Study of PBI-0451 in Healthy Subjects.

NCT05011812 | Completed Phase 1

• 1 other identifier: PBI-0451-0001
• Study Type: interventional
• Target: 130
• Locations: 1 country
• Sites: 1

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.

Conditions

Covid19

Outcome Measures

Primary Outcomes (6)

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

  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.

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

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

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

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

• Number of patients with laboratory abnormalities in SAD

  Hematology and serum chemistry

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

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

  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.

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

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

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

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

• Number of patients with laboratory abnormalities in MAD

  Hematology and serum chemistry

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

Secondary Outcomes (15)

• 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 AUClast 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

Study Arms (14)

Part 1, Treatment A

EXPERIMENTAL

Dose level 1 of PBI-0451

Drug: PBI-0451 Dose 1; Drug: Placebo

Part 1, Treatment B

EXPERIMENTAL

Dose level 2 of PBI-0451

Drug: PBI-0451 Dose 2; Drug: Placebo

Part 1, Treatment C

EXPERIMENTAL

Dose level 3 of PBI-0451

Drug: PBI-0451 Dose 3; Drug: Placebo

Part 1, Treatment D

EXPERIMENTAL

Dose level 4 of PBI-0451

Drug: PBI-0451 Dose 4; Drug: Placebo

Part 2, Treatment E

EXPERIMENTAL

PBI-0451 =/\< Dose level 1

Drug: PBI-0451 Dose 1; Drug: Placebo

Part 2, Treatment F

EXPERIMENTAL

PBI-0451 =/\< Dose level 2

Drug: PBI-0451 Dose 2; Drug: Placebo

Part 2, Treatment G

EXPERIMENTAL

PBI-0451 =/\< Dose level 3

Drug: PBI-0451 Dose 3; Drug: Placebo

Part 2, Treatment H

EXPERIMENTAL

PBI-0451 =/\< Dose level 4

Drug: PBI-0451 Dose 4; Drug: Placebo

Part 3, Treatment J

EXPERIMENTAL

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

Drug: Ritonavir; Drug: Placebo; Drug: PBI-0451

Part 3, Treatment K

EXPERIMENTAL

PBI-0451 + ritonavir

Drug: Ritonavir; Drug: Placebo; Drug: PBI-0451

Part 3, Treatment L

EXPERIMENTAL

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

Drug: Midazolam; Drug: Placebo; Drug: PBI-0451

Part 1, Treatment M

EXPERIMENTAL

Dose level 2 of PBI-0451 with food

Drug: PBI-0451 Dose 2; Drug: Placebo

Part 2, Treatment I

EXPERIMENTAL

PBI-0451 =/\< Dose level 5

Drug: Placebo; Drug: PBI-0451 Dose 5

Part 1, Treatment N

EXPERIMENTAL

Dose Level 5 of PBI-0451

Drug: Placebo; Drug: PBI-0451 Dose 5

Interventions

PBI-0451 Dose 1 DRUG

Dose level 1 of PBI-0451

Also known as: PBI-0451

Part 1, Treatment A; Part 2, Treatment E

PBI-0451 Dose 2 DRUG

Dose level 2 of PBI-0451

Also known as: PBI-0451

Part 1, Treatment B; Part 1, Treatment M; Part 2, Treatment F

PBI-0451 Dose 3 DRUG

Dose level 3 of PBI-0451

Also known as: PBI-0451

Part 1, Treatment C; Part 2, Treatment G

PBI-0451 Dose 4 DRUG

Dose level 4 of PBI-0451

Also known as: PBI-0451

Part 1, Treatment D; Part 2, Treatment H

Ritonavir DRUG

Ritonavir will be co-administered with the study drug in Treatments J and K

Also known as: Norvir

Part 3, Treatment J; Part 3, Treatment K

Midazolam DRUG

Midazolam will be co-administered with the study drug in Treatment L

Part 3, Treatment L

Placebo DRUG

Placebo to match

Part 1, Treatment A; Part 1, Treatment B; Part 1, Treatment C; Part 1, Treatment D; Part 1, Treatment M; Part 1, Treatment N; Part 2, Treatment E; Part 2, Treatment F; Part 2, Treatment G; Part 2, Treatment H; Part 2, Treatment I; Part 3, Treatment J; Part 3, Treatment K; Part 3, Treatment L

PBI-0451 DRUG

Dose level of PBI-0451 with a projected exposure

Part 3, Treatment J; Part 3, Treatment K; Part 3, Treatment L

PBI-0451 Dose 5 DRUG

Dose level 5 of PBI-0451

Also known as: PBi-0451

Part 1, Treatment N; Part 2, Treatment I

Eligibility Criteria

• Age: 18 Years - 59 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Non-smoking, healthy male or female subjects aged 18-59 years.
• Body Mass Index (BMI) of ≥ 19.0 and ≤ 30.0 kg/m2.
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Pardes Biosciences, Inc.: lead

Study Sites (1)

Auckland City Hospital

Auckland, 1010, New Zealand

Location

MeSH Terms

Conditions

COVID-19

Interventions

PBI-0451; Ritonavir; Midazolam

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Mark Marshall

  New Zealand Clinical Research

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Open to Sponsor
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 11, 2021
• First Posted: August 18, 2021
• Study Start: August 14, 2021
• Primary Completion: March 26, 2022
• Study Completion: March 26, 2022
• Last Updated: June 3, 2022

Record last verified: 2022-06

Locations

NZ (1)