A Phase 1, Open-label, Randomized, Parallel-group Study in Healthy Subjects to Investigate the Effect of Different Particle Sizes on the Single-dose Pharmacokinetics of Rilpivirine After Intramuscular Injection of a Long-acting Nanosuspension
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 110
- 试验地点
- 1
- 主要终点
- Session 2: Maximum Observed Plasma Concentration (Cmax)
研究概览
简要总结
The main purpose of this study is to characterize the single-dose pharmacokinetics (PK) of rilpivirine (RPV) after intramuscular (IM) injection of rilpivirine long-acting parenteral formulation (RPV LA) nanosuspensions with different particle size distribution (PSD), in healthy adult participants.
详细描述
This is a phase 1, open-label (all people know the identity of the intervention), randomized (study medication is assigned by chance), parallel-group, sequential study in healthy adult participants to characterize the single-dose pharmacokinetics (PK) of rilpivirine (RPV) after intramuscular (IM) injection of RPV LA nanosuspensions with different particle size distributions (PSD), in healthy adult participants. A total of 110 healthy adult participants will be enrolled in this study. The study will consist of 2 treatment sessions in a fixed sequential order: Session 1- all participants will receive a single oral dose of rilpivirine 25 milligram (mg) as oral immediate release solution on Day 1; Session 2- the participants will be randomized in session 2 on Day 1 in a 1:1:1:1:1 ratio to Treatments A, B, C, D and E. Each treatment group will receive a single IM injection of RPV LA on Day 1 of session 2. Session 1 and 2 will be separated by a washout period of at least 14 days. The total study duration for each participant will be approximately 9.5 months. Safety will be monitored throughout the study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Participant must be willing and able to adhere to the prohibitions and restrictions specified in this protocol
- •Contraceptive use by men or women should be consistent with local regulations regarding the use of contraceptive methods for participants participating in clinical studies
- •A female participant of childbearing potential must have a negative serum beta-human chorionic gonadotropin test at screening and on Day -1 of each session
- •For the duration of the study and for at least 6 months after intramuscular (IM) injection of rilpivirine long-acting parenteral formulation (RPV LA) (or 1 month after administration of rilpivirine (RPV) oral solution for participants who discontinue after Session 1), male and female participants must agree to practice effective methods of contraception, and must agree not to donate sperm (males)/eggs (ova, oocytes; for females) for the purposes of assisted reproduction
- •Participant must be non-smoking for at least 3 months prior to screening
排除标准
- •Female participant who is breastfeeding at screening
- •Participant with a history of any illness that, in the opinion of the investigator, might confound the results of the study or pose an additional risk in administering study drug to the participant or that could prevent, limit or confound the protocol specified assessments. This may include, but is not limited to, renal dysfunction, significant cardiac, vascular, pulmonary, gastrointestinal (such as significant diarrhea, gastric stasis, or constipation that in the investigator's opinion could influence drug absorption or bioavailability), endocrine, neurologic, hematologic, rheumatologic, psychiatric, neoplastic, or metabolic disturbances
- •Participant has a history of clinically relevant arrhythmias or history of risk factors for Torsade de Pointes (hypokalemia, family history of long QT)
- •Participant has clinically relevant, currently active, or underlying gastrointestinal, cardiovascular, nervous system, psychiatric, metabolic, renal, hepatic, respiratory, inflammatory or infectious disease
- •Participant has known allergies, hypersensitivity, or intolerance to RPV or its excipients
研究组 & 干预措施
Cohort 1-RPV LA: Treatment B
Participants will receive single dose of 25 milligram (mg) rilpivirine (RPV) as an oral solution on Day 1 in Session 1 and Treatment B containing a single intramuscular (IM) injection of 600 mg rilpivirine long-acting parenteral formulation (RPV LA) [with different particle size distribution (PSD) as compared to Treatment A, D, C and E] on Day 1 of session 2. Both the sessions are separated by a wash-out Period of at least 14 days.
干预措施: Rilpivirine (Drug)
Cohort 1-RPV LA: Treatment B
Participants will receive single dose of 25 milligram (mg) rilpivirine (RPV) as an oral solution on Day 1 in Session 1 and Treatment B containing a single intramuscular (IM) injection of 600 mg rilpivirine long-acting parenteral formulation (RPV LA) [with different particle size distribution (PSD) as compared to Treatment A, D, C and E] on Day 1 of session 2. Both the sessions are separated by a wash-out Period of at least 14 days.
干预措施: Rilpivirine Long-acting Parenteral Formulation (Drug)
Cohort 1-RPV LA: Treatment D
Participants will receive single dose of 25 mg rilpivirine (RPV) as an oral solution on Day 1 in Session 1 and Treatment D containing a single IM injection of 600 mg RPV LA [with different PSD as compared to Treatment A, B, C and E) on Day 1 of session 2. Both the sessions are separated by a wash-out Period of at least 14 days.
干预措施: Rilpivirine (Drug)
Cohort 1-RPV LA: Treatment D
Participants will receive single dose of 25 mg rilpivirine (RPV) as an oral solution on Day 1 in Session 1 and Treatment D containing a single IM injection of 600 mg RPV LA [with different PSD as compared to Treatment A, B, C and E) on Day 1 of session 2. Both the sessions are separated by a wash-out Period of at least 14 days.
干预措施: Rilpivirine Long-acting Parenteral Formulation (Drug)
Cohort 2-RPV LA: Treatment A
Participants will receive single dose of 25 mg rilpivirine (RPV) as an oral solution on Day 1 in Session 1 and Treatment A containing a single IM injection of 600 mg RPV LA [with different PSD as compared to Treatment B, C, D and E] on Day 1 of session 2. Both the sessions are separated by a wash-out Period of at least 14 days.
干预措施: Rilpivirine (Drug)
Cohort 2-RPV LA: Treatment A
Participants will receive single dose of 25 mg rilpivirine (RPV) as an oral solution on Day 1 in Session 1 and Treatment A containing a single IM injection of 600 mg RPV LA [with different PSD as compared to Treatment B, C, D and E] on Day 1 of session 2. Both the sessions are separated by a wash-out Period of at least 14 days.
干预措施: Rilpivirine Long-acting Parenteral Formulation (Drug)
Cohort 2-RPV LA: Treatment C
Participants will receive single dose of 25 mg rilpivirine (RPV) as an oral solution on Day 1 in Session 1 and Treatment C containing a single IM injection of 600 mg RPV LA [with different PSD as compared to Treatment A, B, D and E] on Day 1 of session 2. Both the sessions are separated by a wash-out Period of at least 14 days.
干预措施: Rilpivirine (Drug)
Cohort 2-RPV LA: Treatment C
Participants will receive single dose of 25 mg rilpivirine (RPV) as an oral solution on Day 1 in Session 1 and Treatment C containing a single IM injection of 600 mg RPV LA [with different PSD as compared to Treatment A, B, D and E] on Day 1 of session 2. Both the sessions are separated by a wash-out Period of at least 14 days.
干预措施: Rilpivirine Long-acting Parenteral Formulation (Drug)
Cohort 2-RPV LA: Treatment E
Participants will receive single dose of 25 mg rilpivirine (RPV) as an oral solution on Day 1 in Session 1 and Treatment E containing a single IM injection of 600 mg RPV LA [with different PSD as compared to Treatment A, B, C and D] on Day 1 of session 2. Both the sessions are separated by a wash-out Period of at least 14 days.
干预措施: Rilpivirine (Drug)
Cohort 2-RPV LA: Treatment E
Participants will receive single dose of 25 mg rilpivirine (RPV) as an oral solution on Day 1 in Session 1 and Treatment E containing a single IM injection of 600 mg RPV LA [with different PSD as compared to Treatment A, B, C and D] on Day 1 of session 2. Both the sessions are separated by a wash-out Period of at least 14 days.
干预措施: Rilpivirine Long-acting Parenteral Formulation (Drug)
结局指标
主要结局
Session 2: Maximum Observed Plasma Concentration (Cmax)
时间窗: Pre-dose, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264, 336, 408, 528, 672, 1344, 2016, 2688, 3360, 4032, 4704, 5376, and 6048 hours post-dose
The Cmax is the maximum observed plasma concentration.
Session 2: Area Under the Plasma Concentration-Time Curve From Time Zero (Day 1) to Day 28 (AUC[0-d28])
时间窗: 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264, 336, 408, and 528 hours post-dose
The AUC (0-d28) is the area under the plasma concentration-time curve from time of administration up to Day 28 postdose.
Session 2: Area Under the Plasma Concentration-Time Curve From Time Zero to Last Quantifiable Time (AUC [0-last])
时间窗: Pre-dose, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264, 336, 408, 528, 672, 1344, 2016, 2688, 3360, 4032, 4704, 5376, and 6048 hours post-dose
The AUC (0-last) is the area under the plasma concentration-time curve from time zero to last quantifiable time.
Session 2: Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC[0-infinity])
时间窗: Pre-dose, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168,216, 264, 336, 408, 528, 672, 1344, 2016, 2688, 3360, 4032, 4704, 5376, and 6048 hours post-dose
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(last) and C(last)/lambda(z); wherein AUC(last) is area under the plasma concentration-time curve from time zero to last quantifiable time, C(last) is the last observed quantifiable concentration, and lambda(z) is elimination rate constant.
次要结局
- Number of Participants With Adverse Events as a Measure of Safety and Tolerability(Baseline, up to 9.5 months)
- Session 1: Maximum Observed Plasma Concentration (Cmax)(Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 9, 12, 16, 24, 48, 72, 120 and 168 hours post-dose)
- Session 1: Area Under the Plasma Concentration-Time Curve From Time Zero (Day 1) to Day 28 AUC (0-d28)(1, 2, 3, 4, 5, 6, 9, 12, 16, 24, 48, 72, 120, 168, hours post-dose)
- Session 1: Area Under the Plasma Concentration-Time Curve From Time Zero to Last Quantifiable Time AUC (0-last)(Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 9, 12, 16, 24, 48, 72, 120 and 168 hours post-dose)
- Session 1: Area Under the Plasma Concentration-Time Curve From Time Zero To Infinite Time AUC (0-infinity)(Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 9, 12, 16, 24, 48, 72, 120 and 168 hours post-dose)