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This is a randomized, double-blind, and placebo-controlled phase I clinical trial. It is designed to assess the safety, tolerability, and pharmacokinetic (PK) profile of SHEN26 capsules after single and multiple ascending dosing in healthy Chinese adult participants, and the food effect on the PK profile of SHEN26 capsules.
This phase of the study includes three parts: single ascending dose (SAD), food effect (FE), and multiple ascending dose (MAD) in healthy participants.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| SHEN26 capsule (SAD and FE part) | Experimental | SHEN26 capsule 50mg, 200mg, 400mg, 800mg, and 1200mg dose groups |
|
| SHEN26 capsule (MAD part) | Experimental | SHEN26 capsule 200mg, 400mg, and 600mg dose groups |
|
| SHEN26 placebo (SAD and FE part) | Placebo Comparator | SHEN26 placebo 50mg, 200mg, 400mg, 800mg, and 1200mg dose groups |
|
| SHEN26 placebo (MAD part) | Placebo Comparator | SHEN26 placebo 200mg, 400mg, and 600mg dose groups |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| SHEN26 capsule | Drug | Specification: 50mg/capsule and 200mg/capsule. Participants will receive SHEN26 capsule(s) orally for a single dose. The specification of 50mg/capsule will only be used for the 50mg dose group in the SAD part. For the other dose groups and other parts of the study, 200mg/capsule will be used. |
| Measure | Description | Time Frame |
|---|---|---|
| AEs and SAEs | The incidence and severity of adverse events (AEs) and serious adverse events (SAEs). | From Screening period up to Day 12 |
| The Number and Percentage of Participants With Clinically Significant Abnormal Vital Signs | Vital Signs: blood pressure (systolic and diastolic), pulse, body temperature (ear temperature), and respiratory rate. The number and percentage of participants with clinically significant abnormal vital signs will be noted. | From Screening period up to Day 12 |
| The Number and Percentage of Participants With Clinically Significant Abnormal Physical Examination Results | Physical Examination: skin, lymph nodes, head and neck, chest, abdomen, spine/extremities/joints, and nervous system. The number and percentage of participants with clinically significant abnormal physical examination results will be noted. | From Screening period up to Day 12 |
| The Number and Percentage of Participants With Clinically Significant Abnormal Laboratory Values | Laboratory Tests: CBC test, CMP test, urinalysis, urine microalbumin test, urinary NAG test, coagulation test, etc. The number and percentage of participants with clinically significant abnormal laboratory values will be noted. | From Screening period up to Day 12 |
| The Number and Percentage of Participants With Clinically Significant Abnormal Abdominal Ultrasound Results | The number and percentage of participants with clinically significant abnormal abdominal ultrasound imaging test results, including liver, gallbladder, pancreas, spleen, and kidney, will be noted. | From Screening period up to Day 12 |
| The Number and Percentage of Participants With Clinically Significant Abnormal Ophthalmology Examination Results |
| Measure | Description | Time Frame |
|---|---|---|
| Cmax After a Single Dose of SHEN26 capsule | The maximum concentration (Cmax) of SHEN26 capsule. | From predose to 72 hours postdose |
| Tmax After a Single Dose of SHEN26 capsule | The time to the maximum concentration (Tmax) of SHEN26 capsule. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Hui Zhao, MMed | The Second Hospital of Anhui Medical University | Principal Investigator |
| Wei Hu, MD | The Second Hospital of Anhui Medical University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| The Second Hospital of Anhui Medical University | Hefei | Anhui | 230601 | China |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 38662639 | Derived | Sun C, Liu H, Ouyang Z, Ding J, Zhang Q, Ma H, Xu D, Zhang Q, Zhou R, Yang M, Hu W. Safety, tolerability, and pharmacokinetics of the novel RdRp inhibitor SHEN26 against SARS-CoV-2: a randomized, placebo-controlled, double-blind Phase I study in healthy subjects. Expert Opin Investig Drugs. 2024 May;33(5):533-542. doi: 10.1080/13543784.2024.2347302. Epub 2024 Apr 30. | |
| 36635259 |
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| SHEN26 capsule | Drug | Specification: 200mg/capsule. Participants will receive SHEN26 capsules orally for Q12h X 5.5 days. |
|
| SHEN26 placebo | Drug | Placebo matching the SHEN26 capsule. Specification: 50mg/capsule and 200mg/capsule. Participants will receive SHEN26 placebo orally for a single dose. |
|
| SHEN26 placebo | Drug | Placebo matching the SHEN26 capsule. Specification: 200mg/capsule. Participants will receive SHEN26 placebo orally for Q12h X 5.5 days. |
|
Ophthalmology Examination: slit lamp examination. The number and percentage of participants with clinically significant abnormal ophthalmological test results will be noted. |
| From Screening period up to Day 12 |
| The Number and Percentage of Participants With Clinically Significant Abnormal 12-lead Electrocardiogram (ECG) Values | 12-lead Electrocardiogram (ECG): heart rate, PR, QRS, QT, and QTcF intervals. The number and percentage of participants with clinically significant abnormal 12-lead Electrocardiogram (ECG) values will be noted. | From Screening period up to Day 12 |
| From predose to 72 hours postdose |
| AUC0-t and AUC0-inf After a Single Dose of SHEN26 capsule | The area under the concentration-time curve (AUC0-t and AUC0-inf) of SHEN26 capsule. | From predose to 72 hours postdose |
| t1/2 After a Single Dose of SHEN26 capsule | The elimination half-life (t1/2) of SHEN26 capsule. | From predose to 72 hours postdose |
| CL/F After a Single Dose of SHEN26 capsule | The apparent clearance (CL/F) of SHEN26 capsule. | From predose to 72 hours postdose |
| Vz/F After a Single Dose of SHEN26 capsule | The apparent volume of distribution (Vz/F) of SHEN26 capsule. | From predose to 72 hours postdose |
| Ke After a Single Dose of SHEN26 capsule | The elimination rate constant (Ke) of SHEN26 capsule. | From predose to 72 hours postdose |
| Ae After a Single Dose of SHEN26 capsule | (For SAD 400mg dose group only) The amount of SHEN26 or its metabolites excreted in urine and feces (Ae). | From predose to 72 hours postdose |
| fe After a Single Dose of SHEN26 capsule | (For SAD 400mg dose group only) The cumulative fraction of SHEN26 excreted in urine and feces (fe). | From predose to 72 hours postdose |
| Cmax,ss After Multiple Doses of SHEN26 capsule | The maximum concentration at steady state (Cmax,ss) of SHEN26 capsule. | From predose to 48 hours postdose |
| Cmin,ss After Multiple Doses of SHEN26 capsule | The minimum concentration at steady state (Cmin,ss) of SHEN26 capsule. | From predose to 48 hours postdose |
| Cavg After Multiple Doses of SHEN26 capsule | The average concentration at steady state (Cavg) of SHEN26 capsule. | From predose to 48 hours postdose |
| Tmax,ss After Multiple Doses of SHEN26 capsule | The time to the maximum concentration at steady state (Tmax,ss) of SHEN26 capsule. | From predose to 48 hours postdose |
| AUCτ After Multiple Doses of SHEN26 capsule | The area under the concentration-time curve during the dosing interval (AUCτ) of SHEN26 capsule. | From predose to 48 hours postdose |
| CLss/F After Multiple Doses of SHEN26 capsule | The apparent clearance at steady state (CLss/F) of SHEN26 capsule. | From predose to 48 hours postdose |
| Vss/F After Multiple Doses of SHEN26 capsule | The apparent volume of distribution at steady state (Vss/F) of SHEN26 capsule. | From predose to 48 hours postdose |
| DF After Multiple Doses of SHEN26 capsule | The degree of fluctuation in the concentration during the dosing interval (DF) of SHEN26 capsule. | From predose to 48 hours postdose |
| Rac,AUC After Multiple Doses of SHEN26 capsule | The accumulation ratio based on AUC (Rac,AUC) of SHEN26 capsule. | From predose to 48 hours postdose |
| Rac,Cmax After Multiple Doses of SHEN26 capsule | The accumulation ratio based on Cmax (Rac,Cmax) of SHEN26 capsule. | From predose to 48 hours postdose |
| Zhou Q, Yang S, Cao L, Yang Y, Xu T, Chen Q, Lu H, Li Y, Guo D, Zhang X. Preclinical characterization and anti-SARS-CoV-2 efficacy of ATV014: an oral cyclohexanecarboxylate prodrug of 1'-CN-4-aza-7,9-dideazaadenosine C-nucleoside. Signal Transduct Target Ther. 2023 Jan 12;8(1):27. doi: 10.1038/s41392-023-01310-0. No abstract available. |