A First-In-Human Study of Single and Multiple Ascending Doses of Oral SUL-238 in Healthy Subjects

NCT06277492 | Completed Phase 1

• 1 other identifier: GN-001
• Study Type: interventional
• Target: 83
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this randomized, double-blind, placebo-controlled, single-center study is to evaluate the safety, tolerability, pharmacokinetics of single and multiple oral doses of SUL-238 in healthy subjects (aged ≥40 years).

Conditions

Healthy Subjects

Keywords

SUL-238; Oral; Safety; Pharmacokinetics; Food effect

Outcome Measures

Primary Outcomes (5)

• Incidence of Treatment-Emergent Adverse Events as Measured by NCI-CTCAE criteria

  The safety and tolerability of SUL-238 will be assessed by documenting adverse events occurring after single dose administration on Day 1 in Part 1, Part 2 and Part 2B until Day 29. After once daily continuous dosing of SUL-238 for 14 Days in Part 3, the safety and tolerability of SUL-238 will be assessed by documenting adverse events occurring after during multiple dose administrations until Day 29. There will be no dosing between Day 15 and 29 in Part 3.

  Up to day 29

• Incidence of Treatment-Emergent Adverse Events as Measured by Clinical Laboratory Measurements According to Established Clinical Normal Ranges

  Clinical laboratory tests include hematology and clinical chemistry including renal function tests, hepatic enzymes, electrolytes and creatine kinase. * Change from baseline (pre-dose sample) at 24 hours (Day 2) and Days 3, 4, 8, 15 and 29 post-dose of SUL-238 (Part 1, Part 2). * Change from baseline (pre-dose sample) at 24 hours (Day 2) and Days 3, 4, 8, and from Day 14 (pre-second dose baseline), at 24 hours post-second dose (Day 16), and Days 17, 18, 22 and 29 post-first dose of SUL-238 (Part 2B). * Change from baseline (pre-dose sample) at 24 hours (Day 2) and at Days 3, 4, 8, 14 (1 hour post-last dose), 15 (24 hours post-last dose), 16, 17, 22 and 29 post-first dose SUL-238 for Part 3. * Blood and urine samples will be taken after administration of SUL-238 and values will be compared to baseline and established normal ranges to determine how SUL-238 administration impacts normal body function.

  Up to day 29

• Incidence of Treatment-Emergent Adverse Events as Measured by ECG

  * As compared to baseline (an ECG taken at 60 minutes pre-dose); ECG evaluations will be performed at 30 minutes, 1 hour, 12 hours post-dose and Days 2 (24 hours), 3, 4, 8, 15 and 29 post-dose of SUL-238 occurring after single dose administration (Part 1 and Part 2). * As compared to baseline (an ECG taken at 60 minutes pre-dose); ECG evaluations will be performed at 30 minutes, 1 hour, 12 hours post-first dose and Days 2 (24 hours), 3, 4, as well as Days 15 (at 60 minutes pre-second dose and at 30 minutes, 1 hour, 12 hours post-second dose), 16 (24 hours post-second dose), 17, 18, 22, and 29 (Part 2B). * As compared to baseline (an ECG taken at 60 minutes pre-dose); ECG evaluations will be performed at 30 minutes, 1 hour, 12 hours post-dose and Days 2 (24 hours), 3, 4, 8, 14 (1-hour post-last dose), 15, 16, 17, 22, and 29 post-dose SUL-238 for Part 3.

  Up to day 29

• Incidence of Treatment-Emergent Adverse Events as Measured by physical examination and vital signs

  Vital signs include blood pressure, heart rate and oral temperature. Change from baseline at every time points defined for Part 1, Part 2, Part 2B, and Part 3 until Day 29 post-first dose of SUL-238.

  Up to day 29

• Incidence of Treatment-Emergent Adverse Events as Measured by central nervous system (CNS) and autonomic nervous system (ANS) examination.

  After each dose of SUL-238 through completion of dosing, up to Day 29 in Part 1, Part 2, Part 2B, and Part 3, at all timepoints defined for the evaluation of adverse events, CNS and ANS examinations will be performed, and outcomes will be documented. CNS examinations should include evaluation of mental status, cranial and peripheral nerves, muscle strength, gait and coordination, sensations and reflexes. For the evaluation of ANS, the presence of postural hypotension, heart rate changes, pupil reflex change to light and signs and symptoms of decreased or absent sweating should be checked.

  Up to day 29

Secondary Outcomes (9)

• PK parameter: Maximum drug concentration in plasma (Cmax) of SUL-238 after a single ascending dose (Part 1 and Part 2).

  Part 1 and Part 2: Up to day 4

• Food effect on PK parameter: Maximum drug concentration in plasma (Cmax) of SUL-238 after a single dose (Part 2B).

  Up to day 18

• PK parameter: Maximum drug concentration in plasma (Cmax) of SUL-238 after multiple ascending doses (Part 3).

  Part 3: Up to day 17

• PK parameter: Area under the concentration-time curve in plasma (AUC) of SUL-238 after single ascending dose (Part 1 and Part 2).

  Part 1 and Part 2: Up to day 4

• Food effect on PK parameter: Area under the concentration-time curve in plasma (AUC) of SUL-238 after single dose in each period (Part 2B).

  Up to day 18

Study Arms (7)

Single dose SUL-238

ACTIVE COMPARATOR

PART 1: Single ascending oral doses of SUL-238 (50 mg, 100 mg, 250 mg, 500 mg, 1000 mg and 2000 mg)

Drug: Single ascending doses SUL-238

Single dose placebo

PLACEBO COMPARATOR

PART 1: Single oral dose of placebo

Drug: Single dose Placebo

Single dose pharmacokinetics of SUL-238

EXPERIMENTAL

PART 2: Single oral dose of SUL-238 (at maximum tolerated dose)

Drug: Single dose SUL-238

Multiple doses SUL-238

ACTIVE COMPARATOR

PART 3: Multiple ascending oral doses of SUL-238 (at maximum tolerated dose and 1 dose level lower than MTD)

Drug: Multiple ascending doses SUL-238

Multiple doses placebo

PLACEBO COMPARATOR

PART 3: Multiple oral doses of placebo

Drug: Multiple doses Placebo

Single dose pharmacokinetics of SUL-238 (food effect)

ACTIVE COMPARATOR

PART 2B: 2000 mg single oral dose of SUL-238

Drug: 2000 mg SUL-238 single dose for pharmacokinetics (food effect)

Single dose Placebo (food effect)

PLACEBO COMPARATOR

PART 2B: Single oral dose of placebo

Drug: Single dose placebo (food effect)

Interventions

Single ascending doses SUL-238 DRUG

PART 1: SUL-238 single ascending doses

Single dose SUL-238

Single dose Placebo DRUG

PART 1: Placebo single dose

Single dose placebo

Single dose SUL-238 DRUG

PART 2: SUL-238 single dose for pharmacokinetics

Single dose pharmacokinetics of SUL-238

Multiple ascending doses SUL-238 DRUG

PART 3: SUL-238 multiple ascending doses

Multiple doses SUL-238

Multiple doses Placebo DRUG

PART 3: Placebo multiple doses

Multiple doses placebo

2000 mg SUL-238 single dose for pharmacokinetics (food effect) DRUG

PART 2B: 2000 mg single dose of SUL-238

Single dose pharmacokinetics of SUL-238 (food effect)

Single dose placebo (food effect) DRUG

PART 2B: Placebo single dose

Single dose Placebo (food effect)

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Healthy as determined by the Investigator, based on a medical evaluation including medical history, physical examination, neurological examination, laboratory tests and cardiac monitoring.
• Men and women aged≥40 years at Screening.
• Subject must understand the nature of the study and provide signed and dated written informed consent in accordance with local regulations before the conduct of any study-related procedures.
• Able to complete all study related testing and evaluations.
• Women and men of child-bearing potential with partners of child-bearing potential must agree to use highly effective contraception. For male subjects, contraception should continue for 90 days after the last dose of investigational medicinal product (IMP, one spermatic cycle).
• Women of non-childbearing potential must be post-menopausal (the last menstrual period was at least 12 months ago, and follicle-stimulating hormone \[FSH\] at Screening confirms post-menopausal status), or have no uterus, ovaries, or fallopian tubes (or have their fallopian tubes tied). All women must have a negative pregnancy test result before administration of test article. Women who are surgically sterile must provide documentation of the procedure by an operative report or by ultrasound.
• Body weight \> 50 kg for men and \> 50 kg for women and Body Mass Index (BMI) within the range 18.5-30.0 kg/m2, inclusive.
• Subject must be, in the opinion of the Investigator, able to participate in all scheduled evaluations, likely to complete all required tests, and likely to be compliant.

You may not qualify if:

• A positive urine drug screen/alcohol breath test at Screening or Day -1.
• Any history of intellectual disability or psychiatric disorders, including substance use disorders, according to the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) criteria, except a history of mild depression/anxiety that has been resolved for at least the past 12 months.
• A positive Hepatitis B surface antigen, Hepatitis C antibody, or Human Immunodeficiency Virus (HIV) antibody test at Screening.
• Alanine aminotransferase or aspartate aminotransferase levels greater than 1.5 times the upper limit of normal (ULN) at Screening or between Screening and first dose administration.
• History of regular alcohol consumption within the last 12 months, defined as an average weekly intake of \>21 alcoholic drinks/week for men or \>14 alcoholic drinks/week for women.
• Regularly consumed (e.g., more days than not) excessive quantities of xanthine-containing beverages (e.g., more than five cups of coffee or the equivalent per day) within 30 days prior to Day -1.
• Received or used an investigational product (including placebo) or device within the following time period prior to Day -1 in the current study: 90 days, 5 half-lives, or twice the duration of the biological effect of the investigational product (whichever is longer).
• Use of prescription or non-prescription drugs, vitamins, herbal, and dietary supplements within 7 days (or 28 days if the drug is a potential hepatic enzyme inducer) or 5 half-lives (whichever is longer) prior to Day -1.
• History of clinically significant sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the Investigator or Medical Monitor, contraindicates their participation.
• A positive serum pregnancy test or lactation.
• A history or presence of any disease, condition, or surgery likely to affect drug absorption, distribution, metabolism, or excretion. Subjects with a history of cholecystectomy should be excluded.
• A history or presence of a clinically significant hepatic, renal, gastrointestinal, cardiovascular, endocrine, pulmonary, ophthalmologic, immunologic, hematologic, dermatologic, or neurologic abnormality.
• Any clinically significant abnormalities in rhythm, conduction, or morphology of the resting ECG and any abnormalities in the 12-lead ECG that, in the judgement of the Investigator or Medical Monitor, may interfere with the interpretation of QTc interval changes, including abnormal ST-T-wave morphology or left ventricular hypertrophy.
• A clinically significant vital signs abnormality at Screening or Day -1 This includes, but is not limited to, the following, in the sitting position (3 measurements, each 5 minutes apart): (a) systolic blood pressure \< 90 or \>140 mmHg, (b) diastolic blood pressure \< 50 or \> 95 mmHg, or (c) heart rate \< 45 or \> 100 beats per minute.
• Subjects who have previously been enrolled in this study.

Sponsors & Collaborators

• GEN İlaç ve Sağlık Ürünleri A.Ş.: lead
• Sulfateq B.V.: collaborator

Study Sites (1)

Erciyes University IKUM Center

Kayseri, 38030, Turkey (Türkiye)

Location

MeSH Terms

Interventions

Pharmacokinetics

Intervention Hierarchy (Ancestors)

Metabolism; Pharmacological and Toxicological Phenomena; Physiological Phenomena

Study Officials

• Zafer Sezer, MD

  Department of Pharmacology, Faculty of Medicine, Erciyes University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 19, 2024
• First Posted: February 26, 2024
• Study Start: February 19, 2024
• Primary Completion: July 11, 2025
• Study Completion: November 27, 2025
• Last Updated: December 1, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

TU (1)