Trial Outcomes & Findings for Study to Assess the Pharmacokinetics, Safety and Tolerability of Baloxavir Marboxil in Healthy Chinese Participants (NCT NCT03959332)
NCT ID: NCT03959332
Last Updated: 2020-08-11
Results Overview
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.
COMPLETED
NA
32 participants
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
2020-08-11
Participant Flow
Participant milestones
| Measure |
Baloxavir Marboxil 40 mg
Administered orally on Day 1
|
Baloxavir Marboxil 80 mg
Administered orally on Day 1
|
|---|---|---|
|
Overall Study
STARTED
|
16
|
16
|
|
Overall Study
COMPLETED
|
16
|
16
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Study to Assess the Pharmacokinetics, Safety and Tolerability of Baloxavir Marboxil in Healthy Chinese Participants
Baseline characteristics by cohort
| Measure |
Baloxavir Marboxil 40 mg
n=16 Participants
Administered orally on Day 1
|
Baloxavir Marboxil 80 mg
n=16 Participants
Administered orally on Day 1
|
Total
n=32 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
28.2 years
STANDARD_DEVIATION 5.82 • n=93 Participants
|
29.5 years
STANDARD_DEVIATION 6.09 • n=4 Participants
|
28.8 years
STANDARD_DEVIATION 5.90 • n=27 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Sex: Female, Male
Male
|
16 Participants
n=93 Participants
|
16 Participants
n=4 Participants
|
32 Participants
n=27 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race (NIH/OMB)
Asian
|
16 Participants
n=93 Participants
|
16 Participants
n=4 Participants
|
32 Participants
n=27 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race (NIH/OMB)
White
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
PRIMARY outcome
Timeframe: Pre-dose and at 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48,72, 120, 168, 216, 264, and 336 hours post-dosePopulation: Only participants with quantifiable drug plasma concentrations were included in the parameter estimate.
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.
Outcome measures
| Measure |
Baloxavir Marboxil 40 mg
n=16 Participants
Administered orally on Day 1
|
Baloxavir Marboxil 80 mg
n=16 Participants
Administered orally on Day 1
|
|---|---|---|
|
Maximum Plasma Concentration (Cmax)
Baloxavir Marboxil
|
—
|
0.5133 nanogram per milliliter (ng/mL)
Geometric Coefficient of Variation 3.7
|
|
Maximum Plasma Concentration (Cmax)
Baloxavir
|
107.6 nanogram per milliliter (ng/mL)
Geometric Coefficient of Variation 24.2
|
206.9 nanogram per milliliter (ng/mL)
Geometric Coefficient of Variation 38.3
|
PRIMARY outcome
Timeframe: Pre-dose and at 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48,72, 120, 168, 216, 264, and 336 hours post-dosePopulation: Only participants with quantifiable drug plasma concentrations were included in the parameter estimate.
Baloxavir marboxil and baloxavir concentrations were analyzed by LC-MS/MS. Non-compartmental analysis was employed to estimate the PK parameters.
Outcome measures
| Measure |
Baloxavir Marboxil 40 mg
n=16 Participants
Administered orally on Day 1
|
Baloxavir Marboxil 80 mg
n=16 Participants
Administered orally on Day 1
|
|---|---|---|
|
Time to Maximum Plasma Concentration (Tmax)
Baloxavir Marboxil
|
—
|
5.50 hours (h)
Interval 5.0 to 6.0
|
|
Time to Maximum Plasma Concentration (Tmax)
Baloxavir
|
4.00 hours (h)
Interval 3.0 to 6.0
|
4.00 hours (h)
Interval 3.0 to 5.0
|
PRIMARY outcome
Timeframe: Pre-dose and at 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48,72, 120, 168, 216, 264, and 336 hours post-dosePopulation: Only participants with quantifiable drug plasma concentrations were included in the parameter estimate.
Baloxavir marboxil and baloxavir concentrations were analyzed by LC-MS/MS. Non-compartmental analysis was employed to estimate the PK parameters.
Outcome measures
| Measure |
Baloxavir Marboxil 40 mg
n=16 Participants
Administered orally on Day 1
|
Baloxavir Marboxil 80 mg
n=16 Participants
Administered orally on Day 1
|
|---|---|---|
|
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
|
9643 ng*h/mL
Geometric Coefficient of Variation 29.4
|
PRIMARY outcome
Timeframe: Pre-dose and at 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48,72, 120, 168, 216, 264, and 336 hours post-dosePopulation: Only participants with quantifiable drug plasma concentrations were included in the parameter estimate.
Baloxavir marboxil and baloxavir concentrations were analyzed by LC-MS/MS. Non-compartmental analysis was employed to estimate the PK parameters.
Outcome measures
| Measure |
Baloxavir Marboxil 40 mg
n=16 Participants
Administered orally on Day 1
|
Baloxavir Marboxil 80 mg
n=16 Participants
Administered orally on Day 1
|
|---|---|---|
|
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
|
9218 ng*h/mL
Geometric Coefficient of Variation 29.2
|
PRIMARY outcome
Timeframe: Pre-dose and at 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48,72, 120, 168, 216, 264, and 336 hours post-dosePopulation: Only participants with quantifiable drug plasma concentrations were included in the parameter estimate.
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.
Outcome measures
| Measure |
Baloxavir Marboxil 40 mg
n=16 Participants
Administered orally on Day 1
|
Baloxavir Marboxil 80 mg
n=16 Participants
Administered orally on Day 1
|
|---|---|---|
|
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
|
9218 ng*h/mL
Geometric Coefficient of Variation 29.2
|
PRIMARY outcome
Timeframe: Pre-dose and at 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48,72, 120, 168, 216, 264, and 336 hours post-dosePopulation: Only participants with quantifiable drug plasma concentrations were included in the parameter estimate.
Baloxavir marboxil and baloxavir concentrations were analyzed by LC-MS/MS. Non-compartmental analysis was employed to estimate the PK parameters.
Outcome measures
| Measure |
Baloxavir Marboxil 40 mg
n=16 Participants
Administered orally on Day 1
|
Baloxavir Marboxil 80 mg
n=16 Participants
Administered orally on Day 1
|
|---|---|---|
|
Terminal Elimination Half-Life (T1/2)
Baloxavir
|
99.74 hours (h)
Geometric Coefficient of Variation 18.0
|
88.89 hours (h)
Geometric Coefficient of Variation 17.1
|
PRIMARY outcome
Timeframe: Pre-dose and at 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48,72, 120, 168, 216, 264, and 336 hours post-dosePopulation: Only participants with quantifiable drug plasma concentrations were included in the parameter estimate.
Baloxavir marboxil and baloxavir concentrations were analyzed by LC-MS/MS. Non-compartmental analysis was employed to estimate the PK parameters.
Outcome measures
| Measure |
Baloxavir Marboxil 40 mg
n=16 Participants
Administered orally on Day 1
|
Baloxavir Marboxil 80 mg
n=16 Participants
Administered orally on Day 1
|
|---|---|---|
|
Apparent Total Oral Clearance (CL/F)
Baloxavir
|
4.866 Liters (L)/h
Geometric Coefficient of Variation 25.5
|
7.019 Liters (L)/h
Geometric Coefficient of Variation 29.4
|
PRIMARY outcome
Timeframe: Pre-dose and at 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48,72, 120, 168, 216, 264, and 336 hours post-dosePopulation: Only participants with quantifiable drug plasma concentrations were included in the parameter estimate.
Baloxavir marboxil and baloxavir concentrations were analyzed by LC-MS/MS. Non-compartmental analysis was employed to estimate the PK parameters.
Outcome measures
| Measure |
Baloxavir Marboxil 40 mg
n=16 Participants
Administered orally on Day 1
|
Baloxavir Marboxil 80 mg
n=16 Participants
Administered orally on Day 1
|
|---|---|---|
|
Apparent Oral Volume of Distribution (Vz/F)
Baloxavir
|
700.1 L
Geometric Coefficient of Variation 26.6
|
900.1 L
Geometric Coefficient of Variation 31.4
|
PRIMARY outcome
Timeframe: 24, 48 and 72 hours postdosePopulation: Only participants with quantifiable drug plasma concentrations were included in the parameter estimate.
Baloxavir marboxil and baloxavir concentrations were analyzed by LC-MS/MS. Non-compartmental analysis was employed to estimate the PK parameters.
Outcome measures
| Measure |
Baloxavir Marboxil 40 mg
n=16 Participants
Administered orally on Day 1
|
Baloxavir Marboxil 80 mg
n=16 Participants
Administered orally on Day 1
|
|---|---|---|
|
Plasma Concentrations 24 (C24), 48 (C48), and 72 Hours (C72) Postdose
Baloxavir C24
|
56.40 ng/mL
Geometric Coefficient of Variation 22.8
|
92.01 ng/mL
Geometric Coefficient of Variation 27.9
|
|
Plasma Concentrations 24 (C24), 48 (C48), and 72 Hours (C72) Postdose
Baloxavir C48
|
41.38 ng/mL
Geometric Coefficient of Variation 22.9
|
60.33 ng/mL
Geometric Coefficient of Variation 33.2
|
|
Plasma Concentrations 24 (C24), 48 (C48), and 72 Hours (C72) Postdose
Baloxavir C72
|
29.27 ng/mL
Geometric Coefficient of Variation 25.0
|
41.78 ng/mL
Geometric Coefficient of Variation 31.6
|
SECONDARY outcome
Timeframe: Up to Day 15Outcome measures
| Measure |
Baloxavir Marboxil 40 mg
n=16 Participants
Administered orally on Day 1
|
Baloxavir Marboxil 80 mg
n=16 Participants
Administered orally on Day 1
|
|---|---|---|
|
Percentage of Participants With Adverse Events (AEs)
|
18.8 percentage of participants
|
68.8 percentage of participants
|
Adverse Events
Baloxavir Marboxil 40 mg
Baloxavir Marboxil 80 mg
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Baloxavir Marboxil 40 mg
n=16 participants at risk
Administered orally on Day 1
|
Baloxavir Marboxil 80 mg
n=16 participants at risk
Administered orally on Day 1
|
|---|---|---|
|
Investigations
Blood bilirubin increased
|
6.2%
1/16 • Baseline up to Day 15
|
12.5%
2/16 • Baseline up to Day 15
|
|
Investigations
Blood uric acid increased
|
6.2%
1/16 • Baseline up to Day 15
|
12.5%
2/16 • Baseline up to Day 15
|
|
Investigations
Electrocardiogram T wave abnormal
|
0.00%
0/16 • Baseline up to Day 15
|
6.2%
1/16 • Baseline up to Day 15
|
|
Nervous system disorders
Dizziness
|
6.2%
1/16 • Baseline up to Day 15
|
12.5%
2/16 • Baseline up to Day 15
|
|
Infections and infestations
Upper respiratory tract infection
|
0.00%
0/16 • Baseline up to Day 15
|
18.8%
3/16 • Baseline up to Day 15
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/16 • Baseline up to Day 15
|
12.5%
2/16 • Baseline up to Day 15
|
|
Cardiac disorders
Defect conduction intraventricular
|
0.00%
0/16 • Baseline up to Day 15
|
6.2%
1/16 • Baseline up to Day 15
|
|
Cardiac disorders
Ventricular extrasystoles
|
0.00%
0/16 • Baseline up to Day 15
|
6.2%
1/16 • Baseline up to Day 15
|
|
General disorders
Fatigue
|
0.00%
0/16 • Baseline up to Day 15
|
6.2%
1/16 • Baseline up to Day 15
|
|
Renal and urinary disorders
Haematuria
|
0.00%
0/16 • Baseline up to Day 15
|
6.2%
1/16 • Baseline up to Day 15
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
- Publication restrictions are in place
Restriction type: OTHER