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Healthy VolunteersPhase 1NCT03991312

Study to Evaluate the Effect of Multiple Doses of Itraconazole and Rifampin on the Single-Dose Pharmacokinetics of Mitapivat Sulfate (AG-348) in Healthy Adult Participants

A Phase 1 study testing itraconazole, rifampin and mitapivat sulfate in people with Healthy Volunteers, run by Agios Pharmaceuticals, Inc. at 1 site in United States.

Completed

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

Official record
Search all trials

Trial summary

Part 1 of this study will determine the effect of multiple-dose itraconazole, a strong cytochrome P450 (CYP) 3A4 and P-glycoprotein (P-gp) inhibitor, on the single-dose pharmacokinetic(s) (PK) of mitapivat sulfate in healthy adult participants. Read more about this study

Who is it for?
Ages 18 to 55 yearsHealthy volunteers can take part
Conditions the study is for
Healthy Volunteers
What is being tested?
itraconazole, rifampin and mitapivat sulfate
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
28 participants
Where
1 siteUnited States
Study dates
20 Jun 2019to 10 Sep 2019
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
  • All sexes
  • Healthy volunteers accepted
  • Adult

Who may be able to join

  • Healthy, adult, male or female (non-childbearing potential), 18-55 years of age, inclusive, at the time of providing written informed consent;
  • Continuous non-smoker who has not used nicotine-containing products for at least 12 months prior to screening, based on participant self-reporting, and agrees to abstain from use throughout the study;
  • Body mass index (BMI) ≥ 18.0 and ≤ 32.0 kilograms per meter squared (kg/m2) at screening;
  • Medically healthy, with no clinically significant conditions or abnormalities, as determined by the principal investigator (PI) or designee, through evaluation of medical history and screening vital signs, 12-lead electrocardiogram (ECG) results, physical examination findings, and clinical laboratory test results;
  • A female participant must be of non-childbearing potential and must have undergone one of the following sterilization procedures at least 6 months prior to the first dosing:
  • hysteroscopic sterilization;
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  • bilateral tubal ligation or bilateral salpingectomy;
  • hysterectomy;
  • bilateral oophorectomy.
  • or be postmenopausal with amenorrhea for at least 1 year prior to the first dosing and follicle-stimulating hormone (FSH) serum levels at screening consistent with postmenopausal status;
  • A male participant (with or without prior vasectomy) must agree to use a condom with spermicide or abstain from sexual intercourse from the time of providing written informed consent until 90 days after the last dose of study drug;
  • If male, must agree not to donate sperm from the first dosing until 90 days after the last dose of study drug;
  • Understands the study procedures in the informed consent form (ICF), and is willing and able to comply with the study procedures and the protocol requirements, and has provided signed written informed consent prior to performing any study procedures, including screening procedures;

Who cannot join

  • Is mentally or legally incapacitated or has significant emotional problems at the time of the screening visit or expected during the conduct of the study;
  • History or presence of any clinically significant medical or psychiatric condition or disease or clinically significant laboratory abnormality that, in the opinion of the PI or designee, might confound the results of the study, compromise the ability of the participant to complete study procedures, and/or pose an additional risk to the participant by their participation in the study. This includes seizure disorders, transient ischemic attacks, or easy bruising;
  • History or presence of a medical condition or surgical procedure that, in the opinion of the PI or designee, may potentially interfere with absorption, distribution, metabolism, or excretion of the study drugs;
  • History or presence of alcohol or drug abuse within the past 2 years prior to screening;
  • History or presence of hypersensitivity, idiosyncratic reaction, or serious adverse reaction to any of the study drugs or to their formulation excipients;
  • Female participants of childbearing potential;
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  • Female participants with a positive serum pregnancy test at screening or check-in or who are breastfeeding;
  • Positive urine drug or alcohol results at screening or check-in;
  • Positive results at screening for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C virus (HCV) antibody;
  • Supine blood pressure is less than 90/40 milliliters of mercury (mmHg) or greater than 140/90 mmHg at screening. If the participant's systolic blood pressure reading exceeds 140 mmHg or the diastolic blood pressure reading exceeds 90 mmHg due to what may be, in the opinion of the PI or designee, an episode of transient anxiety, the reading may be repeated, and the resulting blood pressure measurement used to determine eligibility;
  • Supine heart rate is lower than 40 beats per minute (bpm) or higher than 99 bpm at screening. If the participant's heart rate exceeds 99 bpm due to what may be, in the opinion of the PI or designee, an episode of transient anxiety, the reading may be repeated, and the resulting heart rate measurement used to determine eligibility;
  • QTcF interval is >450 milliseconds (msec) (males) or >470 msec (females) or has ECG findings deemed abnormal with clinical significance by the PI or designee at screening;
  • Estimated creatinine clearance < 90 mL/min at screening (Cockcroft-Gault formula);
  • Unable to refrain from or anticipates the use of any drug, including prescription and non-prescription medications, proton pump inhibitors, H2-antagonists, herbal remedies, and vitamin supplements, beginning 28 days prior to the first dosing and throughout the study. Additionally, any drugs (with the exception of the study drugs) known to be clinically significant inhibitors or inducers of CYP3A, CYP2C9, CYP2C8, CYP2C19, and CYP1A2 enzymes and/or P-gp, including St. John's Wort, beginning 28 days prior to the first dosing and throughout the study. Appropriate sources (e.g., Flockhart TableTM) will be consulted to confirm lack of PK/PD interaction with study drugs. After first dosing, acetaminophen (up to 2 g per 24 hours) may be administered at the discretion of the PI or designee;
  • Has consumed foods or beverages containing caffeine or xanthines 24 hours prior to the first dosing and is not willing to refrain from consumption of these foods or beverages throughout the study;
  • Has consumed alcohol 48 hours prior to the first dosing and is not willing to refrain from consumption of alcohol throughout the study;
  • Has consumed foods or beverages containing grapefruit or Seville oranges for 14 days prior to the first dosing and is not willing to refrain from consumption of these foods or beverages throughout the study;
  • Has consumed fruit juices 72 hours prior to the first dosing and is not willing to refrain from consumption of these juices throughout the study
  • Has consumed vegetables from the mustard green family (e.g., kale, broccoli, watercress, collard greens, kohlrabi, Brussel sprouts, and mustard), and charbroiled meats for 7 days prior to first dosing and is not willing to refrain from consumption of these foods throughout the study;
  • Has been on a diet incompatible with the on-study diet, in the opinion of the PI or designee, within the 30 days prior to the first dosing;
  • Donation of blood or significant blood loss (≥500 mL) within 3 months prior to the first dosing and must be willing to refrain from voluntary blood donation for at least 30 days after the last dose of study drug;
  • Plasma donation within 7 days prior to screening;
  • Has liver function tests including alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and total bilirubin that are greater than the upper limit of normal at screening or check-in (confirmation of results may be done once);
  • Has platelet, hemoglobin, and hematocrit that are below the lower limit of normal at screening or check-in (confirmation of results may be done once).
  • History or presence of liver disease;
  • Are currently enrolled in or have participated in another clinical study involving ongoing therapy with any investigational or marketed product or placebo within 3 months prior to the first dosing. The 3-month window will be derived from the date of the last blood collection or dosing, whichever is later, in the previous study to Day 1 of Treatment Period 1 of the current study;
  • Has exposure to any investigational drug within 5 times the elimination half-life, if known (for marketed product) or within 3 months (if the elimination half-life is unknown) prior to first dosing;
  • Has undergone any major surgical procedure within 3 months prior to Screening;
  • History or presence of a primary malignancy, with the exception of a malignancy that has been curatively treated and for which the participant has displayed no evidence of disease within the 12 months prior to Screening;
  • History or presence of a clinically significant allergy requiring medical treatment, as assessed by the PI or designee;
  • Has glucose-6-phosphate dehydrogenase deficiency;
  • Has veins that are unsuitable for multiple venipunctures/cannulation, as assessed by the PI or designee at screening;
  • For Part 1 Only (Itraconazole):
  • History or presence of any of the following, deemed clinically significant by the PI or designee:
  • History or presence of ventricular dysfunction or risk factors for Torsades de Pointes (e.g., heart failure, cardiomyopathy, myocardial infarction, angina, unexplained syncope, personal or family history of Long QT Syndrome, Brugada syndrome, or sudden death).;
  • Uncorrected hypokalemia (potassium levels < 3.7) and/or hypomagnesemia (magnesium levels < 1.9).

Trial locations and contacts

1 site in 1 country.

United States1 site
  • Celerion, Inc

    Tempe, Arizona, 85283

Other trials in United States

About this study

Official title: A Two-Part, Open-Label, Fixed-Sequence Study to Evaluate the Effect of Multiple Doses of Itraconazole and Rifampin on the Single-Dose Pharmacokinetics of Mitapivat Sulfate (AG-348) in Healthy Adult Subjects

Part 1 of this study will determine the effect of multiple-dose itraconazole, a strong cytochrome P450 (CYP) 3A4 and P-glycoprotein (P-gp) inhibitor, on the single-dose pharmacokinetic(s) (PK) of mitapivat sulfate in healthy adult participants. Part 2 of this study will determine the effect of multiple-dose rifampin, a strong CYP3A4 and P-gp inducer, on the single-dose pharmacokinetic(s) (PK) of mitapivat sulfate in healthy adult participants.

Read the detailed description

This study consists of 2 periods and 2 parts. Participants will be placed in Part 1 or Part 2, and cannot participate in both:

Part 1, Period 1 includes a screening period up to 28 days prior to dosing and treatment on Day 1.

Part 1, Period 2 includes a treatment period from Day 1 to Day 9 and a possible follow-up, up to 28 days after the last dose of study drug.

Part 2, Period 1 includes a screening period up to 28 days prior to dosing and treatment on Day 1.

Part 2, Period 2 includes a treatment period from Day 1 to Day 12 and a possible follow-up, up to 28 days after the last dose of study drug.

Being tested
itraconazole, rifampin, mitapivat sulfate

What participants receive

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

  • itraconazoleDrug

    Participants will receive an oral solution as described in the arm description.

  • rifampinDrug

    Participants will receive oral capsule(s) as described in the arm description.

  • mitapivat sulfateDrug

    Also called AG348

    Participants will receive an oral tablet as described in the arm description.

Study groups in NCT03991312
Study groupRoleWhat they receive
Part 1ExperimentalPeriod 1: Day 1, participants will receive 20 milligrams (mg) of mitapivat sulfate. Period 2: Day 1 to Day 9, participants will receive 200 mg of itraconazole, once daily and 20 mg of mitapivat sulfate on Day 5.
Receives: Drug: itraconazole; Drug: mitapivat sulfate
Part 2ExperimentalPeriod 1: Day 1, participants will receive 50 milligrams (mg) of mitapivat sulfate. Period 2: Day 1 to Day 12, participants will receive 600 mg of rifampin, once daily and 50 mg of mitapivat sulfate on Day 8.
Receives: Drug: rifampin; Drug: mitapivat sulfate

What is being measured

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

  1. Area Under the Concentration-Time Curve, from Time 0 to the Last Measurable Concentration (AUC0-t) of Mitapivat Sulfate with and without Itraconazole

    Measured: Predose and at various timepoints through 120 hours postdose

  2. Area Under the Concentration-Time Curve, from Time 0 to the Last Measurable Concentration (AUC0-t) of Mitapivat Sulfate with and without Rifampin

    Measured: Predose and at various timepoints through 120 hours postdose

  3. Area Under the Concentration-Time Curve from Time 0 Extrapolated to Infinity (AUC0-inf) of Mitapivat Sulfate with and without Itraconazole

    Measured: Predose and at various timepoints through 120 hours postdose

  4. Area Under the Concentration-Time Curve from Time 0 Extrapolated to Infinity (AUC0-inf) of Mitapivat Sulfate with and without Rifampin

    Measured: Predose and at various timepoints through 120 hours postdose

  5. Maximum Observed Plasma Concentration (Cmax) of Mitapivat Sulfate with and without Itraconazole

    Measured: Predose and at various timepoints through 120 hours postdose

  6. Maximum Observed Plasma Concentration (Cmax) of Mitapivat Sulfate with and without Rifampin

    Measured: Predose and at various timepoints through 120 hours postdose

Secondary outcomes (21)
  1. Area Under the Concentration-Time Curve, from Time 0 to Hour 24 (AUC0-24) of Mitapivat Sulfate and AGI-8702 with and without Itraconazole

    Measured: Predose and at various timepoints through 120 hours postdose

  2. Area Under the Concentration-Time Curve, from Time 0 to Hour 24 (AUC0-24) of Mitapivat Sulfate and AGI-8702 with and without Rifampin

    Measured: Predose and at various timepoints through 120 hours postdose

  3. Percent of AUC0-inf Extrapolated (AUC%extrap) of Mitapivat Sulfate and AGI-8702 with and without Itraconazole

    Measured: Predose and at various timepoints through 120 hours postdose

  4. Percent of AUC0-inf Extrapolated (AUC%extrap) of Mitapivat Sulfate and AGI-8702 with and without Rifampin

    Measured: Predose and at various timepoints through 120 hours postdose

  5. Time of the Last Measurable Concentration (Tlast) of Mitapivat Sulfate and AGI-8702 with and without Itraconazole

    Measured: Predose and at various timepoints through 120 hours postdose

  6. Time of the Last Measurable Concentration (Tlast) of Mitapivat Sulfate and AGI-8702 with and without Rifampin

    Measured: Predose and at various timepoints through 120 hours postdose

  7. Time to Reach Cmax (Tmax) of Mitapivat Sulfate and AGI-8702 with and without Itraconazole

    Measured: Predose and at various timepoints through 120 hours postdose

  8. Time to Reach Cmax (Tmax) of Mitapivat Sulfate and AGI-8702 with and without Rifampin

    Measured: Predose and at various timepoints through 120 hours postdose

  9. Apparent First-Order Terminal Elimination Half-Life (t1/2) of Mitapivat Sulfate and AGI-8702 with and without Itraconazole

    Measured: Predose and at various timepoints through 120 hours postdose

  10. Apparent First-Order Terminal Elimination Half-Life (t1/2) of Mitapivat Sulfate and AGI-8702 with and without Rifampin

    Measured: Predose and at various timepoints through 120 hours postdose

  11. Apparent Volume of Distribution During the Terminal Elimination Phase After Oral (Extravascular) Administration (Vz/F) of Mitapivat Sulfate with and without Itraconazole

    Measured: Predose and at various timepoints through 120 hours postdose

  12. Apparent Volume of Distribution During the Terminal Elimination Phase After Oral (Extravascular) Administration (Vz/F) of Mitapivat Sulfate with and without Rifampin

    Measured: Predose and at various timepoints through 120 hours postdose

  13. Apparent Total Plasma Clearance After Oral (Extravascular) Administration (CL/F) of Mitapivat Sulfate with and without Itraconazole

    Measured: Predose and at various timepoints through 120 hours postdose

  14. Apparent Total Plasma Clearance After Oral (Extravascular) Administration (CL/F) of Mitapivat Sulfate with and without Rifampin

    Measured: Predose and at various timepoints through 120 hours postdose

  15. AUC0-t of AGI-8702 with and without Itraconazole

    Measured: Predose and at various timepoints through 120 hours postdose

  16. AUC0-t of AGI-8702 with and without Rifampin

    Measured: Predose and at various timepoints through 120 hours postdose

  17. AUC0-inf of AGI-8702 with and without Itraconazole

    Measured: Predose and at various timepoints through 120 hours postdose

  18. AUC0-inf of AGI-8702 with and without Rifampin

    Measured: Predose and at various timepoints through 120 hours postdose

  19. Cmax of AGI-8702 with and without Itraconazole

    Measured: Predose and at various timepoints through 120 hours postdose

  20. Cmax of AGI-8702 with and without Rifampin

    Measured: Predose and at various timepoints through 120 hours postdose

  21. Percentage of Participants Experiencing an Adverse Event

    Measured: Baseline up to a maximum of 38 days

Timeline

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

  1. First posted19 Jun 2019
  2. Study start20 Jun 2019
  3. Primary completion14 Aug 2019
  4. Study completion10 Sep 2019

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
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
28 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03991312
Sponsor's protocol ID
AG348-C-012
Status last verified
Oct 2019
First submitted
17 Jun 2019
Last updated
23 Oct 2019
Results posted
No
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing itraconazole, rifampin and mitapivat sulfate in people with Healthy Volunteers, run by Agios Pharmaceuticals, Inc. 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 13 inclusion and 36 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 23 Oct 2019. 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?

Area Under the Concentration-Time Curve, from Time 0 to the Last Measurable Concentration (AUC0-t) of Mitapivat Sulfate with and without Itraconazole (time frame: Predose and at various timepoints through 120 hours postdose). The study lists 6 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 23 Oct 2019.

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