Evaluating the Effects of Omeprazole on the Pharmacokinetics of XS004 (Dasatinib) Tablets in Healthy Adult Subjects Under Fasting Conditions

Study Overview
=================
Brief Summary
-----------------
In this open label, single-sequence study, subjects received one dose of XS004 Dasatinib Amorphous Solid Dispersion Film-Coated Tablet, 90 mg Test Formulation at the start of study on Day 1 and Day 6. Omeprazole 40 mg was administered on Day 2, 3, 4, 5 and 6. The study was conducted in two groups.

Official Title
-----------------
An Open Label, Non-Randomized, Two-Treatment, Single-Period, Single-Dose, Drug-Drug Interaction Study to Evaluate the Effects of Omeprazole on the Pharmacokinetics of XS004 (Dasatinib) 90 mg Film-Coated Tablets in Healthy Adult Subjects Under Fasting Conditions

Conditions
-----------------
Pharmacokinetics, Drug Interactions

Intervention / Treatment
-----------------
* Drug: Dasatinib ASD
* Drug: Omeprazole 40 MG


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age: 18-60 years Sex: Healthy adult males (sterile or using contraception) and females of non-childbearing potential Clinical laboratory values should be within the laboratory's stated normal range. If not within this range, they must be without clinical significance, as determined by the Investigator No clinically significant diseases captured in the medical history or evidence of clinically significant findings on the physical examination (including vital signs) and/or ECG, as determined by the Investigator Any abnormalities/deviations from the acceptable range of medical history, laboratory values, ECG, and vital signs that might be considered clinically relevant by the study physician or Investigator will be evaluated as individual cases Able to comply with study procedures, in the opinion of the Investigator(s) Willing to give written consent, pregnancy outcome consent, and adhere to all the requirements of this protocol Exclusion Criteria: Any major illness in the last three months or any significant ongoing chronic medical illness Does not agree to consume the provided meals Participation in any clinical trial 30 days prior to dosing Positive results for drugs of abuse or alcohol breath analysis prior to dosing Positive screening results to HIV Ag/Ab Combo, Hepatitis B surface Antigen, Hepatitis C Virus, or anti-HBc tests Females currently breastfeeding, demonstrating a positive pregnancy screen, or using hormone replacement therapy within three months prior to dosing

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Other
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dasatinib ASD alone<br>At the clinic, participants were administered a single oral dose of 90 mg Dasatinib (Amorphous Solid Dispersion Film-Coated Tablet) on Day 1 after an overnight fast of at least 9 hours. Dasatinib was given with approximately 240 mL of room temperature water. Fasting continued for at least 4 hours following drug administration, after which a standardized lunch was served. | Drug: Dasatinib ASD<br>* XS004 Dasatinib Amorphous Solid Dispersion Film-Coated Tablet, 90 mg Test Formulation<br>|
| Other: Dasatinib ASD + Omeprazole<br>At the clinic, on Day 2 to Day 6, participants were administered a single oral dose of Omeprazole 40 mg × 1 Delayed Release Capsule once before meals in the evening with approximately 150 mL of room temperature water. No food was allowed two hours before and one hour after administration of Omeprazole. In addition, participants were administered a single oral dose of 90 mg Dasatinib (Amorphous Solid Dispersion Film-Coated Tablet) on Day 6 after an overnight fast of at least 9 hours. Dasatinib was given with approximately 240 mL of room temperature water. Fasting continued for at least 4 hours following drug administration, after which a standardized lunch was served. | Drug: Dasatinib ASD<br>* XS004 Dasatinib Amorphous Solid Dispersion Film-Coated Tablet, 90 mg Test Formulation<br>Drug: Omeprazole 40 MG<br>* Omeprazole Delayed Release Capsules, USP 40 mg<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Observed Plasma Concentration of Dasatinib (Cmax) | Pharmacokinetic parameters (Cmax) for plasma dasatinib on Day 1 (Dasatinib alone) and on Day 6 (Dasatinib + Omeprazole) calculated for each subject using drug concentration-time data by non-compartmental methods. | Blood samples collected at 15 time points (including pre-dose) during the study period on Day 1 and Day 6. | 
| Area Under the Plasma Concentration-Time Curve from Zero to 24h | Pharmacokinetic parameters (AUC 0-24) for plasma dasatinib on Day 1 (Dasatinib alone) and on Day 6 (Dasatinib + Omeprazole) calculated for each subject using drug concentration-time data by non-compartmental methods. | Blood samples collected at 15 time points (including pre-dose) during the study period on Day 1 and Day 6. | 
| Area Under the Plasma Concentration-Time Curve from Zero Extrapolated to Infinity | Pharmacokinetic parameters (AUC 0-INF) for plasma dasatinib on Day 1 (Dasatinib alone) and on Day 6 (Dasatinib + Omeprazole) calculated for each subject using drug concentration-time data by non-compartmental methods. | Blood samples collected at 15 time points (including pre-dose) during the study period on Day 1 and Day 6. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Plasma Concentration-Time Curve (Percent Extrapolation) | Pharmacokinetic parameters (AUC %Extrapolation) for plasma dasatinib on Day 1 (Dasatinib alone) and on Day 6 (Dasatinib + Omeprazole) calculated for each subject using drug concentration-time data by non-compartmental methods. | Blood samples collected at 15 time points (including pre-dose) during the study period on Day 1 and Day 6. | 
| Time of Maximum Observed Plasma Concentration of Dasatinib (Tmax) | Pharmacokinetic parameters (Tmax) for plasma dasatinib on Day 1 (Dasatinib alone) and on Day 6 (Dasatinib + Omeprazole) calculated for each subject using drug concentration-time data by non-compartmental methods. | Blood samples collected at 15 time points (including pre-dose) during the study period on Day 1 and Day 6. | 
| Elimination Rate Constant (Kel) | Pharmacokinetic parameters (Kel) for plasma dasatinib on Day 1 (Dasatinib alone) and on Day 6 (Dasatinib + Omeprazole) calculated for each subject using drug concentration-time data by non-compartmental methods. Apparent first order elimination rate constant calculated from a semi-log plot of plasma concentration versus time point. | Blood samples collected at 15 time points (including pre-dose) during the study period on Day 1 and Day 6. | 
| Terminal Half-Life (T1/2) | Pharmacokinetic parameters (T1/2) for plasma dasatinib on Day 1 (Dasatinib alone) and on Day 6 (Dasatinib + Omeprazole) calculated for each subject using drug concentration-time data by non-compartmental methods. | Blood samples collected at 15 time points (including pre-dose) during the study period on Day 1 and Day 6. |