Healthy VolunteersPhase 1NCT02443168
Radiolabeled Study of AG-221 in Healthy Male Subjects.
A Phase 1 study testing AG-221 and 14C AG-221 in people with Healthy Volunteers, run by Celgene.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 55 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Healthy Volunteers
- What is being tested?
- AG-221 and 14C AG-221
- Type of treatment
- Pill or oral medicine, Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 8 participants
- Where
- No sites listed yet
- Study dates
- 14 May 2015to 21 Jul 2015
- 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 55 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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:
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- 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
Who cannot join
- 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.
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- 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.
- Prior appendectomy is acceptable, but prior cholecystectomy would result in exclusion from the study.
- 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.
- Known to have serum hepatitis or known to be a carrier of HBsAg (Hepatitis B surface antigen) or HCV Ab (Hepatitis C viral antibody), or have a positive result to the test for HIV (Human immunodeficiency virus ) antibodies at screening.
- Smokes more than 10 cigarettes per day, or the equivalent in other tobacco products.
- Employed by the clinical site, or is related to an employee of the clinical site.
- History of less than one bowel movements per day.
About this study
Official title: A Phase 1, Open-Label, Two-Part Study to Evaluate the Metabolism, Excretion, and Absolute Bioavailability of AG-221 in Healthy Adult Male Subjects
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.
Read the detailed description
This will be a single-center, open-label, 2-part study in healthy adult males (n = 14). Parts 1 and 2 may be conducted in parallel.
Each subject will participate in a screening phase, a baseline phase, a treatment phase, and a follow up phone call. Subjects who have met all inclusion criteria and none of the exclusion criteria at screening will return to the clinical site on Day 1 for baseline assessments.
Part 1: Absorption, metabolism, and excretion (AME) Approximately 8 subjects will be enrolled in Part 1. Subjects will check into the clinic on the day before dosing. Following a 10 hour overnight fast, subjects will receive a single 100-mg dose of AG-221 solution containing a microtracer of [14C] AG 221 (~ 300 nCi) under fasted conditions. The study drug will be administered as an oral solution with approximately 240 mL of room temperature, non-carbonated water.
Blood, urine, and fecal samples (and vomitus, if applicable) will be collected throughout the study for pharmacokinetic (PK), mass balance, and/or clinical laboratory assessments. Safety will be monitored throughout the study. Subjects will be discharged from the clinical site on Day 22 following completion of the required study procedures. Subjects will return to the unit on Day 29 for the last PK blood draw.
Urine and fecal samples will be collected each day until Day 22 (or the point of discharge if earlier) for measurement of total [14C] radioactivity. Blood samples for radioanalysis and PK assessment, inclusive of metabolite profiling/characterization, will be collected at pre-dose and at specified intervals through Day 29. Total [14C]-radioactivity in whole blood, plasma, urine, and feces (and vomitus, if applicable ) will be determined.
Part 2: Absolute bioavailability:
Approximately 6 subjects will be enrolled in Part 2. Qualified subjects who have met all inclusion criteria and none of the exclusion criteria at screening will return to the clinical site on Day 1, and will be housed at the clinical site from Day 1 until Day 3.
After an overnight fast of at least 10 hours, approximately 6 subjects will receive an oral dose (coated tablet) of 100 mg of AG-221 at Hour 0 on dosing day (Day 1). The study drug will be administered orally with approximately 240 mL of water. Four hours after the oral dose, the subjects will receive 100 micrograms AG-221 containing ~300 nCi of [14C]-AG-221administered as an intravenous bolus over approximately 2 minutes.
Subjects will be discharged from the unit upon completion of the 48 hour PK blood draw on Day 3. Subjects will return to the unit for additional PK blood draws on Days 5, 8, 11, 15, 18, 22, and 29.
No urine and fecal samples will be collected in Part 2.
- Conditions
- Healthy Volunteers
- Being tested
- AG-221, 14C AG-221
- Keywords
- Pharmacokinetic, Healthy, Male, AG-221, [14C], Single dose, Oral, Intravenous
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AG-221Drug
Part 1: oral solution containing 100 mg [14C]-AG-221
14C AG-221Radiation
5 mL of 100 micrograms [14C] AG-221 given intravenously 4 hours after swallowing the formulated tablet.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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 Receives: Drug: AG-221; Radiation: 14C AG-221 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pharmacokinetics - Total [14C] Whole blood and plasma
Total [14C]-radioactivity in whole blood and plasma
Measured: Approximately 3 weeks
Pharmacokinetics - Total [14C] urine and feces
Total [14C]-radioactivity in urine, and feces (and vomitus, if applicable).
Measured: 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)
Measured: approximately 3 weeks
Pharmacokinetics - Total [14C] radioactivity
Total [14C]-radioactivity whole blood-to-plasma ratios
Measured: approximately 4 weeks
Pharmacokinetics - Total [14C] metabolites
Metabolite profiling / characterization in select plasma, urine, and fecal samples
Measured: 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.
Measured: approximately 4 weeks
Pharmacokinetics - Cmax
Maximum observed plasma concentration
Measured: approximately 4 weeks
Pharmacokinetics - AUC
Area under the plasma concentration-time curve
Measured: approximately 4 weeks
Pharmacokinetics - Tmax
Time to maximum observed plasma concentration
Measured: approximately 4 weeks
Pharmacokinetics -T1/2
Estimate of the terminal elimination half-life
Measured: approximately 4 weeks
Secondary outcomes (1)
Adverse Events (AEs)
An adverse event (AE) is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a subject during the course of a study.
Measured: approximately 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 May 2015 (estimated)
- Study start14 May 2015
- Primary completion21 Jul 2015
- Study completion21 Jul 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Healthy VolunteersStudies 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
- Other
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 8 participants (actual)
Sponsor and investigators
- Lead sponsor
- Celgene
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Edward O'Mara, MD, Study director, Celgene Corporation
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02443168
- Sponsor's protocol ID
- AG-221-CP-002
- Status last verified
- Oct 2018
- First submitted
- 11 May 2015
- Last updated
- 30 Oct 2018
- Results posted
- No
- Data monitoring committee
- No
- Expanded access
- Available
Publications
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.
PubMed 32700065
Study at a glance
From the registry record, last updated by the sponsor on 30 Oct 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1, Open-Label, Two-Part Study to Evaluate the Metabolism, Excretion, and Absolute Bioavailability of AG-221 in Healthy Adult Male Subjects
- ClinicalTrials.gov ID
- NCT02443168
- Acronym / sponsor ID
- AG-221-CP-002
- Conditions
- Healthy Volunteers
- Keywords
- Pharmacokinetic, Healthy, Male, AG-221, [14C], Single dose, Oral, Intravenous
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 8 participants (actual)
- Lead sponsor
- CelgeneIndustry (pharma, biotech, devices)
- Study start
- 14 May 2015 (actual)
- Primary completion
- 21 Jul 2015 (actual)
- Study completion
- 21 Jul 2015 (actual)
- First posted
- 13 May 2015 (estimated)
- 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 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.
Detailed description
This will be a single-center, open-label, 2-part study in healthy adult males (n = 14). Parts 1 and 2 may be conducted in parallel.
Each subject will participate in a screening phase, a baseline phase, a treatment phase, and a follow up phone call. Subjects who have met all inclusion criteria and none of the exclusion criteria at screening will return to the clinical site on Day 1 for baseline assessments.
Part 1: Absorption, metabolism, and excretion (AME) Approximately 8 subjects will be enrolled in Part 1. Subjects will check into the clinic on the day before dosing. Following a 10 hour overnight fast, subjects will receive a single 100-mg dose of AG-221 solution containing a microtracer of [14C] AG 221 (~ 300 nCi) under fasted conditions. The study drug will be administered as an oral solution with approximately 240 mL of room temperature, non-carbonated water.
Blood, urine, and fecal samples (and vomitus, if applicable) will be collected throughout the study for pharmacokinetic (PK), mass balance, and/or clinical laboratory assessments. Safety will be monitored throughout the study. Subjects will be discharged from the clinical site on Day 22 following completion of the required study procedures. Subjects will return to the unit on Day 29 for the last PK blood draw.
Urine and fecal samples will be collected each day until Day 22 (or the point of discharge if earlier) for measurement of total [14C] radioactivity. Blood samples for radioanalysis and PK assessment, inclusive of metabolite profiling/characterization, will be collected at pre-dose and at specified intervals through Day 29. Total [14C]-radioactivity in whole blood, plasma, urine, and feces (and vomitus, if applicable ) will be determined.
Part 2: Absolute bioavailability:
Approximately 6 subjects will be enrolled in Part 2. Qualified subjects who have met all inclusion criteria and none of the exclusion criteria at screening will return to the clinical site on Day 1, and will be housed at the clinical site from Day 1 until Day 3.
After an overnight fast of at least 10 hours, approximately 6 subjects will receive an oral dose (coated tablet) of 100 mg of AG-221 at Hour 0 on dosing day (Day 1). The study drug will be administered orally with approximately 240 mL of water. Four hours after the oral dose, the subjects will receive 100 micrograms AG-221 containing ~300 nCi of [14C]-AG-221administered as an intravenous bolus over approximately 2 minutes.
Subjects will be discharged from the unit upon completion of the 48 hour PK blood draw on Day 3. Subjects will return to the unit for additional PK blood draws on Days 5, 8, 11, 15, 18, 22, and 29.
No urine and fecal samples will be collected in Part 2.
Study design
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 100-mg AG-221 oral solution + a microtracer of [14C]-AG- 221 | Experimental | Drug: AG-221Subjects will receive a 100 mg AG-221 to be swallowed with 240 mL of room-temperature, non-carbonated water. |
| 100-mg AG-221 tablet + 100 micrograms [14C] AG-221 | Experimental | Drug: AG-221, Radiation: 14C AG-221Formulated tablet containing 100 mg AG-221 + IV solution containing 100 micrograms [14C] AG-221 |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (9 listed)
- 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.
Key exclusion criteria (20 listed)
- 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).
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 |
|---|---|---|
| AG-221Part 1: oral solution containing 100 mg [14C]-AG-221 | Drug | 100-mg AG-221 oral solution + a microtracer of [14C]-AG- 221, 100-mg AG-221 tablet + 100 micrograms [14C] AG-221 |
| 14C AG-2215 mL of 100 micrograms [14C] AG-221 given intravenously 4 hours after swallowing the formulated tablet. | Radiation | 100-mg AG-221 tablet + 100 micrograms [14C] AG-221 |
Primary outcome
Pharmacokinetics - Total [14C] Whole blood and plasma
Time frame: Approximately 3 weeks
Total [14C]-radioactivity in whole blood and plasma
Pharmacokinetics - Total [14C] urine and feces
Time frame: approximately 3 weeks
Total [14C]-radioactivity in urine, and feces (and vomitus, if applicable).
Pharmacokinetics - Total [14C] Cumulative excretion
Time frame: approximately 3 weeks
Cumulative excretion of total [14C]-radioactivity (as a fraction of the radioactive dose) in urine and feces (and vomitus, if applicable)
Pharmacokinetics - Total [14C] radioactivity
Time frame: approximately 4 weeks
Total [14C]-radioactivity whole blood-to-plasma ratios
Pharmacokinetics - Total [14C] metabolites
Time frame: approximately 3 weeks
Metabolite profiling / characterization in select plasma, urine, and fecal samples
Pharmacokinetics: Metabolite profiling and characterization in select biological matrices (Part 1)
Time frame: approximately 4 weeks
The analysis for metabolite profiles and characterization are qualitative and there are no units for the analysis.
Pharmacokinetics - Cmax
Time frame: approximately 4 weeks
Maximum observed plasma concentration
Pharmacokinetics - AUC
Time frame: approximately 4 weeks
Area under the plasma concentration-time curve
Pharmacokinetics - Tmax
Time frame: approximately 4 weeks
Time to maximum observed plasma concentration
Pharmacokinetics -T1/2
Time frame: approximately 4 weeks
Estimate of the terminal elimination half-life
1 secondary outcome
Adverse Events (AEs)
Time frame: approximately 8 weeks
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 30 Oct 2018.
- Derived from this study: PubMed 32700065Wang 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.
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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.
Edward O'Mara, MD study director
Celgene Corporation
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing AG-221 and 14C AG-221 in people with Healthy Volunteers, run by Celgene.
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 20 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 30 Oct 2018. Status can change between updates, so confirm with the study contact before making plans.
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 - Total [14C] Whole blood and plasma (time frame: Approximately 3 weeks). The study lists 10 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02443168, which also lists 1 linked publication.
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 30 Oct 2018.