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

Официальное название

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

Обзор

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.

Подробное описание

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.

Вмешательства

• Препарат VRB-103
  VRB-103 tablets will be administered orally.
• Другое Placebo
  Placebo tablets will be administered orally.
• Препарат VRB-101
  VRB-101 tablets will be administered orally.

Первичные конечные точки

• Number of Participants with Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) [Срок оценки: 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) [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: Screening up to End of Study (Arm 1: Day 29, Arm 2: Week 10, and Arm 3: Week 20)]

Вторичные конечные точки (7)

• Plasma concentrations of VRB-103 and VRB-101 [Срок оценки: 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 [Срок оценки: Baseline up to End of Study (Arm 1: Day 29, Arm 2: Week 10, and Arm 3: Week 20)]
• Time to Reach Cmax (Tmax) for VRB-103 and VRB-101 [Срок оценки: 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 [Срок оценки: Arm 1: From Baseline up to Day 29]
• Half-life (t1/2) for VRB-103 and VRB-101 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: Baseline up to End of Study (Arm 2: Week 10 and Arm 3: Week 20)]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Тройное слепое

Основная цель

Лечение

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Идентификаторы

NCT: NCT07628127 · VRB-103-101

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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