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

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

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.

Study Overview

• Status: Completed
• Conditions: MELAS Syndrome; Mitochondrial Respiratory Chain Deficiencies
• Intervention / Treatment: Drug: KL1333 25 mg; Drug: Placebo; Drug: KL1333 50 mg; Drug: KL1333 100 mg; Drug: KL1333 200 mg; Drug: KL1333 400 mg; Drug: KL1333 600 mg; Drug: KL1333 800 mg

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 1

Contacts and Locations

Study Locations

• Korea, Republic of
  • Jongno-gu
    • Seoul, Jongno-gu, Korea, Republic of, 110744
      • Seoul National University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

7

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Yungjin Pharm. Co., Ltd.
• Investigators: Study Chair: Kyung-Sang Yu, MD., MBA, Seoul National University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): June 26, 2017
• Primary Completion (Actual): April 16, 2018
• Study Completion (Actual): April 16, 2018

Study Registration Dates

• First Submitted: February 5, 2017
• First Submitted That Met QC Criteria: February 14, 2017
• First Posted (Actual): February 17, 2017

Study Record Updates

• Last Update Posted (Actual): April 27, 2018
• Last Update Submitted That Met QC Criteria: April 25, 2018
• Last Verified: April 1, 2018

More Information

Terms related to this study

• Keywords: Mitochondrial DNA tRNALeu(UUR) m.3243A<G Mutation
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Metabolic Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Diseases; Metabolism, Inborn Errors; Brain Diseases, Metabolic; Brain Diseases, Metabolic, Inborn; Cerebral Small Vessel Diseases; Mitochondrial Encephalomyopathies; Mitochondrial Myopathies; Mitochondrial Diseases; MELAS Syndrome
• Other Study ID Numbers: KL1333_101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No