Study to Assess the Safety, Tolerability and Pharmacokinetics of STI-1558 in Healthy Volunteers

Study Overview
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Brief Summary
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This is a Phase 1, two-part, randomized, double blind, placebo controlled, ascending dose study to evaluate the safety, tolerability, pharmacokinetics of STI-1558 administered orally to healthy volunteers.

Detailed Description
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This is a Phase 1, two-part, randomized, double blind, placebo controlled, single ascending dose (Part 1) and multiple ascending dose (Part 2) study to evaluate the safety, tolerability, pharmacokinetics (PK) of STI-1558 administered orally to healthy volunteers. Part 1 of the study will also incorporate a single-cohort arm to investigate the effect of food on the PK of STI-1558. Dietary status of administration in part 2 (fasted or fed) will be determined by the PK data from Part 1. Part 2 may run in parallel with Part 1, providing that the total daily dose to be administered does not exceed a dose already shown to be safe and well-tolerated in Part 1.

Official Title
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A Randomized, Double-Blind, Placebo-Controlled, Phase I Study to Assess the Safety, Tolerability, and Pharmacokinetics of Single and Multiple Oral Doses of STI-1558 in Healthy Volunteers

Conditions
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COVID-19

Intervention / Treatment
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* Drug: STI-1558
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Body mass index (BMI) is between 18 and 30 kg/m2 (both inclusive), and Body weight between 45 and 100 kg (inclusive) Generally normal, or abnormal with no clinical significance as judged by the primary investigator based on physical examination, vital signs, electrocardiogram, and clinical laboratory tests Willing to follow contraception guidelines Willing and able to comply with study procedures and follow-up visits Exclusion Criteria: Difficulty or history of dizziness during venous blood collection or encountering blood or needles Known or suspected pregnancy, planned pregnancy, a positive pregnancy test at screening or are breastfeeding A clinically relevant intolerance or allergy to drugs, or are known or suspected to have hypersensitivity to any ingredient in STI-1558 capsules Received an experimental agent within 1 month or 5 times half-life (whichever is longer) prior to the first dose of study drug Has a history of gastrointestinal, liver or kidney disease, or other condition that may exclude the subject as determined by the investigator Has a medical history of significant diseases as determined by the investigator Has a history of febrile illness within 14 days prior to the first dose of study drug Has values above the upper limit of normal alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase at screening or Day -1 and judged to be clinically significant by the investigator Prolonged QTcF interval Has had major surgery within 3 months prior to the first dose of study drug or plans to undergo surgery during the study Any marketed medication within 14 days or 5 times the half-life, whichever is longer, prior to the first dose of study drug Vaccinated within 14 days prior to the first dose of study drug or plans to be vaccinated during the study Is unwilling to abstain from quinine containing products or grapefruit during the study Use of BCRP substrates within 7 days prior to the first dose of study drug A known history of drug abuse within 2 years before screening or positive drug abuse test at screening Blood donation or blood loss > 400 mL within 3 months prior to screening Weekly alcohol consumption of more than 14 units of alcohol in any week within the past 3 months prior to screening, or intake of alcohol within 48 hours prior to first dose of study drug, or cannot abstain from alcohol during the study, or positive breath alcohol test at screening or Day -1 Significant smoking history within 3 months before screening Excessive drinking of caffeinated beverages within 3 months before screening, or intake of caffeine-containing products within 48 hours prior to the first dose of study drug Have human immunodeficiency virus (HIV) infection, human T-cell leukemia virus type 1 (HTLV1) infection, or hepatitis B virus (HBV) or hepatitis C virus (HCV) viremia or are at risk for HBV reactivation (at risk for HBV reactivation is defined as being HBs antigen positive, or anti-HBc-antibody positive), or are positive for HBV deoxyribonucleic acid (DNA). HCV ribonucleic acid (RNA) must be undetectable by laboratory test Positive SARS-CoV-2 test on Day -1 Subjects who are judged as not eligible to participate in this study as determined by the investigator or designee

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: STI-1558<br>Subjects will receive in each part either a single ascending dose (SAD): 300 mg, 600 mg, 1200 mg, 2000 mg on Day1 or as part of the multiple ascending dose (MAD): 300 mg, 600 mg, and 800 mg twice a day for 7.5 days | Drug: STI-1558<br>* Orally available protease inhibitor capsule<br>|
| Placebo Comparator: Placebo<br>Subjects will receive placebo orally following either the SAD or MAD dosing schedule | Drug: Placebo<br>* Placebo product capsule<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of adverse events (AEs) (safety) | Safety as assessed by incidence of AEs by type, frequency, severity, and causality using the Common Terminology Criteria for Adverse Events, Version 5 (CTCAEv5) Safety as assessed by incidence of adverse events, clinically significant changes in safety lab results, physical exam, vital signs, and electrocardiogram | baseline through study completion at up to 42 days | 
| Cardiac function (safety) | Heart function as assessed by 12-lead electrocardiogram | baseline through study completion at up to 42 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC of STI-1558 (PK) | Area under the serum concentration-time curve (AUC) of STI-1558 | baseline through study completion at up to 42 days | 
| Cmax of STI-1558 | Maximum observed serum concentration (Cmax) of STI-1558 | baseline through study completion at up to 42 days | 
| t1/2 of STI-1558 | Apparent serum terminal elimination half life (t1/2) of STI-1558 | baseline through study completion at up to 42 days | 
| Tmax of STI-1558 | Time to Cmax (Tmax) of STI-1558 | baseline through study completion at up to 42 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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covid19, COVID-19