable doses (i.e. less than six weeks on a stable dose) or at a dose in excess of the equivalent of 10 mg of prednisone per day (or 20 mg every other day);
- Pregnant or nursing women or women of childbearing potential not using a medically approved means of contraception (i.e. oral contraceptives, intrauterine devices, diaphragm or Norplant®);
- Patients with a history of asthma, allergic rhinitis or atopy or patients with a total blood eosinophil count ≥ 600/mm3. A repeat eosinophil count was not conducted in these patients;
- Patients with history and/or active alcohol or drug abuse.
- Patients who had taken an investigational drug within one month or six half lives (whichever was greater) prior to Screening Visit (Visit 1).
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Tiotropium inhalation capsules
Arm Description
Outcomes
Primary Outcome Measures
Total area under the plasma drug concentration-time curve (AUC 0-4 h)
Urinary excretion of tiotropium (Ae(0-4 hours))
Renal clearance of tiotropium (CLren)
Terminal elimination half-life after the last dose
Secondary Outcome Measures
Plasma concentration of drug 5 min after inhalation (C5min)
tmax (time of occurrence for maximum drug concentration)
Change from baseline in FEV1 (Forced expiratory volume in one second)
Change from baseline in FVC (Forced vital capacity)
FEV1/FVC
Symptom evaluation
Use of salbutamol
Occurrence of Adverse Events
Occurrence of Adverse Events
Changes form baseline in vital signs (pulse rate and blood pressure)
Changes from baseline in laboratory tests (haematology, clinical chemistry and urinalysis)
Changes from baseline in physical examination
Changes from baseline in ECG (Electrocardiogram)
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02172326
Brief Title
Pharmacokinetic Study in Elderly Patients With Chronic Obstructive Bronchitis (COPD)
Official Title
The Pharmacokinetics, Safety and Tolerability of Tiotropium in Elderly COPD Patients (Open Label, Monocenter Study).
Study Type
Interventional
2. Study Status
Record Verification Date
June 2014
Overall Recruitment Status
Completed
Study Start Date
February 1998 (undefined)
Primary Completion Date
September 1998 (Actual)
Study Completion Date
undefined (undefined)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Boehringer Ingelheim
4. Oversight
5. Study Description
Brief Summary
Study to evaluate the pharmacokinetics of tiotropium following 14 days of administration (18µg once per day) in elderly COPD patients.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pulmonary Disease, Chronic Obstructive
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
29 (false)
8. Arms, Groups, and Interventions
Arm Title
Tiotropium inhalation capsules
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Tiotropium inhalation capsules for oral inhalation
Intervention Description
Powder inhalation via HandiHaler®
Primary Outcome Measure Information:
Title
Total area under the plasma drug concentration-time curve (AUC 0-4 h)
Time Frame
pre-dose and 5, 20 min., 1, 2,and 4 hours after dosing on days 1, 7 and 14
Title
Urinary excretion of tiotropium (Ae(0-4 hours))
Time Frame
screening and on days 1, 7, 14, 15, 16, 20, 24, 28, 31, 35, 38
Title
Renal clearance of tiotropium (CLren)
Time Frame
screening and on days 1, 7, 14, 15, 16, 20, 24, 28, 31, 35, 38
Title
Terminal elimination half-life after the last dose
Time Frame
pre dose and 5, 20 min., 1, 2,and 4 hours after dosing on days 1, 7 and 14
Secondary Outcome Measure Information:
Title
Plasma concentration of drug 5 min after inhalation (C5min)
Time Frame
pre dose and 5, 20 min., 1, 2,and 4 hours after dosing on days 1, 7 and 14
Title
tmax (time of occurrence for maximum drug concentration)
Time Frame
pre dose and 5, 20 min., 1, 2,and 4 hours after dosing on days 1, 7 and 14
Title
Change from baseline in FEV1 (Forced expiratory volume in one second)
Time Frame
Baseline, Days 1, 7 and 14
Title
Change from baseline in FVC (Forced vital capacity)
Time Frame
Baseline, Days 1, 7 and 14
Title
FEV1/FVC
Time Frame
Baseline, Days 1, 7 and 14
Title
Symptom evaluation
Time Frame
2 weeks
Title
Use of salbutamol
Time Frame
2 weeks
Title
Occurrence of Adverse Events
Time Frame
up to day 39
Title
Occurrence of Adverse Events
Time Frame
up to day 38
Title
Changes form baseline in vital signs (pulse rate and blood pressure)
Time Frame
up to day 38
Title
Changes from baseline in laboratory tests (haematology, clinical chemistry and urinalysis)
Time Frame
baseline, day 38
Title
Changes from baseline in physical examination
Time Frame
baseline, day 38
Title
Changes from baseline in ECG (Electrocardiogram)
Time Frame
baseline, day 1, 7, 14 and 38
10. Eligibility
Sex
All
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
All patients were required to have a diagnosis of COPD and to meet the following spirometric criteria:
Relatively stable, moderate to severe airway obstruction with an FEV1 ≤ 65% of predicted normal and FEV1/FVC ≤ 70%
Patients were required to have normal renal clearance. Renal clearance will be evaluated by the determination of creatinine clearance. To qualify for this trial, the patient's measured creatinine clearance was required to be within 20% of the calculated creatinine clearance, as given by the following equations:
Males: Calculated Creatinine Clearance (ml/min) = [140 - Age (yrs)] x weight(kg) / 72 x serum creatinine (mg/dL)
Females: Calculated Creatinine Clearance (ml/min) = [140 - Age (yrs)] x weight (kg) / 85 x serum creatinine (mg/dL)
Both male or female patients were eligible. Twelve patients ≥ 70 years old and twelve patients ≤ 50 years
Patients were required to have a smoking history of more than ten pack-years, where a pack-year was defined as the equivalent of smoking one pack of cigarettes per day for a year
Patients must be able to perform all specified procedures and maintain records during the study period as required in the protocol
Patients were required to be able to inhale medication from the HandiHaler®
Patients were required to sign an Informed Consent Form prior to participation in the trial, including any necessary prior to pre-study washout of their usual pulmonary medications
Exclusion Criteria:
Patients with significant diseases other than COPD were excluded from participation in the trial. A significant disease was defined as a disease which in the opinion of the investigator may either have put the patient at risk because of participation in the trial or a disease which may have influenced the results of the trial or the patient's ability to participate in the trial;
Patients with clinically significant abnormal baseline haematology, blood chemistry or urinalysis, if the abnormality defined a disease listed as an exclusion criterion;
Patients with alanine transaminase (ALT/SGOT) > 80 IU/L or aspartate transaminase (AST/SGPT) > 80 IU/L, or bilirubin > 2.0 mg/dL or creatinine > 2.0 mg/dL were excluded from participation in the trial, regardless of the patient's clinical condition. Repeat laboratory evaluations were not conducted in these patients;
Patients with a recent history (i.e., one year or less) of myocardial infarction (MI);
Patients with a recent history (i.e., three years or less) of heart failure or patients with any cardiac arrhythmia requiring drug therapy;
Patients with regular use of daytime oxygen therapy;
Patients with known active tuberculosis;
Patients with a history of cancer within the last five years. However, patients with treated basal cell carcinoma are allowed to participate;
Patients with a history of life-threatening pulmonary obstruction, or a history of cystic fibrosis or bronchiectasis;
Patients who had undergone thoracotomy with pulmonary resection. Patients with a history of a thoracotomy for other reasons were evaluated as per exclusion criterion # 1;
Patients who had developed an upper respiratory tract infection in six weeks prior to the Screening Visit (Visit 1) or during the baseline period;
Patients with known hypersensitivity to anticholinergic drugs, lactose or any other components of the inhalation capsule delivery system;
Patients with known symptomatic prostatic hypertrophy or bladder neck obstruction;
Patients with known narrow-angle glaucoma;
Patients treated with cromolyn sodium or nedocromil sodium;
Patients treated with antihistamines (H1 receptor antagonists);
Patients using oral corticosteroid medication at unstable doses (i.e. less than six weeks on a stable dose) or at a dose in excess of the equivalent of 10 mg of prednisone per day (or 20 mg every other day);
Pregnant or nursing women or women of childbearing potential not using a medically approved means of contraception (i.e. oral contraceptives, intrauterine devices, diaphragm or Norplant®);
Patients with a history of asthma, allergic rhinitis or atopy or patients with a total blood eosinophil count ≥ 600/mm3. A repeat eosinophil count was not conducted in these patients;
Patients with history and/or active alcohol or drug abuse.
Patients who had taken an investigational drug within one month or six half lives (whichever was greater) prior to Screening Visit (Visit 1).
12. IPD Sharing Statement
Links:
URL
http://trials.boehringer-ingelheim.com/content/dam/internet/opu/clinicaltrial/com_EN/results/205/205.133_U00-3029.pdf
Description
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Pharmacokinetic Study in Elderly Patients With Chronic Obstructive Bronchitis (COPD)
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