A Phase 1, Open-Label, Multi-Dose Study to Assess the Systemic and Local Tissue Pharmacokinetics and Pharmacodynamics of JNJ-64251330 in Healthy Participants
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 36
- 试验地点
- 1
- 主要终点
- Part 1: Trough Observed Plasma Concentration (Ctrough) of JNJ-64251330
研究概览
简要总结
The purpose of this study is to evaluate: systemic and local gut (rectum and sigmoid colon) exposure to JNJ-64251330, local tissue Pharmacodynamics (PD) using gut (rectum and sigmoid colon) biopsies (Part 1) and the effect of food on the rate and extent of absorption of JNJ-64251330 from oral tablet dosed with or without food (Part 2).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Body mass index (BMI; weight [kilogram {kg}]/height^2 [meter {m}]^2) between 18.0 and 30.0 kilograms per meter square (kg/m^2) (inclusive), and body weight not less than 50.0 kg
- •12-lead electrocardiogram (ECG) consistent with normal cardiac conduction and function, including: QTc interval less than or equal to (<=) 450 milliseconds (ms) for men and <= 470 ms for women
- •Healthy on the basis of clinical laboratory tests performed at screening. If the results of the serum chemistry panel, lipid panel, hematology, coagulation or urinalysis are outside the normal reference ranges, the participant may be included only if the investigator judges the abnormalities or deviations from normal to be not clinically significant. This determination must be recorded in the participant's source documents and initialed by the investigator
- •Have participant-reported normal consistency, regular bowel movements
- •A woman must have a negative highly sensitive serum (beta-human chorionic gonadotropin [hCG])
排除标准
- •History of hepatic or renal insufficiency; significant cardiac, vascular, pulmonary, endocrine, hematologic, rheumatologic, neurologic, oncologic, or psychiatric disease, or metabolic disturbances or any other illness that the investigator considers should exclude the participant or that could interfere with the interpretation of the study results
- •Active or chronic infection, a nontuberculous mycobacterial infection, or opportunistic infection (example, pneumocystosis and aspergillosis)
- •History of severe allergic reaction to midazolam
- •Contraindications to the use of tofacitinib per summary of product characteristics (SmPC)^14/ local prescribing information
- •Female participant who is a breastfeeding mother
研究组 & 干预措施
Part 1: Treatment A (JNJ-64251330)
Participants will receive JNJ-64251330 (dose 1), once daily for 5 days under fasting conditions.
干预措施: JNJ-64251330 (Drug)
Part 1: Treatment B (JNJ-64251330)
Participants will receive JNJ-64251330 (dose 1), twice daily for 5 days under fasting conditions.
干预措施: JNJ-64251330 (Drug)
Part 1: Treatment C (JNJ-64251330)
Participants will receive JNJ-64251330 (dose 2), twice daily for 5 days under fasting conditions.
干预措施: JNJ-64251330 (Drug)
Part 1: Treatment D (JNJ-64251330)
Participants will receive tofacitinib tablet twice daily for 5 days under fasting conditions.
干预措施: Tofacitinib (Drug)
Part 2: Treatment EF (JNJ-64251330)
Participants will receive a single dose of JNJ-64251330 (dose 2), on Day 1 once under fasting conditions (Treatment E) in Period 1 followed by a single dose of JNJ-64251330 (dose 2), on Day 1 once with high fat breakfast (Treatment F) in Period 2. There will be a minimum of 5 days washout between dosing in the two treatment periods.
干预措施: JNJ-64251330 (Drug)
Part 2: Treatment FE (JNJ-64251330)
Participants will receive a single dose of JNJ-64251330 (dose 2), on Day 1 once with high fat breakfast (Treatment F) in Period 1 followed by a single dose of JNJ-64251330 (dose 2), on Day 1 once under fasting conditions (Treatment E) in Period 2. There will be a minimum of 5 days washout between dosing in the two treatment periods.
干预措施: JNJ-64251330 (Drug)
结局指标
主要结局
Part 1: Trough Observed Plasma Concentration (Ctrough) of JNJ-64251330
时间窗: Predose, 24 hour (h) Postdose on Day 5
Ctrough is observed plasma concentration immediately prior to dosing on Day 5 and 24 h after last dose.
Part 1: Area Under the Plasma Concentration-Time Curve from Time 0 to Time of Last Quantifiable Concentration (AUC [0-Last]) of JNJ-64251330
时间窗: Predose, 0.25 hour (h), 0.5 h, 1 h, 2 h, 4 h, 6 h, 8 h, 12 h, 14 h, 24 h Postdose on Day 1 and Day 5; Predose on Day 2
AUC (0-Last) is defined as area under the plasma concentration versus time curve from time 0 to time of the last quantifiable concentration will be evaluated.
Part 2: Area Under the Plasma Concentration-Time Curve from Time 0 to Infinite Time (AUC [0-Infinite]) of JNJ-64251330
时间窗: Predose, 0.25 hour (h), 0.5 h, 1 h, 2 h, 4 h, 6 h, 8 h, 12 h Postdose on Day 1; 24 h, 32 h, 36 h Postdose on Day 2; 48 h Postdose on Day 3
AUC (0-Infinite) defined as area under the analyte concentration versus time curve from time 0 to infinite time will be evaluated.
Part 2: Area Under the Plasma Concentration-Time Curve from Time 0 to 24 Hour (AUC [0-24 h]) of JNJ-64251330
时间窗: Predose, 0.25 hour (h), 0.5 h, 1 h, 2 h, 4 h, 6 h, 8 h, 12 h, 24 h Postdose on Day 2
AUC (0-24 h) defined as area under the plasma concentration-time curve from time 0 to 24 hour postdose will be evaluated.
Part 1: Maximum Observed Plasma Concentrations (Cmax) of JNJ-64251330
时间窗: Predose, 0.25 hour (h), 0.5 h, 1 h, 2 h, 4 h, 6 h, 8 h, 12 h Postdose on Day 1 and Day 5; Predose on Day 2
Cmax is maximum observed plasma concentrations during a dosing interval.
Part 1: Area Under the Plasma Concentration-Time Curve from 0 to 24 Hour (AUC [0-24 h]) of JNJ-64251330
时间窗: Predose, 0.25 hour (h), 0.5 h, 1 h, 2 h, 4 h, 6 h, 8 h, 12 h, 14 h, 24 h Postdose on Day 1 and Day 5; Predose on Day 2
AUC (0-24 h) is defined as area under the plasma concentration-time curve from time 0 to 24 hours postdose will be evaluated.
Part 1: Biopsy Gut (Rectum and Sigmoid Colon) Tissue Concentration of JNJ-64251330
时间窗: Day 6
Biopsy gut (rectum and sigmoid colon) tissue concentration of JNJ-64251330 will be measured using liquid chromatography-mass spectrometry/mass spectrometry (LC MS/MS) assay method to evaluate systemic and local gut (rectum and sigmoid colon) exposure to JNJ-64251330.
Part 1: Change from Baseline in Levels of Phosphorylated Signal Transducer and Activator of Transcription (pSTATs) and other Pan-Janus kinase (JAK) Biomarkers
时间窗: Baseline up to Day 6
Change from baseline in levels of pSTATs and other JAK biomarkers in gut (rectum and sigmoid colon) biopsies as a function of compound and dose will be measured to evaluate local tissue pharmacodynamics (PD).
Part 2: Maximum Observed Plasma Concentrations (Cmax) of JNJ-64251330
时间窗: Predose, 0.25 hour (h), 0.5 h, 1 h, 2 h, 4 h, 6 h, 8 h, 12 h Postdose on Day 1; 24 h, 32 h, 36 h Postdose on Day 2; 48 h Postdose on Day 3
Cmax is maximum observed plasma concentrations during a dosing interval.
Part 2: Area Under the Plasma Concentration-Time Curve from Time 0 to Time of Last Quantifiable Concentration (AUC [0-Last]) of JNJ-64251330
时间窗: Predose, 0.25 hour (h), 0.5 h, 1 h, 2 h, 4 h, 6 h, 8 h, 12 h Postdose on Day 1; 24 h, 32 h, 36 h Postdose on Day 2; 48 h Postdose on Day 3
AUC (0-Last) defined as area under the plasma concentration versus time curve from time 0 to time of the last quantifiable concentration will be evaluated.
Part 2: Time to achieve Maximum Observed Plasma Concentration (Tmax) of JNJ-64251330
时间窗: Predose, 0.25 hour (h), 0.5 h, 1 h, 2 h, 4 h, 6 h, 8 h, 12 h Postdose on Day 1; 24 h, 32 h, 36 h Postdose on Day 2; 48 h Postdose on Day 3
Tmax is the maximum observed plasma concentration.
次要结局
- Parts 1 and 2: Incidence of Adverse Events (AEs)(Up to 35 days (Part 1); Up to 39 days (Part 2))
- Parts 1 and 2: Number of Participants with Severity of AEs(Up to 35 days (Part 1); Up to 39 days (Part 2))
- Part 1: Ratio of Gut (Rectum and Sigmoid colon) to Systemic Exposure(Up to Day 6)