A Study to Assess the Pharmacokinetics of Enasidenib (CC-90007) in Subjects With Moderate and Severe Hepatic Impairment.

NCT03290443 | Completed Phase 1 FDA Drug

• 2 other identifiers: CC-90007-CP-003U1111-1202-3186
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 5

Brief 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. 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

Conditions

Hepatic Impairment

Keywords

Hepatic; Pharmacokinetics; Phase 1; Enasidenib; CC-90007

Outcome Measures

Primary Outcomes (4)

• Pharmacokinetics - Cmax

  Estimation of maximum observed plasma concentration

  Day 1

• Pharmacokinetics - AUC0-∞

  Estimation of AUC from time zero extrapolated to infinity

  Up to Day 36

• Pharmacokinetics - AUC0-t

  Estimation of AUC from time zero extrapolated to last time point

  Up to Day 36

• Pharmacokinetics - tmax

  Time to reach Cmax

  Day 1

Secondary Outcomes (1)

• Adverse Events (AEs)

  From enrollment until at least 28 days after completion of study treatment

Study Arms (1)

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.

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

You may qualify if:

• 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:
• a. 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:
• a. 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.
• 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:

You may not qualify if:

• 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.
• 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).

Sponsors & Collaborators

• Celgene: lead

Study Sites (5)

DaVita Clinical Research

Lakewood, Colorado, 80228, United States

Location

Clinical Pharmacology of Miami, LLC

Miami, Florida, 33014-3616, United States

Location

Orlando Clinical Research Center OCRC

Orlando, Florida, 32809, United States

Location

DaVita Clinical Research

Minneapolis, Minnesota, 55404, United States

Location

New Orleans Center of Clinical Research

Knoxville, Tennessee, 37920, United States

Location

MeSH Terms

Interventions

enasidenib

Study Officials

• Leon Carayannopoulos, MD

  Celgene

  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
• Expanded Access: Yes

Study Record Dates

• First Submitted: September 19, 2017
• First Posted: September 21, 2017
• Study Start: September 21, 2017
• Primary Completion: October 26, 2018
• Study Completion: October 26, 2018
• Last Updated: July 17, 2020

Record last verified: 2020-07

Locations

US (5)