A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Single and Multiple Dose Escalation Study to Evaluate Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of BLKR201 in Healthy Adult Participants
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 128
- 试验地点
- 2
- 主要终点
- Number of Participants with Treatment-Emergent Adverse Events (TEAEs)
研究概览
简要总结
The goal of this clinical trial is to learn if BLKR201 is safe in healthy adults. Researchers will also learn how the body absorbs and processes BLKR201 and how food may affect it.
The main questions this study aims to answer are:
- Is BLKR201 safe and well tolerated when taken as a single dose or for several days in a row?
- How does BLKR201 move through and leave the body?
- Does taking BLKR201 with food change how the body absorbs it?
Researchers will compare BLKR201 to a placebo (a look-alike tablet that contains no drug) in most parts of the study to see how the drug affects participants.
Participants will:
- Take BLKR201 or a placebo by mouth
- Stay at a clinical research unit for several days during dosing
- Give blood and urine samples
- Have heart tests, vital signs, and lab tests
- Report any side effects
In one part of the study, a small group of participants will receive BLKR201 only (no placebo). These participants will also have a sample of spinal fluid collected to measure how much BLKR201 reaches the fluid around the brain and spinal cord.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Other
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Open-label for CSF cohort only
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
- •Are a healthy man or woman 18 to 55 years old
- •Weigh at least 50 kilograms (110 pounds)
- •Have a body mass index (BMI) between 18 and 30 kg/m2 (inclusive)
- •Are willing to stay at the research unit for the required study visits
- •Are willing to follow study rules about diet, alcohol, tobacco, and medications
- •Are able to understand and sign the informed consent form
- •Women who can become pregnant must:
- •Have a negative pregnancy test before starting
- •Use a highly effective form of birth control during the study and for a period after the last dose
- •Men with partners who can become pregnant must:
- •Use highly effective birth control during the study and for a period after the last dose
- •Not donate sperm during that time
排除标准
- •Have any significant medical condition involving the heart, lungs, liver, kidneys, stomach, intestines, brain, blood, or immune system
- •Have abnormal laboratory test results at screening that the study doctor considers important
- •Have a history of heart rhythm problems or abnormal electrocardiogram (ECG) results
- •Have high blood pressure at screening
- •Have had a serious infection within the past 6 months
- •Test positive for HIV, hepatitis B, hepatitis C, or tuberculosis, or show evidence of hepatitis B infection (positive hepatitis B surface antigen or hepatitis B core antibody). Note: participants with hepatitis B immunity from vaccination alone may still be eligible.
- •Have a history of cancer in the past 5 years (with limited exceptions for certain treated skin cancers)
- •Have a history of serious stomach problems such as ulcers, stomach surgery, or stomach bleeding
- •Use tobacco, nicotine, or marijuana products
- •Test positive for drugs or alcohol at screening
- •Have taken another investigational drug within the required time before this study
- •Have received a live vaccine within 30 days before study start
- •Are pregnant or breastfeeding
- •Have a known allergy to the study drug or similar medicines
- •Additional exclusions:
- •Regular heavy alcohol use
- •Regular use of certain medications such as anti-inflammatory drugs, steroids, or blood thinners
- •Donation of more than 500 milliliters (about one pint) of blood within 1 month before screening
- •For the spinal fluid (CSF) portion of the study, you cannot take part if you:
- •Take blood-thinning medications
- •Have bleeding or clotting problems
- •Have sensitivity to lidocaine, band aids, adhesive dressing, or medical tape
- •Have medical conditions that make a spinal tap unsafe
研究组 & 干预措施
Cerebrospinal Fluid (CSF) Cohort (BLKR201, Open-Label)
Participants receive BLKR201 orally for 10 consecutive days. This cohort is non-randomized and open-label. Cerebrospinal fluid samples are collected on Day 10 to evaluate central nervous system exposure.
干预措施: BLKR201 (Drug)
Single Ascending Dose (SAD) Cohorts (BLKR201 or Placebo)
Participants receive a single oral dose of BLKR201 or matching placebo in sequential dose-escalation cohorts (up to seven escalating doses of BLKR201 to be evaluated). One cohort will receive a second dose under separate fed and fasted dosing periods to evaluate food effect. Participants are randomized within each cohort.
干预措施: Placebo (Drug)
Multiple Ascending Dose (MAD) Cohorts (BLKR201 or Placebo)
Participants receive BLKR201 or matching placebo orally for 7 consecutive days in sequential dose-escalation cohorts (up to four escalating doses of BLKR201 to be evaluated). Participants are randomized within each cohort.
干预措施: BLKR201 (Drug)
Multiple Ascending Dose (MAD) Cohorts (BLKR201 or Placebo)
Participants receive BLKR201 or matching placebo orally for 7 consecutive days in sequential dose-escalation cohorts (up to four escalating doses of BLKR201 to be evaluated). Participants are randomized within each cohort.
干预措施: Placebo (Drug)
Single Ascending Dose (SAD) Cohorts (BLKR201 or Placebo)
Participants receive a single oral dose of BLKR201 or matching placebo in sequential dose-escalation cohorts (up to seven escalating doses of BLKR201 to be evaluated). One cohort will receive a second dose under separate fed and fasted dosing periods to evaluate food effect. Participants are randomized within each cohort.
干预措施: BLKR201 (Drug)
结局指标
主要结局
Number of Participants with Treatment-Emergent Adverse Events (TEAEs)
时间窗: Baseline through approximately 7 days after final dose
Treatment-emergent adverse events are defined as adverse events that begin or worsen after administration of BLKR201 or placebo. Events will be summarized by frequency and severity.
Change From Baseline in Clinical Laboratory Parameters
时间窗: Baseline through approximately 7 days after final dose
Clinical laboratory parameters include hematology, clinical chemistry, coagulation, lipid panel, and urinalysis. Change from baseline values will be summarized at scheduled post-dose assessments.
Change From Baseline in Systolic Blood Pressure
时间窗: Baseline through approximately 7 days after final dose
Systolic blood pressure will be measured in millimeters of mercury (mmHg). Change from baseline will be summarized at scheduled post-dose assessments.
Change From Baseline in Diastolic Blood Pressure
时间窗: Baseline through approximately 7 days after final dose
Diastolic blood pressure will be measured in millimeters of mercury (mmHg). Change from baseline will be summarized at scheduled post-dose assessments.
Change From Baseline in Pulse Rate
时间窗: Baseline through approximately 7 days after final dose
Pulse rate will be measured in beats per minute (bpm). Change from baseline will be summarized at scheduled post-dose assessments.
Change From Baseline in Respiratory Rate
时间窗: Baseline through approximately 7 days after final dose
Respiratory rate will be measured in breaths per minute. Change from baseline will be summarized at scheduled post-dose assessments.
Change From Baseline in Body Temperature
时间窗: Baseline through approximately 7 days after final dose
Body temperature will be measured in degrees Fahrenheit (°F). Change from baseline will be summarized at scheduled post-dose assessments.
Change From Baseline in 12-Lead Electrocardiogram (ECG) Parameters
时间窗: Baseline through approximately 7 days after final dose
ECG parameters include QT interval corrected using Fridericia's formula (QTcF), PR interval, QRS duration, and heart rate. Change from baseline values will be summarized at scheduled post-dose assessments.
次要结局
- Maximum Observed Plasma Concentration (Cmax) of BLKR201 After Single Oral Dose(From predose through approximately 7 days after final dose)
- Area Under the Plasma Concentration-Time Curve (AUC) of BLKR201 After Single Oral Dose(From predose through approximately 7 days after final dose)
- Area Under the Plasma Concentration-Time Curve Over the Dosing Interval (AUCtau) After Multiple Doses(From predose through approximately 7 days after final dose)
- BLKR201 Concentration in Cerebrospinal Fluid (CSF)(Day 7 post-dose in the CSF cohort (single CSF sampling time point per participant))
- Amount of BLKR201 Excreted in Urine(From predose through 48 hours post-dose (in certain SAD cohorts only))
- Ratio of Maximum Observed Plasma Concentration (Cmax) of BLKR201 Under Fed Versus Fasted Conditions(From predose through 48 hours post-dose (in certain SAD cohorts only))
- Ratio of Area Under the Plasma Concentration Versus Time Curve (AUC) of BLKR201 Under Fed Versus Fasted Conditions(From predose through 48 hours post-dose (in certain SAD cohorts only))
- Maximum Observed Plasma Concentration (Cmax) After Multiple Doses(From predose through approximately 7 days after final dose)
- BLKR201 Concentration in Cerebrospinal Fluid (CSF)(Day 10 post-dose in the CSF cohort (single CSF sampling time point per participant))