Healthy Participants
Conditions
Keywords
CYP3A4, AP31969, Carbamazepine, Itraconazole
Brief summary
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.
Interventions
Sponsors
Acesion Pharma
Study design
Allocation
NON_RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
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.
Design outcomes
Primary
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 | AP31969 alone: Days 1 to 4; Carbamazepine alone: Days 4 to 15; Combination: Days 15 to 24 | 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. |
| Part B: Number of Participants with AEs and SAEs of AP31969 When Administered Alone and With Itraconazole | AP31969 alone: Days 1 to 4; Itraconazole alone: Days 4 to 7; Combination: Days 7 to 19 | 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. |
| Part A: Number of Participants with Mild, Moderate and Severe AEs of AP31969 When Administered Alone and With Carbamazepine | AP31969 alone: Days 1 to 4; Carbamazepine alone: Days 4 to 15; Combination: Days 15 to 24 | 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. |
| Part B: Number of Participants with Mild, Moderate and Severe AEs of AP31969 When Administered Alone and With Itraconazole | AP31969 alone: Days 1 to 4; Itraconazole alone: Days 4 to 7; Combination: Days 7 to 19 | 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. |
| Part A: Number of Participants with TEAEs Related to AP31969 When Administered Alone and With Carbamazepine | AP31969 alone: Days 1 to 4; Carbamazepine alone: Days 4 to 15; Combination: Days 15 to 24 | 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. |
| Part B: Number of Participants with TEAEs Related to AP31969 When Administered Alone and With Itraconazole | AP31969 alone: Days 1 to 4; Itraconazole alone: Days 4 to 7; Combination: Days 7 to 19 | 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. |
Countries
United States
Contacts
STUDY_DIRECTORDirector Clinical Operations
Acesion Pharma
Outcome results
None listed