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The primary objective of the trial is to assess the effect of multiple doses of the cytochrome P450 (CYP3A4) enzyme inducer carbamazepine (Part A) or the CYP3A4 inhibitor itraconazole (Part B) on the single-dose pharmacokinetics (PK) of AP31969 in healthy participants.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Part A, Treatment Period 1 + Treatment Period 2: AP31969 + Carbamazepine | Experimental | Part A - Treatment Period 1: Participants will receive a single oral dose of AP31969 350 mg, tablet on Day 1. Part A - Treatment Period 2: Participants will receive a single oral dose of AP31969 350 mg on Day 15. In addition, participants will receive carbamazepine oral capsules administered twice daily (BID) as follows: 100 mg BID on Days 4 to 6, 200 mg BID on Days 7 to 9, and 300 mg BID on Days 10 to 17. |
|
| Part B, Treatment Period 1 + Treatment Period 2: AP31969 + Itraconazole | Experimental | Part B - Treatment Period 1: Participants will receive a single oral dose of AP31969 350 mg, tablet on Day 1. Part B - Treatment Period 2: Participants will receive a single oral dose of AP31969 350 mg, tablet on Day 7. In addition, participants will receive a single oral dose of itraconazole 200 mg, tablets from Day 4 to Day 6 and Days 8 to 12. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| AP31969 | Drug | Oral tablets. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Part A: Maximum Observed Plasma Concentration (Cmax) of AP31969 When Administered Alone and With Carbamazepine | AP31969 alone: predose, and at 0.5 to 72 hours postdose on Day 1 and AP31969 in combination: predose, and at 0.5 to 72 hours postdose on Day 15; Carbamazepine alone: predose on Day 15 and morning on Day 18 | |
| Part B: Cmax of AP31969 When Administered Alone and With Itraconazole | AP31969 alone: predose, and at 0.5 to 72 hours postdose on Day 1, and AP31969 in combination: predose and at 0.5 to 144 hours postdose on Day 15; Itraconazole alone: predose on Day 7 and morning on Day 13 | |
| Part A: Area Under the Plasma Concentration-time Curve (AUC) from Time 0 to Time of Last Quantifiable Concentration (AUC0-last) of AP31969 When Administered Alone and With Carbamazepine | AP31969 alone: predose, and at 0.5 to 72 hours postdose on Day 1 and AP31969 in combination: predose, and at 0.5 to 72 hours postdose on Day 15; Carbamazepine alone: predose on Day 15 and morning on Day 18 | |
| Part B: AUC0-last of AP31969 When Administered Alone and With Itraconazole | AP31969 alone: predose, and at 0.5 to 72 hours postdose on Day 1, and AP31969 in combination: predose and at 0.5 to 144 hours postdose on Day 15; Itraconazole alone: predose on Day 7 and morning on Day 13 | |
| Part A: AUC from Time 0 to Infinity (AUC0-inf) of AP31969 When Administered Alone and With Carbamazepine | AP31969 alone: predose, and at 0.5 to 72 hours postdose on Day 1 and AP31969 in combination: predose, and at 0.5 to 72 hours postdose on Day 15; Carbamazepine alone: predose on Day 15 and morning on Day 18 | |
| Part B: AUC0-inf of AP31969 When Administered Alone and With Itraconazole | AP31969 alone: predose, and at 0.5 to 72 hours postdose on Day 1, and AP31969 in combination: predose and at 0.5 to 144 hours postdose on Day 15; Itraconazole alone: predose on Day 7 and morning on Day 13 |
| Measure | Description | Time Frame |
|---|---|---|
| Part A: Time to Cmax (tmax) of AP31969 When Administered Alone and With Carbamazepine | AP31969 alone: predose, and at 0.5 to 72 hours postdose on Day 1 and AP31969 in combination: predose, and at 0.5 to 72 hours postdose on Day 15; Carbamazepine alone: predose on Day 15 and morning on Day 18 | |
| Part B: tmax of AP31969 When Administered Alone and With Itraconazole |
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Key Inclusion Criteria:
Key Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Director Clinical Operations | Acesion Pharma | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| ICON Early Phase Services, LLC | San Antonio | Texas | 78232 | United States |
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| ID | Term |
|---|---|
| D002220 | Carbamazepine |
| D017964 | Itraconazole |
| ID | Term |
|---|---|
| D003984 | Dibenzazepines |
| D006575 | Heterocyclic Compounds, 3-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
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| Carbamazepine | Drug | Oral capsules. |
|
| Itraconazole | Drug | Oral tablets. |
|
| AP31969 alone: predose, and at 0.5 to 72 hours postdose on Day 1, and AP31969 in combination: predose and at 0.5 to 144 hours postdose on Day 15; Itraconazole alone: predose on Day 7 and morning on Day 13 |
| Part A: Terminal Elimination Half-life (t1/2) of AP31969 When Administered Alone and With Carbamazepine | AP31969 alone: predose, and at 0.5 to 72 hours postdose on Day 1 and AP31969 in combination: predose, and at 0.5 to 72 hours postdose on Day 15; Carbamazepine alone: predose on Day 15 and morning on Day 18 |
| Part B: t1/2 of AP31969 When Administered Alone and With Itraconazole | AP31969 alone: predose, and at 0.5 to 72 hours postdose on Day 1, and AP31969 in combination: predose and at 0.5 to 144 hours postdose on Day 15; Itraconazole alone: predose on Day 7 and morning on Day 13 |
| Part A: AUC from Time 0 to 24 hours (AUC0-24) of AP31969 When Administered Alone and With Carbamazepine | AP31969 alone: predose, and at 0.5 to 24 hours postdose on Day 1 and AP31969 in combination: predose, and at 0.5 to 24 hours postdose on Day 15; Carbamazepine alone: predose on Day 15 and morning on Day 18 |
| Part B: AUC0-24 of AP31969 When Administered Alone and With Itraconazole | AP31969 alone: predose, and at 0.5 to 24 hours postdose on Day 1, and AP31969 in combination: predose and at 0.5 to 24 hours postdose on Day 15; Itraconazole alone: predose on Day 7 and morning on Day 13 |
| Part A: Apparent Oral Clearance (CL/F) of AP31969 When Administered Alone and With Carbamazepine | AP31969 alone: predose, and at 0.5 to 72 hours postdose on Day 1 and AP31969 in combination: predose, and at 0.5 to 72 hours postdose on Day 15; Carbamazepine alone: predose on Day 15 and morning on Day 18 |
| Part B: CL/F of AP31969 When Administered Alone and With Itraconazole | AP31969 alone: predose, and at 0.5 to 72 hours postdose on Day 1, and AP31969 in combination: predose and at 0.5 to 144 hours postdose on Day 15; Itraconazole alone: predose on Day 7 and morning on Day 13 |
| Part A: Apparent Volume of Distribution at Terminal Phase (Vz/F) of AP31969 When Administered Alone and With Carbamazepine | AP31969 alone: predose, and at 0.5 to 72 hours postdose on Day 1 and AP31969 in combination: predose, and at 0.5 to 72 hours postdose on Day 15; Carbamazepine alone: predose on Day 15 and morning on Day 18 |
| Part B: Vz/F of AP31969 When Administered Alone and With Itraconazole | AP31969 alone: predose, and at 0.5 to 72 hours postdose on Day 1, and AP31969 in combination: predose and at 0.5 to 144 hours postdose on Day 15; Itraconazole alone: predose on Day 7 and morning on Day 13 |
| Part A: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) of AP31969 When Administered Alone and With Carbamazepine | Any clinically significant changes in physical examination findings and abnormal objective test findings (e.g., in clinical laboratory, vital signs, ECGs) will be recorded as AEs as per investigators discretion. | AP31969 alone: Days 1 to 4; Carbamazepine alone: Days 4 to 15; Combination: Days 15 to 24 |
| Part B: Number of Participants with AEs and SAEs of AP31969 When Administered Alone and With Itraconazole | Any clinically significant changes in physical examination findings and abnormal objective test findings (e.g., in clinical laboratory, vital signs, ECGs) will be recorded as AEs as per investigators discretion. | AP31969 alone: Days 1 to 4; Itraconazole alone: Days 4 to 7; Combination: Days 7 to 19 |
| Part A: Number of Participants with Mild, Moderate and Severe AEs of AP31969 When Administered Alone and With Carbamazepine | The severity of AEs will be graded as follows: 1. Mild: an AE that is easily tolerated by the participant, causes minimal discomfort, does not interfere with everyday activities, and does not require intervention. 2. Moderate: an AE that is sufficiently discomforting to interfere with normal everyday activities; intervention may be needed. 3. Severe: an AE that prevents normal everyday activities; treatment or other intervention usually needed. | AP31969 alone: Days 1 to 4; Carbamazepine alone: Days 4 to 15; Combination: Days 15 to 24 |
| Part B: Number of Participants with Mild, Moderate and Severe AEs of AP31969 When Administered Alone and With Itraconazole | The severity of AEs will be graded as follows: 1. Mild: an AE that is easily tolerated by the participant, causes minimal discomfort, does not interfere with everyday activities, and does not require intervention. 2. Moderate: an AE that is sufficiently discomforting to interfere with normal everyday activities; intervention may be needed. 3. Severe: an AE that prevents normal everyday activities; treatment or other intervention usually needed. | AP31969 alone: Days 1 to 4; Itraconazole alone: Days 4 to 7; Combination: Days 7 to 19 |
| Part A: Number of Participants with TEAEs Related to AP31969 When Administered Alone and With Carbamazepine | The relationship between the AEs and the trial drug (AP31969, carbamazepine, or itraconazole) will be assessed and graded as none, unlikely, possibly, likely, or definitely. Adverse events graded as possibly, likely, or definitely related will be considered related to the trial drug; AEs graded as none or unlikely related will be considered not related to the trial drug. | AP31969 alone: Days 1 to 4; Carbamazepine alone: Days 4 to 15; Combination: Days 15 to 24 |
| Part B: Number of Participants with TEAEs Related to AP31969 When Administered Alone and With Itraconazole | The relationship between the AEs and the trial drug (AP31969, carbamazepine, or itraconazole) will be assessed and graded as none, unlikely, possibly, likely, or definitely. Adverse events graded as possibly, likely, or definitely related will be considered related to the trial drug; AEs graded as none or unlikely related will be considered not related to the trial drug. | AP31969 alone: Days 1 to 4; Itraconazole alone: Days 4 to 7; Combination: Days 7 to 19 |
| D014230 | Triazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D010879 | Piperazines |