Hepatic ImpairmentPhase 1NCT04643795
Phase 1 Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of Multiple Oral Doses of MGL-3196 in Subjects With Varying Degrees of Hepatic Impairment and Healthy Matched Control Subjects
A Phase 1 study testing MGL-3196 in people with Hepatic Impairment and NASH - Nonalcoholic Steatohepatitis, run by Madrigal Pharmaceuticals, Inc. at 3 sites in United States.
Trial summary
The purpose of this study is to directly characterize the pharmacokinetic (PK) profiles of MGL-3196 and its major metabolite (MGL-3623) following administration of multiple oral doses (QD x 6 days) in subjects with varying degrees of hepatic impairment (HI) compared to healthy matched control subjects with normal… Read more about this study
- Who is it for?
- Ages 18 to 85 yearsHealthy volunteers can take part
- Conditions the study is for
- Hepatic Impairment, NASH - Nonalcoholic Steatohepatitis, Cirrhosis, Liver
- What is being tested?
- MGL-3196
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 87 participants
- Where
- 3 sitesUnited States
- Study dates
- 25 Oct 2018to 4 Aug 2021
- 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 85 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Capable of understanding and willing and able to sign written informed consent
- Male or female, between 18 and 85 years of age (inclusive)
- BMI between 18 and 45 kg/m2 (inclusive)
- In healthy subjects with normal hepatic function:
- Considered by the Investigator to be healthy, based on medical and surgical history, physical examination including vital signs, 12-lead ECG, and laboratory test results
- Match demographically with a subject in the hepatically impaired population according to gender, BMI (±20%), and age (±10 years)
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- In subjects with hepatic impairment:
- Considered by the Investigator to be clinically stable with respect to underlying HI, based on medical and surgical history, physical examination including vital signs, 12-lead ECG, and laboratory test results
- In subjects with NASH:
- Confirmed diagnosis of NASH suggested by historical data, which include a previous liver biopsy within the last 5 years prior to randomization with evidence of NASH.
- BMI ≥18 kg/m2
Who cannot join
- Any clinically significant concomitant disease or condition (including treatment for such conditions) that, in the opinion of the Investigator, could either interfere with the study drug, pose an unacceptable risk to the subject, or compromise interpretation of study data
- Gilbert's syndrome
- Pre-existing condition interfering with normal gastrointestinal anatomy or motility, hepatic and/or renal function that could interfere with the absorption, metabolism, and/or excretion of study drug
- eGFR <60 mL/min/1.73 m2 based on Modification of Diet in Renal Disease (MDRD) equation
- Received an investigational drug or device from another study within 30 days (or 5 half-lives, whichever is longer) prior to study drug administration
- In healthy subjects with normal hepatic function:
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- Systolic blood pressure outside the range of 90 to 150 mmHg, diastolic blood pressure outside the range of 40 to 95 mmHg or heart rate outside the range of 40 to 100 beats per minute (bpm)
- History of regular alcohol consumption exceeding 7 drinks/week for females or 14 drinks/week for men (1 drink = 5 ounces of wine or 12 ounces of beer or 1.5 ounces of hard liquor) within 6 months prior to screening
- In subjects with hepatic impairment:
- Any non-hepatic acute or chronic condition (including, but not limited to, poorly controlled diabetes and encephalopathy Grade ≥3) that, in the opinion of the Investigator, would limit the subject's ability to complete and/or participate in the study
- Acute exacerbation of HI or unstable hepatic function, as determined by the Investigator, 30 days prior to study drug administration
- Has had a Transjugular Intrahepatic Portosystemic Shunt (TIPS) procedure performed
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Madrigal Research Center
Orlando, Florida, 32809
Madrigal Research Center
Saint Paul, Minnesota, 55114
Madrigal Research Center
San Antonio, Texas, 78229
About this study
Official title: A Phase I, Open Label, Non-randomized Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of Multiple Oral Doses of MGL-3196 in Subjects With Varying Degrees of Hepatic Impairment and Healthy Matched Control Subjects With Normal Hepatic Function
The purpose of this study is to directly characterize the pharmacokinetic (PK) profiles of MGL-3196 and its major metabolite (MGL-3623) following administration of multiple oral doses (QD x 6 days) in subjects with varying degrees of hepatic impairment (HI) compared to healthy matched control subjects with normal hepatic function, including a subset of NASH subjects.
- Being tested
- MGL-3196
- Medical subject headings
- Non-alcoholic Fatty Liver Disease, Liver Cirrhosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MGL-3196Drug
Once daily oral dose for 6 days
| Study group | Role | What they receive |
|---|---|---|
| 40 mg MGL-3196 Tablet | Experimental | Multiple cohorts (normal, varying hepatic impairment, NASH non-cirrhosis, and NASH cirrhosis) evaluated Receives: Drug: MGL-3196 |
| 60 mg MGL-3196 Tablet | Experimental | Multiple cohorts (normal, varying hepatic impairment, NASH non-cirrhosis, and NASH cirrhosis) evaluated Receives: Drug: MGL-3196 |
| 80 mg MGL-3196 Tablet | Experimental | Multiple cohorts (normal, varying hepatic impairment, NASH non-cirrhosis, and NASH cirrhosis) evaluated Receives: Drug: MGL-3196 |
| 100 mg MGL-3196 Tablet | Experimental | Multiple cohorts (normal, varying hepatic impairment, NASH non-cirrhosis, and NASH cirrhosis) evaluated Receives: Drug: MGL-3196 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Plasma pharmacokinetics - Cmax
Cmax after administration
Measured: 16 days
Plasma pharmacokinetics - Tmax
Tmax after administration
Measured: 16 days
Plasma pharmacokinetics - AUC (0-last)
AUC (0-last) after administration
Measured: 16 days
Plasma pharmacokinetics - t1/2
t1/2 after administration
Measured: 16 days
Effect on the incidence of adverse events
Measured: 16 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Nov 2020
- Study start25 Oct 2018
- Primary completion4 Aug 2021
- Study completion4 Aug 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hepatic ImpairmentStudies of the same condition, open and under way.
- 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
- 87 participants (actual)
Sponsor and investigators
- Lead sponsor
- Madrigal Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04643795
- Sponsor's protocol ID
- MGL-3196-10
- Status last verified
- Oct 2023
- First submitted
- 22 Oct 2020
- Last updated
- 5 Oct 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Oct 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I, Open Label, Non-randomized Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of Multiple Oral Doses of MGL-3196 in Subjects With Varying Degrees of Hepatic Impairment and Healthy Matched Control Subjects With Normal Hepatic Function
- ClinicalTrials.gov ID
- NCT04643795
- Acronym / sponsor ID
- MGL-3196-10
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 87 participants (actual)
- Lead sponsor
- Madrigal Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Study start
- 25 Oct 2018 (actual)
- Primary completion
- 4 Aug 2021 (actual)
- Study completion
- 4 Aug 2021 (actual)
- First posted
- 25 Nov 2020 (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.
The purpose of this study is to directly characterize the pharmacokinetic (PK) profiles of MGL-3196 and its major metabolite (MGL-3623) following administration of multiple oral doses (QD x 6 days) in subjects with varying degrees of hepatic impairment (HI) compared to healthy matched control subjects with normal hepatic function, including a subset of NASH subjects.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| 40 mg MGL-3196 Tablet | Experimental | Drug: MGL-3196Multiple cohorts (normal, varying hepatic impairment, NASH non-cirrhosis, and NASH cirrhosis) evaluated |
| 60 mg MGL-3196 Tablet | Experimental | Drug: MGL-3196Multiple cohorts (normal, varying hepatic impairment, NASH non-cirrhosis, and NASH cirrhosis) evaluated |
| 80 mg MGL-3196 Tablet | Experimental | Drug: MGL-3196Multiple cohorts (normal, varying hepatic impairment, NASH non-cirrhosis, and NASH cirrhosis) evaluated |
| 100 mg MGL-3196 Tablet | Experimental | Drug: MGL-3196Multiple cohorts (normal, varying hepatic impairment, NASH non-cirrhosis, and NASH cirrhosis) evaluated |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Capable of understanding and willing and able to sign written informed consent
- Male or female, between 18 and 85 years of age (inclusive)
- BMI between 18 and 45 kg/m2 (inclusive)
- In healthy subjects with normal hepatic function:
- In subjects with hepatic impairment:
Key exclusion criteria (12 listed)
- Any clinically significant concomitant disease or condition (including treatment for such conditions) that, in the opinion of the Investigator, could either interfere with the study drug, pose an unacceptable risk to the subject, or compromise interpretation of study data
- Gilbert's syndrome
- Pre-existing condition interfering with normal gastrointestinal anatomy or motility, hepatic and/or renal function that could interfere with the absorption, metabolism, and/or excretion of study drug
- eGFR <60 mL/min/1.73 m2 based on Modification of Diet in Renal Disease (MDRD) equation
- Received an investigational drug or device from another study within 30 days (or 5 half-lives, whichever is longer) prior to study drug administration
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 |
|---|---|---|
| MGL-3196Once daily oral dose for 6 days | Drug | 100 mg MGL-3196 Tablet, 40 mg MGL-3196 Tablet, 60 mg MGL-3196 Tablet, 80 mg MGL-3196 Tablet |
Primary outcome
Plasma pharmacokinetics - Cmax
Time frame: 16 days
Cmax after administration
Plasma pharmacokinetics - Tmax
Time frame: 16 days
Tmax after administration
Plasma pharmacokinetics - AUC (0-last)
Time frame: 16 days
AUC (0-last) after administration
Plasma pharmacokinetics - t1/2
Time frame: 16 days
t1/2 after administration
Effect on the incidence of adverse events
Time frame: 16 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 5 Oct 2023.
- Individual participant dataSharing planned: No
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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.
3 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 MGL-3196 in people with Hepatic Impairment and NASH - Nonalcoholic Steatohepatitis, run by Madrigal Pharmaceuticals, Inc. at 3 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 11 inclusion and 12 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 5 Oct 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 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?
Plasma pharmacokinetics - Cmax (time frame: 16 days). The study lists 5 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 5 Oct 2023.