Evaluation of the Lung Deposition Rate and Distribution Pattern of Tiotropium Via HandiHalerTM in Healthy Subjects and Patients With Chronic Obstructive Pulmonary Disease (COPD)
γ-Scintigraphic Evaluation of the Lung Deposition Rate and Distribution Pattern of a 99mTc-Labelled Tiotropium Powder Formulation Following Multiple Dose Inhalation of Tiotropium Via HandiHalerTM in Healthy Subjects and Patients With COPD
Primary endpoint: whole lung deposition and in-vivo distribution pattern of a 99mTc-labelled tiotropium powder formulation following inhalation via HandiHalerTM in healthy subjects as well as in patients with mild, moderate and severe COPD
Secondary endpoints: pharmacokinetics, pharmacodynamics (effect on lung function), safety and tolerability
研究概览
研究类型
注册 (实际的)
阶段
- 第三阶段
参与标准
资格标准
适合学习的年龄
接受健康志愿者
有资格学习的性别
描述
Inclusion Criteria:
for healthy subjects and COPD patients:
- Males or females 40 years of age or older.
- Subjects/Patients must be able to inhale medication from the HandiHalerTM
- Subjects/Patients must be able to perform all study-related tests including acceptable pulmonary function tests, and must be able to maintain records during the study period as required in the protocol.
- All subjects/patients must sign an Informed Consent Form prior to participation in the trial in accordance with ICH-GCP and the local legislation, i.e., the COPD patients must give written informed consent prior to pre-study washout of their usual pulmonary medications.
for healthy subjects:
- Normal spirometry as evidenced by a baseline FEV1 ≥ 80 % of predicted normal value for age, height and sex, and FEV1 ≥ 70% of FVC
- Lifelong non-smokers or ex-smokers with a non-smoking period of at least five years and a maximum of five pack-years.
for COPD patients:
All patients must have a diagnosis of relatively stable chronic obstructive pulmonary disease and must fulfil the spirometric criteria of the respective sub-group:
- Mild COPD: 50% ≤ FEV1 < 70% of predicted normal; FEV1/FVC < 70%.
- Moderate COPD: 35% ≤ FEV1 < 50% of predicted normal; FEV1/FVC < 70%.
- Severe COPD: FEV1 < 35% of predicted normal; FEV1/FVC < 70%.
Exclusion Criteria:
for healthy subjects and COPD patients:
- Subjects or patients with clinically relevant abnormal baseline haematology, blood chemistry or urinalysis, if the abnormality defines a disease listed as an exclusion criterion will be excluded.
- All subjects/patients with serum glutamic-oxaloacetic transaminase (SGOT) > 80 IU/L, serum glutamic-pyruvic transaminase (SGPT) > 80 IU/L, bilirubin >2.0 mg/dL or creatinine > 2.0 mg/dL will be excluded regardless of clinical condition. Repeat laboratory evaluation will not be conducted in these subjects/patients.
- Subjects/Patients with a recent history (i.e., one year or less) of myocardial infarction.
- Subjects/Patients with any cardiac arrhythmia requiring drug therapy or who have been hospitalised for heart failure within the past three years.
- Subjects/Patients with known active tuberculosis.
- Subjects/Patients with a history of cancer within the last five years.
- Subjects/Patients with a history of life-threatening pulmonary obstruction, or a history of cystic fibrosis or bronchiectasis.
- Subjects/Patients who have undergone thoracotomy with pulmonary resection.
- Patients with any upper respiratory infection in the past six weeks prior to the Screening Visit (Visit 1) or during the run-in period
- Subjects/Patients with known hypersensitivity to anticholinergic drugs, lactose or any other components of the inhalation capsule delivery system
- Subjects/Patients with known symptomatic prostatic hyperplasia or bladder neck obstruction.
- Subjects/Patients with known narrow-angle glaucoma.
- Subjects/Patients with a history of asthma, allergic rhinitis or atopy or who have a total blood eosinophil count ≥ 600 mm3. A repeat eosinophil count will not be conducted in these subjects/patients.
- Subjects/Patients with a history of and/or active significant alcohol or drug abuse.
- Subjects/Patients who have taken an investigational drug within one month or six half lives (whichever is shorter) prior to Screening Visit (Visit 1).
In addition, for female subjects/patients:
- Pregnancy.
- Positive pregnancy test.
- No adequate contraception, e.g. oral contraceptives, sterilisation, intra uterine device (IUD).
- Inability to maintain this adequate contraception during the whole study period.
- Lactation period.
for healthy subjects:
- Subjects with any significant disease will be excluded. A significant disease is defined as a disease which in the opinion of the investigator may either put the subject at risk because of participation in the study or a disease which may influence the results of the study or the subject's ability to participate in the study.
- Use of any drugs which might influence the results of the trial (within one week prior to administration or during the trial).
for COPD patients:
- Patients with significant diseases other than COPD will be excluded. A significant disease is defined as a disease which in the opinion of the investigator may either put the patient at risk because of participation in the study or a disease which may influence the results of the study or the patient's ability to participate in the study.
- COPD patients who regularly use daytime oxygen therapy for more than one hour per day and in the investigator's opinion will be unable to abstain from the use of oxygen therapy.
- Patients who are currently in a pulmonary rehabilitation programme or who have completed a pulmonary rehabilitation programme in the six week prior to the Screening Visit (Visit 1)
- Patients who are being treated with oral beta adrenergics or long-acting beta adrenergics such as salmeterol and formoterol.
- Patients who are being treated with beta blockers.
- Patients who are being treated with antileukotrienes.
- Patients who are being treated with cromolyn sodium or nedocromil sodium.
- Patients who are being treated with antihistamines (H1-receptor antagonists).
- Patients using oral corticosteroid medication at unstable doses (i.e., less than four weeks on a stable dose) or at doses in excess of the equivalent of 10 mg of prednisolone per day or 20 mg every other day.
- Patients who are being treated with monoamine oxidase inhibitors or tricyclic antidepressants.
- Patients with no adequate wash-out period of those medications specified in Section 4.2.2 of the study protocol.
学习计划
研究是如何设计的?
设计细节
- 主要用途:治疗
- 分配:不适用
- 介入模型:单组作业
- 屏蔽:无(打开标签)
武器和干预
参与者组/臂 |
干预/治疗 |
---|---|
实验性的:噻托溴铵
|
研究衡量的是什么?
主要结果指标
结果测量 |
大体时间 |
---|---|
Percentage of the total administered radioactivity of 99mTc-labelled tiotropium
大体时间:Day 15
|
Day 15
|
次要结果测量
结果测量 |
大体时间 |
---|---|
Peak plasma concentration at steady state (Cmax,ss)
大体时间:Day 14
|
Day 14
|
Time to peak plasma concentration at steady state (Tmax,ss)
大体时间:Day 14
|
Day 14
|
Pre-dose plasma concentration (Cpre)
大体时间:Day 1
|
Day 1
|
Area under the curve from 0 to 4 hours at steady state (AUCss,0-4h )
大体时间:Day 14: 5, 10, 20 min, 1, 2, 4 hours after dosing
|
Day 14: 5, 10, 20 min, 1, 2, 4 hours after dosing
|
Renal clearance (CLr)
大体时间:Day 14: 0-4 hours and 4-8 hours after drug administration
|
Day 14: 0-4 hours and 4-8 hours after drug administration
|
Drug concentration (C20min)
大体时间:Day 15: 20 min after drug administration
|
Day 15: 20 min after drug administration
|
Drug concentration (C2h)
大体时间:Day 15: 2 hours after drug administration
|
Day 15: 2 hours after drug administration
|
Change from baseline in forced expiratory volume in the first second (FEV1) in healthy subjects
大体时间:Baseline (day -14), day 15 (pre-dose)
|
Baseline (day -14), day 15 (pre-dose)
|
Change from baseline in forced Vital Capacity (FVC) in healthy subjects
大体时间:Baseline (day -14), day 15 (pre-dose)
|
Baseline (day -14), day 15 (pre-dose)
|
Number of adverse events
大体时间:up to day 38
|
up to day 38
|
Change from baseline in puls rate
大体时间:Baseline, day 28
|
Baseline, day 28
|
Change from baseline in blood pressure
大体时间:Baseline, day 28
|
Baseline, day 28
|
Change from baseline in laboratory tests
大体时间:Baseline, day 28
|
Baseline, day 28
|
Change from baseline in 12 lead electrocardiogram (ECG)
大体时间:Baseline, day 28
|
Baseline, day 28
|
Change from baseline in physical examination
大体时间:Baseline, day 28
|
Baseline, day 28
|
Change from baseline in forced expiratory volume in the first second (FEV1) in COPD patients
大体时间:Baseline (day -14), pre-dose on day 1, 9, 14 (pre-dose and 0.5, 1, 2, and 3 hours after dosing), 15 and 28
|
Baseline (day -14), pre-dose on day 1, 9, 14 (pre-dose and 0.5, 1, 2, and 3 hours after dosing), 15 and 28
|
Change from baseline in forced Vital Capacity (FVC) in COPD patients
大体时间:Baseline (day -14), pre-dose on day 1, 9, 14 (pre-dose and 0.5, 1, 2, and 3 hours after dosing), 15 and 28
|
Baseline (day -14), pre-dose on day 1, 9, 14 (pre-dose and 0.5, 1, 2, and 3 hours after dosing), 15 and 28
|
Pre-dose plasma concentration in steady state (Cpre,ss)
大体时间:day 9, 14, 15
|
day 9, 14, 15
|
Area under the curve from 0 to 8 hours at steady state (AUCss,0-8h )
大体时间:Day 14: 5, 10, 20 min, 1, 2, 4, 8 hours after dosing
|
Day 14: 5, 10, 20 min, 1, 2, 4, 8 hours after dosing
|
Amount excreted into urine from 0 to 4 hours (Aess,0-4h)
大体时间:Day 14: 0-4 hours, day 15: 0-4 hours
|
Day 14: 0-4 hours, day 15: 0-4 hours
|
Amount excreted into urine from 0 to 8 hours (Aess,0-8h)
大体时间:Day 14: 0-8 hours, day 15: 0-8 hours
|
Day 14: 0-8 hours, day 15: 0-8 hours
|
合作者和调查者
出版物和有用的链接
有用的网址
研究记录日期
研究主要日期
学习开始
初级完成 (实际的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (估计)
研究记录更新
最后更新发布 (估计)
上次提交的符合 QC 标准的更新
最后验证
更多信息
此信息直接从 clinicaltrials.gov 网站检索,没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求,请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改,我们的网站上也会自动更新.
99mTc-radiolabelled tiotropium的临床试验
-
Molecular Insight Pharmaceuticals, Inc.完全的
-
British Columbia Cancer AgencyCanadian Institutes of Health Research (CIHR); Lawson Health Research Institute; Centre for Probe... 和其他合作者完全的
-
Peking UniversitySun Yat-sen University; China-Japan Union Hospital, Jilin University完全的
-
Tomsk National Research Medical Center of the Russian...Uppsala University完全的
-
Tomsk National Research Medical Center of the Russian...Uppsala University完全的
-
Mayo Clinic招聘中
-
Fifth Affiliated Hospital, Sun Yat-Sen UniversityPeking University未知