A Phase I Study of AG-348 in Healthy Volunteers
- Registration Number
- NCT02149966
- Lead Sponsor
- Agios Pharmaceuticals, Inc.
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 48
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo Multiple oral doses of placebo. AG-348 AG-348 Multiple oral doses of AG-348
- Primary Outcome Measures
Name Time Method Incidence of adverse events 29 days
- Secondary Outcome Measures
Name Time Method 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.