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 and will include 2 sentinel subjects (1 active and 1 placebo) dosed initially, and the remaining 6 subjects dosed at least 24 hours later. Following completion of each dose level, a Safety Monitoring Committee (SMC) will review the safety and tolerability data, as well as available PK data up to the Follow-Up Visit (Day 8), for at least 6 subjects in the respective cohort, in order to make decisions whether to escalate to the next dose level, decrease the next dose level, repeat a dose level, or to not evaluate any additional dose. The FE study will be conducted with 2 cohorts of 8 healthy participants from the SAD study. Subjects from FE Cohort 3 and, if needed, Cohort 4 will receive the study drug under both fasting (in a first period) and fed conditions (in a second period). There will be a washout period of at least 14 days between dosing of the fasting and the fed periods. Safety, tolerability, and PK data through at least to the Follow-Up Visit (Day 8), from a subsequent cohort will be reviewed by the SMC prior to dosing the fed period of FE Cohort. Therefore, the fed period of a FE Cohort could be dosed in parallel of the SAD Cohort receiving two doses higher. The planned SAD dose range is anticipated to be from 2 mg to 300 mg.~Part B - MAD Cohorts 6 to 8 (Healthy Volunteers):~Part B will consist of 3 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 24 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 SAD Cohort 3 or 4. 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. Following completion of each dose level, a SMC will review the safety and tolerability data, as well as available PK data for at least 6 subjects in the respective cohort, in order to make decisions whether to escalate to the next dose level, decrease the next dose level, repeat a dose level, or to not evaluate any additional dose. The planned MAD dose range is anticipated to be from 10 mg to 100 mg administered q.d. for 14 consecutive days.~Part C - MAD Cohorts 9 and 10 (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. Following completion of Cohort 9, a SMC will review the safety and tolerability data, as well as available PK data for at least 6 subjects in the respective cohort, in order to make decisions whether to escalate to the next dose level, decrease the next dose level, repeat a dose level, or to not evaluate any additional dose.
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 FE evaluation Part B: MAD cohorts with healthy volunteers Part C: MAD cohorts including naïve patients with mild to moderate hypertension and low cardiovascular risk The three parts will be completed sequentially or with partial overlapping.