A Phase 1, Open Label, Drug Interaction Study to Evaluate the Effect of ZYN002 on the Pharmacokinetics of CYP3A4, CYP2C19, CYP2C9, CYP2D6, CYP1A2, CYP2C8, and CYP2B6 Probe Substrates, and Valproate in Healthy Adult Participants
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 29
- 试验地点
- 1
- 主要终点
- Maximum measure plasma concentration (Cmax) of probe substrates and metabolites
研究概览
简要总结
This study is an open-label drug-drug interaction (DDI) study of ZYN002 transdermal gel and multiple drugs.
详细描述
This study is a Phase 1, open-label, 2-part, fixed-sequence, 3-period DDI study to evaluate the effect of ZYN002 transdermal gel on the pharmacokinetics (PK) of probe substrates and their metabolites. In addition, this study is designed to evaluate the safety and tolerability of ZYN002 transdermal gel after multiple-dose topical application to healthy adult participants.
Part 1 - DDI with probe substrates for cytochrome P450 (CYP)3A4, CYP2C19, CYP2C9, CYP2D6, CYP1A2 administered as single oral doses followed by the staggered dosing of probe substrates for CYP2C8 and for CYP2B6 administered as single oral doses.
Part 2 - DDI with valproate (valproic acid [VPA]), a probe substrate for β-oxidation and glucuronidation.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Other
- 盲法
- None
盲法说明
This is an open-label, 2-part, fixed-sequence DDI study.
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
- •Male or female adults, 18-55 years of age, inclusive, at the time of Screening.
- •Judged by the Investigator to be in generally good health at Screening based upon the results of a medical history, physical examination, 12-lead ECG, and clinical laboratory test results. Laboratory results outside of the reference range, but acceptable, must be documented as not clinically significant (NCS) at the discretion of the Investigator.
- •Participants must have a body mass index between 18 and 30 kg/m² at the time of Screening.
- •Females of childbearing potential must have a negative pregnancy test result at the Screening Visit and on Day -1 before admission to the CRU. Females who are not of childbearing potential are defined as being postmenopausal for >=12 months or having a history of hysterectomy and/or bilateral oophorectomy and/or bilateral tubal ligation.
排除标准
- •A) Females who are pregnant, nursing or planning to become pregnant or females of childbearing potential, who are unwilling to use medically acceptable method of contraception or B) Males with a female partner who is pregnant, nursing, or planning to become pregnant or a female partner of childbearing potential who is unwilling to use a medically acceptable method of contraception.
- •Are homozygous for CYP2C19*2 or heterozygous carriers of CYP2C19*2/CYP2C19*3 or CYP2C9*2/CYP2C9*3 or CYP2D6*2/CYP2D6*3 haplotypes categorized as poor metabolizers.
- •Has consumed alcohol 48 hours prior to Day 1 or during the study.
- •Has eaten any food or drink/beverage containing, grapefruit or grapefruit juice, apple, cranberry, Seville orange or orange juice, vegetables from the mustard family (e.g., kale, spinach, broccoli, watercress, collard greens, kohlrabi, brussels sprouts, parsley, mustard greens, endive, red cabbage, asparagus, or mustard), and chargrilled meats within one week prior to study start (Day -1).
研究组 & 干预措施
Part 1: Interaction of ZYN002 and substrates
Substrates: midazolam, omeprazole, losartan, dextromethorphan, caffeine, repaglinide, and bupropion
干预措施: Part 1 (Drug)
Part 2: Interaction of ZYN002 and VPA
干预措施: Part 2 (Drug)
结局指标
主要结局
Maximum measure plasma concentration (Cmax) of probe substrates and metabolites
时间窗: Days 1-3 (Period 1), Days 24-26 (Period 3)
Blood samples collected at pre dose, and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36, and 48 hours post dose.
Cmax of repaglinide and metabolite
时间窗: Days 3 and 4 (Period 1), Days 26 and 27 (Period 3)
Blood samples collected at pre dose, and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, and 24 hours post dose.
Cmax of bupropion and metabolite
时间窗: Days 4-10 (Period 1), Days 27-33 (Period 3)
Blood samples collected at pre dose and at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16, 24, 48, 72, 96, 120, and 144 hours post dose.
Cmax of CBD, delta-9-tetrahydrocannabinol (THC), and CBD metabolites
时间窗: Days 24-33 (Period 3)
Blood samples collected at pre dose and at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16, 24, 36, 48, 72, 96, 120, and 144 hours post dose.
Amount excreted in urine over the collection period (Ae0-12) of CBD and its metabolites
时间窗: Day 17 (Period 2), Days 24 and 32 (Period 3)
Urine samples collected over a 12-hour period.
Cmax of VPA and metabolite
时间窗: Days 1-4 (Period 1), Days 18-21 (Period 3)
Blood samples collected at pre dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours post dose.
Cmax of CBD, THC, and CBD metabolites
时间窗: Days 18-21 (Period 3)
Blood samples collected at pre dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours post dose.
Ae0-12 of VPA and metabolites
时间窗: Days 1-4 (Period 1), Day 17 (Period 2), Days 18-20 (Period 3)
Urine samples collected over a 12-hour period.
Ae0-12 of ZYN002 and metabolites
时间窗: Day 17 (Period 2), Days 18 and 20 (Period 3)
Urine samples collected over a 12-hour period.
次要结局
- Number of participants with skin irritation in ZYN002 application areas(Up to 33 days)
- Number of participants with abnormal physical examination results(Up to 33 days)
- Number of participants with abnormal clinical laboratory results(Up to 33 days)
- Number of participants with abnormal vital sign results(Up to 33 days)
- Number of participants with abnormal continuous pulse oximetry results(Up to 33 days)
- Number of participants with abnormal electrocardiogram (ECG)(Up to 33 days)