A PHASE 1, OPEN-LABEL STUDY IN HEALTHY PARTICIPANTS TO INVESTIGATE THE PHARMACOKINETICS OF RITLECITINIB FOLLOWING SINGLE ORAL ADMINISTRATION OF MODIFIED RELEASE FORMULATIONS UNDER FED AND FASTED CONDITIONS
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Pfizer
- 入组人数
- 12
- 试验地点
- 1
- 主要终点
- Maximum Observed Concentration (Cmax) of Ritlecitinib: MR Capsules vs Oral Solution Under Fasted Condition
研究概览
简要总结
The purpose of this study is to compare if three forms of study medicine (called ritlecitinib) get processed differently in healthy adults.
This study is seeking healthy participants who have:
- Aged 18 years or older;
- male or female who are healthy as determined by medical assessment;
- BMI of 16-32 kg/m2, and a total body weight >45 kg (99 lb).
All participants in this study will receive a ritlecitinib oral dose in three different forms (solution, capsule 1 and capsule 2).
The study will take up to 2.5 months, including the screening period and follow-up phone call. Participants will have to stay at the study clinic for at least 13 days. There will be 4 periods in total for this study. On day 1 of each period, participants will take one form of Riltecitinib without food for the first three periods and with food for the last period. Participants will have blood samples taken both before and after taking ritlecitinib. A follow-up phone call will be made at 28 to 35 days after the last study period.
详细描述
Ritlecitinib is a covalent and irreversible inhibitor of JAK3 with high selectivity over the other JAK isoforms (JAK1, JAK2, and TYK2). Ritlecitinib also inhibits irreversibly the TEC family kinases with selectivity over the broader human kinome. Treatment with ritlecitinib is expected to inhibit the inflammatory pathways mediated by IL 7, IL 15 and IL 21, all implicated in UC, CD, AA, RA, and vitiligo and therefore under development in these indications. Moreover, due to lack of activity against the other JAK isoforms, ritlecitinib is expected to spare immunoregulatory cytokines such as IL 10, IL 27 and IL 35, which are critical to the maintenance of immunosuppressive functions and immune homeostasis.
This study aims to investigate the pharmacokinetics (PK) and relative bioavailability of 2 new modified release (MR) capsule formulations of ritlecitinib, MR1 (release duration: 6-8 hours) and MR2 (release duration:13 15 hours) as single doses in fasted and fed conditions.
This is a single dose, open-label, randomized, 4-period, 6-sequence crossover study in a single cohort of approximately 12 healthy participants randomized to one of the sequences (containing 1 solution and 2 modified release [MR1 and MR2] capsule formulations of ritlecitinib) described in the table below. The first 3 periods are under fasted condition and the fourth period is under fed condition to investigate the effect of food on the PK of MR1 and MR2.
For a given participant, the total study duration from screening to follow-up phone call will be between approximately 8 to 11 weeks.
Screening will occur within 28 days prior to the first dose of the study intervention. Each participant will go through Periods 1 through 4 and dosing in each treatment period will be separated by at least 3 days to minimize any carryover effect.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Male and female participants aged 18 years or older (or the minimum age of consent in accordance with local regulations) at screening who are overtly healthy as determined by medical evaluation including medical history, physical examination, and laboratory tests.
- •BMI of 16-32 kg/m2, and a total body weight >45 kg (99 lb).
- •Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures.
- •Capable of giving signed informed consent
排除标准
- •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).
- •Participants with the acute or chronic infections or infection history
- •History of febrile illness within 5 days prior to the first dose of study intervention.
- •History of any lymphoproliferative disorder such as EBV related lymphoproliferative disorder, history of lymphoma, history of leukemia, or signs or symptoms suggestive of current lymphatic or lymphoid disease.
- •Known present or a history of malignancy other than a successfully treated or excised nonmetastatic basal cell or squamous cell cancer of the skin or cervical carcinoma in situ.
- •History of active or latent Mycobacterium TBA: participant who is currently being treated for active or latent Mycobacterium TB infection or has a history of Mycobacterium TB must be excluded from the study.
- •Any medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality or other conditions that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study.
研究组 & 干预措施
Treatment Sequence 1
Ritlecitinib 100 mg solution (fasted, Period 1), followed by ritlecitinib 100 mg MR capsule 1 (fasted, Period 2), followed by ritlecitinib 100 mg MR capsule 2 (fasted, Period 3), and followed by ritlecitinib 100 mg MR capsule 1 (fed, Period 4)
干预措施: Ritlecitinib (Drug)
Treatment Sequence 2
Ritlecitinib 100 mg MR capsule 1 (fasted, Period 1), followed by ritlecitinib 100 mg MR capsule 2 (fasted, Period 2), followed by ritlecitinib 100 mg solution (fasted, Period 3), and followed by ritlecitinib 100 mg MR capsule 1 (fed, Period 4)
干预措施: Ritlecitinib (Drug)
Treatment Sequence 3
Ritlecitinib 100 mg MR capsule 2 (fasted, Period 1), followed by ritlecitinib 100 mg solution (fasted, Period 2), followed by ritlecitinib 100 mg MR capsule 1 (fasted, Period 3), and followed by ritlecitinib 100 mg MR capsule 1 (fed, Period 4)
干预措施: Ritlecitinib (Drug)
Treatment Sequence 4
Ritlecitinib 100 mg solution (fasted, Period 1), followed by ritlecitinib 100 mg MR capsule 1 (fasted, Period 2), followed by ritlecitinib 100 mg MR capsule 2 (fasted, Period 3), and followed by ritlecitinib 100 mg MR capsule 2 (fed, Period 4)
干预措施: Ritlecitinib (Drug)
Treatment Sequence 5
Ritlecitinib 100 mg MR capsule 1 (fasted, Period 1), followed by ritlecitinib 100 mg MR capsule 2 (fasted, Period 2), followed by ritlecitinib 100 mg solution (fasted, Period 3), and followed by ritlecitinib 100 mg MR capsule 2 (fed, Period 4)
干预措施: Ritlecitinib (Drug)
Treatment Sequence 6
Ritlecitinib 100 mg MR capsule 2 (fasted, Period 1), followed by ritlecitinib 100 mg solution (fasted, Period 2), followed by ritlecitinib 100 mg MR capsule 1 (fasted, Period 3), and followed by ritlecitinib 100 mg MR capsule 2 (fed, Period 4)
干预措施: Ritlecitinib (Drug)
结局指标
主要结局
Maximum Observed Concentration (Cmax) of Ritlecitinib: MR Capsules vs Oral Solution Under Fasted Condition
时间窗: For oral solution: Pre-dose (0 hours), 0.5, 1, 2, 3, 4, 6, 10, 12 and 24 hours post-dose on Day 1 of Period 1, 2 or 3; for MR1 and MR2 capsules: Pre-dose (0 hours), 1, 2, 3, 4, 6, 10, 12,16, 24, 36 and 48 hours post-dose on Day 1 of Period 1, 2 or 3
Area Under the Plasma Concentration-Time Profile From Time Zero (0) Extrapolated to Infinite Time (AUCinf) of Ritlecitinib: MR Capsules vs Oral Solution Under Fasted Condition
时间窗: For oral solution: Pre-dose (0 hours), 0.5, 1, 2, 3, 4, 6, 10, 12 and 24 hours post-dose on Day 1 of Period 1, 2 or 3; for MR1 and MR2 capsules: Pre-dose (0 hours), 1, 2, 3, 4, 6, 10, 12,16, 24, 36 and 48 hours post-dose on Day 1 of Period 1, 2 or 3
AUCinf was calculated as AUClast + (Clast/kel), where Clast was the predicted plasma concentration at the last quantifiable time point from the log-linear regression analysis and kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve.
次要结局
- Cmax of Ritlecitinib: MR Capsules Under Fed vs Fasted Condition(Pre-dose (0 hours), 1, 2, 3, 4, 6, 10, 12,16, 24, 36 and 48 hours post-dose on Day 1 of Period 1, 2, 3 (for fasted) or 4 (for fed))
- AUCinf of Ritlecitinib: MR Capsules Under Fed vs Fasted Condition(Pre-dose (0 hours), 1, 2, 3, 4, 6, 10, 12,16, 24, 36 and 48 hours post-dose on Day 1 of Period 1, 2, 3 (for fasted) or 4 (for fed))
- Number of Participants With Adverse Events (AEs)(From start of study treatment up to 35 days after administration of last dose of study intervention (maximum up to 45 days))
- Number of Participants With Clinically Significant Laboratory Test Abnormalities(From start of study treatment up to Day 3 of Period 4 (maximum up to Day 12, each Period = 3 days))
- Number of Participants With Clinically Significant Vital Signs Abnormalities(From start of study treatment up to Day 3 of Period 4 (maximum up to Day 12, each Period = 3 days))
- Number of Participants With Clinically Significant Electrocardiogram (ECG) Abnormalities(From start of study treatment up to Day 3 of Period 4 (maximum up to Day 12, each Period = 3 days))