A Phase 1, Randomized, Double-Blinded, Placebo-Controlled, Single- and Multiple-Ascending Dose, Dose-Escalation Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of BIIB095 in Healthy Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Biogen
- 入组人数
- 80
- 试验地点
- 2
- 主要终点
- Percentage of Participants with Serious Adverse Events (SAEs)
研究概览
简要总结
The primary objective of the study is to evaluate the safety and tolerability of single- and multiple-ascending oral doses of BIIB095 in healthy participants. The secondary objectives are to characterize the single- and multiple-oral-dose PK of BIIB095 in healthy participants and to investigate the effect of food on the single-oral-dose PK of BIIB095 in healthy participants.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Ability of the subject to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use confidential health information in accordance with national and local subject privacy regulations.
- •Must have a body mass index between 18 and 30 kg/m2, inclusive.
- •All women of childbearing potential and all men must practice highly effective contraception during the study and for 5 times the half-life or 3 months, whichever is longer, after their last dose of study treatment. In addition, subjects should not donate sperm or eggs during the study and for at least 3 months after their last dose of study treatment.
- •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, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, neurologic, dermatologic, psychiatric, or renal disease, or other major disease, as determined by the Investigator.
- •Significant history of fainting or vaso-vagal attacks, as determined by the Investigator.
- •Current condition known to affect cardiac conduction, or a personal or familial history of Brugada syndrome.
- •Congenital nonhemolytic hyperbilirubinemia (Gilbert's syndrome).
- •History or risk of seizures or a history of epilepsy, significant head injury or related neurological disorders (excluding childhood febrile convulsions), as determined by the Investigator.
- •Current enrollment in any other drug, biologic, device, or clinical study, or treatment with an investigational drug or approved therapy for investigational use within 30 days (6 months for biologics) prior to Day -1, or 5 half-lives of the agent, whichever is longer.
- •Exposure to more than 4 experimental chemical entities within 12 months prior to the first dosing day.
- •Breastfeeding, pregnant, or planning to become pregnant during study participation
- •NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
Cohort 1: BIIB095 5 mg
Following an overnight fast from food of at least 8 hours, participants will receive a single dose of either BIIB095 5 mg or placebo orally, followed by a fast of at least 4 hours post dose.
干预措施: BIIB095 (Drug)
Cohort 1: BIIB095 5 mg
Following an overnight fast from food of at least 8 hours, participants will receive a single dose of either BIIB095 5 mg or placebo orally, followed by a fast of at least 4 hours post dose.
干预措施: Placebo (Drug)
Cohort 2: BIIB095 25 mg
Following an overnight fast from food of at least 8 hours, participants will receive a single dose of either BIIB095 25 mg or placebo orally, followed by a fast of at least 4 hours post dose.
干预措施: BIIB095 (Drug)
Cohort 2: BIIB095 25 mg
Following an overnight fast from food of at least 8 hours, participants will receive a single dose of either BIIB095 25 mg or placebo orally, followed by a fast of at least 4 hours post dose.
干预措施: Placebo (Drug)
Cohort 3: BIIB095 100 mg
Following an overnight fast from food of at least 8 hours, participants will receive a single dose of either BIIB095 100 mg or placebo orally, followed by a fast of at least 4 hours post dose.
干预措施: BIIB095 (Drug)
Cohort 3: BIIB095 100 mg
Following an overnight fast from food of at least 8 hours, participants will receive a single dose of either BIIB095 100 mg or placebo orally, followed by a fast of at least 4 hours post dose.
干预措施: Placebo (Drug)
Cohort 4 (Fasted): BIIB095 200 mg
Following an overnight fast from food of at least 8 hours, participants will receive a single dose of either BIIB095 200 mg or placebo orally, followed by a fast of at least 4 hours post dose.
干预措施: BIIB095 (Drug)
Cohort 4 (Fasted): BIIB095 200 mg
Following an overnight fast from food of at least 8 hours, participants will receive a single dose of either BIIB095 200 mg or placebo orally, followed by a fast of at least 4 hours post dose.
干预措施: Placebo (Drug)
Cohort 4 (Fed): BIIB095 200 mg
After a minimum 2 week washout period, followed by an overnight fast of at least 8 hours, participants will consume a high fat breakfast. Participants will then receive a single dose of either BIIB095 200 mg or placebo orally within 30 minutes after starting the breakfast, followed by a fast from food for at least 4 hours post dose.
干预措施: BIIB095 (Drug)
Cohort 4 (Fed): BIIB095 200 mg
After a minimum 2 week washout period, followed by an overnight fast of at least 8 hours, participants will consume a high fat breakfast. Participants will then receive a single dose of either BIIB095 200 mg or placebo orally within 30 minutes after starting the breakfast, followed by a fast from food for at least 4 hours post dose.
干预措施: Placebo (Drug)
Cohort 5: BIIB095 400 mg
Following an overnight fast from food of at least 8 hours, participants will receive a single dose of either BIIB095 400 mg or placebo orally, followed by a fast of at least 4 hours post dose.
干预措施: BIIB095 (Drug)
Cohort 5: BIIB095 400 mg
Following an overnight fast from food of at least 8 hours, participants will receive a single dose of either BIIB095 400 mg or placebo orally, followed by a fast of at least 4 hours post dose.
干预措施: Placebo (Drug)
Cohort 6: BIIB095 600 mg
Following an overnight fast from food of at least 8 hours, participants will receive a single dose of either BIIB095 600 mg or placebo orally, followed by a fast of at least 4 hours post dose.
干预措施: BIIB095 (Drug)
Cohort 6: BIIB095 600 mg
Following an overnight fast from food of at least 8 hours, participants will receive a single dose of either BIIB095 600 mg or placebo orally, followed by a fast of at least 4 hours post dose.
干预措施: Placebo (Drug)
Cohort 7: BIIB095 50 mg BID
Participants will receive a single dose of either BIIB095 50 mg or placebo orally BID approximately 12 hours apart from Days 1 to 13, and once in the morning on Day 14. Morning doses will be preceded by an overnight fast from food of at least 8 hours and will be followed by a fast of at least 2 hours post dose. Evening doses will be preceded by a fast from food of at least 2 hours and will be followed by a fast of at least 2 hours post dose.
干预措施: BIIB095 (Drug)
Cohort 7: BIIB095 50 mg BID
Participants will receive a single dose of either BIIB095 50 mg or placebo orally BID approximately 12 hours apart from Days 1 to 13, and once in the morning on Day 14. Morning doses will be preceded by an overnight fast from food of at least 8 hours and will be followed by a fast of at least 2 hours post dose. Evening doses will be preceded by a fast from food of at least 2 hours and will be followed by a fast of at least 2 hours post dose.
干预措施: Placebo (Drug)
Cohort 8: BIIB095 100 mg BID
Participants will receive a single dose of either BIIB095 100 mg or placebo orally BID approximately 12 hours apart from Days 1 to 13, and once in the morning on Day 14. Morning doses will be preceded by an overnight fast from food of at least 8 hours and will be followed by a fast of at least 2 hours post dose. Evening doses will be preceded by a fast from food of at least 2 hours and will be followed by a fast of at least 2 hours post dose.
干预措施: BIIB095 (Drug)
Cohort 8: BIIB095 100 mg BID
Participants will receive a single dose of either BIIB095 100 mg or placebo orally BID approximately 12 hours apart from Days 1 to 13, and once in the morning on Day 14. Morning doses will be preceded by an overnight fast from food of at least 8 hours and will be followed by a fast of at least 2 hours post dose. Evening doses will be preceded by a fast from food of at least 2 hours and will be followed by a fast of at least 2 hours post dose.
干预措施: Placebo (Drug)
Cohort 9: BIIB095 200 mg BID
Participants will receive a single dose of either BIIB095 200 mg or placebo orally BID approximately 12 hours apart from Days 1 to 13, and once in the morning on Day 14. Morning doses will be preceded by an overnight fast from food of at least 8 hours and will be followed by a fast of at least 2 hours post dose. Evening doses will be preceded by a fast from food of at least 2 hours and will be followed by a fast of at least 2 hours post dose.
干预措施: BIIB095 (Drug)
Cohort 9: BIIB095 200 mg BID
Participants will receive a single dose of either BIIB095 200 mg or placebo orally BID approximately 12 hours apart from Days 1 to 13, and once in the morning on Day 14. Morning doses will be preceded by an overnight fast from food of at least 8 hours and will be followed by a fast of at least 2 hours post dose. Evening doses will be preceded by a fast from food of at least 2 hours and will be followed by a fast of at least 2 hours post dose.
干预措施: Placebo (Drug)
Cohort 10: BIIB095 300 mg BID
Participants will receive a single dose of either BIIB095 300 mg or placebo orally BID approximately 12 hours apart from Days 1 to 13, and once in the morning on Day 14. Morning doses will be preceded by an overnight fast from food of at least 8 hours and will be followed by a fast of at least 2 hours post dose. Evening doses will be preceded by a fast from food of at least 2 hours and will be followed by a fast of at least 2 hours post dose.
干预措施: BIIB095 (Drug)
Cohort 10: BIIB095 300 mg BID
Participants will receive a single dose of either BIIB095 300 mg or placebo orally BID approximately 12 hours apart from Days 1 to 13, and once in the morning on Day 14. Morning doses will be preceded by an overnight fast from food of at least 8 hours and will be followed by a fast of at least 2 hours post dose. Evening doses will be preceded by a fast from food of at least 2 hours and will be followed by a fast of at least 2 hours post dose.
干预措施: Placebo (Drug)
结局指标
主要结局
Percentage of Participants with Serious Adverse Events (SAEs)
时间窗: Signing of Informed Consent (<=28 Days Prior to Day -1, Check-in) to End of Study (Up to 40 Days for Single-Ascending Dose (SAD) Cohorts 1-3 and 5-6; at Least 59 Days for SAD Cohort 4; Up to 53 Days for Multiple-Ascending Dose (MAD) Cohorts 7-10)
An SAE is any untoward medical occurrence that at any dose: Results in death; in the view of the Investigator, places the participant at immediate risk of death (a life threatening event), however, this does not include an event that, had it occurred in a more severe form, might have caused death; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; results in a congenital anomaly/birth defect; is a medically important event
Percentage of Participants with Adverse Events (AEs)
时间窗: Signing of Informed Consent (<=28 Days Prior to Day -1, Check-in) to End of Study (Up to 40 Days for Single-Ascending Dose (SAD) Cohorts 1-3 and 5-6; at Least 59 Days for SAD Cohort 4; Up to 53 Days for Multiple-Ascending Dose (MAD) Cohorts 7-10)
An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product.
Percentage of Participants with Clinically Significant Abnormalities in Clinical Laboratory Assessments
时间窗: Signing of Informed Consent (<=28 Days Prior to Day -1, Check-in) to End of Study (Up to 40 Days for Single-Ascending Dose (SAD) Cohorts 1-3 and 5-6; at Least 59 Days for SAD Cohort 4; Up to 53 Days for Multiple-Ascending Dose (MAD) Cohorts 7-10)
Percentage of Participants with Clinically Significant Abnormalities in Vital Signs
时间窗: Signing of Informed Consent (<=28 Days Prior to Day -1, Check-in) to End of Study (Up to 40 Days for Single-Ascending Dose (SAD) Cohorts 1-3 and 5-6; at Least 59 Days for SAD Cohort 4; Up to 53 Days for Multiple-Ascending Dose (MAD) Cohorts 7-10)
Percentage of Participants with Clinically Significant Abnormalities in 12-Lead Electrocardiogram (ECG) Parameters
时间窗: Signing of Informed Consent (<=28 Days Prior to Day -1, Check-in) to End of Study (Up to 40 Days for Single-Ascending Dose (SAD) Cohorts 1-3 and 5-6; at Least 59 Days for SAD Cohort 4; Up to 53 Days for Multiple-Ascending Dose (MAD) Cohorts 7-10)
Percentage of Participants with Clinically Significant Abnormalities in Physical Examinations
时间窗: Signing of Informed Consent (<=28 Days Prior to Day -1, Check-in) to End of Study (Up to 40 Days for Single-Ascending Dose (SAD) Cohorts 1-3 and 5-6; at Least 59 Days for SAD Cohort 4; Up to 53 Days for Multiple-Ascending Dose (MAD) Cohorts 7-10)
次要结局
- AUC Within a Dosing Interval (AUCtau)(Multiple Time-points on Days 1 through 4 for Single-Ascending Dose (SAD) Cohorts; Multiple Time-points on Days 1 through 15 for Multiple-Ascending Dose (MAD) Cohorts)
- Maximum Observed Concentration (Cmax)(Multiple Time-points on Days 1 through 4 for Single-Ascending Dose (SAD) Cohorts; Multiple Time-points on Days 1 through 15 for Multiple-Ascending Dose (MAD) Cohorts)
- Terminal Elimination Half-Life (t1/2)(Multiple Time-points on Days 1 through 4 for Single-Ascending Dose (SAD) Cohorts; Multiple Time-points on Days 1 through 15 for Multiple-Ascending Dose (MAD) Cohorts)
- Apparent Total Body Clearance (CL/F)(Multiple Time-points on Days 1 through 4 for Single-Ascending Dose (SAD) Cohorts; Multiple Time-points on Days 1 through 15 for Multiple-Ascending Dose (MAD) Cohorts)
- Trough Concentration (Ctrough)(Multiple Time-points on Days 1 through 4 for Single-Ascending Dose (SAD) Cohorts; Multiple Time-points on Days 1 through 15 for Multiple-Ascending Dose (MAD) Cohorts)
- Time to Cmax (Tmax)(Multiple Time-points on Days 1 through 4 for Single-Ascending Dose (SAD) Cohorts; Multiple Time-points on Days 1 through 15 for Multiple-Ascending Dose (MAD) Cohorts)
- Percentage (%fe) Excreted in Urine(Multiple Time-points on Days 1 through 4 for Single-Ascending Dose (SAD) Cohorts; Multiple Time-points on Days 1 through 15 for Multiple-Ascending Dose (MAD) Cohorts)
- Area Under the Concentration-Time Curve (AUC) from Time Zero to the Time of the Last Measurable Concentration (AUClast)(Multiple Time-points on Days 1 through 4 for Single-Ascending Dose (SAD) Cohorts; Multiple Time-points on Days 1 through 15 for Multiple-Ascending Dose (MAD) Cohorts)
- AUC from Time Zero Extrapolated to Infinity (AUC∞)(Multiple Time-points on Days 1 through 4 for Single-Ascending Dose (SAD) Cohorts; Multiple Time-points on Days 1 through 15 for Multiple-Ascending Dose (MAD) Cohorts)
- Apparent Volume of Distribution (Vz/F)(Multiple Time-points on Days 1 through 4 for Single-Ascending Dose (SAD) Cohorts; Multiple Time-points on Days 1 through 15 for Multiple-Ascending Dose (MAD) Cohorts)
- Amount (Aeu) Excreted in Urine(Multiple Time-points on Days 1 through 4 for Single-Ascending Dose (SAD) Cohorts; Multiple Time-points on Days 1 through 15 for Multiple-Ascending Dose (MAD) Cohorts)
- Accumulation Ratio (AR)(Multiple Time-points on Days 1 through 4 for Single-Ascending Dose (SAD) Cohorts; Multiple Time-points on Days 1 through 15 for Multiple-Ascending Dose (MAD) Cohorts)