临床试验/NCT05011812

NCT05011812已完成1 期

A Single and Multiple Ascending Dose Study to Evaluate the Safety, Tolerability and Pharmacokinetics of PBI-0451 in Healthy Subjects.

Pardes Biosciences, Inc.1 个研究点分布在 1 个国家目标入组 130 人开始时间: 2021年8月14日最近更新: 2022年6月3日

适应症

干预措施

试验速览

阶段: 1 期
状态: 已完成
发起方: Pardes Biosciences, Inc.
入组人数: 130
试验地点: 1
主要终点: Number of subjects with treatment emergent adverse events (TEAEs) in Single Ascending Dose (SAD) compared to placebo

研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

This is a phase 1, placebo-controlled, blinded, randomized, dose escalation study of PBI-0451 in healthy subjects. PBI-0451 is a new chemical entity and inhibitor of the main protease of coronaviruses, including the SARS-CoV-2 that causes COVID-19 disease. The study is designed to evaluate the safety, tolerability and pharmacokinetics of PBI-0451 after single and multiple ascending doses and also to explore drug-drug interaction potential of PBI-0451.

详细描述

Combined Three part, double blind, (sponsor open) study. Part 1: Single ascending dose study. Part 2: Multiple ascending dose study. Part 3: Drug-drug interaction study.

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: Triple (Participant, Care Provider, Investigator)

盲法说明

Open to Sponsor

入排标准

年龄范围: 18 Years 至 59 Years（Adult）
性别: All
接受健康志愿者: 是

入选标准

•Non-smoking, healthy male or female subjects aged 18-59 years.
•Body Mass Index (BMI) of ≥ 19.0 and ≤ 30.0 kg/m
•12-Lead electrocardiogram (ECG) evaluation without clinically significant abnormalities.
•Normal renal function, including having a creatinine clearance (CLcr) ≥90mL/min
•Male subjects and female subjects of childbearing potential who engage in heterosexual intercourse must agree to use protocol-specified method(s) of contraception.
•Screening laboratory assessments must be without clinically significant abnormalities as assessed by the investigator.

排除标准

•Pregnant and lactating females
•Have received any investigational drug (or vaccine) within the last 30 days prior to study dosing.
•Have a positive test result for HIV or HBsAg.
•Have poor venous access that limits phlebotomy
•Have taken any prescription medications or over-the-counter medications, including herbal products and dietary supplements within 28 days prior to start of study.
•Have been treated with systemic steroids, immunosuppressant therapies, or chemotherapeutic agents within 3 months prior to Screening or is expected to receive these agents during the study.
•Have a history of lymphoma, leukemia, or any malignancy within the past 5 years except for basal cell or squamous epithelial carcinomas of the skin that have been resected with no evidence of metastatic disease for 3 years.
•Have a history of significant drug sensitivity, cardiac disease, syncope, palpitations, or unexplained dizziness, implanted defibrillator or pacemaker, liver disease, severe peptic ulcer disease, gastroesophageal reflux disease and a medical or surgical treatment that permanently altered gastric absorption.
•Have received inactivated vaccinations within 4 weeks prior to randomization or receive live vaccinations within 4 weeks of Screening.
•Received the COVID-19 vaccine either within 7 days or have not completed the series of required 2 doses.
•Have a history of excessive alcohol use or other illicit drug use within 6 months of screening.

研究组 & 干预措施

Part 1, Treatment N

Experimental

Dose Level 5 of PBI-0451

干预措施: Placebo (Drug)

Part 1, Treatment N

Experimental

Dose Level 5 of PBI-0451

干预措施: PBI-0451 Dose 5 (Drug)

Part 1, Treatment A

Experimental

Dose level 1 of PBI-0451

干预措施: PBI-0451 Dose 1 (Drug)

Part 1, Treatment A

Experimental

Dose level 1 of PBI-0451

干预措施: Placebo (Drug)

Part 1, Treatment B

Experimental

Dose level 2 of PBI-0451

干预措施: PBI-0451 Dose 2 (Drug)

Part 1, Treatment B

Experimental

Dose level 2 of PBI-0451

干预措施: Placebo (Drug)

Part 1, Treatment C

Experimental

Dose level 3 of PBI-0451

干预措施: PBI-0451 Dose 3 (Drug)

Part 1, Treatment C

Experimental

Dose level 3 of PBI-0451

干预措施: Placebo (Drug)

Part 1, Treatment D

Experimental

Dose level 4 of PBI-0451

干预措施: PBI-0451 Dose 4 (Drug)

Part 1, Treatment D

Experimental

Dose level 4 of PBI-0451

干预措施: Placebo (Drug)

Part 2, Treatment E

Experimental

PBI-0451 =/< Dose level 1

干预措施: PBI-0451 Dose 1 (Drug)

Part 2, Treatment E

Experimental

PBI-0451 =/< Dose level 1

干预措施: Placebo (Drug)

Part 2, Treatment F

Experimental

PBI-0451 =/< Dose level 2

干预措施: PBI-0451 Dose 2 (Drug)

Part 2, Treatment F

Experimental

PBI-0451 =/< Dose level 2

干预措施: Placebo (Drug)

Part 2, Treatment G

Experimental

PBI-0451 =/< Dose level 3

干预措施: PBI-0451 Dose 3 (Drug)

Part 2, Treatment G

Experimental

PBI-0451 =/< Dose level 3

干预措施: Placebo (Drug)

Part 2, Treatment H

Experimental

PBI-0451 =/< Dose level 4

干预措施: PBI-0451 Dose 4 (Drug)

Part 2, Treatment H

Experimental

PBI-0451 =/< Dose level 4

干预措施: Placebo (Drug)

Part 3, Treatment J

Experimental

PBI-0451 + ritonavir (a CYP450 3A inhibitor)

干预措施: Ritonavir (Drug)

Part 3, Treatment J

Experimental

PBI-0451 + ritonavir (a CYP450 3A inhibitor)

干预措施: Placebo (Drug)

Part 3, Treatment J

Experimental

PBI-0451 + ritonavir (a CYP450 3A inhibitor)

干预措施: PBI-0451 (Drug)

Part 3, Treatment K

Experimental

PBI-0451 + ritonavir

干预措施: Ritonavir (Drug)

Part 3, Treatment K

Experimental

PBI-0451 + ritonavir

干预措施: Placebo (Drug)

Part 3, Treatment K

Experimental

PBI-0451 + ritonavir

干预措施: PBI-0451 (Drug)

Part 3, Treatment L

Experimental

PBI-0451 dose TBD

midazolam (a sensitive CYP450 3A substrate)

干预措施: Midazolam (Drug)

Part 3, Treatment L

Experimental

PBI-0451 dose TBD

midazolam (a sensitive CYP450 3A substrate)

干预措施: Placebo (Drug)

Part 3, Treatment L

Experimental

PBI-0451 dose TBD

midazolam (a sensitive CYP450 3A substrate)

干预措施: PBI-0451 (Drug)

Part 1, Treatment M

Experimental

Dose level 2 of PBI-0451 with food

干预措施: PBI-0451 Dose 2 (Drug)

Part 1, Treatment M

Experimental

Dose level 2 of PBI-0451 with food

干预措施: Placebo (Drug)

Part 2, Treatment I

Experimental

PBI-0451 =/< Dose level 5

干预措施: Placebo (Drug)

Part 2, Treatment I

Experimental

PBI-0451 =/< Dose level 5

干预措施: PBI-0451 Dose 5 (Drug)

结局指标

主要结局

Number of subjects with treatment emergent adverse events (TEAEs) in Single Ascending Dose (SAD) compared to placebo

时间窗: Day 1- Day 14 (From start of study medication till 14 days of last administration of study drug)

An adverse event is any untoward medical occurrence in patient or clinical study participant temporarily associated with the use of study intervention, whether or not considered related to the study intervention. A serious adverse event (SAE) is defined as any untoward medical occurrence at any dose that results in death; is life threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent disability/incapacity; results in congenital anomaly/birth defect. AEs include both SAEs and AEs. TAEs are AEs that occur following the start of treatment or AEs increasing in severity during treatment.

Number of subjects with treatment emergent adverse events (TEAEs) in Multiple Ascending Dose (MAD) compared to placebo

时间窗: Day 1-Day 11, and Follow up (after 14 days)

Number of subjects with clinically significant change from Baseline in vital signs in SAD

时间窗: Day 1-Day 14 (From start of study medication till 14 days of last administration of study drug)

Vital signs include blood pressure, heart rate, respiratory rate, and temperature

Number of patients with laboratory abnormalities in SAD

时间窗: Day 1-Day 14 (From start of study medication till 14 days of last administration of study drug)

Hematology and serum chemistry

Number of subjects with clinically significant change from Baseline in vital signs in MAD

时间窗: Day 1-Day 11, and Follow up (after 14 days)

Vital signs include blood pressure, heart rate, respiratory rate, and temperature

Number of patients with laboratory abnormalities in MAD

时间窗: Day 1-Day 11, and Follow up (after 14 days)

Hematology and serum chemistry

次要结局

Plasma concentration of each dose of study drug to determine Clast in MAD(Day 4, Day 6, Day 8)
Plasma concentration of each dose of study drug to determine Vz/F(Day 4, Day 6, Day 8)
To collect ECG data for PBI-0451 for the purpose of concentration-QT/QTc modeling(Day 1, 4, 6 and 11)
Plasma concentration of each dose of study drug to determine AUCinf in SAD(Day 1-Day 6)
Plasma concentration of each dose of study drug to determine %AUCexp in SAD(Day 1-Day 6)
Plasma concentration of each dose of study drug to determine CL/F in SAD(Day 1-Day 6)
Plasma concentration of each dose of study drug to determine Tmax in MAD(Day 4, Day 6, Day 8 (Pre dose to 24 hours))
Plasma concentration of each dose of study drug to determine λz in MAD(Day 4, Day 6, Day 8)
Plasma concentration of each dose of study drug to determine AUClast in SAD(Day 1-Day 6)
Plasma concentration of each dose of study drug to determine AUCtau in MAD(Day 4, Day 6, Day 8)
Plasma concentration of each dose of study drug to determine Tlast in MAD(Day 4, Day 6, Day 8)
Plasma concentration of each dose of study drug to determine Ctau in MAD(Day 4, Day 6, Day 8)
Plasma concentration of each dose of study drug to determine CLss/F in MAD(Day 4, Day 6, Day 8)
Plasma concentration of each dose of study drug to determine Cmax in MAD(Day 4, Day 6, Day 8 (Pre dose to 24 hours))
Plasma concentration of each dose of study drug to determine t1/2(Day 1(0 hours- 24 hours post dose), Day 4, Day 6, Day 8)

研究者

发起方

Pardes Biosciences, Inc.

申办方类型

Industry

责任方

Sponsor

研究点 (1)

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