Healthy Adult Subjects
Conditions
Brief summary
To evaluate the effect of MCI-186 on the QT interval corrected for heart rate using Fridericia's formula (QTcF)
Interventions
DRUGMCI-186
A single dose of 60 mg MCI-186 over 60 min will be intravenously administered.
DRUGPlacebo
A single dose of 0.9% w/v saline over 60 min will be intravenously administered.
Sponsors
Shionogi
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
DOUBLE (Subject, Outcomes Assessor)
Masking description
This study is a single-blind study. Subjects and Electrocardiogram (ECG) reviewer will be blinded. Investigator and Sponsor will be unblinded.
Eligibility
Sex/Gender
MALE
Age
20 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy males aged 20 to 55 years (both inclusive) at signature of the Informed Consent Form (ICF). * Able to provide written informed consent to participate in this study after reading the ICF, and after having the opportunity to discuss the study with the Investigator or designee, before any screening or study related procedures take place. * In the Investigator's opinion, subject is able to understand the nature of the study and any risks involved in participation, and willing to cooperate and comply with the protocol restrictions and requirements. * A body weight of ≥45 kg and a body mass index (BMI) ranging from 18 to 30 kg/m2 (both inclusive) at screening and Day -1. * Good health and free from clinically significant illness or disease in the opinion of the investigator on the basis of a physical examination, medical history, ECG, vital sign, and clinical laboratory test (biochemistry, hematology, coagulation and urinalysis) at screening and Day -1. * Male subjects must practice effective contraception during the study, from the time of the first dose of Investigational Medicinal Product (IMP) until 14 days after the last dose of IMP.
Exclusion criteria
* Subjects with PR \>240 msec, QRS ≥120 msec, or QTcF \>450 msec on the screening or Day -1 ECG, or any clinically significant electrocardiographic abnormality in the opinion of the Investigator. * Subject who has a history of cardiac disease or arrhythmias that can cause QTc prolongation. * Subject who has a family history of Torsade de Pointes, long-QT syndrome, hypokalemia or sudden death. * Subjects with potassium levels outside of the laboratory reference ranges at screening or Day -1. * Subjects with clinically significant deviations from normal in physical examination, vital signs, ECG or clinical laboratory test at screening or Day -1 in the opinion of the Investigator. * Presence or history of any clinically significant disease or organ dysfunction in the opinion of the Investigator. * Presence or history of allergy to food, any medical product or relevant excipient that is of clinical significant. * Subjects were previously administered MCI-186. * Presence or history of alcohol abuse or a positive alcohol test. * Presence or history of drug abuse or a positive drug screen test. * Positive test for hepatitis C virus antibody, hepatitis B surface antigen, human immunodeficiency virus (HIV) antigen/antibody or syphilis test at screening. * Participation in another trial within 12 weeks or 5 times the half-life of the drug whichever is longer before providing a signed ICF. For biologics, the minimum period is at least 24 weeks or the period of the pharmacodynamic effect, or 10 times the half-life of the drug, whichever is longer before providing a signed ICF. * Donate blood more than 200 mL within 4 weeks, 400 mL within 12 weeks or 1000 mL within 52 weeks, respectively before providing a signed ICF. * Donate plasma or platelet component within 2 weeks before providing a signed ICF. * Use of any prescription or non-prescription medications including herbal remedies and vitamin/mineral/protein supplements, except for acetylsalicylic acid, within 7 days prior to IMPs dosing. * Use of tobacco or nicotine containing products for 24 hours before each visit of screening or Day -1. * Consumption of alcohol, xanthines, or grapefruit containing products for 24 hours before each visit of screening or Day -1.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in QTcF(ΔQTcF) With Placebo Adjustment (ΔΔQTcF) at Cmax of MCI-186 | 45 min pre-dose to 24 h post-dose | The primary outcome endpoint was based on an analysis of the regression relationship between ΔQTcF and the concentration of MCI-186 at matching times post-dose, including adjustment for placebo treatments. |
Secondary
| Measure | Time frame |
|---|---|
| Change From Baseline of Heart Rate(HR) by Timepoint | Pre-dose to 24h post-dose |
| Change From Baseline of PR Interval by Timepoint | Pre-dose to 24h post-dose |
| Change From Baseline of QRS Interval by Timepoint | Pre-dose to 24h post-dose |
| Change From Baseline of QTcF by Timepoint | Pre-dose to 24h post-dose |
| Plasma Concentration of MCI-186 | Pre-dose to 24h post-dose |
| Pharmacokinetic(PK) Parameters - Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC 0-inf) of MCI-186 | Pre-dose to 24h post-dose |
| PK Parameters - Maximum Plasma Concentration (Cmax) of MCI-186 | Pre-dose to 24h post-dose |
| Number of Participants With Adverse Events (AEs) | Day 1 to 9 |
Countries
Japan
Contacts
STUDY_DIRECTORShionogi Clinical Trials Administrator Clinical Support Help Line
Shionogi
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Sequence 1 (Treatment A, Then Treatment C, Then Treatment B) Participants first received a single intravenous dose of Treatment A as 1-hour infusion. After 14day post treatment, they then received a single intravenous dose of Treatment C as 1-hour infusion. After 14day post treatment, they then received a single intravenous dose of Treatment B as 1-hour infusion. After 14day post treatment. (Treatment A=60mg of MCI-186, Treatment B=300mg of MCI-186, Treatment C=0.9% w/v saline) | 9 |
| Sequence 2 (Treatment B, Then Treatment A, Then Treatment C) Participants first received a single intravenous dose of Treatment B as 1-hour infusion. After 14day post treatment, they then received a single intravenous dose of Treatment A as 1-hour infusion. After 14day post treatment, they then received a single intravenous dose of Treatment C as 1-hour infusion. After 14day post treatment. (Treatment A=60mg of MCI-186, Treatment B=300mg of MCI-186, Treatment C=0.9% w/v saline) | 9 |
| Sequence 3 (Treatment C, Then Treatment B, Then Treatment A) Participants first received a single intravenous dose of Treatment C as 1-hour infusion. After 14day post treatment, they then received a single intravenous dose of Treatment B as 1-hour infusion. After 14day post treatment, they then received a single intravenous dose of Treatment A as 1-hour infusion. After 14day post treatment. (Treatment A=60mg of MCI-186, Treatment B=300mg of MCI-186, Treatment C=0.9% w/v saline) | 9 |
| Total | 27 |
Baseline characteristics
| Characteristic | Sequence 1 (Treatment A, Then Treatment C, Then Treatment B) | Sequence 2 (Treatment B, Then Treatment A, Then Treatment C) | Sequence 3 (Treatment C, Then Treatment B, Then Treatment A) | Total |
|---|---|---|---|---|
| Age, Continuous | 29.3 years STANDARD_DEVIATION 9.8 | 28.7 years STANDARD_DEVIATION 10.6 | 33.6 years STANDARD_DEVIATION 9.8 | 30.5 years STANDARD_DEVIATION 9.9 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 9 Participants | 9 Participants | 9 Participants | 27 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 9 Participants | 9 Participants | 9 Participants | 27 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 27 | 0 / 26 | 0 / 25 |
| other Total, other adverse events | 1 / 27 | 1 / 26 | 1 / 25 |
| serious Total, serious adverse events | 0 / 27 | 0 / 26 | 0 / 25 |
Outcome results
Primary
Change From Baseline in QTcF(ΔQTcF) With Placebo Adjustment (ΔΔQTcF) at Cmax of MCI-186
The primary outcome endpoint was based on an analysis of the regression relationship between ΔQTcF and the concentration of MCI-186 at matching times post-dose, including adjustment for placebo treatments.
Time frame: 45 min pre-dose to 24 h post-dose
Population: All participants who received 600mg, and 300mg of MCI-186 were included in the analysis. One participant on 300mg was not included due to meeting the exclusion criteria (Protocol Violation).~Overall Number of Participants Analyzed was entered as the number at the time of calculation of Cmax.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| MCI-186 60mg | Change From Baseline in QTcF(ΔQTcF) With Placebo Adjustment (ΔΔQTcF) at Cmax of MCI-186 | -0.5 ms |
| MCI-186 300mg | Change From Baseline in QTcF(ΔQTcF) With Placebo Adjustment (ΔΔQTcF) at Cmax of MCI-186 | 0.5 ms |
Secondary
Change From Baseline of Heart Rate(HR) by Timepoint
Time frame: Pre-dose to 24h post-dose
Population: All participants who received 600mg, 300mg, and placebo of MCI-186 were included in the analysis. One participant on 300mg , and one patient on placebo were not included due to meeting the exclusion criteria (Protocol Violation).~One patient on placebo was not included due to withdrawal of the consent.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| MCI-186 60mg | Change From Baseline of Heart Rate(HR) by Timepoint | 30min | 0.2 beats per minute | Standard Error 2.9 |
| MCI-186 60mg | Change From Baseline of Heart Rate(HR) by Timepoint | 60min | 0.6 beats per minute | Standard Error 3.21 |
| MCI-186 60mg | Change From Baseline of Heart Rate(HR) by Timepoint | 75min | 1 beats per minute | Standard Error 3.43 |
| MCI-186 60mg | Change From Baseline of Heart Rate(HR) by Timepoint | 90min | 0.4 beats per minute | Standard Error 3.17 |
| MCI-186 60mg | Change From Baseline of Heart Rate(HR) by Timepoint | 105min | 0.6 beats per minute | Standard Error 3.27 |
| MCI-186 60mg | Change From Baseline of Heart Rate(HR) by Timepoint | 2hr | 1.7 beats per minute | Standard Error 3.56 |
| MCI-186 60mg | Change From Baseline of Heart Rate(HR) by Timepoint | 3hr | 1.8 beats per minute | Standard Error 4.01 |
| MCI-186 60mg | Change From Baseline of Heart Rate(HR) by Timepoint | 4hr | 2.1 beats per minute | Standard Error 4.28 |
| MCI-186 60mg | Change From Baseline of Heart Rate(HR) by Timepoint | 6hr | 7.6 beats per minute | Standard Error 4.69 |
| MCI-186 60mg | Change From Baseline of Heart Rate(HR) by Timepoint | 8hr | 8.1 beats per minute | Standard Error 5.44 |
| MCI-186 60mg | Change From Baseline of Heart Rate(HR) by Timepoint | 12hr | 7.1 beats per minute | Standard Error 4.8 |
| MCI-186 60mg | Change From Baseline of Heart Rate(HR) by Timepoint | 24hr | 1.1 beats per minute | Standard Error 4.52 |
| MCI-186 300mg | Change From Baseline of Heart Rate(HR) by Timepoint | 24hr | 4.6 beats per minute | Standard Error 6.9 |
| MCI-186 300mg | Change From Baseline of Heart Rate(HR) by Timepoint | 30min | -0.2 beats per minute | Standard Error 2.47 |
| MCI-186 300mg | Change From Baseline of Heart Rate(HR) by Timepoint | 3hr | 4 beats per minute | Standard Error 3.69 |
| MCI-186 300mg | Change From Baseline of Heart Rate(HR) by Timepoint | 6hr | 9.3 beats per minute | Standard Error 5.18 |
| MCI-186 300mg | Change From Baseline of Heart Rate(HR) by Timepoint | 60min | 1 beats per minute | Standard Error 3.08 |
| MCI-186 300mg | Change From Baseline of Heart Rate(HR) by Timepoint | 2hr | 3.4 beats per minute | Standard Error 3.24 |
| MCI-186 300mg | Change From Baseline of Heart Rate(HR) by Timepoint | 12hr | 9.1 beats per minute | Standard Error 6.77 |
| MCI-186 300mg | Change From Baseline of Heart Rate(HR) by Timepoint | 75min | 1.1 beats per minute | Standard Error 3.14 |
| MCI-186 300mg | Change From Baseline of Heart Rate(HR) by Timepoint | 4hr | 3.8 beats per minute | Standard Error 4.22 |
| MCI-186 300mg | Change From Baseline of Heart Rate(HR) by Timepoint | 105min | 3.1 beats per minute | Standard Error 3.55 |
| MCI-186 300mg | Change From Baseline of Heart Rate(HR) by Timepoint | 90min | 1.8 beats per minute | Standard Error 3.63 |
| MCI-186 300mg | Change From Baseline of Heart Rate(HR) by Timepoint | 8hr | 10.2 beats per minute | Standard Error 6.26 |
| Placebo | Change From Baseline of Heart Rate(HR) by Timepoint | 90min | 1.6 beats per minute | Standard Error 3.81 |
| Placebo | Change From Baseline of Heart Rate(HR) by Timepoint | 105min | 1.8 beats per minute | Standard Error 3.91 |
| Placebo | Change From Baseline of Heart Rate(HR) by Timepoint | 8hr | 10.3 beats per minute | Standard Error 7.34 |
| Placebo | Change From Baseline of Heart Rate(HR) by Timepoint | 2hr | 3.4 beats per minute | Standard Error 3.8 |
| Placebo | Change From Baseline of Heart Rate(HR) by Timepoint | 3hr | 2.6 beats per minute | Standard Error 3.44 |
| Placebo | Change From Baseline of Heart Rate(HR) by Timepoint | 4hr | 3.1 beats per minute | Standard Error 4.57 |
| Placebo | Change From Baseline of Heart Rate(HR) by Timepoint | 12hr | 7.4 beats per minute | Standard Error 5.83 |
| Placebo | Change From Baseline of Heart Rate(HR) by Timepoint | 30min | 0.1 beats per minute | Standard Error 2.59 |
| Placebo | Change From Baseline of Heart Rate(HR) by Timepoint | 60min | 0.8 beats per minute | Standard Error 3.02 |
| Placebo | Change From Baseline of Heart Rate(HR) by Timepoint | 6hr | 9.1 beats per minute | Standard Error 4.13 |
| Placebo | Change From Baseline of Heart Rate(HR) by Timepoint | 75min | 1.1 beats per minute | Standard Error 3.26 |
| Placebo | Change From Baseline of Heart Rate(HR) by Timepoint | 24hr | 2.7 beats per minute | Standard Error 4.01 |
Secondary
Change From Baseline of PR Interval by Timepoint
Time frame: Pre-dose to 24h post-dose
Population: All participants who received 600mg, 300mg, and placebo of MCI-186 were included in the analysis. One participant on 300mg , and one patient on placebo were not included due to meeting the exclusion criteria (Protocol Violation).~One patient on placebo was not included due to withdrawal of the consent.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| MCI-186 60mg | Change From Baseline of PR Interval by Timepoint | 30min | -0.4 msec | Standard Deviation 3.72 |
| MCI-186 60mg | Change From Baseline of PR Interval by Timepoint | 60min | -2.1 msec | Standard Deviation 3.74 |
| MCI-186 60mg | Change From Baseline of PR Interval by Timepoint | 75min | -2.2 msec | Standard Deviation 4.43 |
| MCI-186 60mg | Change From Baseline of PR Interval by Timepoint | 90min | -2.3 msec | Standard Deviation 4.29 |
| MCI-186 60mg | Change From Baseline of PR Interval by Timepoint | 105min | -1.1 msec | Standard Deviation 4.17 |
| MCI-186 60mg | Change From Baseline of PR Interval by Timepoint | 2hr | -2.8 msec | Standard Deviation 4.51 |
| MCI-186 60mg | Change From Baseline of PR Interval by Timepoint | 3hr | -4 msec | Standard Deviation 6.05 |
| MCI-186 60mg | Change From Baseline of PR Interval by Timepoint | 4hr | -4.6 msec | Standard Deviation 5.81 |
| MCI-186 60mg | Change From Baseline of PR Interval by Timepoint | 6hr | -4.2 msec | Standard Deviation 5.99 |
| MCI-186 60mg | Change From Baseline of PR Interval by Timepoint | 8hr | -7.3 msec | Standard Deviation 6.01 |
| MCI-186 60mg | Change From Baseline of PR Interval by Timepoint | 12h | -2.4 msec | Standard Deviation 7.96 |
| MCI-186 60mg | Change From Baseline of PR Interval by Timepoint | 24hr | 1.4 msec | Standard Deviation 6.87 |
| MCI-186 300mg | Change From Baseline of PR Interval by Timepoint | 24hr | -1 msec | Standard Deviation 7.73 |
| MCI-186 300mg | Change From Baseline of PR Interval by Timepoint | 30min | 0 msec | Standard Deviation 6.14 |
| MCI-186 300mg | Change From Baseline of PR Interval by Timepoint | 3hr | -5.1 msec | Standard Deviation 7.34 |
| MCI-186 300mg | Change From Baseline of PR Interval by Timepoint | 6hr | -5.9 msec | Standard Deviation 8.36 |
| MCI-186 300mg | Change From Baseline of PR Interval by Timepoint | 60min | -0.3 msec | Standard Deviation 6.79 |
| MCI-186 300mg | Change From Baseline of PR Interval by Timepoint | 2hr | -3.2 msec | Standard Deviation 7.96 |
| MCI-186 300mg | Change From Baseline of PR Interval by Timepoint | 12h | -5.5 msec | Standard Deviation 10.72 |
| MCI-186 300mg | Change From Baseline of PR Interval by Timepoint | 75min | -1.8 msec | Standard Deviation 5.53 |
| MCI-186 300mg | Change From Baseline of PR Interval by Timepoint | 4hr | -6.4 msec | Standard Deviation 7.6 |
| MCI-186 300mg | Change From Baseline of PR Interval by Timepoint | 105min | -2.2 msec | Standard Deviation 7.91 |
| MCI-186 300mg | Change From Baseline of PR Interval by Timepoint | 90min | -2.4 msec | Standard Deviation 6.81 |
| MCI-186 300mg | Change From Baseline of PR Interval by Timepoint | 8hr | -7.8 msec | Standard Deviation 8.58 |
| Placebo | Change From Baseline of PR Interval by Timepoint | 90min | -2.8 msec | Standard Deviation 4.91 |
| Placebo | Change From Baseline of PR Interval by Timepoint | 105min | -3.1 msec | Standard Deviation 5.51 |
| Placebo | Change From Baseline of PR Interval by Timepoint | 8hr | -7.9 msec | Standard Deviation 7.49 |
| Placebo | Change From Baseline of PR Interval by Timepoint | 2hr | -2.3 msec | Standard Deviation 7.2 |
| Placebo | Change From Baseline of PR Interval by Timepoint | 3hr | -1.7 msec | Standard Deviation 6.46 |
| Placebo | Change From Baseline of PR Interval by Timepoint | 4hr | -3.4 msec | Standard Deviation 5.99 |
| Placebo | Change From Baseline of PR Interval by Timepoint | 12h | -3.5 msec | Standard Deviation 9.46 |
| Placebo | Change From Baseline of PR Interval by Timepoint | 30min | -1 msec | Standard Deviation 6.29 |
| Placebo | Change From Baseline of PR Interval by Timepoint | 60min | -1.4 msec | Standard Deviation 5.93 |
| Placebo | Change From Baseline of PR Interval by Timepoint | 6hr | -5.3 msec | Standard Deviation 8.64 |
| Placebo | Change From Baseline of PR Interval by Timepoint | 75min | -2.5 msec | Standard Deviation 4.68 |
| Placebo | Change From Baseline of PR Interval by Timepoint | 24hr | -0.6 msec | Standard Deviation 7.16 |
Secondary
Change From Baseline of QRS Interval by Timepoint
Time frame: Pre-dose to 24h post-dose
Population: All participants who received 600mg, 300mg, and placebo of MCI-186 were included in the analysis. One participant on 300mg , and one patient on placebo were not included due to meeting the exclusion criteria (Protocol Violation).~One patient on placebo was not included due to withdrawal of the consent.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| MCI-186 60mg | Change From Baseline of QRS Interval by Timepoint | 6hr | -7.3 msec | Standard Deviation 7.31 |
| MCI-186 60mg | Change From Baseline of QRS Interval by Timepoint | 24hr | -6 msec | Standard Deviation 4.15 |
| MCI-186 60mg | Change From Baseline of QRS Interval by Timepoint | 12hr | -6.4 msec | Standard Deviation 6.26 |
| MCI-186 60mg | Change From Baseline of QRS Interval by Timepoint | 2hr | 1.4 msec | Standard Deviation 3.35 |
| MCI-186 60mg | Change From Baseline of QRS Interval by Timepoint | 30min | 3.4 msec | Standard Deviation 5.03 |
| MCI-186 60mg | Change From Baseline of QRS Interval by Timepoint | 4hr | 0.7 msec | Standard Deviation 5.47 |
| MCI-186 60mg | Change From Baseline of QRS Interval by Timepoint | 105min | 3.2 msec | Standard Deviation 3.94 |
| MCI-186 60mg | Change From Baseline of QRS Interval by Timepoint | 60min | 4.7 msec | Standard Deviation 3.54 |
| MCI-186 60mg | Change From Baseline of QRS Interval by Timepoint | 3hr | 0.2 msec | Standard Deviation 4.57 |
| MCI-186 60mg | Change From Baseline of QRS Interval by Timepoint | 8hr | -6.4 msec | Standard Deviation 7.39 |
| MCI-186 60mg | Change From Baseline of QRS Interval by Timepoint | 75min | 4.1 msec | Standard Deviation 5.02 |
| MCI-186 60mg | Change From Baseline of QRS Interval by Timepoint | 90min | 3.5 msec | Standard Deviation 3.61 |
| MCI-186 300mg | Change From Baseline of QRS Interval by Timepoint | 75min | 4.1 msec | Standard Deviation 3.86 |
| MCI-186 300mg | Change From Baseline of QRS Interval by Timepoint | 90min | 3.5 msec | Standard Deviation 4.4 |
| MCI-186 300mg | Change From Baseline of QRS Interval by Timepoint | 105min | 3.2 msec | Standard Deviation 3.64 |
| MCI-186 300mg | Change From Baseline of QRS Interval by Timepoint | 2hr | 2.1 msec | Standard Deviation 4.62 |
| MCI-186 300mg | Change From Baseline of QRS Interval by Timepoint | 12hr | -7 msec | Standard Deviation 7.86 |
| MCI-186 300mg | Change From Baseline of QRS Interval by Timepoint | 3hr | -0.4 msec | Standard Deviation 4.47 |
| MCI-186 300mg | Change From Baseline of QRS Interval by Timepoint | 24hr | -8 msec | Standard Deviation 5.13 |
| MCI-186 300mg | Change From Baseline of QRS Interval by Timepoint | 6hr | -5.8 msec | Standard Deviation 7.42 |
| MCI-186 300mg | Change From Baseline of QRS Interval by Timepoint | 30min | 3.4 msec | Standard Deviation 3.53 |
| MCI-186 300mg | Change From Baseline of QRS Interval by Timepoint | 4hr | -0.6 msec | Standard Deviation 6.06 |
| MCI-186 300mg | Change From Baseline of QRS Interval by Timepoint | 60min | 5 msec | Standard Deviation 5.23 |
| MCI-186 300mg | Change From Baseline of QRS Interval by Timepoint | 8hr | -6.4 msec | Standard Deviation 6.63 |
| Placebo | Change From Baseline of QRS Interval by Timepoint | 30min | 3.4 msec | Standard Deviation 3.65 |
| Placebo | Change From Baseline of QRS Interval by Timepoint | 4hr | 1.4 msec | Standard Deviation 5.56 |
| Placebo | Change From Baseline of QRS Interval by Timepoint | 6hr | -4.8 msec | Standard Deviation 6.48 |
| Placebo | Change From Baseline of QRS Interval by Timepoint | 8hr | -5.5 msec | Standard Deviation 7.9 |
| Placebo | Change From Baseline of QRS Interval by Timepoint | 12hr | -4.2 msec | Standard Deviation 7.99 |
| Placebo | Change From Baseline of QRS Interval by Timepoint | 24hr | -5.6 msec | Standard Deviation 5.06 |
| Placebo | Change From Baseline of QRS Interval by Timepoint | 3hr | 0.1 msec | Standard Deviation 5.56 |
| Placebo | Change From Baseline of QRS Interval by Timepoint | 60min | 4.1 msec | Standard Deviation 3.95 |
| Placebo | Change From Baseline of QRS Interval by Timepoint | 75min | 3.6 msec | Standard Deviation 3.98 |
| Placebo | Change From Baseline of QRS Interval by Timepoint | 90min | 3.2 msec | Standard Deviation 4.13 |
| Placebo | Change From Baseline of QRS Interval by Timepoint | 105min | 2.9 msec | Standard Deviation 4.45 |
| Placebo | Change From Baseline of QRS Interval by Timepoint | 2hr | 1.9 msec | Standard Deviation 3.85 |
Secondary
Change From Baseline of QTcF by Timepoint
Time frame: Pre-dose to 24h post-dose
Population: All participants who received 600mg, 300mg, and placebo of MCI-186 were included in the analysis. One participant on 300mg , and one patient on placebo were not included due to meeting the exclusion criteria (Protocol Violation).~One patient on placebo was not included due to withdrawal of the consent.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| MCI-186 60mg | Change From Baseline of QTcF by Timepoint | 30min | 0.7 msec | Standard Deviation 1.91 |
| MCI-186 60mg | Change From Baseline of QTcF by Timepoint | 60min | 0.2 msec | Standard Deviation 1.87 |
| MCI-186 60mg | Change From Baseline of QTcF by Timepoint | 75min | -0.6 msec | Standard Deviation 1.83 |
| MCI-186 60mg | Change From Baseline of QTcF by Timepoint | 90min | 0.1 msec | Standard Deviation 2.53 |
| MCI-186 60mg | Change From Baseline of QTcF by Timepoint | 105min | -0.3 msec | Standard Deviation 2.7 |
| MCI-186 60mg | Change From Baseline of QTcF by Timepoint | 2hr | -0.4 msec | Standard Deviation 3.28 |
| MCI-186 60mg | Change From Baseline of QTcF by Timepoint | 3hr | 0.3 msec | Standard Deviation 3.27 |
| MCI-186 60mg | Change From Baseline of QTcF by Timepoint | 4hr | 0.4 msec | Standard Deviation 3.08 |
| MCI-186 60mg | Change From Baseline of QTcF by Timepoint | 6hr | 1.5 msec | Standard Deviation 3.17 |
| MCI-186 60mg | Change From Baseline of QTcF by Timepoint | 8hr | 0.6 msec | Standard Deviation 3.39 |
| MCI-186 60mg | Change From Baseline of QTcF by Timepoint | 12hr | 0.5 msec | Standard Deviation 3.99 |
| MCI-186 60mg | Change From Baseline of QTcF by Timepoint | 24hr | 0 msec | Standard Deviation 3.82 |
| MCI-186 300mg | Change From Baseline of QTcF by Timepoint | 24hr | -0.7 msec | Standard Deviation 5.56 |
| MCI-186 300mg | Change From Baseline of QTcF by Timepoint | 30min | -1.8 msec | Standard Deviation 5.06 |
| MCI-186 300mg | Change From Baseline of QTcF by Timepoint | 3hr | -2 msec | Standard Deviation 5.31 |
| MCI-186 300mg | Change From Baseline of QTcF by Timepoint | 6hr | 3.5 msec | Standard Deviation 6.97 |
| MCI-186 300mg | Change From Baseline of QTcF by Timepoint | 60min | -0.7 msec | Standard Deviation 3.62 |
| MCI-186 300mg | Change From Baseline of QTcF by Timepoint | 2hr | -2.1 msec | Standard Deviation 6.03 |
| MCI-186 300mg | Change From Baseline of QTcF by Timepoint | 12hr | 0.4 msec | Standard Deviation 4.14 |
| MCI-186 300mg | Change From Baseline of QTcF by Timepoint | 75min | -1.1 msec | Standard Deviation 3.59 |
| MCI-186 300mg | Change From Baseline of QTcF by Timepoint | 4hr | -2 msec | Standard Deviation 5.46 |
| MCI-186 300mg | Change From Baseline of QTcF by Timepoint | 105min | -1.3 msec | Standard Deviation 3.41 |
| MCI-186 300mg | Change From Baseline of QTcF by Timepoint | 90min | -1.3 msec | Standard Deviation 4.15 |
| MCI-186 300mg | Change From Baseline of QTcF by Timepoint | 8hr | 0.3 msec | Standard Deviation 5.16 |
| Placebo | Change From Baseline of QTcF by Timepoint | 90min | -0.9 msec | Standard Deviation 3.24 |
| Placebo | Change From Baseline of QTcF by Timepoint | 105min | -0.8 msec | Standard Deviation 2.53 |
| Placebo | Change From Baseline of QTcF by Timepoint | 8hr | 0.9 msec | Standard Deviation 5.32 |
| Placebo | Change From Baseline of QTcF by Timepoint | 2hr | -1.5 msec | Standard Deviation 3.31 |
| Placebo | Change From Baseline of QTcF by Timepoint | 3hr | -0.4 msec | Standard Deviation 2.42 |
| Placebo | Change From Baseline of QTcF by Timepoint | 4hr | -1 msec | Standard Deviation 2.38 |
| Placebo | Change From Baseline of QTcF by Timepoint | 12hr | 0.9 msec | Standard Deviation 3.33 |
| Placebo | Change From Baseline of QTcF by Timepoint | 30min | 0.2 msec | Standard Deviation 1.94 |
| Placebo | Change From Baseline of QTcF by Timepoint | 60min | -0.1 msec | Standard Deviation 1.95 |
| Placebo | Change From Baseline of QTcF by Timepoint | 6hr | 2.1 msec | Standard Deviation 4.05 |
| Placebo | Change From Baseline of QTcF by Timepoint | 75min | -0.7 msec | Standard Deviation 2.92 |
| Placebo | Change From Baseline of QTcF by Timepoint | 24hr | -0.2 msec | Standard Deviation 2.9 |
Secondary
Number of Participants With Adverse Events (AEs)
Time frame: Day 1 to 9
Population: All participants who received 600mg, 300mg, and placebo of MCI-186 were included in the analysis. One participant on 300mg , and one patient on placebo were not included due to meeting the exclusion criteria (Protocol Violation).~One patient on placebo was not included due to withdrawal of the consent.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| MCI-186 60mg | Number of Participants With Adverse Events (AEs) | 1 Participants |
| MCI-186 300mg | Number of Participants With Adverse Events (AEs) | 1 Participants |
| Placebo | Number of Participants With Adverse Events (AEs) | 1 Participants |
Secondary
Pharmacokinetic(PK) Parameters - Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC 0-inf) of MCI-186
Time frame: Pre-dose to 24h post-dose
Population: All participants who received 600mg, and 300mg of MCI-186 were included in the analysis. One participant on 300mg was not included due to meeting the exclusion criteria (Protocol Violation).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| MCI-186 60mg | Pharmacokinetic(PK) Parameters - Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC 0-inf) of MCI-186 | 1549.22 ng·h/mL | Geometric Coefficient of Variation 20.5 |
| MCI-186 300mg | Pharmacokinetic(PK) Parameters - Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC 0-inf) of MCI-186 | 12916.94 ng·h/mL | Geometric Coefficient of Variation 33.3 |
Secondary
PK Parameters - Maximum Plasma Concentration (Cmax) of MCI-186
Time frame: Pre-dose to 24h post-dose
Population: All participants who received 600mg, and 300mg of MCI-186 were included in the analysis. One participant on 300mg was not included due to meeting the exclusion criteria (Protocol Violation).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| MCI-186 60mg | PK Parameters - Maximum Plasma Concentration (Cmax) of MCI-186 | 1030 ng/mL | Geometric Coefficient of Variation 14.1 |
| MCI-186 300mg | PK Parameters - Maximum Plasma Concentration (Cmax) of MCI-186 | 7566 ng/mL | Geometric Coefficient of Variation 25.1 |
Secondary
Plasma Concentration of MCI-186
Time frame: Pre-dose to 24h post-dose
Population: All participants who received 600mg, and 300mg of MCI-186 were included in the analysis. One participant on 300mg was not included due to meeting the exclusion criteria (Protocol Violation).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| MCI-186 60mg | Plasma Concentration of MCI-186 | 30min | 1039 ng/mL | Standard Deviation 140 |
| MCI-186 60mg | Plasma Concentration of MCI-186 | 60min | 791.3 ng/mL | Standard Deviation 147 |
| MCI-186 60mg | Plasma Concentration of MCI-186 | 75min | 454.4 ng/mL | Standard Deviation 101.6 |
| MCI-186 60mg | Plasma Concentration of MCI-186 | 90min | 308.3 ng/mL | Standard Deviation 71.22 |
| MCI-186 60mg | Plasma Concentration of MCI-186 | 105min | 227.6 ng/mL | Standard Deviation 54.48 |
| MCI-186 60mg | Plasma Concentration of MCI-186 | 2hr | 176.1 ng/mL | Standard Deviation 43.85 |
| MCI-186 60mg | Plasma Concentration of MCI-186 | 3hr | 83.60 ng/mL | Standard Deviation 23.66 |
| MCI-186 60mg | Plasma Concentration of MCI-186 | 4hr | 51.28 ng/mL | Standard Deviation 15.49 |
| MCI-186 60mg | Plasma Concentration of MCI-186 | 6hr | 20.39 ng/mL | Standard Deviation 7.148 |
| MCI-186 60mg | Plasma Concentration of MCI-186 | 8hr | 12.34 ng/mL | Standard Deviation 4.689 |
| MCI-186 60mg | Plasma Concentration of MCI-186 | 12hr | 6.522 ng/mL | Standard Deviation 2.652 |
| MCI-186 60mg | Plasma Concentration of MCI-186 | 24hr | 2.684 ng/mL | Standard Deviation 1.547 |
| MCI-186 300mg | Plasma Concentration of MCI-186 | 12hr | 37.48 ng/mL | Standard Deviation 16.83 |
| MCI-186 300mg | Plasma Concentration of MCI-186 | 30min | 7393 ng/mL | Standard Deviation 1770 |
| MCI-186 300mg | Plasma Concentration of MCI-186 | 3hr | 874.5 ng/mL | Standard Deviation 326.8 |
| MCI-186 300mg | Plasma Concentration of MCI-186 | 60min | 7412 ng/mL | Standard Deviation 1968 |
| MCI-186 300mg | Plasma Concentration of MCI-186 | 8hr | 89.91 ng/mL | Standard Deviation 39.59 |
| MCI-186 300mg | Plasma Concentration of MCI-186 | 75min | 4864 ng/mL | Standard Deviation 1606 |
| MCI-186 300mg | Plasma Concentration of MCI-186 | 4hr | 512.7 ng/mL | Standard Deviation 197.6 |
| MCI-186 300mg | Plasma Concentration of MCI-186 | 90min | 3522 ng/mL | Standard Deviation 1235 |
| MCI-186 300mg | Plasma Concentration of MCI-186 | 24hr | 10.65 ng/mL | Standard Deviation 4.026 |
| MCI-186 300mg | Plasma Concentration of MCI-186 | 105min | 2578 ng/mL | Standard Deviation 932.7 |
| MCI-186 300mg | Plasma Concentration of MCI-186 | 6hr | 166.3 ng/mL | Standard Deviation 69.7 |
| MCI-186 300mg | Plasma Concentration of MCI-186 | 2hr | 1990 ng/mL | Standard Deviation 733.5 |