Drug-drug Interaction Trial of AP31969 and Carbamazepine or Itraconazole

Open-label, 2-Part, Fixed-sequence, Crossover Trial Design to Determine the Effect of a Strong CYP3A4 Inducer (Carbamazepine) And a Strong CYP3A4 Inhibitor (Itraconazole) on the Pharmacokinetics of a Single Oral Dose of AP31969 in Healthy Participants

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.

Study Overview

• Status: Completed
• Conditions: Healthy Participants
• Intervention / Treatment: Drug: AP31969; Drug: Carbamazepine; Drug: Itraconazole

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • San Antonio, Texas, United States, 78232
      • ICON Early Phase Services, LLC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Key Inclusion Criteria:

1. Age: 18 to 55 years, inclusive, at screening.
2. Weight: ≥50 kg, at screening.
3. Body mass index (BMI): 18.0 to 32.0 kg/m^2, inclusive, at screening.
4. Sex: male or female; female participants may be of childbearing potential or of nonchildbearing potential.
5. In good physical and mental health.

Key Exclusion Criteria:

1. History and/or presence of any illness or condition that, in the opinion of the Investigator, might confound the results of the trial or pose an additional risk when administering the trial drugs to the participant (with particular focus on cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrinological, hematological, cerebrovascular, and neurological diseases including history of syncope and/or convulsions).
2. Personal or first-degree relative family history of congenital long QT syndrome or sudden death.
3. History of cardiac arrhythmias, except first degree atrial-ventricular block.
4. QT interval corrected using fridericia's formula (QTcF)-interval >450 ms for males and >470 ms for females.
5. Resting supine systolic blood pressure (BP) (average of 3 readings) >160 mmHg or <80 mmHg and diastolic BP (average of 3 readings) >90 mmHg or <50 mmHg at screening or admission. If initial results do not meet these criteria, BP may be repeated if in the judgment of the Investigator there is a reason to believe the initial result is inaccurate (e.g., white coat hypertension).
6. Use of any prescribed medication within 30 days prior to admission, based on Investigator's judgment. An exception is made for hormonal contraceptives, which may be used throughout the trial.
7. Use of any over-the-counter medication, vitamin preparations and other food supplements, or herbal medications (e.g., St. John's wort) within 14 days prior to admission, based on Investigator's judgment. An exception is made for acetaminophen/paracetamol, which is allowed up to 2 g/day.
8. Positive drug and alcohol screen (opiates, methadone, cocaine, amphetamines [including ecstasy], cannabinoids, barbiturates, benzodiazepines, tricyclic antidepressants, and alcohol) at screening or admission.
9. Alcohol consumption exceeding 2 standard drinks per day on average (1 standard drink=12 oz beer, 5 oz wine, and 1.5 oz spirits) within 12 months prior to screening.
10. Use of alcohol within 48 hours (2 days) prior to screening or admission.
11. History of drug addiction (including soft drugs like cannabis products) within 2 years prior to screening.
12. Consumption of grapefruit, Seville oranges, pomelos, star fruit, or cranberries (or their juices) within 14 days prior to the first trial drug administration.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part A, Treatment Period 1 + Treatment Period 2: AP31969 + Carbamazepine; 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.	Drug: AP31969; Oral tablets.; Drug: Carbamazepine; Oral capsules.
Experimental: Part B, Treatment Period 1 + Treatment Period 2: AP31969 + Itraconazole; 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.	Drug: AP31969; Oral tablets.; Drug: Itraconazole; Oral tablets.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Secondary Outcome Measures

Outcome Measure	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		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

Collaborators and Investigators

• Sponsor: Acesion Pharma
• Investigators: Study Director: Director Clinical Operations, Acesion Pharma

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2026
• Primary Completion (Actual): May 9, 2026
• Study Completion (Actual): May 16, 2026

Study Registration Dates

• First Submitted: February 27, 2026
• First Submitted That Met QC Criteria: February 27, 2026
• First Posted (Actual): March 4, 2026

Study Record Updates

• Last Update Posted (Actual): May 22, 2026
• Last Update Submitted That Met QC Criteria: May 20, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Itraconazole; CYP3A4; Carbamazepine; AP31969
• Additional Relevant MeSH Terms: Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, Fused-Ring; Azoles; Triazoles; Dibenzazepines; Heterocyclic Compounds, 3-Ring; Piperazines; Itraconazole; Carbamazepine
• Other Study ID Numbers: AP31969-M103

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No