Healthy VolunteersPhase 1NCT04696393

A Study to Compare the Pharmacokinetics and Safety of Mitapivat 100 mg Tablet Formulation With Mitapivat 2 × 50 mg Tablet Formulation in Healthy Adult Participants

A Phase 1 study testing Mitapivat tablet 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

The primary purpose of this study is to characterize and compare the pharmacokinetic profiles of mitapivat following a single dose administration of 100 mg mitapivat in two tablet formulations (50 mg and 100 mg tablet strengths) in healthy adult participants. Read more about this study

Who is it for?: Ages 18 to 64 yearsHealthy volunteers can take part
Conditions the study is for: Healthy Volunteers
What is being tested?: Mitapivat tablet
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 26 participants
Where: 1 siteUnited States
Study dates: 6 Jan 2021to 19 Mar 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 64 years
All sexes
Healthy volunteers accepted
Adult

Who may be able to join

Has the ability to understand the requirements of the study and a willingness to comply with all study procedures and has provided written informed consent before any study-related procedures are conducted, and is willing to comply with all study procedures for the duration of the study;
Has a body mass index (BMI) ≥18 and ≤32 kilograms per square meter (kg/m^2), at screening;
Has a body weight ≥50 kg at screening;
Is medically healthy, with no clinically significant conditions or abnormalities, as determined by the investigator or designee, through evaluation of medical history and vital sign measurements, 12-lead ECG results, physical examination findings, and clinical laboratory test results (congenital nonhemolytic hyperbilirubinemia [eg, suspicion of Gilbert's syndrome based on total and direct bilirubin] is not acceptable) at screening and check-in;
If female:
Is of childbearing potential and agrees to either abstain from sexual intercourse with a male partner or agrees to use a highly effective form of contraception, beginning at screening and continuing throughout the study and for 28 days after dosing or is postmenopausal (defined as 12 months or more continuously with no menses), or

Show all 14Show fewer

Has a documented medical history of tubal ligation or hysterectomy;
The following are considered highly effective forms of contraception: hormonal oral contraceptives, injectables, and patches; intrauterine devices; double barrier methods (synthetic condom, diaphragm, or cervical cap used with spermicidal foam, cream, or gel); and male partner sterilization;
If male (even if vasectomized):
Agrees to either abstain from sexual intercourse with a female partner, or
Agrees to use a highly effective form of contraception (as defined above), starting at screening and continuing until 90 days after the final dose of mitapivat, and
Agrees to not donate sperm throughout the entirety of the study until 90 days after the final dose of mitapivat;
Agrees to abstain from any alcohol consumption, starting 72 hours prior to check-in and continuing until the follow-up telephone call;
Agrees to refrain from marijuana- or cannabinol-containing products for 7 days prior to screening until after the follow-up telephone call.

Who cannot join

At screening, presents with a condition or has a medical history that, in the opinion of the investigator, may potentially interfere with study drug absorption, distribution, metabolism, and/or excretion (eg, malabsorption [including due to cystic fibrosis, lactose intolerance, celiac disease]);
At screening, presents with a surgical history that, in the opinion of the investigator, may potentially interfere with study drug absorption, distribution, metabolism, and/or excretion (eg, cholecystectomy). Participants who have undergone abdominal surgery or any other major surgical procedure within 6 months prior to screening, must not be enrolled;
Has a history or a 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 12 months prior to screening;
Has a known history or presence of liver disease;
Is pregnant or breastfeeding;
Has a positive test result for hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCVAb), or human immunodeficiency virus (HIV) types 1 or 2 antibodies at screening;

Show all 40Show fewer

Has liver test results including alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase, and total bilirubin that are above the upper limit of normal at screening or check-in (out-of-range test results may be repeated once at screening and check-in, if needed);
Has estimated glomerular filtration rate (eGFR) <60 milliliters per minute (mL/min)/1.73 m^2 using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) 2009 equation;
Has platelet, hemoglobin, or hematocrit test results that are below the lower limit of normal at screening or check-in (out-of-range test results may be repeated once at screening and check-in, if needed);
Has confirmed (ie, 2 consecutive measurements) systolic blood pressure (BP) >150 or <90 millimeters of mercury (mmHg), diastolic blood pressure (BP) >90 or <50 mmHg, and pulse rate >100 or <45 beats per minute (bpm) at screening and check-in;
Has 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 45 bpm and higher than 100 bpm);
Risk factors for torsades de pointes (eg, 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) (male participants) or >450 msec (female participants). In the event a QTcF value is outside of the reference range, it will be confirmed by 2 further 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 clinically significant by the investigator), or severe peripheral arterial circulatory disorders;
Has clinically significant laboratory assessment findings, including hypokalemia, hypercalcemia, or hypomagnesemia;
Has an active infection requiring systemic antimicrobial therapy at any time during the screening period;
Has a positive urine drug screen (including cotinine) at screening or check-in;
Has a positive alcohol breath test result or positive urine drug screen at screening or check-in;
Uses or intends to use any medications/products known to alter drug absorption, metabolism, or elimination processes, including 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 the follow-up telephone call, unless deemed acceptable by the investigator (or designee). Note: After first dosing, acetaminophen (up to 2 grams per 24 hours) may be administered at the discretion of the investigator or designee;
Has used any prescription (excluding hormone replacement therapy and hormonal birth control) medications, including systemic antimicrobial therapies, within 30 days (or 5 half-lives, whichever is longer) before the first dose of study drug or during the study (ie, through the follow-up telephone call);
Is currently enrolled in or has participated in another clinical study to receive any investigational or marketed product or placebo within 2 months (or 5 half-lives, whichever is longer) prior to check-in;
Has donated blood or blood products or experienced blood loss of >450 mL within 30 days prior to check-in;
Has received blood products within 2 months prior to check-in;
Has consumed caffeine- or xanthine-containing products within 24 hours prior to first dose of study drug until after the follow-up telephone call;
Has consumed foods or beverages containing grapefruit or Seville oranges for 7 days prior to the first dosing and is not willing to refrain from consumption of these foods or beverages throughout the study;
Has ingested poppy seeds within 7 days prior to check-in until after the follow-up telephone call;
Has consumed vegetables from the mustard green family (eg, kale, broccoli, watercress, collard greens, kohlrabi, Brussel sprouts, and mustard greens), or charbroiled meats within 7 days prior to first dose of study drug or throughout the study;
Has used nicotine-containing products (eg, snuff, nicotine patch, nicotine chewing gum, mock cigarettes, vaporizers, or inhalers) within 6 months prior to screening, based on participant self-reporting, and does not agree to abstain from use until the follow-up telephone call;
Has a history of active alcoholism or drug/chemical abuse within 2 years prior to check-in;
Average alcohol consumption of >21 units per week for males and >14 units for females (1 unit is equal to approximately 1/2 pint [200 mL] of beer, or 1 small glass [100 mL] of wine, or 1 measure [25 mL] of 40% spirits);
Has a history of relevant drug and/or food allergies (ie, allergy to study drug or excipients [microcrystalline cellulose, croscarmellose sodium, sodium stearyl fumarate, magnesium stearate, and mannitol]);
Has veins that are unsuitable for multiple venipunctures/cannulation, as assessed by the investigator or designee at screening;
Is involved in strenuous activity or contact sports within 24 hours prior to check-in or throughout the study;
Has any medical, hematological, psychological, or behavioral condition(s) or prior or current therapy that, in the opinion of the investigator, may confer an unacceptable risk to participating in the study and/or could confound the interpretation of the study data;
Has a positive test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Note: Testing will be performed according to site procedures.

Trial locations and contacts

1 site in 1 country.

United States1 site

PPD Development, LP
Austin, Texas, 78744

Other trials in United States

About this study

Official title: A Phase 1, Open-Label, Randomized, Two-Period, Crossover Study to Compare the Pharmacokinetics and Safety of Mitapivat 100 mg Tablet Formulation With Mitapivat 2 × 50 mg Tablet Formulation in Healthy Adult Subjects

Conditions: Healthy Volunteers
Being tested: Mitapivat tablet

What participants receive

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

Mitapivat tabletDrug
Also called AG-348, AG-348 sulfate hydrate, Mitapivat sulfate
Oral tablets

Study groups in NCT04696393
Study group	Role	What they receive
Treatment Sequence 1: AB	Experimental	Participants will receive Treatment A (mitapivat 100 milligram [mg] tablet formulation, orally, under fasted conditions once on Day 1 of Period 1), followed by Treatment B (mitapivat 2 x 50 mg tablet formulation, orally, under fasted conditions once on Day 1 of Period 2). Each treatment period will be separated by a washout period of at least 7 days. Receives: Drug: Mitapivat tablet
Treatment Sequence 1: BA	Experimental	Participants will receive Treatment B (mitapivat 2 x 50 mg tablet formulation, orally, under fasted conditions once on Day 1 of Period 1), followed by Treatment A (mitapivat 100 mg tablet formulation, orally, under fasted conditions once on Day 1 of Period 2). Each treatment period will be separated by a washout period of at least 7 days. Receives: Drug: Mitapivat tablet

What is being measured

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

Area Under the Plasma Concentration Versus Time Curve (AUC) of Mitapivat From Time 0 to the Last Quantifiable Concentration (AUC0-t)
Measured: Pre-dose and multiple time points post-dose (up to 120 hours)
AUC of Mitapivat From Time 0 Extrapolated to Infinity (AUC0-inf)
Measured: Pre-dose and multiple time points post-dose (up to 120 hours)
Maximum Observed Plasma Concentration (Cmax) of Mitapivat
Measured: Pre-dose and multiple time points post-dose (up to 120 hours)
Time to Maximum Observed Plasma Concentration (Tmax) of Mitapivat
Measured: Pre-dose and multiple time points post-dose (up to 120 hours)
Apparent Terminal Elimination Rate Constant (λZ) of Mitapivat
Measured: Pre-dose and multiple time points post-dose (up to 120 hours)
Terminal Phase Half-life (t1/2) of Mitapivat
Measured: Pre-dose and multiple time points post-dose (up to 120 hours)
Apparent Oral Clearance (CL/F) of Mitapivat
Measured: Pre-dose and multiple time points post-dose (up to 120 hours)
Apparent Volume of Distribution (Vd/F) of Mitapivat
Measured: Pre-dose and multiple time points post-dose (up to 120 hours)

Secondary outcomes (5)

Number of Participants With Adverse Events (AEs)
Measured: Up to approximately 18 days
Number of Participants With Clinically Significant Abnormal Clinical Laboratory Values
Measured: Up to approximately 18 days
Number of Participants With Clinically Significant Abnormal Findings for Vital Sign Parameters
Measured: Up to approximately 18 days
Number of Participants With Clinically Significant Abnormal Findings for 12-lead Electrocardiogram (ECG) Parameters
Measured: Up to approximately 18 days
Number of Participants With Clinically Significant Abnormal Physical Examination Findings
Measured: Up to approximately 18 days

Timeline

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

6 Jan 202119 Mar 2021

First posted6 Jan 2021
Study start6 Jan 2021
Primary completion19 Mar 2021
Study completion19 Mar 2021

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for Healthy VolunteersStudies 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: Randomised
Intervention model: Crossover
Masking: None (open label)
Enrolment: 26 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04696393
Sponsor's protocol ID: AG348-C-021
Status last verified: Apr 2021
First submitted: 4 Jan 2021
Last updated: 13 Apr 2021
Results posted: No
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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
Not yet recruitingObservational study
Establishment of Biobank of Nasal Epithelium Samples From Healthy Volunteers
Healthy
RecruitingObservational study
Improved Methods of Cell Selection for Bone Marrow Transplant Alternatives
Graft-Versus-Host Disease, Graft-versus-leukemia
Not yet recruitingObservational study
Screening Protocol
Pain

All Healthy Volunteers trials

Study at a glance

From the registry record, last updated by the sponsor on 13 Apr 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase 1, Open-Label, Randomized, Two-Period, Crossover Study to Compare the Pharmacokinetics and Safety of Mitapivat 100 mg Tablet Formulation With Mitapivat 2 × 50 mg Tablet Formulation in Healthy Adult Subjects
ClinicalTrials.gov ID: NCT04696393
Acronym / sponsor ID: AG348-C-021
Conditions: Healthy Volunteers
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 26 participants (actual)
Lead sponsor: Agios Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
Study start: 6 Jan 2021 (actual)
Primary completion: 19 Mar 2021 (actual)
Study completion: 19 Mar 2021 (actual)
First posted: 6 Jan 2021 (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 design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
Treatment Sequence 1: AB	Experimental	Drug: Mitapivat tabletParticipants will receive Treatment A (mitapivat 100 milligram [mg] tablet formulation, orally, under fasted conditions once on Day 1 of Period 1), followed by Treatment B (mitapivat 2 x 50 mg tablet formulation, orally, under fasted conditions once on Day 1 of Period 2). Each treatment period will be separated by a washout period of at least 7 days.
Treatment Sequence 1: BA	Experimental	Drug: Mitapivat tabletParticipants will receive Treatment B (mitapivat 2 x 50 mg tablet formulation, orally, under fasted conditions once on Day 1 of Period 1), followed by Treatment A (mitapivat 100 mg tablet formulation, orally, under fasted conditions once on Day 1 of Period 2). Each treatment period will be separated by a washout period of at least 7 days.

Who may qualify

Ages: 18 to 64 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (14 listed)

Has the ability to understand the requirements of the study and a willingness to comply with all study procedures and has provided written informed consent before any study-related procedures are conducted, and is willing to comply with all study procedures for the duration of the study;
Has a body mass index (BMI) ≥18 and ≤32 kilograms per square meter (kg/m^2), at screening;
Has a body weight ≥50 kg at screening;
Is medically healthy, with no clinically significant conditions or abnormalities, as determined by the investigator or designee, through evaluation of medical history and vital sign measurements, 12-lead ECG results, physical examination findings, and clinical laboratory test results (congenital nonhemolytic hyperbilirubinemia [eg, suspicion of Gilbert's syndrome based on total and direct bilirubin] is not acceptable) at screening and check-in;
If female:

Key exclusion criteria (40 listed)

At screening, presents with a condition or has a medical history that, in the opinion of the investigator, may potentially interfere with study drug absorption, distribution, metabolism, and/or excretion (eg, malabsorption [including due to cystic fibrosis, lactose intolerance, celiac disease]);
At screening, presents with a surgical history that, in the opinion of the investigator, may potentially interfere with study drug absorption, distribution, metabolism, and/or excretion (eg, cholecystectomy). Participants who have undergone abdominal surgery or any other major surgical procedure within 6 months prior to screening, must not be enrolled;
Has a history or a 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 12 months prior to screening;
Has a known history or presence of liver disease;
Is pregnant or breastfeeding;

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
Mitapivat tabletAlso: AG-348, AG-348 sulfate hydrate, Mitapivat sulfateOral tablets	Drug	Treatment Sequence 1: AB, Treatment Sequence 1: BA

Primary outcome

Area Under the Plasma Concentration Versus Time Curve (AUC) of Mitapivat From Time 0 to the Last Quantifiable Concentration (AUC0-t)
Time frame: Pre-dose and multiple time points post-dose (up to 120 hours)
AUC of Mitapivat From Time 0 Extrapolated to Infinity (AUC0-inf)
Time frame: Pre-dose and multiple time points post-dose (up to 120 hours)
Maximum Observed Plasma Concentration (Cmax) of Mitapivat
Time frame: Pre-dose and multiple time points post-dose (up to 120 hours)
Time to Maximum Observed Plasma Concentration (Tmax) of Mitapivat
Time frame: Pre-dose and multiple time points post-dose (up to 120 hours)
Apparent Terminal Elimination Rate Constant (λZ) of Mitapivat
Time frame: Pre-dose and multiple time points post-dose (up to 120 hours)
Terminal Phase Half-life (t1/2) of Mitapivat
Time frame: Pre-dose and multiple time points post-dose (up to 120 hours)
Apparent Oral Clearance (CL/F) of Mitapivat
Time frame: Pre-dose and multiple time points post-dose (up to 120 hours)
Apparent Volume of Distribution (Vd/F) of Mitapivat
Time frame: Pre-dose and multiple time points post-dose (up to 120 hours)

5 secondary outcomes

Number of Participants With Adverse Events (AEs)
Time frame: Up to approximately 18 days
Number of Participants With Clinically Significant Abnormal Clinical Laboratory Values
Time frame: Up to approximately 18 days
Number of Participants With Clinically Significant Abnormal Findings for Vital Sign Parameters
Time frame: Up to approximately 18 days
Number of Participants With Clinically Significant Abnormal Findings for 12-lead Electrocardiogram (ECG) Parameters
Time frame: Up to approximately 18 days
Number of Participants With Clinically Significant Abnormal Physical Examination Findings
Time frame: Up to approximately 18 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 13 Apr 2021.
Individual participant dataSharing planned: No

Related trials for Healthy Volunteers

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
Not yet recruitingObservational study
Establishment of Biobank of Nasal Epithelium Samples From Healthy Volunteers
Healthy
RecruitingObservational study
Improved Methods of Cell Selection for Bone Marrow Transplant Alternatives
Graft-Versus-Host Disease, Graft-versus-leukemia
Not yet recruitingObservational study
Screening Protocol
Pain

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.

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 Mitapivat tablet 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 14 inclusion and 40 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 13 Apr 2021. 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 Plasma Concentration Versus Time Curve (AUC) of Mitapivat From Time 0 to the Last Quantifiable Concentration (AUC0-t) (time frame: Pre-dose and multiple time points post-dose (up to 120 hours)). The study lists 8 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 NCT04696393.

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 13 Apr 2021.