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

Biological Availability Clinical Trial

Official title:

An Open Label, Balanced, Randomized, Two-Treatment, Two-Sequence, Four-Period, Full Replicate, Crossover, Single Dose, Oral Comparative Bioavailability Study of XS004 (Dasatinib) 100 mg Film-Coated Tablets, Formulation G of Xspray Pharma AB, Sweden, and SPRYCEL® (Dasatinib) 140 mg Film-Coated Tablets of Bristol-Myers Squibb Company, Princeton, NJ 08543 USA in Healthy, Adult Subjects Under Fasting Conditions

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05439408
• Other study ID #: XS004-15
• Status: Completed
• Phase: Phase 1
• Start date: June 7, 2021
• Est. completion date: June 25, 2021

Study information

• Verified date: June 2022
• Source: Xspray Pharma AB
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 110
• Est. completion date: June 25, 2021
• Est. primary completion date: June 25, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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

Related Conditions & MeSH terms

• Biological Availability

Intervention

Drug:
• Dasatinib ASD 100 mg
XS004 Dasatinib Amorphous Solid Dispersion Film-Coated Tablet, 100 mg Test Formulation
• Dasatinib 140 MG [Sprycel]
SPRYCEL® (dasatinib) 140 mg Film-Coated Tablets

Locations

Country	Name	City	State
India	QPS Bioserve India Pvt Limited	Hyderabad

Sponsors (2)

Lead Sponsor	Collaborator
Xspray Pharma AB	QPS Bioserve India Pvt Limited

Country where clinical trial is conducted

India, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum Observed Plasma Concentration (Cmax) of XS004 and SPRYCEL®	The pharmacokinetic parameters (Cmax) were determined for the test and reference products (XS004 and SPRYCEL®, respectively) for each subject using non-compartmental methods.	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.
Primary	Area Under the Plasma Concentration-Time Curve from Zero to the Last Measurable Concentration (AUC0-t) of XS004 and SPRYCEL®	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.	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.
Primary	Area Under the Plasma Concentration-Time Curve from Zero Extrapolated to Infinity (AUC0-inf) of XS004 and SPRYCEL®	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.	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.
Secondary	Area Under the Plasma Concentration-Time Curve (Percent Extrapolation) of XS004 and SPRYCEL®	The pharmacokinetic parameters (AUC %Extrap) were determined for the test and reference products (XS004 and SPRYCEL®, respectively) for each subject using non-compartmental methods.	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.
Secondary	Time of Maximum Observed Plasma Concentration (Tmax) of XS004 and SPRYCEL®	The pharmacokinetic parameters (Tmax) were determined for the test and reference products (XS004 and SPRYCEL®, respectively) for each subject using non-compartmental methods.	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.
Secondary	Terminal Half-Life (T1/2) of XS004 and SPRYCEL®	The pharmacokinetic parameters (T1/2) were determined for the test and reference products (XS004 and SPRYCEL®, respectively) for each subject using non-compartmental methods.	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.
Secondary	Elimination Rate Constant (Kel) of XS004 and SPRYCEL®	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.	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.
Secondary	Lower Limit on Time for Elimination Rate Constant (Kel_lower) of XS004 and SPRYCEL®	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.	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.
Secondary	Upper Limit on Time for Elimination Rate Constant (Kel_upper) of XS004 and SPRYCEL®	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.	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.