A Study to Investigate Safety and Tolerability, Pharmacokinetics and Pharmacodynamics of JNJ-64140284 in Healthy Participants
A 3-Part, Randomized, Placebo-controlled, Double-blind, Single Ascending Dose Study to Investigate Safety and Tolerability, Pharmacokinetics and Pharmacodynamics of JNJ-64140284 in Healthy Subjects
調査の概要
状態
状態
条件
条件
介入・治療
介入・治療
研究の種類
研究の種類
入学 (実際)
入学
段階
段階
- フェーズ 1
連絡先と場所
研究場所
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Merksem、ベルギー、2170
- Clinical Pharmacology Unit
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参加基準
適格基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
説明
Inclusion Criteria:
Part 1 and 2:
- Healthy male participants between 18 and 58 years of age, inclusive
Part 1, 2 and 3:
- Participants must be healthy on the basis of clinical laboratory tests performed at screening. If the results of the serum chemistry panel, hematology, or urinalysis are outside the normal reference ranges, retesting of an abnormal lab value(s) that may lead to exclusion will be allowed once during the screening phase. The participant may be included only if the investigator judges the abnormalities or deviations from normal to be not clinically significant or to be appropriate and reasonable for the population under study according to both the investigator and to the Janssen Safety Physician, are acceptable
Part 3:
- Healthy male and female participants between 59 and 75 years of age, inclusive
- Participants must be healthy and medically stable on the basis of clinical laboratory tests (at screening) and physical and neurological examination (at screening and at admission to the clinical unit). If the participant is medically stable with medication, inclusion can be allowed on a case by case basis with written agreement of the sponsor's responsible safety physician
- Women must not be of childbearing potential (must be postmenopausal with amenorrhea for at least 12 months) or permanently sterilized (for example, tubal occlusion, hysterectomy, bilateral salpingectomy)
Exclusion Criteria:
Part 1, 2 and 3:
- Participants with a history of or current significant medical illness including (but not limited to) cardiac arrhythmias or other cardiac disease, hematological disease, lipid abnormalities, bronchospastic respiratory disease, diabetes mellitus, renal or hepatic insufficiency, thyroid disease, Parkinson's disease, infection, or any other illness that the Investigator considers should exclude the participant
- Participants with a serology positive for hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibodies or human immunodeficiency virus (HIV) antibodies
- Participants with a clinically significant acute illness within 7 days prior to study drug administration
- Donation of 1 or more units (approximately 450 milliliter [mL]) of blood or acute loss of an equivalent amount of blood within 90 days prior to study drug administration
Part 3:
- participants having a contraindication for spinal puncture including:
- A relevant history of lower back pain or scoliosis or kyphosis and/or major (lumbar) back surgery (microdiscectomy is allowed) in the opinion of the investigator
- Allergy to local anesthetics and/or iodine/disinfectants
- Clinically significant abnormal values for coagulation at screening
- Use of aspirin (even low dose) within 5 days prior to lumbar puncture
- Use of low molecular weight heparin (LMWH) within 12 hours prior to lumbar puncture
- Use of any anticoagulant treatment (besides LMWH described above) within 1 week prior to lumbar puncture
- Has a topical infection or local dermatological condition at the puncture site prior to puncture
- Has papilloedema or signs of increased intracranial pressure based on fundoscopy at screening
研究計画
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:他の
- 割り当て:ランダム化
- 介入モデル:並列代入
- マスキング:ダブル
アーム数
武器と介入
参加者グループ / アーム参加者グループ / アーム |
介入・治療介入・治療 |
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実験的:Part 1: Cohort 1 (JNJ-64140284 or Placebo)
Participants will receive 0.1 milligram (mg) JNJ-64140284 or matching placebo under fasted condition on Day 1.
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一致するプラセボが投与されます。
0.1 mg of JNJ-64140284 will be administered as an oral solution.
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実験的:Part 1: Cohort 2 (JNJ-64140284 or Placebo)
Participants will receive 0.5 mg JNJ-64140284 or matching placebo under fasted condition on Day 1.
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一致するプラセボが投与されます。
0.5 mg of JNJ-64140284 will be administered as an oral solution.
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実験的:Part 1: Cohort 3 (JNJ-64140284 or Placebo)
Participants will receive 2.5 mg JNJ-64140284 or matching placebo under fasted condition on Day 1.
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一致するプラセボが投与されます。
2.5 mg of JNJ-64140284 will be administered as an oral solution.
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実験的:Part 1: Cohort 4 (JNJ-64140284 or Placebo)
Participants will receive 10 mg JNJ-64140284 or matching placebo under fasted condition on Day 1.
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一致するプラセボが投与されます。
10 mg of JNJ-64140284 will be administered as an oral solution.
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実験的:Part 1: Cohort 5 (JNJ-64140284 or Placebo)
Participants will receive 50 mg JNJ-64140284 or matching placebo under fasted condition on Day 1.
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一致するプラセボが投与されます。
50 mg of JNJ-64140284 will be administered as an oral solution.
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実験的:Part 1: Cohort 6 (JNJ-64140284 or Placebo)
Participants will receive 150 mg JNJ-64140284 or matching placebo under fasted condition on Day 1.
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一致するプラセボが投与されます。
150 mg of JNJ-64140284 will be administered as an oral solution.
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実験的:Part 2: Cohort 7 (JNJ-64140284)
Participants will receive JNJ-64140284 (dose to be determined - the dose of JNJ-64140284 will be determined on the basis of acceptable safety, tolerability and pharmacokinetics [PK] of preceding dose levels; no more than 50 percent (%) of the highest dose tested [though as high as possible within this restriction] and considered well tolerated in Part 1) under fed conditions on Day 1.
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JNJ-64140284 (dose to be determined) will be administered as an oral solution.
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実験的:Part 3: Cohort 8 (JNJ-64140284 or Placebo)
Participants will receive JNJ-64140284 or matching placebo (dose to be determined - dose will be determined based on PK data from previous cohorts and which will be well-tolerated in Part 1) under fasted condition on Day 1.
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一致するプラセボが投与されます。
JNJ-64140284 (dose to be determined) will be administered as an oral solution.
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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
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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Number of Participants With Adverse Events (AEs) as a Measure of Safety and Tolerability: Part 1, Part 2, and Part 3
時間枠:Approximately 40 days
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An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study.
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Approximately 40 days
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Maximum Plasma Concentration (Cmax) of JNJ-64140284: Part 1, Part 2, and Part 3
時間枠:Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 hours post dose
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The Cmax is the maximum observed plasma concentration.
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Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 hours post dose
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Maximum Cerebrospinal Fluid (CSF) Concentration (Cmax) of JNJ-64140284: Part 3
時間枠:Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours post dose
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The Cmax is the maximum observed CSF concentration.
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Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours post dose
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Last Quantifiable Plasma Concentration (Clast) of JNJ-64140284: Part 1, Part 2, and Part 3
時間枠:Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 hours post dose
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The Clast is the last quantifiable plasma concentration.
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Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 hours post dose
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Last Quantifiable CSF Concentration (Clast) of JNJ-64140284: Part 3
時間枠:Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours post dose
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The Clast is the last quantifiable CSF concentration.
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Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours post dose
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Time to Reach Maximum Plasma Concentration (Tmax) of JNJ-64140284: Part 1, Part 2, and Part 3
時間枠:Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 hours post dose
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The Tmax is defined as actual sampling time to reach maximum observed plasma concentration.
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Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 hours post dose
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Time to Reach Maximum CSF Concentration (Tmax) of JNJ-64140284: Part 1, Part 2, and Part 3
時間枠:Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours post dose
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The Tmax is defined as actual sampling time to reach maximum observed CSF concentration.
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Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours post dose
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Time of the Last Quantifiable Plasma Concentration (Tlast) of JNJ-64140284: Part 1, Part 2, and Part 3
時間枠:Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 hours post dose
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The Tlast is defined as the time of the last quantifiable plasma concentration.
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Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 hours post dose
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Time of the Last Quantifiable CSF Concentration (Tlast) of JNJ-64140284: Part 3
時間枠:Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours post dose
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The Tlast is defined as the time of the last quantifiable CSF concentration.
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Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours post dose
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Area Under the Plasma Concentration-Time Curve From Time Zero to Time of the Last Quantifiable Concentration (AUC [0-last]) of JNJ-64140284: Part 1, Part 2, and Part 3
時間枠:Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 hours post dose
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The (AUC [0-last]) is the area under the plasma concentration-time curve from time 0 to time of the last quantifiable concentration.
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Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 hours post dose
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Area Under the CSF Concentration-Time Curve From Time Zero to Time of the Last Quantifiable Concentration (AUC [0-last]) of JNJ-64140284: Part 1, Part 2, and Part 3
時間枠:Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours post dose
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The (AUC [0-last]) is the area under the CSF concentration-time curve from time 0 to time of the last quantifiable concentration.
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Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours post dose
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Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC [0-infinity]) of JNJ-64140284: Part 1, Part 2, and Part 3
時間枠:Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 hours post dose
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The AUC (0-infinity) is the area under the plasma concentration-time curve from time zero to infinite time, calculated as the sum of AUC(0-last) and C(0-last)/lambda(z), wherein AUC(0-last) is the area under the plasma concentration-time curve from time 0 to time of the last quantifiable concentrations; C(0-last) is the last observed quantifiable concentration; and lambda(z) is elimination rate constant.
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Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 hours post dose
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Area Under the CSF Concentration-Time Curve From Time Zero to Infinite Time (AUC [0-infinity]) of JNJ-64140284: Part 3
時間枠:Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours post dose
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The AUC (0-infinity) is the area under the CSF concentration-time curve from time zero to infinite time, calculated as the sum of AUC(0-last) and C(0-last)/lambda(z), wherein AUC(0-last) is the area under the CSF concentration-time curve from time 0 to time of the last quantifiable concentrations; C(0-last) is the last observed quantifiable concentration; and lambda(z) is elimination rate constant.
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Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours post dose
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Elimination Rate Constant (Lambda[z]) of JNJ-64140284: Part 1, Part 2, and Part 3
時間枠:Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 hours post dose
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Lambda(z) is first-order rate constant associated with the terminal portion of the curve, determined as the negative slope of the terminal log-linear phase of the drug concentration-time curve.
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Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 hours post dose
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Elimination Half-life (t1/2) of JNJ-64140284: Part 1, Part 2, and Part 3
時間枠:Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, and 96 hours post dose
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The t1/2 is the time measured for the plasma concentration to decrease by 1 half to its original concentration.
It is associated with the terminal slope of the semi logarithmic drug concentration-time curve, and is calculated as 0.693/lambda(z).
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Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, and 96 hours post dose
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Total Clearance (CL/F) of JNJ-64140284: Part 1, Part 2, and Part 3
時間枠:Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 hours post dose
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CL/F is the total clearance of drug after extravascular administration, uncorrected for absolute bioavailability.
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Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 hours post dose
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Creatinine Clearance (CLcr) of JNJ-64140284: Part 1, Part 2, and Part 3
時間枠:Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 hours post dose
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CLcr will be determined with the Cockcroft-Gault formula.
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Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 hours post dose
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Amount of Drug Excreted in Urine From Time Zero to Infinite Time (Aeinf): Part 1
時間枠:0-1, 1-2, 2-4, 4-12, and 12-24 hours post dose
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Aeinf is the cumulative amount of study drug excreted into urine from time of dosing extrapolated to time infinity.
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0-1, 1-2, 2-4, 4-12, and 12-24 hours post dose
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Renal Clearance (CLr): Part 1
時間枠:0-1, 1-2, 2-4, 4-12, and 12-24 hours post dose
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The CLr is the renal clearance of the drug.
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0-1, 1-2, 2-4, 4-12, and 12-24 hours post dose
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二次結果の測定
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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Bond & Lader Visual Analogue Scale (VAS) Score: Part 1 and Part 3
時間枠:Days -1, 1, 2 and 3
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The VAS is a participant rated scale, made up of 16 (items) pairs of alternative descriptors of mood and attention at either end of a 10 cm line.
The item score ranges from 0 to 100, with a high score reflecting a high level of anxiety, sedation or dysphoria.
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Days -1, 1, 2 and 3
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Karolinska Sleepiness Scale (KSS) Score: Part 1 and Part 3
時間枠:Days -1, 1, 2 and 3
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The KSS is a participant-reported assessment used to rate sleepiness on a scale of 1 to 9, ranging from 'extremely alert' (1) to 'very sleepy, great effort to keep awake, fighting sleep' (9).
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Days -1, 1, 2 and 3
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Profile of Mood States (POMS) Score: Part 1 and Part 3
時間枠:Days -1, 1, 2 and 3
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The POMS is a self-administered scale that assesses individuals' mood states.
This is a validated scale to measure positive and negative mood states.
The POMS contains 30 items describing the feeling/mood state rated by participants on a 5-point scale (where, 0=not at all and 4=extremely).
The greater the score, the greater the corresponding mood state.
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Days -1, 1, 2 and 3
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Body Sway: Part 1
時間枠:Days -1, 1, 2 and 3
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Body sway will be used to measure body movements, providing a measure of postural stability.
The method has been used to demonstrate effects of sleep deprivation, alcohol, and benzodiazepines.
It will be measured either using a stabilometric platform or a pot string meter based on the Wright ataxiameter.
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Days -1, 1, 2 and 3
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Cognitive Test Battery: International Shopping List Test (ISLT): Part 1
時間枠:Days -21 to -2, Day -1, and Day 1 (6 hours post dose)
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The ISLT is a measure of Verbal Learning.
The test measures total number of correct responses remembering the word list on 3 consecutive trials at a single assessment.
Higher score indicates better performance.
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Days -21 to -2, Day -1, and Day 1 (6 hours post dose)
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Cognitive Test Battery: Groton Maze Learning Test (GMLT): Part 1
時間枠:Days -21 to -2, Day -1, Day 1 (2, 4, 6, and 12 hours post dose), and Day 2 (24 hours post dose)
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GMLT is a measure of Executive Function and Spatial Learning.
The test measures total number of errors made while locating and learning 28 step pathway hidden beneath a 10*10 grid on 5 consecutive trials during a single session.
Lower score indicates better performance.
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Days -21 to -2, Day -1, Day 1 (2, 4, 6, and 12 hours post dose), and Day 2 (24 hours post dose)
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Cognitive Test Battery: Detection Task (DET): Part 1
時間枠:Days -21 to -2, Day -1, Day 1 (2, 4, 6, and 12 hours post dose), and Day 2 (24 hours post dose)
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DET is a measure of Psychomotor Function.
The test measures speed of performance; mean of the log10 transformed reaction times for correct responses.
Lower score indicates better performance.
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Days -21 to -2, Day -1, Day 1 (2, 4, 6, and 12 hours post dose), and Day 2 (24 hours post dose)
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Cognitive Test Battery: Identification Task (IDN): Part 1
時間枠:Days -21 to -2, Day -1, Day 1 (2, 4, 6, and 12 hours post dose), and Day 2 (24 hours post dose)
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IDN is a measure of Attention.
The test measures speed of performance; mean of the log10 transformed reaction times for correct responses.
Lower score indicates better performance.
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Days -21 to -2, Day -1, Day 1 (2, 4, 6, and 12 hours post dose), and Day 2 (24 hours post dose)
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Cognitive Test Battery: One Card Learning Task (OCL): Part 1
時間枠:Days -21 to -2, Day -1, Day 1 (2, 4, 6, and 12 hours post dose), and Day 2 (24 hours post dose)
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OCL is a measure of Visual Learning.
The test measures accuracy of performance; arcsine transformation of the square root of the proportion of correct responses.
Higher score indicates better performance.
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Days -21 to -2, Day -1, Day 1 (2, 4, 6, and 12 hours post dose), and Day 2 (24 hours post dose)
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Cognitive Test Battery: One Back Task (ONB): Part 1
時間枠:Days -21 to -2, Day -1, Day 1 (2, 4, 6, and 12 hours post dose), and Day 2 (24 hours post dose)
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ONB is a measure of Working Memory.
The test measures speed of performance; mean of the log10 transformed reaction times for correct responses.
Lower score indicates better performance.
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Days -21 to -2, Day -1, Day 1 (2, 4, 6, and 12 hours post dose), and Day 2 (24 hours post dose)
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Cognitive Test Battery: Groton Maze Learning Test (GMLT) Delayed Recall: Part 1
時間枠:Days -21 to -2, Day -1, and Day 1 (6 hours post dose)
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GMLT delayed recall is a measure of Delayed Spatial Memory.
The test measures number of errors made while locating 28 step pathway hidden beneath a 10*10 grid after a delay.
Lower score indicates better performance.
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Days -21 to -2, Day -1, and Day 1 (6 hours post dose)
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Cognitive Test Battery: International Shopping List Test Delayed (ISLT-D): Part 1
時間枠:Days -21 to -2, Day -1, Predose, Day 1 (6 hours post dose), and Day 2 (24 hours post dose)
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ISLT-D is a measure of Delayed Verbal Memory.
The test measures total number of correct responses recalling the word list learned initially.
Higher score indicates better performance.
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Days -21 to -2, Day -1, Predose, Day 1 (6 hours post dose), and Day 2 (24 hours post dose)
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Sheehan Irritability Scale (SIS) Score: Part 1 and Part 3
時間枠:Day -1, Day 1 (6 and 12 hours post dose), and Day 2 (24 hours post dose)
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The SIS is a 7-item self-report rating scale that assess symptoms of irritability, frustration, edginess/impatience, moodiness, anger with self, anger with others and temper during the past hour.
Each item is assessed on an 11-point numeric rating scale ranging from 0 (not at all) to 10 (extremely).
The SIS total score is calculated by summing of the scores for each of the 7 individual items and ranges from 0 to 70.
A higher score indicates greater symptomatology.
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Day -1, Day 1 (6 and 12 hours post dose), and Day 2 (24 hours post dose)
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Cerebrospinal Fluid (CSF) Biomarkers Level: Brain Derived Neurotrophic Factor (BDNF): Part 3
時間枠:Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12 hours post dose
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BDNF level in the CSF (a CSF biomarker) will be analyzed to evaluate the pharmacodynamic effect of JNJ-64140284.
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Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12 hours post dose
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Cerebrospinal Fluid (CSF) Biomarkers Level: Monoaminergic Neurotransmitters and Their Metabolites: Part 3
時間枠:Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12 hours post dose
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Monoaminergic neurotransmitters (such as dopamine, serotonine and [nor]adrenaline) and their metabolites (such as homovanillic acid [HVA], 3,4-dihydroxyphenyl glycol [DHPG], 5-hydroxyindoleacetic acid [5-HIAA], 3,4-dihydroxyphenylalanine [DOPA], and 3,4-dihydroxyphenylacetic acid [DOPAC]) in the CSF (CSF biomarkers) will be analyzed to evaluate the pharmacodynamic effect of JNJ-64140284.
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Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12 hours post dose
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協力者と研究者
研究記録日
主要日程の研究
研究開始 (実際)
研究開始
一次修了 (実際)
一次修了
研究の完了 (実際)
研究の完了
試験登録日
最初に提出
最初に提出
QC基準を満たした最初の提出物
QC基準を満たした最初の提出物
最初の投稿 (実際)
最初の投稿
学習記録の更新
投稿された最後の更新 (実際)
投稿された最後の更新
QC基準を満たした最後の更新が送信されました
QC基準を満たした最後の更新が送信されました
最終確認日
最終確認日
詳しくは
本研究に関する用語
その他の研究ID番号
その他の研究ID番号
- CR108318
- 2017-000283-16 (EudraCT番号)
- 64140284EDI1001 (その他の識別子:Janssen Research & Development, LLC)
医薬品およびデバイス情報、研究文書
米国FDA規制医薬品の研究
米国FDA規制機器製品の研究
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プラセボの臨床試験
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NCT07264270募集坐骨神経痛 | 坐骨神経根症 | 腰仙神経根症 | 腰仙神経根症候群 | 腰仙部神経根痛 | 坐骨神経痛