A Study to Investigate the Safety, Tolerability and Pharmacokinetics of MT-6345 in Healthy Subjects

Study Overview
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Brief Summary
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The purpose of this study is to Investigate the Safety, Tolerability and Pharmacokinetics of MT-6345 in Healthy Subjects.

Official Title
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A Randomised, Double-Blind, Placebo-Controlled Phase I Study to Investigate the Safety, Tolerability and Pharmacokinetics of Single and Multiple Ascending Doses of MT-6345 in Healthy Subjects

Conditions
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Healthy

Intervention / Treatment
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* Drug: MT-6345
* Drug: MT-6345 Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Additional screening criteria check may apply for qualification: Able to provide written informed consent to participate in this study after reading the participant information sheet and Informed Consent Form (ICF), and after having the opportunity to discuss the study with the Investigator or designee. Healthy and free from clinically significant illness or disease as determined by medical history, physical examination, laboratory and other tests at Screening and Day -1. A body weight of ≥60 kg for males and ≥50 kg for females and a body mass index (BMI) (Quetelet index) ranging from 18 to 30.0 kg/m2 inclusive at Screening and Day -1. In the Investigator's opinion, subject is able to understand the nature of the study and any risks involved in participation, and willing to cooperate and comply with the Protocol restrictions and requirements. Exclusion Criteria: Additional screening criteria check may apply for qualification: Subjects with clinically significant (in the opinion of the Investigator) endocrine, thyroid, hepatic, respiratory, gastrointestinal, neurological, renal, cardiovascular disease, or history (within the last 5 years) of any significant psychiatric/psychotic illness disorder (including anxiety, depression and reactive depression). Female subjects who are pregnant (positive pregnancy test at Screening or Day -1) or lactating. Having previously received MT-6345 as part of this study. Clinically relevant abnormal medical history, physical findings or laboratory values at Screening or Day -1 that could interfere with the objectives of the study or the safety of the subject, as judged by the Investigator. Subjects who test positive for hepatitis B surface antigen, hepatitis B core antibody, hepatitis C antibody, human immunodeficiency virus (HIV)-1 or HIV-2 antibodies at Screening.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

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: Other
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Single Ascending Dose: MT-6345 & Placebo<br> | Drug: MT-6345<br>* MT-6345<br>Drug: MT-6345 Placebo<br>* MT-6345 Placebo<br>|
| Experimental: Multiple Ascending Dose: MT-6345 & Placebo<br> | Drug: MT-6345<br>* MT-6345<br>Drug: MT-6345 Placebo<br>* MT-6345 Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Mild, Moderate and Severe Adverse Events | The criteria of Mild, Moderate and Severe are as follows: Mild: The event is transient and easily tolerated by the subject. Moderate: The event causes discomfort and interferes with the subject's general condition. Severe: The event causes considerable interference with the subject's general condition and may be incapacitating. | Up to 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Plasma Concentration (Cmax) of MT-6345 | Cmax was measured for MT-6345 for the PK analysis set (PKPOP) subjects in Part 1 and Part 2, and on Day 1 in Part 3. | Part 1 and Part 2: Pre-dose and post-dose at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24, 48, 72 (Day 4), 120 (Day 6), 192 (Day 9), and 336 (Day 15 Follow-up Visit) hours. Part 3: Pre-dose and post-dose at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16 and 24 hours. | 
| Time to Maximum Plasma Concentration (Tmax) of MT-6345 | Tmax was measured for MT-6345 for the PKPOP subjects in Part 1 and Part 2, and on Day 1 in Part 3. | Part 1 and Part 2: Pre-dose and post-dose at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24, 48, 72 (Day 4), 120 (Day 6), 192 (Day 9), and 336 (Day 15 Follow-up Visit) hours. Part 3: Pre-dose and post-dose at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16 and 24 hours. | 
| Plasma Terminal Elimination Half Life (t½) of MT-6345 | t1/2 was measured for MT-6345 for the PKPOP subjects in Part 1 and Part 2, and on Day 1 in Part 3. | Part 1 and Part 2: Pre-dose and post-dose at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24, 48, 72 (Day 4), 120 (Day 6), 192 (Day 9), and 336 (Day 15 Follow-up Visit) hours. Part 3: Pre-dose and post-dose at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16 and 24 hours. | 
| Area Under the Plasma Concentration Time Curve From Time Zero to 24 Hours (AUC0-24h) of MT-6345 | AUC(0-24h) was computed for MT-6345 for the PKPOP subjects in Part 1 and Part 2, and on Day 1 in Part 3. | Part 1 and Part 2: Pre-dose and post-dose at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24, 48, 72 (Day 4), 120 (Day 6), 192 (Day 9), and 336 (Day 15 Follow-up Visit) hours. Part 3: Pre-dose and post-dose at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16 and 24 hours. | 
| Area Under the Plasma Concentration Time Curve From Time Zero to the Last Measurable Concentration (AUC0-last) of MT-6345 | AUC(0-last) was computed for MT-6345 for the PKPOP subjects in Part 1 and Part 2, and on Day 1 in Part 3. | Part 1 and Part 2: Pre-dose and post-dose at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24, 48, 72 (Day 4), 120 (Day 6), 192 (Day 9), and 336 (Day 15 Follow-up Visit) hours. Part 3: Pre-dose and post-dose at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16 and 24 hours. | 
| Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-∞) of MT-6345 | AUC(0-∞) was calculated for the PKPOP subjects in Part 1 and Part 2, and on Day 1 in Part 3. | Part 1 and Part 2: Pre-dose and post-dose at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24, 48, 72 (Day 4), 120 (Day 6), 192 (Day 9), and 336 (Day 15 Follow-up Visit) hour. Part 3: Pre-dose and post-dose at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16 and 24 hours. | 
| Terminal Elimination Rate Constant (Kel) of MT-6345 | Kel was estimated for the PKPOP subjects in Part 1 and Part 2, and on Day 1 in Part 3. | Part 1 and Part 2: Pre-dose and post-dose at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24, 48, 72 (Day 4), 120 (Day 6), 192 (Day 9), and 336 (Day 15 Follow-up Visit) hours. Part 3: Pre-dose and post-dose at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16 and 24 hours. | 
| Mean Residence Time (MRT) of MT-6345 | MRT was calculated for the PKPOP subjects in Part 1 and Part 2, and on Day 1 in Part 3. | Part 1 and Part 2: Pre-dose and post-dose at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24, 48, 72 (Day 4), 120 (Day 6), 192 (Day 9), and 336 (Day 15 Follow-up Visit) hours. Part 3: Pre-dose and post-dose at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16 and 24 hours. | 
| Apparent Oral Clearance (CL/F) of MT-6345 | CL/F was measured for MT-6345 in the PKPOP subjects of Part 1 and Part 2, and on Day 1 in Part 3. | Part 1 and Part 2: Pre-dose and post-dose at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24, 48, 72 (Day 4), 120 (Day 6), 192 (Day 9), and 336 (Day 15 Follow-up Visit) hours. Part 3: Pre-dose and post-dose at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16 and 24 hours. | 
| Area Under the Plasma Concentration Time Curve Over the Dosing Interval (AUC0-t) of MT-6345. |  | up to 2 weeks after dosing | 
| Apparent Volume of Distribution at Steady State (Vss/F) of MT-6345 | Vss/F was measured for MT-6345 in the PKPOP subjects of Part 1 and Part 2, and on Day 1 in Part 3. | Part 1 and Part 2: Pre-dose and post-dose at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24, 48, 72 (Day 4), 120 (Day 6), 192 (Day 9), and 336 (Day 15 Follow-up Visit) hours. Part 3: Pre-dose and post-dose at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16 and 24 hours. | 
| Linearity Factor (LF) of MT-6345 |  | up to 2 weeks after dosing | 
| Accumulation Ratio (RA) of MT-6345 |  | up to 2 weeks after dosing | 
| Urinary Excreted Amount of Test Compound (Ae) of MT-6345 | Ae was measured for MT-6345 for the PKPOP subjects in Part 3. | Day 1 (0 hours to 24 hours) and Day 10 (0 hours to 24 hours) | 
| Urinary Excreted Amount of Test Compound Expressed as a Percentage of the Dose Administered (Ae%) of MT-6345 | Ae% was measured for MT-6345 for the PKPOP subjects in Part 3. | Day 1 (pre-dose and post-dose at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12 and 16 hours) and Day 2 to Day 10 (pre-dose on each day) | 
| Renal Clearance (CLR) of MT-6345 | CLR was measured for MT-6345 for the PKPOP subjects in Part 3. For Day 10, CLR was not calculated because AUC(0-24h) on the last day of dosing was not calculated. | Day 1 (0 hours to 24 hours) and Day 10 (0 hours to 24 hours) |