Hepatic Function AbnormalPhase 1NCT05283915
Study to Assess the Plasma Concentration of Tolebrutinib Given as a Tablet to Adult Participants With Mild Hepatic Impairment Compared to Participants With Normal Hepatic Function
A Phase 1 study testing tolebrutinib in people with Hepatic Function Abnormal, run by Sanofi at 2 sites in United States.
Trial summary
The purpose of this parallel group, Phase 1, open-label, 2-arm, single dose, multi-center study is to assess the effect of mild hepatic impairment on pharmacokinetics (PK), safety and tolerability of tolebrutinib compared with normal hepatic function, in male and female participants aged 18 to 79 years. Read more about this study
- Who is it for?
- Ages 18 to 79 years
- Conditions the study is for
- Hepatic Function Abnormal
- What is being tested?
- tolebrutinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 2 sitesUnited States
- Study dates
- 18 Mar 2022to 24 May 2022
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 18 to 79 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- For participants with mild hepatic impairment
- Stable chronic liver disease assessed by medical history, physical examination, and laboratory values
- Child-Pugh total score ranging from 5 to 6, inclusive.
- Laboratory parameters within the acceptable range for participants with hepatic impairment; however, estimated glomerular filtration rate (eGFR) should be above or equal to 60 mL/min
- For all participants
- Body weight between 50.0 and 115.0 kg, inclusive, if male, between 40.0 and 100 kg, inclusive, if female, and body mass index (BMI) within the range 18 to 40 kg/m2, inclusive, at screening.
- Participant with platelet count ≥150 000/μL at the screening visit and at Day -1
Who cannot join
- For all participants :
- Symptomatic postural hypotension, whatever the decrease in blood pressure, or asymptomatic postural hypotension defined as a decrease in systolic blood pressure ≥30 mmHg within 3 minutes when changing from supine to standing position at screening and Day -1
- Frequent headaches and/or migraine, recurrent nausea and/or vomiting (for vomiting only: more than twice a month).
- History of drug or alcohol abuse within 1 year before inclusion.
- Smoking regularly more than 15 cigarettes or equivalent per day, unable to refrain from smoking over 8 cigarettes per day during the institutionalization.
- Any consumption of citrus fruits (grapefruit, orange, etc) or their juices within 72 hours before inclusion.
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- Use of any herbal medicines 2 weeks before IMP administration
- Treatment with a strong or moderate CYP3A inhibitors, a strong, moderate or mild CYP2C8 inhibitors OR CYP3A, CYP2C8 inducers within 14 days before the study treatment administration or 5 half-lives, whichever is longer
- Specific for participants with mild hepatic impairment:
- Uncontrolled clinically relevant cardiovascular, pulmonary, gastrointestinal, metabolic, hematological, neurological, psychiatric, systemic, ocular, gynecologic, renal, infectious disease, moderate or severe hepatic impairment (Child-Pugh total score greater than or equal to 7), or signs of acute illness.
- Hepatocarcinoma.
- Acute liver disease.
- Hepatic encephalopathy Grade 2, 3, and 4.
- Esophageal bleeding which is caused by esophageal varices within 3 months before inclusion.
- NOTE: Other Inclusion/Exclusion criteria may apply. The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Clinical Pharmacology of Miami Site Number : 8400002
Miami, Florida, 33014
Nucleus Network Site Number : 8400001
Saint Paul, Minnesota, 55114
About this study
Official title: An Open-label Phase 1, Pharmacokinetic and Tolerability Study of Tolebrutinib Given as a Single Dose in Adult Participants With Mild Hepatic Impairment, and in Matched Participants With Normal Hepatic Function
The purpose of this parallel group, Phase 1, open-label, 2-arm, single dose, multi-center study is to assess the effect of mild hepatic impairment on pharmacokinetics (PK), safety and tolerability of tolebrutinib compared with normal hepatic function, in male and female participants aged 18 to 79 years.
Read the detailed description
The total duration of the study per participant is up to 41 days including:
- A screening period of up to 4 weeks (Days -28 to -2)
- A 5-day, open-label treatment period
- Up to 7 days post-treatment follow-up period
- Conditions
- Hepatic Function Abnormal
- Being tested
- tolebrutinib
- Medical subject headings
- Liver Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
tolebrutinibDrug
Pharmaceutical form: Film-coated tablet Route of administration: oral
| Study group | Role | What they receive |
|---|---|---|
| Mild hepatic impairment group | Experimental | Single dose of tolebrutinib (SAR442168) will be administered on Day 1 under fed condition Receives: Drug: tolebrutinib |
| Normal hepatic function group | Experimental | Single dose of tolebrutinib (SAR442168) will be administered on Day 1 under fed condition Receives: Drug: tolebrutinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Assessment of PK parameters Tolebrutinib: AUC
Area under the plasma concentration (AUC) versus time curve extrapolated to infinity
Measured: From Day 1 to Day 4
Assessment of PK parameters M2: AUC
Measured: From Day 1 to Day 4
Secondary outcomes (5)
Assessment of PK parameters Tolebrutinib: Cmax
Maximum plasma concentration observed (Cmax)
Measured: From Day 1 to Day 4
Assessment of PK parameters M2: Cmax
Measured: From Day 1 to Day 4
Assessment of PK parameters Tolebrutinib: AUClast
Area under the serum concentration versus time curve calculated using the trapezoidal method from time zero to the real time Tlast
Measured: From Day 1 to Day 4
Assessment of PK parameters M2: AUClast
Measured: From Day 1 to Day 4
Number of participants with treatment-emergent adverse events (TEAEs)
Measured: From Day 1 to Day 8
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Mar 2022
- Study start18 Mar 2022
- Primary completion24 May 2022
- Study completion24 May 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hepatic Function AbnormalStudies of the same condition, open and under way.
- More trials run by SanofiThe 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 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sanofi
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Sciences & Operations, Study director, Sanofi
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05283915
- Sponsor's protocol ID
- POP16398
- Other IDs
- U1111-1269-6849, 2022-003098-47
- Status last verified
- Jan 2025
- First submitted
- 7 Mar 2022
- Last updated
- 15 Jan 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org
Study at a glance
From the registry record, last updated by the sponsor on 15 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label Phase 1, Pharmacokinetic and Tolerability Study of Tolebrutinib Given as a Single Dose in Adult Participants With Mild Hepatic Impairment, and in Matched Participants With Normal Hepatic Function
- ClinicalTrials.gov ID
- NCT05283915
- Acronym / sponsor ID
- POP16398
- Conditions
- Hepatic Function Abnormal
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- SanofiIndustry (pharma, biotech, devices)
- Study start
- 18 Mar 2022 (actual)
- Primary completion
- 24 May 2022 (actual)
- Study completion
- 24 May 2022 (actual)
- First posted
- 17 Mar 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this parallel group, Phase 1, open-label, 2-arm, single dose, multi-center study is to assess the effect of mild hepatic impairment on pharmacokinetics (PK), safety and tolerability of tolebrutinib compared with normal hepatic function, in male and female participants aged 18 to 79 years.
Detailed description
The total duration of the study per participant is up to 41 days including:
- A screening period of up to 4 weeks (Days -28 to -2)
- A 5-day, open-label treatment period
- Up to 7 days post-treatment follow-up period
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Mild hepatic impairment group | Experimental | Drug: tolebrutinibSingle dose of tolebrutinib (SAR442168) will be administered on Day 1 under fed condition |
| Normal hepatic function group | Experimental | Drug: tolebrutinibSingle dose of tolebrutinib (SAR442168) will be administered on Day 1 under fed condition |
Who may qualify
- Ages
- 18 to 79 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- For participants with mild hepatic impairment
- Stable chronic liver disease assessed by medical history, physical examination, and laboratory values
- Child-Pugh total score ranging from 5 to 6, inclusive.
- Laboratory parameters within the acceptable range for participants with hepatic impairment; however, estimated glomerular filtration rate (eGFR) should be above or equal to 60 mL/min
- For all participants
Key exclusion criteria (15 listed)
- Symptomatic postural hypotension, whatever the decrease in blood pressure, or asymptomatic postural hypotension defined as a decrease in systolic blood pressure ≥30 mmHg within 3 minutes when changing from supine to standing position at screening and Day -1
- Frequent headaches and/or migraine, recurrent nausea and/or vomiting (for vomiting only: more than twice a month).
- History of drug or alcohol abuse within 1 year before inclusion.
- Smoking regularly more than 15 cigarettes or equivalent per day, unable to refrain from smoking over 8 cigarettes per day during the institutionalization.
- Any consumption of citrus fruits (grapefruit, orange, etc) or their juices within 72 hours before inclusion.
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 |
|---|---|---|
| tolebrutinibPharmaceutical form: Film-coated tablet Route of administration: oral | Drug | Mild hepatic impairment group, Normal hepatic function group |
Primary outcome
Assessment of PK parameters Tolebrutinib: AUC
Time frame: From Day 1 to Day 4
Area under the plasma concentration (AUC) versus time curve extrapolated to infinity
Assessment of PK parameters M2: AUC
Time frame: From Day 1 to Day 4
5 secondary outcomes
Assessment of PK parameters Tolebrutinib: Cmax
Time frame: From Day 1 to Day 4
Assessment of PK parameters M2: Cmax
Time frame: From Day 1 to Day 4
Assessment of PK parameters Tolebrutinib: AUClast
Time frame: From Day 1 to Day 4
Assessment of PK parameters M2: AUClast
Time frame: From Day 1 to Day 4
Number of participants with treatment-emergent adverse events (TEAEs)
Time frame: From Day 1 to Day 8
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Jan 2025.
- POP16398 Plain language Results SummaryLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org
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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 Sciences & Operations study director
Sanofi
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing tolebrutinib in people with Hepatic Function Abnormal, run by Sanofi at 2 sites in United States.
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 7 inclusion and 15 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 15 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. 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.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Assessment of PK parameters Tolebrutinib: AUC (time frame: From Day 1 to Day 4). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 15 Jan 2025.