HealthyPhase 1NCT02387866
PK and Safety Study of AG-221 in Healthy Male Japanese Subjects and Healthy Male Caucasian Subjects
A Phase 1 study testing AG-221 in people with Healthy, run by Celgene at 1 site in United States.
Trial summary
This is a single ascending dose, open-label study that will evaluate the pharmacokinetics and safety of the AG-221 compound in normal, healthy volunteer male subjects (both Japanese and Caucasian). Read more about this study
- Who is it for?
- Ages 20 to 50 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Healthy
- What is being tested?
- AG-221
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 62 participants
- Where
- 1 siteUnited States
- Study dates
- 2 Mar 2015to 27 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 20 to 50 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Subjects must satisfy the following criteria to be enrolled in the study:
- Applicable to Japanese Subjects Only
- Must have been born in Japan to both a Japanese mother and father and also have maternal and paternal Japanese grandparents.
- Must understand and voluntarily sign an Informed Consent Form (ICF) written in English and Japanese prior to any study related procedures being performed and be able to adhere to restrictions and examination schedules.
- Applicable to Caucasian Subjects Only
- Must understand and voluntarily sign a written Informed Consent Form (ICF) prior to any study related procedures being performed and be able to adhere to restrictions and examination schedules.
Show all 19Show fewer
- Non-Japanese subjects must be Caucasian. Caucasian is defined as being of European or Latin American descent (ie, White).
- Applicable to All Subjects
- Healthy male subjects between 20 to 50 years of age (inclusive)
- Must be able to communicate with the Investigator and understand and comply with the requirements of the study.
- Must be in good health as determined by the Investigator according to past medical history, physical examination, vital signs, electrocardiogram (ECG), and laboratory tests.
- Must have a body mass index (BMI) between 18 and 30 kg/m2 (inclusive).
- Clinical laboratory tests must be within normal limits or considered by the Investigator to be not clinically significant.
- Vital signs (systolic and diastolic blood pressure, pulse rate, and oral body temperature) will be assessed in the supine position after the subject has rested for at least 5 minutes. Subject must be afebrile (febrile is defined as ≥ 38 °C or 100.3° F) with vital signs within the following ranges:
- Systolic blood pressure: 90 to 140 mm Hg
- Diastolic blood pressure: 50 to 90 mm Hg
- Pulse rate: 40 to 110 bpm
- Must have a normal or clinically acceptable physical exam and 12-lead ECG. Subjects must have a QTcF value (Fridericia's Correction Factor) ≤ 450 msec. An ECG may be repeated up to 3 times to determine subject eligibility.
- Subjects (with or without vasectomy) must agree to use barrier contraception (ie, latex condom or any synthetic material condom [eg, polyurethane] NOT made out of natural [animal] membrane) when engaging in sexual activity with women of childbearing potential (WCBP) while participating in the study. Subjects must refrain from sperm donations for the entire duration of the study.
Who cannot join
- The presence of any of the following will exclude a subject from enrollment:
- Any serious medical condition, clinically significant laboratory abnormality, or psychiatric illness that would prevent the subject from signing the ICF and/or participating in the study.
- Recent history (ie, within 3 years prior to dosing) of any clinically significant neurological, gastrointestinal, renal, hepatic, cardiovascular, psychological, pulmonary, metabolic, endocrine, hematological or other major disorders.
- Used any prescribed systemic or topical medication within 30 days of the first dose administration.
- Used any non-prescribed systemic or topical medication (including herbal medicines, eg, St. John's Wort) within 7 days of the first dose administration (with the exception of vitamin/mineral supplements).
- Subjects who have any surgical or medical conditions possibly affecting drug absorption, distribution, metabolism and excretion (ADME) or subjects who plan to have any elective or medical procedures during the conduct of the trial.
Show all 14Show fewer
- Exposure to an investigational drug (new chemical entity) within 30 days prior to the first dose administration or 5 half-lives of that investigational drug, if known (whichever is longer).
- Donated blood or plasma within 8 weeks preceding the first dose administration.
- History of multiple drug allergies (ie, 2 or more).
- Any clinically significant allergic disease.
- History of drug abuse (as defined by the current version of the Diagnostic and Statistical Manual [DSM]) within 2 years prior to dosing, or positive drug screening test due to illicit drugs.
- History of alcohol abuse within 2 years prior to dosing, or positive alcohol screen.
- Subjects who smoke more than 10 cigarettes or consume the equivalent in tobacco per day.
- Known to have hepatitis, or known to be a carrier of the HBsAg, or HCV Ab, or have a positive result to the test for HBsAg, HCV Ab, or HIV antibodies at Screening.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase 1, Single Ascending Dose, Open-label Study to Evaluate the Pharmacokinetics and Safety of AG-221 in Healthy Male Japanese Subjects Relative to Healthy Male Caucasian Subjects
This is a single ascending dose, open-label study that will evaluate the pharmacokinetics and safety of the AG-221 compound in normal, healthy volunteer male subjects (both Japanese and Caucasian).
Read the detailed description
This is a phase 1, single ascending dose study to evaluate the PK and safety of AG-221 in healthy adult male Japanese subjects relative to healthy adult male Caucasian subjects. A total of 60 subjects will be enrolled; 30 will be Japanese subjects and 30 will be Caucasian subjects. There will be a total of 3 cohorts. Cohort A will receive a single dose of 100 mg AG-221. Cohort B will receive a single dose of 50 mg AG-221. Cohort C will receive a single dose of 300 mg AG-221. Within each cohort, 10 subjects will be Japanese and 10 subjects will be Caucasian.
Investigational product (IP) will be administered orally with approximately 240 mL of noncarbonated, room-temperature water. Subjects will enter the clinic prior to the evening meal on the day before dosing (Day -1) and will take a single oral dose of AG-221 at Hour 0 on the dosing day (Day 1), following a 10 hour overnight fast. After the dose is administered, subjects will be observed for 7 days to assess the acute safety profile before the next higher, protocol specified dose cohorts can enroll. The Sponsor and Investigator will review all available safety information prior to escalation to the next cohort to ensure that no safety issues exist.
Subjects will be confined to the study center from Day -1 to Day 3. Subjects will be discharged from the study center upon completion of the 48 hour PK blood draw. Subjects will return to the study center for additional PK blood draws on Days 5, 8, 11, 15, 22 and 29. In the event that a subject discontinues from the study, an early termination visit will be performed.
Blood samples will be collected at the following time (hours) for analysis of AG-221 and AGI-16903 (minor, active metabolite in humans) concentrations: Pre-dose, 1, 2, 3, 4, 6, 9, 12, 18, 24, 48, 96, 168, 240, 336, 504 and 672 hours.
In accordance with the guidance for clinical pharmacokinetic studies in Japan, this study design was selected to obtain PK data from Japanese in comparison to Caucasian healthy subjects. As the IP is an anticancer agent and, following the Japanese guidance for global studies, a single dose design was chosen.
AG-221 is a novel, first-in-class compound targeted specifically to inhibit the mutated IDH2 enzyme. AG-221 is currently being studied in a Phase 1 dose escalation study in subjects with advanced hematologic malignancies harboring an IDH2 mutation (AG221-C-001). The AG221-C-001 study is currently being conducted in the United States and France. This Japanese PK bridging study is intended to provide single dose PK and safety information in healthy Japanese subjects, relative to healthy Caucasian
- Conditions
- Healthy
- Being tested
- AG-221
- Keywords
- Pharmacokinetic, Healthy Volunteers, Male, Japanese, Caucasian, AG-221
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AG-221Drug
| Study group | Role | What they receive |
|---|---|---|
| 50 mg AG-221 tablet | Experimental | 50 mg AG-221 tablet given by mouth with 240 mL of non-carbonated, room temperature water, under fasted conditions Receives: Drug: AG-221 |
| 100 mg AG-221 tablet | Experimental | 100 mg AG-221 tablet given by mouth with 240 mL of non-carbonated, room temperature water, under fasted conditions Receives: Drug: AG-221 |
| 300 mg AG-221 tablet | Experimental | 300 mg AG-221 tablet given by mouth with 240 mL of non-carbonated, room temperature water, under fasted conditions Receives: Drug: AG-221 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pharmacokinetics -AUC 0-t
Area under the plasma concentration-time curve from time zero to time t
Measured: Up to 3 days
Pharmacokinetics - AUC ∞
Area under the plasma concentration-time curve from time zero extrapolated to infinity
Measured: Up to 3 days
Pharmacokinetics - Cmax
Maximum observed plasma concentration
Measured: Up to 3 days
Pharmacokinetics - Tmax
Time to maximum observed plasma concentration
Measured: Up to 3 days
Pharmacokinetics -T1/2
Estimate of the terminal elimination half-life in plasma
Measured: Up to 3 days
Pharmacokinetics -CL/F
Apparent total plasma clearance when dosed orally
Measured: Up to 3 days
Pharmacokinetics -Vz/f
Apparent volume of distribution during terminal phase
Measured: Up to 3 days
Secondary outcomes (1)
Adverse Events (AEs)
Number of participants with adverse events
Measured: Approximately 28 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Mar 2015 (estimated)
- Study start2 Mar 2015
- Primary completion21 May 2015
- Study completion27 Jul 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HealthyStudies 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
- 62 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
- NCT02387866
- Sponsor's protocol ID
- AG-221-CP-001
- Status last verified
- Oct 2018
- First submitted
- 5 Mar 2015
- Last updated
- 30 Oct 2018
- Results posted
- No
- Data monitoring committee
- No
- Expanded access
- Available
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, Single Ascending Dose, Open-label Study to Evaluate the Pharmacokinetics and Safety of AG-221 in Healthy Male Japanese Subjects Relative to Healthy Male Caucasian Subjects
- ClinicalTrials.gov ID
- NCT02387866
- Acronym / sponsor ID
- AG-221-CP-001
- Conditions
- Healthy
- Keywords
- Pharmacokinetic, Healthy Volunteers, Male, Japanese, Caucasian, AG-221
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 62 participants (actual)
- Lead sponsor
- CelgeneIndustry (pharma, biotech, devices)
- Study start
- 2 Mar 2015 (actual)
- Primary completion
- 21 May 2015 (actual)
- Study completion
- 27 Jul 2015 (actual)
- First posted
- 13 Mar 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 ascending dose, open-label study that will evaluate the pharmacokinetics and safety of the AG-221 compound in normal, healthy volunteer male subjects (both Japanese and Caucasian).
Detailed description
This is a phase 1, single ascending dose study to evaluate the PK and safety of AG-221 in healthy adult male Japanese subjects relative to healthy adult male Caucasian subjects. A total of 60 subjects will be enrolled; 30 will be Japanese subjects and 30 will be Caucasian subjects. There will be a total of 3 cohorts. Cohort A will receive a single dose of 100 mg AG-221. Cohort B will receive a single dose of 50 mg AG-221. Cohort C will receive a single dose of 300 mg AG-221. Within each cohort, 10 subjects will be Japanese and 10 subjects will be Caucasian.
Investigational product (IP) will be administered orally with approximately 240 mL of noncarbonated, room-temperature water. Subjects will enter the clinic prior to the evening meal on the day before dosing (Day -1) and will take a single oral dose of AG-221 at Hour 0 on the dosing day (Day 1), following a 10 hour overnight fast. After the dose is administered, subjects will be observed for 7 days to assess the acute safety profile before the next higher, protocol specified dose cohorts can enroll. The Sponsor and Investigator will review all available safety information prior to escalation to the next cohort to ensure that no safety issues exist.
Subjects will be confined to the study center from Day -1 to Day 3. Subjects will be discharged from the study center upon completion of the 48 hour PK blood draw. Subjects will return to the study center for additional PK blood draws on Days 5, 8, 11, 15, 22 and 29. In the event that a subject discontinues from the study, an early termination visit will be performed.
Blood samples will be collected at the following time (hours) for analysis of AG-221 and AGI-16903 (minor, active metabolite in humans) concentrations: Pre-dose, 1, 2, 3, 4, 6, 9, 12, 18, 24, 48, 96, 168, 240, 336, 504 and 672 hours.
In accordance with the guidance for clinical pharmacokinetic studies in Japan, this study design was selected to obtain PK data from Japanese in comparison to Caucasian healthy subjects. As the IP is an anticancer agent and, following the Japanese guidance for global studies, a single dose design was chosen.
AG-221 is a novel, first-in-class compound targeted specifically to inhibit the mutated IDH2 enzyme. AG-221 is currently being studied in a Phase 1 dose escalation study in subjects with advanced hematologic malignancies harboring an IDH2 mutation (AG221-C-001). The AG221-C-001 study is currently being conducted in the United States and France. This Japanese PK bridging study is intended to provide single dose PK and safety information in healthy Japanese subjects, relative to healthy Caucasian
Study design
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 50 mg AG-221 tablet | Experimental | Drug: AG-22150 mg AG-221 tablet given by mouth with 240 mL of non-carbonated, room temperature water, under fasted conditions |
| 100 mg AG-221 tablet | Experimental | Drug: AG-221100 mg AG-221 tablet given by mouth with 240 mL of non-carbonated, room temperature water, under fasted conditions |
| 300 mg AG-221 tablet | Experimental | Drug: AG-221300 mg AG-221 tablet given by mouth with 240 mL of non-carbonated, room temperature water, under fasted conditions |
Who may qualify
- Ages
- 20 to 50 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (19 listed)
- Subjects must satisfy the following criteria to be enrolled in the study:
- Applicable to Japanese Subjects Only
- Must have been born in Japan to both a Japanese mother and father and also have maternal and paternal Japanese grandparents.
- Must understand and voluntarily sign an Informed Consent Form (ICF) written in English and Japanese prior to any study related procedures being performed and be able to adhere to restrictions and examination schedules.
- Applicable to Caucasian Subjects Only
Key exclusion criteria (14 listed)
- The presence of any of the following will exclude a subject from enrollment:
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-221 | Drug | 100 mg AG-221 tablet, 300 mg AG-221 tablet, 50 mg AG-221 tablet |
Primary outcome
Pharmacokinetics -AUC 0-t
Time frame: Up to 3 days
Area under the plasma concentration-time curve from time zero to time t
Pharmacokinetics - AUC ∞
Time frame: Up to 3 days
Area under the plasma concentration-time curve from time zero extrapolated to infinity
Pharmacokinetics - Cmax
Time frame: Up to 3 days
Maximum observed plasma concentration
Pharmacokinetics - Tmax
Time frame: Up to 3 days
Time to maximum observed plasma concentration
Pharmacokinetics -T1/2
Time frame: Up to 3 days
Estimate of the terminal elimination half-life in plasma
Pharmacokinetics -CL/F
Time frame: Up to 3 days
Apparent total plasma clearance when dosed orally
Pharmacokinetics -Vz/f
Time frame: Up to 3 days
Apparent volume of distribution during terminal phase
1 secondary outcome
Adverse Events (AEs)
Time frame: Approximately 28 days
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.
Related trials for Healthy
Recruiting
THE EFFECTS OF GAME-BASED EXERCISE PROGRAMS
Physical Activity, Body Image
Not yet recruitingPhase 1
A Phase I Study of GLR2053 Tablets in Chinese Healthy Adult Participants
Atopic Dermatitis
Recruiting
Colon-delivered Riboflavin and Gut Microbiota Composition
Microbiome Dysbiosis, Gut Health
Not yet recruiting
Neuroergonomic Analysis of a Brain-Computer Interface Device (BCI)
Healthy Volunteers - Male and Female
RecruitingPhase 1
First-in-Human Trial to Assess REGN20423 in Healthy Adult Participants and Adult Participants With Atopic Dermatitis
Healthy Volunteer, Atopic Dermatitis
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
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing AG-221 in people with Healthy, run by Celgene at 1 site 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 19 inclusion and 14 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.
Where is the study taking place?
The record lists 1 site 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 -AUC 0-t (time frame: Up to 3 days). The study lists 7 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 30 Oct 2018.