Hepatic ImpairmentPhase 1NCT03282513
A Study of AG-120 (Ivosidenib) in Subjects With Mild or Moderate Hepatic Impairment or Normal Hepatic Function
A Phase 1 study testing AG-120 (Ivosidenib) in people with Hepatic Impairment, run by Agios Pharmaceuticals, Inc. at 2 sites in United States.
Trial summary
Study AG120-C-012 is a Phase 1, open-label, single-dose study designed to evaluate the PK, safety, and tolerability of a single 500 mg AG-120 (Ivosidenib) dose in subjects with mild or moderate hepatic impairment (HI) compared to subjects with normal hepatic function. The study will be conducted at 2 US centers. Read more about this study
- Who is it for?
- Ages 18 to 70 yearsHealthy volunteers can take part
- Conditions the study is for
- Hepatic Impairment
- What is being tested?
- AG-120 (Ivosidenib)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 33 participants
- Where
- 2 sitesUnited States
- Study dates
- 26 Sep 2017to 31 Mar 2018
- 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 70 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- All subjects:
- Body Mass Index BMI of 19 to 40 kg/m2 (inclusive).
- Willing and able to comply with all study restrictions and requirements.
- Non- smoker, or uses no more nicotine-containing product than the equivalent of smoking ≤10 cigarettes per day, as judged by the investigator.
- Female subjects must be non pregnant and non-lactating and either be post-menopausal, surgically sterile, practice total abstinence from sexual intercourse as the preferred lifestyle or agree to use an appropriate method of birth control consistently throughout the study, from screening until 90 days after study drug administration.
- Male subjects with a partner of child bearing potential must either be sterile, practice total abstinence from sexual intercourse as the preferred life style or agree to use an appropriate method of birth control consistently throughout the study, from screening until 90 days after study drug administration.
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- Subjects with hepatic impairment (Cohorts 1a, 2a)
- Diagnosis of chronic (≥3 months prior to Screening) or stable (no acute episodes of illness within 2 months prior to Screening due to deterioration in hepatic function) hepatic insufficiency, with a Child-Pugh classification score in the mild or moderate range.
- Hepatic insufficiency may be of any etiology associated with an unambiguous medical history (such as evidence of portal hypertension).
- Other than hepatic insufficiency with features of cirrhosis, subjects are in good health based on medical history, physical exam, ECG, clinical laboratory tests, and Investigator's assessment.
- Healthy matched subjects (Cohorts 1b, 2b)
- Have normal hepatic function and considered by the Investigator to be in good health, based on medical and surgical history review, physical exam, ECG, clinical laboratory tests, and Investigator's assessment.
Who cannot join
- All subjects:
- Significant acute, new-onset illness (eg, flu, gastroenteritis) within 2 weeks prior to dosing.
- Positive test for drugs of abuse and/or positive alcohol test at Screening or prior to dosing.
- Medical history of clinically significant ECG abnormalities or a family history of prolonged QT interval syndromes.
- History of immunocompromise, including positivity for HIV, or active viral hepatitis B or C.
- Use of over the counter (OTC) medications, herbal supplements, grapefruit juice, Seville oranges, or vitamins 14 days prior to dosing.
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- A recent (within 6 months prior to dosing) history of acute or chronic bronchospastic disease, including asthma and chronic obstructive pulmonary disease.
- Current or history of hepatic carcinoma, hepatorenal syndrome, portacaval shunt surgery, or pleural effusion. Malignancy, including leukemia and lymphoma, within the last 5 years.
- Any surgical or medical condition that might significantly alter the absorption, distribution, or excretion of AG-120.
- Treatment with strong cytochrome P450 (CYP)3A4 inhibitors or inducers within 14 days prior to AG 120 dosing or during the study.
- Subjects with hepatic impairment (Cohorts 1a, 2a)
- Clinical evidence of moderate to severe ascites.
- Significant history or clinical manifestation of any significant metabolic/endocrine, allergic, dermatologic, renal, hematologic, pulmonary, immune, cardiovascular, gastrointestinal, genitourinary, neurologic, or psychiatric disorder, as determined by the Investigator and/or Sponsor's medical monitor (MM) to be clinically significant (CS.)
- Any evidence of progressive liver disease (within the last 4 weeks prior to dosing)
- Severe or uncontrolled medical conditions within 4 weeks prior to AG-120 dosing, with the exception of illness related to HI.
- Healthy Matched Subjects
- Clinical evidence of liver disease or liver injury
- History or presence of impaired renal function
- QTCF >450 (males) or >460 (females) or ECG findings deemed abnormal by the Investigator
- Use of any prescription medications within 30 days prior to dosing
Trial locations and contacts
2 sites in 1 country.
United States2 sites
DaVita Clinical Research- Colorado
Lakewood, Colorado, 80228
DaVita Clinical Research- Minnesota
Minneapolis, Minnesota, 55404
About this study
Official title: A Phase 1, Open-Label, Single-Dose Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of AG-120 (Ivosidenib) in Subjects With Mild or Moderate Hepatic Impairment or Normal Hepatic Function
Study AG120-C-012 is a Phase 1, open-label, single-dose study designed to evaluate the PK, safety, and tolerability of a single 500 mg AG-120 (Ivosidenib) dose in subjects with mild or moderate hepatic impairment (HI) compared to subjects with normal hepatic function. The study will be conducted at 2 US centers.
- Conditions
- Hepatic Impairment
- Being tested
- AG-120 (Ivosidenib)
- Keywords
- AG-120, Healthy Volunteer, Clinical Pharmacology, Hepatic Impairment
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AG-120 (Ivosidenib)Drug
Single 500 mg dose of AG-120 (Ivosidenib).
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1A: Mild Hepatic Impairment | Experimental | Drug: AG-120 (Ivosidenib)
A single 500 mg oral dose of AG-120 (Ivosidenib) in subjects with mild hepatic impairment(Child-Pugh Score A.) Receives: Drug: AG-120 (Ivosidenib) |
| Cohort 1B: Healthy Volunteers | Active comparator | Drug: AG-120 (Ivosidenib)
A single 500 mg oral dose of AG-120 (Ivosidenib) in subjects with normal hepatic function. Receives: Drug: AG-120 (Ivosidenib) |
| Cohort 2A: Moderate Hepatic Impairment | Experimental | Drug: AG-120 (Ivosidenib)
A single 500 mg oral dose of AG-120 (Ivosidenib) in subjects with moderate hepatic impairment (Child-Pugh Score B.) Receives: Drug: AG-120 (Ivosidenib) |
| Cohort 2B: Healthy Volunteers | Active comparator | Drug: AG-120 (Ivosidenib)
A single 500 mg oral dose of AG-120 (Ivosidenib) in subjects with normal hepatic function. Receives: Drug: AG-120 (Ivosidenib) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum observed plasma concentration (Cmax)
AG-120 Cmax, derived from plasma concentration-time curves
Measured: Predose; 0.5hr, 1hr, 2hr, 3hr, 4hr, 6hr, 9hr, 12hr, 24hr, 48hr, 72hr, 120hr, 168hr, 240hr, 336hr, and 504hr post dose
Area under plasma concentration-time curve (AUC)
AG-120 AUC, derived from plasma concentration-time curves
Measured: Predose; 0.5hr, 1hr, 2hr, 3hr, 4hr, 6hr, 9hr, 12hr, 24hr, 48hr, 72hr, 120hr, 168hr, 240hr, 336hr, and 504hr post dose
Secondary outcomes (2)
Adverse Events (AE) and treatment-related AE
Measured: From the time of study drug administration through the end of study (Day 29 or early termination)
Plasma Protein Binding
Compare the plasma protein binding of AG-120 (Ivosidenib) in subjects with impaired HI with that in subjects with normal hepatic function.
Measured: Time Frame: Pre-dose, Day 1 and Day 2
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Sep 2017
- Study start26 Sep 2017
- Primary completion31 Mar 2018
- Study completion31 Mar 2018
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 Hepatic ImpairmentStudies of the same condition, open and under way.
- More trials run by Agios Pharmaceuticals, Inc.The 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
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 33 participants (actual)
Sponsor and investigators
- Lead sponsor
- Agios Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03282513
- Sponsor's protocol ID
- AG120-C-012
- Status last verified
- Apr 2018
- First submitted
- 8 Sep 2017
- Last updated
- 27 Apr 2018
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Fan B, Dai D, Cohen M, Xu H, Yin F, Nagaraja R, Mobilia M, Almon C, Basile FG, Yang H. Effect of Mild and Moderate Hepatic Impairment on the Pharmacokinetics, Safety, and Tolerability of a Single Dose of Oral Ivosidenib in Otherwise Healthy Participants. Clin Pharmacol Drug Dev. 2021 Jan;10(1):99-109. doi: 10.1002/cpdd.821. Epub 2020 Jul 9.
PubMed 32648303
Study at a glance
From the registry record, last updated by the sponsor on 27 Apr 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1, Open-Label, Single-Dose Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of AG-120 (Ivosidenib) in Subjects With Mild or Moderate Hepatic Impairment or Normal Hepatic Function
- ClinicalTrials.gov ID
- NCT03282513
- Acronym / sponsor ID
- AG120-C-012
- Conditions
- Hepatic Impairment
- Keywords
- AG-120, Healthy Volunteer, Clinical Pharmacology, Hepatic Impairment
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 33 participants (actual)
- Lead sponsor
- Agios Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Study start
- 26 Sep 2017 (actual)
- Primary completion
- 31 Mar 2018 (actual)
- Study completion
- 31 Mar 2018 (actual)
- First posted
- 14 Sep 2017 (actual)
- 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.
Study AG120-C-012 is a Phase 1, open-label, single-dose study designed to evaluate the PK, safety, and tolerability of a single 500 mg AG-120 (Ivosidenib) dose in subjects with mild or moderate hepatic impairment (HI) compared to subjects with normal hepatic function. The study will be conducted at 2 US centers.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Cohort 1A: Mild Hepatic Impairment | Experimental | Drug: AG-120 (Ivosidenib)Drug: AG-120 (Ivosidenib) A single 500 mg oral dose of AG-120 (Ivosidenib) in subjects with mild hepatic impairment(Child-Pugh Score A.) |
| Cohort 1B: Healthy Volunteers | Active comparator | Drug: AG-120 (Ivosidenib)Drug: AG-120 (Ivosidenib) A single 500 mg oral dose of AG-120 (Ivosidenib) in subjects with normal hepatic function. |
| Cohort 2A: Moderate Hepatic Impairment | Experimental | Drug: AG-120 (Ivosidenib)Drug: AG-120 (Ivosidenib) A single 500 mg oral dose of AG-120 (Ivosidenib) in subjects with moderate hepatic impairment (Child-Pugh Score B.) |
| Cohort 2B: Healthy Volunteers | Active comparator | Drug: AG-120 (Ivosidenib)Drug: AG-120 (Ivosidenib) A single 500 mg oral dose of AG-120 (Ivosidenib) in subjects with normal hepatic function. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Body Mass Index BMI of 19 to 40 kg/m2 (inclusive).
- Willing and able to comply with all study restrictions and requirements.
- Non- smoker, or uses no more nicotine-containing product than the equivalent of smoking ≤10 cigarettes per day, as judged by the investigator.
- Female subjects must be non pregnant and non-lactating and either be post-menopausal, surgically sterile, practice total abstinence from sexual intercourse as the preferred lifestyle or agree to use an appropriate method of birth control consistently throughout the study, from screening until 90 days after study drug administration.
- Male subjects with a partner of child bearing potential must either be sterile, practice total abstinence from sexual intercourse as the preferred life style or agree to use an appropriate method of birth control consistently throughout the study, from screening until 90 days after study drug administration.
Key exclusion criteria (20 listed)
- Significant acute, new-onset illness (eg, flu, gastroenteritis) within 2 weeks prior to dosing.
- Positive test for drugs of abuse and/or positive alcohol test at Screening or prior to dosing.
- Medical history of clinically significant ECG abnormalities or a family history of prolonged QT interval syndromes.
- History of immunocompromise, including positivity for HIV, or active viral hepatitis B or C.
- Use of over the counter (OTC) medications, herbal supplements, grapefruit juice, Seville oranges, or vitamins 14 days prior to dosing.
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-120 (Ivosidenib)Single 500 mg dose of AG-120 (Ivosidenib). | Drug | Cohort 1A: Mild Hepatic Impairment, Cohort 1B: Healthy Volunteers, Cohort 2A: Moderate Hepatic Impairment, Cohort 2B: Healthy Volunteers |
Primary outcome
Maximum observed plasma concentration (Cmax)
Time frame: Predose; 0.5hr, 1hr, 2hr, 3hr, 4hr, 6hr, 9hr, 12hr, 24hr, 48hr, 72hr, 120hr, 168hr, 240hr, 336hr, and 504hr post dose
AG-120 Cmax, derived from plasma concentration-time curves
Area under plasma concentration-time curve (AUC)
Time frame: Predose; 0.5hr, 1hr, 2hr, 3hr, 4hr, 6hr, 9hr, 12hr, 24hr, 48hr, 72hr, 120hr, 168hr, 240hr, 336hr, and 504hr post dose
AG-120 AUC, derived from plasma concentration-time curves
2 secondary outcomes
Adverse Events (AE) and treatment-related AE
Time frame: From the time of study drug administration through the end of study (Day 29 or early termination)
Plasma Protein Binding
Time frame: Time Frame: Pre-dose, Day 1 and Day 2
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 27 Apr 2018.
- Derived from this study: PubMed 32648303Fan B, Dai D, Cohen M, Xu H, Yin F, Nagaraja R, Mobilia M, Almon C, Basile FG, Yang H. Effect of Mild and Moderate Hepatic Impairment on the Pharmacokinetics, Safety, and Tolerability of a Single Dose of Oral Ivosidenib in Otherwise Healthy Participants. Clin Pharmacol Drug Dev. 2021 Jan;10(1):99-109. doi: 10.1002/cpdd.821. Epub 2020 Jul 9.
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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.
The record lists no contact. Use the official record to reach the sponsor.
2 sites 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-120 (Ivosidenib) in people with Hepatic Impairment, run by Agios Pharmaceuticals, Inc. at 2 sites 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 12 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 27 Apr 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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?
Maximum observed plasma concentration (Cmax) (time frame: Predose; 0.5hr, 1hr, 2hr, 3hr, 4hr, 6hr, 9hr, 12hr, 24hr, 48hr, 72hr, 120hr, 168hr, 240hr, 336hr, and 504hr post dose). The study lists 2 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 NCT03282513, 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 27 Apr 2018.