Pharmacokinetics of Enasidenib (CC-90007) in Participants With Mild, Moderate and Severe Hepatic Impairment

NCT04573582 | Completed Phase 1 FDA Drug

• 2 other identifiers: CC-90007-CP-007U1111-1257-6808
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 3

Brief Summary

This is a multi-center, open-label study to assess the PK of single 100 mg oral doses of enasidenib (CC-90007) in subjects with mild, moderate, and severe hepatic impairment (HI), 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. Subjects will be enrolled in 4 Groups as follows:

• Group A: Approximately 8 subjects with mild hepatic impairment (with a Child-Pugh score of \< 7) will be enrolled in Group A.
• Group B: Approximately 8 subjects with moderate hepatic impairment (with a Child-Pugh score of ≥ 7 to ≤ 9) will be enrolled in Group B.
• Group C: Approximately 8 subjects with severe hepatic impairment (with a Child-Pugh score of ≥ 10 to ≤ 15) will be enrolled in Group C.
• Group D: Approximately 8-24 healthy subjects with normal hepatic function will be enrolled in Group D. Subjects in Group D will be matched to subjects in Groups A-C with respect to sex, age (± 10 years), and weight (± 30 pounds). More than 1 subject with differing degrees of HI can be matched to a single control; however, all subjects with HI must be matched to at least 1 healthy match subject.

Conditions

Hepatic Impairment

Keywords

Hepatic Impairment; CC-90007; Phase 1; Enasidenib

Outcome Measures

Primary Outcomes (4)

• Pharmacokinetics - Cmax (CC-90007)

  Estimation of maximum observed plasma concentration

  Up to Day 1

• Pharmacokinetics - AUC0-∞ (CC-90007)

  Estimation of AUC from time zero extrapolated to infinity

  Up to Day 36

• Pharmacokinetics - AUC0-t (CC-90007)

  Estimation of AUC from time zero extrapolated to last time point

  Up to Day 36

• Pharmacokinetics - Tmax (CC-90007)

  Time to reach Cmax

  Up to Day 1

Secondary Outcomes (5)

• Pharmacokinetics - Cmax (AGI-16903)

  Up to Day 1

• Pharmacokinetics - AUC0-∞ (AGI-16903)

  Up to Day 36

• Pharmacokinetics - AUC0-t (AGI-16903)

  Up to Day 36

• Pharmacokinetics - Tmax (AGI-16903)

  Up to Day 1

• Adverse Events (AEs)

  From the time the ICF is signed until Day 36 (+/- 2 days) or within 28 days after the last dose of IP, whichever time frame is longer

Study Arms (1)

Enasidenib (CC-90007) tablet

EXPERIMENTAL

Participants will receive one 100 mg enasidenib (CC-90007) tablet the morning of Day 1 which will be administered in the fasted state.

Drug: Enasidenib

Interventions

Enasidenib DRUG

100 mg enasidenib (CC-90007)

Also known as: AG-221, AG-221 mesylate, AGI-12910, AGI-12910 mesylate, CC-90007, IDHIFA

Enasidenib (CC-90007) tablet

Eligibility Criteria

• Age: 40 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subject must understand and voluntarily sign an informed consent form (ICF) prior to any study-related assessments/procedures being conducted.
• Subject is able to communicate with the Investigator, understand and comply with the requirements of the study, and agree to adhere to restrictions and examination schedules and other protocol requirements.
• Subject is willing and able to adhere to the study visit schedule and other protocol requirements, including the restrictions.
• \. Male, or non-pregnant and non-nursing female between ≥ 40 and ≤ 75 years of age the time of signing the ICF..
• Body mass index (BMI) ≥ 18 and ≤ 40 kg/m2 at screening.
• Supine systolic blood pressure (BP): 90 to 160 mmHg, supine diastolic BP:50 to 100 mmHg, and pulse rate: 40 to 100 bpm.
• Subject is afebrile.
• Female subjects NOT of childbearing potential must:
• a. Have been surgically sterilized at least 6 months before screening, or be naturally postmenopausal.
• Females of childbearing potential (FCBP) must have a negative pregnancy test at Screening and Baseline Visits. While receiving IP and for at least 2 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 abstinence or
• agree to use a barrier method of birth control during sexual contact with a pregnant female or FCBP while participating in the study, during dose interruptions, and for at least 2 months after the last dose of IP, even if he has undergone a successful vasectomy.
• Each subject with mild, moderate, or severe hepatic impairment must also meet all the applicable criteria listed below for study entry:
• Subject has moderate or severe hepatic impairment or cirrhosis due to chronic hepatic disease and/or prior alcohol use.

You may not qualify if:

• 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.
• a. Subject has an estimated creatinine clearance \< 60 mL/min as calculated using the Cockcroft-Gault formula- at screening and baseline (Day -1).
• Subject is pregnant or is breastfeeding.
• Subject participated in Study CC-90007-CP-003.
• 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 within 6 months before the first dose administration, or positive alcohol screen.
• Subject has a history of drug abuse 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 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, CYP2B6 CYP2C8, CYP2C9, CYP2C19, CYP2D6, and CYP3A4/5 inducers and/or inhibitors (including St. John's wort) within 14 days or 5 half-lives of screening, whichever is longer.
• 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.

Sponsors & Collaborators

• Celgene: lead

Study Sites (3)

Local Institution - 002

Miami, Florida, 33136, United States

Location

Local Institution - 003

Orlando, Florida, 32809, United States

Location

Volunteer Research Group and New Orleans Center for Clinical Research - Knoxville

Knoxville, Tennessee, 37920, United States

Location

Related Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting

MeSH Terms

Interventions

enasidenib

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 28, 2020
• First Posted: October 5, 2020
• Study Start: November 13, 2020
• Primary Completion: March 8, 2023
• Study Completion: March 8, 2023
• Last Updated: July 15, 2024

Record last verified: 2024-07

Locations

US (3)