A Phase 1, Randomized, Double-Blind, Single-Ascending-Dose Study Evaluating the Safety, Tolerability, and Pharmacokinetics of BT051 in Healthy Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 50
- 试验地点
- 1
- 主要终点
- Evaluate the safety and tolerability of BT051 based on the difference of proportions between treatment groups of subjects observed with a change from baseline in physical examinations, vital signs, and electrocardiograms (ECG).
研究概览
简要总结
This is a randomized, double-blind, placebo-controlled study to assess the safety and tolerability of single ascending doses of BT051 in healthy male or female volunteers aged 18 to <50 years. A total of 50 subjects will be randomized to receive a single oral dose of BT051 or matching placebo in a ratio of 4 active:1 placebo in 5 ascending dose cohorts (10 subjects per cohort) at active dose levels of 100mg, 300mg, 700mg, 1500mg or 3500mg. The study Safety Review Committee (SRC) will evaluate if any dose-limiting adverse events (AEs) occurred in a cohort through Day 3, as well as review cumulative safety data for all previous cohorts and any available pharmacokinetic (PK) data before proceeding to dosing in the next cohort.
详细描述
BT051-1-001 is a phase 1, randomized, double-blind, single center, single-ascending-dose study in which healthy subjects will receive a single oral dose of BT051 or placebo while confined to the clinical unit. Approximately 50 subjects will be enrolled in 5 sequential, ascending dose cohorts.
Healthy male and female adult subjects will be enrolled and screened for participation within 28 days before the scheduled administration of study drug. After written informed consent is obtained, the screening procedures will include: medical history, documentation of prior medications (i.e., medications taken within 30 days before the scheduled dose of study drug), viral serology tests, clinical laboratory testing, pregnancy testing (for women of childbearing potential), 12 lead electrocardiograms (ECGs), vital sign measurements, and physical examination.
After confirmation of inclusion and exclusion criteria, subjects eligible for randomization will be admitted to the clinical unit 1 day before the scheduled administration of study drug (Day -1) and will be confined in the clinical unit until the morning of Day 3. All subjects will return to the clinical unit on Day 7 (-1 or +2 days) and for the last follow-up on Day 30 (±3 days) for study assessments.
A total of 10 subjects will be randomized to receive BT051 or placebo (8 active:2 placebo) in each of the following sequential dose escalating cohorts: 100mg, 300mg, 700mg. 1500mg and 3500mg. Administration of a single dose of study medication on Day 1 will occur under fasted conditions (i.e., no food allowed overnight before dosing until at least 4 hours after dosing). Except for approximately 240-480 mL of water given with study drug, no fluid will be allowed from 1 hour before dosing until 1 hour postdose; water will be provided ad libitum at all other times.
The study Safety Review Committee (SRC) will evaluate if any dose-limiting adverse events (AEs) through Day 3 occurred in a cohort before proceeding to dosing in the next cohort. In addition, cumulative safety data will be reviewed for all previous cohorts along with any available pharmacokinetic (PK) data. A lower dose may be explored in case dose-limiting AEs are observed at a higher dose level.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 49 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Subjects must meet all the following criteria to be considered eligible to participate in the study:
- •Male or female subjects age ≥18 years and <50 years
- •In good health with no clinically significant abnormalities as determined by medical history, physical exam, and laboratory values
- •Able and willing to provide written informed consent
- •Be able to understand the study procedures and agree to participate in the study
- •For male subjects, be surgically sterile or agree to use an appropriate method of contraception (i.e., condom) or have a female sexual partner who is surgically sterile or using an insertable, injectable, transdermal, or combination oral contraceptive with a barrier method approved and deemed highly effective by the United States Food and Drug Administration (FDA) through 30 days after the dose of study drug
- •For female subjects of childbearing potential, be using an insertable, injectable, or transdermal hormonal contraceptive, or combination oral contraceptive with a barrier method approved and deemed highly effective by the FDA through 30 days after the dose of study drug and have negative results on pregnancy tests done at Screening and on Day -
- •NOTE: women who are surgically sterile or postmenopausal (i.e., no menses for at least 2 years or documented by follicle stimulating hormone) are also eligible to participate.
- •Availability to volunteer for the entire study duration and willing to adhere to all protocol requirements, including confinement in the clinical unit through Day 3
- •Body mass index (BMI) >18.5 and <32.0 kg/m^2
- •Ability to fast for at least 10 hours and consume standard meals
- •Willingness to discontinue concomitant medications
排除标准
- •Subjects who meet any of the following criteria will be excluded from participating in the study:
- •Pregnant, breast feeding, or seeking pregnancy while on study
- •Have, as determined by the investigator, a history or clinical manifestations of significant neurologic, renal, hepatic, hematologic, cardiac, pulmonary, metabolic, endocrine, psychiatric, gastrointestinal (GI) disorders (including infectious, ischemic, inflammatory bowel disease, irritable bowel syndrome, known lactose intolerance, or immunological diseases) or other condition that would preclude participation in the study
- •Have a history of a malignancy (or active malignancy), with the exception of subjects with basal cell carcinoma, squamous cell carcinoma, or carcinoma in situ of the cervix who have been treated and cured
- •Have had any symptoms of cold, flu, or febrile illness within 2 weeks prior to dosing
- •Have received any live attenuated vaccine within 30 days of dosing
- •Have received cyclosporine A within the last 1 month, including Restasis® (cyclosporine ophthalmic emulsion) for dry eye syndrome or any other cyclosporine ophthalmic preparation
- •Participation in a clinical trial of an investigational drug or medical device within 30 days before Screening
- •In the opinion of the Investigator, unable to comply with the study protocol
- •Have a history of alcoholism or illicit drug use within 2 years before the scheduled dose of study drug
- •A positive test result for any of the following: human immunodeficiency virus (HIV), hepatitis B virus (HBV) surface antigen, hepatitis C virus (HCV) antibody, drugs of abuse (marijuana, amphetamines, barbiturates, cocaine, opiates, phencyclidine and benzodiazepines), and alcohol.
- •Have donated more than 500 mL of blood within 60 days before the scheduled dose of study drug
- •Have taken prescription medications within 5 half-lives of the specific substance (or, if half-life is not known, within 48 hours) before the scheduled administration of study drug
- •Have taken over-the-counter medication or supplements, including nutritional supplements, stool softeners (e.g., Miralax), or colon preparations within 7 days before dosing
- •History of any hypersensitivity or allergic reaction to cyclosporine
- •History of GI surgery or any part of GI tract removed excluding appendectomy and cholecystectomy
- •Use of tobacco or marijuana products within the previous 6 months
研究组 & 干预措施
BT051 100 mg
Participants will receive a single oral dose of 100mg BT051.
干预措施: BT051 100mg (Drug)
BT051 300 mg
Participants will receive a single oral dose of 300mg BT051.
干预措施: BT051 300mg (Drug)
BT051 700 mg
Participants will receive a single oral dose of 700mg BT051.
干预措施: BT051 700mg (Drug)
BT051 1500 mg
Participants will receive a single oral dose of 1500mg BT051.
干预措施: BT051 1500mg (Drug)
BT051 3500 mg
Participants will receive a single oral dose of 3500mg BT051.
干预措施: BT051 3500mg (Drug)
Placebo
Participants will receive a single oral dose of Placebo matching BT051 dose.
干预措施: Matching Placebo (Drug)
结局指标
主要结局
Evaluate the safety and tolerability of BT051 based on the difference of proportions between treatment groups of subjects observed with a change from baseline in physical examinations, vital signs, and electrocardiograms (ECG).
时间窗: Baseline to Day 30
Proportion of subjects with a change from baseline from normal to abnormal in physical examinations, vital signs, and ECGs will be summarized.
Evaluate the safety and tolerability of BT051 based on the difference of proportions between treatment groups of subjects experiencing treatment-emergent adverse events (TEAEs).
时间窗: Baseline to Day 30
Proportion of subjects experiencing a TEAE will be summarized using the MedDRA system organ class and preferred term.
Evaluate the safety and tolerability of BT051 based on the difference of proportions between treatment groups of subjects experiencing clinically significant changes from baseline in clinical laboratory tests.
时间窗: Baseline to Day 30
Proportion of subjects with a change from baseline from normal to abnormal in clinical laboratory tests (hematology with differential, serum chemistry, coagulation, and urinalysis) will be summarized.
次要结局
- Half-life (t1/2) in whole blood(Baseline to Day 3)
- Stool concentration of BT051 and BT070(Baseline to Day 7)
- Urine concentration of BT051 and BT070(Baseline to Day 3)
- Area Under the Concentration-Time Curve (AUC) in whole blood(Baseline to Day 3)
- Maximum observed concentration (Cmax) in whole blood(Baseline to Day 3)
- Time to maximum observed concentration (Tmax) in whole blood(Baseline to Day 3)