A Phase I Study of AG-348 in Healthy Volunteers

NCT02108106 | Completed Phase 1

• 1 other identifier: AG348-C-001
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief Summary

This is a dose escalation study that will be conducted in healthy volunteers. Multiple cohorts of volunteers will receive ascending oral doses of AG-348 to evaluate the safety and tolerability of a single oral dose of AG-348, the pharmacokinetics (PK) of a single dose of AG-348, and the pharmacodynamic profile of AG-348 with specific biomarkers assessed in the blood.

Conditions

Healthy Volunteer

Keywords

safety and tolerability; pharmacokinetic study

Outcome Measures

Primary Outcomes (1)

• Safety and tolerability

  Incidence of adverse events and descriptive statistics for safety laboratory parameters, physical exam findings, vital signs and ECGs.

  11 days

Secondary Outcomes (2)

• Pharmacokinetics of AG-348

  4 days

• Pharmacodynamic (PD) relationship of AG-348 and metabolic biomarkers

  4 days

Study Arms (2)

AG-348

EXPERIMENTAL

Single oral dose of AG-348

Drug: AG-348

Placebo

PLACEBO COMPARATOR

Single oral dose of placebo

Drug: Placebo

Interventions

AG-348 DRUG

A range of doses of AG-348 will be tested based on assessment of safety and tolerability.

Also known as: AG-348 will be administered as a single oral dose on Day 1.

AG-348

Placebo DRUG

Also known as: Placebo will be administered as a single oral dose on Day 1.

Placebo

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy adult male or female subjects 18 - 60 years, in good general health who are able to understand consent and complete all study procedures.
• Female subjects of non-child bearing potential (surgically sterile or post-menopausal as confirmed by age \[over 50 years\], amenorrhea for 12 consecutive months and FSH).
• Male subjects who are not vasectomized must agree to use contraception up to 30 days after dosing.
• Subjects with body weight ≥50 kg; BMI ≥18.5 and ≤32 kg/m2.
• Subjects who are non-smokers and have not used nicotine containing products for at least 3 months prior to screening.
• Subjects must be willing to refrain from caffeine- or xanthene containing products (chocolate) prior to dosing through 72 hours after dosing.
• Subjects must agree to refrain from strenuous exercise prior to admission through final visit.
• Subjects must refrain from use of alcohol starting 7 days prior to admission through final visit.
• Subjects must agree not to donate blood products for duration of study participation.

You may not qualify if:

• Subjects who have previously received AG-348.
• Subjects with clinically relevant screening laboratory tests.
• Female subjects of childbearing potential.
• Male subjects with QTcF interval ECG \> 450 msec,or female subjects with QTcF interval ECG \> 470 msec.
• Subjects with a history of a serious mental illness.
• Subjects with a clinically relevant medical history or pre-existing medical condition that would interfere with the absorption, metabolism or excretion of the study drug.
• Subjects with a history of any primary malignancy (cancer). Exceptions are certain skin cancers, cervical cancer in situ or other cancers that have been curatively treated without evidence of disease for a minimum of 1 year.
• Subjects with glucose-6-phosphate-dehydrogenase (G6PD) deficiency.
• Subjects who are positive for hepatitis B, hepatitis C or HIV.
• Subjects who have undergone surgery 6 months prior to screening.
• Subjects who have a history of illicit drug use or alcoholism within the last year.
• Subjects who are participating in other concurrent clinical trial of an investigational drug, or have received another investigational agent within the last 2 months.
• Subjects with any conditions which would make the subject unsuitable for enrollment, or could interfere with the subject's participation in or completion of the study.

Sponsors & Collaborators

• Agios Pharmaceuticals, Inc.: lead

Study Sites (1)

Unknown Facility

Baltimore, Maryland, 21225, United States

Location

Related Publications (1)

• Yang H, Merica E, Chen Y, Cohen M, Goldwater R, Kosinski PA, Kung C, Yuan ZJ, Silverman L, Goldwasser M, Silver BA, Agresta S, Barbier AJ. Phase 1 Single- and Multiple-Ascending-Dose Randomized Studies of the Safety, Pharmacokinetics, and Pharmacodynamics of AG-348, a First-in-Class Allosteric Activator of Pyruvate Kinase R, in Healthy Volunteers. Clin Pharmacol Drug Dev. 2019 Feb;8(2):246-259. doi: 10.1002/cpdd.604. Epub 2018 Aug 9.

  PMID: 30091852 DERIVED

MeSH Terms

Interventions

mitapivat

Study Officials

• Samuel Agresta, MD, MPH & TM

  Agios Pharmaceuticals, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 2, 2014
• First Posted: April 9, 2014
• Study Start: March 1, 2014
• Primary Completion: August 1, 2014
• Study Completion: August 1, 2014
• Last Updated: October 22, 2014

Record last verified: 2014-10

Locations

US (1)