An Open-Label, 2-Period, Fixed Sequence Study to Determine the Effect of Multiple Oral Doses of Itraconazole on the Single Dose Pharmacokinetics of AG 120 in Healthy Adult Subjects
Overview
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- Agios Pharmaceuticals, Inc.
- Enrollment
- 22
- Primary Endpoint
- AG120 Area Under the Curve [AUC]
Overview
Brief Summary
An Open-Label, 2-Period, Fixed Sequence Study to Determine the Effect of Multiple Oral Doses of Itraconazole on the Single Dose Pharmacokinetics of AG 120 in Healthy Adult Subjects. Period 1 consists of a single oral dose of AG-120 will be administered at Hour 0 followed by PK sampling for 504 hours (21 days). In Period 2, multiple oral doses of itraconazole will be administered once daily (QD) for 18 consecutive days with a single oral dose of AG-120 coadministered at Hour 0 on Day 1. PK sampling for AG-120 will be taken for 504 hours (21 days) following AG-120 dosing on Day 1.
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 55 Years (Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •Healthy, adult, male or female, 18 - 55 years of age, inclusive, at screening.
- •Continuous non smoker who has not used nicotine containing products for at least 3 months prior to the first dose and throughout the study.
- •BMI ≥ 18.5 and ≤ 32.0 kg/m2 at screening.
- •Medically healthy with no clinically significant medical history, physical examination, laboratory profiles, vital signs or ECGs, as deemed by the PI or designee.
- •For a female of childbearing potential: either be sexually inactive (abstinent) for 14 days prior to the first dose and throughout the study or be using one of the following acceptable birth control methods:
- •non-hormone releasing intrauterine device for at least 3 months prior to the first dose and with either a physical (e.g. condom, diaphragm, or other) or a chemical (e.g., spermicide) barrier method from the time of screening and throughout the study.
- •surgical sterilization of the partner (vasectomy for 4 months minimum the first dose/dosing) and with either a physical (e.g. condom, diaphragm, or other) or a chemical (e.g., spermicide) barrier method from the time of screening and throughout the study.
- •two physical barrier method (e.g. condom, diaphragm, or other) with spermicide for at least 14 days prior to the first dose and throughout the study.
- •In addition, female subjects of childbearing potential will be advised to remain sexually inactive or to keep the same birth control method for at least 90 days following the last dose.
- •For a female of non childbearing potential: must have undergone one of the following sterilization procedures at least 6 months prior to the first dose:
Exclusion Criteria
- •Subject is mentally or legally incapacitated or has significant emotional problems at the time of the screening visit or expected during the conduct of the study.
- •History or presence of clinically significant medical or psychiatric condition or disease in the opinion of the PI or designee.
- •History of any illness that, in the opinion of the PI or designee, might confound the results of the study or poses an additional risk to the subject by their participation in the study.
- •History or presence of alcoholism or drug abuse within the past 2 years prior to the first dose.
- •History or presence of hypersensitivity or idiosyncratic reaction to the study drug(s) or related compounds.
- •History or presence of ventricular dysfunction or risk factors for Torsades de Pointes (e.g., heart failure, cardiomyopathy, family history of Long QT Syndrome).
- •Female subjects with a positive pregnancy test or lactating.
- •Positive urine drug or alcohol results at screening or each check in.
- •Positive results at screening for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV).
- •QTcF interval is \>450 msec (males) or \>460 msec (females) or has ECG findings deemed abnormal with clinical significance by the PI or designee at screening.
Arms & Interventions
Period 1
A single oral dose of AG-120 will be administered at Hour 0 followed by PK sampling for 504 hours (21 days).
Intervention: AG120 (Drug)
Period 2
In Period 2, multiple oral doses of itraconazole will be administered once daily (QD) for 18 consecutive days (Days -4 to 14) with a single oral dose of AG-120 coadministered at Hour 0 on Day 1. PK sampling for AG-120 will be taken for 504 hours (21 days) following AG-120 dosing on Day 1. PK sampling will also be collected for itraconazole and its metabolite, hydroxy-itraconazole, from Day -2 up to Day 13.
Intervention: AG120 (Drug)
Period 2
In Period 2, multiple oral doses of itraconazole will be administered once daily (QD) for 18 consecutive days (Days -4 to 14) with a single oral dose of AG-120 coadministered at Hour 0 on Day 1. PK sampling for AG-120 will be taken for 504 hours (21 days) following AG-120 dosing on Day 1. PK sampling will also be collected for itraconazole and its metabolite, hydroxy-itraconazole, from Day -2 up to Day 13.
Intervention: Itraconazole (Drug)
Outcomes
Primary Outcomes
AG120 Area Under the Curve [AUC]
Time Frame: Period 2: itraconazole administered once daily (QD) for 18 consecutive days (Days -4 to 14) with a single oral dose of AG-120 coadministered at Hour 0 on Day 1. PK sampling for AG-120 will be taken for 504 hours (21 days)
AG120 Maximum Plasma Concentration [Cmax]
Time Frame: Period 2: itraconazole administered once daily (QD) for 18 consecutive days (Days -4 to 14) with a single oral dose of AG-120 coadministered at Hour 0 on Day 1. PK sampling for AG-120 will be taken for 504 hours (21 days)
Itraconazole Area Under the Curve [AUC]
Time Frame: Period 2: itraconazole administered once daily (QD) for 18 consecutive days (Days -4 to 14) with a single oral dose of AG-120 coadministered at Hour 0 on Day 1. PK sampling for AG-120 will be taken for 504 hours (21 days)
Itraconazole Maximum Plasma Concentration [CMAX]
Time Frame: Period 2: itraconazole administered once daily (QD) for 18 consecutive days (Days -4 to 14) with a single oral dose of AG-120 coadministered at Hour 0 on Day 1. PK sampling for AG-120 will be taken for 504 hours (21 days)
Secondary Outcomes
- Hydroxy-itraconazole Area Under the Curve [AUC](Period 2: Day -2 up to Day 13)
- Hydroxy-itraconazole Maximum Plasma Concentration [CMAX](Period 2: Day -2 up to Day 13)