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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
25
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.
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.
CMAX Clinical Research Pty Ltd
Adelaide, South Australia, Australia
Area Under the Plasma Concentration-Time Curve from Time Zero to Infinity (AUC₀-inf) of VRN110755
To evaluate the effect of food and rabeprazole on the extent of systemic exposure of VRN110755 by measuring AUC₀-inf under fasted, fed, and PPI conditions.
Time frame: Up to 312 hours post-dose (for each treatment period)
Maximum Observed Plasma Concentration (Cmax) of VRN110755
To assess the peak plasma concentration of VRN110755 under different dosing conditions (fasted, fed, fed/fasted + PPI).
Time frame: Up to 312 hours post-dose (for each treatment period)
Time to Maximum Observed Concentration (Tmax) of VRN110755
To assess the time to reach peak concentration of VRN110755 after single-dose oral administration under different conditions.
Time frame: Up to 312 hours post-dose (for each treatment period)
Comparison of Pharmacokinetic Parameters (AUC and Cmax Ratios) Across Treatment Conditions
To compare AUC and Cmax values of VRN110755 between fed vs. fasted, and PPI vs. non-PPI conditions using statistical analysis.
Time frame: Up to 312 hours post-dose (for each treatment period)
Incidence of Treatment-Emergent Adverse Events (TEAEs)
To evaluate the safety and tolerability of single oral doses of VRN110755 administered under fasted, fed, and PPI conditions by assessing the incidence, severity, and relationship of TEAEs.
Time frame: From Day 1 of Period 1 through the End of Study (approximately 76 days per participant)
Incidence of Serious Adverse Events (SAEs)
To monitor and document any SAEs occurring after VRN110755 administration under any treatment condition.
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Time frame: From Day 1 of Period 1 through the End of Study (approximately 76 days per participant)
Number of Participants with Abnormal Clinical Laboratory Test Results
The number of participants exhibiting abnormal laboratory values in hematology, biochemistry, coagulation, or urinalysis assessments..
Time frame: Baseline (Day 1), pre-dose on Day 15 and Day 34, and End-of-Study Visit (Day 48)
Change in 12-lead ECG Parameters From Baseline
Change from baseline in ECG parameters, including heart rate, PR interval, QRS duration, QT interval, and QTcF (Fridericia). ECGs will be recorded after at least 5 minutes of rest in the supine position. Triplicate ECGs will be taken at screening; single ECGs will be performed at other scheduled timepoints unless clinically indicated.
Time frame: Baseline (Day 1), pre-dose on Day 15 and Day 34, and End-of-Study Visit (Day 48)
Change in Systolic Blood Pressure From Baseline
Change from baseline in systolic blood pressure measured after at least 5 minutes of rest in the supine position. Triplicate readings will be performed at pre-dose; single measurements at other scheduled timepoints.
Time frame: Baseline (Day 1), pre-dose on Day 15 and Day 34, and End-of-Study Visit (Day 48).
Change in Diastolic Blood Pressure From Baseline
Change from baseline in diastolic blood pressure measured after at least 5 minutes of rest in the supine position. Triplicate readings will be performed at pre-dose; single measurements at other scheduled timepoints.
Time frame: Baseline (Day 1), pre-dose on Day 15 and Day 34, and End-of-Study Visit (Day 48).
Change in Pulse Rate From Baseline
Change from baseline in pulse rate measured after at least 5 minutes of rest in the supine position. Triplicate readings will be performed at pre-dose; single measurements at other scheduled timepoints.
Time frame: Baseline (Day 1), pre-dose on Day 15 and Day 34, and End-of-Study Visit (Day 48).
Change in Respiratory Rate From Baseline
Change from baseline in respiratory rate measured after at least 5 minutes of rest in the supine position. Triplicate readings will be performed at pre-dose; single measurements at other scheduled timepoints.
Time frame: Baseline (Day 1), pre-dose on Day 15 and Day 34, and End-of-Study Visit (Day 48).
Change in Tympanic Temperature From Baseline
Change from baseline in tympanic temperature measured after at least 5 minutes of rest in the supine position. Triplicate readings will be performed at pre-dose; single measurements at other scheduled timepoints.
Time frame: Baseline (Day 1), pre-dose on Day 15 and Day 34, and End-of-Study Visit (Day 48).
Cumulative Amount Excreted (Ae) of VRN110755
Cumulative amount of VRN110755 excreted in urine, measured over 0 to 24 hours post-dose under different study conditions.
Time frame: 0 to 24 hours post-dose in each study period.
Fraction Excreted (Fe) of VRN110755
Fraction of the administered dose of VRN110755 excreted in urine, measured over 0 to 24 hours post-dose under different study conditions.
Time frame: 0 to 24 hours post-dose in each study period.
Renal Clearance (CLr) of VRN110755
Renal clearance of VRN110755, determined from urinary excretion and plasma concentration data under different study conditions.
Time frame: 0 to 24 hours post-dose in each study period.