Study to Assess the Pharmacokinetics, Safety and Tolerability of Baloxavir Marboxil in Healthy Chinese Participants

Study Overview
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Brief Summary
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This study will evaluate the pharmacokinetics, safety and tolerability of a single oral dose of baloxavir marboxil (40 mg or 80 mg) in healthy Chinese participants.

Official Title
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A Phase I, Single-Centre, Open-Label, Parallel, Two Dose Level Study to Investigate the Pharmacokinetics, Safety, and Tolerability Following a Single Dose of Baloxavir Marboxil in Healthy Chinese Volunteers

Conditions
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Healthy Volunteer

Intervention / Treatment
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* Drug: Baloxavir Marboxil


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Chinese participants must have Chinese parents and grandparents, all of whom were born in China. Healthy status as defined by absence of evidence of any active or chronic disease Participants whose body weight is ≥50 to <80 kg and body mass index is ≥18.5 to <26 kg/m2 Exclusion Criteria: Participants with a history of stomach, vagus nerve, or intestinal surgery (except for appendectomy) Participants who have a history of allergic symptoms including food allergy (Note: Non-active allergic rhinitis will be allowed) Participants who require chronic drug therapy or those who have used drugs within 3 days prior to screening or within 14 days prior to Day -1 Participants who have used alcohol-containing, caffeine-containing, grapefruit containing, or St. John's wort-containing products within 72 hours prior to Day -1 Participants who have used tobacco- or nicotine-containing products within 24 weeks prior to screening Participants who have donated > 400 mL of blood within 12 weeks or > 200 mL of blood within 4 weeks prior to screening, or have donated any amount of blood between screening and Day -1

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 59 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: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Baloxavir Marboxil 40 mg<br> | Drug: Baloxavir Marboxil<br>* Participants will receive either 40 mg or 80 mg of baloxavir marboxil on Day 1 as a single oral dose.<br>* Other names: Xofluza;|
| Experimental: Baloxavir Marboxil 80 mg<br> | Drug: Baloxavir Marboxil<br>* Participants will receive either 40 mg or 80 mg of baloxavir marboxil on Day 1 as a single oral dose.<br>* Other names: Xofluza;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Plasma Concentration (Cmax) | Baloxavir marboxil and baloxavir concentrations were analyzed by validated Liquid Chromatography with tandem mass spectrometry (LC-MS/MS). Non-compartmental analysis was employed to estimate the PK parameters. | Pre-dose and at 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48,72, 120, 168, 216, 264, and 336 hours post-dose | 
| Time to Maximum Plasma Concentration (Tmax) | Baloxavir marboxil and baloxavir concentrations were analyzed by LC-MS/MS. Non-compartmental analysis was employed to estimate the PK parameters. | Pre-dose and at 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48,72, 120, 168, 216, 264, and 336 hours post-dose | 
| Area Under the Concentration to Time Curve From Time 0 to Infinity (AUC0-inf) | Baloxavir marboxil and baloxavir concentrations were analyzed by LC-MS/MS. Non-compartmental analysis was employed to estimate the PK parameters. | Pre-dose and at 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48,72, 120, 168, 216, 264, and 336 hours post-dose | 
| Area Under the Concentration to Time Curve From Time 0 to Last Quantifiable Concentration (AUC0-last) | Baloxavir marboxil and baloxavir concentrations were analyzed by LC-MS/MS. Non-compartmental analysis was employed to estimate the PK parameters. | Pre-dose and at 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48,72, 120, 168, 216, 264, and 336 hours post-dose | 
| Area Under the Concentration to Time Curve From Time 0 to Time t (AUC0-t) | Time t may be chosen as a time point where evaluable concentrations are available in at least 90% of participants. Baloxavir marboxil and baloxavir concentrations were analyzed by LC-MS/MS. Non-compartmental analysis was employed to estimate the PK parameters. | Pre-dose and at 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48,72, 120, 168, 216, 264, and 336 hours post-dose | 
| Terminal Elimination Half-Life (T1/2) | Baloxavir marboxil and baloxavir concentrations were analyzed by LC-MS/MS. Non-compartmental analysis was employed to estimate the PK parameters. | Pre-dose and at 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48,72, 120, 168, 216, 264, and 336 hours post-dose | 
| Apparent Total Oral Clearance (CL/F) | Baloxavir marboxil and baloxavir concentrations were analyzed by LC-MS/MS. Non-compartmental analysis was employed to estimate the PK parameters. | Pre-dose and at 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48,72, 120, 168, 216, 264, and 336 hours post-dose | 
| Apparent Oral Volume of Distribution (Vz/F) | Baloxavir marboxil and baloxavir concentrations were analyzed by LC-MS/MS. Non-compartmental analysis was employed to estimate the PK parameters. | Pre-dose and at 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48,72, 120, 168, 216, 264, and 336 hours post-dose | 
| Plasma Concentrations 24 (C24), 48 (C48), and 72 Hours (C72) Postdose | Baloxavir marboxil and baloxavir concentrations were analyzed by LC-MS/MS. Non-compartmental analysis was employed to estimate the PK parameters. | 24, 48 and 72 hours postdose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Adverse Events (AEs) |  | Up to Day 15 |