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

Phase 1

Terminated

Conditions: Healthy

Interventions: Drug: MT-6345
Drug: MT-6345 Placebo

Registration Number: NCT03809039

Lead Sponsor: Mitsubishi Tanabe Pharma America Inc.

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

Detailed Description: Not available

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 52

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Multiple Ascending Dose: MT-6345 & Placebo	MT-6345	-
Multiple Ascending Dose: MT-6345 & Placebo	MT-6345 Placebo	-
Single Ascending Dose: MT-6345 & Placebo	MT-6345	-
Single Ascending Dose: MT-6345 & Placebo	MT-6345 Placebo	-

Primary Outcome Measures

Name	Time	Method
Number of Participants With Mild, Moderate and Severe Adverse Events	Up to 6 weeks	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.

Secondary Outcome Measures

Name	Time	Method
Accumulation Ratio (RA) of MT-6345	up to 2 weeks after dosing
Plasma Terminal Elimination Half Life (t½) of MT-6345	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.	t1/2 was measured for MT-6345 for the PKPOP subjects in Part 1 and Part 2, and on Day 1 in Part 3.
Area Under the Plasma Concentration Time Curve From Time Zero to the Last Measurable Concentration (AUC0-last) of MT-6345	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.	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.
Terminal Elimination Rate Constant (Kel) of MT-6345	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.	Kel was estimated for the PKPOP subjects in Part 1 and Part 2, and on Day 1 in Part 3.
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	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.	Vss/F was measured for MT-6345 in the PKPOP subjects of Part 1 and Part 2, and on Day 1 in Part 3.
Area Under the Plasma Concentration Time Curve From Time Zero to 24 Hours (AUC0-24h) of MT-6345	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.	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.
Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-∞) of MT-6345	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.	AUC(0-∞) was calculated for the PKPOP subjects in Part 1 and Part 2, and on Day 1 in Part 3.
Maximum Plasma Concentration (Cmax) of MT-6345	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.	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.
Urinary Excreted Amount of Test Compound Expressed as a Percentage of the Dose Administered (Ae%) of MT-6345	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)	Ae% was measured for MT-6345 for the PKPOP subjects in Part 3.
Renal Clearance (CLR) of MT-6345	Day 1 (0 hours to 24 hours) and Day 10 (0 hours to 24 hours)	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.
Time to Maximum Plasma Concentration (Tmax) of MT-6345	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.	Tmax was measured for MT-6345 for the PKPOP subjects in Part 1 and Part 2, and on Day 1 in Part 3.
Mean Residence Time (MRT) of MT-6345	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.	MRT was calculated for the PKPOP subjects in Part 1 and Part 2, and on Day 1 in Part 3.
Apparent Oral Clearance (CL/F) of MT-6345	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.	CL/F was measured for MT-6345 in the PKPOP subjects of Part 1 and Part 2, and on Day 1 in Part 3.
Linearity Factor (LF) of MT-6345	up to 2 weeks after dosing
Urinary Excreted Amount of Test Compound (Ae) of MT-6345	Day 1 (0 hours to 24 hours) and Day 10 (0 hours to 24 hours)	Ae was measured for MT-6345 for the PKPOP subjects in Part 3.