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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT05011812




Registration number
NCT05011812
Ethics application status
Date submitted
11/08/2021
Date registered
18/08/2021
Date last updated
3/06/2022

Titles & IDs
Public title
Study of PBI-0451 in Healthy Subjects.
Scientific title
A Single and Multiple Ascending Dose Study to Evaluate the Safety, Tolerability and Pharmacokinetics of PBI-0451 in Healthy Subjects.
Secondary ID [1] 0 0
PBI-0451-0001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Covid19 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - PBI-0451 Dose 1
Treatment: Drugs - PBI-0451 Dose 2
Treatment: Drugs - PBI-0451 Dose 3
Treatment: Drugs - PBI-0451 Dose 4
Treatment: Drugs - Ritonavir
Treatment: Drugs - Midazolam
Treatment: Drugs - Placebo
Treatment: Drugs - PBI-0451
Treatment: Drugs - PBI-0451 Dose 5

Experimental: Part 1, Treatment A - Dose level 1 of PBI-0451

Experimental: Part 1, Treatment B - Dose level 2 of PBI-0451

Experimental: Part 1, Treatment C - Dose level 3 of PBI-0451

Experimental: Part 1, Treatment D - Dose level 4 of PBI-0451

Experimental: Part 2, Treatment E - PBI-0451 =/< Dose level 1

Experimental: Part 2, Treatment F - PBI-0451 =/< Dose level 2

Experimental: Part 2, Treatment G - PBI-0451 =/< Dose level 3

Experimental: Part 2, Treatment H - PBI-0451 =/< Dose level 4

Experimental: Part 3, Treatment J - PBI-0451 + ritonavir (a CYP450 3A inhibitor)

Experimental: Part 3, Treatment K - PBI-0451 + ritonavir

Experimental: Part 3, Treatment L - PBI-0451 dose TBD
+ midazolam (a sensitive CYP450 3A substrate)

Experimental: Part 1, Treatment M - Dose level 2 of PBI-0451 with food

Experimental: Part 2, Treatment I - PBI-0451 =/< Dose level 5

Experimental: Part 1, Treatment N - Dose Level 5 of PBI-0451


Treatment: Drugs: PBI-0451 Dose 1
Dose level 1 of PBI-0451

Treatment: Drugs: PBI-0451 Dose 2
Dose level 2 of PBI-0451

Treatment: Drugs: PBI-0451 Dose 3
Dose level 3 of PBI-0451

Treatment: Drugs: PBI-0451 Dose 4
Dose level 4 of PBI-0451

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

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

Treatment: Drugs: Placebo
Placebo to match

Treatment: Drugs: PBI-0451
Dose level of PBI-0451 with a projected exposure

Treatment: Drugs: PBI-0451 Dose 5
Dose level 5 of PBI-0451
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of subjects with treatment emergent adverse events (TEAEs) in Single Ascending Dose (SAD) compared to placebo
Timepoint [1] 0 0
Day 1- Day 14 (From start of study medication till 14 days of last administration of study drug)
Primary outcome [2] 0 0
Number of subjects with clinically significant change from Baseline in vital signs in SAD
Timepoint [2] 0 0
Day 1-Day 14 (From start of study medication till 14 days of last administration of study drug)
Primary outcome [3] 0 0
Number of patients with laboratory abnormalities in SAD
Timepoint [3] 0 0
Day 1-Day 14 (From start of study medication till 14 days of last administration of study drug)
Primary outcome [4] 0 0
Number of subjects with treatment emergent adverse events (TEAEs) in Multiple Ascending Dose (MAD) compared to placebo
Timepoint [4] 0 0
Day 1-Day 11, and Follow up (after 14 days)
Primary outcome [5] 0 0
Number of subjects with clinically significant change from Baseline in vital signs in MAD
Timepoint [5] 0 0
Day 1-Day 11, and Follow up (after 14 days)
Primary outcome [6] 0 0
Number of patients with laboratory abnormalities in MAD
Timepoint [6] 0 0
Day 1-Day 11, and Follow up (after 14 days)
Secondary outcome [1] 0 0
To collect ECG data for PBI-0451 for the purpose of concentration-QT/QTc modeling
Timepoint [1] 0 0
Day 1, 4, 6 and 11
Secondary outcome [2] 0 0
Plasma concentration of each dose of study drug to determine AUCinf in SAD
Timepoint [2] 0 0
Day 1-Day 6
Secondary outcome [3] 0 0
Plasma concentration of each dose of study drug to determine AUClast in SAD
Timepoint [3] 0 0
Day 1-Day 6
Secondary outcome [4] 0 0
Plasma concentration of each dose of study drug to determine %AUCexp in SAD
Timepoint [4] 0 0
Day 1-Day 6
Secondary outcome [5] 0 0
Plasma concentration of each dose of study drug to determine CL/F in SAD
Timepoint [5] 0 0
Day 1-Day 6
Secondary outcome [6] 0 0
Plasma concentration of each dose of study drug to determine CLss/F in MAD
Timepoint [6] 0 0
Day 4, Day 6, Day 8
Secondary outcome [7] 0 0
Plasma concentration of each dose of study drug to determine AUCtau in MAD
Timepoint [7] 0 0
Day 4, Day 6, Day 8
Secondary outcome [8] 0 0
Plasma concentration of each dose of study drug to determine Cmax in MAD
Timepoint [8] 0 0
Day 4, Day 6, Day 8 (Pre dose to 24 hours)
Secondary outcome [9] 0 0
Plasma concentration of each dose of study drug to determine Tmax in MAD
Timepoint [9] 0 0
Day 4, Day 6, Day 8 (Pre dose to 24 hours)
Secondary outcome [10] 0 0
Plasma concentration of each dose of study drug to determine Tlast in MAD
Timepoint [10] 0 0
Day 4, Day 6, Day 8
Secondary outcome [11] 0 0
Plasma concentration of each dose of study drug to determine Clast in MAD
Timepoint [11] 0 0
Day 4, Day 6, Day 8
Secondary outcome [12] 0 0
Plasma concentration of each dose of study drug to determine Ctau in MAD
Timepoint [12] 0 0
Day 4, Day 6, Day 8
Secondary outcome [13] 0 0
Plasma concentration of each dose of study drug to determine ?z in MAD
Timepoint [13] 0 0
Day 4, Day 6, Day 8
Secondary outcome [14] 0 0
Plasma concentration of each dose of study drug to determine t1/2
Timepoint [14] 0 0
Day 1(0 hours- 24 hours post dose), Day 4, Day 6, Day 8
Secondary outcome [15] 0 0
Plasma concentration of each dose of study drug to determine Vz/F
Timepoint [15] 0 0
Day 4, Day 6, Day 8

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
59 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key 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 design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
14/08/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
26/03/2022
Sample size
Target
Accrual to date
Final
130
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
New Zealand
State/province [1] 0 0
Auckland

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Pardes Biosciences, Inc.
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT05011812
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Mark Marshall
Address 0 0
New Zealand Clinical Research
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries