A Phase 1, Randomized, Double-Blind, Placebo-Controlled Study to Assess the Safety, Tolerability, and Pharmacokinetics of AG-181 in Healthy Participants
Overview
- Phase
- Phase 1
- Intervention
- AG-181
- Conditions
- Healthy Volunteers
- Sponsor
- Agios Pharmaceuticals, Inc.
- Enrollment
- 88
- Locations
- 1
- Primary Endpoint
- SAD: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) by Type, Severity, and Relationship to Study Drug
- Status
- Completed
- Last Updated
- 4 months ago
Overview
Brief Summary
The primary purpose of this study is to assess the safety and tolerability of AG-181 in healthy participants after oral administration of single ascending dose (SAD) of AG-181 in Part 1 and multiple ascending dose (MAD) in Part 2 along with the effect of food on the pharmacokinetics (PK) of single oral doses of AG-181 in healthy participants in Part 3.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Willing to participate in the study, give written informed consent, and comply with the study restrictions.
- •Body mass index in the range of 18.0 to 30.0 kilograms per square meter (kg/m\^2).
- •Weight ≥ 50 kilograms (kg) at screening.
- •Healthy status as defined by the absence of evidence of any clinically significant, in the opinion of the Investigator, active or chronic disease following a detailed medical and surgical history, a complete physical examination including vital signs, 12-lead electrocardiogram (ECG), hematology, blood chemistry, serology, and urinalysis.
- •Ability and willingness to refrain from alcohol-, caffeine-, and methylxanthine-containing beverages or food (e.g., coffee, tea, cola, chocolate, energy drinks) from 72 hours (3 days) before administration of the first dose of study drug through follow-up.
- •All values for hematology and clinical chemistry tests of blood and urine within the normal range or showing no clinically relevant deviations, as judged by the Investigator.
- •For women of child bearing potential (WOCBP)\*, have a negative serum pregnancy test at Screening and during admission to the clinic.
- •a. \*WOCBP are defined as sexually mature women who have not undergone a hysterectomy, bilateral oophorectomy, or tubal occlusion; or who have not been naturally postmenopausal. WOCBP must use an acceptable method of contraception from Screening and until 14 days or 5 half-lives of AG-181, whichever is longer, after last dose of AG-
- •WOCBP using hormonal contraception as a highly effective form of contraception must also use an acceptable barrier method.
- •Male participants with female partners of childbearing potential must use a condom during treatment and for 14 days or 5 half-lives of AG-181, whichever is longer, after last dose of AG-
Exclusion Criteria
- •Women who are pregnant, lactating, or planning to attempt to become pregnant during this study or within 14 days or 5 half-lives of AG-181, whichever is longer, after last dose of study drug.
- •Males with female partners who are pregnant, lactating, or planning to attempt to become pregnant during this study or within 14 days or 5 half-lives of AG-181, whichever is longer, after last dose of study drug.
- •Prior exposure to AG-
- •Use of any investigational drug or device within 30 days before administration of the first dose of study drug.
- •Any disease which, in the opinion of the Investigator, poses an unacceptable risk to the participants.
- •Clinically significant history of, including treatment within an Emergency Department for, any drug sensitivity, drug allergy, or food allergy, as determined by the Investigator (such as anaphylaxis, hepatotoxicity, or treatment with steroids or epinephrine).
- •Creatinine clearance \<90 milliliters per minute (mL/min) (by Cockcroft-Gault formula) at screening.
- •Aspartate aminotransferase \>upper limit of normal (ULN) or alanine aminotransferase \>ULN at screening.
- •Use of tobacco or nicotine products in the 48 hours (2 days) prior to administration of the first dose of study drug.
- •Strenuous activity, sunbathing, and contact sports within 48 hours (2 days) prior to administration of the first dose of study drug.
Arms & Interventions
Part 1: Single Ascending Dose (SAD)
Participants will receive a range of doses of AG-181 or placebo, orally, once on Day 1. AG-181 will be given under fasted conditions.
Intervention: AG-181
Part 1: Single Ascending Dose (SAD)
Participants will receive a range of doses of AG-181 or placebo, orally, once on Day 1. AG-181 will be given under fasted conditions.
Intervention: Placebo
Part 2: Multiple Ascending Dose (MAD)
Participants will receive a range of doses of AG-181 or placebo twice daily (BID) for 13 days and a single dose on Day 14 under fasted conditions.
Intervention: AG-181
Part 2: Multiple Ascending Dose (MAD)
Participants will receive a range of doses of AG-181 or placebo twice daily (BID) for 13 days and a single dose on Day 14 under fasted conditions.
Intervention: Placebo
Part 3: Food Effect - Sequence 1: AB
Participants will receive single oral dose of AG-181 on Day 1 of Period 1 under fasted condition (A) followed by single oral dose of AG-181 on Day 1 of Period 2 under fed (high fat meal) condition (B). Each period will be separated by a washout period of 1 week.
Intervention: AG-181
Part 3: Food Effect - Sequence 2: BA
Participants will receive a single oral dose of AG-181 on Day 1 of Period 1 under fed (high fat meal) condition (B) followed by single oral dose of AG-181 on Day 1 of Period 2 under fasted condition (A). Each period will be separated by a washout period of 1 week.
Intervention: AG-181
Outcomes
Primary Outcomes
SAD: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) by Type, Severity, and Relationship to Study Drug
Time Frame: Up to Day 7
MAD: Number of Participants with AEs and SAEs by Type, Severity, and Relationship to Study Drug
Time Frame: Up to Day 26
Food Effect: Apparent Oral Clearance (CL/F) of AG-181
Time Frame: Predose and multiple time points postdose from Day 1 to Day 4
Food Effect: Maximum Observed Plasma Concentration (Cmax) of AG-181
Time Frame: Predose and multiple time points postdose from Day 1 to Day 4
Food Effect: Area Under the Concentration-time Curve up to the Last Quantifiable Concentration (AUC0-last) of AG-181
Time Frame: Predose and multiple time points postdose from Day 1 to Day 4
Food Effect: Apparent Volume of Distribution at Terminal Phase (Vz/F) of AG-181
Time Frame: Predose and multiple time points postdose from Day 1 to Day 4
Food Effect: Area Under the Concentration-time Curve From Time 0 to Infinity (AUC0-inf) of AG-181
Time Frame: Predose and multiple time points postdose from Day 1 to Day 4
Food Effect: Time to Reach Maximum Observed Concentration (tmax) of AG-181
Time Frame: Predose and multiple time points postdose from Day 1 to Day 4
Food Effect: Terminal Elimination Rate Constant (Kel) of AG-181
Time Frame: Predose and multiple time points postdose from Day 1 to Day 4
Food Effect: Terminal Elimination Half-Life (t1/2) of AG-181
Time Frame: Predose and multiple time points postdose from Day 1 to Day 4
Secondary Outcomes
- SAD: Maximum Observed Plasma Concentration (Cmax) of AG-181(Predose and multiple time points postdose from Day 1 to Day 4)
- MAD: Apparent Volume of Distribution at Terminal Phase (Vz/F) of AG-181(Predose and multiple time points postdose from Day 1 to Day 17)
- MAD: Time to Maximum Observed Plasma Concentration at Steady State (Cmax_ss) of AG-181(Predose and multiple time points postdose from Day 1 to Day 17)
- SAD: Area Under the Concentration-time Curves (AUCs) of AG-181(Predose and multiple time points postdose from Day 1 to Day 4)
- SAD: Apparent Oral Clearance (CL/F) of AG-181(Predose and multiple time points postdose from Day 1 to Day 4)
- SAD: Total Percent of AG-181 Dose Excreted Unchanged in Urine (Fet%)(Predose and multiple time points postdose from Day 1 to Day 3)
- SAD: Cumulative Amount of AG-181 Drug Excreted in Urine (Ae0-t)(Predose and multiple time points postdose from Day 1 to Day 3)
- MAD: Accumulation Ratio for Cmax (RA_Cmax) of AG-181(Predose and multiple time points postdose from Day 1 to Day 14)
- MAD: Time to Reach Maximum Observed Concentration (tmax) of AG-181(Predose and multiple time points postdose from Day 1 to Day 17)
- SAD: Terminal Elimination Rate Constant (Kel) of AG-181(Predose and multiple time points postdose from Day 1 to Day 4)
- SAD: Terminal Elimination Half-Life (t1/2) of AG-181(Predose and multiple time points postdose from Day 1 to Day 4)
- SAD: Apparent Volume of Distribution at Terminal Phase (Vz/F) of AG-181(Predose and multiple time points postdose from Day 1 to Day 4)
- SAD: Percent of AG-181 Dose Excreted Unchanged in Urine Between Time 1 and Time 2 (Fet1-t2%)(Predose and multiple time points postdose from Day 1 to Day 3)
- SAD: Amount of AG-181 Drug Excreted in Urine Between Time 1 and Time 2 (Aet1-t2)(Predose and multiple time points postdose from Day 1 to Day 3)
- MAD: Terminal Elimination Rate Constant (Kel) of AG-181(Predose and multiple time points postdose from Day 1 to Day 17)
- MAD: Area Under the Concentration-time Curve (AUC) of AG-181(Predose and multiple time points postdose from Day 1 to Day 17)
- MAD: Apparent Oral Clearance (CL/F) of AG-181(Predose and multiple time points postdose from Day 1 to Day 17)
- SAD: Time to Reach Maximum Observed Concentration (tmax) of AG-181(Predose and multiple time points postdose from Day 1 to Day 4)
- SAD: Renal Clearance (CLR) of AG-181(Predose and multiple time points postdose from Day 1 to Day 3)
- MAD: Terminal Elimination Half-Life (t1/2) of AG-181(Predose and multiple time points postdose from Day 1 to Day 17)
- MAD: Accumulation Ratio for Area Under the Concentration-time Curve (RA_AUC) of AG-181(Predose and multiple time points postdose from Day 1 to Day 14)
- MAD: Maximum Observed Plasma Concentration (Cmax) of AG-181(Predose and multiple time points postdose from Day 1 to Day 17)
- Food Effect: Number of Participants with AEs and SAEs by Type, Severity, and Relationship to Study Drug(Up to Day 7)