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This study will be conducted to evaluate the safety, tolerability, and pharmacokinetics of single ascending oral doses of E2730 in healthy adult participants.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cohort 1: E2730 40 mg | Experimental | Participants will receive a single oral dose of E2730 40 milligrams (mg) under fasted conditions. |
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| Cohort 1: Matching placebo | Placebo Comparator | Participants will receive a single oral dose of matching placebo under fasted conditions. |
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| Cohort 2: E2730 80 mg | Experimental | Participants will receive a single oral dose of E2730 80 mg under fasted conditions. |
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| Cohort 2: Matching placebo | Placebo Comparator | Participants will receive a single oral dose of matching placebo under fasted conditions. |
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| Cohort 3: E2730 120 mg | Experimental | Participants will receive a single oral dose of E2730 120 mg under fasted conditions. |
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| Cohort 3: Matching placebo | Placebo Comparator |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| E2730 | Drug | oral capsule |
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| Measure | Description | Time Frame |
|---|---|---|
| Mean maximum observed concentration (Cmax) for E2730 and the N-acetyl metabolite (M1) in plasma | predose; 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, and 12 hours (hr) postdose (PD) on Day 1; thereafter on Day 2 (24 hr PD), Day 3 (48 hr PD), Day 4 (72 hr PD), Day 5 (96 hr PD), Day 6 (120 hr PD), Day 7 (144 hr PD), and Day 10 (216 hr PD), and Day 13 (288 hr PD) | |
| Time at which the highest drug concentration (tmax) occurs for E2730 and the N-acetyl metabolite (M1) in plasma | predose; 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, and 12 hours (hr) postdose (PD) on Day 1; thereafter on Day 2 (24 hr PD), Day 3 (48 hr PD), Day 4 (72 hr PD), Day 5 (96 hr PD), Day 6 (120 hr PD), Day 7 (144 hr PD), and Day 10 (216 hr PD), and Day 13 (288 hr PD) | |
| Mean area under the concentration-time curve from zero time to 24 hours after dosing (AUC[0-24h]) for E2730 and the N-acetyl metabolite (M1) in plasma | predose and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, and 12 hours postdose on Day 1; Day 2 (24 hours postdose) | |
| Mean area under the concentration-time curve from zero time to time of last quantifiable concentration (AUC[0-t]) for E2730 and the N-acetyl metabolite (M1) in plasma | predose; 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, and 12 hours (hr) postdose (PD) on Day 1; thereafter on Day 2 (24 hr PD), Day 3 (48 hr PD), Day 4 (72 hr PD), Day 5 (96 hr PD), Day 6 (120 hr PD), Day 7 (144 hr PD), and Day 10 (216 hr PD), and Day 13 (288 hr PD) | |
| Mean area under the concentration-time curve from zero time to 72 hours after dosing (AUC[0-72h]) for E2730 and the N-acetyl metabolite (M1) in plasma | predose and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, and 12 hours postdose on Day 1; thereafter on Day 2 (24 hours postdose), Day 3 (48 hours postdose), Day 4 (72 hours postdose) | |
| Mean area under the concentration-time curve from zero time extrapolated to infinite time (AUC[0-inf]) for E2730 and the N-acetyl metabolite (M1) in plasma |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Collaborative Neuroscience Network | Long Beach | California | 90806 | United States |
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Participants will receive a single oral dose of matching placebo under fasted conditions. |
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| Cohort 4: E2730 160 mg | Experimental | Participants will receive a single oral dose of E2730 160 mg under fasted conditions. |
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| Cohort 4: Matching placebo | Placebo Comparator | Participants will receive a single oral dose of matching placebo under fasted conditions. |
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| Placebo | Drug | oral capsule |
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| predose; 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, and 12 hours (hr) postdose (PD) on Day 1; thereafter on Day 2 (24 hr PD), Day 3 (48 hr PD), Day 4 (72 hr PD), Day 5 (96 hr PD), Day 6 (120 hr PD), Day 7 (144 hr PD), and Day 10 (216 hr PD), and Day 13 (288 hr PD) |
| Mean terminal elimination phase half-life (t1/2) for E2730 and the N-acetyl metabolite (M1) in plasma | predose; 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, and 12 hours (hr) postdose (PD) on Day 1; thereafter on Day 2 (24 hr PD), Day 3 (48 hr PD), Day 4 (72 hr PD), Day 5 (96 hr PD), Day 6 (120 hr PD), Day 7 (144 hr PD), and Day 10 (216 hr PD), and Day 13 (288 hr PD) |
| Mean apparent total clearance following oral administration (CL/F) of E2730 | predose; 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, and 12 hours (hr) postdose (PD) on Day 1; thereafter on Day 2 (24 hr PD), Day 3 (48 hr PD), Day 4 (72 hr PD), Day 5 (96 hr PD), Day 6 (120 hr PD), Day 7 (144 hr PD), and Day 10 (216 hr PD), and Day 13 (288 hr PD) |
| Mean apparent volume of distribution at terminal phase (Vz/F) for E2730 in plasma | predose; 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, and 12 hours (hr) postdose (PD) on Day 1; thereafter on Day 2 (24 hr PD), Day 3 (48 hr PD), Day 4 (72 hr PD), Day 5 (96 hr PD), Day 6 (120 hr PD), Day 7 (144 hr PD), Day 10 (216 hr PD), and Day 13 (288 hr PD) |
| Mean metabolite ratio (%) (MRP) in plasma | Metabolite ratio (%) is calculated as the ratio of plasma AUC(0-inf) of a metabolite to a parent following molar correction. | predose; 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, and 12 hours (hr) postdose (PD) on Day 1; thereafter on Day 2 (24 hr PD), Day 3 (48 hr PD), Day 4 (72 hr PD), Day 5 (96 hr PD), Day 6 (120 hr PD), Day 7 (144 hr PD), and Day 10 (216 hr PD), and Day 13 (288 hr PD) |
| Mean amount of unchanged drug excreted (Ae) in urine for E2730 and the N-acetyl metabolite (M1) | Days 1 through Days 7 at the following intervals: predose; 0 to 4, >4 to 8, >8 to 12, >12 to 24, >24 to 48, >48 to 72, >72 to 96, >96 to 120, and >120 to 144 hours postdose |
| Renal clearance (CLR) of E2730 and the N-acetyl metabolite (M1) | Days 1 through Days 7 at the following intervals: predose; 0 to 4, >4 to 8, >8 to 12, >12 to 24, >24 to 48, >48 to 72, >72 to 96, >96 to 120, and >120 to 144 hours postdose |
| Percent (%) of administered dose of E2730 and the N-acetyl metabolite (M1) excreted in urine | Days 1 through Days 7 at the following intervals: predose; 0 to 4, >4 to 8, >8 to 12, >12 to 24, >24 to 48, >48 to 72, >72 to 96, >96 to 120, and >120 to 144 hours postdose |
| Mean metabolite ratio (%) (MRP) for E2730 and the N-acetyl metabolite (M1) in urine | Days 1 through Days 7 at the following intervals: predose; 0 to 4, >4 to 8, >8 to 12, >12 to 24, >24 to 48, >48 to 72, >72 to 96, >96 to 120, and >120 to 144 hours postdose |