First-in-human Study to Assess the Safety and Pharmacokinetics of LML134 in Healthy Volunteers (LML134)
2016年10月26日 更新者：Novartis Pharmaceuticals
A First-in-human, Randomized, Double-blind, Placebo-controlled, Single and Multiple Ascending Oral Dose Study, to Assess the Safety, Tolerability and Pharmacokinetics of LML134 in Healthy Volunteers
Phase I study to assess the safety, tolerability and pharmacokinetics of ascending single and multiple doses of the investigational medicinal product in healthy volunteers
研究概览
研究类型
介入性
注册 (实际的)
133
阶段
- 阶段1
联系人和位置
本节提供了进行研究的人员的详细联系信息，以及有关进行该研究的地点的信息。
学习地点
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Berlin、德国、14050
- Novartis Investigative Site
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参与标准
研究人员寻找符合特定描述的人，称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。
资格标准
适合学习的年龄
18年 至 55年 (成人)
接受健康志愿者
不
有资格学习的性别
全部
描述
Inclusion Criteria:
- Healthy male and female subjects age 18 to 55 years of age included, and in good health as determined by medical history, physical examination, vital signs, electrocardiogram, and laboratory tests.
- Written informed consent must be obtained before any assessment is performed.
- Able to communicate well with the Investigator, to understand and comply with the requirements of the study.
Exclusion Criteria:
- History or presence of epilepsy or of seizures or convulsions of any kind.
- Any clinically relevant abnormalities identified in the resting EEG during screening, or pre-ictal signs or other clinically relevant abnormalities in the hyperventilation or intermittent photic stimulation EEG during screening.
- History of head trauma leading to clinically significant symptoms in the past two years.
- Applies only to subjects enrolled in Part 2 MAD. Score "yes" on item 4 or item 5 of the Suicidal Ideation section of the C-SSRS, if this ideation occurred in the past 6 months, or "yes" on any item of the Suicidal Behavior section, except for the "Non-Suicidal Self-Injurious Behavior" (item also included in the Suicidal Behavior section), if this behavior occurred in the past 2 years.
- Significant illness including any clinically significant infectious disease which has not resolved within two (2) weeks prior to initial dosing.
- History or presence of significant hematological abnormalities or immunodeficiency or any condition that might compromise the immune system (infection, vaccination), of any etiology as indicated by clinically significantly abnormal values of any of the following hematologic parameters: thrombocyte, RBC count, total WBC count and differentials presented as % of total white blood cell count and as absolute concentrations.
- History or presence of any thyroid disease as indicated by any clinically relevant abnormality on thyroid stimulating hormone test (TSH).
- History or presence of any chronic eye disease other than refractive error, strabismic amblyopia, or anisometropic amblyopia.
- Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant.
学习计划
本节提供研究计划的详细信息，包括研究的设计方式和研究的衡量标准。
研究是如何设计的？
设计细节
- 主要用途：治疗
- 介入模型：并行分配
- 屏蔽：四人间
武器和干预
参与者组/臂 |
干预/治疗 |
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实验性的：Single dose study part
there will be 8 cohorts of healthy volunteers dosed with single doses of LML134 (8 planned dose levels) or with placebo and 2 potential additional cohorts (also dosed with single dose of LML134 or placebo)
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LML134 will be administered first as single doses and then as multiple doses
All study cohorts (except food effect cohort) are placebo controlled
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实验性的：Multiple dose study part
there will be 3 cohorts of healthy volunteers dosed with multiple doses of LML134 (3 planned dose levels) or placebo and one potential additional cohort (also dosed with multiple doses of LML134 or placebo)
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LML134 will be administered first as single doses and then as multiple doses
All study cohorts (except food effect cohort) are placebo controlled
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研究衡量的是什么？
主要结果指标
结果测量 |
措施说明 |
大体时间 |
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基线时单次和多次递增剂量给药后的不良事件评估，并反复进行直至研究完成
大体时间：从给药前约 24 小时开始，一直持续到最后一次给药后约 7-14 天
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该安全性结果结合了对经历不良事件 (AE) 的受试者数量、这些 AE 的性质和严重程度及其与研究治疗的关系的衡量。
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从给药前约 24 小时开始，一直持续到最后一次给药后约 7-14 天
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Cardiovascular safety assessments after single and multiple ascending dose administration at baseline and repeatedly until study completion
大体时间：Starting about 24 hours before dosing and continued until about 7-14 days after last dose
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This safety outcome combines the measure of a set of cardiovascular safety parameters extracted from ECGs, 25 hours-Holter ECGs and from vital signs assessments
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Starting about 24 hours before dosing and continued until about 7-14 days after last dose
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Central nervous system safety assessments after single and multiple ascending dose administration at baseline and repeatedly until study completion
大体时间：Starting about 24 hours before dosing and continued until about 7-14 days after last dose
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This safety outcome combines the measure of a set of central nervous system safety parameters extracted from EEGs and neurological examinations
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Starting about 24 hours before dosing and continued until about 7-14 days after last dose
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Ocular safety assessments after single and multiple ascending dose administration at baseline and repeatedly until study completion
大体时间：Starting about 24 hours before dosing and continued until about 7-14 days after last dose
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This safety outcome combined the measure of a set of ocular parameters including best corrected visual acuity and other parameters assessed by the mean of slit lamp biomicroscopy and dilated ophthalmoscopy examinations and by optical coherence tomography and electroretinography
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Starting about 24 hours before dosing and continued until about 7-14 days after last dose
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General safety assessments after single and multiple ascending dose administration at baseline and repeatedly until study completion
大体时间：Starting about 24 hours before dosing and continued until about 7-14 days after last dose
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This general safety outcome combines the measure of blood laboratory parameters and the outcome of physical examinations
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Starting about 24 hours before dosing and continued until about 7-14 days after last dose
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次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
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Pharmacokinetics (PK) of LML134: time to reach the maximum concentration after a single drug administration (Tmax) in Part 1 and in Part 3
大体时间：Starting 1hour prior to dosing on Day 1 and until 72 hours after dosing (Day 4)
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Serum samples will be collected on Day 1: 1hr predose; 0,25h; 0,5h; 1h; 1,5h; 2h; 3h; 4h; 6h; 8h; 12h; 16h post dose, on Day 2: 24h and 36h post dose, on Day 3: 48h and 60h post dose and on Day 4: 72h post dose. This outcome measure shows the mean of all subject values resulting from each time point specified above, in Parts 1 and 3. In Part 3, the outcome measure is done once without food intake and once after the intake of a high fat breakfast (in 2 different periods). Both outcomes (with and without breakfast intake) will be compared to assess the effect of a high fast breakfast on LML134 Tmax |
Starting 1hour prior to dosing on Day 1 and until 72 hours after dosing (Day 4)
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PK of LML134: Observed maximum serum concentration following single drug administration (Cmax) in Part 1 and Part 3
大体时间：Starting 1hour prior to dosing on Day 1 and until 72 hours after dosing (Day 4)
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Serum samples will be collected on Day 1: 1hr predose; 0,25h; 0,5h; 1h; 1,5h; 2h; 3h; 4h; 6h; 8h; 12h; 16h post dose, on Day 2: 24h and 36h post dose, on Day 3: 48h and 60h post dose and on Day 4: 72h post dose. This outcome measure shows the mean of all subject values resulting from each time point specified above, in Parts 1 and 3. In Part 3, the outcome measure is done once without food intake and once after the intake of a high fat breakfast (in 2 different periods). Both outcomes (with and without breakfast intake) will be compared to assess the effect of a high fast breakfast on LML134 Cmax. |
Starting 1hour prior to dosing on Day 1 and until 72 hours after dosing (Day 4)
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PK of LML134: Area under the serum concentration-time curve from time zero to the time of last quantifiable concentration (AUClast) in Part 1 and Part 3
大体时间：Starting 1hour prior to dosing on Day 1 and until 72 hours after dosing (Day 4)
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Serum samples will be collected on Day 1: 1hr predose; 0,25h; 0,5h; 1h; 1,5h; 2h; 3h; 4h; 6h; 8h; 12h; 16h post dose, on Day 2: 24h and 36h post dose, on Day 3: 48h and 60h post dose and on Day 4: 72h post dose.
This outcome measure shows the mean of all subject values resulting from each time point specified above, in Parts 1 and 3.
In Part 3, the outcome measure is done once without food intake and once after the intake of a high fat breakfast (in 2 different periods).
Both outcomes (with and without breakfast intake) will be compared to assess the effect of a high fast breakfast on LML134 AUClast.
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Starting 1hour prior to dosing on Day 1 and until 72 hours after dosing (Day 4)
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PK of LML134: time to reach the maximum concentration after the first drug administration (Tmax) in Part 2
大体时间：Starting 1hour prior the first dose administration (Day 1) until 24hr after the first dose administration on Day 2
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Serum samples will be collected on Day 1: 1hr predose; 0,25h; 0,5h; 1h; 1,5h; 2h; 3h; 4h; 6h; 8h; 12h; 16h post dose and on Day 2: 24h post dose.
This outcome measure shows the mean of all subject values resulting from each time point specified above.
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Starting 1hour prior the first dose administration (Day 1) until 24hr after the first dose administration on Day 2
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PK of LML134: time to reach the maximum concentration after the last drug administration (Tmax) in Part 2
大体时间：Starting 1hour prior the first dose administration (Day 1) until 48hour after the last dose administration (Day 17)
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Serum samples will be collected on Day 1: 1hr predose; 0,25h; 0,5h; 1h; 1,5h; 2h; 3h; 4h; 6h; 8h; 12h; 16h post dose, on Day 2: 24h post dose, on Day 3: 1hr prior the second dose administration, on Days 4, 5, 6, 8, 10, 12, 13, 14: 1hr prior dosing, on Day 15 (last time the drug is administered): 1hr predose; 0,25h; 0,5h; 1h; 1,5h; 2h; 3h; 4h; 6h; 8h; 12h; 16h post dose, on Day 16: 24h post dose and Day 17: 48h post dose.
This outcome measure shows the mean of all subject values resulting from each time point specified above.
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Starting 1hour prior the first dose administration (Day 1) until 48hour after the last dose administration (Day 17)
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PK of LML134: Observed maximum serum concentration following the first drug administration (Cmax) in Part 2
大体时间：Starting 1hour prior the first dose administration (Day 1) until 24hr after the first dose administration on Day 2
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Serum samples will be collected on Day 1: 1hr predose; 0,25h; 0,5h; 1h; 1,5h; 2h; 3h; 4h; 6h; 8h; 12h; 16h post dose and on Day 2: 24h post dose.
This outcome measure shows the mean of all subject values resulting from each time point specified above.
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Starting 1hour prior the first dose administration (Day 1) until 24hr after the first dose administration on Day 2
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PK of LML134: Observed maximum serum concentration following drug administration at steady state (Cmax,ss) in Part 2
大体时间：Starting 1hour prior the first dose administration (Day 1) until 48hour after the last dose administration (Day 17)
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Serum samples will be collected on Day 1: 1hr predose; 0,25h; 0,5h; 1h; 1,5h; 2h; 3h; 4h; 6h; 8h; 12h; 16h post dose, on Day 2: 24h post dose, on Day 3: 1hr prior the second dose administration, on Days 4, 5, 6, 8, 10, 12, 13, 14: 1hr prior dosing, on Day 15 (last time the drug is administered): 1hr predose; 0,25h; 0,5h; 1h; 1,5h; 2h; 3h; 4h; 6h; 8h; 12h; 16h post dose, on Day 16: 24h post dose and Day 17: 48h post dose.
This outcome measure shows the mean of all subject values resulting from each time point specified above.
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Starting 1hour prior the first dose administration (Day 1) until 48hour after the last dose administration (Day 17)
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PK of LML134: Area under the serum concentration-time curve from time zero to the time of last quantifiable concentration (AUClast) after the first dose administration in Part 2
大体时间：Starting 1hour prior the first dose administration (Day 1) until 24hr after the first dose administration on Day 2
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Serum samples will be collected on Day 1: 1hr predose; 0,25h; 0,5h; 1h; 1,5h; 2h; 3h; 4h; 6h; 8h; 12h; 16h post dose and on Day 2: 24h post dose.
This outcome measure shows the mean of all subject values resulting from each time point specified above.
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Starting 1hour prior the first dose administration (Day 1) until 24hr after the first dose administration on Day 2
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PK of LML134: The area under the serum concentration-time curve from time zero to the end of the dosing interval tau at steady state (AUCtau,ss) in Part 2
大体时间：Starting 1hour prior the first dose administration (Day 1) until 48hour after the last dose administration (Day 17)
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Serum samples will be collected on Day 1: 1hr predose; 0,25h; 0,5h; 1h; 1,5h; 2h; 3h; 4h; 6h; 8h; 12h; 16h post dose, on Day 2: 24h post dose, on Day 3: 1hr prior the second dose administration, on Days 4, 5, 6, 8, 10, 12, 13, 14: 1hr prior dosing, on Day 15 (last time the drug is administered): 1hr predose; 0,25h; 0,5h; 1h; 1,5h; 2h; 3h; 4h; 6h; 8h; 12h; 16h post dose, on Day 16: 24h post dose and Day 17: 48h post dose.
This outcome measure shows the mean of all subject values resulting from each time point specified above.
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Starting 1hour prior the first dose administration (Day 1) until 48hour after the last dose administration (Day 17)
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PK of LML134: The average steady state serum concentration during multiple dosing (Cav,ss) in Part 2
大体时间：Starting 1hour prior the first dose administration (Day 1) until 48hour after the last dose administration (Day 17)
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Serum samples will be collected on Day 1: 1hr predose; 0,25h; 0,5h; 1h; 1,5h; 2h; 3h; 4h; 6h; 8h; 12h; 16h post dose, on Day 2: 24h post dose, on Day 3: 1hr prior the second dose administration, on Days 4, 5, 6, 8, 10, 12, 13, 14: 1hr prior dosing, on Day 15 (last time the drug is administered): 1hr predose; 0,25h; 0,5h; 1h; 1,5h; 2h; 3h; 4h; 6h; 8h; 12h; 16h post dose, on Day 16: 24h post dose and Day 17: 48h post dose.
This outcome measure shows the mean of all subject values resulting from each time point specified above.
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Starting 1hour prior the first dose administration (Day 1) until 48hour after the last dose administration (Day 17)
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PK of LML134: The effective half-life based on drug accumulation at steady state (T1/2,acc) in Part 2
大体时间：Starting 1hour prior the first dose administration (Day 1) until 48hour after the last dose administration (Day 17)
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Serum samples will be collected on Day 1: 1hr predose; 0,25h; 0,5h; 1h; 1,5h; 2h; 3h; 4h; 6h; 8h; 12h; 16h post dose, on Day 2: 24h post dose, on Day 3: 1hr prior the second dose administration, on Days 4, 5, 6, 8, 10, 12, 13, 14: 1hr prior dosing, on Day 15 (last time the drug is administered): 1hr predose; 0,25h; 0,5h; 1h; 1,5h; 2h; 3h; 4h; 6h; 8h; 12h; 16h post dose, on Day 16: 24h post dose and Day 17: 48h post dose.
This outcome measure shows the mean of all subject values resulting from each time point specified above.
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Starting 1hour prior the first dose administration (Day 1) until 48hour after the last dose administration (Day 17)
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PK of LML134: The accumulation ratio (Racc) in Part 2
大体时间：Starting 1hour prior the first dose administration (Day 1) until 48hour after the last dose administration (Day 17)
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Serum samples will be collected on Day 1: 1hr predose; 0,25h; 0,5h; 1h; 1,5h; 2h; 3h; 4h; 6h; 8h; 12h; 16h post dose, on Day 2: 24h post dose, on Day 3: 1hr prior the second dose administration, on Days 4, 5, 6, 8, 10, 12, 13, 14: 1hr prior dosing, on Day 15 (last time the drug is administered): 1hr predose; 0,25h; 0,5h; 1h; 1,5h; 2h; 3h; 4h; 6h; 8h; 12h; 16h post dose, on Day 16: 24h post dose and Day 17: 48h post dose.
This outcome measure shows the mean of all subject values resulting from each time point specified above.
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Starting 1hour prior the first dose administration (Day 1) until 48hour after the last dose administration (Day 17)
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合作者和调查者
在这里您可以找到参与这项研究的人员和组织。
调查人员
- 研究主任：Study Director、Novartis Pharmceuticals
研究记录日期
这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查，以确保它们在发布到公共网站之前符合特定的质量控制标准。
研究主要日期
学习开始
2015年2月1日
初级完成 (实际的)
2016年2月1日
研究完成 (实际的)
2016年2月1日
研究注册日期
首次提交
2014年11月14日
首先提交符合 QC 标准的
2015年1月6日
首次发布 (估计)
2015年1月8日
研究记录更新
最后更新发布 (估计)
2016年10月27日
上次提交的符合 QC 标准的更新
2016年10月26日
最后验证
2016年10月1日
更多信息
与本研究相关的术语
关键字
其他研究编号
- CLML134X2101
- 2014-000937-22 (EudraCT编号)
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.