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
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 28
- 试验地点
- 1
- 主要终点
- Part B: Cmax of AP31969 When Administered Alone and With Itraconazole
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Crossover
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Age: 18 to 55 years, inclusive, at screening.
- •Weight: ≥50 kg, at screening.
- •Body mass index (BMI): 18.0 to 32.0 kg/m^2, inclusive, at screening.
- •Sex: male or female; female participants may be of childbearing potential or of nonchildbearing potential.
- •In good physical and mental health.
排除标准
- •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).
- •Personal or first-degree relative family history of congenital long QT syndrome or sudden death.
- •History of cardiac arrhythmias, except first degree atrial-ventricular block.
- •QT interval corrected using fridericia's formula (QTcF)-interval >450 ms for males and >470 ms for females.
- •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).
- •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.
- •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.
- •Positive drug and alcohol screen (opiates, methadone, cocaine, amphetamines [including ecstasy], cannabinoids, barbiturates, benzodiazepines, tricyclic antidepressants, and alcohol) at screening or admission.
- •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.
- •Use of alcohol within 48 hours (2 days) prior to screening or admission.
- •History of drug addiction (including soft drugs like cannabis products) within 2 years prior to screening.
- •Consumption of grapefruit, Seville oranges, pomelos, star fruit, or cranberries (or their juices) within 14 days prior to the first trial drug administration.
研究组 & 干预措施
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.
干预措施: AP31969 (Drug)
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.
干预措施: AP31969 (Drug)
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.
干预措施: Carbamazepine (Drug)
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.
干预措施: Itraconazole (Drug)
结局指标
主要结局
Part B: Cmax of AP31969 When Administered Alone and With Itraconazole
时间窗: 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: Maximum Observed Plasma Concentration (Cmax) of AP31969 When Administered Alone and With Carbamazepine
时间窗: 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 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
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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
次要结局
- 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: 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: 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: 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)
- 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)
- 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)
- 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)
- 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)
- 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)