Healthy VolunteerNCT03959332

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

A study testing Baloxavir Marboxil in people with Healthy Volunteer, run by Hoffmann-La Roche at 1 site in China.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Trial 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. Read more about this study

Who is it for?: Ages 20 to 59 yearsHealthy volunteers can take part
Conditions the study is for: Healthy Volunteer
What is being tested?: Baloxavir Marboxil
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 32 participants
Where: 1 siteChina
Study dates: 19 Jun 2019to 11 Jul 2019
Phase: Interventional
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 20 to 59 years
All sexes
Healthy volunteers accepted
Adult

Who may be able to join

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

Who cannot join

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

Trial locations and contacts

1 site in 1 country.

China1 site

Shanghai Xuhui Central Hospital
Shanghai, 200031

Other trials in China

About this study

Official title: 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

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.

Conditions: Healthy Volunteer
Being tested: Baloxavir Marboxil

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Baloxavir MarboxilDrug
Also called Xofluza
Participants will receive either 40 mg or 80 mg of baloxavir marboxil on Day 1 as a single oral dose.

Study groups in NCT03959332
Study group	Role	What they receive
Baloxavir Marboxil 40 mg	Experimental	Not described Receives: Drug: Baloxavir Marboxil
Baloxavir Marboxil 80 mg	Experimental	Not described Receives: Drug: Baloxavir Marboxil

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 24, 48 and 72 hours postdose

Secondary outcomes (1)

Percentage of Participants With Adverse Events (AEs)
Measured: Up to Day 15

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

19 Jun 201911 Jul 2019

First posted22 May 2019
Study start19 Jun 2019
Primary completion11 Jul 2019
Study completion11 Jul 2019

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (2)Papers the sponsor has linked to this study.
Other trials for Healthy VolunteerStudies of the same condition, open and under way.
More trials run by Hoffmann-La RocheThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase N/A
Primary purpose: Other
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 32 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03959332
Sponsor's protocol ID: YP40902
Status last verified: Jul 2020
First submitted: 21 May 2019
Last updated: 11 Aug 2020
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: No

Publications

Retout S, De Buck S, Jolivet S, Duval V, Cosson V. A Pharmacokinetics-Time to Alleviation of Symptoms Model to Support Extrapolation of Baloxavir Marboxil Clinical Efficacy in Different Ethnic Groups with Influenza A or B. Clin Pharmacol Ther. 2022 Aug;112(2):372-381. doi: 10.1002/cpt.2648. Epub 2022 Jun 10.
PubMed 35585696
Liu Y, Retout S, Duval V, Jia J, Zou Y, Wang Y, Cosson V, Jolivet S, De Buck S. Pharmacokinetics, safety, and simulated efficacy of an influenza treatment, baloxavir marboxil, in Chinese individuals. Clin Transl Sci. 2022 May;15(5):1196-1203. doi: 10.1111/cts.13237. Epub 2022 Feb 19.
PubMed 35176206

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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All Healthy Volunteer trials

Study at a glance

From the registry record, last updated by the sponsor on 11 Aug 2020. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: 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
ClinicalTrials.gov ID: NCT03959332
Acronym / sponsor ID: YP40902
Conditions: Healthy Volunteer
Study type: Interventional
Recruitment status: Completed
Enrolment: 32 participants (actual)
Lead sponsor: Hoffmann-La RocheIndustry (pharma, biotech, devices)
Collaborators: Shionogi
Study start: 19 Jun 2019 (actual)
Primary completion: 11 Jul 2019 (actual)
Study completion: 11 Jul 2019 (actual)
First posted: 22 May 2019 (actual)
Results: Posted 22 Jun 2020

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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.

Study design

Primary purpose: Other
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
Baloxavir Marboxil 40 mg	Experimental	Drug: Baloxavir Marboxil
Baloxavir Marboxil 80 mg	Experimental	Drug: Baloxavir Marboxil

Who may qualify

Ages: 20 to 59 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (3 listed)

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

Key exclusion criteria (6 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Baloxavir MarboxilAlso: XofluzaParticipants will receive either 40 mg or 80 mg of baloxavir marboxil on Day 1 as a single oral dose.	Drug	Baloxavir Marboxil 40 mg, Baloxavir Marboxil 80 mg

Primary outcome

Maximum Plasma Concentration (Cmax)
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
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)
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
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)
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
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)
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
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)
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
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)
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
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)
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
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)
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
Baloxavir marboxil and baloxavir concentrations were analyzed by LC-MS/MS. Non-compartmental analysis was employed to estimate the PK parameters.
Plasma Concentrations 24 (C24), 48 (C48), and 72 Hours (C72) Postdose
Time frame: 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.

1 secondary outcome

Percentage of Participants With Adverse Events (AEs)
Time frame: Up to Day 15

Results and safety

Results posted to the registry on 22 Jun 2020, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Baloxavir Marboxil 40 mg	16	16
Baloxavir Marboxil 80 mg	16	16

Primary outcome: Maximum Plasma Concentration (Cmax)

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. Geometric mean (Geometric Coefficient of Variation). Unit: nanogram per milliliter (ng/mL)

Measure	Baloxavir Marboxil 40 mg n = 16	Baloxavir Marboxil 80 mg n = 16
Baloxavir Marboxil	–	0.5133 (3.7)
Baloxavir	107.6 (24.2)	206.9 (38.3)

Population analysed: Only participants with quantifiable drug plasma concentrations were included in the parameter estimate.

Primary outcome: Time to Maximum Plasma Concentration (Tmax)

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. Median (Full Range). Unit: hours (h)

Measure	Baloxavir Marboxil 40 mg n = 16	Baloxavir Marboxil 80 mg n = 16
Baloxavir Marboxil	–	5.50 (5.00 to 6.00)
Baloxavir	4.00 (3.00 to 6.00)	4.00 (3.00 to 5.00)

Population analysed: Only participants with quantifiable drug plasma concentrations were included in the parameter estimate.

Primary outcome: Area Under the Concentration to Time Curve From Time 0 to Infinity (AUC0-inf)

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. Geometric mean (Geometric Coefficient of Variation). Unit: ng*h/mL

Measure	Baloxavir Marboxil 40 mg n = 16	Baloxavir Marboxil 80 mg n = 16
Baloxavir	6955 (25.5)	9643 (29.4)

Population analysed: Only participants with quantifiable drug plasma concentrations were included in the parameter estimate.

Primary outcome: Area Under the Concentration to Time Curve From Time 0 to Last Quantifiable Concentration (AUC0-last)

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. Geometric mean (Geometric Coefficient of Variation). Unit: ng*h/mL

Measure	Baloxavir Marboxil 40 mg n = 16	Baloxavir Marboxil 80 mg n = 16
Baloxavir	6442 (24.3)	9218 (29.2)

Population analysed: Only participants with quantifiable drug plasma concentrations were included in the parameter estimate.

1 secondary outcome is reported in the full results.

Adverse events

Time frame: Baseline up to Day 15. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Baloxavir Marboxil 40 mg	0 of 16 (0%)	3 of 16 (18.8%)	0 of 16
Baloxavir Marboxil 80 mg	0 of 16 (0%)	11 of 16 (68.8%)	0 of 16

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 11 Aug 2020.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 35585696Retout S, De Buck S, Jolivet S, Duval V, Cosson V. A Pharmacokinetics-Time to Alleviation of Symptoms Model to Support Extrapolation of Baloxavir Marboxil Clinical Efficacy in Different Ethnic Groups with Influenza A or B. Clin Pharmacol Ther. 2022 Aug;112(2):372-381. doi: 10.1002/cpt.2648. Epub 2022 Jun 10.
Derived from this study: PubMed 35176206Liu Y, Retout S, Duval V, Jia J, Zou Y, Wang Y, Cosson V, Jolivet S, De Buck S. Pharmacokinetics, safety, and simulated efficacy of an influenza treatment, baloxavir marboxil, in Chinese individuals. Clin Transl Sci. 2022 May;15(5):1196-1203. doi: 10.1111/cts.13237. Epub 2022 Feb 19.
Individual participant dataSharing planned: No

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Clinical Trials study director

Hoffmann-La Roche

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A study testing Baloxavir Marboxil in people with Healthy Volunteer, run by Hoffmann-La Roche at 1 site in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 11 Aug 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Yes. Results are posted in the registry (first posted 22 Jun 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Maximum Plasma Concentration (Cmax) (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). The study lists 9 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03959332, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Aug 2020.