Healthy
Conditions
Brief summary
The purpose of this study is to Investigate the Safety, Tolerability and Pharmacokinetics of MT-6345 in Healthy Subjects.
Interventions
DRUGMT-6345
MT-6345
DRUGMT-6345 Placebo
MT-6345 Placebo
Sponsors
Tanabe Pharma America, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
OTHER
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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 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 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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 | 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. |
| 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. |
| 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. |
Countries
United Kingdom
Participant flow
Pre-assignment details
6 subjects of Part 1 were selected for Part 2.
Participants by arm
| Arm | Count |
|---|---|
| Part 1 Placebo Single dose | 11 |
| Part 1: MT-6345 1 mg Single dose | 6 |
| Part 1: MT-6345 5 mg Single dose | 6 |
| Part 1: MT-6345 20 mg Single dose | 6 |
| Part 1: MT-6345 60 mg Single dose | 6 |
| Part 1: MT-6345 120 mg Single dose | 4 |
| Part 1: MT-6345 240 mg Single dose | 5 |
| Part 3 Placebo Multiple dose | 2 |
| Part 3: MT-6345 60 mg Multiple dose | 6 |
| Total | 52 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 |
|---|---|---|---|---|---|---|---|---|---|---|
| Part 1 | Withdrawal by Subject | 1 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Part 3 | Withdrawn by study termination | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 6 |
Baseline characteristics
| Characteristic | Part 1 Placebo | Part 1: MT-6345 1 mg | Part 1: MT-6345 5 mg | Part 1: MT-6345 20 mg | Part 1: MT-6345 60 mg | Part 1: MT-6345 120 mg | Part 1: MT-6345 240 mg | Part 3 Placebo | Part 3: MT-6345 60 mg | Total |
|---|---|---|---|---|---|---|---|---|---|---|
| Age, Customized 18-64 years | 11 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 4 Participants | 5 Participants | 2 Participants | 6 Participants | 52 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 11 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 4 Participants | 5 Participants | 2 Participants | 6 Participants | 52 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 11 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 4 Participants | 5 Participants | 2 Participants | 6 Participants | 52 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 11 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 4 Participants | 5 Participants | 2 Participants | 6 Participants | 52 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 11 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 4 | 0 / 5 | 0 / 1 | 0 / 5 | 0 / 2 | 0 / 6 |
| other Total, other adverse events | 4 / 11 | 0 / 6 | 2 / 6 | 1 / 6 | 2 / 6 | 1 / 4 | 2 / 5 | 0 / 1 | 2 / 5 | 0 / 2 | 2 / 6 |
| serious Total, serious adverse events | 0 / 11 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 4 | 0 / 5 | 0 / 1 | 0 / 5 | 0 / 2 | 0 / 6 |
Outcome results
Primary
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.
Time frame: Up to 6 weeks
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part 1 Placebo | Number of Participants With Mild, Moderate and Severe Adverse Events | Moderate | 0 participants |
| Part 1 Placebo | Number of Participants With Mild, Moderate and Severe Adverse Events | Severe | 0 participants |
| Part 1 Placebo | Number of Participants With Mild, Moderate and Severe Adverse Events | Mild | 4 participants |
| Part 1: MT-6345 1 mg | Number of Participants With Mild, Moderate and Severe Adverse Events | Moderate | 0 participants |
| Part 1: MT-6345 1 mg | Number of Participants With Mild, Moderate and Severe Adverse Events | Mild | 0 participants |
| Part 1: MT-6345 1 mg | Number of Participants With Mild, Moderate and Severe Adverse Events | Severe | 0 participants |
| Part 1: MT-6345 5 mg | Number of Participants With Mild, Moderate and Severe Adverse Events | Severe | 0 participants |
| Part 1: MT-6345 5 mg | Number of Participants With Mild, Moderate and Severe Adverse Events | Mild | 2 participants |
| Part 1: MT-6345 5 mg | Number of Participants With Mild, Moderate and Severe Adverse Events | Moderate | 0 participants |
| Part 1: MT-6345 20 mg | Number of Participants With Mild, Moderate and Severe Adverse Events | Severe | 0 participants |
| Part 1: MT-6345 20 mg | Number of Participants With Mild, Moderate and Severe Adverse Events | Mild | 1 participants |
| Part 1: MT-6345 20 mg | Number of Participants With Mild, Moderate and Severe Adverse Events | Moderate | 0 participants |
| Part 1: MT-6345 60 mg | Number of Participants With Mild, Moderate and Severe Adverse Events | Severe | 0 participants |
| Part 1: MT-6345 60 mg | Number of Participants With Mild, Moderate and Severe Adverse Events | Mild | 2 participants |
| Part 1: MT-6345 60 mg | Number of Participants With Mild, Moderate and Severe Adverse Events | Moderate | 1 participants |
| Part 1: MT-6345 120 mg | Number of Participants With Mild, Moderate and Severe Adverse Events | Severe | 0 participants |
| Part 1: MT-6345 120 mg | Number of Participants With Mild, Moderate and Severe Adverse Events | Mild | 1 participants |
| Part 1: MT-6345 120 mg | Number of Participants With Mild, Moderate and Severe Adverse Events | Moderate | 0 participants |
| Part 1: MT-6345 240 mg | Number of Participants With Mild, Moderate and Severe Adverse Events | Severe | 0 participants |
| Part 1: MT-6345 240 mg | Number of Participants With Mild, Moderate and Severe Adverse Events | Moderate | 0 participants |
| Part 1: MT-6345 240 mg | Number of Participants With Mild, Moderate and Severe Adverse Events | Mild | 2 participants |
| Part 2: Placebo | Number of Participants With Mild, Moderate and Severe Adverse Events | Mild | 0 participants |
| Part 2: Placebo | Number of Participants With Mild, Moderate and Severe Adverse Events | Severe | 0 participants |
| Part 2: Placebo | Number of Participants With Mild, Moderate and Severe Adverse Events | Moderate | 0 participants |
| Part 2: MT-6345 20 mg | Number of Participants With Mild, Moderate and Severe Adverse Events | Moderate | 0 participants |
| Part 2: MT-6345 20 mg | Number of Participants With Mild, Moderate and Severe Adverse Events | Mild | 2 participants |
| Part 2: MT-6345 20 mg | Number of Participants With Mild, Moderate and Severe Adverse Events | Severe | 0 participants |
| Part 3: Placebo | Number of Participants With Mild, Moderate and Severe Adverse Events | Mild | 0 participants |
| Part 3: Placebo | Number of Participants With Mild, Moderate and Severe Adverse Events | Moderate | 0 participants |
| Part 3: Placebo | Number of Participants With Mild, Moderate and Severe Adverse Events | Severe | 0 participants |
| Part 3: MT-6345 60 mg | Number of Participants With Mild, Moderate and Severe Adverse Events | Moderate | 1 participants |
| Part 3: MT-6345 60 mg | Number of Participants With Mild, Moderate and Severe Adverse Events | Mild | 2 participants |
| Part 3: MT-6345 60 mg | Number of Participants With Mild, Moderate and Severe Adverse Events | Severe | 0 participants |
Secondary
Accumulation Ratio (RA) of MT-6345
Time frame: up to 2 weeks after dosing
Population: RA was not collected, and could not be assessed due to early study termination.
Secondary
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.
Time frame: 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.
Population: PKPOP subjects of Part 1, Part 2, and on Day 1 in Part 3.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1 Placebo | Apparent Oral Clearance (CL/F) of MT-6345 | 8.36 litre per hour | Standard Deviation 1.93 |
| Part 1: MT-6345 1 mg | Apparent Oral Clearance (CL/F) of MT-6345 | 6.89 litre per hour | Standard Deviation 1.81 |
| Part 1: MT-6345 5 mg | Apparent Oral Clearance (CL/F) of MT-6345 | 7.14 litre per hour | Standard Deviation 2.93 |
| Part 1: MT-6345 20 mg | Apparent Oral Clearance (CL/F) of MT-6345 | 5.79 litre per hour | Standard Deviation 2.15 |
| Part 1: MT-6345 60 mg | Apparent Oral Clearance (CL/F) of MT-6345 | 6.16 litre per hour | Standard Deviation 2.15 |
| Part 1: MT-6345 120 mg | Apparent Oral Clearance (CL/F) of MT-6345 | 7.30 litre per hour | Standard Deviation 4.17 |
| Part 1: MT-6345 240 mg | Apparent Oral Clearance (CL/F) of MT-6345 | 5.88 litre per hour | Standard Deviation 1.6 |
| Part 2: Placebo | Apparent Oral Clearance (CL/F) of MT-6345 | 6.92 litre per hour | Standard Deviation 2.2 |
Secondary
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.
Time frame: 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.
Population: PKPOP subjects of Part 1, Part 2, and on Day 1 in Part 3.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1 Placebo | Apparent Volume of Distribution at Steady State (Vss/F) of MT-6345 | 335 litre(s) | Standard Deviation 86.7 |
| Part 1: MT-6345 1 mg | Apparent Volume of Distribution at Steady State (Vss/F) of MT-6345 | 271 litre(s) | Standard Deviation 60.3 |
| Part 1: MT-6345 5 mg | Apparent Volume of Distribution at Steady State (Vss/F) of MT-6345 | 286 litre(s) | Standard Deviation 39.8 |
| Part 1: MT-6345 20 mg | Apparent Volume of Distribution at Steady State (Vss/F) of MT-6345 | 318 litre(s) | Standard Deviation 82.4 |
| Part 1: MT-6345 60 mg | Apparent Volume of Distribution at Steady State (Vss/F) of MT-6345 | 314 litre(s) | Standard Deviation 32.2 |
| Part 1: MT-6345 120 mg | Apparent Volume of Distribution at Steady State (Vss/F) of MT-6345 | 319 litre(s) | Standard Deviation 85.5 |
| Part 1: MT-6345 240 mg | Apparent Volume of Distribution at Steady State (Vss/F) of MT-6345 | 284 litre(s) | Standard Deviation 32.6 |
| Part 2: Placebo | Apparent Volume of Distribution at Steady State (Vss/F) of MT-6345 | 280 litre(s) | Standard Deviation 82.4 |
Secondary
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.
Time frame: 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.
Population: PKPOP subjects in Part 1 and Part 2, and on Day 1 in Part 3.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1 Placebo | Area Under the Plasma Concentration Time Curve From Time Zero to 24 Hours (AUC0-24h) of MT-6345 | 59.6 ng.h/mL | Standard Deviation 12.6 |
| Part 1: MT-6345 1 mg | Area Under the Plasma Concentration Time Curve From Time Zero to 24 Hours (AUC0-24h) of MT-6345 | 342 ng.h/mL | Standard Deviation 89.6 |
| Part 1: MT-6345 5 mg | Area Under the Plasma Concentration Time Curve From Time Zero to 24 Hours (AUC0-24h) of MT-6345 | 1350 ng.h/mL | Standard Deviation 293 |
| Part 1: MT-6345 20 mg | Area Under the Plasma Concentration Time Curve From Time Zero to 24 Hours (AUC0-24h) of MT-6345 | 4050 ng.h/mL | Standard Deviation 888 |
| Part 1: MT-6345 60 mg | Area Under the Plasma Concentration Time Curve From Time Zero to 24 Hours (AUC0-24h) of MT-6345 | 7570 ng.h/mL | Standard Deviation 634 |
| Part 1: MT-6345 120 mg | Area Under the Plasma Concentration Time Curve From Time Zero to 24 Hours (AUC0-24h) of MT-6345 | 15100 ng.h/mL | Standard Deviation 2830 |
| Part 1: MT-6345 240 mg | Area Under the Plasma Concentration Time Curve From Time Zero to 24 Hours (AUC0-24h) of MT-6345 | 1400 ng.h/mL | Standard Deviation 288 |
| Part 2: Placebo | Area Under the Plasma Concentration Time Curve From Time Zero to 24 Hours (AUC0-24h) of MT-6345 | 4200 ng.h/mL | Standard Deviation 938 |
Secondary
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.
Time frame: 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.
Population: PKPOP subjects in Part 1, Part 2, and on Day 1 in Part 3.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1 Placebo | Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-∞) of MT-6345 | 126 ng.h/mL | Standard Deviation 31 |
| Part 1: MT-6345 1 mg | Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-∞) of MT-6345 | 786 ng.h/mL | Standard Deviation 285 |
| Part 1: MT-6345 5 mg | Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-∞) of MT-6345 | 3190 ng.h/mL | Standard Deviation 1200 |
| Part 1: MT-6345 20 mg | Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-∞) of MT-6345 | 11200 ng.h/mL | Standard Deviation 2640 |
| Part 1: MT-6345 60 mg | Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-∞) of MT-6345 | 21800 ng.h/mL | Standard Deviation 9300 |
| Part 1: MT-6345 120 mg | Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-∞) of MT-6345 | 42200 ng.h/mL | Standard Deviation 21200 |
| Part 1: MT-6345 240 mg | Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-∞) of MT-6345 | 3650 ng.h/mL | Standard Deviation 1200 |
| Part 2: Placebo | Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-∞) of MT-6345 | 9570 ng.h/mL | Standard Deviation 3530 |
Secondary
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.
Time frame: 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.
Population: PKPOP subjects in Part 1 and Part 2, and on Day 1 in Part 3.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1 Placebo | Area Under the Plasma Concentration Time Curve From Time Zero to the Last Measurable Concentration (AUC0-last) of MT-6345 | 115 ng.h/mL | Standard Deviation 28.6 |
| Part 1: MT-6345 1 mg | Area Under the Plasma Concentration Time Curve From Time Zero to the Last Measurable Concentration (AUC0-last) of MT-6345 | 776 ng.h/mL | Standard Deviation 284 |
| Part 1: MT-6345 5 mg | Area Under the Plasma Concentration Time Curve From Time Zero to the Last Measurable Concentration (AUC0-last) of MT-6345 | 3060 ng.h/mL | Standard Deviation 1080 |
| Part 1: MT-6345 20 mg | Area Under the Plasma Concentration Time Curve From Time Zero to the Last Measurable Concentration (AUC0-last) of MT-6345 | 11100 ng.h/mL | Standard Deviation 2590 |
| Part 1: MT-6345 60 mg | Area Under the Plasma Concentration Time Curve From Time Zero to the Last Measurable Concentration (AUC0-last) of MT-6345 | 21500 ng.h/mL | Standard Deviation 8740 |
| Part 1: MT-6345 120 mg | Area Under the Plasma Concentration Time Curve From Time Zero to the Last Measurable Concentration (AUC0-last) of MT-6345 | 41200 ng.h/mL | Standard Deviation 20100 |
| Part 1: MT-6345 240 mg | Area Under the Plasma Concentration Time Curve From Time Zero to the Last Measurable Concentration (AUC0-last) of MT-6345 | 3590 ng.h/mL | Standard Deviation 1200 |
| Part 2: Placebo | Area Under the Plasma Concentration Time Curve From Time Zero to the Last Measurable Concentration (AUC0-last) of MT-6345 | 4200 ng.h/mL | Standard Deviation 938 |
Secondary
Area Under the Plasma Concentration Time Curve Over the Dosing Interval (AUC0-t) of MT-6345.
Time frame: up to 2 weeks after dosing
Population: AUC0-t was not collected, and could not be assessed due to early study termination.
Secondary
Linearity Factor (LF) of MT-6345
Time frame: up to 2 weeks after dosing
Population: LF was not collected, and could not be assessed due to early study termination.
Secondary
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.
Time frame: 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.
Population: PKPOP subjects in Part 1 and Part 2, and on Day 1 in Part 3.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1 Placebo | Maximum Plasma Concentration (Cmax) of MT-6345 | 8.219 ng/mL | Standard Deviation 1.414 |
| Part 1: MT-6345 1 mg | Maximum Plasma Concentration (Cmax) of MT-6345 | 37.37 ng/mL | Standard Deviation 9.471 |
| Part 1: MT-6345 5 mg | Maximum Plasma Concentration (Cmax) of MT-6345 | 153.3 ng/mL | Standard Deviation 38.85 |
| Part 1: MT-6345 20 mg | Maximum Plasma Concentration (Cmax) of MT-6345 | 386.2 ng/mL | Standard Deviation 65.23 |
| Part 1: MT-6345 60 mg | Maximum Plasma Concentration (Cmax) of MT-6345 | 780.9 ng/mL | Standard Deviation 118.5 |
| Part 1: MT-6345 120 mg | Maximum Plasma Concentration (Cmax) of MT-6345 | 1522 ng/mL | Standard Deviation 301.7 |
| Part 1: MT-6345 240 mg | Maximum Plasma Concentration (Cmax) of MT-6345 | 141.0 ng/mL | Standard Deviation 42.39 |
| Part 2: Placebo | Maximum Plasma Concentration (Cmax) of MT-6345 | 523.8 ng/mL | Standard Deviation 200.7 |
Secondary
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.
Time frame: 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.
Population: PKPOP subjects in Part 1, Part 2 and on Day 1 in Part 3.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1 Placebo | Mean Residence Time (MRT) of MT-6345 | 42.1 hour | Standard Deviation 16.6 |
| Part 1: MT-6345 1 mg | Mean Residence Time (MRT) of MT-6345 | 40.8 hour | Standard Deviation 10 |
| Part 1: MT-6345 5 mg | Mean Residence Time (MRT) of MT-6345 | 43.9 hour | Standard Deviation 11.9 |
| Part 1: MT-6345 20 mg | Mean Residence Time (MRT) of MT-6345 | 57.3 hour | Standard Deviation 14.5 |
| Part 1: MT-6345 60 mg | Mean Residence Time (MRT) of MT-6345 | 58.3 hour | Standard Deviation 28.6 |
| Part 1: MT-6345 120 mg | Mean Residence Time (MRT) of MT-6345 | 58.8 hour | Standard Deviation 40.6 |
| Part 1: MT-6345 240 mg | Mean Residence Time (MRT) of MT-6345 | 50.3 hour | Standard Deviation 9.52 |
| Part 2: Placebo | Mean Residence Time (MRT) of MT-6345 | 42.5 hour | Standard Deviation 11.9 |
Secondary
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.
Time frame: 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.
Population: PKPOP subjects in Part 1 and Part 2, and on Day 1 in Part 3.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1 Placebo | Plasma Terminal Elimination Half Life (t½) of MT-6345 | 34.89 hour | Standard Deviation 12.54 |
| Part 1: MT-6345 1 mg | Plasma Terminal Elimination Half Life (t½) of MT-6345 | 31.83 hour | Standard Deviation 7.16 |
| Part 1: MT-6345 5 mg | Plasma Terminal Elimination Half Life (t½) of MT-6345 | 34.99 hour | Standard Deviation 8.69 |
| Part 1: MT-6345 20 mg | Plasma Terminal Elimination Half Life (t½) of MT-6345 | 44.38 hour | Standard Deviation 10.76 |
| Part 1: MT-6345 60 mg | Plasma Terminal Elimination Half Life (t½) of MT-6345 | 46.03 hour | Standard Deviation 22.76 |
| Part 1: MT-6345 120 mg | Plasma Terminal Elimination Half Life (t½) of MT-6345 | 47.43 hour | Standard Deviation 31.58 |
| Part 1: MT-6345 240 mg | Plasma Terminal Elimination Half Life (t½) of MT-6345 | 39.46 hour | Standard Deviation 8.96 |
| Part 2: Placebo | Plasma Terminal Elimination Half Life (t½) of MT-6345 | 31.09 hour | Standard Deviation 8.69 |
Secondary
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.
Time frame: Day 1 (0 hours to 24 hours) and Day 10 (0 hours to 24 hours)
Population: PKPOP subjects in Part 3.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1 Placebo | Renal Clearance (CLR) of MT-6345 | 0.0390 L/h | Standard Deviation 0.011 |
Secondary
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.
Time frame: 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.
Population: PKPOP subjects in Part 1 and Part 2, and on Day 1 in Part 3.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1 Placebo | Terminal Elimination Rate Constant (Kel) of MT-6345 | 0.0222 /h | Standard Deviation 0.0081 |
| Part 1: MT-6345 1 mg | Terminal Elimination Rate Constant (Kel) of MT-6345 | 0.0226 /h | Standard Deviation 0.0044 |
| Part 1: MT-6345 5 mg | Terminal Elimination Rate Constant (Kel) of MT-6345 | 0.0208 /h | Standard Deviation 0.005 |
| Part 1: MT-6345 20 mg | Terminal Elimination Rate Constant (Kel) of MT-6345 | 0.0166 /h | Standard Deviation 0.005 |
| Part 1: MT-6345 60 mg | Terminal Elimination Rate Constant (Kel) of MT-6345 | 0.0176 /h | Standard Deviation 0.0072 |
| Part 1: MT-6345 120 mg | Terminal Elimination Rate Constant (Kel) of MT-6345 | 0.0198 /h | Standard Deviation 0.0104 |
| Part 1: MT-6345 240 mg | Terminal Elimination Rate Constant (Kel) of MT-6345 | 0.0182 /h | Standard Deviation 0.0038 |
| Part 2: Placebo | Terminal Elimination Rate Constant (Kel) of MT-6345 | 0.0244 /h | Standard Deviation 0.0096 |
Secondary
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.
Time frame: 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.
Population: PKPOP subjects in Part 1 and Part 2, and on Day 1 in Part 3.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1 Placebo | Time to Maximum Plasma Concentration (Tmax) of MT-6345 | 0.75 hour |
| Part 1: MT-6345 1 mg | Time to Maximum Plasma Concentration (Tmax) of MT-6345 | 1.01 hour |
| Part 1: MT-6345 5 mg | Time to Maximum Plasma Concentration (Tmax) of MT-6345 | 1.00 hour |
| Part 1: MT-6345 20 mg | Time to Maximum Plasma Concentration (Tmax) of MT-6345 | 1.50 hour |
| Part 1: MT-6345 60 mg | Time to Maximum Plasma Concentration (Tmax) of MT-6345 | 1.50 hour |
| Part 1: MT-6345 120 mg | Time to Maximum Plasma Concentration (Tmax) of MT-6345 | 1.50 hour |
| Part 1: MT-6345 240 mg | Time to Maximum Plasma Concentration (Tmax) of MT-6345 | 2.00 hour |
| Part 2: Placebo | Time to Maximum Plasma Concentration (Tmax) of MT-6345 | 1.25 hour |
Secondary
Urinary Excreted Amount of Test Compound (Ae) of MT-6345
Ae was measured for MT-6345 for the PKPOP subjects in Part 3.
Time frame: Day 1 (0 hours to 24 hours) and Day 10 (0 hours to 24 hours)
Population: PKPOP subjects in Part 3.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1 Placebo | Urinary Excreted Amount of Test Compound (Ae) of MT-6345 | Day 1 | 0.160 milligram(s) | Standard Deviation 0.044 |
| Part 1 Placebo | Urinary Excreted Amount of Test Compound (Ae) of MT-6345 | Day 10 | 0.255 milligram(s) | Standard Deviation 0.102 |
Secondary
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.
Time frame: 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)
Population: PKPOP subjects in Part 3.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1 Placebo | Urinary Excreted Amount of Test Compound Expressed as a Percentage of the Dose Administered (Ae%) of MT-6345 | Day 10 | 0.4 percentage of dose | Standard Deviation 0.2 |
| Part 1 Placebo | Urinary Excreted Amount of Test Compound Expressed as a Percentage of the Dose Administered (Ae%) of MT-6345 | Day 1 | 0.3 percentage of dose | Standard Deviation 0.1 |