First-in-Human Study of Orally Administered GS-441524 for COVID-19

Study Overview
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Brief Summary
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This is a two-part study is to evaluate the multi-day safety, tolerability, and pharmacokinetics (PK) of orally administered GS-441524 in a healthy human volunteer.

Detailed Description
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Part 1: 750 mg GS-441524 administered once daily (QD) for 7 days. Part 2: 750 mg GS-441524 administered three times daily (TID) for 3 days.

Official Title
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First-in-Human Evaluation of the Safety, Tolerability, and Pharmacokinetics of Orally Administered GS-441524 in a Healthy Human Volunteer

Conditions
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COVID-19

Intervention / Treatment
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* Drug: GS-441524


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Willing and able to provide written informed consent Negative pregnancy test at screening and prior to dosing Minimum body weight of 50 kg and body mass index (BMI) of 18-32 kg/m2 Exclusion Criteria: Use of other investigational drugs within 28 days of dosing Positive pregnancy test Abuse of alcohol or drugs Other clinically significant medical conditions or laboratory abnormalities

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

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: Non-Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1: GS-441524 (QD, 7 days)<br>750 mg GS-441524 administered QD for 7 days | Drug: GS-441524<br>* 750 mg administered as a solution<br>* Other names: Parent nucleoside of remdesivir;|
| Experimental: Part 2: GS-441524 (TID, 3 days)<br>750 mg GS-441524 administered TID for 3 days | Drug: GS-441524<br>* 750 mg administered as a solution<br>* Other names: Parent nucleoside of remdesivir;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Emergence of treatment-related adverse events (AEs) | Treatment-related AEs are defined as significant changes to blood chemistry (CBC, CMP) or 6-lead ECG. | Day 7 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic (PK) Parameter: AUC0-24h of GS-441524 in Parts 1 and 2. | AUC0-24h is defined as the concentration of drug over time between time 0 to time 24 hours. | Intensive PK: Day 1 to Day 7 | 
| PK Parameter: AUClast of GS-441524 in Parts 1 and 2. | AUClast is defined as the concentration of drug from time zero to the last observable concentration. | Intensive PK: Day 1 to Day 7 | 
| PK Parameter: T1/2 of GS-441524 in Parts 1 and 2. | T/2 is defined as the estimate of the terminal elimination half-life of the drug | Intensive PK: Day 1 to Day 7 | 
| PK Parameter: Cmax of GS-441524 in Parts 1 and 2. | Cmax is defined as the maximum observed concentration of drug. | Intensive PK: Day 1 to Day 7 | 
| PK Parameter: Tmax of GS-441524 in Parts 1 and 2. | Tmax is defined as the time (observed time point) of Cmax. | Intensive PK: Day 1 to Day 7 | 
| PK Parameter: Clast of GS-441524 in Parts 1 and 2. | Clast is defined as the last observable concentration of drug. | Intensive PK: Day 1 to Day 7 | 
| PK Parameter: Tlast of GS-441524 in Parts 1 and 2. | Tlast is defined as the time (observed time point) of Clast. | Intensive PK: Day 1 to Day 7 | 
| PK Parameter: AUCtau of GS-441524 in Parts 1 and 2. | AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval). | Intensive PK: Day 1 to Day 7 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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GS-5734, GS-441524, remdesivir, Copycat Sciences, Gilead Sciences, COVID-19, antiviral