A Trial of Oral VRB-103 Alone or in Combination With Oral Ecnoglutide (VRB-101) in Participants With Obesity or Overweight

Other illness

• 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.

Lab values

• 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.
• Have a history of hypocalcemia or ionized serum calcium below the normal range at Screening.

• 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 (Arm 1) OR
  • ≥27 kg/m\^2 and ≤40.0 kg/m\^2 (Arm 2 and Arm 3)
• 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 confirmation (an average of duplicate readings) with 2 or less hypertension-directed medications.