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Moderate Hepatic ImpairmentPhase 1NCT05610657

A Pharmacokinetic Study of Mitapivat in Participants With Moderate Hepatic Impairment Compared to Matched Healthy Control Participants With Normal Hepatic Function

A Phase 1 study testing Mitapivat in people with Moderate Hepatic Impairment, run by Agios Pharmaceuticals, Inc. at 3 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The primary purpose of this study is to compare the pharmacokinetics (PK) of a single oral dose of mitapivat in participants with moderate hepatic impairment to that in matched healthy control participants with normal hepatic function. Read more about this study

Who is it for?
Ages 18 to 65 yearsHealthy volunteers can take part
Conditions the study is for
Moderate Hepatic Impairment
What is being tested?
Mitapivat
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
20 participants
Where
3 sitesUnited States
Study dates
10 Jan 2023to 21 Jul 2023
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 65 years
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • For all Participants-
  • Age: between 18 and 65 years of age;
  • Men and women of any race;
  • Body mass index (BMI) between 18.0 and 34.0 kilograms per square meter (kg/m^2), inclusive with at least 50 kg of body weight;
  • There should be no use of tobacco- or nicotine-containing products within 3 months prior to check-in until completion of the follow-up visit;
  • Male participants must agree not to donate sperm from check-in until 90 days after completion of the follow-up visit;
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  • Females of childbearing potential will agree to use contraception;
  • Able to comprehend the requirements of the study and willing to sign an informed consent form before any study related procedures are conducted and to abide by the study restrictions.
  • For Participants with Normal Hepatic Function-
  • In good health, determined by no clinically significant (CS) findings, as determined by the investigator, from medical and surgical history, physical examination, 12-lead ECG, vital signs measurements, and clinical laboratory evaluations (congenital nonhemolytic hyperbilirubinemia [e.g., suspicion of Gilbert's syndrome based on total and direct bilirubin] is not acceptable) at screening and check-in;
  • Serum electrolytes (sodium, potassium, chloride, bicarbonate, magnesium, and calcium) within normal limits or if deemed not CS by the investigator judgment in the case of minor abnormalities;
  • Matched to participants with moderate hepatic impairment in sex, age (±10 years), and BMI (±20%).
  • For Participants with Moderate Hepatic Impairment-
  • Diagnosis of chronic (≥3 months prior to screening) and stable hepatic insufficiency (no acute episodes of illness or deterioration in hepatic function) as assessed by the investigator with a C-P classification score of 7 to 9 (moderate hepatic impairment). Evidence of liver disease should be corroborated by medical history;
  • Have current, or a history of at least 1 physical sign consistent with a clinical diagnosis of liver cirrhosis;
  • Other than hepatic insufficiency with features of cirrhosis, hepatic impairment participants are in good health and clinically stable based on:
  • stable hepatic function is defined as no recent [i.e., within the preceding 14 days] CS change in disease status according to the investigator's clinical judgment (e.g., no worsening of clinical signs of hepatic impairment, or no worsening of total bilirubin or prothrombin by more than 50%).
  • the investigator's assessment including medical history and surgical history review, a defined complete physical examination, 12-lead ECG, vital signs, and clinical laboratory evaluations (clinical chemistry [including liver function tests], hematology, urinalysis, coagulation tests, thyroid function tests).
  • Abnormal laboratory values (hepatic and nonhepatic) must be clinically acceptable by the investigator (or designee);
  • Participants who need concomitant medications that are not prohibited during this study must have a medication regimen considered to be stable by the investigator. (e.g., no new drugs or significant changes to dosage(s) within 2 weeks [or 5 half-lives, whichever is longer] prior to study drug administration on Day 1; no changes expected during study conduct). Concomitant medications must be reviewed and approved by the investigator and Labcorp medical monitor (or designee).
  • Anemia secondary to hepatic disease will be acceptable if hemoglobin is ≥8 grams per deciliter (g/dL) and anemia symptoms are not CS;
  • Participants must have a platelet count ≥35 × 10^9/L.

Who cannot join

  • For all Participants-
  • Presence or history of any disorder that may prevent the successful completion of the study;
  • Participant is pregnant or breastfeeding;
  • Significant acute, new-onset illness (e.g., flu, gastroenteritis) within 2 weeks prior to dosing;
  • Inability to swallow medication;
  • Has a history of relevant drug and/or food allergies (i.e., allergy to study drug or excipients [microcrystalline cellulose, croscarmellose sodium, sodium stearyl fumarate, mannitol, magnesium stearate, and the Opadry Blue II film-coat [hypromellose, titanium dioxide, lactose monohydrate, triacetin, and FD\&C Blue #2]);
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  • Surgical or medical history that, in the opinion of the investigator, may potentially interfere with study drug absorption, distribution, metabolism, and/or excretion. Participants who have undergone abdominal surgery or any other major surgical procedure within 6 months prior to screening, must not be enrolled; The investigator should be guided by evidence of any of the following:
  • History of inflammatory bowel syndrome, gastritis, ulcers, gastrointestinal or rectal bleeding within the past 3 months.
  • History of major gastrointestinal tract surgery such as gastrectomy, gastroenterostomy, or bowel resection.
  • History of pancreatic injury or pancreatitis in the past 6 months; indications of impaired pancreatic function/injury as indicated by CS abnormal lipase or amylase.
  • History of urinary obstruction or difficulty in voiding in the past 3 months.
  • History or a presence of any malignancy, with the exception of a malignancy that has been curatively treated and for which the Participant has displayed no evidence of disease within 12 months prior to screening. Current or history of hepatic carcinoma, hepatorenal syndrome, portacaval shunt surgery, or pleural effusion. Malignancy, including leukemia and lymphoma, within the last 5 years. Participants with localized, fully-treated carcinoma of the skin may be allowed with investigator (or designee) approval;
  • Confirmed (e.g., 2 consecutive measurements) systolic blood pressure >150 or <90 millimeters of mercury (mmHg), diastolic blood pressure >100 or <50 mmHg, and pulse rate >100 or <40 beats per minute (bpm); (Note: Participants with vital signs outside the above ranges may be eligible if the investigator and Labcorp medical monitor deem the results are not CS.)
  • Clinically significant cardiac history or presence of ECG findings as determined by the investigator at screening and check-in, including any of the following:
  • Abnormal sinus rhythm (heart rate [HR] lower than 40 bpm and higher than 100 bpm)
  • Risk factors for torsades de pointes (e.g., heart failure, cardiomyopathy, or family history of long QT syndrome)
  • Sick sinus syndrome, second- or third-degree atrioventricular block myocardial infarction, pulmonary congestion, cardiac arrhythmia, prolonged QT interval, or conduction abnormalities.
  • QT interval corrected for HR using Fridericia's formula (QTcF) >450 milliseconds (msec) (healthy male participants) or >470 msec (healthy female participants) or >480 msec for hepatically impaired participants; in the event a QTcF value is outside of the reference range, it will be confirmed by 2 repeat measurements, which will then be used to calculate a mean from the original value and the 2 repeat measurements.
  • QRS interval >110 msec, confirmed by manual over read.
  • PR interval <120 and >220 msec.
  • Repeated or frequent syncope or vasovagal episodes.
  • Hypertension, angina, bradycardia (if assessed as CS by the investigator), or severe peripheral arterial circulatory disorders.
  • History of autonomic dysfunction.
  • Has estimated glomerular filtration rate <60 mL/minute/1.73 m^2 using Cockcroft-Gault equation;
  • Administration of a coronavirus disease 2019 vaccine in the past 14 days prior to dosing;
  • Has a positive test for severe acute respiratory syndrome coronavirus 2; Note: Testing will be performed according to site procedures;
  • Has an active infection requiring systemic antimicrobial therapy at any time during the screening period;
  • Is currently enrolled in or has participated in another clinical study to receive any investigational or marketed product or placebo within 4 weeks (or 5 half-lives, whichever is longer) or longer as required by local regulations prior to check-in;
  • History of alcohol abuse within 3 months prior to screening and/or alcohol consumption of >21 units per week for males and >14 units for females. One unit of alcohol equals 12 ounce [oz] (360 mL) beer, 1 1/2 oz (45 mL) liquor, or 5 oz (150 mL) wine;
  • Positive urine, breath, or blood test for alcohol or positive urine drug screen at screening and/or check-in;
  • Positive urine cotinine test screening and/or at check-in (smokers will be defined as any participant who reports current tobacco use and/or who has a positive urine cotinine test);
  • History or suspicion of active substance use disorder prior to check-in (including, but not limited to: cannabinoids, amphetamines, methamphetamines, 3,4-methylenedioxy-N-methylamphetamine [ecstasy], opiates, methadone, oxycodone, phencyclidine, cocaine, cotinine, benzodiazepines, and barbiturates);
  • Ingestion of poppy seed-, Seville orange-, or grapefruit-containing foods or beverages within 7 days prior to check-in and not willing to refrain from consumption of these foods or beverages throughout the study until completion of the follow-up visit;
  • Alcohol consumption, starting 48 hours prior to check-in and continuing until completion of the follow-up visit;
  • Consumption of caffeine- or xanthine-containing products within 48 hours before check-in until completion of the follow-up visit;
  • Consumption of vegetables from the mustard green family (e.g., kale, broccoli, watercress, collard greens, kohlrabi, Brussel sprouts, and mustard greens), or charbroiled meat for 7 days prior to dosing until completion of the follow-up visit;
  • Receipt of blood products within 2 months prior to check-in;
  • Participant has donated (or lost) ≥ 400 mL of red blood cells within 2 months prior to screening, plasma within 2 weeks prior to screening, or platelets within 6 weeks prior to screening; Participant has planned donation of any blood products after screening until 3 months after the follow-up visit;
  • Participants are required to refrain from strenuous exercise from 7 days before check-in until completion of the follow-up visit and will otherwise maintain their normal level of physical activity during this time (i.e., will not begin a new exercise program nor participate in any unusually strenuous physical exertion);
  • Poor peripheral venous access;
  • Participants who, in the opinion of the investigator (or designee), should not participate in this study;
  • Positive hepatitis B surface antigen or human immunodeficiency virus 1 or 2 test.
  • For Participants with Normal Hepatic Function-
  • Liver test results (alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, albumin, or total bilirubin) above the upper limit of normal and/or prolonged prothrombin time (results may be repeated once), at screening and check-in, unless deemed not CS approved by the investigator (or designee);
  • Has a known history or presence of liver disease;
  • Significant history or clinical manifestation of any metabolic, allergic, dermatological, hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal, neurological, or psychiatric disorder (as determined by the investigator);
  • Uses or intends to use any medications/products known to alter drug absorption, metabolism, or elimination processes, including slow-release medications/products, any over-the-counter medications or herbal or nutritional supplements with the exception of vitamins, within 14 days (or 5 half-lives, whichever is longer) prior to check-in and until completion of the follow-up visit, unless deemed acceptable by the investigator (or designee);
  • Has used any prescription medications (excluding hormone replacement therapy, oral, implantable, transdermal, injectable, or intrauterine contraceptives), including systemic antimicrobial therapies, within 30 days (or 5 half-lives, whichever is longer) before dosing or during the study (ie, through the follow-up visit);
  • Positive hepatitis C antibody;
  • History of diabetes mellitus.
  • For Participants with Hepatic Impairment-
  • Participants receiving strong and moderate cytochrome P450 (CYP) 3A inhibitors that have not been stopped for ≥5 days or a time frame equivalent to 5 half-lives (whichever is longer), or strong and moderate CYP3A inducers that have not been stopped for ≥4 weeks or a time frame equivalent to 5 half-lives (whichever is longer), before administration of the study drug;
  • Participants with Grade 2 or higher encephalopathy, as defined by the grading scale in the Food and Drug Administration (FDA) guidance on PK studies in participants;
  • Participant has a portal systemic shunt;
  • Participant demonstrates evidence of hepatorenal syndrome;
  • Participant has required treatment for gastrointestinal bleeding within the 3 months prior to check-in (Participants demonstrating banding procedure within 1 month prior to check-in may be included at the discretion of the investigator [or designee]);
  • Participant has required new medication or a change in dose for hepatic encephalopathy within 3 months prior to check-in, unless approved by the investigator (or designee);
  • Participants who require paracentesis within 3 months prior to check-in or planned during the study;
  • Clinical evidence of moderate to severe ascites;
  • Any evidence of progressive liver disease (between screening and check-in) as indicated by liver transaminases, alkaline phosphatase, or gamma-glutamyl transferase, or a ≥50% worsening of serum bilirubin or prothrombin time.

Trial locations and contacts

3 sites in 1 country.

United States3 sites

  • Clinical Pharmacology of Miami (CPMI)

    Miami, Florida, 33014

  • Orlando Clinical Research Center (OCRC)

    Orlando, Florida, 32809

  • Orange County Research Center (OCRC)

    Tustin, California, 92780

Other trials in United States

About this study

Official title: A Phase 1, Open-label, Single-dose, Pharmacokinetic Study of Mitapivat in Subjects With Moderate Hepatic Impairment Compared to Matched Healthy Control Subjects With Normal Hepatic Function

The primary purpose of this study is to compare the pharmacokinetics (PK) of a single oral dose of mitapivat in participants with moderate hepatic impairment to that in matched healthy control participants with normal hepatic function.

Being tested
Mitapivat
Keywords
AG-348, Healthy Volunteer, Hepatic Impairment, pharmacokinetic

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • MitapivatDrug

    Also called AG-348, AG-348 sulfate hydrate, Mitapivat sulfate

    Mitapivat tablets

Study groups in NCT05610657
Study groupRoleWhat they receive
MitapivatExperimentalMitapivat tablet as a single oral dose, under fasted conditions on Day 1 to compare participants with normal hepatic function to participants with moderate hepatic function (Child-Pugh [C-P] Score B, score of 7 to 9).
Receives: Drug: Mitapivat

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Area Under the Plasma Concentration-Time Curve From Time 0 (Predose) to Extrapolated to Infinity Time (AUC∞) of Mitapivat

    Measured: Pre-dose and at multiple timepoints post-dose up to Day 17

  2. Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC0-t) of Mitapivat

    Measured: Pre-dose and at multiple timepoints post-dose up to Day 17

  3. Maximum Plasma Concentration (Cmax) of Mitapivat

    Measured: Pre-dose and at multiple timepoints post-dose up to Day 17

Secondary outcomes (10)

  1. Time to Reach Cmax (tmax) of Mitapivat

    Measured: Pre-dose and at multiple timepoints post-dose up to Day 17

  2. Terminal Elimination Half-life (t1/2) of Mitapivat

    Measured: Pre-dose and at multiple timepoints post-dose up to Day 17

  3. Apparent Total Clearance (CL/F) of Mitapivat

    Measured: Pre-dose and at multiple timepoints post-dose up to Day 17

  4. Apparent Volume of Distribution During the Terminal Phase (Vz/F) of Mitapivat

    Measured: Pre-dose and at multiple timepoints post-dose up to Day 17

  5. Fraction Unbound (fu) for Mitapivat in Plasma

    Measured: Pre-dose and at multiple timepoints post-dose up to Day 11

  6. Number of Participants With Adverse Events (AEs), AEs by Severity, and Relatedness to Study Treatment

    Measured: Up to Day 17

  7. Number of Participants With Abnormalities in Laboratory Evaluations, Based on Coagulation, Hematology, Clinical Chemistry and Urinalysis Test Results

    Measured: Up to Day 12

  8. Number of Participants With Changes in 12-lead Electrocardiogram (ECG) Parameters

    Measured: Up to Day 12

  9. Number of Participants With Changes in Vital Sign Measurements

    Measured: Up to Day 12

  10. Number of Participants With Changes in Physical Examination Findings

    Measured: Up to Day 12

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted9 Nov 2022
  2. Study start10 Jan 2023
  3. Primary completion21 Jul 2023
  4. Study completion21 Jul 2023

Resources

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
Basic science
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
20 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05610657
Sponsor's protocol ID
AG348-C-024
Status last verified
Sep 2023
First submitted
3 Nov 2022
Last updated
21 Sep 2023
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Mitapivat in people with Moderate Hepatic Impairment, run by Agios 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 22 inclusion and 60 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 21 Sep 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?

Area Under the Plasma Concentration-Time Curve From Time 0 (Predose) to Extrapolated to Infinity Time (AUC∞) of Mitapivat (time frame: Pre-dose and at multiple timepoints post-dose up to Day 17). The study lists 3 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 NCT05610657.

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 21 Sep 2023.

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