Healthy Adult Subjects
Conditions
Brief summary
To evaluate the pharmacokinetics safety, and tolerability of single and multiple doses of edaravone solution and suspension in healthy adult males
Interventions
DRUGMT-1186
Solution or suspension
DRUGMT-1186-matching placebo
Solution or suspension
Sponsors
Shionogi
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
SINGLE (Subject)
Masking description
Single Blind
Eligibility
Sex/Gender
MALE
Age
20 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
Additional screening criteria check may apply for qualification: * Healthy adult male volunteers * Japanese or Caucasian * Subjects aged between 20 and 45 years at the time of informed consent * Subjects who have thoroughly understood the contents of the study and voluntarily provided written informed consent to participate in the study
Exclusion criteria
Additional screening criteria check may apply for qualification: * Subjects with a current or previous history of cardiac, hepatic, renal, gastrointestinal, respiratory, psychiatric/nervous, hematopoietic, or endocrine diseases, and those whom the investigator (or subinvestigator) deems unsuitable for the study * Body mass index (BMI) of \<18.0 or \>30.0, or body weight of \<50 kg (BMI formula: body weight \[kg\]/height \[m\]2, rounded to one decimal place) * Subjects who have undergone any surgery known to affect the gastrointestinal absorption of drugs * Subjects who do not agree to use an effective method of contraception from initiation of study drug administration to 14 days after completion (discontinuation) of study drug administration * Subjects who have previously received edaravone * Subjects who have participated in another clinical study and received a study drug within 12 weeks before providing informed consent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events (Aes) and Adverse Drug Reactions (ADRs) | Day 1 to 8 in Part 1, up to 12 days in Part 2 | — |
| Area Under the Concentration Versus Time Curve (AUC) of Unchanged Edaravone | Part 1: Pre-dose, 0.25, 0.5, 1.5, 2, 4, 6, 8, 12, 24, 36, 48 hrs post-dose, Part 2: Day 1 and 5 at pre-dose, 0.25, 0.5, 1.5, 2, 4, 6, 8, 12 hrs post-dose; Day 2 to 4 at pre-dose; Day 6 at 24 hrs post-dose on Day 5; Day 7 at 48 hrs post-dose on Day 5 | Area under the plasma concentration versus time curve from time zero up to 24 hours (AUC0-24) of unchanged edaravone. |
| Area Under the Concentration Versus Time Curve (AUC) of Sulfate Conjugate | Part 1: Pre-dose, 0.25, 0.5, 1.5, 2, 4, 6, 8, 12, 24, 36, 48 hrs post-dose, Part 2: Day 1 and 5 at pre-dose, 0.25, 0.5, 1.5, 2, 4, 6, 8, 12 hrs post-dose; Day 2 to 4 at pre-dose; Day 6 at 24 hrs post-dose on Day 5; Day 7 at 48 hrs post-dose on Day 5 | Area under the plasma concentration versus time curve from time zero up to 24 hours (AUC0-24) of sulfate conjugate. |
| Area Under the Concentration Versus Time Curve (AUC) of Glucuronide Conjugate | Part 1: Pre-dose, 0.25, 0.5, 1.5, 2, 4, 6, 8, 12, 24, 36, 48 hrs post-dose, Part 2: Day 1 and 5 at pre-dose, 0.25, 0.5, 1.5, 2, 4, 6, 8, 12 hrs post-dose; Day 2 to 4 at pre-dose; Day 6 at 24 hrs post-dose on Day 5; Day 7 at 48 hrs post-dose on Day 5 | Area under the plasma concentration versus time curve from time zero up to 24 hours (AUC0-24) of glucuronide conjugate. |
| Maximum Plasma Concentration (Cmax) of Unchanged Edaravone | Part 1: Pre-dose, 0.25, 0.5, 1.5, 2, 4, 6, 8, 12, 24, 36, 48 hrs post-dose, Part 2: Day 1 and 5 at pre-dose, 0.25, 0.5, 1.5, 2, 4, 6, 8, 12 hrs post-dose; Day 2 to 4 at pre-dose; Day 6 at 24 hrs post-dose on Day 5; Day 7 at 48 hrs post-dose on Day 5 | — |
| Maximum Plasma Concentration (Cmax) of Sulfate Conjugate | Part 1: Pre-dose, 0.25, 0.5, 1.5, 2, 4, 6, 8, 12, 24, 36, 48 hrs post-dose, Part 2: Day 1 and 5 at pre-dose, 0.25, 0.5, 1.5, 2, 4, 6, 8, 12 hrs post-dose; Day 2 to 4 at pre-dose; Day 6 at 24 hrs post-dose on Day 5; Day 7 at 48 hrs post-dose on Day 5 | — |
| Maximum Plasma Concentration (Cmax) of Glucuronide Conjugate | Part 1: Pre-dose, 0.25, 0.5, 1.5, 2, 4, 6, 8, 12, 24, 36, 48 hrs post-dose, Part 2: Day 1 and 5 at pre-dose, 0.25, 0.5, 1.5, 2, 4, 6, 8, 12 hrs post-dose; Day 2 to 4 at pre-dose; Day 6 at 24 hrs post-dose on Day 5; Day 7 at 48 hrs post-dose on Day 5 | — |
| Part 2: Minimum Plasma Concentration at Steady State (Ctrough, ss) | Part 2: Day 1 and 5 at pre-dose, 0.25, 0.5, 1.5, 2, 4, 6, 8, 12 hrs post-dose; Day 2 to 4 at pre-dose; Day 6 at 24 hrs post-dose on Day 5; Day 7 at 48 hrs post-dose on Day 5 | — |
| Time to Reach Maximum Plasma Concentration (Tmax) of Unchanged Edaravone | Part 1: Pre-dose, 0.25, 0.5, 1.5, 2, 4, 6, 8, 12, 24, 36, 48 hrs post-dose, Part 2: Day 1 and 5 at pre-dose, 0.25, 0.5, 1.5, 2, 4, 6, 8, 12 hrs post-dose; Day 2 to 4 at pre-dose; Day 6 at 24 hrs post-dose on Day 5; Day 7 at 48 hrs post-dose on Day 5 | — |
| Time to Reach Maximum Plasma Concentration (Tmax) of Sulfate Conjugate | Part 1: Pre-dose, 0.25, 0.5, 1.5, 2, 4, 6, 8, 12, 24, 36, 48 hrs post-dose, Part 2: Day 1 and 5 at pre-dose, 0.25, 0.5, 1.5, 2, 4, 6, 8, 12 hrs post-dose; Day 2 to 4 at pre-dose; Day 6 at 24 hrs post-dose on Day 5; Day 7 at 48 hrs post-dose on Day 5 | — |
| Time to Reach Maximum Plasma Concentration (Tmax) of Glucuronide Conjugate | Part 1: Pre-dose, 0.25, 0.5, 1.5, 2, 4, 6, 8, 12, 24, 36, 48 hrs post-dose, Part 2: Day 1 and 5 at pre-dose, 0.25, 0.5, 1.5, 2, 4, 6, 8, 12 hrs post-dose; Day 2 to 4 at pre-dose; Day 6 at 24 hrs post-dose on Day 5; Day 7 at 48 hrs post-dose on Day 5 | — |
| Terminal Elimination Half-life (t1/2) of Unchanged Edaravone | Part 1: Pre-dose, 0.25, 0.5, 1.5, 2, 4, 6, 8, 12, 24, 36, 48 hrs post-dose, Part 2: Day 1 and 5 at pre-dose, 0.25, 0.5, 1.5, 2, 4, 6, 8, 12 hrs post-dose; Day 2 to 4 at pre-dose; Day 6 at 24 hrs post-dose on Day 5; Day 7 at 48 hrs post-dose on Day 5 | — |
| Terminal Elimination Half-life (t1/2) of Sulfate Conjugate | Part 1: Pre-dose, 0.25, 0.5, 1.5, 2, 4, 6, 8, 12, 24, 36, 48 hrs post-dose, Part 2: Day 1 and 5 at pre-dose, 0.25, 0.5, 1.5, 2, 4, 6, 8, 12 hrs post-dose; Day 2 to 4 at pre-dose; Day 6 at 24 hrs post-dose on Day 5; Day 7 at 48 hrs post-dose on Day 5 | — |
| Terminal Elimination Half-life (t1/2) of Glucuronide Conjugate | Part 1: Pre-dose, 0.25, 0.5, 1.5, 2, 4, 6, 8, 12, 24, 36, 48 hrs post-dose, Part 2: Day 1 and 5 at pre-dose, 0.25, 0.5, 1.5, 2, 4, 6, 8, 12 hrs post-dose; Day 2 to 4 at pre-dose; Day 6 at 24 hrs post-dose on Day 5; Day 7 at 48 hrs post-dose on Day 5 | — |
| Lambda-z of Unchanged Edaravone | Part 1: Pre-dose, 0.25, 0.5, 1.5, 2, 4, 6, 8, 12, 24, 36, 48 hrs post-dose, Part 2: Day 1 and 5 at pre-dose, 0.25, 0.5, 1.5, 2, 4, 6, 8, 12 hrs post-dose; Day 2 to 4 at pre-dose; Day 6 at 24 hrs post-dose on Day 5; Day 7 at 48 hrs post-dose on Day 5 | — |
| Lambda-z of Sulfate Conjugate | Part 1: Pre-dose, 0.25, 0.5, 1.5, 2, 4, 6, 8, 12, 24, 36, 48 hrs post-dose, Part 2: Day 1 and 5 at pre-dose, 0.25, 0.5, 1.5, 2, 4, 6, 8, 12 hrs post-dose; Day 2 to 4 at pre-dose; Day 6 at 24 hrs post-dose on Day 5; Day 7 at 48 hrs post-dose on Day 5 | — |
| Lambda-z of Glucuronide Conjugate | Part 1: Pre-dose, 0.25, 0.5, 1.5, 2, 4, 6, 8, 12, 24, 36, 48 hrs post-dose, Part 2: Day 1 and 5 at pre-dose, 0.25, 0.5, 1.5, 2, 4, 6, 8, 12 hrs post-dose; Day 2 to 4 at pre-dose; Day 6 at 24 hrs post-dose on Day 5; Day 7 at 48 hrs post-dose on Day 5 | — |
| Mean Residence Time (MRT) of Unchanged Edaravone | Part 1: Pre-dose, 0.25, 0.5, 1.5, 2, 4, 6, 8, 12, 24, 36, 48 hrs post-dose Part 2: Day 1 and 5 at pre-dose, 0.25, 0.5, 1.5, 2, 4, 6, 8, 12 hrs post-dose; Day 2 to 4 at pre-dose; Day 6 at 24 hrs post-dose on Day 5; Day 7 at 48 hrs post-dose on Day 5 | — |
| Apparent Total Clearance (CL/F) of Unchanged Edaravone | Part 1: Pre-dose, 0.25, 0.5, 1.5, 2, 4, 6, 8, 12, 24, 36, 48 hrs post-dose, Part 2: Day 1 and 5 at pre-dose, 0.25, 0.5, 1.5, 2, 4, 6, 8, 12 hrs post-dose; Day 2 to 4 at pre-dose; Day 6 at 24 hrs post-dose on Day 5; Day 7 at 48 hrs post-dose on Day 5 | — |
| Apparent Distribution Volume at Elimination Phase (Vz/F) and Apparent Distribution Volume at Steady State (Vss/F) of Unchanged Edaravone | Part 1: Pre-dose, 0.25, 0.5, 1.5, 2, 4, 6, 8, 12, 24, 36, 48 hrs post-dose, Part 2: Day 1 and 5 at pre-dose, 0.25, 0.5, 1.5, 2, 4, 6, 8, 12 hrs post-dose; Day 2 to 4 at pre-dose; Day 6 at 24 hrs post-dose on Day 5; Day 7 at 48 hrs post-dose on Day 5 | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change of Heart Rate (HR) From Baseline | 0.75, 0.5, and 0.25 hours pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 36, and 48 hours post-dose. | Holter ECG data were recorded in part 1, Cohorts S4, S5, and S6. Baseline is calculated as average HR from 0.75, 0.5, and 0.25 hours pre-dose. |
| Change of PR Interval (PR) From Baseline | 0.75, 0.5, and 0.25 hours pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 36, and 48 hours post-dose. | Holter ECG data were recorded in part 1, Cohorts S4, S5, and S6. Baseline is calculated as average HR from 0.75, 0.5, and 0.25 hours pre-dose. |
| Change of QTcF Interval (QTcF) From Baseline | 0.75, 0.5, and 0.25 hours pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 36, and 48 hours post-dose. | Holter ECG data were recorded in part 1, Cohorts S4, S5, and S6. Baseline is calculated as average HR from 0.75, 0.5, and 0.25 hours pre-dose. |
| Change of QRS Duration (QRS) From Baseline | 0.75, 0.5, and 0.25 hours pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 36, and 48 hours post-dose. | Holter ECG data were recorded in part 1, Cohorts S4, S5, and S6. |
Countries
Japan
Contacts
STUDY_DIRECTORShionogi Clinical Trials Administrator Clinical Support Help Line
Shionogi
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| A Single Dose MT-1186 (Part 1, Cohort S1) Healthy Japanese male subjects receive a single dose of MT-1186 60 mg solution. | 6 |
| A Single Dose MT-1186 (Part 1, Cohort S2) Healthy Japanese male subjects receive a single dose of MT-1186 120 mg suspension. | 6 |
| A Single Dose MT-1186 (Part 1, Cohort S3) Healthy Japanese male subjects receive a single dose of MT-1186 200 mg under fasted condition in period 1, and fed condition in period 2 with washout period at least 4-day. | 6 |
| A Single Dose MT-1186 (Part 1, Cohort S4) Healthy Japanese male subjects receive a single dose of MT-1186 300 mg suspension with xanthan. | 6 |
| A Single Dose MT-1186 (Part 1, Cohort S5) Healthy Japanese male subjects receive a single dose of MT-1186 300 mg suspension. | 6 |
| A Single Dose MT-1186 (Part 1, Cohort S6) Healthy Japanese male subjects receive a single dose of MT-1186 30 mg suspension. | 6 |
| A Single Dose MT-1186 (Part 1, Cohort S7) Healthy Caucasian male subjects receive a single dose of MT-1186 200 mg suspension. | 6 |
| Matching Placebo (a Single Dose Cohorts) Healthy Japanese/Caucasian male subjects receive a single dose of matching placebo. | 14 |
| Multiple Doses MT-1186 (Part 2, Cohort M1) Healthy Japanese male subjects receive multiple doses of MT-1186 120 mg suspension. | 6 |
| Multiple Doses MT-1186 (Part 2, Cohort M2) Healthy Japanese male subjects receive multiple doses of MT-1186 200 mg suspension. | 6 |
| Matching Placebo (Multiple Doses Cohorts) Healthy Japanese male subjects receive multiple doses of matching placebo. | 6 |
| Total | 74 |
Baseline characteristics
| Characteristic | A Single Dose MT-1186 (Part 1, Cohort S1) | A Single Dose MT-1186 (Part 1, Cohort S2) | A Single Dose MT-1186 (Part 1, Cohort S3) | A Single Dose MT-1186 (Part 1, Cohort S4) | A Single Dose MT-1186 (Part 1, Cohort S5) | A Single Dose MT-1186 (Part 1, Cohort S6) | A Single Dose MT-1186 (Part 1, Cohort S7) | Matching Placebo (a Single Dose Cohorts) | Multiple Doses MT-1186 (Part 2, Cohort M1) | Multiple Doses MT-1186 (Part 2, Cohort M2) | Matching Placebo (Multiple Doses Cohorts) | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 14 Participants | 6 Participants | 6 Participants | 6 Participants | 74 Participants |
| Race/Ethnicity, Customized Asian (Japanese) | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 0 Participants | 12 Participants | 6 Participants | 6 Participants | 6 Participants | 66 Participants |
| Race/Ethnicity, Customized White | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 6 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 8 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 | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 14 Participants | 6 Participants | 6 Participants | 6 Participants | 74 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 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 14 | 0 / 6 | 0 / 6 | 0 / 6 |
| other Total, other adverse events | 0 / 6 | 2 / 6 | 3 / 6 | 0 / 6 | 1 / 6 | 1 / 6 | 2 / 6 | 2 / 14 | 2 / 6 | 1 / 6 | 1 / 6 |
| serious Total, serious adverse events | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 14 | 0 / 6 | 0 / 6 | 0 / 6 |
Outcome results
Primary
Apparent Distribution Volume at Elimination Phase (Vz/F) and Apparent Distribution Volume at Steady State (Vss/F) of Unchanged Edaravone
Time frame: Part 1: Pre-dose, 0.25, 0.5, 1.5, 2, 4, 6, 8, 12, 24, 36, 48 hrs post-dose, Part 2: Day 1 and 5 at pre-dose, 0.25, 0.5, 1.5, 2, 4, 6, 8, 12 hrs post-dose; Day 2 to 4 at pre-dose; Day 6 at 24 hrs post-dose on Day 5; Day 7 at 48 hrs post-dose on Day 5
Population: The trial is divided into 2 phases (a single and multiple-dose). A single-dose study included 8 cohorts (total of 56 subjects), with 42 (6x7) subjects receiving MT-1186, and 14 (2x7) receiving the placebo. Multiple-dose study included 2 cohorts (total of 18 subjects), with 12 (6x2) receiving MT-1186, and 6 (3x2) receiving the placebo for 5 days. Since Cohort S3-1 and S3-2 are crossover cohort, the 5 subjects in Cohort S3-2 are overlapped (59 patients receiving MT-1186).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S1) | Apparent Distribution Volume at Elimination Phase (Vz/F) and Apparent Distribution Volume at Steady State (Vss/F) of Unchanged Edaravone | Vz/F (Part 1), Vss/F (Part 2): Day1 | 348.98 L | Standard Deviation 87.82 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S2) | Apparent Distribution Volume at Elimination Phase (Vz/F) and Apparent Distribution Volume at Steady State (Vss/F) of Unchanged Edaravone | Vz/F (Part 1), Vss/F (Part 2): Day1 | 422.67 L | Standard Deviation 126.97 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S3-1) | Apparent Distribution Volume at Elimination Phase (Vz/F) and Apparent Distribution Volume at Steady State (Vss/F) of Unchanged Edaravone | Vz/F (Part 1), Vss/F (Part 2): Day1 | 426.49 L | Standard Deviation 130.84 |
| A Single Dose MT-1186 Under Fed Condition(Part 1, Cohort S3-2) | Apparent Distribution Volume at Elimination Phase (Vz/F) and Apparent Distribution Volume at Steady State (Vss/F) of Unchanged Edaravone | Vz/F (Part 1), Vss/F (Part 2): Day1 | 620.73 L | Standard Deviation 139.24 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S4) | Apparent Distribution Volume at Elimination Phase (Vz/F) and Apparent Distribution Volume at Steady State (Vss/F) of Unchanged Edaravone | Vz/F (Part 1), Vss/F (Part 2): Day1 | 457.99 L | Standard Deviation 188.01 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S5) | Apparent Distribution Volume at Elimination Phase (Vz/F) and Apparent Distribution Volume at Steady State (Vss/F) of Unchanged Edaravone | Vz/F (Part 1), Vss/F (Part 2): Day1 | 457.37 L | Standard Deviation 175.69 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S6) | Apparent Distribution Volume at Elimination Phase (Vz/F) and Apparent Distribution Volume at Steady State (Vss/F) of Unchanged Edaravone | Vz/F (Part 1), Vss/F (Part 2): Day1 | 384.51 L | Standard Deviation 96.92 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S7) | Apparent Distribution Volume at Elimination Phase (Vz/F) and Apparent Distribution Volume at Steady State (Vss/F) of Unchanged Edaravone | Vz/F (Part 1), Vss/F (Part 2): Day1 | 408.95 L | Standard Deviation 121.29 |
| Matching Placebo Under Fasted Condition (a Sngle Dose Cohorts) | Apparent Distribution Volume at Elimination Phase (Vz/F) and Apparent Distribution Volume at Steady State (Vss/F) of Unchanged Edaravone | Vz/F (Part 1), Vss/F (Part 2): Day1 | 126.41 L | Standard Deviation 29.65 |
| Matching Placebo Under Fasted Condition (a Sngle Dose Cohorts) | Apparent Distribution Volume at Elimination Phase (Vz/F) and Apparent Distribution Volume at Steady State (Vss/F) of Unchanged Edaravone | Vss/F (only Part 2): Day 5 | 125.94 L | Standard Deviation 40.36 |
| Multiple Doses MT-1186 (Part 2, Cohort M1) | Apparent Distribution Volume at Elimination Phase (Vz/F) and Apparent Distribution Volume at Steady State (Vss/F) of Unchanged Edaravone | Vz/F (Part 1), Vss/F (Part 2): Day1 | 105.90 L | Standard Deviation 57.04 |
| Multiple Doses MT-1186 (Part 2, Cohort M1) | Apparent Distribution Volume at Elimination Phase (Vz/F) and Apparent Distribution Volume at Steady State (Vss/F) of Unchanged Edaravone | Vss/F (only Part 2): Day 5 | 121.32 L | Standard Deviation 66.83 |
Primary
Apparent Total Clearance (CL/F) of Unchanged Edaravone
Time frame: Part 1: Pre-dose, 0.25, 0.5, 1.5, 2, 4, 6, 8, 12, 24, 36, 48 hrs post-dose, Part 2: Day 1 and 5 at pre-dose, 0.25, 0.5, 1.5, 2, 4, 6, 8, 12 hrs post-dose; Day 2 to 4 at pre-dose; Day 6 at 24 hrs post-dose on Day 5; Day 7 at 48 hrs post-dose on Day 5
Population: The trial is divided into 2 phases (a single and multiple-dose). A single-dose study included 8 cohorts (total of 56 subjects), with 42 (6x7) subjects receiving MT-1186, and 14 (2x7) receiving the placebo. Multiple-dose study included 2 cohorts (total of 18 subjects), with 12 (6x2) receiving MT-1186, and 6 (3x2) receiving the placebo for 5 days. Since Cohort S3-1 and S3-2 are crossover cohort, the 5 subjects in Cohort S3-2 are overlapped (59 patients receiving MT-1186).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S1) | Apparent Total Clearance (CL/F) of Unchanged Edaravone | Day 1 | 79.77 L/h | Standard Deviation 26.21 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S2) | Apparent Total Clearance (CL/F) of Unchanged Edaravone | Day 1 | 60.29 L/h | Standard Deviation 22.9 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S3-1) | Apparent Total Clearance (CL/F) of Unchanged Edaravone | Day 1 | 32.73 L/h | Standard Deviation 6.42 |
| A Single Dose MT-1186 Under Fed Condition(Part 1, Cohort S3-2) | Apparent Total Clearance (CL/F) of Unchanged Edaravone | Day 1 | 87.07 L/h | Standard Deviation 22.96 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S4) | Apparent Total Clearance (CL/F) of Unchanged Edaravone | Day 1 | 26.42 L/h | Standard Deviation 2.3 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S5) | Apparent Total Clearance (CL/F) of Unchanged Edaravone | Day 1 | 36.11 L/h | Standard Deviation 13.62 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S6) | Apparent Total Clearance (CL/F) of Unchanged Edaravone | Day 1 | 119.41 L/h | Standard Deviation 43.64 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S7) | Apparent Total Clearance (CL/F) of Unchanged Edaravone | Day 1 | 46.72 L/h | Standard Deviation 20.27 |
| Matching Placebo Under Fasted Condition (a Sngle Dose Cohorts) | Apparent Total Clearance (CL/F) of Unchanged Edaravone | Day 1 | 64.51 L/h | Standard Deviation 11.64 |
| Matching Placebo Under Fasted Condition (a Sngle Dose Cohorts) | Apparent Total Clearance (CL/F) of Unchanged Edaravone | Day 5 | 57.64 L/h | Standard Deviation 14.54 |
| Multiple Doses MT-1186 (Part 2, Cohort M1) | Apparent Total Clearance (CL/F) of Unchanged Edaravone | Day 1 | 53.40 L/h | Standard Deviation 20.46 |
| Multiple Doses MT-1186 (Part 2, Cohort M1) | Apparent Total Clearance (CL/F) of Unchanged Edaravone | Day 5 | 50.74 L/h | Standard Deviation 18.08 |
Primary
Area Under the Concentration Versus Time Curve (AUC) of Glucuronide Conjugate
Area under the plasma concentration versus time curve from time zero up to 24 hours (AUC0-24) of glucuronide conjugate.
Time frame: Part 1: Pre-dose, 0.25, 0.5, 1.5, 2, 4, 6, 8, 12, 24, 36, 48 hrs post-dose, Part 2: Day 1 and 5 at pre-dose, 0.25, 0.5, 1.5, 2, 4, 6, 8, 12 hrs post-dose; Day 2 to 4 at pre-dose; Day 6 at 24 hrs post-dose on Day 5; Day 7 at 48 hrs post-dose on Day 5
Population: The trial is divided into 2 phases (a single and multiple-dose). A single-dose study included 8 cohorts (total of 56 subjects), with 42 (6x7) subjects receiving MT-1186, and 14 (2x7) receiving the placebo. Multiple-dose study included 2 cohorts (total of 18 subjects), with 12 (6x2) receiving MT-1186, and 6 (3x2) receiving the placebo for 5 days. Since Cohort S3-1 and S3-2 are crossover cohort, the 5 subjects in Cohort S3-2 are overlapped (59 patients receiving MT-1186).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S1) | Area Under the Concentration Versus Time Curve (AUC) of Glucuronide Conjugate | AUC from time zero to 24 hour (AUC 0-24):Day 1 | 2360 ng*h/mL | Standard Deviation 648 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S2) | Area Under the Concentration Versus Time Curve (AUC) of Glucuronide Conjugate | AUC from time zero to 24 hour (AUC 0-24):Day 1 | 4815 ng*h/mL | Standard Deviation 910 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S3-1) | Area Under the Concentration Versus Time Curve (AUC) of Glucuronide Conjugate | AUC from time zero to 24 hour (AUC 0-24):Day 1 | 8146 ng*h/mL | Standard Deviation 1275 |
| A Single Dose MT-1186 Under Fed Condition(Part 1, Cohort S3-2) | Area Under the Concentration Versus Time Curve (AUC) of Glucuronide Conjugate | AUC from time zero to 24 hour (AUC 0-24):Day 1 | 7406 ng*h/mL | Standard Deviation 1368 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S4) | Area Under the Concentration Versus Time Curve (AUC) of Glucuronide Conjugate | AUC from time zero to 24 hour (AUC 0-24):Day 1 | 14403 ng*h/mL | Standard Deviation 1557 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S5) | Area Under the Concentration Versus Time Curve (AUC) of Glucuronide Conjugate | AUC from time zero to 24 hour (AUC 0-24):Day 1 | 12499 ng*h/mL | Standard Deviation 3457 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S6) | Area Under the Concentration Versus Time Curve (AUC) of Glucuronide Conjugate | AUC from time zero to 24 hour (AUC 0-24):Day 1 | 1201 ng*h/mL | Standard Deviation 454 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S7) | Area Under the Concentration Versus Time Curve (AUC) of Glucuronide Conjugate | AUC from time zero to 24 hour (AUC 0-24):Day 1 | 8038 ng*h/mL | Standard Deviation 1898 |
| Matching Placebo Under Fasted Condition (a Sngle Dose Cohorts) | Area Under the Concentration Versus Time Curve (AUC) of Glucuronide Conjugate | AUC from time zero to 24 hour (AUC 0-24):Day 1 | 4806 ng*h/mL | Standard Deviation 509 |
| Matching Placebo Under Fasted Condition (a Sngle Dose Cohorts) | Area Under the Concentration Versus Time Curve (AUC) of Glucuronide Conjugate | AUC from time zero to 24 hour (AUC 0-24): Day 5, only part 2 | 4698 ng*h/mL | Standard Deviation 499 |
| Multiple Doses MT-1186 (Part 2, Cohort M1) | Area Under the Concentration Versus Time Curve (AUC) of Glucuronide Conjugate | AUC from time zero to 24 hour (AUC 0-24):Day 1 | 7932 ng*h/mL | Standard Deviation 1190 |
| Multiple Doses MT-1186 (Part 2, Cohort M1) | Area Under the Concentration Versus Time Curve (AUC) of Glucuronide Conjugate | AUC from time zero to 24 hour (AUC 0-24): Day 5, only part 2 | 8059 ng*h/mL | Standard Deviation 1278 |
Primary
Area Under the Concentration Versus Time Curve (AUC) of Sulfate Conjugate
Area under the plasma concentration versus time curve from time zero up to 24 hours (AUC0-24) of sulfate conjugate.
Time frame: Part 1: Pre-dose, 0.25, 0.5, 1.5, 2, 4, 6, 8, 12, 24, 36, 48 hrs post-dose, Part 2: Day 1 and 5 at pre-dose, 0.25, 0.5, 1.5, 2, 4, 6, 8, 12 hrs post-dose; Day 2 to 4 at pre-dose; Day 6 at 24 hrs post-dose on Day 5; Day 7 at 48 hrs post-dose on Day 5
Population: The trial is divided into 2 phases (a single and multiple-dose). A single-dose study included 8 cohorts (total of 56 subjects), with 42 (6x7) subjects receiving MT-1186, and 14 (2x7) receiving the placebo. Multiple-dose study included 2 cohorts (total of 18 subjects), with 12 (6x2) receiving MT-1186, and 6 (3x2) receiving the placebo for 5 days. Since Cohort S3-1 and S3-2 are crossover cohort, the 5 subjects in Cohort S3-2 are overlapped (59 patients receiving MT-1186).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S1) | Area Under the Concentration Versus Time Curve (AUC) of Sulfate Conjugate | AUC from time zero to 24 hour (AUC 0-24): Day 1 | 16251 ng*h/mL | Standard Deviation 7143 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S2) | Area Under the Concentration Versus Time Curve (AUC) of Sulfate Conjugate | AUC from time zero to 24 hour (AUC 0-24): Day 1 | 30004 ng*h/mL | Standard Deviation 6103 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S3-1) | Area Under the Concentration Versus Time Curve (AUC) of Sulfate Conjugate | AUC from time zero to 24 hour (AUC 0-24): Day 1 | 45666 ng*h/mL | Standard Deviation 10447 |
| A Single Dose MT-1186 Under Fed Condition(Part 1, Cohort S3-2) | Area Under the Concentration Versus Time Curve (AUC) of Sulfate Conjugate | AUC from time zero to 24 hour (AUC 0-24): Day 1 | 38244 ng*h/mL | Standard Deviation 4602 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S4) | Area Under the Concentration Versus Time Curve (AUC) of Sulfate Conjugate | AUC from time zero to 24 hour (AUC 0-24): Day 1 | 67693 ng*h/mL | Standard Deviation 14170 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S5) | Area Under the Concentration Versus Time Curve (AUC) of Sulfate Conjugate | AUC from time zero to 24 hour (AUC 0-24): Day 1 | 68126 ng*h/mL | Standard Deviation 15067 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S6) | Area Under the Concentration Versus Time Curve (AUC) of Sulfate Conjugate | AUC from time zero to 24 hour (AUC 0-24): Day 1 | 6709 ng*h/mL | Standard Deviation 2171 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S7) | Area Under the Concentration Versus Time Curve (AUC) of Sulfate Conjugate | AUC from time zero to 24 hour (AUC 0-24): Day 1 | 44797 ng*h/mL | Standard Deviation 16374 |
| Matching Placebo Under Fasted Condition (a Sngle Dose Cohorts) | Area Under the Concentration Versus Time Curve (AUC) of Sulfate Conjugate | AUC from time zero to 24 hour (AUC 0-24): Day 1 | 26132 ng*h/mL | Standard Deviation 4083 |
| Matching Placebo Under Fasted Condition (a Sngle Dose Cohorts) | Area Under the Concentration Versus Time Curve (AUC) of Sulfate Conjugate | AUC from time zero to 24 hour (AUC 0-24): Day 5, only part 2 | 24578 ng*h/mL | Standard Deviation 4186 |
| Multiple Doses MT-1186 (Part 2, Cohort M1) | Area Under the Concentration Versus Time Curve (AUC) of Sulfate Conjugate | AUC from time zero to 24 hour (AUC 0-24): Day 1 | 39516 ng*h/mL | Standard Deviation 3331 |
| Multiple Doses MT-1186 (Part 2, Cohort M1) | Area Under the Concentration Versus Time Curve (AUC) of Sulfate Conjugate | AUC from time zero to 24 hour (AUC 0-24): Day 5, only part 2 | 39102 ng*h/mL | Standard Deviation 4208 |
Primary
Area Under the Concentration Versus Time Curve (AUC) of Unchanged Edaravone
Area under the plasma concentration versus time curve from time zero up to 24 hours (AUC0-24) of unchanged edaravone.
Time frame: Part 1: Pre-dose, 0.25, 0.5, 1.5, 2, 4, 6, 8, 12, 24, 36, 48 hrs post-dose, Part 2: Day 1 and 5 at pre-dose, 0.25, 0.5, 1.5, 2, 4, 6, 8, 12 hrs post-dose; Day 2 to 4 at pre-dose; Day 6 at 24 hrs post-dose on Day 5; Day 7 at 48 hrs post-dose on Day 5
Population: The trial is divided into 2 phases (a single and multiple-dose). A single-dose study included 8 cohorts (total of 56 subjects), with 42 (6x7) subjects receiving MT-1186, and 14 (2x7) receiving the placebo. Multiple-dose study included 2 cohorts (total of 18 subjects), with 12 (6x2) receiving MT-1186, and 6 (3x2) receiving the placebo for 5 days. Since Cohort S3-1 and S3-2 are crossover cohort, the 5 subjects in Cohort S3-2 are overlapped (59 patients receiving MT-1186).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S1) | Area Under the Concentration Versus Time Curve (AUC) of Unchanged Edaravone | AUC from time zero to 24 hour (AUC 0-24): Day 1 | 816 ng*h/mL | Standard Deviation 231 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S2) | Area Under the Concentration Versus Time Curve (AUC) of Unchanged Edaravone | AUC from time zero to 24 hour (AUC 0-24): Day 1 | 2242 ng*h/mL | Standard Deviation 911 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S3-1) | Area Under the Concentration Versus Time Curve (AUC) of Unchanged Edaravone | AUC from time zero to 24 hour (AUC 0-24): Day 1 | 6254 ng*h/mL | Standard Deviation 1236 |
| A Single Dose MT-1186 Under Fed Condition(Part 1, Cohort S3-2) | Area Under the Concentration Versus Time Curve (AUC) of Unchanged Edaravone | AUC from time zero to 24 hour (AUC 0-24): Day 1 | 2443 ng*h/mL | Standard Deviation 813 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S4) | Area Under the Concentration Versus Time Curve (AUC) of Unchanged Edaravone | AUC from time zero to 24 hour (AUC 0-24): Day 1 | 11319 ng*h/mL | Standard Deviation 1053 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S5) | Area Under the Concentration Versus Time Curve (AUC) of Unchanged Edaravone | AUC from time zero to 24 hour (AUC 0-24): Day 1 | 9034 ng*h/mL | Standard Deviation 2738 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S6) | Area Under the Concentration Versus Time Curve (AUC) of Unchanged Edaravone | AUC from time zero to 24 hour (AUC 0-24): Day 1 | 285 ng*h/mL | Standard Deviation 113 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S7) | Area Under the Concentration Versus Time Curve (AUC) of Unchanged Edaravone | AUC from time zero to 24 hour (AUC 0-24): Day 1 | 4935 ng*h/mL | Standard Deviation 1980 |
| Matching Placebo Under Fasted Condition (a Sngle Dose Cohorts) | Area Under the Concentration Versus Time Curve (AUC) of Unchanged Edaravone | AUC from time zero to 24 hour (AUC 0-24): Day 1 | 1917 ng*h/mL | Standard Deviation 383 |
| Matching Placebo Under Fasted Condition (a Sngle Dose Cohorts) | Area Under the Concentration Versus Time Curve (AUC) of Unchanged Edaravone | AUC from time zero to 24 hour (AUC 0-24): Day 5, only Part 2 | 2189 ng*h/mL | Standard Deviation 516 |
| Multiple Doses MT-1186 (Part 2, Cohort M1) | Area Under the Concentration Versus Time Curve (AUC) of Unchanged Edaravone | AUC from time zero to 24 hour (AUC 0-24): Day 1 | 4133 ng*h/mL | Standard Deviation 1260 |
| Multiple Doses MT-1186 (Part 2, Cohort M1) | Area Under the Concentration Versus Time Curve (AUC) of Unchanged Edaravone | AUC from time zero to 24 hour (AUC 0-24): Day 5, only Part 2 | 4279 ng*h/mL | Standard Deviation 1166 |
Primary
Lambda-z of Glucuronide Conjugate
Time frame: Part 1: Pre-dose, 0.25, 0.5, 1.5, 2, 4, 6, 8, 12, 24, 36, 48 hrs post-dose, Part 2: Day 1 and 5 at pre-dose, 0.25, 0.5, 1.5, 2, 4, 6, 8, 12 hrs post-dose; Day 2 to 4 at pre-dose; Day 6 at 24 hrs post-dose on Day 5; Day 7 at 48 hrs post-dose on Day 5
Population: The trial is divided into 2 phases (a single and multiple-dose). A single-dose study included 8 cohorts (total of 56 subjects), with 42 (6x7) subjects receiving MT-1186, and 14 (2x7) receiving the placebo. Multiple-dose study included 2 cohorts (total of 18 subjects), with 12 (6x2) receiving MT-1186, and 6 (3x2) receiving the placebo for 5 days. Since Cohort S3-1 and S3-2 are crossover cohort, the 5 subjects in Cohort S3-2 are overlapped (59 patients receiving MT-1186).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S1) | Lambda-z of Glucuronide Conjugate | Day 1 | 0.23 1/h | Standard Deviation 0.09 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S2) | Lambda-z of Glucuronide Conjugate | Day 1 | 0.23 1/h | Standard Deviation 0.07 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S3-1) | Lambda-z of Glucuronide Conjugate | Day 1 | 0.17 1/h | Standard Deviation 0.03 |
| A Single Dose MT-1186 Under Fed Condition(Part 1, Cohort S3-2) | Lambda-z of Glucuronide Conjugate | Day 1 | 0.19 1/h | Standard Deviation 0.05 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S4) | Lambda-z of Glucuronide Conjugate | Day 1 | 0.12 1/h | Standard Deviation 0.02 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S5) | Lambda-z of Glucuronide Conjugate | Day 1 | 0.15 1/h | Standard Deviation 0.01 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S6) | Lambda-z of Glucuronide Conjugate | Day 1 | 0.27 1/h | Standard Deviation 0.07 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S7) | Lambda-z of Glucuronide Conjugate | Day 1 | 0.16 1/h | Standard Deviation 0.04 |
| Matching Placebo Under Fasted Condition (a Sngle Dose Cohorts) | Lambda-z of Glucuronide Conjugate | Day 1 | 0.20 1/h | Standard Deviation 0.01 |
| Matching Placebo Under Fasted Condition (a Sngle Dose Cohorts) | Lambda-z of Glucuronide Conjugate | Day 5 | 0.18 1/h | Standard Deviation 0.01 |
| Multiple Doses MT-1186 (Part 2, Cohort M1) | Lambda-z of Glucuronide Conjugate | Day 1 | 0.22 1/h | Standard Deviation 0.03 |
| Multiple Doses MT-1186 (Part 2, Cohort M1) | Lambda-z of Glucuronide Conjugate | Day 5 | 0.15 1/h | Standard Deviation 0.05 |
Primary
Lambda-z of Sulfate Conjugate
Time frame: Part 1: Pre-dose, 0.25, 0.5, 1.5, 2, 4, 6, 8, 12, 24, 36, 48 hrs post-dose, Part 2: Day 1 and 5 at pre-dose, 0.25, 0.5, 1.5, 2, 4, 6, 8, 12 hrs post-dose; Day 2 to 4 at pre-dose; Day 6 at 24 hrs post-dose on Day 5; Day 7 at 48 hrs post-dose on Day 5
Population: The trial is divided into 2 phases (a single and multiple-dose). A single-dose study included 8 cohorts (total of 56 subjects), with 42 (6x7) subjects receiving MT-1186, and 14 (2x7) receiving the placebo. Multiple-dose study included 2 cohorts (total of 18 subjects), with 12 (6x2) receiving MT-1186, and 6 (3x2) receiving the placebo for 5 days. Since Cohort S3-1 and S3-2 are crossover cohort, the 5 subjects in Cohort S3-2 are overlapped (59 patients receiving MT-1186).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S1) | Lambda-z of Sulfate Conjugate | Day 1 | 0.10 1/h | Standard Deviation 0.03 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S2) | Lambda-z of Sulfate Conjugate | Day 1 | 0.11 1/h | Standard Deviation 0.04 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S3-1) | Lambda-z of Sulfate Conjugate | Day 1 | 0.12 1/h | Standard Deviation 0.02 |
| A Single Dose MT-1186 Under Fed Condition(Part 1, Cohort S3-2) | Lambda-z of Sulfate Conjugate | Day 1 | 0.14 1/h | Standard Deviation 0.03 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S4) | Lambda-z of Sulfate Conjugate | Day 1 | 0.12 1/h | Standard Deviation 0.03 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S5) | Lambda-z of Sulfate Conjugate | Day 1 | 0.14 1/h | Standard Deviation 0.01 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S6) | Lambda-z of Sulfate Conjugate | Day 1 | 0.14 1/h | Standard Deviation 0.02 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S7) | Lambda-z of Sulfate Conjugate | Day 1 | 0.12 1/h | Standard Deviation 0.03 |
| Matching Placebo Under Fasted Condition (a Sngle Dose Cohorts) | Lambda-z of Sulfate Conjugate | Day 1 | 0.19 1/h | Standard Deviation 0.01 |
| Matching Placebo Under Fasted Condition (a Sngle Dose Cohorts) | Lambda-z of Sulfate Conjugate | Day 5 | 0.11 1/h | Standard Deviation 0.01 |
| Multiple Doses MT-1186 (Part 2, Cohort M1) | Lambda-z of Sulfate Conjugate | Day 1 | 0.20 1/h | Standard Deviation 0.02 |
| Multiple Doses MT-1186 (Part 2, Cohort M1) | Lambda-z of Sulfate Conjugate | Day 5 | 0.10 1/h | Standard Deviation 0.02 |
Primary
Lambda-z of Unchanged Edaravone
Time frame: Part 1: Pre-dose, 0.25, 0.5, 1.5, 2, 4, 6, 8, 12, 24, 36, 48 hrs post-dose, Part 2: Day 1 and 5 at pre-dose, 0.25, 0.5, 1.5, 2, 4, 6, 8, 12 hrs post-dose; Day 2 to 4 at pre-dose; Day 6 at 24 hrs post-dose on Day 5; Day 7 at 48 hrs post-dose on Day 5
Population: The trial is divided into 2 phases (a single and multiple-dose). A single-dose study included 8 cohorts (total of 56 subjects), with 42 (6x7) subjects receiving MT-1186, and 14 (2x7) receiving the placebo. Multiple-dose study included 2 cohorts (total of 18 subjects), with 12 (6x2) receiving MT-1186, and 6 (3x2) receiving the placebo for 5 days. Since Cohort S3-1 and S3-2 are crossover cohort, the 5 subjects in Cohort S3-2 are overlapped (59 patients receiving MT-1186).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S1) | Lambda-z of Unchanged Edaravone | Day 1 | 0.23 1/h | Standard Deviation 0.05 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S2) | Lambda-z of Unchanged Edaravone | Day 1 | 0.14 1/h | Standard Deviation 0.03 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S3-1) | Lambda-z of Unchanged Edaravone | Day 1 | 0.08 1/h | Standard Deviation 0.02 |
| A Single Dose MT-1186 Under Fed Condition(Part 1, Cohort S3-2) | Lambda-z of Unchanged Edaravone | Day 1 | 0.14 1/h | Standard Deviation 0.04 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S4) | Lambda-z of Unchanged Edaravone | Day 1 | 0.07 1/h | Standard Deviation 0.02 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S5) | Lambda-z of Unchanged Edaravone | Day 1 | 0.08 1/h | Standard Deviation 0.02 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S6) | Lambda-z of Unchanged Edaravone | Day 1 | 0.31 1/h | Standard Deviation 0.11 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S7) | Lambda-z of Unchanged Edaravone | Day 1 | 0.11 1/h | Standard Deviation 0.03 |
| Matching Placebo Under Fasted Condition (a Sngle Dose Cohorts) | Lambda-z of Unchanged Edaravone | Day 1 | 0.15 1/h | Standard Deviation 0.01 |
| Matching Placebo Under Fasted Condition (a Sngle Dose Cohorts) | Lambda-z of Unchanged Edaravone | Day 5 | 0.09 1/h | Standard Deviation 0.03 |
| Multiple Doses MT-1186 (Part 2, Cohort M1) | Lambda-z of Unchanged Edaravone | Day 1 | 0.17 1/h | Standard Deviation 0.01 |
| Multiple Doses MT-1186 (Part 2, Cohort M1) | Lambda-z of Unchanged Edaravone | Day 5 | 0.06 1/h | Standard Deviation 0.01 |
Primary
Maximum Plasma Concentration (Cmax) of Glucuronide Conjugate
Time frame: Part 1: Pre-dose, 0.25, 0.5, 1.5, 2, 4, 6, 8, 12, 24, 36, 48 hrs post-dose, Part 2: Day 1 and 5 at pre-dose, 0.25, 0.5, 1.5, 2, 4, 6, 8, 12 hrs post-dose; Day 2 to 4 at pre-dose; Day 6 at 24 hrs post-dose on Day 5; Day 7 at 48 hrs post-dose on Day 5
Population: The trial is divided into 2 phases (a single and multiple-dose). A single-dose study included 8 cohorts (total of 56 subjects), with 42 (6x7) subjects receiving MT-1186, and 14 (2x7) receiving the placebo. Multiple-dose study included 2 cohorts (total of 18 subjects), with 12 (6x2) receiving MT-1186, and 6 (3x2) receiving the placebo for 5 days. Since Cohort S3-1 and S3-2 are crossover cohort, the 5 subjects in Cohort S3-2 are overlapped (59 patients receiving MT-1186).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S1) | Maximum Plasma Concentration (Cmax) of Glucuronide Conjugate | Day 1 | 1313 ng/mL | Standard Deviation 378 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S2) | Maximum Plasma Concentration (Cmax) of Glucuronide Conjugate | Day 1 | 2272 ng/mL | Standard Deviation 279 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S3-1) | Maximum Plasma Concentration (Cmax) of Glucuronide Conjugate | Day 1 | 3507 ng/mL | Standard Deviation 158 |
| A Single Dose MT-1186 Under Fed Condition(Part 1, Cohort S3-2) | Maximum Plasma Concentration (Cmax) of Glucuronide Conjugate | Day 1 | 1893 ng/mL | Standard Deviation 358 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S4) | Maximum Plasma Concentration (Cmax) of Glucuronide Conjugate | Day 1 | 5322 ng/mL | Standard Deviation 958 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S5) | Maximum Plasma Concentration (Cmax) of Glucuronide Conjugate | Day 1 | 3968 ng/mL | Standard Deviation 912 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S6) | Maximum Plasma Concentration (Cmax) of Glucuronide Conjugate | Day 1 | 750 ng/mL | Standard Deviation 263 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S7) | Maximum Plasma Concentration (Cmax) of Glucuronide Conjugate | Day 1 | 3361 ng/mL | Standard Deviation 1183 |
| Matching Placebo Under Fasted Condition (a Sngle Dose Cohorts) | Maximum Plasma Concentration (Cmax) of Glucuronide Conjugate | Day 1 | 2145 ng/mL | Standard Deviation 356 |
| Matching Placebo Under Fasted Condition (a Sngle Dose Cohorts) | Maximum Plasma Concentration (Cmax) of Glucuronide Conjugate | Day 5 | 2209 ng/mL | Standard Deviation 156 |
| Multiple Doses MT-1186 (Part 2, Cohort M1) | Maximum Plasma Concentration (Cmax) of Glucuronide Conjugate | Day 1 | 3219 ng/mL | Standard Deviation 666 |
| Multiple Doses MT-1186 (Part 2, Cohort M1) | Maximum Plasma Concentration (Cmax) of Glucuronide Conjugate | Day 5 | 3439 ng/mL | Standard Deviation 428 |
Primary
Maximum Plasma Concentration (Cmax) of Sulfate Conjugate
Time frame: Part 1: Pre-dose, 0.25, 0.5, 1.5, 2, 4, 6, 8, 12, 24, 36, 48 hrs post-dose, Part 2: Day 1 and 5 at pre-dose, 0.25, 0.5, 1.5, 2, 4, 6, 8, 12 hrs post-dose; Day 2 to 4 at pre-dose; Day 6 at 24 hrs post-dose on Day 5; Day 7 at 48 hrs post-dose on Day 5
Population: The trial is divided into 2 phases (a single and multiple-dose). A single-dose study included 8 cohorts (total of 56 subjects), with 42 (6x7) subjects receiving MT-1186, and 14 (2x7) receiving the placebo. Multiple-dose study included 2 cohorts (total of 18 subjects), with 12 (6x2) receiving MT-1186, and 6 (3x2) receiving the placebo for 5 days. Since Cohort S3-1 and S3-2 are crossover cohort, the 5 subjects in Cohort S3-2 are overlapped (59 patients receiving MT-1186).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S1) | Maximum Plasma Concentration (Cmax) of Sulfate Conjugate | Day 1 | 5481 ng/mL | Standard Deviation 2337 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S2) | Maximum Plasma Concentration (Cmax) of Sulfate Conjugate | Day 1 | 9108 ng/mL | Standard Deviation 2104 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S3-1) | Maximum Plasma Concentration (Cmax) of Sulfate Conjugate | Day 1 | 12190 ng/mL | Standard Deviation 2087 |
| A Single Dose MT-1186 Under Fed Condition(Part 1, Cohort S3-2) | Maximum Plasma Concentration (Cmax) of Sulfate Conjugate | Day 1 | 7324 ng/mL | Standard Deviation 743 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S4) | Maximum Plasma Concentration (Cmax) of Sulfate Conjugate | Day 1 | 14590 ng/mL | Standard Deviation 2102 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S5) | Maximum Plasma Concentration (Cmax) of Sulfate Conjugate | Day 1 | 14080 ng/mL | Standard Deviation 4787 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S6) | Maximum Plasma Concentration (Cmax) of Sulfate Conjugate | Day 1 | 2913 ng/mL | Standard Deviation 870 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S7) | Maximum Plasma Concentration (Cmax) of Sulfate Conjugate | Day 1 | 11510 ng/mL | Standard Deviation 2502 |
| Matching Placebo Under Fasted Condition (a Sngle Dose Cohorts) | Maximum Plasma Concentration (Cmax) of Sulfate Conjugate | Day 1 | 7318 ng/mL | Standard Deviation 612 |
| Matching Placebo Under Fasted Condition (a Sngle Dose Cohorts) | Maximum Plasma Concentration (Cmax) of Sulfate Conjugate | Day 5 | 7402 ng/mL | Standard Deviation 954 |
| Multiple Doses MT-1186 (Part 2, Cohort M1) | Maximum Plasma Concentration (Cmax) of Sulfate Conjugate | Day 1 | 10830 ng/mL | Standard Deviation 2346 |
| Multiple Doses MT-1186 (Part 2, Cohort M1) | Maximum Plasma Concentration (Cmax) of Sulfate Conjugate | Day 5 | 11200 ng/mL | Standard Deviation 1744 |
Primary
Maximum Plasma Concentration (Cmax) of Unchanged Edaravone
Time frame: Part 1: Pre-dose, 0.25, 0.5, 1.5, 2, 4, 6, 8, 12, 24, 36, 48 hrs post-dose, Part 2: Day 1 and 5 at pre-dose, 0.25, 0.5, 1.5, 2, 4, 6, 8, 12 hrs post-dose; Day 2 to 4 at pre-dose; Day 6 at 24 hrs post-dose on Day 5; Day 7 at 48 hrs post-dose on Day 5
Population: The trial is divided into 2 phases (a single and multiple-dose). A single-dose study included 8 cohorts (total of 56 subjects), with 42 (6x7) subjects receiving MT-1186, and 14 (2x7) receiving the placebo. Multiple-dose study included 2 cohorts (total of 18 subjects), with 12 (6x2) receiving MT-1186, and 6 (3x2) receiving the placebo for 5 days. Since Cohort S3-1 and S3-2 are crossover cohort, the 5 subjects in Cohort S3-2 are overlapped (59 patients receiving MT-1186).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S1) | Maximum Plasma Concentration (Cmax) of Unchanged Edaravone | Day 1 | 755 ng/mL | Standard Deviation 356 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S2) | Maximum Plasma Concentration (Cmax) of Unchanged Edaravone | Day 1 | 1735 ng/mL | Standard Deviation 738 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S3-1) | Maximum Plasma Concentration (Cmax) of Unchanged Edaravone | Day 1 | 4933 ng/mL | Standard Deviation 1268 |
| A Single Dose MT-1186 Under Fed Condition(Part 1, Cohort S3-2) | Maximum Plasma Concentration (Cmax) of Unchanged Edaravone | Day 1 | 899 ng/mL | Standard Deviation 464 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S4) | Maximum Plasma Concentration (Cmax) of Unchanged Edaravone | Day 1 | 8805 ng/mL | Standard Deviation 933 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S5) | Maximum Plasma Concentration (Cmax) of Unchanged Edaravone | Day 1 | 5426 ng/mL | Standard Deviation 2496 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S6) | Maximum Plasma Concentration (Cmax) of Unchanged Edaravone | Day 1 | 208 ng/mL | Standard Deviation 112 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S7) | Maximum Plasma Concentration (Cmax) of Unchanged Edaravone | Day 1 | 3692 ng/mL | Standard Deviation 1529 |
| Matching Placebo Under Fasted Condition (a Sngle Dose Cohorts) | Maximum Plasma Concentration (Cmax) of Unchanged Edaravone | Day 1 | 1953 ng/mL | Standard Deviation 838 |
| Matching Placebo Under Fasted Condition (a Sngle Dose Cohorts) | Maximum Plasma Concentration (Cmax) of Unchanged Edaravone | Day 5 | 2308 ng/mL | Standard Deviation 941 |
| Multiple Doses MT-1186 (Part 2, Cohort M1) | Maximum Plasma Concentration (Cmax) of Unchanged Edaravone | Day 1 | 3855 ng/mL | Standard Deviation 1676 |
| Multiple Doses MT-1186 (Part 2, Cohort M1) | Maximum Plasma Concentration (Cmax) of Unchanged Edaravone | Day 5 | 4092 ng/mL | Standard Deviation 1715 |
Primary
Mean Residence Time (MRT) of Unchanged Edaravone
Time frame: Part 1: Pre-dose, 0.25, 0.5, 1.5, 2, 4, 6, 8, 12, 24, 36, 48 hrs post-dose Part 2: Day 1 and 5 at pre-dose, 0.25, 0.5, 1.5, 2, 4, 6, 8, 12 hrs post-dose; Day 2 to 4 at pre-dose; Day 6 at 24 hrs post-dose on Day 5; Day 7 at 48 hrs post-dose on Day 5
Population: The trial is divided into 2 phases (a single and multiple-dose). A single-dose study included 8 cohorts (total of 56 subjects), with 42 (6x7) subjects receiving MT-1186, and 14 (2x7) receiving the placebo. Multiple-dose study included 2 cohorts (total of 18 subjects), with 12 (6x2) receiving MT-1186, and 6 (3x2) receiving the placebo for 5 days. Since Cohort S3-1 and S3-2 are crossover cohort, the 5 subjects in Cohort S3-2 are overlapped (59 patients receiving MT-1186).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S1) | Mean Residence Time (MRT) of Unchanged Edaravone | Day 1 | 1.92 h | Standard Deviation 0.46 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S2) | Mean Residence Time (MRT) of Unchanged Edaravone | Day 1 | 2.07 h | Standard Deviation 0.26 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S3-1) | Mean Residence Time (MRT) of Unchanged Edaravone | Day 1 | 1.98 h | Standard Deviation 0.15 |
| A Single Dose MT-1186 Under Fed Condition(Part 1, Cohort S3-2) | Mean Residence Time (MRT) of Unchanged Edaravone | Day 1 | 3.41 h | Standard Deviation 0.62 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S4) | Mean Residence Time (MRT) of Unchanged Edaravone | Day 1 | 2.14 h | Standard Deviation 0.2 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S5) | Mean Residence Time (MRT) of Unchanged Edaravone | Day 1 | 2.42 h | Standard Deviation 0.45 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S6) | Mean Residence Time (MRT) of Unchanged Edaravone | Day 1 | 2.02 h | Standard Deviation 0.2 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S7) | Mean Residence Time (MRT) of Unchanged Edaravone | Day 1 | 2.02 h | Standard Deviation 0.32 |
| Matching Placebo Under Fasted Condition (a Sngle Dose Cohorts) | Mean Residence Time (MRT) of Unchanged Edaravone | Day 1 | 1.94 h | Standard Deviation 0.15 |
| Matching Placebo Under Fasted Condition (a Sngle Dose Cohorts) | Mean Residence Time (MRT) of Unchanged Edaravone | Day 5 | 2.17 h | Standard Deviation 0.24 |
| Multiple Doses MT-1186 (Part 2, Cohort M1) | Mean Residence Time (MRT) of Unchanged Edaravone | Day 1 | 1.90 h | Standard Deviation 0.26 |
| Multiple Doses MT-1186 (Part 2, Cohort M1) | Mean Residence Time (MRT) of Unchanged Edaravone | Day 5 | 2.28 h | Standard Deviation 0.37 |
Primary
Number of Participants With Adverse Events (Aes) and Adverse Drug Reactions (ADRs)
Time frame: Day 1 to 8 in Part 1, up to 12 days in Part 2
Population: The trial is divided into 2 phases (a single and multiple-dose). A single-dose study included 8 cohorts (total of 56 subjects), with 42 (6x7) subjects receiving MT-1186, and 14 (2x7) receiving the placebo. Multiple-dose study included 2 cohorts (total of 18 subjects), with 12 (6x2) receiving MT-1186, and 6 (3x2) receiving the placebo for 5 days. Since Cohort S3-1 and S3-2 are crossover cohort, the 5 subjects in Cohort S3-2 are overlapped (total of 79 subjects).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S1) | Number of Participants With Adverse Events (Aes) and Adverse Drug Reactions (ADRs) | Participants with AEs | 0 Participants |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S1) | Number of Participants With Adverse Events (Aes) and Adverse Drug Reactions (ADRs) | Participants with ADRs | 0 Participants |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S2) | Number of Participants With Adverse Events (Aes) and Adverse Drug Reactions (ADRs) | Participants with AEs | 2 Participants |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S2) | Number of Participants With Adverse Events (Aes) and Adverse Drug Reactions (ADRs) | Participants with ADRs | 0 Participants |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S3-1) | Number of Participants With Adverse Events (Aes) and Adverse Drug Reactions (ADRs) | Participants with AEs | 3 Participants |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S3-1) | Number of Participants With Adverse Events (Aes) and Adverse Drug Reactions (ADRs) | Participants with ADRs | 0 Participants |
| A Single Dose MT-1186 Under Fed Condition(Part 1, Cohort S3-2) | Number of Participants With Adverse Events (Aes) and Adverse Drug Reactions (ADRs) | Participants with AEs | 0 Participants |
| A Single Dose MT-1186 Under Fed Condition(Part 1, Cohort S3-2) | Number of Participants With Adverse Events (Aes) and Adverse Drug Reactions (ADRs) | Participants with ADRs | 0 Participants |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S4) | Number of Participants With Adverse Events (Aes) and Adverse Drug Reactions (ADRs) | Participants with ADRs | 0 Participants |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S4) | Number of Participants With Adverse Events (Aes) and Adverse Drug Reactions (ADRs) | Participants with AEs | 0 Participants |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S5) | Number of Participants With Adverse Events (Aes) and Adverse Drug Reactions (ADRs) | Participants with AEs | 1 Participants |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S5) | Number of Participants With Adverse Events (Aes) and Adverse Drug Reactions (ADRs) | Participants with ADRs | 0 Participants |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S6) | Number of Participants With Adverse Events (Aes) and Adverse Drug Reactions (ADRs) | Participants with ADRs | 0 Participants |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S6) | Number of Participants With Adverse Events (Aes) and Adverse Drug Reactions (ADRs) | Participants with AEs | 1 Participants |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S7) | Number of Participants With Adverse Events (Aes) and Adverse Drug Reactions (ADRs) | Participants with AEs | 2 Participants |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S7) | Number of Participants With Adverse Events (Aes) and Adverse Drug Reactions (ADRs) | Participants with ADRs | 1 Participants |
| Matching Placebo Under Fasted Condition (a Sngle Dose Cohorts) | Number of Participants With Adverse Events (Aes) and Adverse Drug Reactions (ADRs) | Participants with ADRs | 0 Participants |
| Matching Placebo Under Fasted Condition (a Sngle Dose Cohorts) | Number of Participants With Adverse Events (Aes) and Adverse Drug Reactions (ADRs) | Participants with AEs | 2 Participants |
| Multiple Doses MT-1186 (Part 2, Cohort M1) | Number of Participants With Adverse Events (Aes) and Adverse Drug Reactions (ADRs) | Participants with ADRs | 0 Participants |
| Multiple Doses MT-1186 (Part 2, Cohort M1) | Number of Participants With Adverse Events (Aes) and Adverse Drug Reactions (ADRs) | Participants with AEs | 2 Participants |
| Multiple Doses MT-1186 (Part 2, Cohort M2) | Number of Participants With Adverse Events (Aes) and Adverse Drug Reactions (ADRs) | Participants with ADRs | 0 Participants |
| Multiple Doses MT-1186 (Part 2, Cohort M2) | Number of Participants With Adverse Events (Aes) and Adverse Drug Reactions (ADRs) | Participants with AEs | 1 Participants |
| Matching Placebo (Multiple Doses Cohorts) | Number of Participants With Adverse Events (Aes) and Adverse Drug Reactions (ADRs) | Participants with ADRs | 0 Participants |
| Matching Placebo (Multiple Doses Cohorts) | Number of Participants With Adverse Events (Aes) and Adverse Drug Reactions (ADRs) | Participants with AEs | 1 Participants |
Primary
Part 2: Minimum Plasma Concentration at Steady State (Ctrough, ss)
Time frame: Part 2: Day 1 and 5 at pre-dose, 0.25, 0.5, 1.5, 2, 4, 6, 8, 12 hrs post-dose; Day 2 to 4 at pre-dose; Day 6 at 24 hrs post-dose on Day 5; Day 7 at 48 hrs post-dose on Day 5
Population: The trial is divided into 2 phases (a single and multiple-dose). A single-dose study included 8 cohorts (S3-1 and S3-2 are crossover cohort, total of 56 subjects), with 42 (6x7) subjects receiving MT-1186, and 14 (2x7) receiving the placebo. Multiple-dose study included a total of 2 cohorts (total of 18 subjects), with 12 (6x2) receiving MT-1186, and 6 (3x2) receiving the placebo for 5 days.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S1) | Part 2: Minimum Plasma Concentration at Steady State (Ctrough, ss) | Unchanged Edaravone | 2.34 ng/mL | Standard Deviation 0.3 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S1) | Part 2: Minimum Plasma Concentration at Steady State (Ctrough, ss) | Sulfate conjugate | 32.91 ng/mL | Standard Deviation 9.01 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S1) | Part 2: Minimum Plasma Concentration at Steady State (Ctrough, ss) | Glucuronide conjugate | 2.69 ng/mL | Standard Deviation 0.3 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S2) | Part 2: Minimum Plasma Concentration at Steady State (Ctrough, ss) | Unchanged Edaravone | 3.79 ng/mL | Standard Deviation 0.8 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S2) | Part 2: Minimum Plasma Concentration at Steady State (Ctrough, ss) | Sulfate conjugate | 49.98 ng/mL | Standard Deviation 11.22 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S2) | Part 2: Minimum Plasma Concentration at Steady State (Ctrough, ss) | Glucuronide conjugate | 5.48 ng/mL | Standard Deviation 1.9 |
Primary
Terminal Elimination Half-life (t1/2) of Glucuronide Conjugate
Time frame: Part 1: Pre-dose, 0.25, 0.5, 1.5, 2, 4, 6, 8, 12, 24, 36, 48 hrs post-dose, Part 2: Day 1 and 5 at pre-dose, 0.25, 0.5, 1.5, 2, 4, 6, 8, 12 hrs post-dose; Day 2 to 4 at pre-dose; Day 6 at 24 hrs post-dose on Day 5; Day 7 at 48 hrs post-dose on Day 5
Population: The trial is divided into 2 phases (a single and multiple-dose). A single-dose study included 8 cohorts (total of 56 subjects), with 42 (6x7) subjects receiving MT-1186, and 14 (2x7) receiving the placebo. Multiple-dose study included 2 cohorts (total of 18 subjects), with 12 (6x2) receiving MT-1186, and 6 (3x2) receiving the placebo for 5 days. Since Cohort S3-1 and S3-2 are crossover cohort, the 5 subjects in Cohort S3-2 are overlapped (59 patients receiving MT-1186).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S1) | Terminal Elimination Half-life (t1/2) of Glucuronide Conjugate | Day 1 | 3.4 h | Standard Deviation 1.1 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S2) | Terminal Elimination Half-life (t1/2) of Glucuronide Conjugate | Day 1 | 3.2 h | Standard Deviation 0.9 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S3-1) | Terminal Elimination Half-life (t1/2) of Glucuronide Conjugate | Day 1 | 4.3 h | Standard Deviation 0.7 |
| A Single Dose MT-1186 Under Fed Condition(Part 1, Cohort S3-2) | Terminal Elimination Half-life (t1/2) of Glucuronide Conjugate | Day 1 | 3.8 h | Standard Deviation 0.9 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S4) | Terminal Elimination Half-life (t1/2) of Glucuronide Conjugate | Day 1 | 5.9 h | Standard Deviation 1.4 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S5) | Terminal Elimination Half-life (t1/2) of Glucuronide Conjugate | Day 1 | 4.8 h | Standard Deviation 0.5 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S6) | Terminal Elimination Half-life (t1/2) of Glucuronide Conjugate | Day 1 | 2.8 h | Standard Deviation 0.9 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S7) | Terminal Elimination Half-life (t1/2) of Glucuronide Conjugate | Day 1 | 4.7 h | Standard Deviation 1.2 |
| Matching Placebo Under Fasted Condition (a Sngle Dose Cohorts) | Terminal Elimination Half-life (t1/2) of Glucuronide Conjugate | Day 1 | 3.5 h | Standard Deviation 0.2 |
| Matching Placebo Under Fasted Condition (a Sngle Dose Cohorts) | Terminal Elimination Half-life (t1/2) of Glucuronide Conjugate | Day 5 | 3.9 h | Standard Deviation 0.3 |
| Multiple Doses MT-1186 (Part 2, Cohort M1) | Terminal Elimination Half-life (t1/2) of Glucuronide Conjugate | Day 1 | 3.2 h | Standard Deviation 0.4 |
| Multiple Doses MT-1186 (Part 2, Cohort M1) | Terminal Elimination Half-life (t1/2) of Glucuronide Conjugate | Day 5 | 5.2 h | Standard Deviation 2 |
Primary
Terminal Elimination Half-life (t1/2) of Sulfate Conjugate
Time frame: Part 1: Pre-dose, 0.25, 0.5, 1.5, 2, 4, 6, 8, 12, 24, 36, 48 hrs post-dose, Part 2: Day 1 and 5 at pre-dose, 0.25, 0.5, 1.5, 2, 4, 6, 8, 12 hrs post-dose; Day 2 to 4 at pre-dose; Day 6 at 24 hrs post-dose on Day 5; Day 7 at 48 hrs post-dose on Day 5
Population: The trial is divided into 2 phases (a single and multiple-dose). A single-dose study included 8 cohorts (total of 56 subjects), with 42 (6x7) subjects receiving MT-1186, and 14 (2x7) receiving the placebo. Multiple-dose study included 2 cohorts (total of 18 subjects), with 12 (6x2) receiving MT-1186, and 6 (3x2) receiving the placebo for 5 days. Since Cohort S3-1 and S3-2 are crossover cohort, the 5 subjects in Cohort S3-2 are overlapped (59 patients receiving MT-1186).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S1) | Terminal Elimination Half-life (t1/2) of Sulfate Conjugate | Day 1 | 7.9 h | Standard Deviation 2.6 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S2) | Terminal Elimination Half-life (t1/2) of Sulfate Conjugate | Day 1 | 7.3 h | Standard Deviation 2.6 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S3-1) | Terminal Elimination Half-life (t1/2) of Sulfate Conjugate | Day 1 | 5.9 h | Standard Deviation 1.7 |
| A Single Dose MT-1186 Under Fed Condition(Part 1, Cohort S3-2) | Terminal Elimination Half-life (t1/2) of Sulfate Conjugate | Day 1 | 5.1 h | Standard Deviation 1.3 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S4) | Terminal Elimination Half-life (t1/2) of Sulfate Conjugate | Day 1 | 6.0 h | Standard Deviation 1.6 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S5) | Terminal Elimination Half-life (t1/2) of Sulfate Conjugate | Day 1 | 4.9 h | Standard Deviation 0.3 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S6) | Terminal Elimination Half-life (t1/2) of Sulfate Conjugate | Day 1 | 5.2 h | Standard Deviation 0.6 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S7) | Terminal Elimination Half-life (t1/2) of Sulfate Conjugate | Day 1 | 6.4 h | Standard Deviation 2.6 |
| Matching Placebo Under Fasted Condition (a Sngle Dose Cohorts) | Terminal Elimination Half-life (t1/2) of Sulfate Conjugate | Day 1 | 3.7 h | Standard Deviation 0.2 |
| Matching Placebo Under Fasted Condition (a Sngle Dose Cohorts) | Terminal Elimination Half-life (t1/2) of Sulfate Conjugate | Day 5 | 6.2 h | Standard Deviation 0.4 |
| Multiple Doses MT-1186 (Part 2, Cohort M1) | Terminal Elimination Half-life (t1/2) of Sulfate Conjugate | Day 1 | 3.4 h | Standard Deviation 0.3 |
| Multiple Doses MT-1186 (Part 2, Cohort M1) | Terminal Elimination Half-life (t1/2) of Sulfate Conjugate | Day 5 | 6.8 h | Standard Deviation 1 |
Primary
Terminal Elimination Half-life (t1/2) of Unchanged Edaravone
Time frame: Part 1: Pre-dose, 0.25, 0.5, 1.5, 2, 4, 6, 8, 12, 24, 36, 48 hrs post-dose, Part 2: Day 1 and 5 at pre-dose, 0.25, 0.5, 1.5, 2, 4, 6, 8, 12 hrs post-dose; Day 2 to 4 at pre-dose; Day 6 at 24 hrs post-dose on Day 5; Day 7 at 48 hrs post-dose on Day 5
Population: The trial is divided into 2 phases (a single and multiple-dose). A single-dose study included 8 cohorts (total of 56 subjects), with 42 (6x7) subjects receiving MT-1186, and 14 (2x7) receiving the placebo. Multiple-dose study included 2 cohorts (total of 18 subjects), with 12 (6x2) receiving MT-1186, and 6 (3x2) receiving the placebo for 5 days. Since Cohort S3-1 and S3-2 are crossover cohort, the 5 subjects in Cohort S3-2 are overlapped (59 patients receiving MT-1186).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S1) | Terminal Elimination Half-life (t1/2) of Unchanged Edaravone | Day 1 | 3.2 h | Standard Deviation 0.9 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S2) | Terminal Elimination Half-life (t1/2) of Unchanged Edaravone | Day 1 | 5.1 h | Standard Deviation 1.5 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S3-1) | Terminal Elimination Half-life (t1/2) of Unchanged Edaravone | Day 1 | 9.1 h | Standard Deviation 2.4 |
| A Single Dose MT-1186 Under Fed Condition(Part 1, Cohort S3-2) | Terminal Elimination Half-life (t1/2) of Unchanged Edaravone | Day 1 | 5.2 h | Standard Deviation 1.7 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S4) | Terminal Elimination Half-life (t1/2) of Unchanged Edaravone | Day 1 | 11.8 h | — |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S5) | Terminal Elimination Half-life (t1/2) of Unchanged Edaravone | Day 1 | 9.1 h | Standard Deviation 3.3 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S6) | Terminal Elimination Half-life (t1/2) of Unchanged Edaravone | Day 1 | 2.4 h | Standard Deviation 0.7 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S7) | Terminal Elimination Half-life (t1/2) of Unchanged Edaravone | Day 1 | 6.5 h | Standard Deviation 1.7 |
| Matching Placebo Under Fasted Condition (a Sngle Dose Cohorts) | Terminal Elimination Half-life (t1/2) of Unchanged Edaravone | Day 1 | 4.6 h | Standard Deviation 0.4 |
| Matching Placebo Under Fasted Condition (a Sngle Dose Cohorts) | Terminal Elimination Half-life (t1/2) of Unchanged Edaravone | Day 5 | 8.7 h | Standard Deviation 3.2 |
| Multiple Doses MT-1186 (Part 2, Cohort M1) | Terminal Elimination Half-life (t1/2) of Unchanged Edaravone | Day 1 | 4.2 h | Standard Deviation 0.2 |
| Multiple Doses MT-1186 (Part 2, Cohort M1) | Terminal Elimination Half-life (t1/2) of Unchanged Edaravone | Day 5 | 12.4 h | Standard Deviation 1.9 |
Primary
Time to Reach Maximum Plasma Concentration (Tmax) of Glucuronide Conjugate
Time frame: Part 1: Pre-dose, 0.25, 0.5, 1.5, 2, 4, 6, 8, 12, 24, 36, 48 hrs post-dose, Part 2: Day 1 and 5 at pre-dose, 0.25, 0.5, 1.5, 2, 4, 6, 8, 12 hrs post-dose; Day 2 to 4 at pre-dose; Day 6 at 24 hrs post-dose on Day 5; Day 7 at 48 hrs post-dose on Day 5
Population: The trial is divided into 2 phases (a single and multiple-dose). A single-dose study included 8 cohorts (total of 56 subjects), with 42 (6x7) subjects receiving MT-1186, and 14 (2x7) receiving the placebo. Multiple-dose study included 2 cohorts (total of 18 subjects), with 12 (6x2) receiving MT-1186, and 6 (3x2) receiving the placebo for 5 days. Since Cohort S3-1 and S3-2 are crossover cohort, the 5 subjects in Cohort S3-2 are overlapped (59 patients receiving MT-1186).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S1) | Time to Reach Maximum Plasma Concentration (Tmax) of Glucuronide Conjugate | Day 1 | 0.5 h | Standard Deviation 0.3 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S2) | Time to Reach Maximum Plasma Concentration (Tmax) of Glucuronide Conjugate | Day 1 | 0.6 h | Standard Deviation 0.2 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S3-1) | Time to Reach Maximum Plasma Concentration (Tmax) of Glucuronide Conjugate | Day 1 | 0.6 h | Standard Deviation 0.2 |
| A Single Dose MT-1186 Under Fed Condition(Part 1, Cohort S3-2) | Time to Reach Maximum Plasma Concentration (Tmax) of Glucuronide Conjugate | Day 1 | 1.2 h | Standard Deviation 0.6 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S4) | Time to Reach Maximum Plasma Concentration (Tmax) of Glucuronide Conjugate | Day 1 | 1.0 h | Standard Deviation 0.3 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S5) | Time to Reach Maximum Plasma Concentration (Tmax) of Glucuronide Conjugate | Day 1 | 1.1 h | Standard Deviation 0.4 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S6) | Time to Reach Maximum Plasma Concentration (Tmax) of Glucuronide Conjugate | Day 1 | 0.5 h | Standard Deviation 0.3 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S7) | Time to Reach Maximum Plasma Concentration (Tmax) of Glucuronide Conjugate | Day 1 | 0.9 h | Standard Deviation 0.4 |
| Matching Placebo Under Fasted Condition (a Sngle Dose Cohorts) | Time to Reach Maximum Plasma Concentration (Tmax) of Glucuronide Conjugate | Day 1 | 0.7 h | Standard Deviation 0.3 |
| Matching Placebo Under Fasted Condition (a Sngle Dose Cohorts) | Time to Reach Maximum Plasma Concentration (Tmax) of Glucuronide Conjugate | Day 5 | 0.6 h | Standard Deviation 0.2 |
| Multiple Doses MT-1186 (Part 2, Cohort M1) | Time to Reach Maximum Plasma Concentration (Tmax) of Glucuronide Conjugate | Day 1 | 0.6 h | Standard Deviation 0.2 |
| Multiple Doses MT-1186 (Part 2, Cohort M1) | Time to Reach Maximum Plasma Concentration (Tmax) of Glucuronide Conjugate | Day 5 | 0.7 h | Standard Deviation 0.3 |
Primary
Time to Reach Maximum Plasma Concentration (Tmax) of Sulfate Conjugate
Time frame: Part 1: Pre-dose, 0.25, 0.5, 1.5, 2, 4, 6, 8, 12, 24, 36, 48 hrs post-dose, Part 2: Day 1 and 5 at pre-dose, 0.25, 0.5, 1.5, 2, 4, 6, 8, 12 hrs post-dose; Day 2 to 4 at pre-dose; Day 6 at 24 hrs post-dose on Day 5; Day 7 at 48 hrs post-dose on Day 5
Population: The trial is divided into 2 phases (a single and multiple-dose). A single-dose study included 8 cohorts (total of 56 subjects), with 42 (6x7) subjects receiving MT-1186, and 14 (2x7) receiving the placebo. Multiple-dose study included 2 cohorts (total of 18 subjects), with 12 (6x2) receiving MT-1186, and 6 (3x2) receiving the placebo for 5 days. Since Cohort S3-1 and S3-2 are crossover cohort, the 5 subjects in Cohort S3-2 are overlapped (59 patients receiving MT-1186).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S1) | Time to Reach Maximum Plasma Concentration (Tmax) of Sulfate Conjugate | Day 1 | 0.6 h | Standard Deviation 0.2 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S2) | Time to Reach Maximum Plasma Concentration (Tmax) of Sulfate Conjugate | Day 1 | 0.8 h | Standard Deviation 0.3 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S3-1) | Time to Reach Maximum Plasma Concentration (Tmax) of Sulfate Conjugate | Day 1 | 1.0 h | Standard Deviation 0 |
| A Single Dose MT-1186 Under Fed Condition(Part 1, Cohort S3-2) | Time to Reach Maximum Plasma Concentration (Tmax) of Sulfate Conjugate | Day 1 | 1.3 h | Standard Deviation 0.5 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S4) | Time to Reach Maximum Plasma Concentration (Tmax) of Sulfate Conjugate | Day 1 | 1.3 h | Standard Deviation 0.3 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S5) | Time to Reach Maximum Plasma Concentration (Tmax) of Sulfate Conjugate | Day 1 | 1.4 h | Standard Deviation 0.4 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S6) | Time to Reach Maximum Plasma Concentration (Tmax) of Sulfate Conjugate | Day 1 | 0.5 h | Standard Deviation 0.3 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S7) | Time to Reach Maximum Plasma Concentration (Tmax) of Sulfate Conjugate | Day 1 | 0.9 h | Standard Deviation 0.4 |
| Matching Placebo Under Fasted Condition (a Sngle Dose Cohorts) | Time to Reach Maximum Plasma Concentration (Tmax) of Sulfate Conjugate | Day 1 | 0.8 h | Standard Deviation 0.3 |
| Matching Placebo Under Fasted Condition (a Sngle Dose Cohorts) | Time to Reach Maximum Plasma Concentration (Tmax) of Sulfate Conjugate | Day 5 | 0.8 h | Standard Deviation 0.3 |
| Multiple Doses MT-1186 (Part 2, Cohort M1) | Time to Reach Maximum Plasma Concentration (Tmax) of Sulfate Conjugate | Day 1 | 0.9 h | Standard Deviation 0.2 |
| Multiple Doses MT-1186 (Part 2, Cohort M1) | Time to Reach Maximum Plasma Concentration (Tmax) of Sulfate Conjugate | Day 5 | 0.8 h | Standard Deviation 0.3 |
Primary
Time to Reach Maximum Plasma Concentration (Tmax) of Unchanged Edaravone
Time frame: Part 1: Pre-dose, 0.25, 0.5, 1.5, 2, 4, 6, 8, 12, 24, 36, 48 hrs post-dose, Part 2: Day 1 and 5 at pre-dose, 0.25, 0.5, 1.5, 2, 4, 6, 8, 12 hrs post-dose; Day 2 to 4 at pre-dose; Day 6 at 24 hrs post-dose on Day 5; Day 7 at 48 hrs post-dose on Day 5
Population: The trial is divided into 2 phases (a single and multiple-dose). A single-dose study included 8 cohorts (total of 56 subjects), with 42 (6x7) subjects receiving MT-1186, and 14 (2x7) receiving the placebo. Multiple-dose study included 2 cohorts (total of 18 subjects), with 12 (6x2) receiving MT-1186, and 6 (3x2) receiving the placebo for 5 days. Since Cohort S3-1 and S3-2 are crossover cohort, the 5 subjects in Cohort S3-2 are overlapped (59 patients receiving MT-1186).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S1) | Time to Reach Maximum Plasma Concentration (Tmax) of Unchanged Edaravone | Day 1 | 0.3 h | Standard Deviation 0.1 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S2) | Time to Reach Maximum Plasma Concentration (Tmax) of Unchanged Edaravone | Day 1 | 0.4 h | Standard Deviation 0.1 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S3-1) | Time to Reach Maximum Plasma Concentration (Tmax) of Unchanged Edaravone | Day 1 | 0.4 h | Standard Deviation 0.1 |
| A Single Dose MT-1186 Under Fed Condition(Part 1, Cohort S3-2) | Time to Reach Maximum Plasma Concentration (Tmax) of Unchanged Edaravone | Day 1 | 1.4 h | Standard Deviation 1.6 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S4) | Time to Reach Maximum Plasma Concentration (Tmax) of Unchanged Edaravone | Day 1 | 0.6 h | Standard Deviation 0.3 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S5) | Time to Reach Maximum Plasma Concentration (Tmax) of Unchanged Edaravone | Day 1 | 0.8 h | Standard Deviation 0.4 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S6) | Time to Reach Maximum Plasma Concentration (Tmax) of Unchanged Edaravone | Day 1 | 0.4 h | Standard Deviation 0.1 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S7) | Time to Reach Maximum Plasma Concentration (Tmax) of Unchanged Edaravone | Day 1 | 0.6 h | Standard Deviation 0.3 |
| Matching Placebo Under Fasted Condition (a Sngle Dose Cohorts) | Time to Reach Maximum Plasma Concentration (Tmax) of Unchanged Edaravone | Day 1 | 0.4 h | Standard Deviation 0.1 |
| Matching Placebo Under Fasted Condition (a Sngle Dose Cohorts) | Time to Reach Maximum Plasma Concentration (Tmax) of Unchanged Edaravone | Day 5 | 0.4 h | Standard Deviation 0.1 |
| Multiple Doses MT-1186 (Part 2, Cohort M1) | Time to Reach Maximum Plasma Concentration (Tmax) of Unchanged Edaravone | Day 1 | 0.4 h | Standard Deviation 0.1 |
| Multiple Doses MT-1186 (Part 2, Cohort M1) | Time to Reach Maximum Plasma Concentration (Tmax) of Unchanged Edaravone | Day 5 | 0.4 h | Standard Deviation 0.1 |
Secondary
Change of Heart Rate (HR) From Baseline
Holter ECG data were recorded in part 1, Cohorts S4, S5, and S6. Baseline is calculated as average HR from 0.75, 0.5, and 0.25 hours pre-dose.
Time frame: 0.75, 0.5, and 0.25 hours pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 36, and 48 hours post-dose.
Population: Pharmacodynamic data were collected in Cohort S4, S5 and S6 with 18 (6x3 subjects receiving MT-1186), and 6 (2x3) receiving the placebo of Part 1.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S1) | Change of Heart Rate (HR) From Baseline | 24h | 1.3 bpm | Standard Error 1.54 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S1) | Change of Heart Rate (HR) From Baseline | 48h | 4.3 bpm | Standard Error 2.51 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S1) | Change of Heart Rate (HR) From Baseline | 8h | 4.4 bpm | Standard Error 1.72 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S1) | Change of Heart Rate (HR) From Baseline | 0.25h | 1.8 bpm | Standard Error 0.91 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S1) | Change of Heart Rate (HR) From Baseline | 12h | 1.9 bpm | Standard Error 2.07 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S1) | Change of Heart Rate (HR) From Baseline | 1h | -0.1 bpm | Standard Error 1.28 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S1) | Change of Heart Rate (HR) From Baseline | 1.5h | -1.2 bpm | Standard Error 1 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S1) | Change of Heart Rate (HR) From Baseline | 0.5h | -0.2 bpm | Standard Error 1.01 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S1) | Change of Heart Rate (HR) From Baseline | 36h | 8.1 bpm | Standard Error 3.07 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S1) | Change of Heart Rate (HR) From Baseline | 2h | -0.1 bpm | Standard Error 0.95 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S1) | Change of Heart Rate (HR) From Baseline | 4h | -0.7 bpm | Standard Error 1.36 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S1) | Change of Heart Rate (HR) From Baseline | 6h | 3.2 bpm | Standard Error 1.88 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S2) | Change of Heart Rate (HR) From Baseline | 0.5h | 0.2 bpm | Standard Error 1.01 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S2) | Change of Heart Rate (HR) From Baseline | 6h | 6.4 bpm | Standard Error 1.87 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S2) | Change of Heart Rate (HR) From Baseline | 1.5h | -0.3 bpm | Standard Error 1 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S2) | Change of Heart Rate (HR) From Baseline | 12h | 10.1 bpm | Standard Error 2.07 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S2) | Change of Heart Rate (HR) From Baseline | 24h | 1.7 bpm | Standard Error 1.54 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S2) | Change of Heart Rate (HR) From Baseline | 8h | 4.1 bpm | Standard Error 1.72 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S2) | Change of Heart Rate (HR) From Baseline | 0.25h | -1.2 bpm | Standard Error 0.91 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S2) | Change of Heart Rate (HR) From Baseline | 4h | -1.6 bpm | Standard Error 1.36 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S2) | Change of Heart Rate (HR) From Baseline | 2h | 0.4 bpm | Standard Error 0.95 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S2) | Change of Heart Rate (HR) From Baseline | 1h | -1.7 bpm | Standard Error 1.28 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S2) | Change of Heart Rate (HR) From Baseline | 48h | 8.2 bpm | Standard Error 2.51 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S2) | Change of Heart Rate (HR) From Baseline | 36h | 9.9 bpm | Standard Error 3.06 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S3-1) | Change of Heart Rate (HR) From Baseline | 8h | 6.2 bpm | Standard Error 1.8 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S3-1) | Change of Heart Rate (HR) From Baseline | 0.25h | 1.8 bpm | Standard Error 0.96 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S3-1) | Change of Heart Rate (HR) From Baseline | 0.5h | 1.3 bpm | Standard Error 1.06 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S3-1) | Change of Heart Rate (HR) From Baseline | 1h | 0.2 bpm | Standard Error 1.34 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S3-1) | Change of Heart Rate (HR) From Baseline | 1.5h | 0.2 bpm | Standard Error 1.04 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S3-1) | Change of Heart Rate (HR) From Baseline | 2h | 0.9 bpm | Standard Error 0.99 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S3-1) | Change of Heart Rate (HR) From Baseline | 4h | -0.1 bpm | Standard Error 1.42 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S3-1) | Change of Heart Rate (HR) From Baseline | 6h | 3.8 bpm | Standard Error 1.96 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S3-1) | Change of Heart Rate (HR) From Baseline | 12h | 7.6 bpm | Standard Error 2.16 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S3-1) | Change of Heart Rate (HR) From Baseline | 24h | 2.2 bpm | Standard Error 1.61 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S3-1) | Change of Heart Rate (HR) From Baseline | 36h | 13.2 bpm | Standard Error 3.21 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S3-1) | Change of Heart Rate (HR) From Baseline | 48h | 8.4 bpm | Standard Error 2.62 |
| A Single Dose MT-1186 Under Fed Condition(Part 1, Cohort S3-2) | Change of Heart Rate (HR) From Baseline | 4h | -1.5 bpm | Standard Error 1.37 |
| A Single Dose MT-1186 Under Fed Condition(Part 1, Cohort S3-2) | Change of Heart Rate (HR) From Baseline | 2h | -0.1 bpm | Standard Error 0.96 |
| A Single Dose MT-1186 Under Fed Condition(Part 1, Cohort S3-2) | Change of Heart Rate (HR) From Baseline | 0.25h | -0.2 bpm | Standard Error 0.92 |
| A Single Dose MT-1186 Under Fed Condition(Part 1, Cohort S3-2) | Change of Heart Rate (HR) From Baseline | 24h | -1 bpm | Standard Error 1.55 |
| A Single Dose MT-1186 Under Fed Condition(Part 1, Cohort S3-2) | Change of Heart Rate (HR) From Baseline | 1.5h | -0.1 bpm | Standard Error 1.01 |
| A Single Dose MT-1186 Under Fed Condition(Part 1, Cohort S3-2) | Change of Heart Rate (HR) From Baseline | 1h | -0.2 bpm | Standard Error 1.29 |
| A Single Dose MT-1186 Under Fed Condition(Part 1, Cohort S3-2) | Change of Heart Rate (HR) From Baseline | 48h | 2.4 bpm | Standard Error 2.53 |
| A Single Dose MT-1186 Under Fed Condition(Part 1, Cohort S3-2) | Change of Heart Rate (HR) From Baseline | 36h | 5.7 bpm | Standard Error 3.1 |
| A Single Dose MT-1186 Under Fed Condition(Part 1, Cohort S3-2) | Change of Heart Rate (HR) From Baseline | 8h | 3.4 bpm | Standard Error 1.74 |
| A Single Dose MT-1186 Under Fed Condition(Part 1, Cohort S3-2) | Change of Heart Rate (HR) From Baseline | 6h | 3.8 bpm | Standard Error 1.89 |
| A Single Dose MT-1186 Under Fed Condition(Part 1, Cohort S3-2) | Change of Heart Rate (HR) From Baseline | 0.5h | 1.2 bpm | Standard Error 1.02 |
| A Single Dose MT-1186 Under Fed Condition(Part 1, Cohort S3-2) | Change of Heart Rate (HR) From Baseline | 12h | 4.6 bpm | Standard Error 2.09 |
Secondary
Change of PR Interval (PR) From Baseline
Holter ECG data were recorded in part 1, Cohorts S4, S5, and S6. Baseline is calculated as average HR from 0.75, 0.5, and 0.25 hours pre-dose.
Time frame: 0.75, 0.5, and 0.25 hours pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 36, and 48 hours post-dose.
Population: Pharmacodynamic data were collected in Cohort S4, S5 and S6 with 18 (6x3 subjects receiving MT-1186), and 6 (2x3) receiving the placebo of Part 1.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S1) | Change of PR Interval (PR) From Baseline | 24h | -2.1 msec | Standard Error 2.62 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S1) | Change of PR Interval (PR) From Baseline | 48h | -3.3 msec | Standard Error 2.63 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S1) | Change of PR Interval (PR) From Baseline | 8h | -11.6 msec | Standard Error 2.6 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S1) | Change of PR Interval (PR) From Baseline | 0.25h | -6.8 msec | Standard Error 1.91 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S1) | Change of PR Interval (PR) From Baseline | 12h | -6.6 msec | Standard Error 3.91 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S1) | Change of PR Interval (PR) From Baseline | 1h | -4.2 msec | Standard Error 1.68 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S1) | Change of PR Interval (PR) From Baseline | 1.5h | -5.2 msec | Standard Error 2.23 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S1) | Change of PR Interval (PR) From Baseline | 0.5h | -4.2 msec | Standard Error 1.35 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S1) | Change of PR Interval (PR) From Baseline | 36h | -5.7 msec | Standard Error 3.77 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S1) | Change of PR Interval (PR) From Baseline | 2h | -5.9 msec | Standard Error 1.9 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S1) | Change of PR Interval (PR) From Baseline | 4h | -3.0 msec | Standard Error 2.64 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S1) | Change of PR Interval (PR) From Baseline | 6h | -5.5 msec | Standard Error 1.91 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S2) | Change of PR Interval (PR) From Baseline | 0.5h | 0.1 msec | Standard Error 1.4 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S2) | Change of PR Interval (PR) From Baseline | 6h | -9.6 msec | Standard Error 1.98 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S2) | Change of PR Interval (PR) From Baseline | 1.5h | 0.0 msec | Standard Error 2.31 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S2) | Change of PR Interval (PR) From Baseline | 12h | -12.0 msec | Standard Error 4.06 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S2) | Change of PR Interval (PR) From Baseline | 24h | -1.6 msec | Standard Error 2.72 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S2) | Change of PR Interval (PR) From Baseline | 8h | -9.0 msec | Standard Error 2.7 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S2) | Change of PR Interval (PR) From Baseline | 0.25h | -3.3 msec | Standard Error 1.99 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S2) | Change of PR Interval (PR) From Baseline | 4h | -3.0 msec | Standard Error 2.74 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S2) | Change of PR Interval (PR) From Baseline | 2h | -0.8 msec | Standard Error 1.97 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S2) | Change of PR Interval (PR) From Baseline | 1h | 2.1 msec | Standard Error 1.74 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S2) | Change of PR Interval (PR) From Baseline | 48h | 0.6 msec | Standard Error 2.73 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S2) | Change of PR Interval (PR) From Baseline | 36h | -6.8 msec | Standard Error 3.91 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S3-1) | Change of PR Interval (PR) From Baseline | 8h | -9.9 msec | Standard Error 2.62 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S3-1) | Change of PR Interval (PR) From Baseline | 0.25h | -5.7 msec | Standard Error 1.92 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S3-1) | Change of PR Interval (PR) From Baseline | 0.5h | -2.4 msec | Standard Error 1.36 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S3-1) | Change of PR Interval (PR) From Baseline | 1h | -4.0 msec | Standard Error 1.68 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S3-1) | Change of PR Interval (PR) From Baseline | 1.5h | -4.8 msec | Standard Error 2.24 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S3-1) | Change of PR Interval (PR) From Baseline | 2h | -4.5 msec | Standard Error 1.91 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S3-1) | Change of PR Interval (PR) From Baseline | 4h | -5.3 msec | Standard Error 2.66 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S3-1) | Change of PR Interval (PR) From Baseline | 6h | -6.3 msec | Standard Error 1.92 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S3-1) | Change of PR Interval (PR) From Baseline | 12h | -9.0 msec | Standard Error 3.93 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S3-1) | Change of PR Interval (PR) From Baseline | 24h | -8.9 msec | Standard Error 2.63 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S3-1) | Change of PR Interval (PR) From Baseline | 36h | -6.2 msec | Standard Error 3.78 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S3-1) | Change of PR Interval (PR) From Baseline | 48h | -3.2 msec | Standard Error 2.64 |
| A Single Dose MT-1186 Under Fed Condition(Part 1, Cohort S3-2) | Change of PR Interval (PR) From Baseline | 4h | -5.4 msec | Standard Error 2.85 |
| A Single Dose MT-1186 Under Fed Condition(Part 1, Cohort S3-2) | Change of PR Interval (PR) From Baseline | 2h | -5.9 msec | Standard Error 2.05 |
| A Single Dose MT-1186 Under Fed Condition(Part 1, Cohort S3-2) | Change of PR Interval (PR) From Baseline | 0.25h | -4.5 msec | Standard Error 2.06 |
| A Single Dose MT-1186 Under Fed Condition(Part 1, Cohort S3-2) | Change of PR Interval (PR) From Baseline | 24h | -1.1 msec | Standard Error 2.82 |
| A Single Dose MT-1186 Under Fed Condition(Part 1, Cohort S3-2) | Change of PR Interval (PR) From Baseline | 1.5h | -5.3 msec | Standard Error 2.4 |
| A Single Dose MT-1186 Under Fed Condition(Part 1, Cohort S3-2) | Change of PR Interval (PR) From Baseline | 1h | -4.7 msec | Standard Error 1.8 |
| A Single Dose MT-1186 Under Fed Condition(Part 1, Cohort S3-2) | Change of PR Interval (PR) From Baseline | 48h | -5.4 msec | Standard Error 2.83 |
| A Single Dose MT-1186 Under Fed Condition(Part 1, Cohort S3-2) | Change of PR Interval (PR) From Baseline | 36h | -9.5 msec | Standard Error 4.06 |
| A Single Dose MT-1186 Under Fed Condition(Part 1, Cohort S3-2) | Change of PR Interval (PR) From Baseline | 8h | -11.9 msec | Standard Error 2.8 |
| A Single Dose MT-1186 Under Fed Condition(Part 1, Cohort S3-2) | Change of PR Interval (PR) From Baseline | 6h | -6.6 msec | Standard Error 2.06 |
| A Single Dose MT-1186 Under Fed Condition(Part 1, Cohort S3-2) | Change of PR Interval (PR) From Baseline | 0.5h | -3.4 msec | Standard Error 1.45 |
| A Single Dose MT-1186 Under Fed Condition(Part 1, Cohort S3-2) | Change of PR Interval (PR) From Baseline | 12h | -11.8 msec | Standard Error 4.21 |
Secondary
Change of QRS Duration (QRS) From Baseline
Holter ECG data were recorded in part 1, Cohorts S4, S5, and S6.
Time frame: 0.75, 0.5, and 0.25 hours pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 36, and 48 hours post-dose.
Population: Pharmacodynamic data were collected in Cohort S4, S5 and S6 with 18 (6x3 subjects receiving MT-1186), and 6 (2x3) receiving the placebo of Part 1.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S1) | Change of QRS Duration (QRS) From Baseline | 0.25h | -0.7 msec | Standard Error 0.85 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S1) | Change of QRS Duration (QRS) From Baseline | 0.5h | -0.3 msec | Standard Error 0.77 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S1) | Change of QRS Duration (QRS) From Baseline | 1h | -0.3 msec | Standard Error 0.7 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S1) | Change of QRS Duration (QRS) From Baseline | 1.5h | -0.4 msec | Standard Error 0.7 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S1) | Change of QRS Duration (QRS) From Baseline | 4h | -0.5 msec | Standard Error 1.36 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S1) | Change of QRS Duration (QRS) From Baseline | 6h | -0.3 msec | Standard Error 1.31 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S1) | Change of QRS Duration (QRS) From Baseline | 8h | -1.2 msec | Standard Error 1.5 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S1) | Change of QRS Duration (QRS) From Baseline | 12h | 0.4 msec | Standard Error 1.71 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S1) | Change of QRS Duration (QRS) From Baseline | 24h | -0.9 msec | Standard Error 1.26 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S1) | Change of QRS Duration (QRS) From Baseline | 36h | -0.2 msec | Standard Error 1.76 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S1) | Change of QRS Duration (QRS) From Baseline | 48h | -1.7 msec | Standard Error 1.18 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S1) | Change of QRS Duration (QRS) From Baseline | 2h | -1.5 msec | Standard Error 0.98 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S2) | Change of QRS Duration (QRS) From Baseline | 36h | -1.5 msec | Standard Error 1.75 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S2) | Change of QRS Duration (QRS) From Baseline | 1.5h | -0.7 msec | Standard Error 0.8 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S2) | Change of QRS Duration (QRS) From Baseline | 4h | -2.1 msec | Standard Error 1.36 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S2) | Change of QRS Duration (QRS) From Baseline | 6h | 1.1 msec | Standard Error 1.31 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S2) | Change of QRS Duration (QRS) From Baseline | 2h | -0.5 msec | Standard Error 0.98 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S2) | Change of QRS Duration (QRS) From Baseline | 8h | 0.0 msec | Standard Error 1.5 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S2) | Change of QRS Duration (QRS) From Baseline | 48h | -1.5 msec | Standard Error 1.17 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S2) | Change of QRS Duration (QRS) From Baseline | 12h | -2.1 msec | Standard Error 1.71 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S2) | Change of QRS Duration (QRS) From Baseline | 24h | -2.2 msec | Standard Error 1.25 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S2) | Change of QRS Duration (QRS) From Baseline | 0.25h | -0.4 msec | Standard Error 0.84 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S2) | Change of QRS Duration (QRS) From Baseline | 0.5h | -0.8 msec | Standard Error 0.77 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S2) | Change of QRS Duration (QRS) From Baseline | 1h | -1.5 msec | Standard Error 0.69 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S3-1) | Change of QRS Duration (QRS) From Baseline | 6h | -0.8 msec | Standard Error 1.36 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S3-1) | Change of QRS Duration (QRS) From Baseline | 1h | 0.5 msec | Standard Error 0.72 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S3-1) | Change of QRS Duration (QRS) From Baseline | 8h | -2.4 msec | Standard Error 1.55 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S3-1) | Change of QRS Duration (QRS) From Baseline | 0.5h | -0.5 msec | Standard Error 0.8 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S3-1) | Change of QRS Duration (QRS) From Baseline | 12h | -2.0 msec | Standard Error 1.77 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S3-1) | Change of QRS Duration (QRS) From Baseline | 48h | -1.4 msec | Standard Error 1.22 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S3-1) | Change of QRS Duration (QRS) From Baseline | 24h | -1.4 msec | Standard Error 1.3 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S3-1) | Change of QRS Duration (QRS) From Baseline | 1.5h | 0.4 msec | Standard Error 0.83 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S3-1) | Change of QRS Duration (QRS) From Baseline | 2h | 0.2 msec | Standard Error 1.01 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S3-1) | Change of QRS Duration (QRS) From Baseline | 36h | -2.4 msec | Standard Error 1.81 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S3-1) | Change of QRS Duration (QRS) From Baseline | 0.25h | 0.4 msec | Standard Error 0.87 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S3-1) | Change of QRS Duration (QRS) From Baseline | 4h | -0.4 msec | Standard Error 1.41 |
| A Single Dose MT-1186 Under Fed Condition(Part 1, Cohort S3-2) | Change of QRS Duration (QRS) From Baseline | 4h | -0.5 msec | Standard Error 1.42 |
| A Single Dose MT-1186 Under Fed Condition(Part 1, Cohort S3-2) | Change of QRS Duration (QRS) From Baseline | 6h | 0.7 msec | Standard Error 1.37 |
| A Single Dose MT-1186 Under Fed Condition(Part 1, Cohort S3-2) | Change of QRS Duration (QRS) From Baseline | 24h | -1.2 msec | Standard Error 1.31 |
| A Single Dose MT-1186 Under Fed Condition(Part 1, Cohort S3-2) | Change of QRS Duration (QRS) From Baseline | 1h | -1.4 msec | Standard Error 0.72 |
| A Single Dose MT-1186 Under Fed Condition(Part 1, Cohort S3-2) | Change of QRS Duration (QRS) From Baseline | 36h | 0.4 msec | Standard Error 1.83 |
| A Single Dose MT-1186 Under Fed Condition(Part 1, Cohort S3-2) | Change of QRS Duration (QRS) From Baseline | 8h | -1.3 msec | Standard Error 1.57 |
| A Single Dose MT-1186 Under Fed Condition(Part 1, Cohort S3-2) | Change of QRS Duration (QRS) From Baseline | 1.5h | -1.4 msec | Standard Error 0.72 |
| A Single Dose MT-1186 Under Fed Condition(Part 1, Cohort S3-2) | Change of QRS Duration (QRS) From Baseline | 0.5h | -1.6 msec | Standard Error 0.8 |
| A Single Dose MT-1186 Under Fed Condition(Part 1, Cohort S3-2) | Change of QRS Duration (QRS) From Baseline | 0.25h | -2.0 msec | Standard Error 0.88 |
| A Single Dose MT-1186 Under Fed Condition(Part 1, Cohort S3-2) | Change of QRS Duration (QRS) From Baseline | 12h | 0.0 msec | Standard Error 1.78 |
| A Single Dose MT-1186 Under Fed Condition(Part 1, Cohort S3-2) | Change of QRS Duration (QRS) From Baseline | 2h | -2.7 msec | Standard Error 1.02 |
| A Single Dose MT-1186 Under Fed Condition(Part 1, Cohort S3-2) | Change of QRS Duration (QRS) From Baseline | 48h | -0.1 msec | Standard Error 1.23 |
Secondary
Change of QTcF Interval (QTcF) From Baseline
Holter ECG data were recorded in part 1, Cohorts S4, S5, and S6. Baseline is calculated as average HR from 0.75, 0.5, and 0.25 hours pre-dose.
Time frame: 0.75, 0.5, and 0.25 hours pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 36, and 48 hours post-dose.
Population: Pharmacodynamic data were collected in Cohort S4, S5 and S6 with 18 (6x3 subjects receiving MT-1186), and 6 (2x3) receiving the placebo of Part 1.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S1) | Change of QTcF Interval (QTcF) From Baseline | 24h | 2.0 msec | Standard Error 2.42 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S1) | Change of QTcF Interval (QTcF) From Baseline | 48h | -1.0 msec | Standard Error 3.22 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S1) | Change of QTcF Interval (QTcF) From Baseline | 8h | -5.3 msec | Standard Error 2.62 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S1) | Change of QTcF Interval (QTcF) From Baseline | 0.25h | 2.0 msec | Standard Error 1.6 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S1) | Change of QTcF Interval (QTcF) From Baseline | 12h | -2.3 msec | Standard Error 2.42 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S1) | Change of QTcF Interval (QTcF) From Baseline | 1h | 0.3 msec | Standard Error 2.02 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S1) | Change of QTcF Interval (QTcF) From Baseline | 1.5h | -5.2 msec | Standard Error 2.23 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S1) | Change of QTcF Interval (QTcF) From Baseline | 0.5h | -2.2 msec | Standard Error 1.32 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S1) | Change of QTcF Interval (QTcF) From Baseline | 36h | -3.0 msec | Standard Error 2.96 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S1) | Change of QTcF Interval (QTcF) From Baseline | 2h | 1.2 msec | Standard Error 1.68 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S1) | Change of QTcF Interval (QTcF) From Baseline | 4h | 2.3 msec | Standard Error 2.85 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S1) | Change of QTcF Interval (QTcF) From Baseline | 6h | -5.7 msec | Standard Error 2.96 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S2) | Change of QTcF Interval (QTcF) From Baseline | 0.5h | 1.1 msec | Standard Error 1.31 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S2) | Change of QTcF Interval (QTcF) From Baseline | 6h | -2.9 msec | Standard Error 2.96 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S2) | Change of QTcF Interval (QTcF) From Baseline | 1.5h | 2.7 msec | Standard Error 1.68 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S2) | Change of QTcF Interval (QTcF) From Baseline | 12h | -4.0 msec | Standard Error 2.42 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S2) | Change of QTcF Interval (QTcF) From Baseline | 24h | -1.2 msec | Standard Error 2.42 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S2) | Change of QTcF Interval (QTcF) From Baseline | 8h | -2.9 msec | Standard Error 2.62 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S2) | Change of QTcF Interval (QTcF) From Baseline | 0.25h | 0.7 msec | Standard Error 1.6 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S2) | Change of QTcF Interval (QTcF) From Baseline | 4h | -0.9 msec | Standard Error 2.85 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S2) | Change of QTcF Interval (QTcF) From Baseline | 2h | 1.5 msec | Standard Error 2.34 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S2) | Change of QTcF Interval (QTcF) From Baseline | 1h | -0.1 msec | Standard Error 2.02 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S2) | Change of QTcF Interval (QTcF) From Baseline | 48h | -1.5 msec | Standard Error 3.22 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S2) | Change of QTcF Interval (QTcF) From Baseline | 36h | -5.0 msec | Standard Error 2.96 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S3-1) | Change of QTcF Interval (QTcF) From Baseline | 8h | -7.0 msec | Standard Error 2.66 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S3-1) | Change of QTcF Interval (QTcF) From Baseline | 0.25h | 1.6 msec | Standard Error 1.63 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S3-1) | Change of QTcF Interval (QTcF) From Baseline | 0.5h | -3.8 msec | Standard Error 1.34 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S3-1) | Change of QTcF Interval (QTcF) From Baseline | 1h | -4.7 msec | Standard Error 2.06 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S3-1) | Change of QTcF Interval (QTcF) From Baseline | 1.5h | -1.9 msec | Standard Error 1.71 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S3-1) | Change of QTcF Interval (QTcF) From Baseline | 2h | -5.1 msec | Standard Error 2.39 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S3-1) | Change of QTcF Interval (QTcF) From Baseline | 4h | 1.4 msec | Standard Error 2.9 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S3-1) | Change of QTcF Interval (QTcF) From Baseline | 6h | -7.6 msec | Standard Error 3.01 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S3-1) | Change of QTcF Interval (QTcF) From Baseline | 12h | -3.1 msec | Standard Error 2.47 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S3-1) | Change of QTcF Interval (QTcF) From Baseline | 24h | -5.7 msec | Standard Error 2.46 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S3-1) | Change of QTcF Interval (QTcF) From Baseline | 36h | -5.1 msec | Standard Error 3.01 |
| A Single Dose MT-1186 Under Fasted Condition (Part 1, Cohort S3-1) | Change of QTcF Interval (QTcF) From Baseline | 48h | -4.4 msec | Standard Error 3.28 |
| A Single Dose MT-1186 Under Fed Condition(Part 1, Cohort S3-2) | Change of QTcF Interval (QTcF) From Baseline | 4h | 0.7 msec | Standard Error 3.06 |
| A Single Dose MT-1186 Under Fed Condition(Part 1, Cohort S3-2) | Change of QTcF Interval (QTcF) From Baseline | 2h | 0.8 msec | Standard Error 1.8 |
| A Single Dose MT-1186 Under Fed Condition(Part 1, Cohort S3-2) | Change of QTcF Interval (QTcF) From Baseline | 0.25h | 0.8 msec | Standard Error 1.71 |
| A Single Dose MT-1186 Under Fed Condition(Part 1, Cohort S3-2) | Change of QTcF Interval (QTcF) From Baseline | 24h | -3.1 msec | Standard Error 2.6 |
| A Single Dose MT-1186 Under Fed Condition(Part 1, Cohort S3-2) | Change of QTcF Interval (QTcF) From Baseline | 1.5h | -5.3 msec | Standard Error 2.4 |
| A Single Dose MT-1186 Under Fed Condition(Part 1, Cohort S3-2) | Change of QTcF Interval (QTcF) From Baseline | 1h | 0.5 msec | Standard Error 2.17 |
| A Single Dose MT-1186 Under Fed Condition(Part 1, Cohort S3-2) | Change of QTcF Interval (QTcF) From Baseline | 48h | -0.1 msec | Standard Error 3.46 |
| A Single Dose MT-1186 Under Fed Condition(Part 1, Cohort S3-2) | Change of QTcF Interval (QTcF) From Baseline | 36h | -1.4 msec | Standard Error 3.18 |
| A Single Dose MT-1186 Under Fed Condition(Part 1, Cohort S3-2) | Change of QTcF Interval (QTcF) From Baseline | 8h | -6.9 msec | Standard Error 2.81 |
| A Single Dose MT-1186 Under Fed Condition(Part 1, Cohort S3-2) | Change of QTcF Interval (QTcF) From Baseline | 6h | -2.4 msec | Standard Error 3.18 |
| A Single Dose MT-1186 Under Fed Condition(Part 1, Cohort S3-2) | Change of QTcF Interval (QTcF) From Baseline | 0.5h | -4.9 msec | Standard Error 1.41 |
| A Single Dose MT-1186 Under Fed Condition(Part 1, Cohort S3-2) | Change of QTcF Interval (QTcF) From Baseline | 12h | -3.3 msec | Standard Error 2.6 |