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

NCT05967377 | Completed Phase 1

• 1 other identifier: XS005-01
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (6)

• Time of Maximum Observed Plasma Concentration (Tmax) of XS005 and Nexavar®

  The pharmacokinetic parameters (Tmax) were determined for the test and reference products (XS005 Sorafenib Capsule A, 2 x 50 mg and XS005 Tablet A, 100 mg and reference Sorafenib tablets (Nexavar®), respectively) for each subject using non-compartmental methods.

  For each study period, blood samples collected at 15 time points (including pre-dose) during the study period on Day 1 and Day 4.

• Maximum Observed Plasma Concentration (Cmax) of XS005 and Nexavar®

  The pharmacokinetic parameters (Cmax) were determined for the test and reference products (XS005 Sorafenib Capsule A, 2 x 50 mg and XS005 Tablet A, 100 mg and reference Sorafenib tablets (Nexavar®), respectively) for each subject using non-compartmental methods.

  For each study period, blood samples collected at 15 time points (including pre-dose) during the study period on Day 1 and Day 4.

• Area Under the Plasma Concentration-Time Curve from 0 time to the last measurable of concentration AUC(0-last) of XS005 and Nexavar®

  The pharmacokinetic parameters AUC(0-last) were determined for the test and reference products (XS005 Sorafenib Capsule A, 2 x 50 mg and XS005 Tablet A, 100 mg and reference Sorafenib tablets (Nexavar®), respectively) for each subject using non-compartmental methods.

  For each study period, blood samples collected at 15 time points (including pre-dose) during the study period on Day 1 and Day 4.

• Area Under the Plasma Concentration-Time Curve from 0 time Extrapolated to Infinity (AUC0-inf) of XS005 and Nexavar®

  The pharmacokinetic parameters (AUC 0-inf) were determined for the test and reference products (XS005 Sorafenib Capsule A, 2 x 50 mg and XS005 Tablet A, 100 mg and reference Sorafenib tablets (Nexavar®), respectively) for each subject using non-compartmental methods.

  For each study period, blood samples collected at 15 time points (including pre-dose) during the study period on Day 1 and Day 4.

• Plasma half-life of drug (T1/2) of XS005 and Nexavar®

  The pharmacokinetic parameters (T1/2) were determined for the test and reference products (XS005 Sorafenib Capsule A, 2 x 50 mg and XS005 Tablet A, 100 mg and reference Sorafenib tablets (Nexavar®), respectively) for each subject using non-compartmental methods.

  For each study period, blood samples collected at 15 time points (including pre-dose) during the study period on Day 1 and Day 4.

• Relative bioavailability (Frel) of XS005 and Nexavar®

  The relative bioavailability (Frel) of Sorafenib following administration of XS005 Sorafenib Capsule A, 50 mg and Tablet A, 100 mg compared to reference Sorafenib tablets (Nexavar®).

  For each study period, blood samples collected at 15 time points (including pre-dose) during the study period on Day 1 and Day 4.

Secondary Outcomes (15)

• Treatment-emergent adverse events (TEAEs) (ie those beginning after dosing with study drug)

  Adverse event (AE) information collected through study completion, an average of 10 weeks.

• Systolic Blood Pressure (mmHg)

  For each study period, Systolic Blood Pressure were collected at 4 time points (including pre-dose) during the study period on Day 1 and Day 2.

• Diastolic Blood Pressure (mmHg)

  For each study period, Diastolic Blood Pressure were collected at 4 time points (including pre-dose) during the study period on Day 1 and Day 2.

• Heart Rate (HR) (bpm)

  For each study period, HR were collected at 4 time points (including pre-dose) during the study period on Day 1 and Day 2.

• ECG (12-lead electrocardiogram) - Ventricular Rate (HR) (bpm)

  For each study period, ECG were collected at 4 time points (including pre-dose) during the study period on Day 1 and Day 2.

Study Arms (9)

Sorafenib - Period 1

ACTIVE COMPARATOR

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.

Drug: Sorafenib - Period 1

XS005 Sorafenib Capsule A - Period 1

EXPERIMENTAL

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.

Drug: XS005 Sorafenib Capsule A - Period 1

XS005 Sorafenib Tablet A - Period 1

EXPERIMENTAL

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.

Drug: XS005 Sorafenib Tablet A - Period 1

XS005 Sorafenib Capsule A - Period 2

EXPERIMENTAL

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.

Drug: XS005 Sorafenib Capsule A - Period 2

XS005 Sorafenib Tablet A - Period 2

EXPERIMENTAL

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.

Drug: XS005 Sorafenib Tablet A - Period 2

Sorafenib - Period 2

ACTIVE COMPARATOR

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.

Drug: Sorafenib - Period 2

XS005 Sorafenib Tablet A - Period 3

EXPERIMENTAL

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.

Drug: XS005 Sorafenib Tablet A - Period 3

Sorafenib - Period 3

ACTIVE COMPARATOR

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.

Drug: Sorafenib - Period 3

XS005 Sorafenib Capsule A - Period 3

EXPERIMENTAL

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.

Drug: XS005 Sorafenib Capsule A - Period 3

Interventions

Sorafenib - Period 1 DRUG

Sorafenib (Nexavar®) Tablet, 200 mg

Also known as: Regimen A (reference)

Sorafenib - Period 1

XS005 Sorafenib Capsule A - Period 1 DRUG

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

Also known as: Regimen B

XS005 Sorafenib Capsule A - Period 1

XS005 Sorafenib Tablet A - Period 1 DRUG

XS005 Sorafenib Tablet A, 100 mg

Also known as: Regimen C

XS005 Sorafenib Tablet A - Period 1

XS005 Sorafenib Capsule A - Period 2 DRUG

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

Also known as: Regimen B

XS005 Sorafenib Capsule A - Period 2

XS005 Sorafenib Tablet A - Period 2 DRUG

XS005 Sorafenib Tablet A, 100 mg

Also known as: Regimen C

XS005 Sorafenib Tablet A - Period 2

Sorafenib - Period 2 DRUG

Sorafenib (Nexavar®) Tablet, 200 mg

Also known as: Regimen A (reference)

Sorafenib - Period 2

XS005 Sorafenib Tablet A - Period 3 DRUG

XS005 Sorafenib Tablet A, 100 mg

Also known as: Regimen C

XS005 Sorafenib Tablet A - Period 3

Sorafenib - Period 3 DRUG

Sorafenib (Nexavar®) Tablet, 200 mg

Also known as: Regimen A (reference)

Sorafenib - Period 3

XS005 Sorafenib Capsule A - Period 3 DRUG

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

Also known as: Regimen B

XS005 Sorafenib Capsule A - Period 3

Eligibility Criteria

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

You may qualify if:

• Healthy males.
• Age 18 to 55 years of age.
• Body mass index (BMI) of 18.0 to 32.0 kg/m2.
• Must be willing and able to communicate and participate in the whole study.
• Must provide written informed consent.
• 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).
• Must adhere to the contraception requirements.

You may not qualify if:

• Subjects who have received any IMP in a clinical research study within the previous 3 months.
• Subjects who are study site employees, or immediate family members of a study site or sponsor employee.
• Subjects who have previously been enrolled in this study.
• History of any drug or alcohol abuse in the past 2 years.
• 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).
• 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.
• Current users of e-cigarettes and nicotine replacement products and those who have used these products within the last 12 months.
• Subjects who do not have suitable veins for multiple venepunctures/cannulation as assessed by the investigator at screening.
• Clinically significant abnormal biochemistry, haematology or urinalysis as judged by the investigator.
• Subjects has amylase or lipase result exceeding \>1.5 x upper limit of normal (ULN) at screening.
• Positive drugs of abuse or alcohol breath test result.
• Positive hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab) or human immunodeficiency virus (HIV) results.
• History of clinically significant cardiovascular, renal, hepatic, chronic respiratory or gastrointestinal disease, neurological or psychiatric disorder, as judged by the investigator.
• 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).
• Serious adverse reaction or serious hypersensitivity to any drug or the formulation excipients.

Sponsors & Collaborators

• Xspray Pharma AB: lead

Study Sites (1)

Quotient Sciences

Nottingham, NG11 6JS, United Kingdom

Location

MeSH Terms

Interventions

Regimen B

Study Officials

• Sharan Sidhu, MBChB, BAO, MRCS, MFPM

  Quotient Sciences

  PRINCIPAL INVESTIGATOR

Study Design

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

Model Details: Single centre, open-label, randomised, single dose, 3-way crossover comparative (PK) and bioavailability study.

Study Record Dates

• First Submitted: June 26, 2023
• First Posted: August 1, 2023
• Study Start: November 16, 2018
• Primary Completion: February 12, 2019
• Study Completion: February 12, 2019
• Last Updated: August 1, 2023

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)