Hepatic ImpairmentPhase 1NCT04772612
A Study to Evaluate the Effect of Mild, Moderate, and Severe Hepatic Impairment on Pharmacokinetics of Sitravatinib
A Phase 1 study testing sitravatinib in people with Hepatic Impairment, run by Mirati Therapeutics Inc. at 5 sites in United States.
Trial summary
A Phase 1, Multicenter, Open-Label Study to Evaluate the Effect of Mild, Moderate, and Severe Hepatic Impairment on the Single-Dose Pharmacokinetics of Sitravatinib Read more about this study
- Who is it for?
- Ages 18 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- Hepatic Impairment
- What is being tested?
- sitravatinib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 5 sitesUnited States
- Study dates
- 12 Mar 2021to 13 Apr 2023
- 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 75 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Males or females, of any race, between 18 and 75 years of age, inclusive, at screening.
- Body mass index between 18.0 and 40.0 kg/m2, inclusive, at screening.
- Females of childbearing potential will not be pregnant or lactating and must have a negative result on an approved pregnancy test at screening and check-in. Females of childbearing potential must agree to use contraception by a method of proven reliability (including abstinence) as detailed in the protocol.
- Male subjects must agree to use contraception as detailed in the protocol.
- Able to comprehend and willing to sign an ICF and to abide by the study restrictions.
- Participants with normal hepatic function must also satisfy the following criteria:
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- Participants with normal hepatic function must be in good health, determined by no clinically significant findings from medical history, physical examination, 12-lead ECG, vital signs measurements, or clinical laboratory evaluations at screening and check-in as assessed by the investigator.
- Participants with hepatic impairment must also satisfy the following criteria:
- Participants must meet the criteria for mild, moderate, or severe hepatic impairment based on Child Pugh (CP) score and classification as detailed in the protocol. Hepatically-impaired participants will be assigned to groups according to CP scores calculated at screening; CP scores will be recalculated at check-in to confirm that subjects do not have significant changes in status to ensure subject safety for the study, as determined by the investigator and medical monitor.
Who cannot join
- Significant history or clinical manifestation of any metabolic, allergic, dermatological, renal, hematological, pulmonary, cardiovascular, gastrointestinal, neurological, respiratory, endocrine, or psychiatric disorder, as determined by the investigator.
- History of intestinal disease, inflammatory bowel disease, major gastric surgery, or other gastrointestinal conditions (eg, uncontrolled nausea, vomiting, malabsorption syndrome) likely to alter absorption of study treatment or result in inability to swallow oral medications (Cholecystectomy is not allowed.).
- Participation in a clinical study involving administration of an investigational drug (new chemical entity) in the past 30 days or 5 half-lives prior to dosing, whichever is longer.
- Participants who, in the opinion of the investigator, should not participate in this study.
- Participants with normal hepatic function will be excluded from the study if any of the following criteria are applicable:
- Significant history or clinical manifestation of any hepatic disease, as determined by lab abnormalities: AST, ALT, alkaline phosphatase, or alpha-fetoprotein >1 × upper limit of normal or as deemed clinically significant by the investigator.
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- Participant has creatinine clearance <80 mL/minute as calculated by using the Cockcroft-Gault equation.
- Use or intend to use any prescription medications/products within 14 days prior to dosing, unless deemed acceptable by the investigator, medical monitor, and sponsor.
- Participants with hepatic impairment will be excluded from the study if any of the following criteria are applicable:
- Ventricular dysfunction or history of risk factors for Torsades de Pointes (eg, unexplained syncope, known long QT syndrome, heart failure, and cardiomyopathy).
- Participant has had a change in disease status within 90 days prior to the study drug administration on Day 1, as documented by the subject's medical history, deemed clinically significant by the investigator.
- Participant has required a new medication or a change in medication dose within 2 weeks before dosing with sitravatinib.
- Participant has a current functioning organ transplant or is waiting for an organ transplant.
- History of unstable diabetes mellitus as evidenced by hemoglobin A1c ≥9% at screening.
- Uncontrolled arterial hypertension (> 150 mm Hg systolic or >100 mm Hg diastolic) on multiple observations despite standard of care treatment.
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United States5 sites
Texas Liver Institute
Austin, Texas, 78757
Clinical Pharmacology of Miami
Miami, Florida, 33014
Orlando Clinical Research Center
Orlando, Florida, 32809
Nucleus Network
Saint Paul, Minnesota, 55114
Orange County Research Center
Tustin, California, 92780
About this study
Official title: A Phase 1, Multicenter, Open-Label Study to Evaluate the Effect of Mild, Moderate, and Severe Hepatic Impairment on the Single-Dose Pharmacokinetics of Sitravatinib
A Phase 1, Multicenter, Open-Label Study to Evaluate the Effect of Mild, Moderate, and Severe Hepatic Impairment on the Single-Dose Pharmacokinetics of Sitravatinib
- Conditions
- Hepatic Impairment
- Being tested
- sitravatinib
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
sitravatinibDrug
sitravatinib
| Study group | Role | What they receive |
|---|---|---|
| Sitravatinib in healthy subjects | Experimental | Participants will receive a single dose of sitravatinib 100 mg receive on Day 1 in healthy subjects. Receives: Drug: sitravatinib |
| Sitravatinib in subjects with mild hepatic impairment | Experimental | Participants will receive a single dose of sitravatinib 100 mg receive on Day 1 in subjects with mild hepatic impairment Receives: Drug: sitravatinib |
| Sitravatinib in subjects with moderate hepatic impairment | Experimental | Participants will receive a single dose of sitravatinib 100 mg receive on Day 1 in subjects with moderate hepatic impairment Receives: Drug: sitravatinib |
| Sitravatinib in subjects with severe hepatic impairment | Experimental | Participants will receive a single dose of sitravatinib 100 mg receive on Day 1 in subjects with severe hepatic impairment Receives: Drug: sitravatinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pharmacokinetics - AUClast (sitravatinib)
AUC from time zero to the last measured time point
Measured: 9 days
Pharmacokinetics - Tmax (sitravatinib)
Time to reach maximum observed plasma concentration
Measured: 9 days
Pharmacokinetics - AUC∞ (sitravatinib)
Area under the plasma concentration-time curve from time zero extrapolated to infinity moderate, or severe hepatic impairment compared to control subjects with normal hepatic function
Measured: 9 days
Pharmacokinetics - Cmax (sitravatinib)
Maximum observed plasma concentration
Measured: 9 days
Pharmacokinetics - t1/2 (sitravatinib)
Terminal elimination half-life
Measured: 9 days
Pharmacokinetics - CL/F (sitravatinib)
Apparent total plasma clearance when dosed orally
Measured: 9 days
Pharmacokinetics - Vz/F (sitravatinib)
Apparent volume of distribution when dosed orally
Measured: 9 days
Pharmacokinetics - fu (sitravatinib)
Unbound fraction
Measured: days 1 - 4
Secondary outcomes (1)
Adverse Events (AEs)
Incidence and severity of adverse events (AEs).
Measured: From the time the ICF is signed until 14 ± 2 days after the last dose of sitravatinib treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Feb 2021
- Study start12 Mar 2021
- Primary completion13 Jul 2022
- Study completion13 Apr 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hepatic ImpairmentStudies of the same condition, open and under way.
- 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
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mirati Therapeutics Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Curtis Chin, MD, Study director, Mirati Therapeutics
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04772612
- Sponsor's protocol ID
- 516-012
- Status last verified
- Oct 2023
- First submitted
- 23 Feb 2021
- Last updated
- 23 Oct 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 Oct 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1, Multicenter, Open-Label Study to Evaluate the Effect of Mild, Moderate, and Severe Hepatic Impairment on the Single-Dose Pharmacokinetics of Sitravatinib
- ClinicalTrials.gov ID
- NCT04772612
- Acronym / sponsor ID
- 516-012
- Conditions
- Hepatic Impairment
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Mirati Therapeutics Inc.Industry (pharma, biotech, devices)
- Study start
- 12 Mar 2021 (actual)
- Primary completion
- 13 Jul 2022 (actual)
- Study completion
- 13 Apr 2023 (actual)
- First posted
- 26 Feb 2021 (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.
A Phase 1, Multicenter, Open-Label Study to Evaluate the Effect of Mild, Moderate, and Severe Hepatic Impairment on the Single-Dose Pharmacokinetics of Sitravatinib
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Sitravatinib in healthy subjects | Experimental | Drug: sitravatinibParticipants will receive a single dose of sitravatinib 100 mg receive on Day 1 in healthy subjects. |
| Sitravatinib in subjects with mild hepatic impairment | Experimental | Drug: sitravatinibParticipants will receive a single dose of sitravatinib 100 mg receive on Day 1 in subjects with mild hepatic impairment |
| Sitravatinib in subjects with moderate hepatic impairment | Experimental | Drug: sitravatinibParticipants will receive a single dose of sitravatinib 100 mg receive on Day 1 in subjects with moderate hepatic impairment |
| Sitravatinib in subjects with severe hepatic impairment | Experimental | Drug: sitravatinibParticipants will receive a single dose of sitravatinib 100 mg receive on Day 1 in subjects with severe hepatic impairment |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Males or females, of any race, between 18 and 75 years of age, inclusive, at screening.
- Body mass index between 18.0 and 40.0 kg/m2, inclusive, at screening.
- Females of childbearing potential will not be pregnant or lactating and must have a negative result on an approved pregnancy test at screening and check-in. Females of childbearing potential must agree to use contraception by a method of proven reliability (including abstinence) as detailed in the protocol.
- Male subjects must agree to use contraception as detailed in the protocol.
- Able to comprehend and willing to sign an ICF and to abide by the study restrictions.
Key exclusion criteria (15 listed)
- Significant history or clinical manifestation of any metabolic, allergic, dermatological, renal, hematological, pulmonary, cardiovascular, gastrointestinal, neurological, respiratory, endocrine, or psychiatric disorder, as determined by the investigator.
- History of intestinal disease, inflammatory bowel disease, major gastric surgery, or other gastrointestinal conditions (eg, uncontrolled nausea, vomiting, malabsorption syndrome) likely to alter absorption of study treatment or result in inability to swallow oral medications (Cholecystectomy is not allowed.).
- Participation in a clinical study involving administration of an investigational drug (new chemical entity) in the past 30 days or 5 half-lives prior to dosing, whichever is longer.
- Participants who, in the opinion of the investigator, should not participate in this study.
- Participants with normal hepatic function will be excluded from the study if any of the following criteria are applicable:
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 |
|---|---|---|
| sitravatinibsitravatinib | Drug | Sitravatinib in healthy subjects, Sitravatinib in subjects with mild hepatic impairment, Sitravatinib in subjects with moderate hepatic impairment, Sitravatinib in subjects with severe hepatic impairment |
Primary outcome
Pharmacokinetics - AUClast (sitravatinib)
Time frame: 9 days
AUC from time zero to the last measured time point
Pharmacokinetics - Tmax (sitravatinib)
Time frame: 9 days
Time to reach maximum observed plasma concentration
Pharmacokinetics - AUC∞ (sitravatinib)
Time frame: 9 days
Area under the plasma concentration-time curve from time zero extrapolated to infinity moderate, or severe hepatic impairment compared to control subjects with normal hepatic function
Pharmacokinetics - Cmax (sitravatinib)
Time frame: 9 days
Maximum observed plasma concentration
Pharmacokinetics - t1/2 (sitravatinib)
Time frame: 9 days
Terminal elimination half-life
Pharmacokinetics - CL/F (sitravatinib)
Time frame: 9 days
Apparent total plasma clearance when dosed orally
Pharmacokinetics - Vz/F (sitravatinib)
Time frame: 9 days
Apparent volume of distribution when dosed orally
Pharmacokinetics - fu (sitravatinib)
Time frame: days 1 - 4
Unbound fraction
1 secondary outcome
Adverse Events (AEs)
Time frame: From the time the ICF is signed until 14 ± 2 days after the last dose of sitravatinib treatment
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 23 Oct 2023.
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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.
Curtis Chin, MD study director
Mirati Therapeutics
5 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 sitravatinib in people with Hepatic Impairment, run by Mirati Therapeutics Inc. at 5 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 9 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 23 Oct 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 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?
Pharmacokinetics - AUClast (sitravatinib) (time frame: 9 days). The study lists 8 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 23 Oct 2023.