Relapsing Forms of Multiple Sclerosis
Conditions
Brief summary
The primary objectives of this study are to determine the safety and tolerability of DRF administered for up to 24 weeks in adult East Asian participants with RMS (Part 1) and to determine the safety and tolerability of DRF administered for up to 48 weeks in adult East Asian participants with RMS (Part 2). The secondary objective of this study is to evaluate the pharmacokinetic(s) (PK) of DRF metabolites (monomethyl fumarate \[MMF\] and 2-hydroxyethyl succinimide \[HES\]) following multiple doses of DRF in a subset of adult East Asian participants with RMS (Part 1).
Interventions
Administered as specified in the treatment arm
Sponsors
Biogen
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Must have a diagnosis of RMS, as defined by revised 2017 McDonald's criteria. * Expanded Disability Status Scale (EDSS) score between 0.0 and 5.0, inclusive, at screening and baseline visit (Day 1). * Neurologically stable with no evidence of relapse within 30 days prior to baseline visit (Day 1). * For Japanese participants: Born in Japan and biological parents and grandparents were of Japanese origin. If previously lived outside of Japan for more than 5 years, must not have had a significantly modified diet since leaving Japan. * For Chinese participants: Born in China, and biological parents and grandparents were of Chinese origin. If previously lived outside of China for more than 5 years, must not have had a significantly modified diet since leaving China. Key
Exclusion criteria
* Has a multiple sclerosis (MS) relapse that has occurred within the 30 days prior to randomization and/or the participant has not stabilized from a previous relapse prior to randomization. * History of severe allergic or anaphylactic reactions or of any allergic reactions that, in the opinion of the investigator, are likely to be exacerbated by any component of the study treatment. * History of, or ongoing, malignant disease, including solid tumors and hematologic malignancies. * Has a history of gastrointestinal (GI) surgery (except appendectomy or cholecystectomy that occurred more than 6 months prior to screening), irritable bowel syndrome, inflammatory bowel disease (Crohn's disease, ulcerative colitis), or other clinically significant and active GI condition per the investigator's discretion. * History of clinically significant recurring or active GI symptoms (e.g., nausea, diarrhea, dyspepsia, constipation) within 90 days of screening, including symptoms that require the initiation of symptomatic medical treatment (e.g., initiation of a medication to treat gastroesophageal reflux disease) or a change in symptomatic medical treatment (e.g., an increase in dose) within 90 days prior to screening. * History of systemic hypersensitivity reaction to DRF, dimethyl fumarate (DMF), MMF or other fumaric esters, the excipients contained in the formulation, and if appropriate, any diagnostic agents to be administered during the study. * Evidence of current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection within 14 days prior to Screening, between screening and baseline visit (Day 1), or at baseline visit (Day 1), including but not limited to a fever (temperature \>37.5 degrees Celsius \[°C\]), new and persistent cough, breathlessness, or loss of taste and/or smell. Evidence of current SARS-CoV-2 infection within 14 days prior to Screening or during Screening, will be eligible for rescreening, provided that the participant is asymptomatic for 14 days prior to rescreening. * Have close contact within 14 days prior to Day 1 with individual(s) with suspected SARS-CoV-2 infection. * For participants who had close contact with individual(s) with suspected SARS-CoV-2 infection within 14 days prior to Day 1, as determined by the Investigator, will be eligible for rescreening, provided that the participant is asymptomatic for 14 days after the contact. * History or positive test result at screening for human immunodeficiency virus (HIV). * Previous participation in this study or previous studies with DRF, DMF, or MMF. * Has a clinically significant history of suicidal ideation or suicidal behavior occurring in the past 12 months as assessed by the C-SSRS at Screening. NOTE: Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part 1: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | Baseline (Day 1) up to Week 24 (for prematurely discontinued participants, AEs were reported up to 2 weeks post discontinuation) | An adverse event (AE) was any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether/not related to the medicinal (investigational) product. An AE was considered treatment-emergent if it starts or worsens on or after the date of the first dose of study drug in the study until 1 day after the last dose of treatment, or completion of the safety follow-up visit, if applicable.(i.e. for participants who prematurely discontinued study treatment or withdrew from the study) . An SAE is any untoward medical occurrence that at any dose results in death, is a life-threatening event, requires inpatient hospitalization or prolongation of existing hospitalization, results in a significant disability/incapacity or congenital anomaly, is a medically important event. TEAEs included both serious and non-serious TEAEs. |
| Part 1: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters | Baseline (Day 1) to Week 24 | Laboratory assessments included hematology, blood chemistry, and urinalysis parameters. Hematology parameters:basophils, hematocrit, red blood cell, total and differential leukocytes, platelets, lymphocytes, monocytes, neutrophils, eosinophils, hemoglobin. Blood chemistry parameters:sodium, potassium, chloride, glucose, calcium, uric acid, total protein, albumin, creatine phosphokinase, Lipid profile: blood cholesterol,high-density lipoprotein,low-density lipoprotein, and triglycerides,serum follicle-stimulating hormone,Vitamin D,thyroid stimulating hormone,serum pregnancy, HIV/Hepatitis screen,tuberculosis test,alanine aminotransferase,aspartate aminotransferase,Lactate Dehydrogenase,alkaline phosphatase,gamma glutamyl transferase,total bilirubin,blood urea nitrogen,creatinine and bicarbonate. Urinalysis parameters:color,pH,specific gravity,ketones,protein,glucose, bilirubin,nitrite,urobilinogen,occult blood,microscopic examination,urine albumin,beta-2-microglobulin,urine creatinine. |
| Part 1: Number of Participants With Abnormal Shift in 12-Lead Electrocardiogram (ECG) Values | Baseline (Day 1) to Week 24 | The number of participants with shifts to categorical values of ECG interpretation (e.g. abnormal) were presented by each cohort. Abnormal shift includes a shift from normal or unknown to abnormal. |
| Part 1: Number of Participants With Clinically Relevant Abnormalities in Vital Sign Parameters | Baseline (Day 1) to Week 24 | Vital sign assessment included temperature, pulse rate systolic blood pressure, diastolic blood pressure, and respiratory rate. The criteria for determining potentially clinically relevant abnormalities in vital signs included: temperature \< 36 and \> 38 degrees Celsius (C), pulse rate \< 60 and \> 100 beats per minute (bpm), systolic blood pressure (\< 90, \> 140 and \> 160 millimeters of mercury \[mmHg\]), diastolic blood pressure \< 50, \> 90 and \> 100 mmHg, weight (7% or more increase from baseline, 7% or more decrease from baseline) and respiratory rate \< 12 and \> 20 breaths per minute. |
| Part 1: Number of Participants With Columbia Suicide Severity Rating Scale (C-SSRS) Events | Baseline (Day 1) to Week 24 | The C-SSRS was an interview-based rating scale to systematically assess suicidal ideation, suicidal behavior and non-suicidal self-injurious behavior. The C-SSRS includes 'yes' or 'no' responses for assessment of suicidal behavior (preparatory acts or behavior, aborted attempt, interrupted attempt, Suicidal behavior, completed suicide), suicidal ideation (wish to be dead, non-specific active suicidal thoughts, active suicidal ideation with any methods, active suicidal ideation with some intent, active suicidal ideation with specific plan and intent) and non-suicidal self-injurious behavior. |
| Parts 1 and 2: Number of Participants With TEAEs and TESAEs | From Day 1 up to the end of the study (up to Week 50) | An AE was any unfavorable and unintended sign, symptom, or disease temporally associated with use of medicinal (investigational) product, whether/not related to medicinal (investigational) product. AE was considered treatment-emergent if it starts or worsens on or after the date of the first dose of study drug in the study until 1 day after the last dose of treatment. SAE is any untoward medical occurrence that at any dose results in death, is a life-threatening event, requires inpatient hospitalization or prolongation of existing hospitalization, results in a significant disability/incapacity or congenital anomaly, is a medically important event. TEAEs included both serious and non-serious TEAEs. TEAEs and TESAEs for participants were collected cumulatively for Parts 1 and 2. |
| Part 2: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters | Baseline (Day 1) to Week 48 | Laboratory assessments included hematology, blood chemistry, and urinalysis parameters. Hematology parameters:basophils, hematocrit, red blood cell, total and differential leukocytes, platelets, lymphocytes, monocytes, neutrophils, eosinophils, hemoglobin. Blood chemistry parameters:sodium, potassium, chloride, glucose, calcium, uric acid, total protein, albumin, creatine phosphokinase, Lipid profile: blood cholesterol,high-density lipoprotein,low-density lipoprotein, and triglycerides,serum follicle-stimulating hormone,Vitamin D,thyroid stimulating hormone,serum pregnancy, HIV/Hepatitis screen,tuberculosis test,alanine aminotransferase,aspartate aminotransferase,Lactate Dehydrogenase,alkaline phosphatase,gamma glutamyl transferase,total bilirubin,blood urea nitrogen,creatinine and bicarbonate. Urinalysis parameters:color,pH,specific gravity,ketones,protein,glucose, bilirubin,nitrite,urobilinogen,occult blood,microscopic examination,urine albumin,beta-2-microglobulin,urine creatinine. |
| Part 2: Number of Participants With Abnormal Shift in 12-Lead ECG Values | Baseline (Day 1) to Week 48 | The number of participants with shifts to categorical values of ECG interpretation (e.g. abnormal) were presented by each cohort. Abnormal shift includes a shift from normal or unknown to abnormal. |
| Part 2: Number of Participants With Clinically Relevant Abnormalities in Vital Sign Parameters | Baseline (Day 1) to Week 48 | Vital sign assessment included temperature, pulse rate systolic blood pressure, diastolic blood pressure, and respiratory rate. The criteria for determining potentially clinically relevant abnormalities in vital signs included: temperature \< 36 and \> 38 degrees C, pulse rate \< 60 and \> 100 bpm, systolic blood pressure (\< 90, \> 140 and \> 160 mmHg), diastolic blood pressure \< 50, \> 90 and \> 100 mmHg, weight (7% or more increase from baseline, 7% or more decrease from baseline) and respiratory rate \< 12 and \> 20 breaths per minute. |
| Part 2: Number of Participants With C-SSRS Events | Baseline (Day 1) to Week 48 | The C-SSRS was an interview-based rating scale to systematically assess suicidal ideation, suicidal behavior and non-suicidal self-injurious behavior. The C-SSRS includes 'yes' or 'no' responses for assessment of suicidal behavior (preparatory acts or behavior, aborted attempt, interrupted attempt, Suicidal behavior, completed suicide), suicidal ideation (wish to be dead, non-specific active suicidal thoughts, active suicidal ideation with any methods, active suicidal ideation with some intent, active suicidal ideation with specific plan and intent) and non-suicidal self-injurious behavior. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part 1: Plasma Concentrations of Monomethyl Fumarate (MMF)-Intensive Pharmacokinetic (PK) Analysis Set | Pre-dose and at 0.5,1,2,3,4,6, and 8 hours post-dose from Day 29 to Day 169 | Summarized data for plasma concentration of MMF at all timepoints is reported. |
| Part 1: Elimination Half-Life (t½) of MMF-Intensive PK Analysis Set | Pre-dose and at 0.5,1,2,3,4,6, and 8 hours post-dose from Day 29 to Day 169 | Summarized data for t½ at all timepoints is reported. |
| Part 1: Plasma Concentration of 2-Hydroxyethyl Succinimide (HES)-Intensive PK Analysis Set | Pre-dose and at 0.5,1,2,3,4,6, and 8 hours post-dose from Day 29 to Day 169 | Summarized data for plasma concentration of HES at all timepoints is reported. |
| Part 1: Plasma Concentrations of MMF-Sparse PK Analysis Set | Pre-dose and 2 to 3 hours post-dose on Day 29 and Day 57 | — |
| Part 1: Plasma Concentrations of HES-Sparse PK Analysis Set | Pre-dose and 2 to 3 hours post-dose on Day 29 and Day 57 | — |
| Part 1: Maximum Observed Concentration (Cmax) of MMF-Intensive PK Analysis Set | Pre-dose and at 0.5,1,2,3,4,6, and 8 hours post-dose from Day 29 to Day 169 | Summarized data for Cmax at all timepoints is reported. |
| Part 1: Cmax of HES-Intensive PK Analysis Set | Pre-dose and at 0.5,1,2,3,4,6, and 8 hours post-dose from Day 29 to Day 169 | Summarized data for Cmax at all timepoints is reported. |
| Part 1: Area Under the Concentration-Time Curve From Time Zero to Time of Last Measurable Concentration (AUClast) of MMF-Intensive PK Analysis Set | Pre-dose and at 0.5,1,2,3,4,6, and 8 hours post-dose from Day 29 to Day 169 | Summarized data for AUClast at all timepoints is reported. |
| Part 1: AUClast of HES-Intensive PK Analysis Set | Pre-dose and at 0.5,1,2,3,4,6, and 8 hours post-dose from Day 29 to Day 169 | Summarized data for AUClast at all timepoints is reported. |
| Part 1: Time to Reach Cmax (Tmax) of MMF-Intensive PK Analysis Set | Pre-dose and at 0.5,1,2,3,4,6, and 8 hours post-dose from Day 29 to Day 169 | Summarized data for Tmax at all timepoints is reported. |
| Part 1: Tmax of HES-Intensive PK Analysis Set | Pre-dose and at 0.5,1,2,3,4,6, and 8 hours post-dose from Day 29 to Day 169 | Summarized data for Tmax at all timepoints is reported. |
Countries
China, Japan
Participant flow
Recruitment details
Participants took part in the multiple investigative sites from 18 November 2021 to 11 September 2024.
Pre-assignment details
Total of 136 participants diagnosed with relapsing forms of multiple sclerosis (RMS) were enrolled in this study. Of these, 102 participants received study treatment. Study consists of 2 parts: Part 1 (Day 1 to Week 24) and Part 2 (Week 24 to Week 48).
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1: Japanese Participants Japanese participants received DRF 231 mg, oral capsule, BID on Day 1 through Day 7, followed by DRF 462 (2\*231) mg, oral capsules, BID from Day 8 up to Week 48, with allowable dose reduction for tolerability from Day 8 onwards at investigator's discretion. | 52 |
| Cohort 2: Chinese Participants Chinese participants received DRF 231 mg, oral capsule, BID, on Day 1 through Day 7, followed by DRF 462 (2\*231) mg, oral capsules, BID from Day 8 up to Week 48, with allowable dose reduction for tolerability from Day 8 onwards at investigator's discretion. | 50 |
| Total | 102 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 0 |
| Overall Study | Lack of Efficacy | 1 | 3 |
| Overall Study | Reason Not Specified | 0 | 1 |
| Overall Study | Withdrawal by Subject | 2 | 6 |
Baseline characteristics
| Characteristic | Cohort 2: Chinese Participants | Total | Cohort 1: Japanese Participants |
|---|---|---|---|
| Age, Continuous | 35.6 years STANDARD_DEVIATION 10.49 | 37.9 years STANDARD_DEVIATION 10.23 | 40.1 years STANDARD_DEVIATION 9.56 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 50 Participants | 102 Participants | 52 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 50 Participants | 102 Participants | 52 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 42 Participants | 82 Participants | 40 Participants |
| Sex: Female, Male Male | 8 Participants | 20 Participants | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 52 | 0 / 50 |
| other Total, other adverse events | 50 / 52 | 42 / 50 |
| serious Total, serious adverse events | 6 / 52 | 6 / 50 |
Outcome results
Primary
Part 1: Number of Participants With Abnormal Shift in 12-Lead Electrocardiogram (ECG) Values
The number of participants with shifts to categorical values of ECG interpretation (e.g. abnormal) were presented by each cohort. Abnormal shift includes a shift from normal or unknown to abnormal.
Time frame: Baseline (Day 1) to Week 24
Population: Safety analysis set included all participants who had received at least 1 dose of study treatment. Here, 'overall number of participants analyzed' signifies the participants who had at least one post baseline value and the baseline value was not abnormal.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1: Japanese Participants | Part 1: Number of Participants With Abnormal Shift in 12-Lead Electrocardiogram (ECG) Values | 5 Participants |
| Cohort 2: Chinese Participants | Part 1: Number of Participants With Abnormal Shift in 12-Lead Electrocardiogram (ECG) Values | 3 Participants |
Primary
Part 1: Number of Participants With Clinically Relevant Abnormalities in Vital Sign Parameters
Vital sign assessment included temperature, pulse rate systolic blood pressure, diastolic blood pressure, and respiratory rate. The criteria for determining potentially clinically relevant abnormalities in vital signs included: temperature \< 36 and \> 38 degrees Celsius (C), pulse rate \< 60 and \> 100 beats per minute (bpm), systolic blood pressure (\< 90, \> 140 and \> 160 millimeters of mercury \[mmHg\]), diastolic blood pressure \< 50, \> 90 and \> 100 mmHg, weight (7% or more increase from baseline, 7% or more decrease from baseline) and respiratory rate \< 12 and \> 20 breaths per minute.
Time frame: Baseline (Day 1) to Week 24
Population: Safety analysis set included all participants who had received at least 1 dose of study treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1: Japanese Participants | Part 1: Number of Participants With Clinically Relevant Abnormalities in Vital Sign Parameters | Temperature <36 degrees C | 8 Participants |
| Cohort 1: Japanese Participants | Part 1: Number of Participants With Clinically Relevant Abnormalities in Vital Sign Parameters | Temperature >38 degrees C | 1 Participants |
| Cohort 1: Japanese Participants | Part 1: Number of Participants With Clinically Relevant Abnormalities in Vital Sign Parameters | Pulse Rate <60 bpm | 9 Participants |
| Cohort 1: Japanese Participants | Part 1: Number of Participants With Clinically Relevant Abnormalities in Vital Sign Parameters | Pulse Rate >100 bpm | 4 Participants |
| Cohort 1: Japanese Participants | Part 1: Number of Participants With Clinically Relevant Abnormalities in Vital Sign Parameters | Systolic Blood Pressure <90 mmHg | 4 Participants |
| Cohort 1: Japanese Participants | Part 1: Number of Participants With Clinically Relevant Abnormalities in Vital Sign Parameters | Systolic Blood Pressure >140 mmHg | 2 Participants |
| Cohort 1: Japanese Participants | Part 1: Number of Participants With Clinically Relevant Abnormalities in Vital Sign Parameters | Systolic Blood Pressure >160 mmHg | 0 Participants |
| Cohort 1: Japanese Participants | Part 1: Number of Participants With Clinically Relevant Abnormalities in Vital Sign Parameters | Diastolic Blood Pressure <50 mmHg | 2 Participants |
| Cohort 1: Japanese Participants | Part 1: Number of Participants With Clinically Relevant Abnormalities in Vital Sign Parameters | Diastolic Blood Pressure >90 mmHg | 13 Participants |
| Cohort 1: Japanese Participants | Part 1: Number of Participants With Clinically Relevant Abnormalities in Vital Sign Parameters | Diastolic Blood Pressure >100 mmHg | 2 Participants |
| Cohort 1: Japanese Participants | Part 1: Number of Participants With Clinically Relevant Abnormalities in Vital Sign Parameters | Weight 7% or more increase from baseline | 1 Participants |
| Cohort 1: Japanese Participants | Part 1: Number of Participants With Clinically Relevant Abnormalities in Vital Sign Parameters | Weight 7% or more decrease from baseline | 3 Participants |
| Cohort 1: Japanese Participants | Part 1: Number of Participants With Clinically Relevant Abnormalities in Vital Sign Parameters | Respiratory Rate <12 breaths/min | 3 Participants |
| Cohort 1: Japanese Participants | Part 1: Number of Participants With Clinically Relevant Abnormalities in Vital Sign Parameters | Respiratory Rate >20 breaths/min | 8 Participants |
| Cohort 2: Chinese Participants | Part 1: Number of Participants With Clinically Relevant Abnormalities in Vital Sign Parameters | Weight 7% or more increase from baseline | 5 Participants |
| Cohort 2: Chinese Participants | Part 1: Number of Participants With Clinically Relevant Abnormalities in Vital Sign Parameters | Temperature <36 degrees C | 2 Participants |
| Cohort 2: Chinese Participants | Part 1: Number of Participants With Clinically Relevant Abnormalities in Vital Sign Parameters | Diastolic Blood Pressure <50 mmHg | 0 Participants |
| Cohort 2: Chinese Participants | Part 1: Number of Participants With Clinically Relevant Abnormalities in Vital Sign Parameters | Temperature >38 degrees C | 0 Participants |
| Cohort 2: Chinese Participants | Part 1: Number of Participants With Clinically Relevant Abnormalities in Vital Sign Parameters | Respiratory Rate <12 breaths/min | 0 Participants |
| Cohort 2: Chinese Participants | Part 1: Number of Participants With Clinically Relevant Abnormalities in Vital Sign Parameters | Pulse Rate <60 bpm | 3 Participants |
| Cohort 2: Chinese Participants | Part 1: Number of Participants With Clinically Relevant Abnormalities in Vital Sign Parameters | Diastolic Blood Pressure >90 mmHg | 4 Participants |
| Cohort 2: Chinese Participants | Part 1: Number of Participants With Clinically Relevant Abnormalities in Vital Sign Parameters | Pulse Rate >100 bpm | 2 Participants |
| Cohort 2: Chinese Participants | Part 1: Number of Participants With Clinically Relevant Abnormalities in Vital Sign Parameters | Weight 7% or more decrease from baseline | 2 Participants |
| Cohort 2: Chinese Participants | Part 1: Number of Participants With Clinically Relevant Abnormalities in Vital Sign Parameters | Systolic Blood Pressure <90 mmHg | 1 Participants |
| Cohort 2: Chinese Participants | Part 1: Number of Participants With Clinically Relevant Abnormalities in Vital Sign Parameters | Diastolic Blood Pressure >100 mmHg | 0 Participants |
| Cohort 2: Chinese Participants | Part 1: Number of Participants With Clinically Relevant Abnormalities in Vital Sign Parameters | Systolic Blood Pressure >140 mmHg | 1 Participants |
| Cohort 2: Chinese Participants | Part 1: Number of Participants With Clinically Relevant Abnormalities in Vital Sign Parameters | Respiratory Rate >20 breaths/min | 0 Participants |
| Cohort 2: Chinese Participants | Part 1: Number of Participants With Clinically Relevant Abnormalities in Vital Sign Parameters | Systolic Blood Pressure >160 mmHg | 1 Participants |
Primary
Part 1: Number of Participants With Columbia Suicide Severity Rating Scale (C-SSRS) Events
The C-SSRS was an interview-based rating scale to systematically assess suicidal ideation, suicidal behavior and non-suicidal self-injurious behavior. The C-SSRS includes 'yes' or 'no' responses for assessment of suicidal behavior (preparatory acts or behavior, aborted attempt, interrupted attempt, Suicidal behavior, completed suicide), suicidal ideation (wish to be dead, non-specific active suicidal thoughts, active suicidal ideation with any methods, active suicidal ideation with some intent, active suicidal ideation with specific plan and intent) and non-suicidal self-injurious behavior.
Time frame: Baseline (Day 1) to Week 24
Population: Safety analysis set included all participants who had received at least 1 dose of study treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1: Japanese Participants | Part 1: Number of Participants With Columbia Suicide Severity Rating Scale (C-SSRS) Events | Suicidal Ideation | 0 Participants |
| Cohort 1: Japanese Participants | Part 1: Number of Participants With Columbia Suicide Severity Rating Scale (C-SSRS) Events | Suicidal Behavior | 0 Participants |
| Cohort 1: Japanese Participants | Part 1: Number of Participants With Columbia Suicide Severity Rating Scale (C-SSRS) Events | Non-suicidal Self-injurious Behavior | 0 Participants |
| Cohort 2: Chinese Participants | Part 1: Number of Participants With Columbia Suicide Severity Rating Scale (C-SSRS) Events | Suicidal Ideation | 1 Participants |
| Cohort 2: Chinese Participants | Part 1: Number of Participants With Columbia Suicide Severity Rating Scale (C-SSRS) Events | Suicidal Behavior | 0 Participants |
| Cohort 2: Chinese Participants | Part 1: Number of Participants With Columbia Suicide Severity Rating Scale (C-SSRS) Events | Non-suicidal Self-injurious Behavior | 0 Participants |
Primary
Part 1: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters
Laboratory assessments included hematology, blood chemistry, and urinalysis parameters. Hematology parameters:basophils, hematocrit, red blood cell, total and differential leukocytes, platelets, lymphocytes, monocytes, neutrophils, eosinophils, hemoglobin. Blood chemistry parameters:sodium, potassium, chloride, glucose, calcium, uric acid, total protein, albumin, creatine phosphokinase, Lipid profile: blood cholesterol,high-density lipoprotein,low-density lipoprotein, and triglycerides,serum follicle-stimulating hormone,Vitamin D,thyroid stimulating hormone,serum pregnancy, HIV/Hepatitis screen,tuberculosis test,alanine aminotransferase,aspartate aminotransferase,Lactate Dehydrogenase,alkaline phosphatase,gamma glutamyl transferase,total bilirubin,blood urea nitrogen,creatinine and bicarbonate. Urinalysis parameters:color,pH,specific gravity,ketones,protein,glucose, bilirubin,nitrite,urobilinogen,occult blood,microscopic examination,urine albumin,beta-2-microglobulin,urine creatinine.
Time frame: Baseline (Day 1) to Week 24
Population: Safety analysis set included all participants who had received at least 1 dose of study treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1: Japanese Participants | Part 1: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters | Aspartate Aminotransferase >5 x ULN | 0 Participants |
| Cohort 1: Japanese Participants | Part 1: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters | Neutrophils <1.5 x 10^9/L | 5 Participants |
| Cohort 1: Japanese Participants | Part 1: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters | Aspartate Aminotransferase >10 x ULN | 0 Participants |
| Cohort 1: Japanese Participants | Part 1: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters | Platelets <=75 x 10^9/L | 0 Participants |
| Cohort 1: Japanese Participants | Part 1: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters | Alkaline Phosphatase >3 x ULN | 0 Participants |
| Cohort 1: Japanese Participants | Part 1: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters | Lymphocytes <0.91 x 10^9/L | 25 Participants |
| Cohort 1: Japanese Participants | Part 1: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters | Alkaline Phosphatase >5 x ULN | 0 Participants |
| Cohort 1: Japanese Participants | Part 1: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters | Platelets >=700 x 10^9/L | 0 Participants |
| Cohort 1: Japanese Participants | Part 1: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters | Alkaline Phosphatase >10 x ULN | 0 Participants |
| Cohort 1: Japanese Participants | Part 1: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters | Neutrophils<1 x 10^9/L | 1 Participants |
| Cohort 1: Japanese Participants | Part 1: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters | Gamma Glutamyl Transferase >=3 x ULN | 3 Participants |
| Cohort 1: Japanese Participants | Part 1: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters | Alanine Aminotransferase >=3 x upper limit of normal (ULN) | 7 Participants |
| Cohort 1: Japanese Participants | Part 1: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters | Bilirubin >1.5 x ULN | 0 Participants |
| Cohort 1: Japanese Participants | Part 1: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters | Lymphocytes <0.5 x 10^9/L | 2 Participants |
| Cohort 1: Japanese Participants | Part 1: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters | Bilirubin >2 x ULN | 0 Participants |
| Cohort 1: Japanese Participants | Part 1: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters | Alanine Aminotransferase >5 x ULN | 1 Participants |
| Cohort 1: Japanese Participants | Part 1: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters | Urea Nitrogen >10.71 Millimoles per Liter (mmol/L) | 0 Participants |
| Cohort 1: Japanese Participants | Part 1: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters | Eosinophils >1.0 x 10^9/L | 7 Participants |
| Cohort 1: Japanese Participants | Part 1: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters | Creatinine >=176.8 Micromole per Litre (umol/L) | 0 Participants |
| Cohort 1: Japanese Participants | Part 1: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters | Alanine Aminotransferase >10 x ULN | 0 Participants |
| Cohort 1: Japanese Participants | Part 1: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters | Bicarbonate <15 mmol/L | 0 Participants |
| Cohort 1: Japanese Participants | Part 1: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters | Lymphocytes <0.8 x 10^9/L | 15 Participants |
| Cohort 1: Japanese Participants | Part 1: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters | Bicarbonate >31 mmol/L | 0 Participants |
| Cohort 1: Japanese Participants | Part 1: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters | Aspartate Aminotransferase >=3 x ULN | 2 Participants |
| Cohort 1: Japanese Participants | Part 1: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters | Ketones >=4+ | 1 Participants |
| Cohort 1: Japanese Participants | Part 1: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters | Hemoglobin <=95 gram per liter (g/L) for Female or <=115g/L for Male | 0 Participants |
| Cohort 1: Japanese Participants | Part 1: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters | Protein >=2+ | 1 Participants |
| Cohort 1: Japanese Participants | Part 1: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters | Leukocytes <=2.8 x 10^9 per liter (L) | 3 Participants |
| Cohort 2: Chinese Participants | Part 1: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters | Protein >=2+ | 0 Participants |
| Cohort 2: Chinese Participants | Part 1: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters | Leukocytes <=2.8 x 10^9 per liter (L) | 1 Participants |
| Cohort 2: Chinese Participants | Part 1: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters | Lymphocytes <0.91 x 10^9/L | 11 Participants |
| Cohort 2: Chinese Participants | Part 1: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters | Lymphocytes <0.8 x 10^9/L | 3 Participants |
| Cohort 2: Chinese Participants | Part 1: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters | Lymphocytes <0.5 x 10^9/L | 0 Participants |
| Cohort 2: Chinese Participants | Part 1: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters | Neutrophils <1.5 x 10^9/L | 2 Participants |
| Cohort 2: Chinese Participants | Part 1: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters | Neutrophils<1 x 10^9/L | 0 Participants |
| Cohort 2: Chinese Participants | Part 1: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters | Eosinophils >1.0 x 10^9/L | 0 Participants |
| Cohort 2: Chinese Participants | Part 1: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters | Hemoglobin <=95 gram per liter (g/L) for Female or <=115g/L for Male | 1 Participants |
| Cohort 2: Chinese Participants | Part 1: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters | Platelets <=75 x 10^9/L | 0 Participants |
| Cohort 2: Chinese Participants | Part 1: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters | Platelets >=700 x 10^9/L | 0 Participants |
| Cohort 2: Chinese Participants | Part 1: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters | Alanine Aminotransferase >=3 x upper limit of normal (ULN) | 3 Participants |
| Cohort 2: Chinese Participants | Part 1: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters | Alanine Aminotransferase >5 x ULN | 0 Participants |
| Cohort 2: Chinese Participants | Part 1: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters | Alanine Aminotransferase >10 x ULN | 0 Participants |
| Cohort 2: Chinese Participants | Part 1: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters | Aspartate Aminotransferase >=3 x ULN | 0 Participants |
| Cohort 2: Chinese Participants | Part 1: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters | Aspartate Aminotransferase >5 x ULN | 0 Participants |
| Cohort 2: Chinese Participants | Part 1: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters | Aspartate Aminotransferase >10 x ULN | 0 Participants |
| Cohort 2: Chinese Participants | Part 1: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters | Alkaline Phosphatase >3 x ULN | 0 Participants |
| Cohort 2: Chinese Participants | Part 1: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters | Alkaline Phosphatase >5 x ULN | 0 Participants |
| Cohort 2: Chinese Participants | Part 1: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters | Alkaline Phosphatase >10 x ULN | 0 Participants |
| Cohort 2: Chinese Participants | Part 1: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters | Gamma Glutamyl Transferase >=3 x ULN | 1 Participants |
| Cohort 2: Chinese Participants | Part 1: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters | Bilirubin >1.5 x ULN | 1 Participants |
| Cohort 2: Chinese Participants | Part 1: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters | Bilirubin >2 x ULN | 0 Participants |
| Cohort 2: Chinese Participants | Part 1: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters | Urea Nitrogen >10.71 Millimoles per Liter (mmol/L) | 0 Participants |
| Cohort 2: Chinese Participants | Part 1: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters | Creatinine >=176.8 Micromole per Litre (umol/L) | 0 Participants |
| Cohort 2: Chinese Participants | Part 1: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters | Bicarbonate <15 mmol/L | 0 Participants |
| Cohort 2: Chinese Participants | Part 1: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters | Bicarbonate >31 mmol/L | 0 Participants |
| Cohort 2: Chinese Participants | Part 1: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters | Ketones >=4+ | 0 Participants |
Primary
Part 1: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)
An adverse event (AE) was any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether/not related to the medicinal (investigational) product. An AE was considered treatment-emergent if it starts or worsens on or after the date of the first dose of study drug in the study until 1 day after the last dose of treatment, or completion of the safety follow-up visit, if applicable.(i.e. for participants who prematurely discontinued study treatment or withdrew from the study) . An SAE is any untoward medical occurrence that at any dose results in death, is a life-threatening event, requires inpatient hospitalization or prolongation of existing hospitalization, results in a significant disability/incapacity or congenital anomaly, is a medically important event. TEAEs included both serious and non-serious TEAEs.
Time frame: Baseline (Day 1) up to Week 24 (for prematurely discontinued participants, AEs were reported up to 2 weeks post discontinuation)
Population: Safety analysis set included all participants who had received at least 1 dose of study treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1: Japanese Participants | Part 1: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | TEAEs | 50 Participants |
| Cohort 1: Japanese Participants | Part 1: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | TESAEs | 3 Participants |
| Cohort 2: Chinese Participants | Part 1: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | TEAEs | 45 Participants |
| Cohort 2: Chinese Participants | Part 1: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | TESAEs | 5 Participants |
Primary
Part 2: Number of Participants With Abnormal Shift in 12-Lead ECG Values
The number of participants with shifts to categorical values of ECG interpretation (e.g. abnormal) were presented by each cohort. Abnormal shift includes a shift from normal or unknown to abnormal.
Time frame: Baseline (Day 1) to Week 48
Population: Safety analysis set included all participants who had received at least 1 dose of study treatment. Here, 'overall number of participants analyzed' signifies the participants who had at least one post baseline value and the baseline value was not abnormal.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1: Japanese Participants | Part 2: Number of Participants With Abnormal Shift in 12-Lead ECG Values | 7 Participants |
| Cohort 2: Chinese Participants | Part 2: Number of Participants With Abnormal Shift in 12-Lead ECG Values | 5 Participants |
Primary
Part 2: Number of Participants With Clinically Relevant Abnormalities in Vital Sign Parameters
Vital sign assessment included temperature, pulse rate systolic blood pressure, diastolic blood pressure, and respiratory rate. The criteria for determining potentially clinically relevant abnormalities in vital signs included: temperature \< 36 and \> 38 degrees C, pulse rate \< 60 and \> 100 bpm, systolic blood pressure (\< 90, \> 140 and \> 160 mmHg), diastolic blood pressure \< 50, \> 90 and \> 100 mmHg, weight (7% or more increase from baseline, 7% or more decrease from baseline) and respiratory rate \< 12 and \> 20 breaths per minute.
Time frame: Baseline (Day 1) to Week 48
Population: Safety analysis set included all participants who had received at least 1 dose of study treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1: Japanese Participants | Part 2: Number of Participants With Clinically Relevant Abnormalities in Vital Sign Parameters | Temperature <36 degrees C | 12 Participants |
| Cohort 1: Japanese Participants | Part 2: Number of Participants With Clinically Relevant Abnormalities in Vital Sign Parameters | Temperature >38 degrees C | 1 Participants |
| Cohort 1: Japanese Participants | Part 2: Number of Participants With Clinically Relevant Abnormalities in Vital Sign Parameters | Pulse Rate <60 bpm | 9 Participants |
| Cohort 1: Japanese Participants | Part 2: Number of Participants With Clinically Relevant Abnormalities in Vital Sign Parameters | Pulse Rate >100 bpm | 6 Participants |
| Cohort 1: Japanese Participants | Part 2: Number of Participants With Clinically Relevant Abnormalities in Vital Sign Parameters | Systolic Blood Pressure <90 mmHg | 7 Participants |
| Cohort 1: Japanese Participants | Part 2: Number of Participants With Clinically Relevant Abnormalities in Vital Sign Parameters | Systolic Blood Pressure >140 mmHg | 3 Participants |
| Cohort 1: Japanese Participants | Part 2: Number of Participants With Clinically Relevant Abnormalities in Vital Sign Parameters | Systolic Blood Pressure >160 mmHg | 0 Participants |
| Cohort 1: Japanese Participants | Part 2: Number of Participants With Clinically Relevant Abnormalities in Vital Sign Parameters | Diastolic Blood Pressure <50 mmHg | 3 Participants |
| Cohort 1: Japanese Participants | Part 2: Number of Participants With Clinically Relevant Abnormalities in Vital Sign Parameters | Diastolic Blood Pressure >90 mmHg | 14 Participants |
| Cohort 1: Japanese Participants | Part 2: Number of Participants With Clinically Relevant Abnormalities in Vital Sign Parameters | Diastolic Blood Pressure >100 mmHg | 4 Participants |
| Cohort 1: Japanese Participants | Part 2: Number of Participants With Clinically Relevant Abnormalities in Vital Sign Parameters | Weight 7% or more increase from baseline | 3 Participants |
| Cohort 1: Japanese Participants | Part 2: Number of Participants With Clinically Relevant Abnormalities in Vital Sign Parameters | Weight 7% or more decrease from baseline | 5 Participants |
| Cohort 1: Japanese Participants | Part 2: Number of Participants With Clinically Relevant Abnormalities in Vital Sign Parameters | Respiratory Rate <12 breaths/min | 6 Participants |
| Cohort 1: Japanese Participants | Part 2: Number of Participants With Clinically Relevant Abnormalities in Vital Sign Parameters | Respiratory Rate >20 breaths/min | 13 Participants |
| Cohort 2: Chinese Participants | Part 2: Number of Participants With Clinically Relevant Abnormalities in Vital Sign Parameters | Weight 7% or more increase from baseline | 6 Participants |
| Cohort 2: Chinese Participants | Part 2: Number of Participants With Clinically Relevant Abnormalities in Vital Sign Parameters | Temperature <36 degrees C | 2 Participants |
| Cohort 2: Chinese Participants | Part 2: Number of Participants With Clinically Relevant Abnormalities in Vital Sign Parameters | Diastolic Blood Pressure <50 mmHg | 1 Participants |
| Cohort 2: Chinese Participants | Part 2: Number of Participants With Clinically Relevant Abnormalities in Vital Sign Parameters | Temperature >38 degrees C | 0 Participants |
| Cohort 2: Chinese Participants | Part 2: Number of Participants With Clinically Relevant Abnormalities in Vital Sign Parameters | Respiratory Rate <12 breaths/min | 0 Participants |
| Cohort 2: Chinese Participants | Part 2: Number of Participants With Clinically Relevant Abnormalities in Vital Sign Parameters | Pulse Rate <60 bpm | 7 Participants |
| Cohort 2: Chinese Participants | Part 2: Number of Participants With Clinically Relevant Abnormalities in Vital Sign Parameters | Diastolic Blood Pressure >90 mmHg | 5 Participants |
| Cohort 2: Chinese Participants | Part 2: Number of Participants With Clinically Relevant Abnormalities in Vital Sign Parameters | Pulse Rate >100 bpm | 3 Participants |
| Cohort 2: Chinese Participants | Part 2: Number of Participants With Clinically Relevant Abnormalities in Vital Sign Parameters | Weight 7% or more decrease from baseline | 7 Participants |
| Cohort 2: Chinese Participants | Part 2: Number of Participants With Clinically Relevant Abnormalities in Vital Sign Parameters | Systolic Blood Pressure <90 mmHg | 2 Participants |
| Cohort 2: Chinese Participants | Part 2: Number of Participants With Clinically Relevant Abnormalities in Vital Sign Parameters | Diastolic Blood Pressure >100 mmHg | 0 Participants |
| Cohort 2: Chinese Participants | Part 2: Number of Participants With Clinically Relevant Abnormalities in Vital Sign Parameters | Systolic Blood Pressure >140 mmHg | 1 Participants |
| Cohort 2: Chinese Participants | Part 2: Number of Participants With Clinically Relevant Abnormalities in Vital Sign Parameters | Respiratory Rate >20 breaths/min | 1 Participants |
| Cohort 2: Chinese Participants | Part 2: Number of Participants With Clinically Relevant Abnormalities in Vital Sign Parameters | Systolic Blood Pressure >160 mmHg | 1 Participants |
Primary
Part 2: Number of Participants With C-SSRS Events
The C-SSRS was an interview-based rating scale to systematically assess suicidal ideation, suicidal behavior and non-suicidal self-injurious behavior. The C-SSRS includes 'yes' or 'no' responses for assessment of suicidal behavior (preparatory acts or behavior, aborted attempt, interrupted attempt, Suicidal behavior, completed suicide), suicidal ideation (wish to be dead, non-specific active suicidal thoughts, active suicidal ideation with any methods, active suicidal ideation with some intent, active suicidal ideation with specific plan and intent) and non-suicidal self-injurious behavior.
Time frame: Baseline (Day 1) to Week 48
Population: Safety analysis set included all participants who had received at least 1 dose of study treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1: Japanese Participants | Part 2: Number of Participants With C-SSRS Events | Suicidal Ideation | 0 Participants |
| Cohort 1: Japanese Participants | Part 2: Number of Participants With C-SSRS Events | Suicidal Behavior | 0 Participants |
| Cohort 1: Japanese Participants | Part 2: Number of Participants With C-SSRS Events | Non-suicidal Self-injurious Behavior | 0 Participants |
| Cohort 2: Chinese Participants | Part 2: Number of Participants With C-SSRS Events | Suicidal Ideation | 2 Participants |
| Cohort 2: Chinese Participants | Part 2: Number of Participants With C-SSRS Events | Suicidal Behavior | 0 Participants |
| Cohort 2: Chinese Participants | Part 2: Number of Participants With C-SSRS Events | Non-suicidal Self-injurious Behavior | 0 Participants |
Primary
Part 2: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters
Laboratory assessments included hematology, blood chemistry, and urinalysis parameters. Hematology parameters:basophils, hematocrit, red blood cell, total and differential leukocytes, platelets, lymphocytes, monocytes, neutrophils, eosinophils, hemoglobin. Blood chemistry parameters:sodium, potassium, chloride, glucose, calcium, uric acid, total protein, albumin, creatine phosphokinase, Lipid profile: blood cholesterol,high-density lipoprotein,low-density lipoprotein, and triglycerides,serum follicle-stimulating hormone,Vitamin D,thyroid stimulating hormone,serum pregnancy, HIV/Hepatitis screen,tuberculosis test,alanine aminotransferase,aspartate aminotransferase,Lactate Dehydrogenase,alkaline phosphatase,gamma glutamyl transferase,total bilirubin,blood urea nitrogen,creatinine and bicarbonate. Urinalysis parameters:color,pH,specific gravity,ketones,protein,glucose, bilirubin,nitrite,urobilinogen,occult blood,microscopic examination,urine albumin,beta-2-microglobulin,urine creatinine.
Time frame: Baseline (Day 1) to Week 48
Population: Safety analysis set included all participants who had received at least 1 dose of study treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1: Japanese Participants | Part 2: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters | Aspartate Aminotransferase >5 x ULN | 0 Participants |
| Cohort 1: Japanese Participants | Part 2: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters | Neutrophils <1.5 x 10^9/L | 8 Participants |
| Cohort 1: Japanese Participants | Part 2: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters | Aspartate Aminotransferase >10 x ULN | 0 Participants |
| Cohort 1: Japanese Participants | Part 2: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters | Platelets <=75 x 10^9/L | 0 Participants |
| Cohort 1: Japanese Participants | Part 2: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters | Alkaline Phosphatase >3 x ULN | 0 Participants |
| Cohort 1: Japanese Participants | Part 2: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters | Lymphocytes <0.91 x 10^9/L | 28 Participants |
| Cohort 1: Japanese Participants | Part 2: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters | Alkaline Phosphatase >5 x ULN | 0 Participants |
| Cohort 1: Japanese Participants | Part 2: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters | Platelets >=700 x 10^9/L | 0 Participants |
| Cohort 1: Japanese Participants | Part 2: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters | Alkaline Phosphatase >10 x ULN | 0 Participants |
| Cohort 1: Japanese Participants | Part 2: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters | Neutrophils <1 x 10^9/L | 2 Participants |
| Cohort 1: Japanese Participants | Part 2: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters | Gamma Glutamyl Transferase >=3 x ULN | 4 Participants |
| Cohort 1: Japanese Participants | Part 2: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters | Alanine Aminotransferase >=3 x ULN | 7 Participants |
| Cohort 1: Japanese Participants | Part 2: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters | Bilirubin >1.5 x ULN | 0 Participants |
| Cohort 1: Japanese Participants | Part 2: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters | Lymphocytes <0.5 x 10^9/L | 5 Participants |
| Cohort 1: Japanese Participants | Part 2: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters | Bilirubin >2 x ULN | 0 Participants |
| Cohort 1: Japanese Participants | Part 2: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters | Alanine Aminotransferase >5 x ULN | 1 Participants |
| Cohort 1: Japanese Participants | Part 2: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters | Urea Nitrogen >10.71 mmol/L | 0 Participants |
| Cohort 1: Japanese Participants | Part 2: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters | Eosinophils >1.0 x 10^9/L | 7 Participants |
| Cohort 1: Japanese Participants | Part 2: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters | Creatinine >=176.8 umol/L | 0 Participants |
| Cohort 1: Japanese Participants | Part 2: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters | Alanine Aminotransferase >10 x ULN | 0 Participants |
| Cohort 1: Japanese Participants | Part 2: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters | Bicarbonate <15 mmol/L | 0 Participants |
| Cohort 1: Japanese Participants | Part 2: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters | Lymphocytes <0.8 x 10^9/L | 20 Participants |
| Cohort 1: Japanese Participants | Part 2: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters | Bicarbonate >31 mmol/L | 0 Participants |
| Cohort 1: Japanese Participants | Part 2: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters | Aspartate Aminotransferase >=3 x ULN | 2 Participants |
| Cohort 1: Japanese Participants | Part 2: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters | Ketones >=4+ | 1 Participants |
| Cohort 1: Japanese Participants | Part 2: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters | Hemoglobin <=95g/L for Female or <=115g/L for Male | 3 Participants |
| Cohort 1: Japanese Participants | Part 2: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters | Protein >=2+ | 3 Participants |
| Cohort 1: Japanese Participants | Part 2: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters | Leukocytes <=2.8 x 10^9/L | 6 Participants |
| Cohort 2: Chinese Participants | Part 2: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters | Protein >=2+ | 0 Participants |
| Cohort 2: Chinese Participants | Part 2: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters | Leukocytes <=2.8 x 10^9/L | 3 Participants |
| Cohort 2: Chinese Participants | Part 2: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters | Lymphocytes <0.91 x 10^9/L | 16 Participants |
| Cohort 2: Chinese Participants | Part 2: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters | Lymphocytes <0.8 x 10^9/L | 11 Participants |
| Cohort 2: Chinese Participants | Part 2: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters | Lymphocytes <0.5 x 10^9/L | 1 Participants |
| Cohort 2: Chinese Participants | Part 2: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters | Neutrophils <1.5 x 10^9/L | 4 Participants |
| Cohort 2: Chinese Participants | Part 2: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters | Neutrophils <1 x 10^9/L | 2 Participants |
| Cohort 2: Chinese Participants | Part 2: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters | Eosinophils >1.0 x 10^9/L | 0 Participants |
| Cohort 2: Chinese Participants | Part 2: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters | Hemoglobin <=95g/L for Female or <=115g/L for Male | 2 Participants |
| Cohort 2: Chinese Participants | Part 2: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters | Platelets <=75 x 10^9/L | 0 Participants |
| Cohort 2: Chinese Participants | Part 2: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters | Platelets >=700 x 10^9/L | 0 Participants |
| Cohort 2: Chinese Participants | Part 2: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters | Alanine Aminotransferase >=3 x ULN | 4 Participants |
| Cohort 2: Chinese Participants | Part 2: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters | Alanine Aminotransferase >5 x ULN | 0 Participants |
| Cohort 2: Chinese Participants | Part 2: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters | Alanine Aminotransferase >10 x ULN | 0 Participants |
| Cohort 2: Chinese Participants | Part 2: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters | Aspartate Aminotransferase >=3 x ULN | 0 Participants |
| Cohort 2: Chinese Participants | Part 2: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters | Aspartate Aminotransferase >5 x ULN | 0 Participants |
| Cohort 2: Chinese Participants | Part 2: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters | Aspartate Aminotransferase >10 x ULN | 0 Participants |
| Cohort 2: Chinese Participants | Part 2: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters | Alkaline Phosphatase >3 x ULN | 0 Participants |
| Cohort 2: Chinese Participants | Part 2: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters | Alkaline Phosphatase >5 x ULN | 0 Participants |
| Cohort 2: Chinese Participants | Part 2: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters | Alkaline Phosphatase >10 x ULN | 0 Participants |
| Cohort 2: Chinese Participants | Part 2: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters | Gamma Glutamyl Transferase >=3 x ULN | 2 Participants |
| Cohort 2: Chinese Participants | Part 2: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters | Bilirubin >1.5 x ULN | 1 Participants |
| Cohort 2: Chinese Participants | Part 2: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters | Bilirubin >2 x ULN | 0 Participants |
| Cohort 2: Chinese Participants | Part 2: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters | Urea Nitrogen >10.71 mmol/L | 0 Participants |
| Cohort 2: Chinese Participants | Part 2: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters | Creatinine >=176.8 umol/L | 0 Participants |
| Cohort 2: Chinese Participants | Part 2: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters | Bicarbonate <15 mmol/L | 0 Participants |
| Cohort 2: Chinese Participants | Part 2: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters | Bicarbonate >31 mmol/L | 0 Participants |
| Cohort 2: Chinese Participants | Part 2: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters | Ketones >=4+ | 0 Participants |
Primary
Parts 1 and 2: Number of Participants With TEAEs and TESAEs
An AE was any unfavorable and unintended sign, symptom, or disease temporally associated with use of medicinal (investigational) product, whether/not related to medicinal (investigational) product. AE was considered treatment-emergent if it starts or worsens on or after the date of the first dose of study drug in the study until 1 day after the last dose of treatment. SAE is any untoward medical occurrence that at any dose results in death, is a life-threatening event, requires inpatient hospitalization or prolongation of existing hospitalization, results in a significant disability/incapacity or congenital anomaly, is a medically important event. TEAEs included both serious and non-serious TEAEs. TEAEs and TESAEs for participants were collected cumulatively for Parts 1 and 2.
Time frame: From Day 1 up to the end of the study (up to Week 50)
Population: Safety analysis set included all participants who had received at least 1 dose of study treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1: Japanese Participants | Parts 1 and 2: Number of Participants With TEAEs and TESAEs | TEAEs | 52 Participants |
| Cohort 1: Japanese Participants | Parts 1 and 2: Number of Participants With TEAEs and TESAEs | TESAEs | 6 Participants |
| Cohort 2: Chinese Participants | Parts 1 and 2: Number of Participants With TEAEs and TESAEs | TEAEs | 47 Participants |
| Cohort 2: Chinese Participants | Parts 1 and 2: Number of Participants With TEAEs and TESAEs | TESAEs | 6 Participants |
Secondary
Part 1: Area Under the Concentration-Time Curve From Time Zero to Time of Last Measurable Concentration (AUClast) of MMF-Intensive PK Analysis Set
Summarized data for AUClast at all timepoints is reported.
Time frame: Pre-dose and at 0.5,1,2,3,4,6, and 8 hours post-dose from Day 29 to Day 169
Population: PK analysis set included all participants who received at least 1 dose of study treatment and had at least 1 post-dose plasma concentration for MMF. The intensive PK analysis set consisted of a subset of participants in the Japanese cohort.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1: Japanese Participants | Part 1: Area Under the Concentration-Time Curve From Time Zero to Time of Last Measurable Concentration (AUClast) of MMF-Intensive PK Analysis Set | 3.6 hour*microgram per milliliter (h*ug/mL) | Geometric Coefficient of Variation 36.34 |
Secondary
Part 1: AUClast of HES-Intensive PK Analysis Set
Summarized data for AUClast at all timepoints is reported.
Time frame: Pre-dose and at 0.5,1,2,3,4,6, and 8 hours post-dose from Day 29 to Day 169
Population: PK analysis set included all participants who received at least 1 dose of study treatment and had at least 1 post-dose plasma concentration for HES. The intensive PK analysis set consisted of a subset of participants in the Japanese cohort.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1: Japanese Participants | Part 1: AUClast of HES-Intensive PK Analysis Set | 75.3 h*ug/mL | Geometric Coefficient of Variation 29.31 |
Secondary
Part 1: Cmax of HES-Intensive PK Analysis Set
Summarized data for Cmax at all timepoints is reported.
Time frame: Pre-dose and at 0.5,1,2,3,4,6, and 8 hours post-dose from Day 29 to Day 169
Population: PK analysis set included all participants who received at least 1 dose of study treatment and had at least 1 post-dose plasma concentration for HES. The intensive PK analysis set consisted of a subset of participants in the Japanese cohort.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1: Japanese Participants | Part 1: Cmax of HES-Intensive PK Analysis Set | 11.6 ug/mL | Geometric Coefficient of Variation 26.49 |
Secondary
Part 1: Elimination Half-Life (t½) of MMF-Intensive PK Analysis Set
Summarized data for t½ at all timepoints is reported.
Time frame: Pre-dose and at 0.5,1,2,3,4,6, and 8 hours post-dose from Day 29 to Day 169
Population: PK analysis set included all participants who received at least 1 dose of study treatment and had at least 1 post-dose plasma concentration for MMF. The intensive PK analysis set consisted of a subset of participants in the Japanese cohort.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1: Japanese Participants | Part 1: Elimination Half-Life (t½) of MMF-Intensive PK Analysis Set | 1.3 hours |
Secondary
Part 1: Maximum Observed Concentration (Cmax) of MMF-Intensive PK Analysis Set
Summarized data for Cmax at all timepoints is reported.
Time frame: Pre-dose and at 0.5,1,2,3,4,6, and 8 hours post-dose from Day 29 to Day 169
Population: PK analysis set included all participants who received at least 1 dose of study treatment and had at least 1 post-dose plasma concentration for MMF. The intensive PK analysis set consisted of a subset of participants in the Japanese cohort.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1: Japanese Participants | Part 1: Maximum Observed Concentration (Cmax) of MMF-Intensive PK Analysis Set | 1.2 ug/mL | Geometric Coefficient of Variation 56.85 |
Secondary
Part 1: Plasma Concentration of 2-Hydroxyethyl Succinimide (HES)-Intensive PK Analysis Set
Summarized data for plasma concentration of HES at all timepoints is reported.
Time frame: Pre-dose and at 0.5,1,2,3,4,6, and 8 hours post-dose from Day 29 to Day 169
Population: PK analysis set included all participants who had received at least 1 dose of study treatment and had at least 1 post-dose plasma concentration for HES. The intensive PK analysis set consisted of a subset of participants in the Japanese cohort.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: Japanese Participants | Part 1: Plasma Concentration of 2-Hydroxyethyl Succinimide (HES)-Intensive PK Analysis Set | Pre-dose | 9.0 ug/mL | Geometric Coefficient of Variation 23.11 |
| Cohort 1: Japanese Participants | Part 1: Plasma Concentration of 2-Hydroxyethyl Succinimide (HES)-Intensive PK Analysis Set | 0.5 Hour Post-dose | 8.7 ug/mL | Geometric Coefficient of Variation 23.59 |
| Cohort 1: Japanese Participants | Part 1: Plasma Concentration of 2-Hydroxyethyl Succinimide (HES)-Intensive PK Analysis Set | 1 Hour Post-dose | 8.4 ug/mL | Geometric Coefficient of Variation 28.42 |
| Cohort 1: Japanese Participants | Part 1: Plasma Concentration of 2-Hydroxyethyl Succinimide (HES)-Intensive PK Analysis Set | 2 Hour Post-dose | 8.4 ug/mL | Geometric Coefficient of Variation 30.88 |
| Cohort 1: Japanese Participants | Part 1: Plasma Concentration of 2-Hydroxyethyl Succinimide (HES)-Intensive PK Analysis Set | 3 Hour Post-dose | 9.5 ug/mL | Geometric Coefficient of Variation 23.84 |
| Cohort 1: Japanese Participants | Part 1: Plasma Concentration of 2-Hydroxyethyl Succinimide (HES)-Intensive PK Analysis Set | 4 Hour Post-dose | 9.5 ug/mL | Geometric Coefficient of Variation 31.92 |
| Cohort 1: Japanese Participants | Part 1: Plasma Concentration of 2-Hydroxyethyl Succinimide (HES)-Intensive PK Analysis Set | 6 Hour Post-dose | 9.9 ug/mL | Geometric Coefficient of Variation 45.11 |
| Cohort 1: Japanese Participants | Part 1: Plasma Concentration of 2-Hydroxyethyl Succinimide (HES)-Intensive PK Analysis Set | 8 Hour Post-dose | 11.2 ug/mL | Geometric Coefficient of Variation 26.05 |
Secondary
Part 1: Plasma Concentrations of HES-Sparse PK Analysis Set
Time frame: Pre-dose and 2 to 3 hours post-dose on Day 29 and Day 57
Population: PK analysis set was used. Sparse PK set consisted of 49 Japanese participants (including participants from the intensive analysis set, except that sparse PK samples were not collected on the same day as intensive PK sampling) and 48 Chinese participants (total participants in Chinese cohort). Number analysed indicates the number of participants evaluable for the specified timepoint.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: Japanese Participants | Part 1: Plasma Concentrations of HES-Sparse PK Analysis Set | Day 29 (Pre-dose) | 8.2 ug/mL | Geometric Coefficient of Variation 28.13 |
| Cohort 1: Japanese Participants | Part 1: Plasma Concentrations of HES-Sparse PK Analysis Set | Day 29 (2-3 Hours Post-dose) | 9.1 ug/mL | Geometric Coefficient of Variation 37.57 |
| Cohort 1: Japanese Participants | Part 1: Plasma Concentrations of HES-Sparse PK Analysis Set | Day 57 (Pre-dose) | 8.4 ug/mL | Geometric Coefficient of Variation 40.45 |
| Cohort 1: Japanese Participants | Part 1: Plasma Concentrations of HES-Sparse PK Analysis Set | Day 57 (2-3 Hours Post-dose) | 9.5 ug/mL | Geometric Coefficient of Variation 34.59 |
| Cohort 2: Chinese Participants | Part 1: Plasma Concentrations of HES-Sparse PK Analysis Set | Day 57 (2-3 Hours Post-dose) | 9.7 ug/mL | Geometric Coefficient of Variation 31.27 |
| Cohort 2: Chinese Participants | Part 1: Plasma Concentrations of HES-Sparse PK Analysis Set | Day 29 (Pre-dose) | 8.0 ug/mL | Geometric Coefficient of Variation 32.54 |
| Cohort 2: Chinese Participants | Part 1: Plasma Concentrations of HES-Sparse PK Analysis Set | Day 57 (Pre-dose) | 8.3 ug/mL | Geometric Coefficient of Variation 34.97 |
| Cohort 2: Chinese Participants | Part 1: Plasma Concentrations of HES-Sparse PK Analysis Set | Day 29 (2-3 Hours Post-dose) | 9.7 ug/mL | Geometric Coefficient of Variation 38.05 |
Secondary
Part 1: Plasma Concentrations of MMF-Sparse PK Analysis Set
Time frame: Pre-dose and 2 to 3 hours post-dose on Day 29 and Day 57
Population: PK analysis set was used. Sparse PK set consisted of 49 Japanese participants (including participants from the intensive analysis set, except that sparse PK samples were not collected on the same day as intensive PK sampling) and 48 Chinese participants (total participants in Chinese cohort). Number analysed indicates the number of participants evaluable for the specified timepoint.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: Japanese Participants | Part 1: Plasma Concentrations of MMF-Sparse PK Analysis Set | Day 29 (Pre-dose) | 0.1 ug/mL | Geometric Coefficient of Variation 79.06 |
| Cohort 1: Japanese Participants | Part 1: Plasma Concentrations of MMF-Sparse PK Analysis Set | Day 29 (2-3 Hours Post-dose) | 0.9 ug/mL | Geometric Coefficient of Variation 246.46 |
| Cohort 1: Japanese Participants | Part 1: Plasma Concentrations of MMF-Sparse PK Analysis Set | Day 57 (Pre-dose) | 0.1 ug/mL | Geometric Coefficient of Variation 90.08 |
| Cohort 1: Japanese Participants | Part 1: Plasma Concentrations of MMF-Sparse PK Analysis Set | Day 57 (2-3 Hours Post-dose) | 0.7 ug/mL | Geometric Coefficient of Variation 234.8 |
| Cohort 2: Chinese Participants | Part 1: Plasma Concentrations of MMF-Sparse PK Analysis Set | Day 57 (2-3 Hours Post-dose) | 1.1 ug/mL | Geometric Coefficient of Variation 131.05 |
| Cohort 2: Chinese Participants | Part 1: Plasma Concentrations of MMF-Sparse PK Analysis Set | Day 29 (Pre-dose) | 0.1 ug/mL | Geometric Coefficient of Variation 144.66 |
| Cohort 2: Chinese Participants | Part 1: Plasma Concentrations of MMF-Sparse PK Analysis Set | Day 57 (Pre-dose) | 0.1 ug/mL | Geometric Coefficient of Variation 91.21 |
| Cohort 2: Chinese Participants | Part 1: Plasma Concentrations of MMF-Sparse PK Analysis Set | Day 29 (2-3 Hours Post-dose) | 0.8 ug/mL | Geometric Coefficient of Variation 223.71 |
Secondary
Part 1: Plasma Concentrations of Monomethyl Fumarate (MMF)-Intensive Pharmacokinetic (PK) Analysis Set
Summarized data for plasma concentration of MMF at all timepoints is reported.
Time frame: Pre-dose and at 0.5,1,2,3,4,6, and 8 hours post-dose from Day 29 to Day 169
Population: PK analysis set included all participants who had received at least 1 dose of study treatment and had at least 1 post-dose plasma concentration for MMF. The intensive PK analysis set consisted of a subset of participants in the Japanese cohort.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: Japanese Participants | Part 1: Plasma Concentrations of Monomethyl Fumarate (MMF)-Intensive Pharmacokinetic (PK) Analysis Set | Pre-dose | 0.1 Microgram per milliliter (ug/mL) | Geometric Coefficient of Variation 67.69 |
| Cohort 1: Japanese Participants | Part 1: Plasma Concentrations of Monomethyl Fumarate (MMF)-Intensive Pharmacokinetic (PK) Analysis Set | 0.5 Hour Post-dose | 0.1 Microgram per milliliter (ug/mL) | Geometric Coefficient of Variation 37.55 |
| Cohort 1: Japanese Participants | Part 1: Plasma Concentrations of Monomethyl Fumarate (MMF)-Intensive Pharmacokinetic (PK) Analysis Set | 1 Hour Post-dose | 0.1 Microgram per milliliter (ug/mL) | Geometric Coefficient of Variation 73.6 |
| Cohort 1: Japanese Participants | Part 1: Plasma Concentrations of Monomethyl Fumarate (MMF)-Intensive Pharmacokinetic (PK) Analysis Set | 2 Hours Post-dose | 0.2 Microgram per milliliter (ug/mL) | Geometric Coefficient of Variation 184.48 |
| Cohort 1: Japanese Participants | Part 1: Plasma Concentrations of Monomethyl Fumarate (MMF)-Intensive Pharmacokinetic (PK) Analysis Set | 3 Hours Post-dose | 0.5 Microgram per milliliter (ug/mL) | Geometric Coefficient of Variation 210.05 |
| Cohort 1: Japanese Participants | Part 1: Plasma Concentrations of Monomethyl Fumarate (MMF)-Intensive Pharmacokinetic (PK) Analysis Set | 4 Hours Post-dose | 0.9 Microgram per milliliter (ug/mL) | Geometric Coefficient of Variation 63.43 |
| Cohort 1: Japanese Participants | Part 1: Plasma Concentrations of Monomethyl Fumarate (MMF)-Intensive Pharmacokinetic (PK) Analysis Set | 6 Hours Post-dose | 0.4 Microgram per milliliter (ug/mL) | Geometric Coefficient of Variation 88.04 |
| Cohort 1: Japanese Participants | Part 1: Plasma Concentrations of Monomethyl Fumarate (MMF)-Intensive Pharmacokinetic (PK) Analysis Set | 8 Hours Post-dose | 0.1 Microgram per milliliter (ug/mL) | Geometric Coefficient of Variation 58.32 |
Secondary
Part 1: Time to Reach Cmax (Tmax) of MMF-Intensive PK Analysis Set
Summarized data for Tmax at all timepoints is reported.
Time frame: Pre-dose and at 0.5,1,2,3,4,6, and 8 hours post-dose from Day 29 to Day 169
Population: PK analysis set included all participants who received at least 1 dose of study treatment and had at least 1 post-dose plasma concentration for MMF. The intensive PK analysis set consisted of a subset of participants in the Japanese cohort.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1: Japanese Participants | Part 1: Time to Reach Cmax (Tmax) of MMF-Intensive PK Analysis Set | 3.8 hours |
Secondary
Part 1: Tmax of HES-Intensive PK Analysis Set
Summarized data for Tmax at all timepoints is reported.
Time frame: Pre-dose and at 0.5,1,2,3,4,6, and 8 hours post-dose from Day 29 to Day 169
Population: PK analysis set included all participants who received at least 1 dose of study treatment and had at least 1 post-dose plasma concentration for HES. The intensive PK analysis set consisted of a subset of participants in the Japanese cohort.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1: Japanese Participants | Part 1: Tmax of HES-Intensive PK Analysis Set | 5.80 hours |