Study of PBI-0451 in Healthy Subjects.

June 1, 2022 updated by: Pardes Biosciences, Inc.

A Single and Multiple Ascending Dose Study to Evaluate the Safety, Tolerability and Pharmacokinetics 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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
130

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • New Zealand
      • Auckland, New Zealand, 1010
        • Auckland City Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 59 years (ADULT)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: TRIPLE

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
EXPERIMENTAL: Part 1, Treatment A
Dose level 1 of PBI-0451
Drug: Placebo
Placebo to match
Drug: PBI-0451 Dose 1
Dose level 1 of PBI-0451
Other Names:
  • PBI-0451
EXPERIMENTAL: Part 1, Treatment B
Dose level 2 of PBI-0451
Drug: Placebo
Placebo to match
Drug: PBI-0451 Dose 2
Dose level 2 of PBI-0451
Other Names:
  • PBI-0451
EXPERIMENTAL: Part 1, Treatment C
Dose level 3 of PBI-0451
Drug: Placebo
Placebo to match
Drug: PBI-0451 Dose 3
Dose level 3 of PBI-0451
Other Names:
  • PBI-0451
EXPERIMENTAL: Part 1, Treatment D
Dose level 4 of PBI-0451
Drug: Placebo
Placebo to match
Drug: PBI-0451 Dose 4
Dose level 4 of PBI-0451
Other Names:
  • PBI-0451
EXPERIMENTAL: Part 2, Treatment E
PBI-0451 =/< Dose level 1
Drug: Placebo
Placebo to match
Drug: PBI-0451 Dose 1
Dose level 1 of PBI-0451
Other Names:
  • PBI-0451
EXPERIMENTAL: Part 2, Treatment F
PBI-0451 =/< Dose level 2
Drug: Placebo
Placebo to match
Drug: PBI-0451 Dose 2
Dose level 2 of PBI-0451
Other Names:
  • PBI-0451
EXPERIMENTAL: Part 2, Treatment G
PBI-0451 =/< Dose level 3
Drug: Placebo
Placebo to match
Drug: PBI-0451 Dose 3
Dose level 3 of PBI-0451
Other Names:
  • PBI-0451
EXPERIMENTAL: Part 2, Treatment H
PBI-0451 =/< Dose level 4
Drug: Placebo
Placebo to match
Drug: PBI-0451 Dose 4
Dose level 4 of PBI-0451
Other Names:
  • PBI-0451
EXPERIMENTAL: Part 3, Treatment J
PBI-0451 + ritonavir (a CYP450 3A inhibitor)
Drug: Placebo
Placebo to match
Drug: Ritonavir
Ritonavir will be co-administered with the study drug in Treatments J and K
Other Names:
  • Norvir
Drug: PBI-0451
Dose level of PBI-0451 with a projected exposure
EXPERIMENTAL: Part 3, Treatment K
PBI-0451 + ritonavir
Drug: Placebo
Placebo to match
Drug: Ritonavir
Ritonavir will be co-administered with the study drug in Treatments J and K
Other Names:
  • Norvir
Drug: PBI-0451
Dose level of PBI-0451 with a projected exposure
EXPERIMENTAL: Part 3, Treatment L

PBI-0451 dose TBD

+ midazolam (a sensitive CYP450 3A substrate)
Drug: Placebo
Placebo to match
Drug: PBI-0451
Dose level of PBI-0451 with a projected exposure
Drug: Midazolam
Midazolam will be co-administered with the study drug in Treatment L
EXPERIMENTAL: Part 1, Treatment M
Dose level 2 of PBI-0451 with food
Drug: Placebo
Placebo to match
Drug: PBI-0451 Dose 2
Dose level 2 of PBI-0451
Other Names:
  • PBI-0451
EXPERIMENTAL: Part 2, Treatment I
PBI-0451 =/< Dose level 5
Drug: Placebo
Placebo to match
Drug: PBI-0451 Dose 5
Dose level 5 of PBI-0451
Other Names:
  • PBi-0451
EXPERIMENTAL: Part 1, Treatment N
Dose Level 5 of PBI-0451
Drug: Placebo
Placebo to match
Drug: PBI-0451 Dose 5
Dose level 5 of PBI-0451
Other Names:
  • PBi-0451

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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.
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
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
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
Time Frame: Day 1-Day 14 (From start of study medication till 14 days of last administration of study drug)
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
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.
Day 1-Day 11, and Follow up (after 14 days)
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
Day 1-Day 11, and Follow up (after 14 days)
Number of patients with laboratory abnormalities in MAD
Time Frame: Day 1-Day 11, and Follow up (after 14 days)
Hematology and serum chemistry
Day 1-Day 11, and Follow up (after 14 days)

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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.
Day 1, 4, 6 and 11
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.
Day 1-Day 6
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.
Day 1-Day 6
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
Day 1-Day 6
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
Day 1-Day 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
Day 4, Day 6, Day 8
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.
Day 4, Day 6, Day 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.
Day 4, Day 6, Day 8 (Pre dose to 24 hours)
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
Day 4, Day 6, Day 8 (Pre dose to 24 hours)
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
Day 4, Day 6, Day 8
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)
Day 4, Day 6, Day 8
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
Day 4, Day 6, Day 8
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.
Day 4, Day 6, Day 8
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.
Day 1(0 hours- 24 hours post dose), Day 4, Day 6, Day 8
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.
Day 4, Day 6, Day 8

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Pardes Biosciences, Inc.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
August 14, 2021

Primary Completion (ACTUAL)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
March 26, 2022

Study Completion (ACTUAL)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
March 26, 2022

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
August 11, 2021

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 13, 2021

First Posted (ACTUAL)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
August 18, 2021

Study Record Updates

Last Update Posted (ACTUAL)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
June 3, 2022

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 1, 2022

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
June 1, 2022

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • PBI-0451-0001

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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