xml: <clinical_study>
    <!-- This xml conforms to an XML Schema at:
      https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
    <required_header>
      <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
      <link_text>Link to the current ClinicalTrials.gov record.</link_text>
      <url>https://clinicaltrials.gov/ct2/show/NCT05967377</url>
    </required_header>
    <id_info>
      <org_study_id>XS005-01</org_study_id>
      <nct_id>NCT05967377</nct_id>
    </id_info>
    <brief_title>Evaluating the Pharmacokinetic Parameters and Relative Bioavailability of Sorafenib (XS005) in Healthy Male Subjects</brief_title>
    <official_title>A Single Part, Open-Label, Randomised, Three-Way Crossover Study Designed to Evaluate the Pharmacokinetic Parameters and Relative Bioavailability of Sorafenib From Sorafenib (XS005) Tablets and Capsules Compared With Nexavar® (Reference Product) in Healthy Male Subjects</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Xspray Pharma AB</agency>
        <agency_class>Industry</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Xspray Pharma AB</source>
    <oversight_info>
      <has_dmc>No</has_dmc>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
      <is_us_export>No</is_us_export>
    </oversight_info>
    <brief_summary>
      <textblock>
        This is a single centre, open-label, randomised, single dose, 3-way crossover comparative&#xD;
        (PK) and bioavailability study in healthy male subjects comparing a 200 mg Sorafenib&#xD;
        (Nexavar®) reference tablet (Regimen A) to XS005 Sorafenib Capsule A, 2 x 50 mg (Regimen B)&#xD;
        and XS005 Sorafenib Tablet A,100 mg (Regimen C) formulation. It is planned to enroll 15&#xD;
        subjects who will receive single oral doses of investigational medicinal product (IMP) across&#xD;
        3 treatment periods.&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Completed</overall_status>
    <start_date type="Actual">November 16, 2018</start_date>
    <completion_date type="Actual">February 12, 2019</completion_date>
    <primary_completion_date type="Actual">February 12, 2019</primary_completion_date>
    <phase>Phase 1</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>Randomized</allocation>
      <intervention_model>Crossover Assignment</intervention_model>
      <intervention_model_description>Single centre, open-label, randomised, single dose, 3-way crossover comparative (PK) and bioavailability study.</intervention_model_description>
      <primary_purpose>Other</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Time of Maximum Observed Plasma Concentration (Tmax) of XS005 and Nexavar®</measure>
      <time_frame>For each study period, blood samples collected at 15 time points (including pre-dose) during the study period on Day 1 and Day 4.</time_frame>
      <description>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.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Maximum Observed Plasma Concentration (Cmax) of XS005 and Nexavar®</measure>
      <time_frame>For each study period, blood samples collected at 15 time points (including pre-dose) during the study period on Day 1 and Day 4.</time_frame>
      <description>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.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Area Under the Plasma Concentration-Time Curve from 0 time to the last measurable of concentration AUC(0-last) of XS005 and Nexavar®</measure>
      <time_frame>For each study period, blood samples collected at 15 time points (including pre-dose) during the study period on Day 1 and Day 4.</time_frame>
      <description>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.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Area Under the Plasma Concentration-Time Curve from 0 time Extrapolated to Infinity (AUC0-inf) of XS005 and Nexavar®</measure>
      <time_frame>For each study period, blood samples collected at 15 time points (including pre-dose) during the study period on Day 1 and Day 4.</time_frame>
      <description>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.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Plasma half-life of drug (T1/2) of XS005 and Nexavar®</measure>
      <time_frame>For each study period, blood samples collected at 15 time points (including pre-dose) during the study period on Day 1 and Day 4.</time_frame>
      <description>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.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Relative bioavailability (Frel) of XS005 and Nexavar®</measure>
      <time_frame>For each study period, blood samples collected at 15 time points (including pre-dose) during the study period on Day 1 and Day 4.</time_frame>
      <description>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®).</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Treatment-emergent adverse events (TEAEs) (ie those beginning after dosing with study drug)</measure>
      <time_frame>Adverse event (AE) information collected through study completion, an average of 10 weeks.</time_frame>
      <description>The safety parameters TEAEs were were determined for XS005 Sorafenib Capsule A, 50 mg and Tablet A, 100 mg compared to reference Sorafenib tablets (Nexavar®) for each study subjects using descriptive statistics.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Systolic Blood Pressure (mmHg)</measure>
      <time_frame>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.</time_frame>
      <description>The safety parameters Systolic Blood Pressure (mmHg) were determined for XS005 Sorafenib Capsule A, 50 mg and Tablet A, 100 mg compared to reference Sorafenib tablets (Nexavar®) for each study subjects using descriptive statistics.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Diastolic Blood Pressure (mmHg)</measure>
      <time_frame>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.</time_frame>
      <description>The safety parameters Diastolic Blood Pressure (mmHg) were determined for XS005 Sorafenib Capsule A, 50 mg and Tablet A, 100 mg compared to reference Sorafenib tablets (Nexavar®) for each study subjects using descriptive statistics.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Heart Rate (HR) (bpm)</measure>
      <time_frame>For each study period, HR were collected at 4 time points (including pre-dose) during the study period on Day 1 and Day 2.</time_frame>
      <description>The safety parameters HR summarizes were determined for XS005 Sorafenib Capsule A, 50 mg and Tablet A, 100 mg compared to reference Sorafenib tablets (Nexavar®) for each study subjects using descriptive statistics.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>ECG (12-lead electrocardiogram) - Ventricular Rate (HR) (bpm)</measure>
      <time_frame>For each study period, ECG were collected at 4 time points (including pre-dose) during the study period on Day 1 and Day 2.</time_frame>
      <description>The safety parameters ECG - Ventricular Rate were determined for XS005 Sorafenib Capsule A, 50 mg and Tablet A, 100 mg compared to reference Sorafenib tablets (Nexavar®) for each study subjects using descriptive statistics.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>ECG (12-lead electrocardiogram) - PR Interval (msec)</measure>
      <time_frame>For each study period, ECG were collected at 4 time points (including pre-dose) during the study period on Day 1 and Day 2.</time_frame>
      <description>The safety parameters ECG - PR Interval were determined for XS005 Sorafenib Capsule A, 50 mg and Tablet A, 100 mg compared to reference Sorafenib tablets (Nexavar®) for each study subjects using descriptive statistics.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>ECG (12-lead electrocardiogram) - QRS Duration (msec)</measure>
      <time_frame>For each study period, ECG were collected at 4 time points (including pre-dose) during the study period on Day 1 and Day 2.</time_frame>
      <description>The safety parameters ECG - QRS Duration were determined for XS005 Sorafenib Capsule A, 50 mg and Tablet A, 100 mg compared to reference Sorafenib tablets (Nexavar®) for each study subjects using descriptive statistics.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>ECG (12-lead electrocardiogram) - QT Interval (msec)</measure>
      <time_frame>For each study period, ECG were collected at 4 time points (including pre-dose) during the study period on Day 1 and Day 2.</time_frame>
      <description>The safety parameters ECG - QT Interval were determined for XS005 Sorafenib Capsule A, 50 mg and Tablet A, 100 mg compared to reference Sorafenib tablets (Nexavar®) for each study subjects using descriptive statistics.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>ECG (12-lead electrocardiogram) - QRS Axis (°)</measure>
      <time_frame>For each study period, ECG were collected at 4 time points (including pre-dose) during the study period on Day 1 and Day 2.</time_frame>
      <description>The safety parameters ECG - QRS Axis were determined for XS005 Sorafenib Capsule A, 50 mg and Tablet A, 100 mg compared to reference Sorafenib tablets (Nexavar®) for each study subjects using descriptive statistics.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>ECG (12-lead electrocardiogram) - QTcF Interval (msec)</measure>
      <time_frame>For each study period, ECG were collected at 4 time points (including pre-dose) during the study period on Day 1 and Day 2.</time_frame>
      <description>The safety parameters ECG - QTcF Interval were determined for XS005 Sorafenib Capsule A, 50 mg and Tablet A, 100 mg compared to reference Sorafenib tablets (Nexavar®) for each study subjects using descriptive statistics.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Number of participants with abnormal laboratory values of Clinical Chemistry</measure>
      <time_frame>For each study period, blood samples were collected at 2 time points (including pre-dose) during the study period on Day 1 and Day 2.</time_frame>
      <description>The safety parameters Clinical Chemistry were determined for XS005 Sorafenib Capsule A, 50 mg and Tablet A, 100 mg compared to reference Sorafenib tablets (Nexavar®) for each study subjects using descriptive statistics and presented as number of participants with abnormal laboratory values</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Number of participants with abnormal hematology values</measure>
      <time_frame>For each study period, blood samples were collected at 2 time points (including pre-dose) during the study period on Day1 and Day 2.</time_frame>
      <description>The safety parameters Haematology were determined for XS005 Sorafenib Capsule A, 50 mg and Tablet A, 100 mg compared to reference Sorafenib tablets (Nexavar®) for each study subjects using descriptive statistics and presented as number of participants with abnormal laboratory values</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Number of participants with abnormal urinalysis values</measure>
      <time_frame>For each study period, urine samples were collected at 2 time points (including pre-dose) during the study period on Day1 and Day 2.</time_frame>
      <description>The safety parameters Urinalysis were determined for XS005 Sorafenib Capsule A, 50 mg and Tablet A, 100 mg compared to reference Sorafenib tablets (Nexavar®) for each study subjects using descriptive statistics and presented as number of participants with abnormal laboratory values.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Number of participants with abnormal physical examination outcome</measure>
      <time_frame>For each study period, target (symptom driven) physical examination; each subject was assessed by a physician and a physical examination was performed if the subject reported any AEs, on Day 2.</time_frame>
      <description>The safety parameters physical examination outcome were determined for XS005 Sorafenib Capsule A, 50 mg and Tablet A, 100 mg compared to reference Sorafenib tablets (Nexavar®) for each study subjects using descriptive statistics and presented as number of subjects with abnormal physical examination outcome.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Number of participants with abnormal skin examination outcome</measure>
      <time_frame>For each study period, skin assessments were done at 2 time points (including pre-dose) during the study period on Day 1 and Day 2.</time_frame>
      <description>The safety parameters Skin assessment outcome were determined for XS005 Sorafenib Capsule A, 50 mg and Tablet A, 100 mg compared to reference Sorafenib tablets (Nexavar®) for each study subjects using descriptive statistics and presented as number of subjects with abnormal skin examination outcome.</description>
    </secondary_outcome>
    <number_of_arms>9</number_of_arms>
    <enrollment type="Actual">15</enrollment>
    <condition>Pharmacokinetics</condition>
    <condition>Bioavailability</condition>
    <arm_group>
      <arm_group_label>Sorafenib - Period 1</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <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.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>XS005 Sorafenib Capsule A - Period 1</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <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.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>XS005 Sorafenib Tablet A - Period 1</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <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.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>XS005 Sorafenib Capsule A - Period 2</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <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.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>XS005 Sorafenib Tablet A - Period 2</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <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.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Sorafenib - Period 2</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <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.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>XS005 Sorafenib Tablet A - Period 3</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <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.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Sorafenib - Period 3</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <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.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>XS005 Sorafenib Capsule A - Period 3</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <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.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Sorafenib - Period 1</intervention_name>
      <description>Sorafenib (Nexavar®) Tablet, 200 mg</description>
      <arm_group_label>Sorafenib - Period 1</arm_group_label>
      <other_name>Regimen A (reference)</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>XS005 Sorafenib Capsule A - Period 1</intervention_name>
      <description>XS005 Sorafenib Capsule A, 100 mg (2 x 50 mg)</description>
      <arm_group_label>XS005 Sorafenib Capsule A - Period 1</arm_group_label>
      <other_name>Regimen B</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>XS005 Sorafenib Tablet A - Period 1</intervention_name>
      <description>XS005 Sorafenib Tablet A, 100 mg</description>
      <arm_group_label>XS005 Sorafenib Tablet A - Period 1</arm_group_label>
      <other_name>Regimen C</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>XS005 Sorafenib Capsule A - Period 2</intervention_name>
      <description>XS005 Sorafenib Capsule A, 100 mg (2 x 50 mg)</description>
      <arm_group_label>XS005 Sorafenib Capsule A - Period 2</arm_group_label>
      <other_name>Regimen B</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>XS005 Sorafenib Tablet A - Period 2</intervention_name>
      <description>XS005 Sorafenib Tablet A, 100 mg</description>
      <arm_group_label>XS005 Sorafenib Tablet A - Period 2</arm_group_label>
      <other_name>Regimen C</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Sorafenib - Period 2</intervention_name>
      <description>Sorafenib (Nexavar®) Tablet, 200 mg</description>
      <arm_group_label>Sorafenib - Period 2</arm_group_label>
      <other_name>Regimen A (reference)</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>XS005 Sorafenib Tablet A - Period 3</intervention_name>
      <description>XS005 Sorafenib Tablet A, 100 mg</description>
      <arm_group_label>XS005 Sorafenib Tablet A - Period 3</arm_group_label>
      <other_name>Regimen C</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Sorafenib - Period 3</intervention_name>
      <description>Sorafenib (Nexavar®) Tablet, 200 mg</description>
      <arm_group_label>Sorafenib - Period 3</arm_group_label>
      <other_name>Regimen A (reference)</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>XS005 Sorafenib Capsule A - Period 3</intervention_name>
      <description>XS005 Sorafenib Capsule A, 100 mg (2 x 50 mg)</description>
      <arm_group_label>XS005 Sorafenib Capsule A - Period 3</arm_group_label>
      <other_name>Regimen B</other_name>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. Healthy males.&#xD;
  &#xD;
            2. Age 18 to 55 years of age.&#xD;
  &#xD;
            3. Body mass index (BMI) of 18.0 to 32.0 kg/m2.&#xD;
  &#xD;
            4. Must be willing and able to communicate and participate in the whole study.&#xD;
  &#xD;
            5. Must provide written informed consent.&#xD;
  &#xD;
            6. Good state of health (mentally and physically) as indicated by a comprehensive&#xD;
               clinical assessment (detailed medical history and a complete physical examination),&#xD;
               ECG and laboratory investigations (haematology, biochemistry and urinalysis).&#xD;
  &#xD;
            7. Must adhere to the contraception requirements.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. Subjects who have received any IMP in a clinical research study within the previous 3&#xD;
               months.&#xD;
  &#xD;
            2. Subjects who are study site employees, or immediate family members of a study site or&#xD;
               sponsor employee.&#xD;
  &#xD;
            3. Subjects who have previously been enrolled in this study.&#xD;
  &#xD;
            4. History of any drug or alcohol abuse in the past 2 years.&#xD;
  &#xD;
            5. Regular alcohol consumption &gt;21 units per week (1 unit = ½ pint beer, or a 25 mL shot&#xD;
               of 40% spirit, 1.5 to 2 Units = 125 mL glass of wine, depending on type).&#xD;
  &#xD;
            6. Current smokers and those who have smoked within the last 12 months. A breath carbon&#xD;
               monoxide reading of greater than 10 ppm at screening and admission.&#xD;
  &#xD;
            7. Current users of e-cigarettes and nicotine replacement products and those who have&#xD;
               used these products within the last 12 months.&#xD;
  &#xD;
            8. Subjects who do not have suitable veins for multiple venepunctures/cannulation as&#xD;
               assessed by the investigator at screening.&#xD;
  &#xD;
            9. Clinically significant abnormal biochemistry, haematology or urinalysis as judged by&#xD;
               the investigator.&#xD;
  &#xD;
           10. Subjects has amylase or lipase result exceeding &gt;1.5 x upper limit of normal (ULN) at&#xD;
               screening.&#xD;
  &#xD;
           11. Positive drugs of abuse or alcohol breath test result.&#xD;
  &#xD;
           12. Positive hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab) or&#xD;
               human immunodeficiency virus (HIV) results.&#xD;
  &#xD;
           13. History of clinically significant cardiovascular, renal, hepatic, chronic respiratory&#xD;
               or gastrointestinal disease, neurological or psychiatric disorder, as judged by the&#xD;
               investigator.&#xD;
  &#xD;
           14. Subject has a QT interval corrected by Fredericia (QTcF) &gt;450 ms based on ECG at&#xD;
               screening or at pre-dose Period 1 or a history of additional risk factors for Torsades&#xD;
               de Pointe (eg hypokalaemia, hypomagnesia, a family history of long QT syndrome).&#xD;
  &#xD;
           15. Serious adverse reaction or serious hypersensitivity to any drug or the formulation&#xD;
               excipients.&#xD;
  &#xD;
           16. Presence or history of clinically significant allergy requiring treatment, as judged&#xD;
               by the investigator. Hayfever is allowed unless it is active.&#xD;
  &#xD;
           17. Donation or loss of greater than 400 mL of blood within the previous 3 months.&#xD;
  &#xD;
           18. Subjects who are taking, or have taken, any prescribed or over-the-counter drug (other&#xD;
               than 4 g per day paracetamol) or herbal remedies in the 14 days before IMP&#xD;
               administration. Exceptions may apply on a case by case basis, if considered not to&#xD;
               interfere with the objectives of the study, as agreed by the PI and sponsor's medical&#xD;
               monitor.&#xD;
  &#xD;
           19. Subjects with pregnant partners.&#xD;
  &#xD;
           20. Failure to satisfy the investigator of fitness to participate for any other reason.&#xD;
        </textblock>
      </criteria>
      <gender>Male</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>55 Years</maximum_age>
      <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Sharan Sidhu, MBChB, BAO, MRCS, MFPM</last_name>
      <role>Principal Investigator</role>
      <affiliation>Quotient Sciences</affiliation>
    </overall_official>
    <location>
      <facility>
        <name>Quotient Sciences</name>
        <address>
          <city>Nottingham</city>
          <zip>NG11 6JS</zip>
          <country>United Kingdom</country>
        </address>
      </facility>
    </location>
    <location_countries>
      <country>United Kingdom</country>
    </location_countries>
    <verification_date>July 2023</verification_date>
    <study_first_submitted>June 26, 2023</study_first_submitted>
    <study_first_submitted_qc>July 20, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 1, 2023</study_first_posted>
    <last_update_submitted>July 20, 2023</last_update_submitted>
    <last_update_submitted_qc>July 20, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 1, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Leucovorin</mesh_term>
      <mesh_term>Sorafenib</mesh_term>
      <mesh_term>Fluorouracil</mesh_term>
      <mesh_term>Methotrexate</mesh_term>
      <mesh_term>Carboplatin</mesh_term>
    </intervention_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: download date: ClinicalTrials.gov processed this data on September 20, 2023
  link text: Link to the current ClinicalTrials.gov record.
  url: https://clinicaltrials.gov/ct2/show/NCT05967377
  org study id: XS005-01
  nct id: NCT05967377
  lead sponsor: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  is us export: No
  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.
  allocation: Randomized
  intervention model: Crossover Assignment
  intervention model description: Single centre, open-label, randomised, single dose, 3-way crossover comparative (PK) and bioavailability study.
  primary purpose: Other
  masking: None (Open Label)
  measure: Time of Maximum Observed Plasma Concentration (Tmax) of XS005 and Nexavar®
  time frame: For each study period, blood samples collected at 15 time points (including pre-dose) during the study period on Day 1 and Day 4.
  description: 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.
  measure: Maximum Observed Plasma Concentration (Cmax) of XS005 and Nexavar®
  time frame: For each study period, blood samples collected at 15 time points (including pre-dose) during the study period on Day 1 and Day 4.
  description: 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.
  measure: Area Under the Plasma Concentration-Time Curve from 0 time to the last measurable of concentration AUC(0-last) of XS005 and Nexavar®
  time frame: For each study period, blood samples collected at 15 time points (including pre-dose) during the study period on Day 1 and Day 4.
  description: 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.
  measure: Area Under the Plasma Concentration-Time Curve from 0 time Extrapolated to Infinity (AUC0-inf) of XS005 and Nexavar®
  time frame: For each study period, blood samples collected at 15 time points (including pre-dose) during the study period on Day 1 and Day 4.
  description: 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.
  measure: Plasma half-life of drug (T1/2) of XS005 and Nexavar®
  time frame: For each study period, blood samples collected at 15 time points (including pre-dose) during the study period on Day 1 and Day 4.
  description: 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.
  measure: Relative bioavailability (Frel) of XS005 and Nexavar®
  time frame: For each study period, blood samples collected at 15 time points (including pre-dose) during the study period on Day 1 and Day 4.
  description: 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®).
  measure: Treatment-emergent adverse events (TEAEs) (ie those beginning after dosing with study drug)
  time frame: Adverse event (AE) information collected through study completion, an average of 10 weeks.
  description: The safety parameters TEAEs were were determined for XS005 Sorafenib Capsule A, 50 mg and Tablet A, 100 mg compared to reference Sorafenib tablets (Nexavar®) for each study subjects using descriptive statistics.
  measure: Systolic Blood Pressure (mmHg)
  time frame: 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.
  description: The safety parameters Systolic Blood Pressure (mmHg) were determined for XS005 Sorafenib Capsule A, 50 mg and Tablet A, 100 mg compared to reference Sorafenib tablets (Nexavar®) for each study subjects using descriptive statistics.
  measure: Diastolic Blood Pressure (mmHg)
  time frame: 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.
  description: The safety parameters Diastolic Blood Pressure (mmHg) were determined for XS005 Sorafenib Capsule A, 50 mg and Tablet A, 100 mg compared to reference Sorafenib tablets (Nexavar®) for each study subjects using descriptive statistics.
  measure: Heart Rate (HR) (bpm)
  time frame: For each study period, HR were collected at 4 time points (including pre-dose) during the study period on Day 1 and Day 2.
  description: The safety parameters HR summarizes were determined for XS005 Sorafenib Capsule A, 50 mg and Tablet A, 100 mg compared to reference Sorafenib tablets (Nexavar®) for each study subjects using descriptive statistics.
  measure: ECG (12-lead electrocardiogram) - Ventricular Rate (HR) (bpm)
  time frame: For each study period, ECG were collected at 4 time points (including pre-dose) during the study period on Day 1 and Day 2.
  description: The safety parameters ECG - Ventricular Rate were determined for XS005 Sorafenib Capsule A, 50 mg and Tablet A, 100 mg compared to reference Sorafenib tablets (Nexavar®) for each study subjects using descriptive statistics.
  measure: ECG (12-lead electrocardiogram) - PR Interval (msec)
  time frame: For each study period, ECG were collected at 4 time points (including pre-dose) during the study period on Day 1 and Day 2.
  description: The safety parameters ECG - PR Interval were determined for XS005 Sorafenib Capsule A, 50 mg and Tablet A, 100 mg compared to reference Sorafenib tablets (Nexavar®) for each study subjects using descriptive statistics.
  measure: ECG (12-lead electrocardiogram) - QRS Duration (msec)
  time frame: For each study period, ECG were collected at 4 time points (including pre-dose) during the study period on Day 1 and Day 2.
  description: The safety parameters ECG - QRS Duration were determined for XS005 Sorafenib Capsule A, 50 mg and Tablet A, 100 mg compared to reference Sorafenib tablets (Nexavar®) for each study subjects using descriptive statistics.
  measure: ECG (12-lead electrocardiogram) - QT Interval (msec)
  time frame: For each study period, ECG were collected at 4 time points (including pre-dose) during the study period on Day 1 and Day 2.
  description: The safety parameters ECG - QT Interval were determined for XS005 Sorafenib Capsule A, 50 mg and Tablet A, 100 mg compared to reference Sorafenib tablets (Nexavar®) for each study subjects using descriptive statistics.
  measure: ECG (12-lead electrocardiogram) - QRS Axis (°)
  time frame: For each study period, ECG were collected at 4 time points (including pre-dose) during the study period on Day 1 and Day 2.
  description: The safety parameters ECG - QRS Axis were determined for XS005 Sorafenib Capsule A, 50 mg and Tablet A, 100 mg compared to reference Sorafenib tablets (Nexavar®) for each study subjects using descriptive statistics.
  measure: ECG (12-lead electrocardiogram) - QTcF Interval (msec)
  time frame: For each study period, ECG were collected at 4 time points (including pre-dose) during the study period on Day 1 and Day 2.
  description: The safety parameters ECG - QTcF Interval were determined for XS005 Sorafenib Capsule A, 50 mg and Tablet A, 100 mg compared to reference Sorafenib tablets (Nexavar®) for each study subjects using descriptive statistics.
  measure: Number of participants with abnormal laboratory values of Clinical Chemistry
  time frame: For each study period, blood samples were collected at 2 time points (including pre-dose) during the study period on Day 1 and Day 2.
  description: The safety parameters Clinical Chemistry were determined for XS005 Sorafenib Capsule A, 50 mg and Tablet A, 100 mg compared to reference Sorafenib tablets (Nexavar®) for each study subjects using descriptive statistics and presented as number of participants with abnormal laboratory values
  measure: Number of participants with abnormal hematology values
  time frame: For each study period, blood samples were collected at 2 time points (including pre-dose) during the study period on Day1 and Day 2.
  description: The safety parameters Haematology were determined for XS005 Sorafenib Capsule A, 50 mg and Tablet A, 100 mg compared to reference Sorafenib tablets (Nexavar®) for each study subjects using descriptive statistics and presented as number of participants with abnormal laboratory values
  measure: Number of participants with abnormal urinalysis values
  time frame: For each study period, urine samples were collected at 2 time points (including pre-dose) during the study period on Day1 and Day 2.
  description: The safety parameters Urinalysis were determined for XS005 Sorafenib Capsule A, 50 mg and Tablet A, 100 mg compared to reference Sorafenib tablets (Nexavar®) for each study subjects using descriptive statistics and presented as number of participants with abnormal laboratory values.
  measure: Number of participants with abnormal physical examination outcome
  time frame: For each study period, target (symptom driven) physical examination; each subject was assessed by a physician and a physical examination was performed if the subject reported any AEs, on Day 2.
  description: The safety parameters physical examination outcome were determined for XS005 Sorafenib Capsule A, 50 mg and Tablet A, 100 mg compared to reference Sorafenib tablets (Nexavar®) for each study subjects using descriptive statistics and presented as number of subjects with abnormal physical examination outcome.
  measure: Number of participants with abnormal skin examination outcome
  time frame: For each study period, skin assessments were done at 2 time points (including pre-dose) during the study period on Day 1 and Day 2.
  description: The safety parameters Skin assessment outcome were determined for XS005 Sorafenib Capsule A, 50 mg and Tablet A, 100 mg compared to reference Sorafenib tablets (Nexavar®) for each study subjects using descriptive statistics and presented as number of subjects with abnormal skin examination outcome.
  arm group label: Sorafenib - Period 1
  arm group type: Active Comparator
  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.
  arm group label: XS005 Sorafenib Capsule A - Period 1
  arm group type: Experimental
  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.
  arm group label: XS005 Sorafenib Tablet A - Period 1
  arm group type: Experimental
  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.
  arm group label: XS005 Sorafenib Capsule A - Period 2
  arm group type: Experimental
  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.
  arm group label: XS005 Sorafenib Tablet A - Period 2
  arm group type: Experimental
  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.
  arm group label: Sorafenib - Period 2
  arm group type: Active Comparator
  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.
  arm group label: XS005 Sorafenib Tablet A - Period 3
  arm group type: Experimental
  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.
  arm group label: Sorafenib - Period 3
  arm group type: Active Comparator
  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.
  arm group label: XS005 Sorafenib Capsule A - Period 3
  arm group type: Experimental
  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.
  intervention type: Drug
  intervention name: Sorafenib - Period 1
  description: Sorafenib (Nexavar®) Tablet, 200 mg
  arm group label: Sorafenib - Period 1
  other name: Regimen A (reference)
  intervention type: Drug
  intervention name: XS005 Sorafenib Capsule A - Period 1
  description: XS005 Sorafenib Capsule A, 100 mg (2 x 50 mg)
  arm group label: XS005 Sorafenib Capsule A - Period 1
  other name: Regimen B
  intervention type: Drug
  intervention name: XS005 Sorafenib Tablet A - Period 1
  description: XS005 Sorafenib Tablet A, 100 mg
  arm group label: XS005 Sorafenib Tablet A - Period 1
  other name: Regimen C
  intervention type: Drug
  intervention name: XS005 Sorafenib Capsule A - Period 2
  description: XS005 Sorafenib Capsule A, 100 mg (2 x 50 mg)
  arm group label: XS005 Sorafenib Capsule A - Period 2
  other name: Regimen B
  intervention type: Drug
  intervention name: XS005 Sorafenib Tablet A - Period 2
  description: XS005 Sorafenib Tablet A, 100 mg
  arm group label: XS005 Sorafenib Tablet A - Period 2
  other name: Regimen C
  intervention type: Drug
  intervention name: Sorafenib - Period 2
  description: Sorafenib (Nexavar®) Tablet, 200 mg
  arm group label: Sorafenib - Period 2
  other name: Regimen A (reference)
  intervention type: Drug
  intervention name: XS005 Sorafenib Tablet A - Period 3
  description: XS005 Sorafenib Tablet A, 100 mg
  arm group label: XS005 Sorafenib Tablet A - Period 3
  other name: Regimen C
  intervention type: Drug
  intervention name: Sorafenib - Period 3
  description: Sorafenib (Nexavar®) Tablet, 200 mg
  arm group label: Sorafenib - Period 3
  other name: Regimen A (reference)
  intervention type: Drug
  intervention name: XS005 Sorafenib Capsule A - Period 3
  description: XS005 Sorafenib Capsule A, 100 mg (2 x 50 mg)
  arm group label: XS005 Sorafenib Capsule A - Period 3
  other name: Regimen B
  criteria: 
  gender: Male
  minimum age: 18 Years
  maximum age: 55 Years
  healthy volunteers: Accepts Healthy Volunteers
  last name: Sharan Sidhu, MBChB, BAO, MRCS, MFPM
  role: Principal Investigator
  affiliation: Quotient Sciences
  facility: 
  country: United Kingdom
  responsible party type: Sponsor
  mesh term: Leucovorin
  mesh term: Sorafenib
  mesh term: Fluorouracil
  mesh term: Methotrexate
  mesh term: Carboplatin
  sharing ipd: No