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
• Target enrollment: 0
• Participant gender: All

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
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Syneos Health

Criteria

Inclusion Criteria:

• Male or female, non-smoker (no use of tobacco or nicotine products within 1 month prior to screening), ≥18 and ≤55 years of age, with BMI >18.0 and <32.0 kg/m2.

• Male subjects who are not vasectomized for at least 6 months, and who are sexually active with a female partner of childbearing potential (childbearing potential females are defined as women that are neither post-menopausal nor surgically sterile) must be willing to use one of the following acceptable contraceptive methods from (the first) study drug administration and for 90 days after (the last) study drug administration:

1. simultaneous use of a male condom and, for the female partner, oral contraceptives containing combined estrogen and progesterone beginning a least 4 weeks prior to screening, a vaginal ring, injectable and implantable hormonal contraceptives, intrauterine hormone-releasing system (e.g. Mirena), and progestogen-only hormonal contraception associated with inhibition of ovulation, placed at least 4 weeks prior to the first study drug administration.

2. simultaneous use of a male condom and, for the female partner, nonhormonal intrauterine device (IUD) placed at least 4 weeks prior to the first study drug.

Exclusion Criteria:

• Any laboratory test results deemed clinically significant by the Investigator or positive test for HIV, HBsAg, or HCV.

• Clinically significant ECG abnormalities or vital sign abnormalities (systolic BP lower than 90 or over 140 mmHg (except for hypertensive patients), diastolic BP lower than 40 or over 90 mmHg, HR less than 40 or over 100 bpm, or RR less than 10 or over 22 bpm) at screening.

• Orthostatic hypotension at Screening or Day -1 (Systolic BP falls > 20 mm Hg or Diastolic BP falls > 10 mm Hg on standing)

• History of significant alcohol abuse within 1 year prior to screening or regular use of alcohol within 6 months prior to the screening visit (more than 14 units of alcohol per week [1 unit = 375 mL of beer 3.5%, 100 mL of wine 13.5%, or 30 mL of distilled alcohol 40%]).

• Donation of plasma within 7 days prior to dosing. Donation or loss of blood (excluding volume drawn at screening) of 50 mL to 499 mL of blood within 30 days, or more than 499 mL within 56 days prior to the first dosing.