Healthy Volunteer
Conditions
Brief summary
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.
Interventions
Participants will receive either 40 mg or 80 mg of baloxavir marboxil on Day 1 as a single oral dose.
Sponsors
Shionogi
Hoffmann-La Roche
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to 59 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Plasma Concentrations 24 (C24), 48 (C48), and 72 Hours (C72) Postdose | 24, 48 and 72 hours postdose | Baloxavir marboxil and baloxavir concentrations were analyzed by LC-MS/MS. Non-compartmental analysis was employed to estimate the PK parameters. |
| Maximum Plasma Concentration (Cmax) | 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 | 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. |
| Time to Maximum Plasma Concentration (Tmax) | 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 | Baloxavir marboxil and baloxavir concentrations were analyzed by LC-MS/MS. Non-compartmental analysis was employed to estimate the PK parameters. |
| Area Under the Concentration to Time Curve From Time 0 to Infinity (AUC0-inf) | 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 | Baloxavir marboxil and baloxavir concentrations were analyzed by LC-MS/MS. Non-compartmental analysis was employed to estimate the PK parameters. |
| Area Under the Concentration to Time Curve From Time 0 to Last Quantifiable Concentration (AUC0-last) | 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 | Baloxavir marboxil and baloxavir concentrations were analyzed by LC-MS/MS. Non-compartmental analysis was employed to estimate the PK parameters. |
| Area Under the Concentration to Time Curve From Time 0 to Time t (AUC0-t) | 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 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. |
| Terminal Elimination Half-Life (T1/2) | 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 | Baloxavir marboxil and baloxavir concentrations were analyzed by LC-MS/MS. Non-compartmental analysis was employed to estimate the PK parameters. |
| Apparent Total Oral Clearance (CL/F) | 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 | Baloxavir marboxil and baloxavir concentrations were analyzed by LC-MS/MS. Non-compartmental analysis was employed to estimate the PK parameters. |
| Apparent Oral Volume of Distribution (Vz/F) | 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 | Baloxavir marboxil and baloxavir concentrations were analyzed by LC-MS/MS. Non-compartmental analysis was employed to estimate the PK parameters. |
Secondary
| Measure | Time frame |
|---|---|
| Percentage of Participants With Adverse Events (AEs) | Up to Day 15 |
Countries
China
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Baloxavir Marboxil 40 mg Administered orally on Day 1 | 16 |
| Baloxavir Marboxil 80 mg Administered orally on Day 1 | 16 |
| Total | 32 |
Baseline characteristics
| Characteristic | Baloxavir Marboxil 80 mg | Total | Baloxavir Marboxil 40 mg |
|---|---|---|---|
| Age, Continuous | 29.5 years STANDARD_DEVIATION 6.09 | 28.8 years STANDARD_DEVIATION 5.9 | 28.2 years STANDARD_DEVIATION 5.82 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 16 Participants | 32 Participants | 16 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 16 Participants | 32 Participants | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 16 | 0 / 16 |
| other Total, other adverse events | 3 / 16 | 11 / 16 |
| serious Total, serious adverse events | 0 / 16 | 0 / 16 |
Outcome results
Primary
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.
Time frame: 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
Population: Only participants with quantifiable drug plasma concentrations were included in the parameter estimate.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Baloxavir Marboxil 40 mg | Apparent Oral Volume of Distribution (Vz/F) | Baloxavir | 700.1 L | Geometric Coefficient of Variation 26.6 |
| Baloxavir Marboxil 80 mg | Apparent Oral Volume of Distribution (Vz/F) | Baloxavir | 900.1 L | Geometric Coefficient of Variation 31.4 |
| Unknown | Apparent Oral Volume of Distribution (Vz/F) | Baloxavir Marboxil | — L | — |
Primary
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.
Time frame: 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
Population: Only participants with quantifiable drug plasma concentrations were included in the parameter estimate.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Baloxavir Marboxil 40 mg | Apparent Total Oral Clearance (CL/F) | Baloxavir | 4.866 Liters (L)/h | Geometric Coefficient of Variation 25.5 |
| Baloxavir Marboxil 80 mg | Apparent Total Oral Clearance (CL/F) | Baloxavir | 7.019 Liters (L)/h | Geometric Coefficient of Variation 29.4 |
| Unknown | Apparent Total Oral Clearance (CL/F) | Baloxavir Marboxil | — Liters (L)/h | — |
Primary
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.
Time frame: 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
Population: Only participants with quantifiable drug plasma concentrations were included in the parameter estimate.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Baloxavir Marboxil 40 mg | Area Under the Concentration to Time Curve From Time 0 to Infinity (AUC0-inf) | Baloxavir | 6955 ng*h/mL | Geometric Coefficient of Variation 25.5 |
| Baloxavir Marboxil 80 mg | Area Under the Concentration to Time Curve From Time 0 to Infinity (AUC0-inf) | Baloxavir | 9643 ng*h/mL | Geometric Coefficient of Variation 29.4 |
| Unknown | Area Under the Concentration to Time Curve From Time 0 to Infinity (AUC0-inf) | Baloxavir Marboxil | — ng*h/mL | — |
Primary
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.
Time frame: 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
Population: Only participants with quantifiable drug plasma concentrations were included in the parameter estimate.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Baloxavir Marboxil 40 mg | Area Under the Concentration to Time Curve From Time 0 to Last Quantifiable Concentration (AUC0-last) | Baloxavir | 6442 ng*h/mL | Geometric Coefficient of Variation 24.3 |
| Baloxavir Marboxil 80 mg | Area Under the Concentration to Time Curve From Time 0 to Last Quantifiable Concentration (AUC0-last) | Baloxavir | 9218 ng*h/mL | Geometric Coefficient of Variation 29.2 |
| Unknown | Area Under the Concentration to Time Curve From Time 0 to Last Quantifiable Concentration (AUC0-last) | Baloxavir Marboxil | — ng*h/mL | — |
Primary
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.
Time frame: 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
Population: Only participants with quantifiable drug plasma concentrations were included in the parameter estimate.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Baloxavir Marboxil 40 mg | Area Under the Concentration to Time Curve From Time 0 to Time t (AUC0-t) | Baloxavir | 6442 ng*h/mL | Geometric Coefficient of Variation 24.3 |
| Baloxavir Marboxil 80 mg | Area Under the Concentration to Time Curve From Time 0 to Time t (AUC0-t) | Baloxavir | 9218 ng*h/mL | Geometric Coefficient of Variation 29.2 |
| Unknown | Area Under the Concentration to Time Curve From Time 0 to Time t (AUC0-t) | Baloxavir Marboxil | — ng*h/mL | — |
Primary
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.
Time frame: 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
Population: Only participants with quantifiable drug plasma concentrations were included in the parameter estimate.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Baloxavir Marboxil 40 mg | Maximum Plasma Concentration (Cmax) | Baloxavir | 107.6 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 24.2 |
| Baloxavir Marboxil 80 mg | Maximum Plasma Concentration (Cmax) | Baloxavir Marboxil | 0.5133 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 3.7 |
| Baloxavir Marboxil 80 mg | Maximum Plasma Concentration (Cmax) | Baloxavir | 206.9 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 38.3 |
Primary
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.
Time frame: 24, 48 and 72 hours postdose
Population: Only participants with quantifiable drug plasma concentrations were included in the parameter estimate.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Baloxavir Marboxil 40 mg | Plasma Concentrations 24 (C24), 48 (C48), and 72 Hours (C72) Postdose | Baloxavir C48 | 41.38 ng/mL | Geometric Coefficient of Variation 22.9 |
| Baloxavir Marboxil 40 mg | Plasma Concentrations 24 (C24), 48 (C48), and 72 Hours (C72) Postdose | Baloxavir C72 | 29.27 ng/mL | Geometric Coefficient of Variation 25 |
| Baloxavir Marboxil 40 mg | Plasma Concentrations 24 (C24), 48 (C48), and 72 Hours (C72) Postdose | Baloxavir C24 | 56.40 ng/mL | Geometric Coefficient of Variation 22.8 |
| Baloxavir Marboxil 80 mg | Plasma Concentrations 24 (C24), 48 (C48), and 72 Hours (C72) Postdose | Baloxavir C24 | 92.01 ng/mL | Geometric Coefficient of Variation 27.9 |
| Baloxavir Marboxil 80 mg | Plasma Concentrations 24 (C24), 48 (C48), and 72 Hours (C72) Postdose | Baloxavir C72 | 41.78 ng/mL | Geometric Coefficient of Variation 31.6 |
| Baloxavir Marboxil 80 mg | Plasma Concentrations 24 (C24), 48 (C48), and 72 Hours (C72) Postdose | Baloxavir C48 | 60.33 ng/mL | Geometric Coefficient of Variation 33.2 |
| Unknown | Plasma Concentrations 24 (C24), 48 (C48), and 72 Hours (C72) Postdose | Baloxavir Marboxil | — ng/mL | — |
Primary
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.
Time frame: 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
Population: Only participants with quantifiable drug plasma concentrations were included in the parameter estimate.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Baloxavir Marboxil 40 mg | Terminal Elimination Half-Life (T1/2) | Baloxavir | 99.74 hours (h) | Geometric Coefficient of Variation 18 |
| Baloxavir Marboxil 80 mg | Terminal Elimination Half-Life (T1/2) | Baloxavir | 88.89 hours (h) | Geometric Coefficient of Variation 17.1 |
| Unknown | Terminal Elimination Half-Life (T1/2) | Baloxavir Marboxil | — hours (h) | — |
Primary
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.
Time frame: 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
Population: Only participants with quantifiable drug plasma concentrations were included in the parameter estimate.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Baloxavir Marboxil 40 mg | Time to Maximum Plasma Concentration (Tmax) | Baloxavir | 4.00 hours (h) |
| Baloxavir Marboxil 80 mg | Time to Maximum Plasma Concentration (Tmax) | Baloxavir Marboxil | 5.50 hours (h) |
| Baloxavir Marboxil 80 mg | Time to Maximum Plasma Concentration (Tmax) | Baloxavir | 4.00 hours (h) |
Secondary
Percentage of Participants With Adverse Events (AEs)
Time frame: Up to Day 15
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Baloxavir Marboxil 40 mg | Percentage of Participants With Adverse Events (AEs) | 18.8 percentage of participants |
| Baloxavir Marboxil 80 mg | Percentage of Participants With Adverse Events (AEs) | 68.8 percentage of participants |