A Randomized, Double-blind, Placebo-controlled, First-in-Human Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Oral VRB-103 Alone or in Combination With Oral Ecnoglutide (VRB-101) in Participants With Obesity or Overweight
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 336
- 试验地点
- 1
- 主要终点
- Number of Participants with Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
研究概览
简要总结
The primary objective is to evaluate the safety and tolerability of VRB-103 tablets administered as monotherapy or VRB-103 tablets administered in combination with oral ecnoglutide tablets (VRB-101 tablets) in a single-dose regimen or in a multiple dose regimen.
详细描述
For Arm 1 (single ascending dose [SAD] part), the primary objective is to evaluate the safety and tolerability of VRB-103 tablets administered as monotherapy or VRB-103 tablets administered in combination with oral ecnoglutide tablets (VRB-101 tablets) in a single-dose regimen to participants with elevated body mass index (BMI) (≥25 kg/m^2 and ≤35 kg/m^2) who are otherwise healthy. For Arm 2 and Arm 3 (multiple ascending dose [MAD] parts), the primary objective is to evaluate the safety and tolerability of multiple ascending doses of VRB-103 tablets administered as monotherapy, VRB-101 tablets administered as monotherapy, or VRB-103 tablets administered in combination with VRB-101 tablets to participants with elevated BMI (≥27 kg/m^2 and ≤40 kg/m^2) who are otherwise healthy.
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
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Male or female assigned at birth, inclusive of all gender identities.
- •Have HbA1c ≤6.4% at Screening and Day -2 eligibility confirmation.
- •Have a BMI of:
- •≥25 kg/m^2 and ≤35.0 kg/m^2 (Part A) OR
- •≥27 kg/m^2 and ≤40.0 kg/m^2 (Part B and Part C)
- •Weight ≥70 kg with self-reported stable body weight (≤5% body weight change) for the 3 months prior to randomization.
- •Otherwise healthy, as defined by the absence of any clinically significant, in the Investigator's opinion, active or chronic disease (e.g., Type 2 diabetes mellitus [T2DM], cardiovascular [CV] disease, cancer, and any acute or chronic illness that could pose a problem to completing the study) as determined through a comprehensive medical and surgical history, a thorough physical exam (PE) that includes vital signs, a 12-lead Electrocardiogram (ECG), hematology, blood chemistry, serology, and urinalysis. Cardiovascular (CV) risk factors, such as dyslipidemia and mild hypertension, are expected and are allowed.
- •Have an estimated glomerular filtration rate (eGFR) >60 mL/min at Screening and Day -2 eligibility confirmation, as calculated using the 2021 Chronic Kidney Disease Epidemiology (CKD-EPI) creatinine equation, with no other clinical or laboratory evidence of renal dysfunction or impairment.
- •Persons of childbearing potential must be non-pregnant and non-lactating and must agree to use study-specified contraceptive methods.
- •Have a resting BP of ≤140/90 millimeters of mercury (mmHg) at Screening and Day -2 eligibility with 2 or less hypertension-directed medications.
排除标准
- •Have any prior diagnosis of type 1 diabetes mellitus or T2DM, or other forms of diabetes mellitus. A participant with a history of gestational diabetes may be included in the study if the participant has HbA1c ≤6.4% at Screening and Day -2 eligibility confirmation and is not on medication to lower glucose.
- •Have at least 1 laboratory value suggestive of diabetes at Screening and Day -2 eligibility confirmation, including 1 or more of HbA1c >6.4% (48 mmol/mol) or random glucose ≥200 mg/dL (11.1 mmol/L).
- •Have had exposure to GLP-1, glucose-dependent insulinotropic peptide (GIP), or amylin analogs within 6 months prior to Screening or any prior history of known or suspected hypersensitivity/allergies, intolerability, or lack of efficacy to these medications. Have known or suspected hypersensitivity to study product(s), to amylin analogs, to selective GLP-1 receptor agonist (RAs), or to GIP/GLP-1 or GLP-1/glucagon dual RAs.
- •Presence or history of clinically significant cardiovascular, renal, hepatic, dermatological, respiratory, neurological, psychiatric, malignant, metabolic, endocrinological, hematological, or venereal disorder, as judged by the Investigator.
- •Have a medical history of clinically significant gastric emptying abnormality (for example, severe gastroparesis or gastric outlet obstruction), chronically take drugs that directly affect gastrointestinal (GI) motility, or have a history of any clinically relevant GI diseases or symptoms of GI disorders potentially affecting interpretation of study data.
- •Have a history of hypocalcemia or ionized serum calcium below the normal range at Screening and Day -2 eligibility confirmation.
研究组 & 干预措施
Arm 3, MAD: VRB-103 or VRB-101 or Placebo
Each participant will receive oral doses of VRB-103 alone, VRB-101 alone, VRB-103 co-administered with VRB-101, or placebo, once weekly.
干预措施: VRB-101 (Drug)
Arm 2, MAD: VRB-103 or VRB-101 or Placebo
Each participant will receive oral doses of VRB-103 alone, VRB-101 alone, VRB-103 co-administered with VRB-101, or placebo, once weekly or once daily.
干预措施: VRB-101 (Drug)
Arm 1, SAD: VRB-103 or VRB-101 or Placebo
Each participant will receive a single oral dose of VRB-103 alone, VRB-103 co-administered with VRB-101, or placebo once.
干预措施: VRB-101 (Drug)
Arm 2, MAD: VRB-103 or VRB-101 or Placebo
Each participant will receive oral doses of VRB-103 alone, VRB-101 alone, VRB-103 co-administered with VRB-101, or placebo, once weekly or once daily.
干预措施: VRB-103 (Drug)
Arm 2, MAD: VRB-103 or VRB-101 or Placebo
Each participant will receive oral doses of VRB-103 alone, VRB-101 alone, VRB-103 co-administered with VRB-101, or placebo, once weekly or once daily.
干预措施: Placebo (Other)
Arm 3, MAD: VRB-103 or VRB-101 or Placebo
Each participant will receive oral doses of VRB-103 alone, VRB-101 alone, VRB-103 co-administered with VRB-101, or placebo, once weekly.
干预措施: VRB-103 (Drug)
Arm 3, MAD: VRB-103 or VRB-101 or Placebo
Each participant will receive oral doses of VRB-103 alone, VRB-101 alone, VRB-103 co-administered with VRB-101, or placebo, once weekly.
干预措施: Placebo (Other)
Arm 1, SAD: VRB-103 or VRB-101 or Placebo
Each participant will receive a single oral dose of VRB-103 alone, VRB-103 co-administered with VRB-101, or placebo once.
干预措施: VRB-103 (Drug)
Arm 1, SAD: VRB-103 or VRB-101 or Placebo
Each participant will receive a single oral dose of VRB-103 alone, VRB-103 co-administered with VRB-101, or placebo once.
干预措施: Placebo (Other)
结局指标
主要结局
Number of Participants with Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
时间窗: Screening up to End of Study (Arm 1: Day 29, Arm 2: Week 10, and Arm 3: Week 20)
Any clinically significant changes in lab parameters, hematology, ECG parameters, will be reported as TEAEs.
Number of Participants with Adverse Events of Special Interest (AESIs)
时间窗: Screening up to End of Study (Arm 1: Day 29, Arm 2: Week 10, and Arm 3: Week 20)
Change in Columbia-Suicide Severity Rating Scale (C-SSRS) from Baseline
时间窗: Screening up to End of Study (Arm 1: Day 29, Arm 2: Week 10, and Arm 3: Week 20)
The C-SSRS systematically assesses suicidal ideation and behavior using yes/no questions, ordinal severity ratings (0-5), and intensity subscales. Results at End of Study will be compared to Baseline.
Change in Patient Health Questionnaire-9 (PHQ-9) Scores from Baseline
时间窗: Screening up to End of Study (Arm 1: Day 29, Arm 2: Week 10, and Arm 3: Week 20)
The PHQ-9 is a 9-item validated assessment, measures the severity of depression. Each item is rated from 0 to 3, for a total score out of 27. A score of 15-19 indicates moderately severe depression, and a score of 20-27 indicates severe depression.
次要结局
- Plasma concentrations of VRB-103 and VRB-101(Baseline up to End of Study (Arm 1: Day 29, Arm 2: Week 10, and Arm 3: Week 20))
- Maximum Observed Plasma Concentration (Cmax) for VRB-103 and VRB-101(Baseline up to End of Study (Arm 1: Day 29, Arm 2: Week 10, and Arm 3: Week 20))
- Trough Concentration (Ctrough) of VRB-103 and VRB-101(Baseline up to End of Study (Arm 2: Week 10 and Arm 3: Week 20))
- AUC Over the Dosing Interval (AUCtau) of VRB-103 and VRB-101(Baseline up to End of Study (Arm 2: Week 10 and Arm 3: Week 20))
- Time to Reach Cmax (Tmax) for VRB-103 and VRB-101(Baseline up to End of Study (Arm 1: Day 29, Arm 2: Week 10, and Arm 3: Week 20))
- Area Under the Plasma Concentration-time Curve Extrapolated to Infinity (AUCinf) for VRB-103 and VRB-101(Arm 1: From Baseline up to Day 29)
- Half-life (t1/2) for VRB-103 and VRB-101(Baseline up to End of Study (Arm 1: Day 29, Arm 2: Week 10, and Arm 3: Week 20))