Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
This study will assess absorption, distribution, metabolism, excretion and absolute bioavailability of AG-348 in healthy male participants. Potential participants will be screened within 29 days prior to dose administration to determine eligibility. Eligible Participants will be admitted into the Clinical Research Unit (CRU) one day prior to administration of AG-348 and will be confined to the CRU until at least Day 8. If participants are not eligible for discharge on Day 8, they may remain in the CRU up to Day 11. Radiolabelled analytes of AG-348 will be administered in a single oral and intravenous (IV) dose on Day 1. Participants will be required to fast pre-dose, remain in a supine position for 1 hour post-dose and avoid water for 2 hours post-dose.
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| AG-348 | Experimental | On Day 1, participants fasting for at least 10 hours the night before will receive oral AG-348 followed by intravenous (IV) [13C6]AG-348, 1 hour post-oral dose. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| AG-348 | Drug | 120 milligrams (mg) oral capsule, single dose, contains 100 microcuries (μCi) of radio labelled [14C]AG-348. |
|
| Measure | Description | Time Frame |
|---|---|---|
| AG-348 Excreted Through Urine [A(eu)] | Pre-oral dose and 0-4 hours (hr), 4-8 hr, 8-12 hr, 12-24 hr, 24-36 hr, 36-48 hr, 48-72 hr, 72-96 hr, 96-120 hr, 120-144 hr and 168 hr post-oral dose | |
| AG-348 Excreted through Feces [A(ef)] | Pre-oral dose and 0-24 hr, 24-48 hr, 48-72 hr, 72-96 hr, 96-120 hr, 120-144 hr and 168 hr post-oral dose | |
| Total Amount Excreted Through Urine [Cumulative A(eu)] of AG-348 | Pre-oral dose and 0-4 hours (hr), 4-8 hr, 8-12 hr, 12-24 hr, 24-36 hr, 36-48 hr, 48-72 hr, 72-96 hr, 96-120 hr, 120-144 hr and 168 hr post-oral dose | |
| Total Amount Excreted Through Feces [Cumulative A(ef)] of AG-348 | Pre-oral dose and 0-24 hr, 24-48 hr, 48-72 hr, 72-96 hr, 96-120 hr, 120-144 hr and 168 hr post-oral dose | |
| Percentage Excreted in Urine [f(eu)] of AG-348 | Pre-oral dose and 0-4 hours (hr), 4-8 hr, 8-12 hr, 12-24 hr, 24-36 hr, 36-48 hr, 48-72 hr, 72-96 hr, 96-120 hr, 120-144 hr and 168 hr post-oral dose | |
| Percentage Excreted in Feces [f(ef)] of AG-348 | Pre-oral dose and 0-24 hr, 24-48 hr, 48-72 hr, 72-96 hr, 96-120 hr, 120-144 hr and 168 hr post-oral dose | |
| Renal Clearance [CL(R)] for AG-348 | Pre-oral dose and 0-4 hours (hr), 4-8 hr, 8-12 hr, 12-24 hr, 24-36 hr, 36-48 hr, 48-72 hr, 72-96 hr, 96-120 hr, 120-144 hr and 168 hr post-oral dose | |
| Percentage of Total Radioactivity in Total Excreta (Urine and Feces) | Pre-oral dose and 0-4 hours (hr), 4-8 hr, 8-12 hr, 12-24 hr, 24-36 hr, 36-48 hr, 48-72 hr, 72-96 hr, 96-120 hr, 120-144 hr and 168 hr post-oral dose |
| Measure | Description | Time Frame |
|---|---|---|
| Concentration of AG-348 Metabolites in Urine | Pre-oral dose and 0-4 hours (hr), 4-8 hr, 8-12 hr, 12-24 hr, 24-36 hr, 36-48 hr, 48-72 hr, 72-96 hr, 96-120 hr, 120-144 hr and 168 hr post-oral dose | |
| Concentration of AG-348 Metabolites in Feces | Pre-oral dose and 0-24 hr, 24-48 hr, 48-72 hr, 72-96 hr, 96-120 hr, 120-144 hr and 168 hr post-oral dose |
Not provided
Inclusion Criteria
Exclusion Criteria
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Medical Affairs | Agios Pharmaceuticals, Inc. | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Covance | Madison | Wisconsin | 53704 | United States |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| [13C6]AG-348 | Drug | IV microdose of approximately 100 micrograms (mcg), single dose. |
|
| Area Under the Concentration-Time Curve From Time Zero to the Last Non-Zero Concentration [AUC(0- t)] | Pre-oral dose and 15 min, 30 min, 45 min, 60 min, 61 min, 62 min, 75 min, 90, min 105 min, 2 hr, 3hr, 4 hr, 6 hr, 8 hr, 10 hr, 12, hr 16, hr 24 hr, 36 hr, 48 hr and 72 hr post-oral dose |
| Area Under the Concentration-Time Curve From Time Zero to Infinity Concentration [AUC(0-inf)] | Pre-oral dose and 15 min, 30 min, 45 min, 60 min, 61 min, 62 min, 75 min, 90, min 105 min, 2 hr, 3hr, 4 hr, 6 hr, 8 hr, 10 hr, 12, hr 16, hr 24 hr, 36 hr, 48 hr and 72 hr post-oral dose |
| Maximum Observed Concentration (Cmax) | Pre-oral dose and 15 min, 30 min, 45 min, 60 min, 61 min, 62 min, 75 min, 90, min 105 min, 2 hr, 3hr, 4 hr, 6 hr, 8 hr, 10 hr, 12, hr 16, hr 24 hr, 36 hr, 48 hr and 72 hr post-oral dose |
| Time of Observed Cmax (Tmax) | Pre-oral dose and 15 min, 30 min, 45 min, 60 min, 61 min, 62 min, 75 min, 90, min 105 min, 2 hr, 3hr, 4 hr, 6 hr, 8 hr, 10 hr, 12, hr 16, hr 24 hr, 36 hr, 48 hr and 72 hr post-oral dose |
| Apparent Terminal Elimination Half-life [t(1/2)] | Pre-oral dose and 15 min, 30 min, 45 min, 60 min, 61 min, 62 min, 75 min, 90, min 105 min, 2 hr, 3hr, 4 hr, 6 hr, 8 hr, 10 hr, 12, hr 16, hr 24 hr, 36 hr, 48 hr and 72 hr post-oral dose |
| Ratio of [AUC(0-inf)] of Plasma AG-348 Relative to [AUC(0-inf)] of Plasma Total Radioactivity, [AUC(0-inf)] Plasma AG-348/Total Radioactivity Ratio | Pre-dose and 15, 30, 45, 61, and 90 min and 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72, 96, 120, and 144, and 168 hr post-dose |
| Ratio of [AUC(0-inf)] of Whole Blood Total Radioactivity Relative to [AUC(0-inf)] of Plasma Total Radioactivity, [AUC(0-inf)] Blood/Plasma Ratio | Pre-dose and 15, 30, 45, 61, and 90 min and 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72, 96, 120, and 144, and 168 hr post-dose |
| Total Clearance (CL) of [13C6]AG-348 | Pre-oral dose and 15 min, 30 min, 45 min, 60 min, 61 min, 62 min, 75 min, 90, min 105 min, 2 hr, 3hr, 4 hr, 6 hr, 8 hr, 10 hr, 12, hr 16, hr 24 hr, 36 hr, 48 hr and 72 hr post-oral dose |
| Volume of Distribution [V(z)] of [13C6]AG-348 | Pre-oral dose and 15 min, 30 min, 45 min, 60 min, 61 min, 62 min, 75 min, 90, min 105 min, 2 hr, 3hr, 4 hr, 6 hr, 8 hr, 10 hr, 12, hr 16, hr 24 hr, 36 hr, 48 hr and 72 hr post-oral dose |
| Volume of Distribution at Steady State [V(ss)] for [13C6]AG-348 | Pre-oral dose and 15 min, 30 min, 45 min, 60 min, 61 min, 62 min, 75 min, 90, min 105 min, 2 hr, 3hr, 4 hr, 6 hr, 8 hr, 10 hr, 12, hr 16, hr 24 hr, 36 hr, 48 hr and 72 hr post-oral dose |
| Absolute Bioavailability (F) for AG-348 | Pre-oral dose and 15 min, 30 min, 45 min, 60 min, 61 min, 62 min, 75 min, 90, min 105 min, 2 hr, 3hr, 4 hr, 6 hr, 8 hr, 10 hr, 12, hr 16, hr 24 hr, 36 hr, 48 hr and 72 hr post-oral dose |
| Plasma Concentrations of AG-348 Metabolites | Pre-dose and 30 min, 61 min, 2 hr, 4 hr, 8 hr, 12 hr, 24, hr, 48 hr, 72 hr, 120 hr and 168 hr post-oral dose |
| Percentage of Participants Experiencing an Adverse Event | Screening to the end of study (up to 40 days) |
| ID | Term |
|---|---|
| C000634504 | mitapivat |
Not provided
Not provided
Not provided