A Study to Evaluate the Effect of Food and a Proton Pump Inhibitor on the Pharmacokinetics of VRN110755

NCT ID: NCT07141381

Last Updated: 2025-09-23

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-08-27
• Study Completion Date: 2026-01-30

Brief Summary

This is a Phase 1, open-label, randomized, single-center study to evaluate the effect of food and a proton pump inhibitor (PPI) on the pharmacokinetics (PK) of VRN110755 in healthy adult participants. The primary aim of this study is to assess the impact of food and rabeprazole co-administration on the systemic exposure of VRN110755. Safety and tolerability will also be evaluated.

Detailed Description

The study consists of two treatment sequences in a 3-period, crossover design. Approximately 24 healthy adult participants will be randomized 1:1 to one of the following sequences:

Sequence 1: Participants will receive VRN110755 80 mg orally in the fasted state (Period 1), then in the fed state (Period 2), and finally in the fed state with 5 days of rabeprazole pre-treatment (Period 3).

Sequence 2: Participants will receive VRN110755 80 mg orally in the fed state (Period 1), then in the fasted state (Period 2), and finally in the fasted state with 5 days of rabeprazole pre-treatment (Period 3).

Rabeprazole 20 mg will be administered orally once daily for 5 consecutive days prior to the final dosing of VRN110755 in Period 3.

All participants will remain under clinical observation for safety monitoring and pharmacokinetic sampling throughout each period. Blood and urine samples will be collected at defined intervals for the analysis of VRN110755 and its metabolites.

Each participant's total study duration will be approximately 76 days, including screening, treatment, and follow-up.

Conditions

Healthy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Sequence 1: Fasted → Fed → Fed with PPI

Participants in this sequence will receive VRN110755 80 mg orally under the following conditions across three periods:

Period 1: Fasted state Period 2: Fed state (standard high-fat meal) Period 3: Fed state after 5 days of rabeprazole 20 mg daily

Group Type: EXPERIMENTAL

VRN110755

Intervention Type: DRUG

VRN110755 is an investigational EGFR inhibitor administered as an 80 mg oral capsule. It will be given to all participants under fasted, fed, and PPI pre-treated conditions across three periods in a crossover design.

Sequence 2: Fed → Fasted → Fasted with PPI

Participants in this sequence will receive VRN110755 80 mg orally under the following conditions across three periods:

Period 1: Fed state (standard high-fat meal) Period 2: Fasted state Period 3: Fasted state after 5 days of rabeprazole 20 mg daily

Group Type: EXPERIMENTAL

Rabeprazole

Intervention Type: DRUG

Rabeprazole 20 mg will be administered orally once daily for 5 days prior to VRN110755 dosing in Period 3. This is to assess the effect of increased gastric pH (via proton pump inhibition) on the pharmacokinetics of VRN110755.

Interventions

VRN110755

VRN110755 is an investigational EGFR inhibitor administered as an 80 mg oral capsule. It will be given to all participants under fasted, fed, and PPI pre-treated conditions across three periods in a crossover design.

Intervention Type: DRUG

Rabeprazole

Rabeprazole 20 mg will be administered orally once daily for 5 days prior to VRN110755 dosing in Period 3. This is to assess the effect of increased gastric pH (via proton pump inhibition) on the pharmacokinetics of VRN110755.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Male or female participants aged between 18 and 65 years, inclusive, at the time of informed consent.

2. In good general health, with no significant medical history and no clinically significant abnormalities on physical examination, as determined by the investigator.

3. Body mass index (BMI) between 18.0 and 32.0 kg/m², and weight ≥ 50 kg at screening.

4. Clinical laboratory values within normal ranges, unless deemed not clinically significant by the investigator.

5. Female participants of childbearing potential who are sexually active with a male partner must agree to use highly effective contraception methods from screening through 6 months after the last dose of investigational product.

6. Female participants must have a negative pregnancy test at screening and pre-dose.

7. Women not of childbearing potential must be surgically sterile or postmenopausal for ≥12 months.

8. Male participants must agree to use barrier contraception in conjunction with a highly effective method if engaging with women of childbearing potential, from screening through 6 months after the last dose.

9. Male participants must not donate sperm, and female participants must not donate ova, from the first dose through 6 months after the last dose.

10. Able and willing to comply with study procedures and site visits.

11. Able and willing to provide written informed consent before any study procedures are performed.

Exclusion Criteria

1. Any significant medical or psychiatric condition that may interfere with study participation or interpretation of results, as determined by the investigator.

2. Clinically significant abnormal ECG findings, including QTcF > 450 ms (males) or > 470 ms (females).

3. Abnormal vital signs at screening (e.g., systolic BP > 140 or < 90 mmHg, diastolic BP > 90 or < 60 mmHg, or history of symptomatic hypotension).

4. Active liver disease, or AST/ALT > 1.5 × upper limit of normal.

5. Known or suspected gastrointestinal disorders that may interfere with drug absorption (e.g., IBD, chronic diarrhea, malabsorption).

6. Positive urine drug screen or alcohol breath test at screening.

7. Regular alcohol use >14 standard drinks/week or >3 drinks/day.

8. Positive test for HIV, Hepatitis B (HBsAg), or Hepatitis C antibody.

9. History of severe allergies or anaphylaxis, or known hypersensitivity to study drug components.

10. Recent infections requiring parenteral antibiotics within 6 months before first dose.

11. Vaccination with live vaccine within 4 weeks prior to first dose.

12. Blood donation >400 mL within 60 days, or component donation within 30 days prior to dosing.

13. eGFR ≤ 90 mL/min/1.73 m² at screening.

14. Use of nicotine-containing products within 7 days before dosing or unwillingness to abstain during the study.

15. Use of prescription/OTC medications, herbal products, or supplements within 14 days prior to dosing, unless approved by the investigator.

16. Use of CYP3A4 inhibitors/inducers or medications affecting metabolism of VRN110755 within 14 days prior to dosing.

17. Unwillingness to follow dietary restrictions (e.g., cannot consume high-fat meals).

18. Use of proton pump inhibitors, H2 blockers, or antacids within 8 weeks prior to first dose (except planned rabeprazole use in study).

19. Known hypersensitivity to PPIs (e.g., rabeprazole).

20. Planned or current participation in another investigational trial or use of another investigational product within 30 days or 5 half-lives.

21. Poor peripheral venous access.

22. Any condition that, in the opinion of the investigator, would jeopardize participant safety or interfere with study compliance or data integrity.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Voronoi, Inc

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

CMAX Clinical Research Pty Ltd

Adelaide, South Australia, Australia

Site Status: RECRUITING

Countries

Australia

Central Contacts

Rutu Dabhi

Role: CONTACT

dabhirutu@voronoi.io

+1 201-515-9340

Other Identifiers

VRN110755-001

Identifier Type: -

Identifier Source: org_study_id