Healthy Volunteer
Conditions
Keywords
safety and tolerability, pharmacokinetic study
Brief summary
This is a dose escalation study that will be conducted in healthy volunteers. Multiple cohorts of volunteers will receive ascending (increasingly higher) oral doses of AG-348 daily for 14 days to evaluate the safety and tolerability of multiple oral doses of AG-348, the pharmacokinetics (PK) of multiple doses of AG-348, and the pharmacodynamic profile of AG-348 with specific biomarkers assessed in the blood.
Interventions
DRUGAG-348
A range of doses of AG-348 will be tested based on the assessment of safety and tolerability. AG-348 will be administered by mouth (orally) each day for a period of 14 days.
DRUGPlacebo
Placebo will be administered by mouth (orally) each day for a period of 14 days.
Sponsors
Agios Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
Yes
Inclusion criteria
* 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 (coffee, tea, chocolate) for 48 hours prior to dosing through discharge from the clinical facility. * Subjects must agree to refrain from strenuous exercise starting 72 hours prior to admission through final follow-up visit. * Subjects must refrain from use of alcohol starting 7 days (14 days for red wine) prior to admission through final follow-up visit. * Subjects must agree not to donate blood products for duration of study participation.
Exclusion criteria
* Subjects who have previously received AG-348. * Subjects with clinically relevant screening laboratory tests. * Female subjects who are not post-menopausal. * Subjects with recent use of prescription, over the counter (OTC), herbal and/or dietary medications and/or supplements. * 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence of adverse events | 29 days |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics parameters of AG-348 | 17 days | Descriptive statistics will be used to summarize PK parameters of AG-348 for each dose group and, where appropriate, for the entire population. Standard non-compartmental PK parameters will be calculated from individual plasma concentration data. |
| Pharmacodynamic (PD) relationship of AG-348 and metabolic biomarkers | 17 days | The potential relationship between AG-348 and metabolic biomarkers will be explored with descriptive and graphical methods. Details on the evaluation of pyruvate kinase (PKR) activity and other potential PD biomarkers will be described. |
Countries
United States
Outcome results
None listed