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Comparative Bioavailability of XS004 (Dasatinib) Formulation G and SPRYCEL® (Dasatinib) in Healthy, Adult Subjects Under Fasting Conditions

Phase 1
Completed
Conditions
Biological Availability
Interventions
Registration Number
NCT05439408
Lead Sponsor
Xspray Pharma AB
Brief Summary

An open label, single-center, balanced, randomized, two-treatment, two-sequence, four-period, full replicate, crossover, single dose, Phase I, oral comparative bioavailability study in healthy, adult participants (male subjects and female subjects of non-childbearing potential) under fasting conditions with a screening period of 21 days prior to enrollment. In each study period, 21 blood samples were collected from each participant to analyze the pharmacokinetic profile of the test as well as the reference drug.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
110
Inclusion Criteria
  • Healthy males (sterile or using contraception) or females of non-childbearing potential 18 and 55 years of age
  • Acceptable medical history, physical examination, laboratory investigations within 21 days prior to enrollment
  • Clinical laboratory values were within the laboratory's stated normal range. If not within this range, they must be without clinical significance, as determined by the Investigator
  • The subject is able to communicate meaningfully with study personnel and is anticipated to be able to comply fully with study procedures
Exclusion Criteria
  • Any history of impairment of cardiovascular, pulmonary, hepatic, renal, gastrointestinal, endocrine, immunological, dermatological, neurological, psychiatric disease or disorder
  • Participated in any other clinical study or donated blood in last 90 days
  • Positive screens for serum hepatitis B surface antigen (HbsAg), hepatitis C antibody (HepC) or human immunodeficiency virus (HIV)
  • Female subjects demonstrating a positive pregnancy screen, currently breastfeeding or using hormone replacement therapy within three months prior to dosing of test product

Study & Design

Study Type
INTERVENTIONAL
Study Design
CROSSOVER
Arm && Interventions
GroupInterventionDescription
XS004 - Period 2Dasatinib ASD 100 mgAt the clinic, after an overnight fast of at least 10 hours, a single oral dose of 100 mg tablet was administered to each participant in a sitting posture with about 240 mL of drinking water in the presence of the principal investigator and quality assurance personnel and in accordance with the randomization schedule.
XS004 - Period 1Dasatinib ASD 100 mgAt the clinic, after an overnight fast of at least 10 hours, a single oral dose of 100 mg tablet was administered to each participant in a sitting posture with about 240 mL of drinking water in the presence of the principal investigator and quality assurance personnel and in accordance with the randomization schedule.
SPRYCEL - Period 3Dasatinib 140 MG [Sprycel]At the clinic, after an overnight fast of at least 10 hours, a single oral dose of 140 mg tablet was administered to each participant in a sitting posture with about 240 mL of drinking water in the presence of the principal investigator and quality assurance personnel, and in accordance with the randomization schedule.
XS004 - Period 4Dasatinib ASD 100 mgAt the clinic, after an overnight fast of at least 10 hours, a single oral dose of 100 mg tablet was administered to each participant in a sitting posture with about 240 mL of drinking water in the presence of the principal investigator and quality assurance personnel and in accordance with the randomization schedule.
SPRYCEL - Period 4Dasatinib 140 MG [Sprycel]At the clinic, after an overnight fast of at least 10 hours, a single oral dose of 140 mg tablet was administered to each participant in a sitting posture with about 240 mL of drinking water in the presence of the principal investigator and quality assurance personnel, and in accordance with the randomization schedule.
SPRYCEL - Period 1Dasatinib 140 MG [Sprycel]At the clinic, after an overnight fast of at least 10 hours, a single oral dose of 140 mg tablet was administered to each participant in a sitting posture with about 240 mL of drinking water in the presence of the principal investigator and quality assurance personnel, and in accordance with the randomization schedule.
XS004 - Period 3Dasatinib ASD 100 mgAt the clinic, after an overnight fast of at least 10 hours, a single oral dose of 100 mg tablet was administered to each participant in a sitting posture with about 240 mL of drinking water in the presence of the principal investigator and quality assurance personnel and in accordance with the randomization schedule.
SPRYCEL - Period 2Dasatinib 140 MG [Sprycel]At the clinic, after an overnight fast of at least 10 hours, a single oral dose of 140 mg tablet was administered to each participant in a sitting posture with about 240 mL of drinking water in the presence of the principal investigator and quality assurance personnel, and in accordance with the randomization schedule.
Primary Outcome Measures
NameTimeMethod
Area Under the Plasma Concentration-Time Curve from Zero to the Last Measurable Concentration (AUC0-t) of XS004 and SPRYCEL®For each study period, blood samples were drawn at pre-dose (0.00) and at 0.25, 0.33, 0.50, 0.75, 1.00, 1.25, 1.50, 1.75, 2.00, 2.50, 3.00, 4.00, 5.00, 6.00, 8.00, 12.00, 16.00, 20.00, 24.00, and 30.00 hours post-dose.

The pharmacokinetic parameters (AUC 0-t) were determined for the test and reference products (XS004 and SPRYCEL®, respectively) for each subject using non-compartmental methods.

Maximum Observed Plasma Concentration (Cmax) of XS004 and SPRYCEL®For each study period, blood samples were drawn at pre-dose (0.00) and at 0.25, 0.33, 0.50, 0.75, 1.00, 1.25, 1.50, 1.75, 2.00, 2.50, 3.00, 4.00, 5.00, 6.00, 8.00, 12.00, 16.00, 20.00, 24.00, and 30.00 hours post-dose.

The pharmacokinetic parameters (Cmax) were determined for the test and reference products (XS004 and SPRYCEL®, respectively) for each subject using non-compartmental methods.

Area Under the Plasma Concentration-Time Curve from Zero Extrapolated to Infinity (AUC0-inf) of XS004 and SPRYCEL®For each study period, blood samples were drawn at pre-dose (0.00) and at 0.25, 0.33, 0.50, 0.75, 1.00, 1.25, 1.50, 1.75, 2.00, 2.50, 3.00, 4.00, 5.00, 6.00, 8.00, 12.00, 16.00, 20.00, 24.00, and 30.00 hours post-dose.

The pharmacokinetic parameters (AUC 0-inf) were determined for the test and reference products (XS004 and SPRYCEL®, respectively) for each subject using non-compartmental methods.

Secondary Outcome Measures
NameTimeMethod
Time of Maximum Observed Plasma Concentration (Tmax) of XS004 and SPRYCEL®For each study period, blood samples were drawn at pre-dose (0.00) and at 0.25, 0.33, 0.50, 0.75, 1.00, 1.25, 1.50, 1.75, 2.00, 2.50, 3.00, 4.00, 5.00, 6.00, 8.00, 12.00, 16.00, 20.00, 24.00, and 30.00 hours post-dose.

The pharmacokinetic parameters (Tmax) were determined for the test and reference products (XS004 and SPRYCEL®, respectively) for each subject using non-compartmental methods.

Lower Limit on Time for Elimination Rate Constant (Kel_lower) of XS004 and SPRYCEL®For each study period, blood samples were drawn at pre-dose (0.00) and at 0.25, 0.33, 0.50, 0.75, 1.00, 1.25, 1.50, 1.75, 2.00, 2.50, 3.00, 4.00, 5.00, 6.00, 8.00, 12.00, 16.00, 20.00, 24.00, and 30.00 hours post-dose.

The pharmacokinetic parameters (Kel_lower) were determined for the test and reference products (XS004 and SPRYCEL®, respectively) for each subject using non-compartmental methods. Apparent first-order terminal elimination rate constant calculated from a semi-log plot of the plasma concentration versus time curve. Kel_lower is the lower limit on time for the elimination rate constant.

Area Under the Plasma Concentration-Time Curve (Percent Extrapolation) of XS004 and SPRYCEL®For each study period, blood samples were drawn at pre-dose (0.00) and at 0.25, 0.33, 0.50, 0.75, 1.00, 1.25, 1.50, 1.75, 2.00, 2.50, 3.00, 4.00, 5.00, 6.00, 8.00, 12.00, 16.00, 20.00, 24.00, and 30.00 hours post-dose.

The pharmacokinetic parameters (AUC %Extrap) were determined for the test and reference products (XS004 and SPRYCEL®, respectively) for each subject using non-compartmental methods.

Elimination Rate Constant (Kel) of XS004 and SPRYCEL®For each study period, blood samples were drawn at pre-dose (0.00) and at 0.25, 0.33, 0.50, 0.75, 1.00, 1.25, 1.50, 1.75, 2.00, 2.50, 3.00, 4.00, 5.00, 6.00, 8.00, 12.00, 16.00, 20.00, 24.00, and 30.00 hours post-dose.

The pharmacokinetic parameters (Kel) were determined for the test and reference products (XS004 and SPRYCEL®, respectively) for each subject using non-compartmental methods. Apparent first-order terminal elimination rate constant calculated from a semi-log plot of the plasma concentration versus time curve.

Upper Limit on Time for Elimination Rate Constant (Kel_upper) of XS004 and SPRYCEL®For each study period, blood samples were drawn at pre-dose (0.00) and at 0.25, 0.33, 0.50, 0.75, 1.00, 1.25, 1.50, 1.75, 2.00, 2.50, 3.00, 4.00, 5.00, 6.00, 8.00, 12.00, 16.00, 20.00, 24.00, and 30.00 hours post-dose.

The pharmacokinetic parameters (Kel_upper) were determined for the test and reference products (XS004 and SPRYCEL®, respectively) for each subject using non-compartmental methods. Apparent first-order terminal elimination rate constant calculated from a semi-log plot of the plasma concentration versus time curve. Kel_upper is the upper limit on time for the elimination rate constant.

Terminal Half-Life (T1/2) of XS004 and SPRYCEL®For each study period, blood samples were drawn at pre-dose (0.00) and at 0.25, 0.33, 0.50, 0.75, 1.00, 1.25, 1.50, 1.75, 2.00, 2.50, 3.00, 4.00, 5.00, 6.00, 8.00, 12.00, 16.00, 20.00, 24.00, and 30.00 hours post-dose.

The pharmacokinetic parameters (T1/2) were determined for the test and reference products (XS004 and SPRYCEL®, respectively) for each subject using non-compartmental methods.

Trial Locations

Locations (1)

QPS Bioserve India Pvt Limited

🇮🇳

Hyderabad, India

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