A Safety and Tolerability Study of AG-519 in Healthy Subjects

June 27, 2017 updated by: Agios Pharmaceuticals, Inc.

A Phase I Randomized, Double-blind, Five-Part Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single and Multiple Ascending Oral Doses of AG-519, the Relative Bioavailability of Prototype Tablet Formulations Compared With a Suspension Formulation, and to Evaluate the Pharmacokinetics of a Selected Tablet Formulation Under Fed and Fasted Conditions in Healthy Subjects

The purpose of the study is to investigate a drug called AG-519, which is being developed for the treatment of a disease called pyruvate kinase deficiency (also known as PK deficiency) and other forms of anemia. This study is a 5 part study with Part 1 enrolling healthy volunteers into single ascending dose (SAD) groups, Part 2 enrolling healthy volunteers into multiple ascending dose (MAD) groups and Part 3 enrolling healthy volunteers to investigate how much of the study drug is taken up by the body and how food affects the uptake of a prototype formulation of AG-519, Part 4 enrolling healthy volunteers of Japanese origin to compare to the results of subjects of non-Japanese origin, and Part 5 a non-randomized, open-label, multiple dose study enrolling healthy volunteers to further investigate how much of the study drug is taken up by the body when dosed over 14 days.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
108

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United Kingdom
    • Nottingham
      • Ruddington Fields, Nottingham, United Kingdom, NG11 6JS
        • Quotient Clinical

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 60 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Healthy adult male or female subjects. Female subjects must be of non-childbearing potential.
  2. Age 18 to 60 years inclusive at time of consent.
  3. Body mass index (BMI) of ≥18.5 to ≤32.0 kg/m2 or, if outside the range, considered not clinically significant by the investigator.
  4. Good state of health (mentally and physically) as indicated by a comprehensive clinical assessment (detailed medical history and a complete physical examination), ECG and laboratory investigations.
  5. Subjects who are actively non-smokers and have not used other nicotine-containing products for at least 12 months prior to the screening assessment.
  6. Must be willing and able to communicate and participate in the whole study.
  7. Must provide written informed consent.
  8. Must agree to use an adequate method of contraception.
  9. Japanese subjects enrolled in Part 4 must be first generation: born in Japan, not having lived outside Japan for 5 to 10 years, able to trace maternal and paternal Japanese ancestry, with no significant change in lifestyle, including diet (at least one Japanese meal consumed per day), since leaving Japan.

Exclusion Criteria:

  1. Participation in a clinical research study within the previous 3 months.
  2. Subjects who are study site employees, or immediate family members of a study site or sponsor employee.
  3. Subjects who have previously been enrolled in this study.
  4. History of any drug or alcohol abuse in the past 2 years.
  5. Regular alcohol consumption in males >21 units per week and females >14 units per week (1 unit = ½ pint beer, 25 mL of 40% spirit or a 125 mL glass of wine).
  6. Current smokers and those who have smoked within the last 12 months. A breath carbon monoxide reading of greater than 10 ppm at screening.
  7. Any females of childbearing potential.
  8. Subjects who do not have suitable veins for multiple venepunctures/cannulation as assessed by the investigator at screening.
  9. Subjects who, after 10 min of supine rest, have a systolic blood pressure (BP) ≥140 mmHg (≥150 mmHg in subjects >45 years of age) or a diastolic BP of ≥90 mmHg.
  10. Male subjects with QTcF interval (Fridericia's correction factor) ECG >450 msec, or female subjects with QTcF interval ECG >470 msec on screening or Day 1 (pre dose) ECG.
  11. Subjects with a history of serious mental illness, that includes, but is not limited to schizophrenia, bipolar disorder, and major depression.
  12. Subjects with glucose-6-phosphate-dehydrogenase (G6PD) deficiency.
  13. Subjects with a history of any primary malignancy, including a history of melanoma or suspicious undiagnosed skin lesions.
  14. Subjects with any other medical or psychological condition, deemed by the investigator to be likely to interfere with a subject's ability to sign informed consent, cooperate, or participate in the study.
  15. Subjects who have undergone major surgery within 6 months prior to screening.
  16. Clinically significant abnormal biochemistry, hematology or urinalysis as judged by the investigator.
  17. Positive drugs of abuse test result at screening or admission.
  18. Positive hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab) or human immunodeficiency virus (HIV) results.
  19. Subjects who are taking, or have taken, any prescribed or over-the-counter drug.
  20. Subjects who have used St. John's Wort within 28 days before the first dose of study drug.
  21. History of cardiovascular, renal, hepatic, chronic respiratory or GI disease, or hematologic, lymphatic, neurolologic, endocrine, psychiatric, musculoskeletal, genitourinary, immunologic, dermatologic or connective tissue disease or disorders, as judged by the investigator.
  22. Serious adverse reaction or serious hypersensitivity to any drug or the formulation excipients, including history of allergy to sulfonamides.
  23. Presence or history of clinically significant allergy requiring treatment, as judged by the investigator.
  24. Donation or loss of greater than 400 mL of blood within the previous 3 months.
  25. Failure to satisfy the investigator of fitness to participate for any other reason.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Placebo Comparator: Part 1 Single-Ascending (SAD Phase)
A range of doses of AG519 will be tested based on the assessment of safety and tolerability. A single dose of AG-519 will be administered by mouth (orally).
Drug: AG-519
AG519 will be tested.
Drug: Placebo
Placebo will be tested.
Placebo Comparator: Part 2 Multiple-Ascending (MAD Phase)
A range of doses of AG519 will be tested based on the assessment of safety and tolerability. AG519 will be administered by mouth (orally) each day for a period up to 14 days.
Drug: AG-519
AG519 will be tested.
Drug: Placebo
Placebo will be tested.
Experimental: Part 3 Bioavailability & Food Effect
The dose to be assessed in Part 3 will be selected based on emerging safety, tolerability and PK/PD data from preceding cohorts in Part 1 and Part 2, which will be reviewed during a dose decision meeting.
Drug: AG-519
AG519 will be tested.
Experimental: Experimental Part 4 (Subjects of Japanese Origin)
Two dose levels of AG-519 will be tested based on the assessment of safety and tolerability in preceding cohorts in Part 1, Part 2, and Part 3
Drug: AG-519
AG519 will be tested.
Experimental: Experimental Part 5 Open-label Multiple-Ascending (MAD)
Up to two dose levels of AG-519 will be tested based on the assessment of safety and tolerability in preceding cohorts in Part 1, Part 2, and Part 3. AG519 will be administered by mouth (orally) each day for a period up to 14 days.
Drug: AG-519
AG519 will be tested.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Incidence of Treatment-Emergent Adverse Events
Time Frame: 14 days
Incidence of adverse events and descriptive statistics for safety laboratory parameters, physical exam findings, vital signs and ECGs. This outcome applies to all Parts of the study
14 days

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Cmax of AG-519
Time Frame: 4 days (Parts 1, 3, & 4) 17 days (Parts 2 & 5)
Descriptive statistics will be used to summarize PK parameters of AG-519 for each dose group and, where appropriate, for the entire population. Standard non-compartmental PK parameters will be calculated from individual plasma concentration data.
4 days (Parts 1, 3, & 4) 17 days (Parts 2 & 5)
Tmax of AG-519
Time Frame: 4 days (Parts 1, 3, & 4) 17 days (Parts 2 & 5)
Descriptive statistics will be used to summarize PK parameters of AG-519 for each dose group and, where appropriate, for the entire population. Standard non-compartmental PK parameters will be calculated from individual plasma concentration data.
4 days (Parts 1, 3, & 4) 17 days (Parts 2 & 5)
AUC of AG-519
Time Frame: 4 days (Parts 1, 3, & 4) 17 days (Parts 2 & 5)
Descriptive statistics will be used to summarize PK parameters of AG-519 for each dose group and, where appropriate, for the entire population. Standard non-compartmental PK parameters will be calculated from individual plasma concentration data.
4 days (Parts 1, 3, & 4) 17 days (Parts 2 & 5)
Change from baseline in whole blood concentration of adenosine triphosphate (ATP)
Time Frame: 4 days (Parts 1 & 3) 17 days (Part 2)
The potential relationship between AG-519 and metabolic biomarkers will be explored with descriptive and graphical methods.
4 days (Parts 1 & 3) 17 days (Part 2)
Change from baseline in whole blood concentration of 2,3 - diphosphoglycerate (2,3-DPG)
Time Frame: 4 days (Parts 1 & 3) 17 days (Part 2)
The potential relationship between AG-519 and metabolic biomarkers will be explored with descriptive and graphical methods.
4 days (Parts 1 & 3) 17 days (Part 2)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Agios Pharmaceuticals, Inc.

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Gary A Connor, RN, Agios Pharmaceuticals, Inc.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
December 1, 2015

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 1, 2016

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 1, 2016

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
December 8, 2015

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 14, 2015

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
December 15, 2015

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
June 29, 2017

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 27, 2017

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
June 1, 2017

More Information

Terms related to this study

Keywords

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • AG519-C-001

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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