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

Hypertension Clinical Trial

Official title: A Phase I/IB, First-Time-in-Human, Single Centre, Double-Blind, Randomized, Placebo-controlled, Dose Escalating Study of the Safety, Tolerability and Pharmacokinetics of Single and Repeat Doses of VB0004 Administered Orally to Healthy Volunteers; and to Patients With Mild to Moderate Hypertension With Low Cardiovascular Risk.

Status Recruiting

Clinical Trial 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 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.

Clinical Trial Description

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. ;

Related Conditions & MeSH terms

• Hypertension

• NCT number: NCT04925050
• Study type: Interventional
• Source: Syneos Health
• Contact: Recruitment Officer
• Phone: 1800 243 733
• Email: Recruitment@nucleusnetwork.com.au
• Status: Recruiting
• Phase: Phase 1
• Start date: June 17, 2021
• Completion date: January 23, 2024