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This study is a four-part, single-center, Open label phase I clinical study to characterize the DDIs potential of GP681 With Rosuvastatin, Digoxin, Itraconazole or Oseltamivir in Chinese healthy volunteers. This study also aims to evaluate the safety and tolerability of GP681 in the presence of Rosuvastatin, Digoxin, Itraconazole, or Oseltamivir.
GP681 is a potent polymerase acidic (PA) protein endonuclease inhibitor. This study will be run in four parts to characterize the DDIs potential of GP681 with the expected concomitant drugs (Rosuvastatin, Digoxin, Itraconazole, Oseltamivir) in Healthy Subjects. Each part of this study consists of a screening period (Day -14 to Day -1), a baseline period (Day -1), a treatment period, and a follow-up telephone call for safety.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| The DDI of GP681 and Rosuvastatin Calcium Tablets | Experimental | Subjects will receive a single dose of Rosuvastatin Calcium 10 mg on Day 1, then take a single doses of 40mg GP681, 10mg Rosuvastatin Calcium on Day 8. |
|
| The DDI of GP681 and Digoxin Tablets | Experimental | Subjects will receive a single dose of Digoxin 0.25 mg on Day 1, then take a single doses of 40mg GP681, 0.25mg Digoxin on Day 15. |
|
| The DDI of GP681 and Itraconazole Capsules | Experimental | Subjects will receive a single dose of GP681 20mg on Day 1, then take Itraconazole 200 mg twice-daily on Day 22 and 200 mg once-daily on Day 23 through Day 36, and took a single dose of GP681 20 mg on Day 26. |
|
| The DDI of GP681 and Oseltamivir Capsules | Experimental | Subjects will receive all three treatments in a crossover fashion according to the randomized sequence. The treatments were as follows: single oral administration of GP681 at 40 mg on day 1 in the fasted state; single oral administration of oseltamivir at 75 mg on day 1 and day 5in the fasted state, followed by repeated twice-daily administration of oseltamivir at 75 mg until day 5 after each meal; co-administration of GP681 at 40 mg and oseltamivir at 75 mg simultaneously on day 1 in the fasted state, followed by repeated twice-daily administration of oseltamivir at 75 mg until day5 after each meal. There was an at least 21-day washout interval between each treatment. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| GP681 | Drug | GP681, tablet, oral |
|
| Measure | Description | Time Frame |
|---|---|---|
| Part one: Peak plasma concentration (Cmax) of Rosuvastatin | Day 1 to Day 4, and Day 8 to Day 11 | |
| Part one: Area under the plasma concentration versus time curve (AUC) of Rosuvastatin | Day 1 to Day 4, and Day 8 to Day 11 | |
| Part two: Peak plasma concentration (Cmax) of Digoxin | Day 1 to Day8, and Day 15 to Day 22 | |
| Part two: Area under the plasma concentration versus time curve (AUC) of Digoxin | Day 1 to Day 8, and Day 15 to Day 22 | |
| Part three: Peak plasma concentration (Cmax) of GP681 | Day 1 to Day12, and Day26 to Day 37 | |
| Part three: Area under the plasma concentration versus time curve (AUC) of GP681 | Day 1 to Day 12, and Day26 to Day 37 | |
| Part Four: Peak plasma concentration (Cmax) of GP681 | 264 hours after GP681 administration | |
| Part Four: Area under the plasma concentration versus time curve (AUC) of GP681 | 264 hours after GP681 administration | |
| Part Four: Peak plasma concentration (Cmax) of Oseltamivir | 12 hours after Oseltamivir administration | |
| Part Four: Area under the plasma concentration versus time curve (AUC) of Oseltamivir |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Jintong Li | China-Japan Friendship Hospital | Principal Investigator |
| Gang Cui | China-Japan Friendship Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| China-Japan Friendship Hospital | Beijing | China |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 40291342 | Derived | Han M, Cui G, Zhao Y, Zuo X, Wang X, Zhang X, Mi N, Jin J, Xiao C, Wang J, Wu W, Li Y, Li J. Evaluation of drug-drug interaction between Suraxavir Marboxil (GP681) and itraconazole, and assessment of the impact of gene polymorphism. Front Pharmacol. 2025 Apr 11;15:1505557. doi: 10.3389/fphar.2024.1505557. eCollection 2024. |
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|
| Rosuvastatin | Drug | Rosuvastatin, tablet, oral |
|
| Digoxin | Drug | Digoxin, tablet, oral |
|
| Itraconazole | Drug | Itraconazole, capsule, oral |
|
| Oseltamivir | Drug | Oseltamivir, capsule, oral |
|
| 12 hours after Oseltamivir administration |
| ID | Term |
|---|---|
| D000068718 | Rosuvastatin Calcium |
| D004077 | Digoxin |
| D017964 | Itraconazole |
| D053139 | Oseltamivir |
| ID | Term |
|---|---|
| D013449 | Sulfonamides |
| D000577 | Amides |
| D009930 | Organic Chemicals |
| D005464 | Fluorobenzenes |
| D006845 | Hydrocarbons, Fluorinated |
| D006846 | Hydrocarbons, Halogenated |
| D006838 | Hydrocarbons |
| D013450 | Sulfones |
| D013457 | Sulfur Compounds |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D004071 | Digitalis Glycosides |
| D002298 | Cardenolides |
| D002301 | Cardiac Glycosides |
| D002297 | Cardanolides |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
| D006027 | Glycosides |
| D002241 | Carbohydrates |
| D014230 | Triazoles |
| D001393 | Azoles |
| D010879 | Piperazines |
| D000081 | Acetamides |
| D053138 | Cyclohexenes |
| D003510 | Cyclohexanes |
| D003516 | Cycloparaffins |
| D006840 | Hydrocarbons, Alicyclic |
| D006844 | Hydrocarbons, Cyclic |
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