Randomized, Single and Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of EP547 in Healthy Subjects and Subjects With Cholestatic or Uremic Pruritus
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 89
- 试验地点
- 4
- 主要终点
- Incidence of Adverse Events
研究概览
简要总结
This first in human, Phase 1/1b trial will evaluate the safety, tolerability, and pharmacokinetics of single and multiple ascending doses of EP547 in healthy subjects and subjects with cholestatic or uremic pruritus.
详细描述
This study consists of both single and multiple ascending doses in healthy subjects and in subjects with cholestatic or uremic pruritus.
Up to 48 healthy subjects will receive a single dose of EP547 or placebo. There will be a screening period of up to 28 days prior to the first dose, and a follow up visit 7 days after dosing is completed.
24 healthy subjects will receive multiple doses of EP547 or placebo for 7 days. There will be a screening period of up to 28 days prior to the first dose, and a follow up visit 7 days and then 14 days after dosing is completed.
6 subjects with cholestatic disease will receive a single dose of EP547. There will be a screening period of up to 28 days prior to the first dose, and a follow up visit 7 days after dosing is completed.
Up to 16 subjects with cholestatic pruritus will receive multiple doses of EP547 or placebo for 7 days. There will be a screening period of up to 28 days prior to the first dose, and a follow up visit 7 days and then 14 days after dosing is completed.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy Subjects:
- •Age 18 to 60 years, inclusive
- •Body mass index greater than or equal to 19 to less than or equal to 35 kg/m2
- •Medically healthy with no clinically significant medical history, physical examination, vital sign, standard 12- lead ECG, chemistry, hematology, urinalysis, or coagulation results at Screening as deemed by the Investigator
- •Male and female subjects must use adequate birth control and agree not to donate sperm or eggs for the time periods specified in the protocol
- •Subjects with Cholestatic Pruritus:
- •Age 18 to 80 years, inclusive
- •Has a cholestatic disorder
- •Has experienced daily or near-daily moderate to severe pruritus for greater than 4 weeks before Screening and at study entry has itch scores indicative of moderate to severe pruritus
- •If currently taking medications to treat the cholestatic disorder, must be on a stable dose for greater than 12 weeks before Screening and plans to maintain the regimen throughout the study
- •If currently taking medications known to impact pruritus, must be on a stable dose for greater than 4 weeks before Screening and plans to maintain the regimen throughout the study
- •Male and female subjects must use adequate birth control and agree not to donate sperm or eggs for the time periods specified in the protocol
- •Subjects with Uremic Pruritus
- •Age 18 to 80 years, inclusive
- •Has ESRD and is receiving hemodialysis 3× per week
- •Has experienced daily or near-daily moderate to severe pruritus for greater than 4 weeks before Screening and at study entry has itch scores indicative of moderate to severe pruritus
- •If currently taking medications known to impact pruritus, must be on a stable dose for greater than 4 weeks before Screening and plans to maintain the regimen throughout the study
- •Male and female subjects must use adequate birth control and agree not to donate sperm or eggs for the time periods specified in the protocol
排除标准
- •Healthy Subjects:
- •Any prescription medications within 14 days of Screening
- •Positive result for HIV HBV, or HCV at Screening
- •History of malignancy within the past 5 years
- •Tobacco product or electronic cigarette use within 90 days of Day -1
- •Positive drug, alcohol, or cotinine screen results at Screening or Day -1
- •Significant history of abuse of drugs, solvents, or alcohol in the past 2 years
- •Subjects with Cholestatic Pruritus:
- •Scheduled to receive a liver transplant during the study (placement on a transplant waiting list is not exclusionary)
- •Is receiving ongoing UVB treatment or anticipates receiving such treatment during the study
- •Pruritus is secondary to biliary obstruction
- •History or presence of hepatocellular carcinoma, hepatic abscess, or acute portal vein Thrombosis
- •Subjects with Uremic Pruritus:
- •Scheduled to receive a kidney transplant during the study (placement on a transplant waiting list is not exclusionary)
- •Is receiving ongoing UVB treatment or anticipates receiving such treatment during the study
- •Known noncompliance with hemodialysis treatment that, in the opinion of the Investigator, would impede completion or validity of the study
- •Pruritus is attributed mainly to any disease unrelated to kidney disease, is only present during the hemodialysis sessions, or is attributed to a skin disorder that occurs in this population with associated itch (eg, acquired perforating dermatosis)
研究组 & 干预措施
EP547 Single Dose
Single doses of EP547
干预措施: EP547 (Drug)
EP547 Multiple Doses
Multiple doses of EP547
干预措施: EP547 (Drug)
Placebo Single Dose
Single doses of placebo
干预措施: Placebo (Drug)
Placebo Multiple Doses
Multiple doses of placebo
干预措施: Placebo (Drug)
结局指标
主要结局
Incidence of Adverse Events
时间窗: Measured from Day 1 to End of Study or Early Termination (up to 3 weeks)
To assess safety and tolerability of EP547 following single and multiple oral administration
次要结局
- Maximum Plasma Concentration [Cmax] After Single Dose of EP547(Pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 9, and 12 hours post-dose on Day 1)
- Maximum Plasma Concentration [Cmax] After Multiple Doses of EP547(Pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 9, 12, and 24 hours post-dose on Day 7)