Study of PBI-0451 in Healthy Subjects.

Pardes Biosciences

Status and phase: Completed; Phase 1

Conditions: Covid19

Treatments: Drug: Ritonavir; Drug: PBI-0451 Dose 5; Drug: PBI-0451 Dose 1; Drug: PBI-0451 Dose 2; Drug: PBI-0451; Drug: Placebo; Drug: PBI-0451 Dose 4; Drug: PBI-0451 Dose 3; Drug: Midazolam

Study type: Interventional

Funder types: Industry

Identifiers

NCT05011812

PBI-0451-0001

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 130 patients

Sex: All

Ages: 18 to 59 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

1. Non-smoking, healthy male or female subjects aged 18-59 years.
2. Body Mass Index (BMI) of ≥ 19.0 and ≤ 30.0 kg/m2.
3. 12-Lead electrocardiogram (ECG) evaluation without clinically significant abnormalities.
4. Normal renal function, including having a creatinine clearance (CLcr) ≥90mL/min
5. Male subjects and female subjects of childbearing potential who engage in heterosexual intercourse must agree to use protocol-specified method(s) of contraception.
6. Screening laboratory assessments must be without clinically significant abnormalities as assessed by the investigator.

Exclusion criteria

1. Pregnant and lactating females
2. Have received any investigational drug (or vaccine) within the last 30 days prior to study dosing.
3. Have a positive test result for HIV or HBsAg.
4. Have poor venous access that limits phlebotomy
5. Have taken any prescription medications or over-the-counter medications, including herbal products and dietary supplements within 28 days prior to start of study.
6. 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.
7. 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.
8. 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.
9. Have received inactivated vaccinations within 4 weeks prior to randomization or receive live vaccinations within 4 weeks of Screening.
10. Received the COVID-19 vaccine either within 7 days or have not completed the series of required 2 doses.
11. Have a history of excessive alcohol use or other illicit drug use within 6 months of screening.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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130 participants in 14 patient groups

Part 1, Treatment A

Experimental group

Description:

Dose level 1 of PBI-0451

Treatment:

Drug: Placebo

Drug: PBI-0451 Dose 1

Part 1, Treatment B

Experimental group

Description:

Dose level 2 of PBI-0451

Treatment:

Drug: Placebo

Drug: PBI-0451 Dose 2

Part 1, Treatment C

Experimental group

Description:

Dose level 3 of PBI-0451

Treatment:

Drug: PBI-0451 Dose 3

Drug: Placebo

Part 1, Treatment D

Experimental group

Description:

Dose level 4 of PBI-0451

Treatment:

Drug: PBI-0451 Dose 4

Drug: Placebo

Part 2, Treatment E

Experimental group

Description:

PBI-0451 =/\< Dose level 1

Treatment:

Drug: Placebo

Drug: PBI-0451 Dose 1

Part 2, Treatment F

Experimental group

Description:

PBI-0451 =/\< Dose level 2

Treatment:

Drug: Placebo

Drug: PBI-0451 Dose 2

Part 2, Treatment G

Experimental group

Description:

PBI-0451 =/\< Dose level 3

Treatment:

Drug: PBI-0451 Dose 3

Drug: Placebo

Part 2, Treatment H

Experimental group

Description:

PBI-0451 =/\< Dose level 4

Treatment:

Drug: PBI-0451 Dose 4

Drug: Placebo

Part 3, Treatment J

Experimental group

Description:

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

Treatment:

Drug: PBI-0451

Drug: Placebo

Drug: Ritonavir

Part 3, Treatment K

Experimental group

Description:

PBI-0451 + ritonavir

Treatment:

Drug: PBI-0451

Drug: Placebo

Drug: Ritonavir

Part 3, Treatment L

Experimental group

Description:

PBI-0451 dose TBD + midazolam (a sensitive CYP450 3A substrate)

Treatment:

Drug: Midazolam

Drug: PBI-0451

Drug: Placebo

Part 1, Treatment M

Experimental group

Description:

Dose level 2 of PBI-0451 with food

Treatment:

Drug: Placebo

Drug: PBI-0451 Dose 2

Part 2, Treatment I

Experimental group

Description:

PBI-0451 =/\< Dose level 5

Treatment:

Drug: Placebo

Drug: PBI-0451 Dose 5

Part 1, Treatment N

Experimental group

Description:

Dose Level 5 of PBI-0451

Treatment:

Drug: Placebo

Drug: PBI-0451 Dose 5