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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Arm 1, SAD: VRB-103 or VRB-101 or Placebo | Experimental | Each participant will receive a single oral dose of VRB-103 alone, VRB-103 co-administered with VRB-101, or placebo once. |
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| Arm 2, MAD: VRB-103 or VRB-101 or Placebo | Experimental | 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. |
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| Arm 3, MAD: VRB-103 or VRB-101 or Placebo | Experimental | Each participant will receive oral doses of VRB-103 alone, VRB-101 alone, VRB-103 co-administered with VRB-101, or placebo, once weekly. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| VRB-103 | Drug | VRB-103 tablets will be administered orally. |
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| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants with Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Any clinically significant changes in lab parameters, hematology, ECG parameters, will be reported as TEAEs. | Screening up to End of Study (Arm 1: Day 29, Arm 2: Week 10, and Arm 3: Week 20) |
| Number of Participants with Adverse Events of Special Interest (AESIs) | 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 | 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. | Screening up to End of Study (Arm 1: Day 29, Arm 2: Week 10, and Arm 3: Week 20) |
| Change in Patient Health Questionnaire-9 (PHQ-9) Scores from Baseline | 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. | Screening up to End of Study (Arm 1: Day 29, Arm 2: Week 10, and Arm 3: Week 20) |
| Measure | Description | Time Frame |
|---|---|---|
| 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) |
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Inclusion Criteria:
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:
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.
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Verdiva Bio Medical Affairs | Contact | medical.affairs@verdivabio.com |
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| ID | Term |
|---|---|
| D009765 | Obesity |
| D050177 | Overweight |
| ID | Term |
|---|---|
| D044343 | Overnutrition |
| D009748 | Nutrition Disorders |
| D009750 | Nutritional and Metabolic Diseases |
| D001835 | Body Weight |
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| Placebo | Other | Placebo tablets will be administered orally. |
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| VRB-101 | Drug | VRB-101 tablets will be administered orally. |
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| 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) |
| 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) |
| D012816 |
| Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |