A Phase 1, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Single Ascending Doses of PBI-4547 in Healthy Subjects
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- Number of participants with clinically significant laboratory evaluation findings
研究概览
简要总结
This study will evaluate the safety, tolerability, and pharmacokinetics (PK) of PBI-4547 in healthy adult participants.
详细描述
This is a first-in-human, single-ascending dose study of PBI-4547 in healthy adult participants. PBI-4547 is a synthetic ligand of G protein-coupled receptor (GPR)40 and GPR84, which have been reported to play a role in fibrosis in various animal models as well as in tissue culture.
A total of 40 healthy adult participants will sequentially receive 1 of 5 doses of PBI-4547 (Dose1, 2, 3, 4 or 5) or matching placebo, with each cohort of 8 participants randomized in a 3:1 ratio to receive PBI-4547 or matching placebo.
A food-effect cohort will be added after review of the PK results of at least the first dose, and the following 2 doses, if needed. In this cohort participants will initially receive the study drug under fasting conditions (Period 1) followed by the same dose after the ingestion of a high-fat meal (Period 2) after a 14-day washout period.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •Healthy male participants or non-childbearing potential female participants, ≥18 and ≤55 years.
- •Body mass index > 18.5 and < 30.0 kg/m^2, and body weight ≥ 50.0 kg for male participants and ≥ 45.0 kg for female participants.
- •Continuous non-smoker who has not used tobacco or nicotine-containing products for at least 3 months prior to screening.
- •Male participants with a pregnant partner must agree to use a condom from the first dosing until at least 90 days after study drug administration.
- •Male participants must be willing not to donate sperm until 90 days after study drug administration.
排除标准
- •Any clinically significant abnormality or abnormal laboratory test results.
- •An estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m^
- •Positive urine drug screen and history of significant drug abuse.
- •History of significant allergic reactions to any drug.
- •Use of any drugs known to induce or inhibit hepatic drug metabolism.
- •Positive pregnancy test or breast-feeding participant.
- •Clinically significant abnormalities in ECG, blood pressure, and heart rate at screening.
- •History of significant alcohol abuse or regular use of alcohol.
- •Use of medication other than topical products without significant systemic absorption.
- •Donation of plasma.
研究组 & 干预措施
Cohort 1, Dose 1 of PBI-4547 or Placebo
Dose 1 of PBI-4547 or matching Placebo tablets by mouth
干预措施: PBI-4547 (Drug)
Cohort 1, Dose 1 of PBI-4547 or Placebo
Dose 1 of PBI-4547 or matching Placebo tablets by mouth
干预措施: Placebo (Other)
Cohort 2, Dose 2 of PBI-4547 or Placebo
Dose 2 of PBI-4547 or matching Placebo tablets by mouth
干预措施: PBI-4547 (Drug)
Cohort 2, Dose 2 of PBI-4547 or Placebo
Dose 2 of PBI-4547 or matching Placebo tablets by mouth
干预措施: Placebo (Other)
Cohort 3, Dose 3 of PBI-4547 or Placebo
Dose 3 of PBI-4547 or matching Placebo tablets by mouth
干预措施: PBI-4547 (Drug)
Cohort 3, Dose 3 of PBI-4547 or Placebo
Dose 3 of PBI-4547 or matching Placebo tablets by mouth
干预措施: Placebo (Other)
Cohort 4, Dose 4 of PBI-4547 or Placebo
Dose 4 of PBI-4547 or matching Placebo tablets by mouth
干预措施: PBI-4547 (Drug)
Cohort 4, Dose 4 of PBI-4547 or Placebo
Dose 4 of PBI-4547 or matching Placebo tablets by mouth
干预措施: Placebo (Other)
Cohort 5, Dose 5 of PBI-4547 or Placebo
Dose 5 of PBI-4547 or matching Placebo tablets by mouth
干预措施: PBI-4547 (Drug)
Cohort 5, Dose 5 of PBI-4547 or Placebo
Dose 5 of PBI-4547 or matching Placebo tablets by mouth
干预措施: Placebo (Other)
结局指标
主要结局
Number of participants with clinically significant laboratory evaluation findings
时间窗: 5-6 days
Laboratory tests for hematology, serum chemistry and urinalysis will be performed upon admission, at discharge, and at the follow-up visit (5 ± 1 day post-dose).
Number of participants with clinically significant electrocardiogram (ECG) Findings
时间窗: 5-6 days
Triplicate ECG will be performed upon admission, pre-dose, and approximately 1, 2, 8, and 24 hours post-dose, and at the follow-up visit (5 ± 1 day post-dose). Subjects will be continuously monitored using a Holter monitor from approximately 1 hour pre-dose until approximately 24 hours post-dose.
Number of participants with physical examination findings
时间窗: 5-6 days
Brief physical examination will be conducted upon admission and at discharge. A complete physical examination will be conducted at screening and follow-up visit.
Number of participants with treatment-emergent adverse events (TEAEs)
时间窗: 5-6 days
TEAE is any untoward medical occurrence in a subject who has been administered a pharmaceutical product or not, which does not necessarily have a causal relationship with this treatment.
Number of participants with clinically significant vital sign findings
时间窗: 5-6 days
Vital signs include blood pressure, heart rate, respiratory rate, and oral body temperature will be measured upon admission, before discharge from the clinic and at the follow-up visit (5 ± 1 day post-dose).
次要结局
- Cmax for PBI-4547(48 hours)
- T1/2 el for PBI-4547(48 hours)
- AUC0-inf for PBI-4547 under fed condition(48 hours)
- Cmax for PBI-4547 under fed condition(48 hours)
- MRT for PBI-4547(48 hours)
- Vd/F for PBI-4547(48 hours)
- AUC0-t for PBI-4547 under fed condition(48 hours)
- AUC0-t for PBI-4547(48 hours)
- Residual area for PBI-4547(48 hours)
- Tmax for PBI-4547(48 hours)
- AUC0-inf for PBI-4547(48 hours)
- Kel for PBI-4547(48 hours)
- Cl/F for PBI-4547(48 hours)
- Rkel for PBI-4547(48 hours)
- Tmax for PBI-4547 under fed condition(48 hours)