A Phase 1b, Randomized, Double-Blind, Placebo-Controlled, Dose-Range Finding Study of the Efficacy, Safety, and Pharmacokinetics of CRB-913 in Participants With Obesity With a Single Cohort Open-label Exploratory Pharmacokinetic Lead-In
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 252
- 试验地点
- 15
- 主要终点
- Part 1: To evaluate the PK of a single dose of CRB-913 - Cmax
研究概览
简要总结
This study will assess the safety of the investigational drug CRB-913 and how it is processed in the body.
The study has two parts: Part 1 will measure drug levels in healthy adults after taking CRB-913 tablets, and Part 2 will compare three doses of CRB-913 with placebo to evaluate safety, effects on body weight, and drug levels in the blood.
Part 2 is blinded, meaning participants, study doctors, and the sponsor will not know which treatment is given.
Participants in Part 2 will take study treatment for 12 weeks and will be followed for 28 days after treatment ends.
详细描述
CRB-913 is a novel cannabinoid receptor type 1 (CB1) inverse agonist (CB1-IA) that is being developed for once-daily treatment of obesity.
This study will look at how the investigational drug CRB-913 behaves in the body and how it affects body weight.
The study has two parts:
Part 1 will include healthy adult participants. They will receive CRB-913 in tablet form. Researchers will measure how much of the drug enters the bloodstream and how long it stays there.
Part 2 will include participants who will receive one of three different doses of CRB-913 or a placebo (a tablet with no active drug). This part of the study will look at the safety of CRB-913 and its effects on body weight. Researchers will also measure the amount of CRB-913 in the blood.
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
- Double (Participant, Investigator)
盲法说明
Part 1 is open label. Part 2 is double blind.
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Part 1: Participants with BMI 18.0-25.0 kg/m²
- •Part 2: Obese participants with BMI ≥30 kg/m²
排除标准
- •Significant liver disease or moderate-severe hepatic impairment
- •History of seizures, epilepsy, or intracranial surgery
- •Diabetes mellitus (Type 1 or Type 2), except gestational
- •Bariatric surgery or >5 kg weight change in past 3 months
- •Recent use (within 3 months) of GLP-1 agonists or other weight-loss medications
- •Major depression within 2 years.
- •Any history of suicidal ideation/attempt
- •Severe psychiatric disorders (e.g., schizophrenia, bipolar disorder)
- •Elevated screening scores: PHQ-9 >4, GAD-7 >4, or positive C-SSRS Items 1-2
- •Active or recent (within 5 years) malignancy (exceptions: in situ and fully resected nonmelanoma skin cancer)
- •Abnormal thyroid function: TSH >6 mIU/L unless stable on replacement therapy
- •QTc >470 msec (females) or >450 msec (males) or history of long QT syndrome
- •Use of systemic corticosteroids or unstable chronic medications affecting BP, lipids, or glucose
- •Use of CYP3A4 substrates or strong P-gp substrates/inhibitors
- •Investigational drug use within 28 days
- •Prior exposure to CRB-913 or other CB1 inverse agonists/antagonists
- •Substance abuse history
- •Pregnancy, breastfeeding, or unwillingness to use highly effective contraception
- •Positive drug or alcohol screen
- •Any condition that, in the investigator's judgment, makes participation unsafe or non-feasible
研究组 & 干预措施
Part 1: PK Lead-in
Primary Treatment Period (Day 1): Participants will receive a single dose of CRB-913. Following Part 1 of the study Part 2 will open for recruitment.
Safety Follow-up Period: Participants who complete or discontinue the primary treatment period are followed for safety for 28 days. No treatment is administered during this period.
干预措施: CRB-913 (Drug)
Part 2: CRB-913 low dose
Primary Treatment Period (Day 0-Day 85): Participants will receive CRB-913 low dose which is maintained up to day 85.
Safety Follow-up Period: Participants who complete or discontinue the primary treatment period are followed for safety for 28 days. No treatment is administered during this period.
干预措施: CRB-913 (Drug)
Part 2: CRB-913 Medium Dose
Primary Treatment Period (Day 0-Day 85): Participants will receive CRB-913 starting at low dose for 14 days and increasing to medium dose at day 15 which is maintained up to day 85.
Safety Follow-up Period: Participants who complete or discontinue the primary treatment period are followed for safety for 28 days. No treatment is administered during this period.
干预措施: CRB-913 (Drug)
Part 2: CRB-913 High Dose
Primary Treatment Period (Day 0 - Day 85): Participants will receive CRB-913 starting at low dose for 14 days, increasing to medium dose at day 15 for 14 days and then increased to high dose at day 29 which is maintained up to day 85.
Safety Follow-up Period: Participants who complete or discontinue the primary treatment period are followed for safety for 28 days. No treatment is administered during this period.
干预措施: CRB-913 (Drug)
Part 2: Placebo
Primary Treatment Period (Day 0-Day 85): Participants will receive CRB-913 matching placebo which is maintained up to day 85.
Safety Follow-up Period: Participants who complete or discontinue the primary treatment period are followed for safety for 28 days. No treatment is administered during this period.
干预措施: Placebo (Drug)
结局指标
主要结局
Part 1: To evaluate the PK of a single dose of CRB-913 - Cmax
时间窗: 0 to 48 hours
Maximum plasma concentration (Cmax)
Part 1: To evaluate the PK of a single dose of CRB-913 - Tmax
时间窗: 0 to 48 hours
Time to maximum plasma concentration (Tmax)
Part 1: To evaluate the PK of a single dose of CRB-913 - T1/2
时间窗: 0 to 48 hours
Terminal elimination half-life (T1/2)
Part 2: To evaluate the safety of CRB-913 - TEAE
时间窗: Day 1 to 28 days post final dose
Incidence and severity of treatment emergent adverse events
Part 2: To evaluate the safety of CRB-913 - AESI
时间窗: Day 1 to 28 days post final dose
Incidence of adverse events of special interest
次要结局
- Part 1: To evaluate the safety of a single dose of CRB-913 - TEAE(Day 1 to 28 days post final dose)
- Part 2: To evaluate the effect of CRB-913 on weight(Day 1 to 28 days post final dose)
- Part 2: To evaluate the PK of CRB-913 - Cmax(Day 1 to 28 days post final dose)
- Part 2: To evaluate the PK of CRB-913 - Tmax(Day 1 to 28 days post final dose)