Study of PBI-0451 in Healthy Subjects.

Covid19 Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05011812
• Other study ID #: PBI-0451-0001
• Status: Completed
• Phase: Phase 1
• Start date: August 14, 2021
• Est. completion date: March 26, 2022

Study information

• Verified date: June 2022
• Source: Pardes Biosciences, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 130
• Est. completion date: March 26, 2022
• Est. primary completion date: March 26, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 59 Years

Eligibility

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.

Related Conditions & MeSH terms

• Covid19

Intervention

Drug:
• PBI-0451 Dose 1
Dose level 1 of PBI-0451
• PBI-0451 Dose 2
Dose level 2 of PBI-0451
• PBI-0451 Dose 3
Dose level 3 of PBI-0451
• PBI-0451 Dose 4
Dose level 4 of PBI-0451
• Ritonavir
Ritonavir will be co-administered with the study drug in Treatments J and K
• Midazolam
Midazolam will be co-administered with the study drug in Treatment L
• Placebo
Placebo to match
• PBI-0451
Dose level of PBI-0451 with a projected exposure
• PBI-0451 Dose 5
Dose level 5 of PBI-0451

Locations

Country	Name	City	State
New Zealand	Auckland City Hospital	Auckland

Sponsors (1)

Lead Sponsor	Collaborator
Pardes Biosciences, Inc.

Country where clinical trial is conducted

New Zealand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	Number of patients with laboratory abnormalities in MAD	Hematology and serum chemistry	Day 1-Day 11, and Follow up (after 14 days)
Secondary	To collect ECG data for PBI-0451 for the purpose of concentration-QT/QTc modeling	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
Secondary	Plasma concentration of each dose of study drug to determine AUCinf in SAD	AUCinf = Area under the plasma concentration versus time curve (AUC) from time 0 to extrapolated infinite time.	Day 1-Day 6
Secondary	Plasma concentration of each dose of study drug to determine AUClast in SAD	AUClast is summarized by dosing regimen and determined by linear/log trapezoidal method.	Day 1-Day 6
Secondary	Plasma concentration of each dose of study drug to determine %AUCexp in SAD	%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
Secondary	Plasma concentration of each dose of study drug to determine CL/F in SAD	CL/F is a measure of the rate at which a drug is metabolized or eliminated by normal biological process	Day 1-Day 6
Secondary	Plasma concentration of each dose of study drug to determine CLss/F in MAD	CLss/F is the total body clearance for extravascular administration divided by the fraction of dose absorbed	Day 4, Day 6, Day 8
Secondary	Plasma concentration of each dose of study drug to determine AUCtau in MAD	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
Secondary	Plasma concentration of each dose of study drug to determine Cmax in MAD	Observed Cmax is estimated based on the plasma concentrations.	Day 4, Day 6, Day 8 (Pre dose to 24 hours)
Secondary	Plasma concentration of each dose of study drug to determine Tmax in MAD	Tmax is summarized by dosing regimen	Day 4, Day 6, Day 8 (Pre dose to 24 hours)
Secondary	Plasma concentration of each dose of study drug to determine Tlast in MAD	Tlast is the time of last measurable concentration	Day 4, Day 6, Day 8
Secondary	Plasma concentration of each dose of study drug to determine Clast in MAD	Clast is the last measurable concentration (above the quantification limit)	Day 4, Day 6, Day 8
Secondary	Plasma concentration of each dose of study drug to determine Ctau in MAD	Ctau is the concentration at the end of dosing interval	Day 4, Day 6, Day 8
Secondary	Plasma concentration of each dose of study drug to determine ?z in MAD	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
Secondary	Plasma concentration of each dose of study drug to determine t1/2	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
Secondary	Plasma concentration of each dose of study drug to determine Vz/F	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