<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/NCT04505397</url>
  </required_header>
  <id_info>
    <org_study_id>SKL24741C001</org_study_id>
    <nct_id>NCT04505397</nct_id>
  </id_info>
  <brief_title>Single-Dose Escalation Study Followed by a Multiple-Dose Escalation Study of SKL24741 in Healthy Subjects</brief_title>
  <official_title>A Phase 1, Randomized, Double-Blinded, Single-Dose Escalation Study Followed by a Multiple-Dose Escalation Study of SKL24741 in Healthy Subjects</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>SK Life Science, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Spaulding Clinical Research LLC</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Covance</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>SK Life Science, Inc.</source>
  <oversight_info>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study evaluates SKL24741 safety and tolerability in healthy subjects. Subjects will be&#xD;
      randomized to receive oral doses of SKL24741 or placebo. This is a two-part, double-blinded,&#xD;
      randomized study of SKL24741.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The study includes a sequential cohort design that is intended to optimize subject safety and&#xD;
      assess tolerability, safety, and PK of SKL24741. In the single-dose escalation part of the&#xD;
      study (Part A), tolerability, safety, and PK of SKL24741 will be assessed in healthy male&#xD;
      subjects under fasting conditions. At an appropriate dose based on PK results, additional&#xD;
      cohorts will be repeated with the subjects under fed conditions, in order to evaluate the&#xD;
      magnitude on the disposition of SKL24741. To assess the gender effect on the disposition of&#xD;
      SKL24741, female subjects will be treated at one dose level under fasting conditions. A&#xD;
      preliminary formulation effect may be assessed in a cohort of subjects to compare the capsule&#xD;
      versus tablet formulation on the disposition of SKL24741.&#xD;
&#xD;
      Part A Primary Objective: To evaluate the safety and tolerability of single oral ascending&#xD;
      doses of SKL24741 administered to healthy male subjects&#xD;
&#xD;
      Part A Secondary Objectives:&#xD;
&#xD;
        -  To evaluate the PK of SKL24741 (R-enantiomer), SKL24742 (S-enantiomer) (if appropriate),&#xD;
           and its possible metabolites (if deemed necessary) following administration of single&#xD;
           oral ascending doses of SKL24741 administered to healthy male subjects&#xD;
&#xD;
        -  To assess the food effect on the PK of SKL24741 and SKL24742 (if appropriate) following&#xD;
           administration of a single oral dose of SKL24741 administered to healthy male subjects&#xD;
&#xD;
        -  To assess the gender effect on the PK of SKL24741 and SKL24742 (if appropriate)&#xD;
           following administration of a single oral dose of SKL24741 administered to healthy&#xD;
           female subjects&#xD;
&#xD;
      Part A Exploratory Objective: To assess the formulation effect on the PK of SKL24741 and&#xD;
      SKL24742 (if appropriate) following administration of a single oral dose of SKL24741&#xD;
      administered to healthy male subjects&#xD;
&#xD;
      Part B Primary Objective: To evaluate safety and tolerability of multiple oral ascending&#xD;
      doses of SKL24741 administered for 14 days to healthy male subjects&#xD;
&#xD;
      Part B Secondary Objective: To evaluate the PK of SKL24741, SKL24742 (if appropriate), and&#xD;
      its possible metabolites (if deemed necessary) following administration of multiple oral&#xD;
      ascending doses of SKL24741 administered to healthy male subjects&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">February 13, 2020</start_date>
  <completion_date type="Anticipated">December 30, 2022</completion_date>
  <primary_completion_date type="Anticipated">December 30, 2022</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>Sequential Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Adverse events (Incidence of treatment-emergent adverse events)</measure>
    <time_frame>From Screening until follow-up (14-16 days after dosing day or final dosing day)</time_frame>
    <description>The number [count] and percentage [%] of subjects experiencing an adverse event</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Clinically significant laboratory assessments</measure>
    <time_frame>From Screening until follow-up (14-16 days after dosing day or final dosing day)</time_frame>
    <description>Hematology, coagulation, clinical chemistry, urinalysis, and cholesterol</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Electrocardiogram outcomes</measure>
    <time_frame>From Screening until follow-up, including time-point assessments (In Part A, pre-dose until 24 hours post-dose. In Part B, Day1: pre-dose until 8 hours post-dose; Day 2-13: pre-dose only; Day 14: pre-dose until 24 hours post-dose)</time_frame>
    <description>Standard electrocardiograms (ECGs) parameters will be measured, including heart rate (HR) [beats/min], RR [millisecond], PR [millisecond], QT [millisecond], QTc intervals [millisecond], and QRS duration [millisecond]. Extensive triplicate 12-lead ECGs, except for the food effect cohort, will be collected at various time points.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Vital sign</measure>
    <time_frame>From Screening until follow-up, including time-point assessments (In Part A, Day1: pre-dose until 12 hours post-dose. In Part B, Day1: pre-dose until 12 hours post-dose; Day 2-14: pre-dose until 8 hours post-dose)</time_frame>
    <description>Blood pressure (systolic and diastolic measurements in supine and standing in the same sequence in each subject, in order to allow orthostatic measurements) [mmHg]</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Vital sign</measure>
    <time_frame>From Screening until follow-up, including time-point assessments (In Part A, Day1: pre-dose until 12 hours post-dose. In Part B, Day1: pre-dose until 12 hours post-dose; Day 2-14: pre-dose until 8 hours post-dose)</time_frame>
    <description>Temperature [Celsius]</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Vital sign</measure>
    <time_frame>From Screening until follow-up, including time-point assessments (In Part A, Day1: pre-dose until 12 hours post-dose. In Part B, Day1: pre-dose until 12 hours post-dose; Day 2-14: pre-dose until 8 hours post-dose)</time_frame>
    <description>Heart rate [beats/min]</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Vital sign</measure>
    <time_frame>From Screening until follow-up, including time-point assessments (In Part A, Day1: pre-dose until 12 hours post-dose. In Part B, Day1: pre-dose until 12 hours post-dose; Day 2-14: pre-dose until 8 hours post-dose)</time_frame>
    <description>Respiratory rate [breaths/min]</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Vital signs</measure>
    <time_frame>From Screening until follow-up, including time-point assessments (In Part A, Day1: pre-dose until 12 hours post-dose. In Part B, Day1: pre-dose until 12 hours post-dose; Day 2-14: pre-dose until 8 hours post-dose)</time_frame>
    <description>Arterial oxygen saturation (SaO2) (using pulse oximetry) [%]</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Physical examination</measure>
    <time_frame>Full (complete) physical examination at screening only. From Screening until follow-up (14-16 days after dosing day or final dosing day)</time_frame>
    <description>Full physical examination (review of all body systems - head/neck/thyroid, eyes/ears/nose/throat, respiratory, cardiovascular, lymph nodes, abdomen, skin, musculoskeletal, and neurological. Breast, anorectal, and genital examinations)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Physical examination</measure>
    <time_frame>Full (complete) physical examination at screening only. From Screening until follow-up (14-16 days after dosing day or final dosing day)</time_frame>
    <description>Height [centimeter]</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Physical examination</measure>
    <time_frame>Full (complete) physical examination at screening only. From Screening until follow-up (14-16 days after dosing day or final dosing day)</time_frame>
    <description>Weight [kg]</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Physical examination</measure>
    <time_frame>Full (complete) physical examination at screening only. From Screening until follow-up (14-16 days after dosing day or final dosing day)</time_frame>
    <description>BMI [kg/m^2]</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Physical examination</measure>
    <time_frame>Full (complete) physical examination at screening only. From Screening until follow-up (14-16 days after dosing day or final dosing day)</time_frame>
    <description>Abbreviated (symptom-directed) physical examination.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Peak expiratory flow rate</measure>
    <time_frame>Assessed at admission (Day -1), pre-dose (baseline), 2 and 24 hours post-dose after the first dose (Day 1 dosing) and the last dose (Day 14 dosing for Part B), and follow-up (14-16 days after dosing day or final dosing day)</time_frame>
    <description>Peak expiratory flow rate [L/min], the maximum rate that a person can exhale during a short maximal expiratory effort after a full inspiration</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Columbia-Suicide Severity Rating Scale (Part B only)</measure>
    <time_frame>From Screening until follow-up (14-16 days after dosing day or final dosing day). Baseline (&quot;Lifetime/Recent&quot;) at Screening and &quot;Since Last Visit&quot; versions on other visits</time_frame>
    <description>Columbia-Suicide Severity Rating Scale (C-SSRS) is a brief questionnaire that provides for the identification, quantification, and standardized assessment of the occurrences and severity of suicidal ideation and behavior. The changes from baseline and clinical abnormalities will be assessed (units on a scale).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Maximum concentration (Cmax) of SKL24741, SKL24742 (if appropriate), and possible metabolites (if deemed necessary) following the single and/or multiple dose administration of SKL24741</measure>
    <time_frame>In Part A, pre-dose and up to 240 hours post-dose plasma samples. In Part B, Days 1 and 7: pre-dose and up to 24 hours post-dose, Days 3-6 and 9-13: pre-dose only, and Day 14: Pre-dose and up to 240 hours post-dose plasma samples</time_frame>
    <description>Maximum concentration (Cmax) [ng/mL] of SKL24741, SKL24742 (if appropriate), and possible metabolites (if deemed necessary) for the plasma concentration-time profiles</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to maximum concentration (tmax) of SKL24741, SKL24742 (if appropriate), and possible metabolites (if deemed necessary) following the single and/or multiple dose administration of SKL24741</measure>
    <time_frame>In Part A, pre-dose and up to 240 hours post-dose plasma samples. In Part B, Days 1 and 7: pre-dose and up to 24 hours post-dose, Days 3-6 and 9-13: pre-dose only, and Day 14: Pre-dose and up to 240 hours post-dose plasma samples</time_frame>
    <description>Time to maximum concentration (tmax) [hours, or h] of SKL24741, SKL24742 (if appropriate), and possible metabolites (if deemed necessary) for the plasma concentration-time profiles</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area under the concentration-time curve (AUC) from 0 to infinity (AUC∞) of SKL24741, SKL24742 (if appropriate), and possible metabolites (if deemed necessary) following the single and/or multiple dose administration of SKL24741</measure>
    <time_frame>In Part A, pre-dose and up to 240 hours post-dose plasma samples. In Part B, Days 1 and 7: pre-dose and up to 24 hours post-dose, Days 3-6 and 9-13: pre-dose only, and Day 14: Pre-dose and up to 240 hours post-dose plasma samples</time_frame>
    <description>Area under the concentration-time curve (AUC) from 0 to infinity (AUC∞) [ng*h/mL] of SKL24741, SKL24742 (if appropriate), and possible metabolites (if deemed necessary) for the plasma concentration-time profiles after a single dose administration</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUC from time 0 to a given time t (AUCt) of SKL24741, SKL24742 (if appropriate), and possible metabolites (if deemed necessary) following the single and/or multiple dose administration of SKL24741</measure>
    <time_frame>In Part A, pre-dose and up to 240 hours post-dose plasma samples. In Part B, Days 1 and 7: pre-dose and up to 24 hours post-dose, Days 3-6 and 9-13: pre-dose only, and Day 14: Pre-dose and up to 240 hours post-dose plasma samples</time_frame>
    <description>AUC from time 0 to a given time t (AUCt) [ng*h/mL] of SKL24741, SKL24742 (if appropriate), and possible metabolites (if deemed necessary) for the plasma concentration-time profiles</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUC over the dosing interval (AUCτ) of SKL24741, SKL24742 (if appropriate), and possible metabolites (if deemed necessary) following the single and/or multiple dose administration of SKL24741</measure>
    <time_frame>In Part A, pre-dose and up to 240 hours post-dose plasma samples. In Part B, Days 1 and 7: pre-dose and up to 24 hours post-dose, Days 3-6 and 9-13: pre-dose only, and Day 14: Pre-dose and up to 240 hours post-dose plasma samples</time_frame>
    <description>AUC over the dosing interval (AUCτ) [ng*h/mL] of SKL24741, SKL24742 (if appropriate), and possible metabolites (if deemed necessary) for the plasma concentration-time profiles</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Apparent clearance (CL/F) of SKL24741, SKL24742 (if appropriate), and possible metabolites (if deemed necessary) following the single and/or multiple dose administration of SKL24741</measure>
    <time_frame>In Part A, pre-dose and up to 240 hours post-dose plasma samples. In Part B, Days 1 and 7: pre-dose and up to 24 hours post-dose, Days 3-6 and 9-13: pre-dose only, and Day 14: Pre-dose and up to 240 hours post-dose plasma samples</time_frame>
    <description>Apparent clearance (CL/F) [L/h] of SKL24741, SKL24742 (if appropriate), and possible metabolites (if deemed necessary) for the plasma concentration-time profiles</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Apparent volume of distribution (Vd/F) of SKL24741, SKL24742 (if appropriate), and possible metabolites (if deemed necessary) following the single and/or multiple dose administration of SKL24741</measure>
    <time_frame>In Part A, pre-dose and up to 240 hours post-dose plasma samples. In Part B, Days 1 and 7: pre-dose and up to 24 hours post-dose, Days 3-6 and 9-13: pre-dose only, and Day 14: Pre-dose and up to 240 hours post-dose plasma samples</time_frame>
    <description>Apparent volume of distribution (Vd/F) [Liter, or L] of SKL24741, SKL24742 (if appropriate), and possible metabolites (if deemed necessary) for the plasma concentration-time profiles</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Half-life (t1/2) of SKL24741, SKL24742 (if appropriate), and possible metabolites (if deemed necessary) following the single and/or multiple dose administration of SKL24741</measure>
    <time_frame>In Part A, pre-dose and up to 240 hours post-dose plasma samples. In Part B, Days 1 and 7: pre-dose and up to 24 hours post-dose, Days 3-6 and 9-13: pre-dose only, and Day 14: Pre-dose and up to 240 hours post-dose plasma samples</time_frame>
    <description>Half-life (t1/2) [hour] of SKL24741, SKL24742 (if appropriate), and possible metabolites (if deemed necessary) for the plasma concentration-time profiles</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Accumulation ratio (Racc) of SKL24741, SKL24742 (if appropriate), and possible metabolites (if deemed necessary) following the single and/or multiple dose administration of SKL24741</measure>
    <time_frame>In Part A, pre-dose and up to 240 hours post-dose plasma samples. In Part B, Days 1 and 7: pre-dose and up to 24 hours post-dose, Days 3-6 and 9-13: pre-dose only, and Day 14: Pre-dose and up to 240 hours post-dose plasma samples</time_frame>
    <description>Accumulation ratio (Racc) [unit of ratio] of SKL24741, SKL24742 (if appropriate), and possible metabolites (if deemed necessary) for the plasma concentration-time profiles</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Fraction excreted unchanged in the urine (fe) of SKL24741, SKL24742 (if appropriate), and possible metabolites (if deemed necessary) following the single dose administration of SKL24741</measure>
    <time_frame>In Part A, pre-dose and up to 240 hours post-dose urine samples.</time_frame>
    <description>Fraction excreted unchanged in the urine (fe) [unit of fraction] of SKL24741, SKL24742 (if appropriate), and possible metabolites (if deemed necessary) for the urine concentration-time profiles</description>
  </other_outcome>
  <other_outcome>
    <measure>Renal clearance (CLr) of SKL24741, SKL24742 (if appropriate), and possible metabolites (if deemed necessary) following the single dose administration of SKL24741</measure>
    <time_frame>In Part A, pre-dose and up to 240 hours post-dose urine samples.</time_frame>
    <description>Renal clearance (CLr) [Liter/h or milliliter/min] of SKL24741, SKL24742 (if appropriate), and possible metabolites (if deemed necessary) for the urine concentration-time profiles</description>
  </other_outcome>
  <number_of_arms>22</number_of_arms>
  <enrollment type="Actual">111</enrollment>
  <condition>Healthy</condition>
  <arm_group>
    <arm_group_label>Single Ascending Dose Level 1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>4 Subjects will receive one dose of 10 mg and 2 subjects will receive one dose of placebo</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Single Ascending Dose Level 2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>4 Subjects will receive one dose of 25 mg and 2 subjects will receive one dose of placebo</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Single Ascending Dose Level 3</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>4 Subjects will receive one dose of 50 mg and 2 subjects will receive one dose of placebo</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Single Ascending Dose Level 4</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>4 Subjects will receive one dose of 100 mg and 2 subjects will receive one dose of placebo</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Single Ascending Dose Level 5</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>4 Subjects will receive one dose of 200 mg and 2 subjects will receive one dose of placebo</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Single Ascending Dose Level 6</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>4 Subjects will receive one dose of 300 mg and 2 subjects will receive one dose of placebo</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Single Ascending Dose Level 7</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>4 Subjects will receive one dose of 400 mg and 2 subjects will receive one dose of placebo</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Single Ascending Dose Level 8</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>4 Subjects will receive one dose of 800 mg and 2 subjects will receive one dose of placebo</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Single Ascending Dose Level 9</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>4 Subjects will receive one dose of 1200 mg and 2 subjects will receive one dose of placebo</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Single Ascending Dose Level 10</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>4 Subjects will receive one dose on the outcome of preceding dose levels and 2 subjects will receive one dose of placebo</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Multiple Ascending Dose Level 1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>6 Subjects will receive one dose of 50 mg each day for 14 days and 2 subjects will receive one dose placebo every day for 14 days. The dose will be determined based on the outcome of Part A (Single Ascending Dose).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Multiple Ascending Dose Level 2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>6 Subjects will receive one dose of 200 mg each day for 14 days and 2 subjects will receive one dose placebo every day for 14 days. The dose will be determined based on the outcome of Part A (Single Ascending Dose) and/or preceding dose levels of Part B (Multiple Ascending Dose).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Multiple Ascending Dose Level 3</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>6 Subjects will receive one dose of 400 mg each day for 14 days and 2 subjects will receive one dose placebo every day for 14 days. The dose will be determined based on the outcome of Part A (Single Ascending Dose) and/or preceding dose levels of Part B (Multiple Ascending Dose).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Multiple Ascending Dose Level 4</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>6 Subjects will receive one dose of 800 mg each day for 14 days and 2 subjects will receive one dose placebo every day for 14 days. The dose will be determined based on the outcome of Part A (Single Ascending Dose) and/or preceding dose levels of Part B (Multiple Ascending Dose).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Multiple Ascending Dose Level 5</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>6 Subjects will receive one dose of 1200 mg each day for 14 days and 2 subjects will receive one dose placebo every day for 14 days. The dose will be determined based on the outcome of Part A (Single Ascending Dose) and/or preceding dose levels of Part B (Multiple Ascending Dose).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Multiple Ascending Dose Level 6</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>6 Subjects will receive one dose of 1200 mg each day (using tablet formulation instead of capsule formulation*) for 14 days and 2 subjects will receive one dose placebo every day for 14 days. The dose will be determined based on the outcome of Part A (Single Ascending Dose) and/or preceding dose levels of Part B (Multiple Ascending Dose).&#xD;
*Tablet formulation is utilized, instead of capsule formulation, in the marked dose levels.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Food Effect Cohort</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>After completing the fasting Single Ascending Dose escalation, the same 6 subjects who received one dose of 50 mg under fasting conditions will return to the clinic after a washout period for a second confinement to receive a second dose (same as fasting) under fed conditions.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Gender Effect Cohort</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>6 female subjects of non-childbearing potential will receive one dose of 50 mg under fasting conditions.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Optional Food Effect Cohort</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Up to 12 male subjects will undergo an open-label, two period, two-sequence crossover design at the maximum daily dose tested in Part A.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Optional Formulation Effect Cohort</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Up to 12 male subjects will be treated with the maximum daily dose tested in Part A using open-label, two period, two-sequence crossover design.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Multiple Ascending Dose Level 7</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>6 Subjects will receive one dose of 2000 mg each day (using tablet formulation instead of capsule formulation*) for 14 days and 2 subjects will receive one dose placebo every day for 14 days. The dose will be determined based on the outcome of Part A (Single Ascending Dose) and/or preceding dose levels of Part B (Multiple Ascending Dose).&#xD;
*Tablet formulation is utilized, instead of capsule formulation, in the marked dose levels.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Multiple Ascending Dose Level 8</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>6 Subjects will receive one dose each day (using tablet formulation instead of capsule formulation*) for 14 days and 2 subjects will receive one dose placebo every day for 14 days. The dose will be determined based on the outcome of Part A (Single Ascending Dose) and/or preceding dose levels of Part B (Multiple Ascending Dose).&#xD;
*Tablet formulation is utilized, instead of capsule formulation, in the marked dose levels.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>SKL24741</intervention_name>
    <description>An inhibitor of voltage-gated sodium channels and a possible activator of Big Potassium channels. Administered as an oral dose in the form of a capsule or tablet.</description>
    <arm_group_label>Food Effect Cohort</arm_group_label>
    <arm_group_label>Gender Effect Cohort</arm_group_label>
    <arm_group_label>Multiple Ascending Dose Level 1</arm_group_label>
    <arm_group_label>Multiple Ascending Dose Level 2</arm_group_label>
    <arm_group_label>Multiple Ascending Dose Level 3</arm_group_label>
    <arm_group_label>Multiple Ascending Dose Level 4</arm_group_label>
    <arm_group_label>Multiple Ascending Dose Level 5</arm_group_label>
    <arm_group_label>Multiple Ascending Dose Level 6</arm_group_label>
    <arm_group_label>Multiple Ascending Dose Level 7</arm_group_label>
    <arm_group_label>Multiple Ascending Dose Level 8</arm_group_label>
    <arm_group_label>Optional Food Effect Cohort</arm_group_label>
    <arm_group_label>Optional Formulation Effect Cohort</arm_group_label>
    <arm_group_label>Single Ascending Dose Level 1</arm_group_label>
    <arm_group_label>Single Ascending Dose Level 10</arm_group_label>
    <arm_group_label>Single Ascending Dose Level 2</arm_group_label>
    <arm_group_label>Single Ascending Dose Level 3</arm_group_label>
    <arm_group_label>Single Ascending Dose Level 4</arm_group_label>
    <arm_group_label>Single Ascending Dose Level 5</arm_group_label>
    <arm_group_label>Single Ascending Dose Level 6</arm_group_label>
    <arm_group_label>Single Ascending Dose Level 7</arm_group_label>
    <arm_group_label>Single Ascending Dose Level 8</arm_group_label>
    <arm_group_label>Single Ascending Dose Level 9</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Sugar pill manufactured to mimic SKL24741</description>
    <arm_group_label>Multiple Ascending Dose Level 1</arm_group_label>
    <arm_group_label>Multiple Ascending Dose Level 2</arm_group_label>
    <arm_group_label>Multiple Ascending Dose Level 3</arm_group_label>
    <arm_group_label>Multiple Ascending Dose Level 4</arm_group_label>
    <arm_group_label>Multiple Ascending Dose Level 5</arm_group_label>
    <arm_group_label>Multiple Ascending Dose Level 6</arm_group_label>
    <arm_group_label>Multiple Ascending Dose Level 7</arm_group_label>
    <arm_group_label>Multiple Ascending Dose Level 8</arm_group_label>
    <arm_group_label>Single Ascending Dose Level 1</arm_group_label>
    <arm_group_label>Single Ascending Dose Level 10</arm_group_label>
    <arm_group_label>Single Ascending Dose Level 2</arm_group_label>
    <arm_group_label>Single Ascending Dose Level 3</arm_group_label>
    <arm_group_label>Single Ascending Dose Level 4</arm_group_label>
    <arm_group_label>Single Ascending Dose Level 5</arm_group_label>
    <arm_group_label>Single Ascending Dose Level 6</arm_group_label>
    <arm_group_label>Single Ascending Dose Level 7</arm_group_label>
    <arm_group_label>Single Ascending Dose Level 8</arm_group_label>
    <arm_group_label>Single Ascending Dose Level 9</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Male subjects of 18 to 50 years of age (inclusive) except for the gender effect cohort&#xD;
&#xD;
          2. Able to read, understand, sign, and date a written informed consent form (ICF) before&#xD;
             study participation at screening&#xD;
&#xD;
          3. Agree to use 2 highly effective methods of contraception, including at least one&#xD;
             barrier method (Section 10.6.7 for details)&#xD;
&#xD;
          4. Body mass index (BMI) between 18.0 and 30.0 kg/m2 (inclusive) at screening&#xD;
&#xD;
          5. Judged to be in good health on the basis of medical history, physical examination, and&#xD;
             routine laboratory measurements (i.e., without clinically relevant pathology)&#xD;
&#xD;
          6. Normal electrocardiogram (ECG) (12-lead), arterial blood pressure, and heart rate&#xD;
             within the normal range of the study center or considered not clinically significant&#xD;
             by the investigator and in agreement with the Sponsor&#xD;
&#xD;
          7. Able to understand and comply with protocol requirements and instructions and likely&#xD;
             to complete the study as planned&#xD;
&#xD;
          8. For Part A (gender effect cohort): Female of non-childbearing potential (18 to 50&#xD;
             years of age (inclusive)), who have undergone a sterilization procedure at least 6&#xD;
             months prior to dosing with official documentation (e.g., hysteroscopic sterilization,&#xD;
             bilateral tubal ligation or bilateral salpingectomy, hysterectomy, or bilateral&#xD;
             oophorectomy), or be postmenopausal with amenorrhea for at least 1 year prior to&#xD;
             dosing and follicle-stimulating hormone (FSH) serum levels consistent with&#xD;
             postmenopausal status as per Principal Investigator's judgment&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. History of any illness or condition that, in the opinion of the investigator, might&#xD;
             confound the results of the study or pose an additional risk in administering study&#xD;
             drug to the subjects.&#xD;
&#xD;
          2. Smokers (subjects who have smoked within 6 months at screening or those with positive&#xD;
             results from smoking screening).&#xD;
&#xD;
          3. Cholecystectomy and/or surgery of the gastrointestinal tract that could interfere with&#xD;
             pharmacokinetics of the trial medication (except appendectomy and simple hernia&#xD;
             repair).&#xD;
&#xD;
          4. Regular treatment with prescription medications. Subjects should have ended any&#xD;
             prescription medications at least 14 days before the first dosing of the study drug.&#xD;
             Potential subjects should only stop any prescribed medication at the direction of a&#xD;
             physician.&#xD;
&#xD;
          5. Regular treatment with nonprescription medications. Subjects should have ended any&#xD;
             nonprescription medications at least 14 days before the first dosing of the study&#xD;
             drug. Potential subjects should consult a physician before stopping any regular&#xD;
             treatment with nonprescription medication.&#xD;
&#xD;
          6. Consumption of herbal medications, dietary supplements, and specific fruit products.&#xD;
             Subjects should have stopped consumption of herbal medications or dietary supplements&#xD;
             (e.g., St. John's Wort, ginkgo biloba, and garlic supplements), vitamins, and&#xD;
             grapefruit or grapefruit juice, or Seville oranges at least 14 days before the first&#xD;
             dosing of study drug.&#xD;
&#xD;
          7. History of drug or alcohol abuse or addiction within 2 years before the start of study&#xD;
             drug dosing, or a positive test results for alcohol or drugs of abuse, such as&#xD;
             amphetamine, barbiturate, benzodiazepine, cocaine, methadone, opiates, oxycodone,&#xD;
             phencyclidine, propoxyphene, cannabinoid (THC), MDMA (Ecstasy), methaqualone, and&#xD;
             tricyclic antidepressant (TCA).&#xD;
&#xD;
          8. Regular consumption of more than 2 units of alcoholic beverages per day or more than&#xD;
             14 units per week (1 unit of alcohol equals 1 pint [473 mL] of beer or lager, 1 glass&#xD;
             [125 mL] of wine, 25 mL shot of 40% spirit) before screening. Subjects may not consume&#xD;
             any alcohol from 72 hours before the first dosing of study drug through the completion&#xD;
             of the last PK sampling.&#xD;
&#xD;
          9. Consumption of an average of more than 5 servings (8 ounces per serving) per day of&#xD;
             coffee, cola, or other caffeinated beverage before screening. Subjects may not consume&#xD;
             any caffeinated beverages from 48 hours prior to dosing until the collection of the&#xD;
             last PK sample.&#xD;
&#xD;
         10. Participation in a clinical study involving administration of either an&#xD;
             investigational or a marketed drug within 2 months or 7 half-lives (whichever is&#xD;
             longer) before screening.&#xD;
&#xD;
         11. Blood donation or a significant loss of blood within 60 days of the start of study&#xD;
             drug dosing or donation of more than 1 unit of plasma within 7 days before screening.&#xD;
&#xD;
         12. Positive result at screening for any of the following infectious disease tests:&#xD;
             hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab), human&#xD;
             immunodeficiency virus antigen and antibody (HIV Ag, HIV Ab)&#xD;
&#xD;
         13. Illness within 5 days before the start of study drug dosing (&quot;illness&quot; is defined as&#xD;
             an acute [serious or non-serious] condition [e.g., the flu or the common cold])&#xD;
&#xD;
         14. History of any known relevant allergy/hypersensitivity (including allergy to the trial&#xD;
             medication or its excipients)&#xD;
&#xD;
         15. Subject who is judged not eligible for study participation by investigator&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <gender_based>Yes</gender_based>
    <gender_description>This study will enroll up to 138 Healthy Male Subjects and 6 Non-childbearing potential Female Subjects.</gender_description>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>50 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Vijaykumar Vashi, PhD</last_name>
    <role>Study Director</role>
    <affiliation>SK Life Science, Inc.</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Spaulding Clinical Research</name>
      <address>
        <city>West Bend</city>
        <state>Wisconsin</state>
        <zip>53095</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>October 2022</verification_date>
  <study_first_submitted>January 30, 2020</study_first_submitted>
  <study_first_submitted_qc>August 5, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">August 10, 2020</study_first_posted>
  <last_update_submitted>October 12, 2022</last_update_submitted>
  <last_update_submitted_qc>October 12, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">October 17, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>February 21, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/97/NCT04505397/Prot_000.pdf</document_url>
    </provided_document>
  </provided_document_section>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


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/NCT04505397
org study id: SKL24741C001
nct id: NCT04505397
lead sponsor: 
collaborator: 
collaborator: 
is fda regulated drug: Yes
is fda regulated device: No
This study evaluates SKL24741 safety and tolerability in healthy subjects. Subjects will be
      randomized to receive oral doses of SKL24741 or placebo. This is a two-part, double-blinded,
      randomized study of SKL24741.
The study includes a sequential cohort design that is intended to optimize subject safety and
      assess tolerability, safety, and PK of SKL24741. In the single-dose escalation part of the
      study (Part A), tolerability, safety, and PK of SKL24741 will be assessed in healthy male
      subjects under fasting conditions. At an appropriate dose based on PK results, additional
      cohorts will be repeated with the subjects under fed conditions, in order to evaluate the
      magnitude on the disposition of SKL24741. To assess the gender effect on the disposition of
      SKL24741, female subjects will be treated at one dose level under fasting conditions. A
      preliminary formulation effect may be assessed in a cohort of subjects to compare the capsule
      versus tablet formulation on the disposition of SKL24741.

      Part A Primary Objective: To evaluate the safety and tolerability of single oral ascending
      doses of SKL24741 administered to healthy male subjects

      Part A Secondary Objectives:

        -  To evaluate the PK of SKL24741 (R-enantiomer), SKL24742 (S-enantiomer) (if appropriate),
           and its possible metabolites (if deemed necessary) following administration of single
           oral ascending doses of SKL24741 administered to healthy male subjects

        -  To assess the food effect on the PK of SKL24741 and SKL24742 (if appropriate) following
           administration of a single oral dose of SKL24741 administered to healthy male subjects

        -  To assess the gender effect on the PK of SKL24741 and SKL24742 (if appropriate)
           following administration of a single oral dose of SKL24741 administered to healthy
           female subjects

      Part A Exploratory Objective: To assess the formulation effect on the PK of SKL24741 and
      SKL24742 (if appropriate) following administration of a single oral dose of SKL24741
      administered to healthy male subjects

      Part B Primary Objective: To evaluate safety and tolerability of multiple oral ascending
      doses of SKL24741 administered for 14 days to healthy male subjects

      Part B Secondary Objective: To evaluate the PK of SKL24741, SKL24742 (if appropriate), and
      its possible metabolites (if deemed necessary) following administration of multiple oral
      ascending doses of SKL24741 administered to healthy male subjects
allocation: Randomized
intervention model: Sequential Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Adverse events (Incidence of treatment-emergent adverse events)
time frame: From Screening until follow-up (14-16 days after dosing day or final dosing day)
description: The number [count] and percentage [%] of subjects experiencing an adverse event
measure: Clinically significant laboratory assessments
time frame: From Screening until follow-up (14-16 days after dosing day or final dosing day)
description: Hematology, coagulation, clinical chemistry, urinalysis, and cholesterol
measure: Electrocardiogram outcomes
time frame: From Screening until follow-up, including time-point assessments (In Part A, pre-dose until 24 hours post-dose. In Part B, Day1: pre-dose until 8 hours post-dose; Day 2-13: pre-dose only; Day 14: pre-dose until 24 hours post-dose)
description: Standard electrocardiograms (ECGs) parameters will be measured, including heart rate (HR) [beats/min], RR [millisecond], PR [millisecond], QT [millisecond], QTc intervals [millisecond], and QRS duration [millisecond]. Extensive triplicate 12-lead ECGs, except for the food effect cohort, will be collected at various time points.
measure: Vital sign
time frame: From Screening until follow-up, including time-point assessments (In Part A, Day1: pre-dose until 12 hours post-dose. In Part B, Day1: pre-dose until 12 hours post-dose; Day 2-14: pre-dose until 8 hours post-dose)
description: Blood pressure (systolic and diastolic measurements in supine and standing in the same sequence in each subject, in order to allow orthostatic measurements) [mmHg]
measure: Vital sign
time frame: From Screening until follow-up, including time-point assessments (In Part A, Day1: pre-dose until 12 hours post-dose. In Part B, Day1: pre-dose until 12 hours post-dose; Day 2-14: pre-dose until 8 hours post-dose)
description: Temperature [Celsius]
measure: Vital sign
time frame: From Screening until follow-up, including time-point assessments (In Part A, Day1: pre-dose until 12 hours post-dose. In Part B, Day1: pre-dose until 12 hours post-dose; Day 2-14: pre-dose until 8 hours post-dose)
description: Heart rate [beats/min]
measure: Vital sign
time frame: From Screening until follow-up, including time-point assessments (In Part A, Day1: pre-dose until 12 hours post-dose. In Part B, Day1: pre-dose until 12 hours post-dose; Day 2-14: pre-dose until 8 hours post-dose)
description: Respiratory rate [breaths/min]
measure: Vital signs
time frame: From Screening until follow-up, including time-point assessments (In Part A, Day1: pre-dose until 12 hours post-dose. In Part B, Day1: pre-dose until 12 hours post-dose; Day 2-14: pre-dose until 8 hours post-dose)
description: Arterial oxygen saturation (SaO2) (using pulse oximetry) [%]
measure: Physical examination
time frame: Full (complete) physical examination at screening only. From Screening until follow-up (14-16 days after dosing day or final dosing day)
description: Full physical examination (review of all body systems - head/neck/thyroid, eyes/ears/nose/throat, respiratory, cardiovascular, lymph nodes, abdomen, skin, musculoskeletal, and neurological. Breast, anorectal, and genital examinations)
measure: Physical examination
time frame: Full (complete) physical examination at screening only. From Screening until follow-up (14-16 days after dosing day or final dosing day)
description: Height [centimeter]
measure: Physical examination
time frame: Full (complete) physical examination at screening only. From Screening until follow-up (14-16 days after dosing day or final dosing day)
description: Weight [kg]
measure: Physical examination
time frame: Full (complete) physical examination at screening only. From Screening until follow-up (14-16 days after dosing day or final dosing day)
description: BMI [kg/m^2]
measure: Physical examination
time frame: Full (complete) physical examination at screening only. From Screening until follow-up (14-16 days after dosing day or final dosing day)
description: Abbreviated (symptom-directed) physical examination.
measure: Peak expiratory flow rate
time frame: Assessed at admission (Day -1), pre-dose (baseline), 2 and 24 hours post-dose after the first dose (Day 1 dosing) and the last dose (Day 14 dosing for Part B), and follow-up (14-16 days after dosing day or final dosing day)
description: Peak expiratory flow rate [L/min], the maximum rate that a person can exhale during a short maximal expiratory effort after a full inspiration
measure: Columbia-Suicide Severity Rating Scale (Part B only)
time frame: From Screening until follow-up (14-16 days after dosing day or final dosing day). Baseline ("Lifetime/Recent") at Screening and "Since Last Visit" versions on other visits
description: Columbia-Suicide Severity Rating Scale (C-SSRS) is a brief questionnaire that provides for the identification, quantification, and standardized assessment of the occurrences and severity of suicidal ideation and behavior. The changes from baseline and clinical abnormalities will be assessed (units on a scale).
measure: Maximum concentration (Cmax) of SKL24741, SKL24742 (if appropriate), and possible metabolites (if deemed necessary) following the single and/or multiple dose administration of SKL24741
time frame: In Part A, pre-dose and up to 240 hours post-dose plasma samples. In Part B, Days 1 and 7: pre-dose and up to 24 hours post-dose, Days 3-6 and 9-13: pre-dose only, and Day 14: Pre-dose and up to 240 hours post-dose plasma samples
description: Maximum concentration (Cmax) [ng/mL] of SKL24741, SKL24742 (if appropriate), and possible metabolites (if deemed necessary) for the plasma concentration-time profiles
measure: Time to maximum concentration (tmax) of SKL24741, SKL24742 (if appropriate), and possible metabolites (if deemed necessary) following the single and/or multiple dose administration of SKL24741
time frame: In Part A, pre-dose and up to 240 hours post-dose plasma samples. In Part B, Days 1 and 7: pre-dose and up to 24 hours post-dose, Days 3-6 and 9-13: pre-dose only, and Day 14: Pre-dose and up to 240 hours post-dose plasma samples
description: Time to maximum concentration (tmax) [hours, or h] of SKL24741, SKL24742 (if appropriate), and possible metabolites (if deemed necessary) for the plasma concentration-time profiles
measure: Area under the concentration-time curve (AUC) from 0 to infinity (AUC∞) of SKL24741, SKL24742 (if appropriate), and possible metabolites (if deemed necessary) following the single and/or multiple dose administration of SKL24741
time frame: In Part A, pre-dose and up to 240 hours post-dose plasma samples. In Part B, Days 1 and 7: pre-dose and up to 24 hours post-dose, Days 3-6 and 9-13: pre-dose only, and Day 14: Pre-dose and up to 240 hours post-dose plasma samples
description: Area under the concentration-time curve (AUC) from 0 to infinity (AUC∞) [ng*h/mL] of SKL24741, SKL24742 (if appropriate), and possible metabolites (if deemed necessary) for the plasma concentration-time profiles after a single dose administration
measure: AUC from time 0 to a given time t (AUCt) of SKL24741, SKL24742 (if appropriate), and possible metabolites (if deemed necessary) following the single and/or multiple dose administration of SKL24741
time frame: In Part A, pre-dose and up to 240 hours post-dose plasma samples. In Part B, Days 1 and 7: pre-dose and up to 24 hours post-dose, Days 3-6 and 9-13: pre-dose only, and Day 14: Pre-dose and up to 240 hours post-dose plasma samples
description: AUC from time 0 to a given time t (AUCt) [ng*h/mL] of SKL24741, SKL24742 (if appropriate), and possible metabolites (if deemed necessary) for the plasma concentration-time profiles
measure: AUC over the dosing interval (AUCτ) of SKL24741, SKL24742 (if appropriate), and possible metabolites (if deemed necessary) following the single and/or multiple dose administration of SKL24741
time frame: In Part A, pre-dose and up to 240 hours post-dose plasma samples. In Part B, Days 1 and 7: pre-dose and up to 24 hours post-dose, Days 3-6 and 9-13: pre-dose only, and Day 14: Pre-dose and up to 240 hours post-dose plasma samples
description: AUC over the dosing interval (AUCτ) [ng*h/mL] of SKL24741, SKL24742 (if appropriate), and possible metabolites (if deemed necessary) for the plasma concentration-time profiles
measure: Apparent clearance (CL/F) of SKL24741, SKL24742 (if appropriate), and possible metabolites (if deemed necessary) following the single and/or multiple dose administration of SKL24741
time frame: In Part A, pre-dose and up to 240 hours post-dose plasma samples. In Part B, Days 1 and 7: pre-dose and up to 24 hours post-dose, Days 3-6 and 9-13: pre-dose only, and Day 14: Pre-dose and up to 240 hours post-dose plasma samples
description: Apparent clearance (CL/F) [L/h] of SKL24741, SKL24742 (if appropriate), and possible metabolites (if deemed necessary) for the plasma concentration-time profiles
measure: Apparent volume of distribution (Vd/F) of SKL24741, SKL24742 (if appropriate), and possible metabolites (if deemed necessary) following the single and/or multiple dose administration of SKL24741
time frame: In Part A, pre-dose and up to 240 hours post-dose plasma samples. In Part B, Days 1 and 7: pre-dose and up to 24 hours post-dose, Days 3-6 and 9-13: pre-dose only, and Day 14: Pre-dose and up to 240 hours post-dose plasma samples
description: Apparent volume of distribution (Vd/F) [Liter, or L] of SKL24741, SKL24742 (if appropriate), and possible metabolites (if deemed necessary) for the plasma concentration-time profiles
measure: Half-life (t1/2) of SKL24741, SKL24742 (if appropriate), and possible metabolites (if deemed necessary) following the single and/or multiple dose administration of SKL24741
time frame: In Part A, pre-dose and up to 240 hours post-dose plasma samples. In Part B, Days 1 and 7: pre-dose and up to 24 hours post-dose, Days 3-6 and 9-13: pre-dose only, and Day 14: Pre-dose and up to 240 hours post-dose plasma samples
description: Half-life (t1/2) [hour] of SKL24741, SKL24742 (if appropriate), and possible metabolites (if deemed necessary) for the plasma concentration-time profiles
measure: Accumulation ratio (Racc) of SKL24741, SKL24742 (if appropriate), and possible metabolites (if deemed necessary) following the single and/or multiple dose administration of SKL24741
time frame: In Part A, pre-dose and up to 240 hours post-dose plasma samples. In Part B, Days 1 and 7: pre-dose and up to 24 hours post-dose, Days 3-6 and 9-13: pre-dose only, and Day 14: Pre-dose and up to 240 hours post-dose plasma samples
description: Accumulation ratio (Racc) [unit of ratio] of SKL24741, SKL24742 (if appropriate), and possible metabolites (if deemed necessary) for the plasma concentration-time profiles
measure: Fraction excreted unchanged in the urine (fe) of SKL24741, SKL24742 (if appropriate), and possible metabolites (if deemed necessary) following the single dose administration of SKL24741
time frame: In Part A, pre-dose and up to 240 hours post-dose urine samples.
description: Fraction excreted unchanged in the urine (fe) [unit of fraction] of SKL24741, SKL24742 (if appropriate), and possible metabolites (if deemed necessary) for the urine concentration-time profiles
measure: Renal clearance (CLr) of SKL24741, SKL24742 (if appropriate), and possible metabolites (if deemed necessary) following the single dose administration of SKL24741
time frame: In Part A, pre-dose and up to 240 hours post-dose urine samples.
description: Renal clearance (CLr) [Liter/h or milliliter/min] of SKL24741, SKL24742 (if appropriate), and possible metabolites (if deemed necessary) for the urine concentration-time profiles
arm group label: Single Ascending Dose Level 1
arm group type: Experimental
description: 4 Subjects will receive one dose of 10 mg and 2 subjects will receive one dose of placebo
arm group label: Single Ascending Dose Level 2
arm group type: Experimental
description: 4 Subjects will receive one dose of 25 mg and 2 subjects will receive one dose of placebo
arm group label: Single Ascending Dose Level 3
arm group type: Experimental
description: 4 Subjects will receive one dose of 50 mg and 2 subjects will receive one dose of placebo
arm group label: Single Ascending Dose Level 4
arm group type: Experimental
description: 4 Subjects will receive one dose of 100 mg and 2 subjects will receive one dose of placebo
arm group label: Single Ascending Dose Level 5
arm group type: Experimental
description: 4 Subjects will receive one dose of 200 mg and 2 subjects will receive one dose of placebo
arm group label: Single Ascending Dose Level 6
arm group type: Experimental
description: 4 Subjects will receive one dose of 300 mg and 2 subjects will receive one dose of placebo
arm group label: Single Ascending Dose Level 7
arm group type: Experimental
description: 4 Subjects will receive one dose of 400 mg and 2 subjects will receive one dose of placebo
arm group label: Single Ascending Dose Level 8
arm group type: Experimental
description: 4 Subjects will receive one dose of 800 mg and 2 subjects will receive one dose of placebo
arm group label: Single Ascending Dose Level 9
arm group type: Experimental
description: 4 Subjects will receive one dose of 1200 mg and 2 subjects will receive one dose of placebo
arm group label: Single Ascending Dose Level 10
arm group type: Experimental
description: 4 Subjects will receive one dose on the outcome of preceding dose levels and 2 subjects will receive one dose of placebo
arm group label: Multiple Ascending Dose Level 1
arm group type: Experimental
description: 6 Subjects will receive one dose of 50 mg each day for 14 days and 2 subjects will receive one dose placebo every day for 14 days. The dose will be determined based on the outcome of Part A (Single Ascending Dose).
arm group label: Multiple Ascending Dose Level 2
arm group type: Experimental
description: 6 Subjects will receive one dose of 200 mg each day for 14 days and 2 subjects will receive one dose placebo every day for 14 days. The dose will be determined based on the outcome of Part A (Single Ascending Dose) and/or preceding dose levels of Part B (Multiple Ascending Dose).
arm group label: Multiple Ascending Dose Level 3
arm group type: Experimental
description: 6 Subjects will receive one dose of 400 mg each day for 14 days and 2 subjects will receive one dose placebo every day for 14 days. The dose will be determined based on the outcome of Part A (Single Ascending Dose) and/or preceding dose levels of Part B (Multiple Ascending Dose).
arm group label: Multiple Ascending Dose Level 4
arm group type: Experimental
description: 6 Subjects will receive one dose of 800 mg each day for 14 days and 2 subjects will receive one dose placebo every day for 14 days. The dose will be determined based on the outcome of Part A (Single Ascending Dose) and/or preceding dose levels of Part B (Multiple Ascending Dose).
arm group label: Multiple Ascending Dose Level 5
arm group type: Experimental
description: 6 Subjects will receive one dose of 1200 mg each day for 14 days and 2 subjects will receive one dose placebo every day for 14 days. The dose will be determined based on the outcome of Part A (Single Ascending Dose) and/or preceding dose levels of Part B (Multiple Ascending Dose).
arm group label: Multiple Ascending Dose Level 6
arm group type: Experimental
description: 6 Subjects will receive one dose of 1200 mg each day (using tablet formulation instead of capsule formulation*) for 14 days and 2 subjects will receive one dose placebo every day for 14 days. The dose will be determined based on the outcome of Part A (Single Ascending Dose) and/or preceding dose levels of Part B (Multiple Ascending Dose).
*Tablet formulation is utilized, instead of capsule formulation, in the marked dose levels.
arm group label: Food Effect Cohort
arm group type: Experimental
description: After completing the fasting Single Ascending Dose escalation, the same 6 subjects who received one dose of 50 mg under fasting conditions will return to the clinic after a washout period for a second confinement to receive a second dose (same as fasting) under fed conditions.
arm group label: Gender Effect Cohort
arm group type: Experimental
description: 6 female subjects of non-childbearing potential will receive one dose of 50 mg under fasting conditions.
arm group label: Optional Food Effect Cohort
arm group type: Experimental
description: Up to 12 male subjects will undergo an open-label, two period, two-sequence crossover design at the maximum daily dose tested in Part A.
arm group label: Optional Formulation Effect Cohort
arm group type: Experimental
description: Up to 12 male subjects will be treated with the maximum daily dose tested in Part A using open-label, two period, two-sequence crossover design.
arm group label: Multiple Ascending Dose Level 7
arm group type: Experimental
description: 6 Subjects will receive one dose of 2000 mg each day (using tablet formulation instead of capsule formulation*) for 14 days and 2 subjects will receive one dose placebo every day for 14 days. The dose will be determined based on the outcome of Part A (Single Ascending Dose) and/or preceding dose levels of Part B (Multiple Ascending Dose).
*Tablet formulation is utilized, instead of capsule formulation, in the marked dose levels.
arm group label: Multiple Ascending Dose Level 8
arm group type: Experimental
description: 6 Subjects will receive one dose each day (using tablet formulation instead of capsule formulation*) for 14 days and 2 subjects will receive one dose placebo every day for 14 days. The dose will be determined based on the outcome of Part A (Single Ascending Dose) and/or preceding dose levels of Part B (Multiple Ascending Dose).
*Tablet formulation is utilized, instead of capsule formulation, in the marked dose levels.
intervention type: Drug
intervention name: SKL24741
description: An inhibitor of voltage-gated sodium channels and a possible activator of Big Potassium channels. Administered as an oral dose in the form of a capsule or tablet.
arm group label: Food Effect Cohort
arm group label: Gender Effect Cohort
arm group label: Multiple Ascending Dose Level 1
arm group label: Multiple Ascending Dose Level 2
arm group label: Multiple Ascending Dose Level 3
arm group label: Multiple Ascending Dose Level 4
arm group label: Multiple Ascending Dose Level 5
arm group label: Multiple Ascending Dose Level 6
arm group label: Multiple Ascending Dose Level 7
arm group label: Multiple Ascending Dose Level 8
arm group label: Optional Food Effect Cohort
arm group label: Optional Formulation Effect Cohort
arm group label: Single Ascending Dose Level 1
arm group label: Single Ascending Dose Level 10
arm group label: Single Ascending Dose Level 2
arm group label: Single Ascending Dose Level 3
arm group label: Single Ascending Dose Level 4
arm group label: Single Ascending Dose Level 5
arm group label: Single Ascending Dose Level 6
arm group label: Single Ascending Dose Level 7
arm group label: Single Ascending Dose Level 8
arm group label: Single Ascending Dose Level 9
intervention type: Drug
intervention name: Placebo
description: Sugar pill manufactured to mimic SKL24741
arm group label: Multiple Ascending Dose Level 1
arm group label: Multiple Ascending Dose Level 2
arm group label: Multiple Ascending Dose Level 3
arm group label: Multiple Ascending Dose Level 4
arm group label: Multiple Ascending Dose Level 5
arm group label: Multiple Ascending Dose Level 6
arm group label: Multiple Ascending Dose Level 7
arm group label: Multiple Ascending Dose Level 8
arm group label: Single Ascending Dose Level 1
arm group label: Single Ascending Dose Level 10
arm group label: Single Ascending Dose Level 2
arm group label: Single Ascending Dose Level 3
arm group label: Single Ascending Dose Level 4
arm group label: Single Ascending Dose Level 5
arm group label: Single Ascending Dose Level 6
arm group label: Single Ascending Dose Level 7
arm group label: Single Ascending Dose Level 8
arm group label: Single Ascending Dose Level 9
criteria: 
gender: All
gender based: Yes
gender description: This study will enroll up to 138 Healthy Male Subjects and 6 Non-childbearing potential Female Subjects.
minimum age: 18 Years
maximum age: 50 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Vijaykumar Vashi, PhD
role: Study Director
affiliation: SK Life Science, Inc.
facility: 
country: United States
responsible party type: Sponsor
sharing ipd: No
provided document: 