Hepatic ImpairmentPhase 1NCT03290443
A Study to Assess the Pharmacokinetics of Enasidenib (CC-90007) in Subjects With Moderate and Severe Hepatic Impairment.
A Phase 1 study testing Enasidenib in people with Hepatic Impairment, run by Celgene at 5 sites in United States.
Trial summary
This is a multi-center, open-label study to assess the PK of single 100 mg oral dose of enasidenib (CC-90007) in subjects with moderate and severe hepatic impairment, and in matched healthy control subjects with normal hepatic function. Read more about this study
- Who is it for?
- Ages 40 to 65 years
- Conditions the study is for
- Hepatic Impairment
- What is being tested?
- Enasidenib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 31 participants
- Where
- 5 sitesUnited States
- Study dates
- 21 Sep 2017to 26 Oct 2018
- 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 40 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Each subject must satisfy all of the following criteria to be enrolled in the study:
- Subject must understand and voluntarily sign an informed consent form (ICF) prior to any study-related assessments/procedures being conducted.
- Subject is male, or non-pregnant and non-nursing female between ≥ 40 and ≤ 65 years of age at the time of signing the ICF.
- Subject has body mass index (BMI) ≥ 18 and ≤ 40 kg/m2 at screening.
- Subject has seated systolic blood pressure (BP): 90 to 160 mmHg, seated diastolic BP: 50 to 100 mmHg, and pulse rate: 40 to 100 bpm.
- Female subjects NOT of childbearing potential must:
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- Have been surgically sterilized (hysterectomy or bilateral oophorectomy; proper documentation required) at least 6 months before screening, or be postmenopausal (defined as 24 consecutive months without menses before screening, with a follicle-stimulating hormone [FSH] level of > 40 IU/L at screening).
- Females of childbearing potential (FCBP)1 must have a negative pregnancy test at the Screening and Baseline Visits. While receiving IP and for at least 4 months after taking the last dose of IP, FCBP who engage in activity in which conception is possible must use one of the approved contraceptive options.
- Male subjects must:
- Practice true abstinence2 (which must be reviewed on a monthly basis and source documented) or agree to use a barrier method of birth control (condoms not made out of natural [animal] membrane [latex condoms are recommended]) during sexual contact with a pregnant female or FCBP while participating in the study, during dose interruptions, and for at least 4 months after the last dose of IP, even if he has undergone a successful vasectomy.
- Inclusion Criteria for Subjects with Moderate or Severe Hepatic Impairment (Groups 1 and 3) Each subject with moderate or severe renal impairment must also meet ALL of the criteria listed below for entry:
- Subject has moderate or severe hepatic impairment or cirrhosis due to chronic hepatic disease and/or prior alcohol use.
- Subject has moderate (Group 1), or severe (Group 3) hepatic impairment as defined by Child-Pugh Score.
- Group 1 subjects must have moderate hepatic impairment and are required to have documentary confirmation of the diagnosis of cirrhosis made by biopsy, laparoscopy, or imaging study with a Child-Pugh score of ≥ 7 to ≤ 9, at screening.
- Group 3 subjects must have severe hepatic impairment. If biopsy or laparoscopy is not performed prior to screening, subject can be included only if they have chronic liver disease and objective evidence of portal hypertension (ascites diagnosis by imaging or varices), or current medication for consequences of portal hypertension. In either case a Child-Pugh score of ≥ 10 to ≤ 13 at screening is required.
- Subject has a normal or clinically acceptable 12-lead ECG at screening. In addition:
- Subject (male or female) has a QTcF value ≤ 480 msec at screening.
- Must be stable in concomitant medication regimen (defined as not starting a new medication[s] or a change in the dosage or frequency of the concomitant medication[s] within 7 days or 5 half-lives [whichever is longer] before dosing with study drug).
- Subjects may be treated with diuretics for ascites; however, subjects with severe ascites at time of enrollment may only be included at the discretion of the investigator with agreement of the Sponsor.
- Subjects may have a history of encephalopathy; however, they must be on stable treatment for at least 1 month prior to screening, and must not have had an acute encephalopathic episode in the 1 months prior to screening.
- Subjects must not have history of hepatorenal syndrome or hemolysis. Inclusion Criteria for a Matched Healthy Subject (Groups 2 and 4)
- Each matched healthy subject must meet ALL the criteria listed below for entry:
- Subject must be free of any clinically significant disease that would interfere with the study evaluations.
- Subject must have liver-related laboratory test results within the respective reference ranges or with clinically insignificant excursions therefrom as agreed by the Investigator and Celgene's Medical Monitor.
- Subject must match a subject in Group 1 or 3, as needed with respect to sex, age (± 10 years), and weight (± 30 pounds).
- Subject must be in good health as determined by past medical history, PE, vital signs, ECG, and clinical laboratory safety tests. Clinical laboratory safety tests (ie, hematology, chemistry, and urinalysis) and 12-lead ECGs must be within normal limits or clinically acceptable as judged by the Investigator.
- Subject has a normal or clinically acceptable 12-lead ECG at screening. In addition:
- If male, subject has a QTcF value ≤ 450 msec at screening.
- If female, subject has a QTcF value ≤ 470 msec at screening.
Who cannot join
- The presence of any of the following will exclude a subject from enrollment:
- Subject has any condition or circumstance that prevents the subject from understanding and signing the ICF.
- Subject has any condition that places the subject at an unacceptable risk from participating in the study or would confound the ability to interpret data from the study.
- Subject has any significant medical condition or psychiatric illness that would prevent the subject from participating in the study at Investigator discretion.
- Subject has any surgical or medical condition(s) possibly affecting drug absorption, distribution, metabolism, excretion, eg, bariatric procedure. Subjects with cholecystectomy and appendectomy may be included.
- Subject is a pregnant or is breastfeeding.
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- Subject donated blood or plasma within 2 weeks before dose administration to a blood bank or blood donation center.
- Subject has a history of alcohol abuse (as defined by the current version of the Diagnostic and Statistical Manual [DSM]) within 6 months before the first dose administration, or positive alcohol screen.
- Subject has a history of drug abuse (as defined by the current version of the DSM) within 6 months before the first dose administration, or positive drug screen that is not consistent with the patient's prescribed medication and or/medical history.
- Subject is known to have active serum hepatitis, or have a positive result to the test for Human immunodeficiency virus (HIV) antibodies at screening.
- Chronic or resolved Hepatitis B or Hepatitis C are acceptable only if sequelae are limited to hepatic involvement and its consequent comorbidities. (ie, vasculitis, clinically significant cryoglobulinemia, etc. are unacceptable).
- Subject was exposed to an investigational drug (new chemical entity) within 30 days before dosing, or 5 half-lives of that investigational drug, if known (whichever is longer).
- Subject used approved medications or herbal medicines that are moderate or strong cytochrome P450 (CYP)1A2 or 3A4/5 inducers and/or inhibitors (including St. John's wort) within 14 days or 5 half-lives of screening, whichever is longer.
- The Indiana University "Cytochrome P450 Drug Interaction Table" should be utilized to determine inhibitors and/or inducers of CYP1A2 and CYP3A4/5.
- (http://medicine.iupui.edu/clinpharm/ddis/table.aspx).
- Subject will have consumed Seville oranges, grapefruit or grapefruit juice and/or pomelos, exotic citrus fruits, or grapefruit hybrids within 14 days or 5 half-lives of dosing, whichever is longer.
- Subject smokes more than 10 cigarettes per day, or the equivalent in other tobacco products (self-reported).
- Subject has a history of multiple drug allergies or drug-related anaphylaxis.
- Subject has received live vaccination (excluding seasonal flu vaccination) within 90 days of dosing.
- Subject is part of the staff personnel or a family member of the investigational study staff.
- Subject is, for any reason, deemed by the investigator to be inappropriate for this study, including a subjects who is unable to communicate or to cooperate with the investigator or the clinical staff. Exclusion Criteria for Subjects with Moderate or Severe Hepatic Impairment (Groups 1 and 3)
- The presence of any of the following will exclude a hepatic impaired subject from enrollment:
- Subject has any unstable medical condition occurring within 3 months prior to signing the ICF (excluding hepatic impairment and associated comorbidities per Investigator discretion).
- Subject has any serious medical condition (excluding hepatic impairment and related complications), clinically significant laboratory abnormality not related to hepatic impairment and related complications, or psychiatric illness that would prevent the subject from signing the ICF and participating in the study per Investigator discretion.
- Subject has hepatic encephalopathy with time- or place- disorientation, somnolence, stupor, rigidity, coma, no personality/behavior, rigidity, or hyperactive reflexes - or has had such within 1 month of screening.
- Subject has a history of incipient/planned liver transplantation within 6 months of screening or has received a liver transplant.
- Exclusion Criteria for a Matched Healthy Subject (Groups 2 and4)
- Each matched healthy subject will be excluded from entry if ANY of the criteria listed below are met:
- Subject has any clinically significant laboratory abnormality that in the opinion of the Investigator, is considered to prevent the subject from safely completing the study.
- Subject has any unstable clinically significant illness within 3 months prior to the study.
- Subject has any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study.
- Positive testing for any active hepatitis, or history of Hepatitis B or C.
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United States5 sites
New Orleans Center of Clinical Research
Knoxville, Tennessee, 37920
DaVita Clinical Research
Lakewood, Colorado, 80228
Clinical Pharmacology of Miami, LLC
Miami, Florida, 33014-3616
DaVita Clinical Research
Minneapolis, Minnesota, 55404
Orlando Clinical Research Center OCRC
Orlando, Florida, 32809
About this study
Official title: A Phase 1, Open-Label Single-Dose Study to Assess the Pharmacokinetics of Enasidenib (AG 221, CC 90007) in Subjects With Moderate and Severe Hepatic Impairment.
This is a multi-center, open-label study to assess the PK of single 100 mg oral dose of enasidenib (CC-90007) in subjects with moderate and severe hepatic impairment, and in matched healthy control subjects with normal hepatic function.
Degrees of hepatic impairment will be determined during screening by the subject's score according to Pugh's Modification of Child's Classification of Severity of Liver Disease
Read the detailed description
Subjects will be enrolled in Groups 1 through 4 as follows:
- Group 1: Approximately 6 to 8 male and female subjects with moderate hepatic impairment (with a Child-Pugh score of ≥ 7 to ≤ 9) will be enrolled in Group 1.
- Group 2: Approximately 6 to 8 healthy male and female subjects with normal hepatic function will be enrolled in Group 2. Subjects in Group 2 will be matched to subjects in Group 1 with respect to sex, age (± 10 years), and weight (± 30 pounds).
- Group 3: Approximately 6 to 8 male and female subjects with severe hepatic impairment (with a Child-Pugh score of ≥ 10 to ≤ 13) will be enrolled in Group 3.
- Group 4: Approximately 6 to 8 healthy male and female subjects with normal hepatic function will be enrolled in Group 4. Subjects in Group 4 will be matched to subjects in Group 3 with respect to sex, age (± 10 years), and weight (± 30 pounds). This study employs a staged design as follows.
- At least 4 subjects with moderate hepatic impairment must demonstrate satisfactory safety and tolerability for up to 8 days after dosing, before subjects with severe hepatic impairment may be dosed.
- Two subjects with severe hepatic impairment must demonstrate satisfactory safety and tolerability for up to 8 days after dosing, before the remaining subjects with severe hepatic impairment may be dosed.
- Conditions
- Hepatic Impairment
- Being tested
- Enasidenib
- Keywords
- Hepatic, Pharmacokinetics, Phase 1, Enasidenib, CC-90007
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EnasidenibDrug
Also called AG-221, AG-221 mesylate, AGI-12910, AGI-12910 mesylate
100 mg enasidenib (CC-90007)
| Study group | Role | What they receive |
|---|---|---|
| Enasidenib (CC-90007) tablet | Experimental | Subjects will receive one 100 mg enasidenib (CC-90007) tablet the morning of Day 1 which will be administered in the fasted state. Receives: Drug: Enasidenib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pharmacokinetics - Cmax
Estimation of maximum observed plasma concentration
Measured: Day 1
Pharmacokinetics - AUC0-∞
Estimation of AUC from time zero extrapolated to infinity
Measured: Up to Day 36
Pharmacokinetics - AUC0-t
Estimation of AUC from time zero extrapolated to last time point
Measured: Up to Day 36
Pharmacokinetics - tmax
Time to reach Cmax
Measured: Day 1
Secondary outcomes (1)
Adverse Events (AEs)
Number of participants with adverse events
Measured: From enrollment until at least 28 days after completion of study treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Sep 2017
- Study start21 Sep 2017
- Primary completion26 Oct 2018
- Study completion26 Oct 2018
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.
- More trials run by CelgeneThe 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 31 participants (actual)
Sponsor and investigators
- Lead sponsor
- Celgene
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Leon Carayannopoulos, MD, Study director, Celgene
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03290443
- Sponsor's protocol ID
- CC-90007-CP-003
- Other IDs
- U1111-1202-3186
- Status last verified
- Jul 2020
- First submitted
- 19 Sep 2017
- Last updated
- 17 Jul 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Expanded access
- Available
Study at a glance
From the registry record, last updated by the sponsor on 17 Jul 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1, Open-Label Single-Dose Study to Assess the Pharmacokinetics of Enasidenib (AG 221, CC 90007) in Subjects With Moderate and Severe Hepatic Impairment.
- ClinicalTrials.gov ID
- NCT03290443
- Acronym / sponsor ID
- CC-90007-CP-003
- Conditions
- Hepatic Impairment
- Keywords
- Hepatic, Pharmacokinetics, Phase 1, Enasidenib, CC-90007
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 31 participants (actual)
- Lead sponsor
- CelgeneIndustry (pharma, biotech, devices)
- Study start
- 21 Sep 2017 (actual)
- Primary completion
- 26 Oct 2018 (actual)
- Study completion
- 26 Oct 2018 (actual)
- First posted
- 21 Sep 2017 (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.
This is a multi-center, open-label study to assess the PK of single 100 mg oral dose of enasidenib (CC-90007) in subjects with moderate and severe hepatic impairment, and in matched healthy control subjects with normal hepatic function.
Degrees of hepatic impairment will be determined during screening by the subject's score according to Pugh's Modification of Child's Classification of Severity of Liver Disease
Detailed description
Subjects will be enrolled in Groups 1 through 4 as follows:
- Group 1: Approximately 6 to 8 male and female subjects with moderate hepatic impairment (with a Child-Pugh score of ≥ 7 to ≤ 9) will be enrolled in Group 1.
- Group 2: Approximately 6 to 8 healthy male and female subjects with normal hepatic function will be enrolled in Group 2. Subjects in Group 2 will be matched to subjects in Group 1 with respect to sex, age (± 10 years), and weight (± 30 pounds).
- Group 3: Approximately 6 to 8 male and female subjects with severe hepatic impairment (with a Child-Pugh score of ≥ 10 to ≤ 13) will be enrolled in Group 3.
- Group 4: Approximately 6 to 8 healthy male and female subjects with normal hepatic function will be enrolled in Group 4. Subjects in Group 4 will be matched to subjects in Group 3 with respect to sex, age (± 10 years), and weight (± 30 pounds). This study employs a staged design as follows.
- At least 4 subjects with moderate hepatic impairment must demonstrate satisfactory safety and tolerability for up to 8 days after dosing, before subjects with severe hepatic impairment may be dosed.
- Two subjects with severe hepatic impairment must demonstrate satisfactory safety and tolerability for up to 8 days after dosing, before the remaining subjects with severe hepatic impairment may be dosed.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Enasidenib (CC-90007) tablet | Experimental | Drug: EnasidenibSubjects will receive one 100 mg enasidenib (CC-90007) tablet the morning of Day 1 which will be administered in the fasted state. |
Who may qualify
- Ages
- 40 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (29 listed)
- Subject must understand and voluntarily sign an informed consent form (ICF) prior to any study-related assessments/procedures being conducted.
- Subject is male, or non-pregnant and non-nursing female between ≥ 40 and ≤ 65 years of age at the time of signing the ICF.
- Subject has body mass index (BMI) ≥ 18 and ≤ 40 kg/m2 at screening.
- Subject has seated systolic blood pressure (BP): 90 to 160 mmHg, seated diastolic BP: 50 to 100 mmHg, and pulse rate: 40 to 100 bpm.
- Female subjects NOT of childbearing potential must:
Key exclusion criteria (32 listed)
- Subject has any condition or circumstance that prevents the subject from understanding and signing the ICF.
- Subject has any condition that places the subject at an unacceptable risk from participating in the study or would confound the ability to interpret data from the study.
- Subject has any significant medical condition or psychiatric illness that would prevent the subject from participating in the study at Investigator discretion.
- Subject has any surgical or medical condition(s) possibly affecting drug absorption, distribution, metabolism, excretion, eg, bariatric procedure. Subjects with cholecystectomy and appendectomy may be included.
- Subject is a pregnant or is breastfeeding.
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 |
|---|---|---|
| EnasidenibAlso: AG-221, AG-221 mesylate, AGI-12910, AGI-12910 mesylate100 mg enasidenib (CC-90007) | Drug | Enasidenib (CC-90007) tablet |
Primary outcome
Pharmacokinetics - Cmax
Time frame: Day 1
Estimation of maximum observed plasma concentration
Pharmacokinetics - AUC0-∞
Time frame: Up to Day 36
Estimation of AUC from time zero extrapolated to infinity
Pharmacokinetics - AUC0-t
Time frame: Up to Day 36
Estimation of AUC from time zero extrapolated to last time point
Pharmacokinetics - tmax
Time frame: Day 1
Time to reach Cmax
1 secondary outcome
Adverse Events (AEs)
Time frame: From enrollment until at least 28 days after completion of study 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 17 Jul 2020.
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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.
Leon Carayannopoulos, MD study director
Celgene
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 Enasidenib in people with Hepatic Impairment, run by Celgene 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 29 inclusion and 32 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 17 Jul 2020. 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 - Cmax (time frame: Day 1). The study lists 4 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 17 Jul 2020.