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
調査の概要
研究の種類
介入
入学 (実際)
133
段階
- フェーズ 1
連絡先と場所
このセクションには、調査を実施する担当者の連絡先の詳細と、この調査が実施されている場所に関する情報が記載されています。
研究場所
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Berlin、ドイツ、14050
- Novartis Investigative Site
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参加基準
研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。
適格基準
就学可能な年齢
18年～55年 (大人)
健康ボランティアの受け入れ
いいえ
受講資格のある性別
全て
説明
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.
研究計画
このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：処理
- 介入モデル：並列代入
- マスキング：4倍
武器と介入
参加者グループ / アーム |
介入・治療 |
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実験的：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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実験的：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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この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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ベースラインでの単回および複数回の漸増用量投与後の有害事象の評価および研究完了までの反復投与
時間枠：投与の約24時間前に開始し、最後の投与後約7～14日まで継続
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この安全性の結果は、有害事象（AE）を経験した被験者の数の尺度、それらのAEの性質と重症度、および試験治療との関係を組み合わせたものです。
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投与の約24時間前に開始し、最後の投与後約7～14日まで継続
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Cardiovascular safety assessments after single and multiple ascending dose administration at baseline and repeatedly until study completion
時間枠：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
時間枠：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
時間枠：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
時間枠：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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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
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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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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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協力者と研究者
ここでは、この調査に関係する人々や組織を見つけることができます。
スポンサー
捜査官
- スタディディレクター：Study Director、Novartis Pharmceuticals
研究記録日
これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。
主要日程の研究
研究開始
2015年2月1日
一次修了 (実際)
2016年2月1日
研究の完了 (実際)
2016年2月1日
試験登録日
最初に提出
2014年11月14日
QC基準を満たした最初の提出物
2015年1月6日
最初の投稿 (見積もり)
2015年1月8日
学習記録の更新
投稿された最後の更新 (見積もり)
2016年10月27日
QC基準を満たした最後の更新が送信されました
2016年10月26日
最終確認日
2016年10月1日
詳しくは
本研究に関する用語
キーワード
その他の研究ID番号
- CLML134X2101
- 2014-000937-22 (EudraCT番号)
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