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Completed

NCT Number: NCT05011812

Study of PBI-0451 in Healthy Subjects.

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.

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Key information

Conditions

Covid19 COVID-19 Coronaviridae Infections Coronavirus Infections Infections Lung Diseases Nidovirales Infections Pneumonia Pneumonia, Viral RNA Virus Infections Respiratory Tract Diseases Respiratory Tract Infections Virus Diseases

Age range

18 year–59 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Auckland City Hospital

Auckland, 1010, New Zealand

About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

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

Exclusion criteria

  • 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.

Treatment and study plan

PBI-0451 Dose 1

Drug

Dose level 1 of PBI-0451

Other names: PBI-0451

PBI-0451 Dose 2

Drug

Dose level 2 of PBI-0451

Other names: PBI-0451

PBI-0451 Dose 3

Drug

Dose level 3 of PBI-0451

Other names: PBI-0451

PBI-0451 Dose 4

Drug

Dose level 4 of PBI-0451

Other names: PBI-0451

Ritonavir

Drug

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

Other names: Norvir

midazolam

Drug

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

Placebo

Drug

Placebo to match

PBI-0451

Drug

Dose level of PBI-0451 with a projected exposure

PBI-0451 Dose 5

Drug

Dose level 5 of PBI-0451

Other names: PBi-0451

Primary outcomes

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

    Time frame: 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.

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

    Time frame: 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

  3. Number of patients with laboratory abnormalities in SAD

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

    Hematology and serum chemistry

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

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

    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.

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

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

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

  6. Number of patients with laboratory abnormalities in MAD

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

    Hematology and serum chemistry

Secondary outcomes

  1. To collect ECG data for PBI-0451 for the purpose of concentration-QT/QTc modeling

    Time frame: Day 1, 4, 6 and 11

    Criteria for clinically significant changes in ECG (12 lead) are defined as: a postdose QTc interval increase by =/>30msec from the baseline and is >450 msec; or an absolute QTc value is =/> 500 msec for any scheduled ECG.

  2. Plasma concentration of each dose of study drug to determine AUCinf in SAD

    Time frame: Day 1-Day 6

    AUCinf = Area under the plasma concentration versus time curve (AUC) from time 0 to extrapolated infinite time.

  3. Plasma concentration of each dose of study drug to determine AUClast in SAD

    Time frame: Day 1-Day 6

    AUClast is summarized by dosing regimen and determined by linear/log trapezoidal method.

  4. Plasma concentration of each dose of study drug to determine %AUCexp in SAD

    Time frame: Day 1-Day 6

    %AUCexp is summarized by dosing regimen and expressed as area under the plasma concentration-time curve extrapolated from time (tau) to infinity as a percentage of total AUC

  5. Plasma concentration of each dose of study drug to determine CL/F in SAD

    Time frame: Day 1-Day 6

    CL/F is a measure of the rate at which a drug is metabolized or eliminated by normal biological process

  6. Plasma concentration of each dose of study drug to determine CLss/F in MAD

    Time frame: Day 4, Day 6, Day 8

    CLss/F is the total body clearance for extravascular administration divided by the fraction of dose absorbed

  7. Plasma concentration of each dose of study drug to determine AUCtau in MAD

    Time frame: Day 4, Day 6, Day 8

    Area under the plasma concentration- Time profile from Time zero to end of dosing interval. AUCtau is summarized by dosing regimen and period.

  8. Plasma concentration of each dose of study drug to determine Cmax in MAD

    Time frame: Day 4, Day 6, Day 8 (Pre dose to 24 hours)

    Observed Cmax is estimated based on the plasma concentrations.

  9. Plasma concentration of each dose of study drug to determine Tmax in MAD

    Time frame: Day 4, Day 6, Day 8 (Pre dose to 24 hours)

    Tmax is summarized by dosing regimen

  10. Plasma concentration of each dose of study drug to determine Tlast in MAD

    Time frame: Day 4, Day 6, Day 8

    Tlast is the time of last measurable concentration

  11. Plasma concentration of each dose of study drug to determine Clast in MAD

    Time frame: Day 4, Day 6, Day 8

    Clast is the last measurable concentration (above the quantification limit)

  12. Plasma concentration of each dose of study drug to determine Ctau in MAD

    Time frame: Day 4, Day 6, Day 8

    Ctau is the concentration at the end of dosing interval

  13. Plasma concentration of each dose of study drug to determine λz in MAD

    Time frame: Day 4, Day 6, Day 8

    Individual estimate of terminal elimination rate constant, calculated using log-linear regression of the terminal portions of the plasma concentration-versus-time curves.

  14. Plasma concentration of each dose of study drug to determine t1/2

    Time frame: Day 1(0 hours- 24 hours post dose), Day 4, Day 6, Day 8

    t1/2 is summarized by dosing regimen . It is determined by loge(2)/kel, where kel is the terminal phase rate constant calculated by a linear regression of the log linear concentration time curve. Only those data points judged to describe the terminal log linear decline is used in the regression.

  15. Plasma concentration of each dose of study drug to determine Vz/F

    Time frame: Day 4, Day 6, Day 8

    Vz/F is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. VZ/F after oral dose is influenced by the fraction absorbed.

Sponsors and collaborators

Lead sponsor

Pardes Biosciences, Inc.

Industry

Registry information

Official study title

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

Important dates

Study start
2021
Primary completion
2022
Study completion
2022
First posted
Aug 18, 2021
Registry last updated
Jun 3, 2022

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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