A Phase 1, Open-label, Fixed-sequence Study to Evaluate the Effect of UGT Inhibition by Valproic Acid on the Pharmacokinetics of BIIB074 in Healthy Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Biogen
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Maximum Observed Concentration (Cmax) of BIIB074
研究概览
简要总结
The primary objective of this study is to evaluate the effect of multiple doses of the UGT inhibitor valproic acid on the single-dose pharmacokinetics of BIIB074. The secondary objectives of this study are to evaluate the safety and tolerability of BIIB074 when administered alone and when coadministered with the UGT inhibitor valproic acid and to evaluate the effect of the UGT inhibitor valproic acid on the PK of the M13, M14, and M16 metabolites of BIIB074.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 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
- •Must have a body mass index between 18 and 32 kg/m^2, inclusive.
- •Must be male, postmenopausal female, or surgically sterile female
- •Must be in good health as determined by the Investigator, based on medical history and screening evaluations.
排除标准
- •History of any clinically significant cardiac, endocrine, gastrointestinal (GI), hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, neurologic, dermatologic, psychiatric, or renal disease, or other major disease, as determined by the Investigator
- •Clinically significant abnormal laboratory test values, as determined by the Investigator, at Screening or Day -1
- •History of, or positive test result at Screening for, human immunodeficiency virus (HIV)
- •Treatment with any prescription or over-the-counter oral medication (excluding acetaminophen) within 14 days prior to Day -1 and an unwillingness or inability to refrain from this treatment during study participation, unless specifically permitted elsewhere within this protocol.
- •Other unspecified reasons that, in the opinion of the Investigator or Sponsor, make the subject unsuitable for enrollment.
- •NOTE: Other protocol defined Inclusion/Exclusion criteria may apply
研究组 & 干预措施
BIIB074 150 mg and Valproic Acid 500 mg
Participants will receive BIIB074 in tablet form in 150 mg doses. BIIB074 will be taken once daily (QD) on Days 1-16 after an 8-hour fast. Valproic Acid will be given in capsule form in 500 mg doses on prescription (TID) every 8 hours on Days 8-22. The morning dose on Day 16 will be coadministered with BIIB074 following an 8-hour fast.
干预措施: BIIB074 (Drug)
BIIB074 150 mg and Valproic Acid 500 mg
Participants will receive BIIB074 in tablet form in 150 mg doses. BIIB074 will be taken once daily (QD) on Days 1-16 after an 8-hour fast. Valproic Acid will be given in capsule form in 500 mg doses on prescription (TID) every 8 hours on Days 8-22. The morning dose on Day 16 will be coadministered with BIIB074 following an 8-hour fast.
干预措施: Valproic Acid (Drug)
结局指标
主要结局
Maximum Observed Concentration (Cmax) of BIIB074
时间窗: Day 1 through Day 8, Day 16 through Day 23
Area Under the Concentration-Time Curve from Time 0 to Infinity (AUCinf) of BIIB074
时间窗: Day 1 through Day 8, Day 16 through Day 23
Apparent Clearance (CL/F) of BIIB074
时间窗: Day 1 through Day 8, Day 16 through Day 23
Area Under the Concentration-Time Curve from Time Zero to Time of the Last Measurable Concentration (AUClast) of BIIB074
时间窗: Day 1 through Day 8, Day 16 through Day 23
Time to Reach Maximum Observed Concentration (Tmax) for BIIB074
时间窗: Day 1 through Day 8, Day 16 through Day 23
Time of Last Measured Serum Concentration (Tlast) of BIIB074
时间窗: Day 1 through Day 8, Day 16 through Day 23
Apparent Volume of Distribution (V/F) of BIIB074
时间窗: Day 1 through Day 8, Day 16 through Day 23
Elimination Half-Life (T 1/2) of BIIB074
时间窗: Day 1 through Day 8, Day 16 through Day 23
次要结局
- Metabolite-to-Parent Ratio in AUC (MRauc) of BIIB074 Metabolites M13, M14, and M16(Day 1 through Day 8, Day 16 through Day 23)
- Percentage of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)(Up to Day 32)
- Number of Participants with Abnormal Change from Baseline of Clinical Laboratory Parameters up to Day 23(Day 3, 8, 13, 16, 18, 23)
- Cmax of BIIB074 Metabolites M13, M14, and M16(Day 1 through Day 8, Day 16 through Day 23)
- T1/2 of BIIB074 Metabolites M13, M14, and M16(Day 1 through Day 8, Day 16 through Day 23)
- Number of Participants with Abnormal Change from Baseline in Columbia Suicide Severity Rating (C-SSRS) scale(Day 8, 23, and once between Day 29-32)
- Number of Participants with Abnormal Change from Baseline of Electrocardiogram (ECG) up to Day 23(Day 1, 3, 8, 13, 16, 18, 23)
- Number of Participants with Abnormal Change from Baseline of Vital Signs up to Day 23(Day 1, 3, 8, 13, 16, 18, 23)
- AUCinf of BIIB074 Metabolites M13, M14, and M16(Day 1 through Day 8, Day 16 through Day 23)
- Tlast of BIIB074 Metabolites M13, M14, and M16(Day 1 through Day 8, Day 16 through Day 23)
- AUClast of BIIB074 Metabolites M13, M14, and M16(Day 1 through Day 8, Day 16 through Day 23)
- Tmax of BIIB074 Metabolites M13, M14, and M16(Day 1 through Day 8, Day 16 through Day 23)