Radiolabeled Study of AG-221 in Healthy Male Subjects.

NCT02443168 | Completed Phase 1

• 1 other identifier: AG-221-CP-002
• Study Type: interventional
• Target: 8
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a single-center, 2-part, open-label study to evaluate the metabolism and excretion and absolute bioavailability of \[14C\]-AG-221 in healthy male subjects. It is planned for 14 subjects to be enrolled; each subject will participate in a screening phase, a baseline phase, a treatment phase, and a follow up phone call. Blood, urine and fecal samples will be collected in Part 1 for analyses. Blood samples will be collected in Part 2. Subjects can only participate in either Part 1 or Part 2.

Conditions

Healthy Volunteers

Keywords

Pharmacokinetic; Healthy; Male; AG-221; [14C]; Single dose; Oral; Intravenous

Outcome Measures

Primary Outcomes (10)

• Pharmacokinetics - Total [14C] Whole blood and plasma

  Total \[14C\]-radioactivity in whole blood and plasma

  Approximately 3 weeks

• Pharmacokinetics - Total [14C] urine and feces

  Total \[14C\]-radioactivity in urine, and feces (and vomitus, if applicable).

  approximately 3 weeks

• Pharmacokinetics - Total [14C] Cumulative excretion

  Cumulative excretion of total \[14C\]-radioactivity (as a fraction of the radioactive dose) in urine and feces (and vomitus, if applicable)

  approximately 3 weeks

• Pharmacokinetics - Total [14C] radioactivity

  Total \[14C\]-radioactivity whole blood-to-plasma ratios

  approximately 4 weeks

• Pharmacokinetics - Total [14C] metabolites

  Metabolite profiling / characterization in select plasma, urine, and fecal samples

  approximately 3 weeks

• Pharmacokinetics: Metabolite profiling and characterization in select biological matrices (Part 1)

  The analysis for metabolite profiles and characterization are qualitative and there are no units for the analysis.

  approximately 4 weeks

• Pharmacokinetics - Cmax

  Maximum observed plasma concentration

  approximately 4 weeks

• Pharmacokinetics - AUC

  Area under the plasma concentration-time curve

  approximately 4 weeks

• Pharmacokinetics - Tmax

  Time to maximum observed plasma concentration

  approximately 4 weeks

• Pharmacokinetics -T1/2

  Estimate of the terminal elimination half-life

  approximately 4 weeks

Secondary Outcomes (1)

• Adverse Events (AEs)

  approximately 8 weeks

Study Arms (2)

100-mg AG-221 oral solution + a microtracer of [14C]-AG- 221

EXPERIMENTAL

Subjects will receive a 100 mg AG-221 to be swallowed with 240 mL of room-temperature, non-carbonated water.

Drug: AG-221

100-mg AG-221 tablet + 100 micrograms [14C] AG-221

EXPERIMENTAL

Formulated tablet containing 100 mg AG-221 + IV solution containing 100 micrograms \[14C\] AG-221

Drug: AG-221; Radiation: 14C AG-221

Interventions

AG-221 DRUG

Part 1: oral solution containing 100 mg \[14C\]-AG-221

100-mg AG-221 oral solution + a microtracer of [14C]-AG- 221; 100-mg AG-221 tablet + 100 micrograms [14C] AG-221

14C AG-221 RADIATION

5 mL of 100 micrograms \[14C\] AG-221 given intravenously 4 hours after swallowing the formulated tablet.

100-mg AG-221 tablet + 100 micrograms [14C] AG-221

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Is a healthy adult male of any race and between 18 to 55 years of age, inclusive, at the time of signing the informed consent document.
• Understands and voluntarily signs an informed consent document before any study related assessments/procedures are conducted.
• Subject is willing and able to adhere to the study visit schedule and other protocol requirements.
• Must practice true abstinence1 or agree to use a condom (a latex condom is recommended) during sexual contact with a pregnant female or a female of childbearing potential (FCBP)2 while participating in the study and for at least 28 days following the last dose of Investigational Product (IP), even if he has undergone a successful vasectomy.
• Must have a Body Mass Index (BMI) between 18 and 33 kg/m2, inclusive, at screening.
• Must be healthy as determined by the Investigator on the basis of medical history, physical examination (PE), clinical laboratory test results, vital signs, and 12-lead Electrocardiograms (ECG) at screening:
• Must be afebrile (febrile is defined as ≥ 38.5°C or 101.3°F)
• Supine systolic blood pressure (BP) must be in the range of 90 to 140 mmHg, supine diastolic BP must be in the range of 50 to 90 mmHg, and pulse rate must be in the range of 40 to 110 bpm
• Normal or clinically acceptable 12-lead ECG, with a QT interval, corrected for heart rate using the Fridericia formula (QTcF) value ≤ 430 msec

You may not qualify if:

• History of any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study.
• Any condition, including the presence of clinically significant (CS) laboratory abnormalities, which places the subject at unacceptable risk if he were to participate in the study.
• Any condition that confounds the ability to interpret data.
• Exposed to an investigational drug (new chemical entity) within 30 days preceding dose administration, or five half-lives of that investigational drug, if known (whichever is longer).
• Participation in more than one other radiolabeled investigational drug study within 12 months prior to check-in (Day -1).
• Note: The previous radiolabeled investigational drug must have been received more than 6 months prior to check-in (Day -1) and the total planned exposure from this current study and the previous study must be within the recommended levels considered safe, per US CFR governing Protection of Human Subjects; radioactive drugs for certain research uses.
• Exposure to significant radiation (eg, serial X-ray or computed tomography scans, barium meal, current employment in a job requiring radiation exposure monitoring) within 12 months prior to check-in (Day -1).
• Used any prescribed systemic or topical medication (including but not limited to analgesics, anesthetics, etc) within 30 days of dose administration.
• Used any nonprescription systemic or topical medication (including vitamin/mineral supplements, and herbal medicines) within 14 days of dose administration.
• Used cytochrome P450 (CYP)3A inducers and/or inhibitors (including St. John's wort) within 30 days of dose administration. The Indiana University "Cytochrome P450 Drug Interaction Table" should be utilized to determine inhibitors and/or inducers of CYP3A.
• Received a live vaccination within 90 days of dose administration.
• Has any surgical or medical conditions possibly affecting ADME (Absorption, distribution, metabolism, and excretion), eg, bariatric procedure, or plans to have elective or medical procedures performed during the conduct of the trial.
• Donated blood or plasma within 8 weeks before dose administration to a blood bank or blood donation center.
• History of drug abuse (as defined by the current version of the Diagnostic and Statistical Manual \[DSM\]) within 2 years before dose administration, or positive drug screening test reflecting consumption of illicit drugs.
• History of alcohol abuse within 2 years before dose administration, or positive alcohol screen.

Sponsors & Collaborators

• Celgene: lead

Related Publications (1)

• Wang X, Chen J, Reyes J, Zhou S, Palmisano M, Li Y. A Phase 1, Open-Label Study in Healthy Subjects to Evaluate the Absolute Bioavailability of AG-221 by a Microtracer Approach. Oncol Ther. 2020 Jun;8(1):91-102. doi: 10.1007/s40487-019-0097-7. Epub 2019 Jul 19.

  PMID: 32700065 DERIVED

MeSH Terms

Interventions

enasidenib

Study Officials

• Edward O'Mara, MD

  Celgene Corporation

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: May 11, 2015
• First Posted: May 13, 2015
• Study Start: May 14, 2015
• Primary Completion: July 21, 2015
• Study Completion: July 21, 2015
• Last Updated: October 30, 2018

Record last verified: 2018-10