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

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

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.

Study Overview

• Status: Completed
• Conditions: Pharmacokinetics; Drug Interactions
• Intervention / Treatment: Drug: Dasatinib ASD; Drug: Omeprazole 40 MG

• Study Type: Interventional
• Enrollment (Actual): 17
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Dilworth, Minnesota, United States, 56529-1342
      • Axis Clinicals

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dasatinib ASD alone; 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; XS004 Dasatinib Amorphous Solid Dispersion Film-Coated Tablet, 90 mg Test Formulation
Other: Dasatinib ASD + Omeprazole; 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; XS004 Dasatinib Amorphous Solid Dispersion Film-Coated Tablet, 90 mg Test Formulation; Drug: Omeprazole 40 MG; Omeprazole Delayed Release Capsules, USP 40 mg

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.

Collaborators and Investigators

• Sponsor: Xspray Pharma AB
• Collaborators: Axis Clinicals Limited
• Investigators: Study Director: Per Andersson, PhD, Xspray Pharma AB

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2020
• Primary Completion (Actual): December 19, 2020
• Study Completion (Actual): December 19, 2020

Study Registration Dates

• First Submitted: June 21, 2022
• First Submitted That Met QC Criteria: June 21, 2022
• First Posted (Actual): June 27, 2022

Study Record Updates

• Last Update Posted (Actual): June 27, 2022
• Last Update Submitted That Met QC Criteria: June 21, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Gastrointestinal Agents; Protein Kinase Inhibitors; Anti-Ulcer Agents; Proton Pump Inhibitors; Omeprazole; Dasatinib
• Other Study ID Numbers: XS004-09

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No