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

Xspray Pharma

Status and phase: Completed; Phase 1

Conditions: Bioavailability; Pharmacokinetics

Treatments: Drug: XS005 Sorafenib Capsule A - Period 3; Drug: Sorafenib - Period 3; Drug: XS005 Sorafenib Capsule A - Period 2; Drug: XS005 Sorafenib Tablet A - Period 1; Drug: XS005 Sorafenib Tablet A - Period 3; Drug: Sorafenib - Period 2; Drug: Sorafenib - Period 1; Drug: XS005 Sorafenib Capsule A - Period 1; Drug: XS005 Sorafenib Tablet A - Period 2

Study type: Interventional

Funder types: Industry

Identifiers

NCT05967377

XS005-01

Details and patient eligibility

About

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.

Enrollment: 15 patients

Sex: Male

Ages: 18 to 55 years old

Volunteers: Accepts Healthy Volunteers

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.

Trial design

Primary purpose: Other

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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15 participants in 9 patient groups

Sorafenib - Period 1

Active Comparator group

Description:

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.

Treatment:

Drug: Sorafenib - Period 1

XS005 Sorafenib Capsule A - Period 1

Experimental group

Description:

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.

Treatment:

Drug: XS005 Sorafenib Capsule A - Period 1

XS005 Sorafenib Tablet A - Period 1

Experimental group

Description:

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.

Treatment:

Drug: XS005 Sorafenib Tablet A - Period 1

XS005 Sorafenib Capsule A - Period 2

Experimental group

Description:

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.

Treatment:

Drug: XS005 Sorafenib Capsule A - Period 2

XS005 Sorafenib Tablet A - Period 2

Experimental group

Description:

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.

Treatment:

Drug: XS005 Sorafenib Tablet A - Period 2

Sorafenib - Period 2

Active Comparator group

Description:

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.

Treatment:

Drug: Sorafenib - Period 2

XS005 Sorafenib Tablet A - Period 3

Experimental group

Description:

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.

Treatment:

Drug: XS005 Sorafenib Tablet A - Period 3

Sorafenib - Period 3

Active Comparator group

Description:

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.

Treatment:

Drug: Sorafenib - Period 3

XS005 Sorafenib Capsule A - Period 3

Experimental group

Description:

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.

Treatment:

Drug: XS005 Sorafenib Capsule A - Period 3