AN OPEN LABEL, PHASE 1, TWO-ARM STUDY TO ASSESS TARGET OCCUPANCY AND FUNCTIONAL INHIBITION OF JAK3 AND TEC KINASES BY SINGLE DOSES OF RITLECITINIB IN HEALTHY ADULT PARTICIPANTS
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Pfizer
- 入组人数
- 16
- 试验地点
- 1
- 主要终点
- Percent Target Occupancy for ITK
研究概览
简要总结
This is a phase 1, open label, two-arm study to assess target occupancy and functional inhibition of JAK3 and TEC kinases by Ritlecitinib in healthy adult participants
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 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
- •Participants are eligible to be included in the study only if all the following criteria apply:
- •Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures.
- •Male and female participants who are overtly healthy as determined by medical evaluation including medical history, physical examination including BP and pulse rate measurement, 12-lead ECG, or clinical and laboratory tests.
- •BMI of 17.5 to 30.5 kg/m2; and a total body weight >50 kg (110 lb).
排除标准
- •Participants are excluded from the study if any of the following criteria apply:
- •Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurological, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at the time of dosing).
- •Infection with HIV, hepatitis B or hepatitis C viruses
- •Have evidence of untreated or inadequately treated active or latent Mycobacterium TB infection
- •Known active or history of recurrent bacterial, viral, fungal, mycobacterial or other infections.
- •Have received only one of the 2 required doses of COVID-19 vaccine.
- •Participants have a known present or a history of malignancy other than a successfully treated or excised non metastatic basal cell or squamous cell cancer of the skin or cervical carcinoma in situ.
研究组 & 干预措施
Cohort 1
Subjects will be dosed with 50 mg Ritlecitinib on Day 1 and followed up till Day 3
干预措施: Ritlecitinib 50 mg (Drug)
Cohort 2
Subjects will be dosed with 200 mg Ritlecitinib on Day 1 and followed up till Day 3
干预措施: Ritlecitinib 200 mg (Drug)
结局指标
主要结局
Percent Target Occupancy for ITK
时间窗: -1 (pre-dose), 0 (pre-dose), 1, 2, 4, 8, 24, 48 hours post-dose
Target occupancy forIL 2 inducible T-cell kinase (ITK) in PBMCs by ritlecitinib was investigated in human blood by chemical probe-based enrichment and LC-MS/MS analysis. % TO is calculated as \[(baseline value - value at specified time point)\*100/baseline value\], where baseline value in this formula is defined as the mean of the two pre-dose measurements at Hour -1 and Hour 0 on Day 1. Since (baseline value - value at specified time point)=0 at baseline, % TO at baseline is 0.
Percent Target Occupancy for BMX
时间窗: -1 (pre-dose), 0 (pre-dose), 1, 2, 4, 8, 24, 48 hours post-dose
Target occupancy for bone marrow tyrosine kinase gene in chromosome X (BMX) in PBMCs by ritlecitinib was investigated in human blood by chemical probe-based enrichment and LC-MS/MS analysis. % TO is calculated as \[(baseline value - value at specified time point) \*100/baseline value\], where baseline value in this formula is defined as the mean of the two pre-dose measurements at Hour -1 and Hour 0 on Day 1. Since (baseline value - value at specified time point)=0 at baseline, % TO at baseline is 0.
Percent Target Occupancy for JAK3
时间窗: -1 (pre-dose), 0 (pre-dose), 1, 2, 4, 8, 24, 48 hours post-dose
Target occupancy for janus kinase 3 (JAK3) in peripheral blood mononuclear cells (PBMCs) by ritlecitinib was investigated in human blood by chemical probe-based enrichment and liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) analysis. % TO is calculated as \[(baseline value - value at specified time point)\*100/baseline value\], where baseline value in this formula is defined as the mean of the two pre-dose measurements at Hour -1 and Hour 0 on Day 1. Since (baseline value - value at specified time point)=0 at baseline, % TO at baseline is 0.
Percent Target Occupancy for TXK
时间窗: -1 (pre-dose), 0 (pre-dose), 1, 2, 4, 8, 24, 48 hours post-dose
Target occupancy for tyrosine kinase expressed in T cells (TXK) in PBMCs by ritlecitinib was investigated in human blood by chemical probe-based enrichment and LC-MS/MS analysis. % TO is calculated as \[(baseline value - value at specified time point)\*100/baseline value\], where baseline value in this formula is defined as the mean of the two pre-dose measurements at Hour -1 and Hour 0 on Day 1. Since (baseline value - value at specified time point)=0 at baseline, % TO at baseline is 0.
Percent Target Occupancy for TEC
时间窗: -1 (pre-dose), 0 (pre-dose), 1, 2, 4, 8, 24, 48 hours post-dose
Target occupancy for tyrosine kinase expressed carcinoma (TEC) in PBMCs by ritlecitinib was investigated in human blood by chemical probe-based enrichment and LC-MS/MS analysis. % TO is calculated as \[(baseline value - value at specified time point)\*100/baseline value\], where baseline value in this formula is defined as the mean of the two pre-dose measurements at Hour -1 and Hour 0 on Day 1. Since (baseline value - value at specified time point)=0 at baseline, % TO at baseline is 0.
Percent Target Occupancy for BTK
时间窗: -1 (pre-dose), 0 (pre-dose), 1, 2, 4, 8, 24, 48 hours post-dose
Target occupancy for Bruton's tyrosine kinase (BTK) in PBMCs by ritlecitinib was investigated in human blood by chemical probe-based enrichment and LC-MS/MS analysis. % TO is calculated as \[(baseline value - value at specified time point)\*100/baseline value\], where baseline value in this formula is defined as the mean of the two pre-dose measurements at Hour -1 and Hour 0 on Day 1. Since (baseline value - value at specified time point)=0 at baseline, % TO at baseline is 0.
次要结局
- Maximum Observed Plasma Concentration (Cmax) of Ritlecitinib(0 (pre-dose), 1, 2, 4, 8, 24, 48 hours post-dose)
- Number of Participants With All-Causality and Treatment-Related Treatment-Emergent Adverse Events (TEAEs)(From the first dose of study treatment up to 35 days after the last dose of study treatment (up to 35 days))
- Last Quantifiable Plasma Concentration (Clast) of Ritlecitinib(0 (pre-dose), 1, 2, 4, 8, 24, 48 hours post-dose)
- Number of Participants With Treatment-Emergent Adverse Events by Severity(From the first dose of study treatment up to 35 days after the last dose of study treatment (up to 35 days))
- Time to Reach Maximum Observed Plasma Concentration (Tmax) of Ritlecitinib(0 (pre-dose), 1, 2, 4, 8, 24, 48 hours post-dose)
- Average Plasma Concentration From Time 0 to 24 Hours (Cav) of Ritlecitinib(0 (pre-dose), 1, 2, 4, 8, 24 hours post-dose)
- Area Under the Curve From Time 0 to 24 Hours (AUC24) of Ritlecitinib(0 (pre-dose), 1, 2, 4, 8, 24 hours post-dose)
- Number of Participants With Laboratory Abnormalities Without Regard to Baseline Abnormality(From the first dose of study treatment up to 35 days after the last dose of study treatment (up to 35 days))
- Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of Ritlecitinib(0 (pre-dose), 1, 2, 4, 8, 24, 48 hours post-dose)
- Number of Participants With Pre-defined Criteria for Vital Signs(From the first dose of study treatment up to 35 days after the last dose of study treatment (up to 35 days))