Safety, Tolerability and Pharmacokinetic Study of KL1333 in Healthy Male Volunteers

Study Overview
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Brief Summary
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The purpose of this First In Human study is to investigate the safety and tolerability of KL1333 after a single oral dose and to investigate the pharmacokinetic characteristics of KL1333 after a single oral dose.

Official Title
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A Dose Block-randomized, Double-blind, Placebo-controlled, Single-dose, Dose-escalation, Phase I Clinical Study

Conditions
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MELAS Syndrome, Mitochondrial Respiratory Chain Deficiencies

Intervention / Treatment
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* Drug: KL1333 25 mg
* Drug: KL1333 50 mg
* Drug: KL1333 100 mg
* Drug: KL1333 200 mg
* Drug: KL1333 400 mg
* Drug: KL1333 600 mg
* Drug: KL1333 800 mg
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 19 - 45 years of age at the time of screening Subjects weighing ≥55 and ≤90 kg with BMI between 18 and 27 kg/m2 Subjects who agreed to voluntarily participate in this study and comply with all the study requirements by signing informed consent form after being informed of the nature of this study and understanding all aspects of this study Exclusion Criteria: History of clinically significant hepatic, renal, neurologic, immunologic, respiratory, endocrine disease or hematologic•oncologic disease, cardiovascular, psychiatric disease History of disease or surgery of the gastrointestinal tract that could interfere with kinetics of the study drug. Simple hernia repair or appendectomy are excepted. History of clinically significant or relevant allergy/hypersensitivity Blood AST (SGOT), ALT (SGPT) >1.5 of upper limit eGFR value of ≤90mL/min/1.73m2 Systolic blood pressure of <100 mmHg or >160 mmHg Diastolic blood pressure of <60 mmHg or >100 mmHg Any abnormalities in 12-lead ECG at screening visit Subjects who showed positive result in drug abuse tests, or who has history of drug abuse within 60 days prior to the time of screening Subjects who took prescribed medications or oriental medicine within 14 days or over-the-counter (OTC) medications or vitamins within 7 days prior to the dose of the study drug (however, the subject can be included if other criteria are met according to the discretion of the investigator) Subjects who were administered any investigational products within 3 months from the first dose of the study drug Subjects who have donated whole blood (60 days) or partial blood (30 days), or received blood transfusion Subjects who have had alcohol consistently (>21units/week, 1unit=10 g of pure alcohol) or who is not able to stop drinking alcohol throughout the study period Subjects who have smoked until 90 days prior to the study initiation or who are not able to stop smoking throughout the study period Subjects who are not able to stop taking grapefruit/caffeine from 3 days prior to the first dose of the study drug throughout the study period Subjects who plan for pregnancy during the study period or who are not able to use established contraceptive method Subject who judged not eligible for study participation by investigator

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: KL1333 25mg<br>Group 1 | Drug: KL1333 25 mg<br>* oral administration, single dose, 25 mg 1 tab<br>Drug: Placebo<br>* oral administration, placebo<br>|
| Experimental: KL1333 50mg<br>Group 2 | Drug: KL1333 50 mg<br>* oral administration, single dose, 25 mg 2 tabs<br>Drug: Placebo<br>* oral administration, placebo<br>|
| Experimental: KL1333 100mg<br>Group 3 | Drug: KL1333 100 mg<br>* oral administration, single dose, 100 mg 1 tab<br>Drug: Placebo<br>* oral administration, placebo<br>|
| Experimental: KL1333 200mg<br>Group 4 | Drug: KL1333 200 mg<br>* oral administration, single dose, 100 mg 2 tabs<br>Drug: Placebo<br>* oral administration, placebo<br>|
| Experimental: KL1333 400mg<br>Group 5 | Drug: KL1333 400 mg<br>* oral administration, single dose, 100 mg 4 tabs<br>Drug: Placebo<br>* oral administration, placebo<br>|
| Experimental: KL1333 600mg<br>Group 6 | Drug: KL1333 600 mg<br>* oral administration, single dose, 100 mg 6 tabs<br>Drug: Placebo<br>* oral administration, placebo<br>|
| Experimental: KL1333 800mg<br>Group 7 | Drug: KL1333 800 mg<br>* oral administration, single dose, 100 mg 8 tabs<br>Drug: Placebo<br>* oral administration, placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of reported adverse events |  | from day 1 to day 15 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum plasma concentration (Cmax) of KL1333 |  | from day 1 to day 15 | 
| Area Under the Curve (AUC) of KL1333 |  | from day 1 to day 15 | 
| Half-life (T1/2) of KL1333 |  | from day 1 to day 15 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Mitochondrial DNA tRNALeu(UUR) m.3243A<G Mutation