A Phase 1 Study to Evaluate the Potential Drug Interactions Between ALXN2080 and Itraconazole, Fluconazole, and Carbamazepine in Healthy Adult Participants
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- Area Under the Curve From Time 0 to the Time of Last Measurable Concentration (AUC0-last) of ALXN2080
研究概览
简要总结
The primary objectives of this study are to determine the effect of multiple doses of itraconazole on the single dose PK of ALXN2080, to determine the effect of multiple doses of fluconazole on the single dose PK of ALXN2080 (optional), and to determine the effect of multiple doses of carbamazepine on the single dose PK of ALXN2080.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 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
- •Healthy males or non-pregnant, non-lactating healthy females.
- •Participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, vital signs, triplicate 12-lead ECG, screening clinical laboratory profiles (hematology, clinical chemistry, coagulation, and urinalysis), as deemed by the Investigator or designee.
- •Female participants of childbearing potential and male participants must follow protocol-specified contraception guidance
- •BMI within the range of 18.0 to 32.0 kg/m2 (inclusive) and a minimum body weight of 50.0 kg at screening.
排除标准
- •History of clinically significant cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrinological, hematological, neurological, psychiatric or other disorders; constituting a risk when taking the study intervention; or interfering with the interpretation of data.
- •History of meningococcal infection.
- •History of additional risk factors for Torsades de Pointes (eg, heart failure, hypokalemia, family history of Long QT syndrome).
- •History of unexplained, recurrent infection, or infection requiring treatment with systemic antibiotics within 14 days prior to Period 1 Day
- •History of significant multiple and/or severe allergies (hay fever is allowed unless it is active), including significant hypersensitivity reactions to commonly used antibacterial agents, including beta-lactams, penicillin, amoxicillin, aminopenicillin, fluoroquinolones (specifically including ciprofloxacin), cephalosporins, and carbapenems, which in the opinion of the Investigator would make it difficult to provide empiric antibiotic therapy or treat an active infection.
- •Diseases or conditions or previous procedures known to interfere with the absorption, distribution, metabolism, or excretion of drugs.
- •History of malignancy within 5 years prior to screening, with the exception of nonmelanoma skin cancer or carcinoma in situ of the cervix that has been treated with no evidence of recurrence.
- •Known hepatic or biliary abnormalities (including participants with Gilbert's syndrome).
研究组 & 干预措施
Part 1
During Part 1, Period 1, participants will receive a single dose of ALXN2080 on the morning of Day 1. In Part 1, Period 2, participants will receive a dose of itraconazole orally once daily on the morning of Day 1 to Day 13. On the morning of Day 5, participants will be given a single dose of ALXN2080 co-administered with itraconazole.
干预措施: ALXN2080 (Drug)
Part 1
During Part 1, Period 1, participants will receive a single dose of ALXN2080 on the morning of Day 1. In Part 1, Period 2, participants will receive a dose of itraconazole orally once daily on the morning of Day 1 to Day 13. On the morning of Day 5, participants will be given a single dose of ALXN2080 co-administered with itraconazole.
干预措施: Itraconazole (Drug)
Part 2 (Optional)
During Part 2, Period 1, participants will receive a single dose of ALXN2080 on the morning of Day 1. In Part 2, Period 2, participants will receive a single loading dose of fluconazole, followed by a dose of fluconazole qd on the morning of Day 2 to Day 10. On the morning of Day 4, participants will be given a single dose of ALXN2080 co-administered with fluconazole.
干预措施: ALXN2080 (Drug)
Part 2 (Optional)
During Part 2, Period 1, participants will receive a single dose of ALXN2080 on the morning of Day 1. In Part 2, Period 2, participants will receive a single loading dose of fluconazole, followed by a dose of fluconazole qd on the morning of Day 2 to Day 10. On the morning of Day 4, participants will be given a single dose of ALXN2080 co-administered with fluconazole.
干预措施: Fluconazole (AxMP) (Drug)
Part 3
During Part 3, Period 1 participants will receive a single dose of ALXN2080 on the morning of Day 1. In Part 3, Period 2, participants will receive a dose of carbamazepine bid on the morning and evening of Day 1 to Day 3, followed by a dose of carbamazepine bid on the morning and evening of Day 4 to Day 6 and a dose of carbamazepine bid on the morning and evening of Day 7 to Day 23. On the morning of Day 19, participants will be given a single dose of ALXN2080 co-administered with carbamazepine.
干预措施: ALXN2080 (Drug)
Part 3
During Part 3, Period 1 participants will receive a single dose of ALXN2080 on the morning of Day 1. In Part 3, Period 2, participants will receive a dose of carbamazepine bid on the morning and evening of Day 1 to Day 3, followed by a dose of carbamazepine bid on the morning and evening of Day 4 to Day 6 and a dose of carbamazepine bid on the morning and evening of Day 7 to Day 23. On the morning of Day 19, participants will be given a single dose of ALXN2080 co-administered with carbamazepine.
干预措施: Carbamazepine (AxMP) (Drug)
结局指标
主要结局
Area Under the Curve From Time 0 to the Time of Last Measurable Concentration (AUC0-last) of ALXN2080
时间窗: Day 1 up to Day 24
Maximum Observed Plasma Concentration (Cmax) of ALXN2080
时间窗: Day 1 up to Day 24
次要结局
- Cmax of Fluconazole(Day 2 up to Day 5)
- Number of Participants with Treatment-emergent Adverse Events (TEAEs)(Baseline up to Day 34)
- Area under the Curve for the Defined Interval Between Doses AUC(tau) of Itraconazole(Day 4 up to Day 6)
- Cmax of Carbamazepine(Day 2 up to Day 20)
- Cmax of Itraconazole(Day 4 up to Day 6)
- AUC(tau) of Fluconazole(Day 2 up to Day 5)
- AUC(tau) of Carbamazepine(Day 2 up to Day 20)