Evaluating the Pharmacokinetic Parameters and Relative Bioavailability of Sorafenib (XS005) in Healthy Male Subjects

NCT ID: NCT05967377

Last Updated: 2023-08-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 15 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-11-16
• Study Completion Date: 2019-02-12

Brief Summary

This is a single centre, open-label, randomised, single dose, 3-way crossover comparative (PK) and bioavailability study in healthy male subjects comparing a 200 mg Sorafenib (Nexavar®) reference tablet (Regimen A) to XS005 Sorafenib Capsule A, 2 x 50 mg (Regimen B) and XS005 Sorafenib Tablet A,100 mg (Regimen C) formulation. It is planned to enroll 15 subjects who will receive single oral doses of investigational medicinal product (IMP) across 3 treatment periods.

Conditions

Pharmacokinetics; Bioavailability

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

Sorafenib - Period 1

Subjects were admitted to the clinical unit in the morning of Day 1, and dosed with 200 mg Sorafenib (Nexavar®) in the morning of Day 1 following an overnight fast of a minimum of 10 h. Subjects remained in clinical unit until 24 h post dose (Day 2) when they were discharged from the clinical unit, and then returned to the clinical unit at 48 h and 72 h post-dose (Days 3 and 4) for a PK blood sample.The minimum washout before the next dosing period was 10 days.

Group Type: ACTIVE_COMPARATOR

Sorafenib - Period 1

Intervention Type: DRUG

Sorafenib (Nexavar®) Tablet, 200 mg

XS005 Sorafenib Capsule A - Period 1

Subjects were admitted to the clinical unit in the morning of Day 1, and dosed with 100 mg (2 x 50 mg) XS005 Sorafenib Capsule A in the morning of Day 1 following an overnight fast of a minimum of 10 h. Subjects remained in clinical unit until 24 h post dose (Day 2) when they were discharged from the clinical unit, and then returned to the clinical unit at 48 h and 72 h post-dose (Days 3 and 4) for a PK blood sample.The minimum washout before the next dosing period was 10 days.

Group Type: EXPERIMENTAL

XS005 Sorafenib Capsule A - Period 1

Intervention Type: DRUG

XS005 Sorafenib Capsule A, 100 mg (2 x 50 mg)

XS005 Sorafenib Tablet A - Period 1

Subjects were admitted to the clinical unit in the morning of Day 1, and dosed with 100 mg XS005 Sorafenib Tablet A in the morning of Day 1 following an overnight fast of a minimum of 10 h. Subjects remained in clinical unit until 24 h post dose (Day 2) when they were discharged from the clinical unit, and then returned to the clinical unit at 48 h and 72 h post-dose (Days 3 and 4) for a PK blood sample.The minimum washout before the next dosing period was 10 days.

Group Type: EXPERIMENTAL

XS005 Sorafenib Tablet A - Period 1

Intervention Type: DRUG

XS005 Sorafenib Tablet A, 100 mg

XS005 Sorafenib Capsule A - Period 2

Subjects were admitted to the clinical unit in the morning of Day 1, and dosed with 100 mg (2 x 50 mg) XS005 Sorafenib Capsule A in the morning of Day 1 following an overnight fast of a minimum of 10 h. Subjects remained in clinical unit until 24 h post dose (Day 2) when they were discharged from the clinical unit, and then returned to the clinical unit at 48 h and 72 h post-dose (Days 3 and 4) for a PK blood sample.The minimum washout before the next dosing period was 10 days.

Group Type: EXPERIMENTAL

XS005 Sorafenib Capsule A - Period 2

Intervention Type: DRUG

XS005 Sorafenib Capsule A, 100 mg (2 x 50 mg)

XS005 Sorafenib Tablet A - Period 2

Subjects were admitted to the clinical unit in the morning of Day 1, and dosed with 100 mg XS005 Sorafenib Tablet A in the morning of Day 1 following an overnight fast of a minimum of 10 h. Subjects remained in clinical unit until 24 h post dose (Day 2) when they were discharged from the clinical unit, and then returned to the clinical unit at 48 h and 72 h post-dose (Days 3 and 4) for a PK blood sample.The minimum washout before the next dosing period was 10 days.

Group Type: EXPERIMENTAL

XS005 Sorafenib Tablet A - Period 2

Intervention Type: DRUG

XS005 Sorafenib Tablet A, 100 mg

Sorafenib - Period 2

Subjects were admitted to the clinical unit in the morning of Day 1, and dosed with 200 mg Sorafenib (Nexavar®) in the morning of Day 1 following an overnight fast of a minimum of 10 h. Subjects remained in clinical unit until 24 h post dose (Day 2) when they were discharged from the clinical unit, and then returned to the clinical unit at 48 h and 72 h post-dose (Days 3 and 4) for a PK blood sample.The minimum washout before the next dosing period was 10 days.

Group Type: ACTIVE_COMPARATOR

Sorafenib - Period 2

Intervention Type: DRUG

Sorafenib (Nexavar®) Tablet, 200 mg

XS005 Sorafenib Tablet A - Period 3

Subjects were admitted to the clinical unit in the morning of Day 1, and dosed with 100 mg XS005 Sorafenib Tablet A in the morning of Day 1 following an overnight fast of a minimum of 10 h. Subjects remained in clinical unit until 24 h post dose (Day 2) when they were discharged from the clinical unit, and then returned to the clinical unit at 48 h and 72 h post-dose (Days 3 and 4) for a PK blood sample.The minimum washout before the next dosing period was 10 days.

Group Type: EXPERIMENTAL

XS005 Sorafenib Tablet A - Period 3

Intervention Type: DRUG

XS005 Sorafenib Tablet A, 100 mg

Sorafenib - Period 3

Subjects were admitted to the clinical unit in the morning of Day 1, and dosed with 200 mg Sorafenib (Nexavar®) in the morning of Day 1 following an overnight fast of a minimum of 10 h. Subjects remained in clinical unit until 24 h post dose (Day 2) when they were discharged from the clinical unit, and then returned to the clinical unit at 48 h and 72 h post-dose (Days 3 and 4) for a PK blood sample.The minimum washout before the next dosing period was 10 days.

Group Type: ACTIVE_COMPARATOR

Sorafenib - Period 3

Intervention Type: DRUG

Sorafenib (Nexavar®) Tablet, 200 mg

XS005 Sorafenib Capsule A - Period 3

Subjects were admitted to the clinical unit in the morning of Day 1, and dosed with 100 mg (2 x 50 mg) XS005 Sorafenib Capsule A in the morning of Day 1 following an overnight fast of a minimum of 10 h. Subjects remained in clinical unit until 24 h post dose (Day 2) when they were discharged from the clinical unit, and then returned to the clinical unit at 48 h and 72 h post-dose (Days 3 and 4) for a PK blood sample.The minimum washout before the next dosing period was 10 days.

Group Type: EXPERIMENTAL

XS005 Sorafenib Capsule A - Period 3

Intervention Type: DRUG

XS005 Sorafenib Capsule A, 100 mg (2 x 50 mg)

Interventions

Sorafenib - Period 1

Sorafenib (Nexavar®) Tablet, 200 mg

Intervention Type: DRUG

XS005 Sorafenib Capsule A - Period 1

XS005 Sorafenib Capsule A, 100 mg (2 x 50 mg)

Intervention Type: DRUG

XS005 Sorafenib Tablet A - Period 1

XS005 Sorafenib Tablet A, 100 mg

Intervention Type: DRUG

XS005 Sorafenib Capsule A - Period 2

XS005 Sorafenib Capsule A, 100 mg (2 x 50 mg)

Intervention Type: DRUG

XS005 Sorafenib Tablet A - Period 2

XS005 Sorafenib Tablet A, 100 mg

Intervention Type: DRUG

Sorafenib - Period 2

Sorafenib (Nexavar®) Tablet, 200 mg

Intervention Type: DRUG

XS005 Sorafenib Tablet A - Period 3

XS005 Sorafenib Tablet A, 100 mg

Intervention Type: DRUG

Sorafenib - Period 3

Sorafenib (Nexavar®) Tablet, 200 mg

Intervention Type: DRUG

XS005 Sorafenib Capsule A - Period 3

XS005 Sorafenib Capsule A, 100 mg (2 x 50 mg)

Intervention Type: DRUG

Other Intervention Names

Regimen A (reference); Regimen B; Regimen C; Regimen B; Regimen C; Regimen A (reference); Regimen C; Regimen A (reference); Regimen B

Eligibility Criteria

Inclusion Criteria

1. Healthy males.

2. Age 18 to 55 years of age.

3. Body mass index (BMI) of 18.0 to 32.0 kg/m2.

4. Must be willing and able to communicate and participate in the whole study.

5. Must provide written informed consent.

6. Good state of health (mentally and physically) as indicated by a comprehensive clinical assessment (detailed medical history and a complete physical examination), ECG and laboratory investigations (haematology, biochemistry and urinalysis).

7. Must adhere to the contraception requirements.

Exclusion Criteria

1. Subjects who have received any IMP in a clinical research study within the previous 3 months.

2. Subjects who are study site employees, or immediate family members of a study site or sponsor employee.

3. Subjects who have previously been enrolled in this study.

4. History of any drug or alcohol abuse in the past 2 years.

5. Regular alcohol consumption >21 units per week (1 unit = ½ pint beer, or a 25 mL shot of 40% spirit, 1.5 to 2 Units = 125 mL glass of wine, depending on type).

6. Current smokers and those who have smoked within the last 12 months. A breath carbon monoxide reading of greater than 10 ppm at screening and admission.

7. Current users of e-cigarettes and nicotine replacement products and those who have used these products within the last 12 months.

8. Subjects who do not have suitable veins for multiple venepunctures/cannulation as assessed by the investigator at screening.

9. Clinically significant abnormal biochemistry, haematology or urinalysis as judged by the investigator.

10. Subjects has amylase or lipase result exceeding >1.5 x upper limit of normal (ULN) at screening.

11. Positive drugs of abuse or alcohol breath test result.

12. Positive hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab) or human immunodeficiency virus (HIV) results.

13. History of clinically significant cardiovascular, renal, hepatic, chronic respiratory or gastrointestinal disease, neurological or psychiatric disorder, as judged by the investigator.

14. Subject has a QT interval corrected by Fredericia (QTcF) >450 ms based on ECG at screening or at pre-dose Period 1 or a history of additional risk factors for Torsades de Pointe (eg hypokalaemia, hypomagnesia, a family history of long QT syndrome).

15. Serious adverse reaction or serious hypersensitivity to any drug or the formulation excipients.

16. Presence or history of clinically significant allergy requiring treatment, as judged by the investigator. Hayfever is allowed unless it is active.

17. Donation or loss of greater than 400 mL of blood within the previous 3 months.

18. Subjects who are taking, or have taken, any prescribed or over-the-counter drug (other than 4 g per day paracetamol) or herbal remedies in the 14 days before IMP administration. Exceptions may apply on a case by case basis, if considered not to interfere with the objectives of the study, as agreed by the PI and sponsor's medical monitor.

19. Subjects with pregnant partners.

20. Failure to satisfy the investigator of fitness to participate for any other reason.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: Yes

Sponsors

Xspray Pharma AB

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Sharan Sidhu, MBChB, BAO, MRCS, MFPM

Role: PRINCIPAL_INVESTIGATOR

Quotient Sciences

Locations

Quotient Sciences

Nottingham, , United Kingdom

Countries

United Kingdom

Other Identifiers

XS005-01

Identifier Type: -

Identifier Source: org_study_id