First-in-Human Study of VB0004 in Healthy Subjects and to Patients With Mild to Moderate Hypertension With Low Cardiovascular Risk

• Status: Recruiting
• Trial end date: 2022-05-23

Summary

This will be a single center, Phase I/IB, randomized, double-blind, placebo controlled, sequential SAD/MAD/FE study, with a patients arm. The study will be divided into three parts:

Part A: SAD cohorts, with food-effect (FE) evaluation Part B: MAD cohorts with healthy volunteers Part C: MAD cohorts including naïve patients with mild to moderate hypertension The three parts will be completed sequentially.

Part A - SAD Cohorts 1 to 5:

Part 1 will consist of up to 5 cohorts (1 cohort per dose level). Each cohort will include 8 subjects (6 subjects receiving the active study drug and 2 subjects receiving matching placebo), for a total of 40 subjects. ). Efforts will be made to have gender-balanced cohorts.

A staggered dosing schedule will be used for dosing of each cohort (under fasting conditions) and will include 2 sentinel subjects (1 active and 1 placebo) dosed initially, and the remaining 6 subjects dosed at least 24 hours later.

The FE study will be conducted with 2 cohorts of 8 healthy participants from the SAD study. Subjects from FE Cohort 3 and Cohort 4 will receive the study drug under both fasting (in a first period) and fed conditions (in a second period). Participants in the fasted and fed cohort will be randomized to active or placebo in a ratio of 3:1. There will be a washout period of at least 14 days between dosing of the fasting and the fed periods. All subjects will be dosed on the same day in the fed period. After a supervised fast of at least 10 hours, subjects will be served a high-fat, high-calorie meal of approximately 800 to 1000 calories (approximately 50% of total caloric content of the meal derived from fat). This meal should derive approximately 150, 250, and 500-600 calories from protein, carbohydrate, and fat, respectively. The meal will consist of two eggs fried in butter, two slices of toast with butter, two strips of bacon, approximately 120 g of hash brown potatoes, and 200 mL of whole milk. Subjects will be required to start their meal as soon as it is served and to complete it in 30 minutes or less. Drug administration will occur 30 ± 1 minutes after the meal has been started. No food will be allowed until at least 4 hours after dosing. Except for fluids provided with the breakfast and water given with the study drug, no fluids will be allowed from 1 hour before until 1 hour after dosing. Water will be provided ad libitum at all other times.

The planned SAD dose range is anticipated to be from 2 mg to 300 mg. The mode of administration is oral. The doses are specified for fasted cohorts. To monitor adherence to the intervention, participants will remain at the unit for the duration of dosing and treatment period.

Part B - MAD Cohorts 6 to 9 (Healthy Volunteers):

Part B will consist of 4 cohorts (1 cohort per dose level). Each cohort will include 8 subjects (6 subjects receiving the study drug and 2 subjects receiving matching placebo daily for 14 consecutive days), for a total of 32 subjects. Efforts will be made to have gender-balanced cohorts.

Part B can be initiated only following review of the safety, tolerability, and PK data following dosing of the last SAD Cohort.

A staggered dosing schedule might be used for the first dose level, including 2 sentinel subjects (1 active and 1 placebo) initiating dosing first and the remaining 6 subjects initiating dosing at least 24 hours later.

The planned MAD dose range is anticipated to be from 2 mg to 100 mg administered q.d. for 14 consecutive days.

Part C - MAD Cohorts 10 and 11 (Patients with mild to moderate hypertension):

Part C will consist of 2 cohorts (1 cohort per dose level). Each cohort will include a maximum of 8 patients with mild to moderate hypertension with low cardiovascular risk (6 subjects receiving the study drug and 2 subjects receiving matching placebo daily for 28 consecutive days), for a total of 16 patients. The doses of VB0004 administered will be determined by the SAD and MAD PK data.

• Phase: Phase 1

Details

• Lead Sponsor: Syneos Health