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

Healthy Subjects Clinical Trial

Official title: A Randomized, Double-blind, Placebo-controlled Phase 1 Study to Evaluate the Safety, Tolerability, Pharmacokinetics of Single and Multiple Ascending Oral Doses of SUL-238 in Healthy Subjects

Status Recruiting

Clinical Trial 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).

Clinical Trial Description

This double-blind placebo-controlled study will be completed in 3 parts.

First part will be single ascending dose in which 6 different oral doses (50 mg, 100 mg, 250 mg, 500 mg, 1000 mg and 2000 mg) will be administered to healthy adult male subjects. Each dosing group, including dose escalations, will be performed as described below:

Dose escalation will be performed until suspected adverse events (AEs) are observed. AEs will be evaluated by the blinded investigator, based on clinical signs detailed in the MedDRA criteria. At each dose level, 2 subjects will be administered SUL-238, whereas 1 subject will be administered the placebo. Escalation to the next higher dose level may occur only if no treatment-emergent AEs are observed in the 2 subjects that received SUL-238. If 1 out of 2 subjects experiences a suspected AE, 5 new subjects will be enrolled at the same dose level (4 subjects will receive one SUL-238 tablet and 1 subject will receive one placebo tablet). If no further suspected AEs occur, escalation to the next higher dose level will be performed. If any additional suspected AE is noted, dose escalation is stopped, and the previous dose level is considered the MTD. If suspected AE are observed in 2 subjects, dose escalation will be stopped and 5 new subjects (4 subjects will receive one SUL-238 tablet and 1 subject will receive one placebo tablet) will be enrolled at the next lower dose level. If no further suspected AE are observed, this dose level is considered the MTD.

The second part of the study will be single dose pharmacokinetics (SDPK) which 1 dose level below that with suspected AEs will be administered to 10 healthy adult male or female subjects (aged ≥40 years). Five male subjects and 5 female subjects will receive SUL-238. After obtaining the initial PK results from Part 1, at least 3 volunteers who accept to be tapped for a Cerebrospinal Fluid (CSF) will provide one CSF sample on Day 1, at the time point of 1 hour after reaching Cmax during Part 2 of the study.

The third part of the study will be multiple ascending oral doses of SUL-238 or placebo which 30 healthy elderly subjects (aged ≥40 years) will be included. There will be 2 dosing groups (n=15 for each) once (or twice) daily (5 male subjects and 5 female subjects) in each dosing group for SUL-238, dosing regimen and doses of SUL-238 will be decided after Part 2.

The maximum tolerated dose (MTD) will be the dose for the first dosing group. The second dosing group will be one below the MTD level (e.g., if MTD is 1000 mg, the second dosing group will receive 500 mg SUL-238). In the first dosing group three 3 male and 2 female subjects and in the second dosing group 2 male and 3 female subjects will receive placebo. PK parameters as well as renal clearance and percentage of drug excreted in urine and feces will be measured in both dosing groups. At least 3 volunteers who agreed to be tapped for a CSF in both dosing groups receiving SUL-238 will provide one CSF sample on day 15, at the time point of CSF sample obtained during Part 2 of the study.

In Part 1 and 2, blood samples will be drawn, before drug administration (0 hours), after 30 minutes and at the following time points: 1, 2, 4, 8, 12, 18, 24, 32, 48 and 72 hours. In Part 3, blood samples will be drawn, before drug administration (0 hours), after 30 minutes and at the following time points: 1, 2, 4, 8, 12, 18, 24, 32, 48 and 72 hours, Days 28 (pre-last dose baseline, post- last dose at 30 minutes, 1, 2, 4, 8, 12 and 18 hours), 29, 30 and 31. The subject randomized to placebo arm will provide blood samples as subjects randomized to active drug.

In Part 1 and Part 2, ambulatory visits will be performed at Day 8, 11, 15, 22 and 29 after dosing on which volunteers will visit the clinical investigational site. The volunteers will be followed up until Day 29. In Part 3, ambulatory visits will be performed at Day 8, 11, 15, 22, 35, 38, 42, 49 and 57 after dosing on which volunteers will visit the clinical investigational site. ;

Related Conditions & MeSH terms

• Healthy Subjects

• NCT number: NCT06277492
• Study type: Interventional
• Source: GEN Ilaç ve Saglik Ürünleri A.S.
• Contact: Nadir Ulu, MD, PhD
• Phone: +905334510385
• Email: n.ulu@genilac.com
• Status: Recruiting
• Phase: Phase 1
• Start date: February 19, 2024
• Completion date: November 8, 2025