Clinical trial NCT05011812: Study of PBI-0451 in Healthy Subjects.
Official title: A Single and Multiple Ascending Dose Study to Evaluate the Safety, Tolerability and Pharmacokinetics of PBI-0451 in Healthy Subjects.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Covid19
Lead sponsor: Pardes Biosciences, Inc.
Sponsor class: INDUSTRY
First posted: 2021-08-18
Enrollment: 130
Sex: ALL
Minimum age (years): 18
Maximum age (years): 59
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Number of subjects with treatment emergent adverse events (TEAEs) in Single Ascending Dose (SAD) compared to placebo
timeFrame: Day 1- Day 14 (From start of study medication till 14 days of last administration of study drug)
measure: Number of subjects with clinically significant change from Baseline in vital signs in SAD
timeFrame: Day 1-Day 14 (From start of study medication till 14 days of last administration of study drug)
measure: Number of patients with laboratory abnormalities in SAD
timeFrame: Day 1-Day 14 (From start of study medication till 14 days of last administration of study drug)
measure: Number of subjects with treatment emergent adverse events (TEAEs) in Multiple Ascending Dose (MAD) compared to placebo
timeFrame: Day 1-Day 11, and Follow up (after 14 days)
measure: Number of subjects with clinically significant change from Baseline in vital signs in MAD
timeFrame: Day 1-Day 11, and Follow up (after 14 days)
measure: Number of patients with laboratory abnormalities in MAD
timeFrame: Day 1-Day 11, and Follow up (after 14 days)
Secondary outcomes:
measure: To collect ECG data for PBI-0451 for the purpose of concentration-QT/QTc modeling
timeFrame: Day 1, 4, 6 and 11
measure: Plasma concentration of each dose of study drug to determine AUCinf in SAD
timeFrame: Day 1-Day 6
measure: Plasma concentration of each dose of study drug to determine AUClast in SAD
timeFrame: Day 1-Day 6
measure: Plasma concentration of each dose of study drug to determine %AUCexp in SAD
timeFrame: Day 1-Day 6
measure: Plasma concentration of each dose of study drug to determine CL/F in SAD
timeFrame: Day 1-Day 6
measure: Plasma concentration of each dose of study drug to determine CLss/F in MAD
timeFrame: Day 4, Day 6, Day 8
measure: Plasma concentration of each dose of study drug to determine AUCtau in MAD
timeFrame: Day 4, Day 6, Day 8
measure: Plasma concentration of each dose of study drug to determine Cmax in MAD
timeFrame: Day 4, Day 6, Day 8 (Pre dose to 24 hours)
measure: Plasma concentration of each dose of study drug to determine Tmax in MAD
timeFrame: Day 4, Day 6, Day 8 (Pre dose to 24 hours)
measure: Plasma concentration of each dose of study drug to determine Tlast in MAD
timeFrame: Day 4, Day 6, Day 8
measure: Plasma concentration of each dose of study drug to determine Clast in MAD
timeFrame: Day 4, Day 6, Day 8
measure: Plasma concentration of each dose of study drug to determine Ctau in MAD
timeFrame: Day 4, Day 6, Day 8
measure: Plasma concentration of each dose of study drug to determine λz in MAD
timeFrame: Day 4, Day 6, Day 8
measure: Plasma concentration of each dose of study drug to determine t1/2
timeFrame: Day 1(0 hours- 24 hours post dose), Day 4, Day 6, Day 8
measure: Plasma concentration of each dose of study drug to determine Vz/F
timeFrame: Day 4, Day 6, Day 8
Other outcomes:
Locations:
city: Auckland
country: New Zealand
facility: Auckland City Hospital
Study officials:
affiliation: New Zealand Clinical Research
name: Mark Marshall
role: PRINCIPAL_INVESTIGATOR
References: