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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/study/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.
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Scientific title
A Single and Multiple Ascending Dose Study to Evaluate the Safety, Tolerability and Pharmacokinetics of PBI-0451 in Healthy Subjects.
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Secondary ID [1]
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PBI-0451-0001
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Universal Trial Number (UTN)
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Trial acronym
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Covid19
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Condition category
Condition code
Intervention/exposure
Study type
Interventional
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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
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Intervention code [1]
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Treatment: Drugs
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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Number of subjects with treatment emergent adverse events (TEAEs) in Single Ascending Dose (SAD) compared to placebo
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Assessment method [1]
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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.
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Timepoint [1]
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Day 1- Day 14 (From start of study medication till 14 days of last administration of study drug)
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Primary outcome [2]
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Number of subjects with clinically significant change from Baseline in vital signs in SAD
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Assessment method [2]
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Vital signs include blood pressure, heart rate, respiratory rate, and temperature
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Timepoint [2]
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Day 1-Day 14 (From start of study medication till 14 days of last administration of study drug)
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Primary outcome [3]
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Number of patients with laboratory abnormalities in SAD
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Assessment method [3]
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Hematology and serum chemistry
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Timepoint [3]
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Day 1-Day 14 (From start of study medication till 14 days of last administration of study drug)
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Primary outcome [4]
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Number of subjects with treatment emergent adverse events (TEAEs) in Multiple Ascending Dose (MAD) compared to placebo
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Assessment method [4]
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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.
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Timepoint [4]
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Day 1-Day 11, and Follow up (after 14 days)
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Primary outcome [5]
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Number of subjects with clinically significant change from Baseline in vital signs in MAD
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Assessment method [5]
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Vital signs include blood pressure, heart rate, respiratory rate, and temperature
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Timepoint [5]
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Day 1-Day 11, and Follow up (after 14 days)
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Primary outcome [6]
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Number of patients with laboratory abnormalities in MAD
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Assessment method [6]
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Hematology and serum chemistry
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Timepoint [6]
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Day 1-Day 11, and Follow up (after 14 days)
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Secondary outcome [1]
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To collect ECG data for PBI-0451 for the purpose of concentration-QT/QTc modeling
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Assessment method [1]
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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.
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Timepoint [1]
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Day 1, 4, 6 and 11
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Secondary outcome [2]
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Plasma concentration of each dose of study drug to determine AUCinf in SAD
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Assessment method [2]
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AUCinf = Area under the plasma concentration versus time curve (AUC) from time 0 to extrapolated infinite time.
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Timepoint [2]
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Day 1-Day 6
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Secondary outcome [3]
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Plasma concentration of each dose of study drug to determine AUClast in SAD
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Assessment method [3]
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AUClast is summarized by dosing regimen and determined by linear/log trapezoidal method.
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Timepoint [3]
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Day 1-Day 6
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Secondary outcome [4]
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Plasma concentration of each dose of study drug to determine %AUCexp in SAD
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Assessment method [4]
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%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
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Timepoint [4]
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Day 1-Day 6
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Secondary outcome [5]
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Plasma concentration of each dose of study drug to determine CL/F in SAD
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Assessment method [5]
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CL/F is a measure of the rate at which a drug is metabolized or eliminated by normal biological process
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Timepoint [5]
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Day 1-Day 6
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Secondary outcome [6]
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Plasma concentration of each dose of study drug to determine CLss/F in MAD
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Assessment method [6]
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CLss/F is the total body clearance for extravascular administration divided by the fraction of dose absorbed
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Timepoint [6]
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Day 4, Day 6, Day 8
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Secondary outcome [7]
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Plasma concentration of each dose of study drug to determine AUCtau in MAD
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Assessment method [7]
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Area under the plasma concentration- Time profile from Time zero to end of dosing interval. AUCtau is summarized by dosing regimen and period.
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Timepoint [7]
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Day 4, Day 6, Day 8
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Secondary outcome [8]
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Plasma concentration of each dose of study drug to determine Cmax in MAD
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Assessment method [8]
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Observed Cmax is estimated based on the plasma concentrations.
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Timepoint [8]
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Day 4, Day 6, Day 8 (Pre dose to 24 hours)
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Secondary outcome [9]
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Plasma concentration of each dose of study drug to determine Tmax in MAD
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Assessment method [9]
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Tmax is summarized by dosing regimen
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Timepoint [9]
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Day 4, Day 6, Day 8 (Pre dose to 24 hours)
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Secondary outcome [10]
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Plasma concentration of each dose of study drug to determine Tlast in MAD
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Assessment method [10]
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Tlast is the time of last measurable concentration
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Timepoint [10]
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Day 4, Day 6, Day 8
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Secondary outcome [11]
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Plasma concentration of each dose of study drug to determine Clast in MAD
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Assessment method [11]
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Clast is the last measurable concentration (above the quantification limit)
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Timepoint [11]
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Day 4, Day 6, Day 8
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Secondary outcome [12]
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Plasma concentration of each dose of study drug to determine Ctau in MAD
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Assessment method [12]
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Ctau is the concentration at the end of dosing interval
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Timepoint [12]
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Day 4, Day 6, Day 8
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Secondary outcome [13]
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Plasma concentration of each dose of study drug to determine ?z in MAD
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Assessment method [13]
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Individual estimate of terminal elimination rate constant, calculated using log-linear regression of the terminal portions of the plasma concentration-versus-time curves.
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Timepoint [13]
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Day 4, Day 6, Day 8
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Secondary outcome [14]
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Plasma concentration of each dose of study drug to determine t1/2
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Assessment method [14]
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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.
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Timepoint [14]
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Day 1(0 hours- 24 hours post dose), Day 4, Day 6, Day 8
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Secondary outcome [15]
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Plasma concentration of each dose of study drug to determine Vz/F
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Assessment method [15]
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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.
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Timepoint [15]
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Day 4, Day 6, Day 8
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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.
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Minimum age
18
Years
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Maximum age
59
Years
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Sex
Both males and females
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Can healthy volunteers participate?
Yes
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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.
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Study design
Purpose of the study
Treatment
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Allocation to intervention
Randomised controlled trial
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
Blinded (masking used)
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Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people analysing the results/data
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Intervention assignment
Parallel
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Other design features
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Phase
Phase 1
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Type of endpoint/s
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Statistical methods / analysis
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Recruitment
Recruitment status
Completed
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Data analysis
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Reason for early stopping/withdrawal
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Other reasons
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Date of first participant enrolment
Anticipated
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Actual
14/08/2021
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Date of last participant enrolment
Anticipated
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Actual
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Date of last data collection
Anticipated
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Actual
26/03/2022
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Sample size
Target
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Accrual to date
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Final
130
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Recruitment in Australia
Recruitment state(s)
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Recruitment outside Australia
Country [1]
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New Zealand
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State/province [1]
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Auckland
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Funding & Sponsors
Primary sponsor type
Commercial sector/industry
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Name
Pardes Biosciences, Inc.
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Address
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Country
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Ethics approval
Ethics application status
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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.
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Trial website
https://clinicaltrials.gov/study/NCT05011812
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Trial related presentations / publications
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Public notes
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Contacts
Principal investigator
Name
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Mark Marshall
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Address
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New Zealand Clinical Research
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Country
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Phone
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Fax
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Email
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Contact person for public queries
Name
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Address
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Country
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Phone
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Fax
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Email
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Contact person for scientific queries
No information has been provided regarding IPD availability
What supporting documents are/will be available?
No Supporting Document Provided
Results publications and other study-related documents
No documents have been uploaded by study researchers.
Results not provided in
https://clinicaltrials.gov/study/NCT05011812
Download to PDF