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

NCT05439408 | Completed Phase 1 FDA Drug

• 1 other identifier: XS004-15
• Study Type: interventional
• Target: 110
• Locations: 1 country
• Sites: 1

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.

Conditions

Biological Availability

Outcome Measures

Primary Outcomes (3)

• 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.

• 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.

• 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 Outcomes (6)

• 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.

• 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.

• 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.

• 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.

• 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.

Study Arms (8)

XS004 - Period 1

EXPERIMENTAL

At 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.

Drug: Dasatinib ASD 100 mg

SPRYCEL - Period 1

ACTIVE COMPARATOR

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.

Drug: Dasatinib 140 MG [Sprycel]

XS004 - Period 2

EXPERIMENTAL

At 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.

Drug: Dasatinib ASD 100 mg

SPRYCEL - Period 2

ACTIVE COMPARATOR

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.

Drug: Dasatinib 140 MG [Sprycel]

XS004 - Period 3

EXPERIMENTAL

At 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.

Drug: Dasatinib ASD 100 mg

SPRYCEL - Period 3

ACTIVE COMPARATOR

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.

Drug: Dasatinib 140 MG [Sprycel]

XS004 - Period 4

EXPERIMENTAL

At 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.

Drug: Dasatinib ASD 100 mg

SPRYCEL - Period 4

ACTIVE COMPARATOR

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.

Drug: Dasatinib 140 MG [Sprycel]

Interventions

Dasatinib ASD 100 mg DRUG

XS004 Dasatinib Amorphous Solid Dispersion Film-Coated Tablet, 100 mg Test Formulation

XS004 - Period 1; XS004 - Period 2; XS004 - Period 3; XS004 - Period 4

Dasatinib 140 MG [Sprycel] DRUG

SPRYCEL® (dasatinib) 140 mg Film-Coated Tablets

SPRYCEL - Period 1; SPRYCEL - Period 2; SPRYCEL - Period 3; SPRYCEL - Period 4

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Xspray Pharma AB: lead
• QPS Bioserve India Pvt Limited: collaborator

Study Sites (1)

QPS Bioserve India Pvt Limited

Hyderabad, 500037, India

Location

MeSH Terms

Interventions

Dasatinib

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines

Study Officials

• Per Andersson, PhD

  Xspray Pharma AB

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 21, 2022
• First Posted: June 30, 2022
• Study Start: June 7, 2021
• Primary Completion: June 25, 2021
• Study Completion: June 25, 2021
• Last Updated: June 30, 2022

Record last verified: 2022-06

Data Sharing

• IPD Sharing: Will not share

Locations

IN (1)