HealthyPhase 1NCT04505397

Single-Dose Escalation Study Followed by a Multiple-Dose Escalation Study of SKL24741 in Healthy Subjects

A Phase 1 study testing SKL24741 in people with Healthy, run by SK Life Science, Inc. at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Trial summary

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. Read more about this study

Who is it for?: Ages 18 to 50 yearsHealthy volunteers can take part
Conditions the study is for: Healthy
What is being tested?: SKL24741
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 111 participants
Where: 1 siteUnited States
Study dates: 13 Feb 2020to 27 Oct 2022
Phase: Phase 1
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 50 years
All sexes
Healthy volunteers accepted
Adult

Who may be able to join

Male subjects of 18 to 50 years of age (inclusive) except for the gender effect cohort
Able to read, understand, sign, and date a written informed consent form (ICF) before study participation at screening
Agree to use 2 highly effective methods of contraception, including at least one barrier method (Section 10.6.7 for details)
Body mass index (BMI) between 18.0 and 30.0 kg/m2 (inclusive) at screening
Judged to be in good health on the basis of medical history, physical examination, and routine laboratory measurements (i.e., without clinically relevant pathology)
Normal electrocardiogram (ECG) (12-lead), arterial blood pressure, and heart rate within the normal range of the study center or considered not clinically significant by the investigator and in agreement with the Sponsor
Able to understand and comply with protocol requirements and instructions and likely to complete the study as planned
For Part A (gender effect cohort): Female of non-childbearing potential (18 to 50 years of age (inclusive)), who have undergone a sterilization procedure at least 6 months prior to dosing with official documentation (e.g., hysteroscopic sterilization, bilateral tubal ligation or bilateral salpingectomy, hysterectomy, or bilateral oophorectomy), or be postmenopausal with amenorrhea for at least 1 year prior to dosing and follicle-stimulating hormone (FSH) serum levels consistent with postmenopausal status as per Principal Investigator's judgment

Who cannot join

History of any illness or condition that, in the opinion of the investigator, might confound the results of the study or pose an additional risk in administering study drug to the subjects.
Smokers (subjects who have smoked within 6 months at screening or those with positive results from smoking screening).
Cholecystectomy and/or surgery of the gastrointestinal tract that could interfere with pharmacokinetics of the trial medication (except appendectomy and simple hernia repair).
Regular treatment with prescription medications. Subjects should have ended any prescription medications at least 14 days before the first dosing of the study drug. Potential subjects should only stop any prescribed medication at the direction of a physician.
Regular treatment with nonprescription medications. Subjects should have ended any nonprescription medications at least 14 days before the first dosing of the study drug. Potential subjects should consult a physician before stopping any regular treatment with nonprescription medication.
Consumption of herbal medications, dietary supplements, and specific fruit products. Subjects should have stopped consumption of herbal medications or dietary supplements (e.g., St. John's Wort, ginkgo biloba, and garlic supplements), vitamins, and grapefruit or grapefruit juice, or Seville oranges at least 14 days before the first dosing of study drug.

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History of drug or alcohol abuse or addiction within 2 years before the start of study drug dosing, or a positive test results for alcohol or drugs of abuse, such as amphetamine, barbiturate, benzodiazepine, cocaine, methadone, opiates, oxycodone, phencyclidine, propoxyphene, cannabinoid (THC), MDMA (Ecstasy), methaqualone, and tricyclic antidepressant (TCA).
Regular consumption of more than 2 units of alcoholic beverages per day or more than 14 units per week (1 unit of alcohol equals 1 pint [473 mL] of beer or lager, 1 glass [125 mL] of wine, 25 mL shot of 40% spirit) before screening. Subjects may not consume any alcohol from 72 hours before the first dosing of study drug through the completion of the last PK sampling.
Consumption of an average of more than 5 servings (8 ounces per serving) per day of coffee, cola, or other caffeinated beverage before screening. Subjects may not consume any caffeinated beverages from 48 hours prior to dosing until the collection of the last PK sample.
Participation in a clinical study involving administration of either an investigational or a marketed drug within 2 months or 7 half-lives (whichever is longer) before screening.
Blood donation or a significant loss of blood within 60 days of the start of study drug dosing or donation of more than 1 unit of plasma within 7 days before screening.
Positive result at screening for any of the following infectious disease tests: hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab), human immunodeficiency virus antigen and antibody (HIV Ag, HIV Ab)
Illness within 5 days before the start of study drug dosing ("illness" is defined as an acute [serious or non-serious] condition [e.g., the flu or the common cold])
History of any known relevant allergy/hypersensitivity (including allergy to the trial medication or its excipients)
Subject who is judged not eligible for study participation by investigator

Trial locations and contacts

1 site in 1 country.

United States1 site

Spaulding Clinical Research
West Bend, Wisconsin, 53095

Other trials in United States

About this study

Official title: A Phase 1, Randomized, Double-Blinded, Single-Dose Escalation Study Followed by a Multiple-Dose Escalation Study of SKL24741 in Healthy Subjects

Read the detailed description

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

Conditions: Healthy
Being tested: SKL24741, Placebo

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

SKL24741Drug
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.
PlaceboDrug
Sugar pill manufactured to mimic SKL24741

Study groups in NCT04505397
Study group	Role	What they receive
Single Ascending Dose Level 1	Experimental	4 Subjects will receive one dose of 10 mg and 2 subjects will receive one dose of placebo Receives: Drug: SKL24741; Drug: Placebo
Single Ascending Dose Level 2	Experimental	4 Subjects will receive one dose of 25 mg and 2 subjects will receive one dose of placebo Receives: Drug: SKL24741; Drug: Placebo
Single Ascending Dose Level 3	Experimental	4 Subjects will receive one dose of 50 mg and 2 subjects will receive one dose of placebo Receives: Drug: SKL24741; Drug: Placebo
Single Ascending Dose Level 4	Experimental	4 Subjects will receive one dose of 100 mg and 2 subjects will receive one dose of placebo Receives: Drug: SKL24741; Drug: Placebo
Single Ascending Dose Level 5	Experimental	4 Subjects will receive one dose of 200 mg and 2 subjects will receive one dose of placebo Receives: Drug: SKL24741; Drug: Placebo
Single Ascending Dose Level 6	Experimental	4 Subjects will receive one dose of 300 mg and 2 subjects will receive one dose of placebo Receives: Drug: SKL24741; Drug: Placebo
Single Ascending Dose Level 7	Experimental	4 Subjects will receive one dose of 400 mg and 2 subjects will receive one dose of placebo Receives: Drug: SKL24741; Drug: Placebo
Single Ascending Dose Level 8	Experimental	4 Subjects will receive one dose of 800 mg and 2 subjects will receive one dose of placebo Receives: Drug: SKL24741; Drug: Placebo
Single Ascending Dose Level 9	Experimental	4 Subjects will receive one dose of 1200 mg and 2 subjects will receive one dose of placebo Receives: Drug: SKL24741; Drug: Placebo
Single Ascending Dose Level 10	Experimental	4 Subjects will receive one dose on the outcome of preceding dose levels and 2 subjects will receive one dose of placebo Receives: Drug: SKL24741; Drug: Placebo
Multiple Ascending Dose Level 1	Experimental	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). Receives: Drug: SKL24741; Drug: Placebo
Multiple Ascending Dose Level 2	Experimental	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). Receives: Drug: SKL24741; Drug: Placebo
Multiple Ascending Dose Level 3	Experimental	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). Receives: Drug: SKL24741; Drug: Placebo
Multiple Ascending Dose Level 4	Experimental	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). Receives: Drug: SKL24741; Drug: Placebo
Multiple Ascending Dose Level 5	Experimental	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). Receives: Drug: SKL24741; Drug: Placebo
Multiple Ascending Dose Level 6	Experimental	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. Receives: Drug: SKL24741; Drug: Placebo
Food Effect Cohort	Experimental	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. Receives: Drug: SKL24741
Gender Effect Cohort	Experimental	6 female subjects of non-childbearing potential will receive one dose of 50 mg under fasting conditions. Receives: Drug: SKL24741
Optional Food Effect Cohort	Experimental	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. Receives: Drug: SKL24741
Optional Formulation Effect Cohort	Experimental	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. Receives: Drug: SKL24741
Multiple Ascending Dose Level 7	Experimental	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. Receives: Drug: SKL24741; Drug: Placebo
Multiple Ascending Dose Level 8	Experimental	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. Receives: Drug: SKL24741; Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

Adverse events (Incidence of treatment-emergent adverse events)
The number [count] and percentage [%] of subjects experiencing an adverse event
Measured: From Screening until follow-up (14-16 days after dosing day or final dosing day)
Clinically significant laboratory assessments
Hematology, coagulation, clinical chemistry, urinalysis, and cholesterol
Measured: From Screening until follow-up (14-16 days after dosing day or final dosing day)
Electrocardiogram outcomes
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.
Measured: 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)
Vital sign
Blood pressure (systolic and diastolic measurements in supine and standing in the same sequence in each subject, in order to allow orthostatic measurements) [mmHg]
Measured: 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)
Vital sign
Temperature [Celsius]
Measured: 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)
Vital sign
Heart rate [beats/min]
Measured: 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)
Vital sign
Respiratory rate [breaths/min]
Measured: 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)
Vital signs
Arterial oxygen saturation (SaO2) (using pulse oximetry) [%]
Measured: 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)
Physical examination
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)
Measured: Full (complete) physical examination at screening only. From Screening until follow-up (14-16 days after dosing day or final dosing day)
Physical examination
Height [centimeter]
Measured: Full (complete) physical examination at screening only. From Screening until follow-up (14-16 days after dosing day or final dosing day)
Physical examination
Weight [kg]
Measured: Full (complete) physical examination at screening only. From Screening until follow-up (14-16 days after dosing day or final dosing day)
Physical examination
BMI [kg/m^2]
Measured: Full (complete) physical examination at screening only. From Screening until follow-up (14-16 days after dosing day or final dosing day)
Physical examination
Abbreviated (symptom-directed) physical examination.
Measured: Full (complete) physical examination at screening only. From Screening until follow-up (14-16 days after dosing day or final dosing day)
Peak expiratory flow rate
Peak expiratory flow rate [L/min], the maximum rate that a person can exhale during a short maximal expiratory effort after a full inspiration
Measured: 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)
Columbia-Suicide Severity Rating Scale (Part B only)
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).
Measured: 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

Secondary outcomes (9)

Maximum concentration (Cmax) of SKL24741, SKL24742 (if appropriate), and possible metabolites (if deemed necessary) following the single and/or multiple dose administration of SKL24741
Maximum concentration (Cmax) [ng/mL] of SKL24741, SKL24742 (if appropriate), and possible metabolites (if deemed necessary) for the plasma concentration-time profiles
Measured: 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 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 to maximum concentration (tmax) [hours, or h] of SKL24741, SKL24742 (if appropriate), and possible metabolites (if deemed necessary) for the plasma concentration-time profiles
Measured: 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
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
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
Measured: 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
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
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
Measured: 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
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
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
Measured: 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
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
Apparent clearance (CL/F) [L/h] of SKL24741, SKL24742 (if appropriate), and possible metabolites (if deemed necessary) for the plasma concentration-time profiles
Measured: 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
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
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
Measured: 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
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
Half-life (t1/2) [hour] of SKL24741, SKL24742 (if appropriate), and possible metabolites (if deemed necessary) for the plasma concentration-time profiles
Measured: 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
Accumulation ratio (Racc) of SKL24741, SKL24742 (if appropriate), and possible metabolites (if deemed necessary) following the single and/or multiple dose administration of SKL24741
Accumulation ratio (Racc) [unit of ratio] of SKL24741, SKL24742 (if appropriate), and possible metabolites (if deemed necessary) for the plasma concentration-time profiles
Measured: 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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

13 Feb 202027 Oct 2022

First posted10 Aug 2020
Study start13 Feb 2020
Primary completion27 Oct 2022
Study completion27 Oct 2022

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for HealthyStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Sequential
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 111 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04505397
Sponsor's protocol ID: SKL24741C001
Status last verified: Dec 2023
First submitted: 30 Jan 2020
Last updated: 21 Dec 2023
Results posted: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 21 Dec 2023. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase 1, Randomized, Double-Blinded, Single-Dose Escalation Study Followed by a Multiple-Dose Escalation Study of SKL24741 in Healthy Subjects
ClinicalTrials.gov ID: NCT04505397
Acronym / sponsor ID: SKL24741C001
Conditions: Healthy
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 111 participants (actual)
Lead sponsor: SK Life Science, Inc.Industry (pharma, biotech, devices)
Collaborators: Spaulding Clinical Research LLC, Covance
Study start: 13 Feb 2020 (actual)
Primary completion: 27 Oct 2022 (actual)
Study completion: 27 Oct 2022 (actual)
First posted: 10 Aug 2020 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

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

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Sequential
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 22

Arm	Type	Receives
Single Ascending Dose Level 1	Experimental	Drug: SKL24741, Drug: Placebo4 Subjects will receive one dose of 10 mg and 2 subjects will receive one dose of placebo
Single Ascending Dose Level 2	Experimental	Drug: SKL24741, Drug: Placebo4 Subjects will receive one dose of 25 mg and 2 subjects will receive one dose of placebo
Single Ascending Dose Level 3	Experimental	Drug: SKL24741, Drug: Placebo4 Subjects will receive one dose of 50 mg and 2 subjects will receive one dose of placebo
Single Ascending Dose Level 4	Experimental	Drug: SKL24741, Drug: Placebo4 Subjects will receive one dose of 100 mg and 2 subjects will receive one dose of placebo
Single Ascending Dose Level 5	Experimental	Drug: SKL24741, Drug: Placebo4 Subjects will receive one dose of 200 mg and 2 subjects will receive one dose of placebo
Single Ascending Dose Level 6	Experimental	Drug: SKL24741, Drug: Placebo4 Subjects will receive one dose of 300 mg and 2 subjects will receive one dose of placebo
Single Ascending Dose Level 7	Experimental	Drug: SKL24741, Drug: Placebo4 Subjects will receive one dose of 400 mg and 2 subjects will receive one dose of placebo
Single Ascending Dose Level 8	Experimental	Drug: SKL24741, Drug: Placebo4 Subjects will receive one dose of 800 mg and 2 subjects will receive one dose of placebo
Single Ascending Dose Level 9	Experimental	Drug: SKL24741, Drug: Placebo4 Subjects will receive one dose of 1200 mg and 2 subjects will receive one dose of placebo
Single Ascending Dose Level 10	Experimental	Drug: SKL24741, Drug: Placebo4 Subjects will receive one dose on the outcome of preceding dose levels and 2 subjects will receive one dose of placebo
Multiple Ascending Dose Level 1	Experimental	Drug: SKL24741, Drug: Placebo6 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).
Multiple Ascending Dose Level 2	Experimental	Drug: SKL24741, Drug: Placebo6 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).
Multiple Ascending Dose Level 3	Experimental	Drug: SKL24741, Drug: Placebo6 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).
Multiple Ascending Dose Level 4	Experimental	Drug: SKL24741, Drug: Placebo6 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).
Multiple Ascending Dose Level 5	Experimental	Drug: SKL24741, Drug: Placebo6 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).
Multiple Ascending Dose Level 6	Experimental	Drug: SKL24741, Drug: Placebo6 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.
Food Effect Cohort	Experimental	Drug: SKL24741After 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.
Gender Effect Cohort	Experimental	Drug: SKL247416 female subjects of non-childbearing potential will receive one dose of 50 mg under fasting conditions.
Optional Food Effect Cohort	Experimental	Drug: SKL24741Up to 12 male subjects will undergo an open-label, two period, two-sequence crossover design at the maximum daily dose tested in Part A.
Optional Formulation Effect Cohort	Experimental	Drug: SKL24741Up 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.
Multiple Ascending Dose Level 7	Experimental	Drug: SKL24741, Drug: Placebo6 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.
Multiple Ascending Dose Level 8	Experimental	Drug: SKL24741, Drug: Placebo6 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.

Who may qualify

Ages: 18 to 50 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (8 listed)

Male subjects of 18 to 50 years of age (inclusive) except for the gender effect cohort
Able to read, understand, sign, and date a written informed consent form (ICF) before study participation at screening
Agree to use 2 highly effective methods of contraception, including at least one barrier method (Section 10.6.7 for details)
Body mass index (BMI) between 18.0 and 30.0 kg/m2 (inclusive) at screening
Judged to be in good health on the basis of medical history, physical examination, and routine laboratory measurements (i.e., without clinically relevant pathology)

Key exclusion criteria (15 listed)

History of any illness or condition that, in the opinion of the investigator, might confound the results of the study or pose an additional risk in administering study drug to the subjects.
Smokers (subjects who have smoked within 6 months at screening or those with positive results from smoking screening).
Cholecystectomy and/or surgery of the gastrointestinal tract that could interfere with pharmacokinetics of the trial medication (except appendectomy and simple hernia repair).
Regular treatment with prescription medications. Subjects should have ended any prescription medications at least 14 days before the first dosing of the study drug. Potential subjects should only stop any prescribed medication at the direction of a physician.
Regular treatment with nonprescription medications. Subjects should have ended any nonprescription medications at least 14 days before the first dosing of the study drug. Potential subjects should consult a physician before stopping any regular treatment with nonprescription medication.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
SKL24741An 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.	Drug	Food Effect Cohort, Gender Effect Cohort, Multiple Ascending Dose Level 1, Multiple Ascending Dose Level 2, Multiple Ascending Dose Level 3, Multiple Ascending Dose Level 4, Multiple Ascending Dose Level 5, Multiple Ascending Dose Level 6, Multiple Ascending Dose Level 7, Multiple Ascending Dose Level 8, Optional Food Effect Cohort, Optional Formulation Effect Cohort, Single Ascending Dose Level 1, Single Ascending Dose Level 10, Single Ascending Dose Level 2, Single Ascending Dose Level 3, Single Ascending Dose Level 4, Single Ascending Dose Level 5, Single Ascending Dose Level 6, Single Ascending Dose Level 7, Single Ascending Dose Level 8, Single Ascending Dose Level 9
PlaceboSugar pill manufactured to mimic SKL24741	Drug	Multiple Ascending Dose Level 1, Multiple Ascending Dose Level 2, Multiple Ascending Dose Level 3, Multiple Ascending Dose Level 4, Multiple Ascending Dose Level 5, Multiple Ascending Dose Level 6, Multiple Ascending Dose Level 7, Multiple Ascending Dose Level 8, Single Ascending Dose Level 1, Single Ascending Dose Level 10, Single Ascending Dose Level 2, Single Ascending Dose Level 3, Single Ascending Dose Level 4, Single Ascending Dose Level 5, Single Ascending Dose Level 6, Single Ascending Dose Level 7, Single Ascending Dose Level 8, Single Ascending Dose Level 9

Primary outcome

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)
The number [count] and percentage [%] of subjects experiencing an adverse event
Clinically significant laboratory assessments
Time frame: From Screening until follow-up (14-16 days after dosing day or final dosing day)
Hematology, coagulation, clinical chemistry, urinalysis, and cholesterol
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)
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.
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)
Blood pressure (systolic and diastolic measurements in supine and standing in the same sequence in each subject, in order to allow orthostatic measurements) [mmHg]
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)
Temperature [Celsius]
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)
Heart rate [beats/min]
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)
Respiratory rate [breaths/min]
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)
Arterial oxygen saturation (SaO2) (using pulse oximetry) [%]
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)
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)
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)
Height [centimeter]
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)
Weight [kg]
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)
BMI [kg/m^2]
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)
Abbreviated (symptom-directed) physical examination.
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)
Peak expiratory flow rate [L/min], the maximum rate that a person can exhale during a short maximal expiratory effort after a full inspiration
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
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).

9 secondary outcomes

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
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
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
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
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
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
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
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
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

Results and safety

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 21 Dec 2023.
Individual participant dataSharing planned: No

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Vijaykumar Vashi, PhD study director

SK Life Science, Inc.

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing SKL24741 in people with Healthy, run by SK Life Science, Inc. at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 21 Dec 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome 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)). The study lists 15 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04505397.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Dec 2023.