Trial Outcomes & Findings for A Study of Diroximel Fumarate (DRF) in Adult Participants From the Asia-Pacific Region With Relapsing Forms of Multiple Sclerosis (RMS) (NCT NCT05083923)

Last Updated: 2025-10-24

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

136 participants

Primary outcome timeframe

Baseline (Day 1) up to Week 24 (for prematurely discontinued participants, AEs were reported up to 2 weeks post discontinuation)

Results posted on

2025-10-24

Participant Flow

Participants took part in the multiple investigative sites from 18 November 2021 to 11 September 2024.

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).

Participant milestones

Participant milestones
Measure	Cohort 1: Japanese Participants Japanese participants received Diroximel Fumarate (DRF) 231 milligrams (mg), oral capsule, twice daily (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.	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.
Overall Study STARTED	52	50
Overall Study COMPLETED	47	40
Overall Study NOT COMPLETED	5	10

Reasons for withdrawal

Reasons for withdrawal
Measure	Cohort 1: Japanese Participants Japanese participants received Diroximel Fumarate (DRF) 231 milligrams (mg), oral capsule, twice daily (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.	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.
Overall Study Adverse Event	2	0
Overall Study Lack of Efficacy	1	3
Overall Study Withdrawal by Subject	2	6
Overall Study Reason Not Specified	0	1

Baseline Characteristics

A Study of Diroximel Fumarate (DRF) in Adult Participants From the Asia-Pacific Region With Relapsing Forms of Multiple Sclerosis (RMS)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cohort 1: Japanese Participants n=52 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.	Cohort 2: Chinese Participants n=50 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.	Total n=102 Participants Total of all reporting groups
Age, Continuous	40.1 years STANDARD_DEVIATION 9.56 • n=5 Participants	35.6 years STANDARD_DEVIATION 10.49 • n=7 Participants	37.9 years STANDARD_DEVIATION 10.23 • n=5 Participants
Sex: Female, Male Female	40 Participants n=5 Participants	42 Participants n=7 Participants	82 Participants n=5 Participants
Sex: Female, Male Male	12 Participants n=5 Participants	8 Participants n=7 Participants	20 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	52 Participants n=5 Participants	50 Participants n=7 Participants	102 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	52 Participants n=5 Participants	50 Participants n=7 Participants	102 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Cohort 1: Japanese Participants n=52 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.	Cohort 2: Chinese Participants n=50 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.
Part 1: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) TEAEs	50 Participants	45 Participants
Part 1: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) TESAEs	3 Participants	5 Participants

PRIMARY outcome

Timeframe: Baseline (Day 1) to Week 24

Population: Safety analysis set included all participants who had received at least 1 dose of study treatment.

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.

Outcome measures

Outcome measures
Measure	Cohort 1: Japanese Participants n=52 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.	Cohort 2: Chinese Participants n=50 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.
Part 1: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters Neutrophils <1.5 x 10^9/L	5 Participants	2 Participants
Part 1: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters Creatinine >=176.8 Micromole per Litre (umol/L)	0 Participants	0 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	1 Participants
Part 1: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters Lymphocytes <0.91 x 10^9/L	25 Participants	11 Participants
Part 1: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters Lymphocytes <0.8 x 10^9/L	15 Participants	3 Participants
Part 1: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters Lymphocytes <0.5 x 10^9/L	2 Participants	0 Participants
Part 1: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters Neutrophils<1 x 10^9/L	1 Participants	0 Participants
Part 1: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters Eosinophils >1.0 x 10^9/L	7 Participants	0 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	1 Participants
Part 1: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters Platelets <=75 x 10^9/L	0 Participants	0 Participants
Part 1: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters Platelets >=700 x 10^9/L	0 Participants	0 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	3 Participants
Part 1: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters Alanine Aminotransferase >5 x ULN	1 Participants	0 Participants
Part 1: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters Alanine Aminotransferase >10 x ULN	0 Participants	0 Participants
Part 1: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters Aspartate Aminotransferase >=3 x ULN	2 Participants	0 Participants
Part 1: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters Aspartate Aminotransferase >5 x ULN	0 Participants	0 Participants
Part 1: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters Aspartate Aminotransferase >10 x ULN	0 Participants	0 Participants
Part 1: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters Alkaline Phosphatase >3 x ULN	0 Participants	0 Participants
Part 1: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters Alkaline Phosphatase >5 x ULN	0 Participants	0 Participants
Part 1: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters Alkaline Phosphatase >10 x ULN	0 Participants	0 Participants
Part 1: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters Gamma Glutamyl Transferase >=3 x ULN	3 Participants	1 Participants
Part 1: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters Bilirubin >1.5 x ULN	0 Participants	1 Participants
Part 1: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters Bilirubin >2 x ULN	0 Participants	0 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	0 Participants
Part 1: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters Bicarbonate <15 mmol/L	0 Participants	0 Participants
Part 1: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters Bicarbonate >31 mmol/L	0 Participants	0 Participants
Part 1: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters Ketones >=4+	1 Participants	0 Participants
Part 1: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters Protein >=2+	1 Participants	0 Participants

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Cohort 1: Japanese Participants n=49 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.	Cohort 2: Chinese Participants n=48 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.
Part 1: Number of Participants With Abnormal Shift in 12-Lead Electrocardiogram (ECG) Values	5 Participants	3 Participants

PRIMARY outcome

Timeframe: Baseline (Day 1) to Week 24

Population: Safety analysis set included all participants who had received at least 1 dose of study treatment.

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.

Outcome measures

Outcome measures
Measure	Cohort 1: Japanese Participants n=52 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.	Cohort 2: Chinese Participants n=50 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.
Part 1: Number of Participants With Clinically Relevant Abnormalities in Vital Sign Parameters Respiratory Rate >20 breaths/min	8 Participants	0 Participants
Part 1: Number of Participants With Clinically Relevant Abnormalities in Vital Sign Parameters Temperature <36 degrees C	8 Participants	2 Participants
Part 1: Number of Participants With Clinically Relevant Abnormalities in Vital Sign Parameters Temperature >38 degrees C	1 Participants	0 Participants
Part 1: Number of Participants With Clinically Relevant Abnormalities in Vital Sign Parameters Pulse Rate <60 bpm	9 Participants	3 Participants
Part 1: Number of Participants With Clinically Relevant Abnormalities in Vital Sign Parameters Pulse Rate >100 bpm	4 Participants	2 Participants
Part 1: Number of Participants With Clinically Relevant Abnormalities in Vital Sign Parameters Systolic Blood Pressure <90 mmHg	4 Participants	1 Participants
Part 1: Number of Participants With Clinically Relevant Abnormalities in Vital Sign Parameters Systolic Blood Pressure >140 mmHg	2 Participants	1 Participants
Part 1: Number of Participants With Clinically Relevant Abnormalities in Vital Sign Parameters Systolic Blood Pressure >160 mmHg	0 Participants	1 Participants
Part 1: Number of Participants With Clinically Relevant Abnormalities in Vital Sign Parameters Diastolic Blood Pressure <50 mmHg	2 Participants	0 Participants
Part 1: Number of Participants With Clinically Relevant Abnormalities in Vital Sign Parameters Diastolic Blood Pressure >90 mmHg	13 Participants	4 Participants
Part 1: Number of Participants With Clinically Relevant Abnormalities in Vital Sign Parameters Diastolic Blood Pressure >100 mmHg	2 Participants	0 Participants
Part 1: Number of Participants With Clinically Relevant Abnormalities in Vital Sign Parameters Weight 7% or more increase from baseline	1 Participants	5 Participants
Part 1: Number of Participants With Clinically Relevant Abnormalities in Vital Sign Parameters Weight 7% or more decrease from baseline	3 Participants	2 Participants
Part 1: Number of Participants With Clinically Relevant Abnormalities in Vital Sign Parameters Respiratory Rate <12 breaths/min	3 Participants	0 Participants

PRIMARY outcome

Timeframe: Baseline (Day 1) to Week 24

Population: Safety analysis set included all participants who had received at least 1 dose of study treatment.

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.

Outcome measures

Outcome measures
Measure	Cohort 1: Japanese Participants n=52 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.	Cohort 2: Chinese Participants n=50 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.
Part 1: Number of Participants With Columbia Suicide Severity Rating Scale (C-SSRS) Events Suicidal Ideation	0 Participants	1 Participants
Part 1: Number of Participants With Columbia Suicide Severity Rating Scale (C-SSRS) Events Suicidal Behavior	0 Participants	0 Participants
Part 1: Number of Participants With Columbia Suicide Severity Rating Scale (C-SSRS) Events Non-suicidal Self-injurious Behavior	0 Participants	0 Participants

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Cohort 1: Japanese Participants n=52 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.	Cohort 2: Chinese Participants n=50 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.
Parts 1 and 2: Number of Participants With TEAEs and TESAEs TEAEs	52 Participants	47 Participants
Parts 1 and 2: Number of Participants With TEAEs and TESAEs TESAEs	6 Participants	6 Participants

PRIMARY outcome

Timeframe: Baseline (Day 1) to Week 48

Population: Safety analysis set included all participants who had received at least 1 dose of study treatment.

Outcome measures

Outcome measures
Measure	Cohort 1: Japanese Participants n=52 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.	Cohort 2: Chinese Participants n=50 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.
Part 2: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters Leukocytes <=2.8 x 10^9/L	6 Participants	3 Participants
Part 2: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters Lymphocytes <0.91 x 10^9/L	28 Participants	16 Participants
Part 2: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters Lymphocytes <0.8 x 10^9/L	20 Participants	11 Participants
Part 2: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters Lymphocytes <0.5 x 10^9/L	5 Participants	1 Participants
Part 2: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters Neutrophils <1.5 x 10^9/L	8 Participants	4 Participants
Part 2: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters Neutrophils <1 x 10^9/L	2 Participants	2 Participants
Part 2: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters Eosinophils >1.0 x 10^9/L	7 Participants	0 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	2 Participants
Part 2: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters Platelets <=75 x 10^9/L	0 Participants	0 Participants
Part 2: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters Platelets >=700 x 10^9/L	0 Participants	0 Participants
Part 2: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters Alanine Aminotransferase >=3 x ULN	7 Participants	4 Participants
Part 2: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters Alanine Aminotransferase >5 x ULN	1 Participants	0 Participants
Part 2: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters Alanine Aminotransferase >10 x ULN	0 Participants	0 Participants
Part 2: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters Aspartate Aminotransferase >=3 x ULN	2 Participants	0 Participants
Part 2: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters Aspartate Aminotransferase >5 x ULN	0 Participants	0 Participants
Part 2: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters Aspartate Aminotransferase >10 x ULN	0 Participants	0 Participants
Part 2: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters Alkaline Phosphatase >3 x ULN	0 Participants	0 Participants
Part 2: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters Alkaline Phosphatase >5 x ULN	0 Participants	0 Participants
Part 2: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters Alkaline Phosphatase >10 x ULN	0 Participants	0 Participants
Part 2: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters Gamma Glutamyl Transferase >=3 x ULN	4 Participants	2 Participants
Part 2: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters Bilirubin >1.5 x ULN	0 Participants	1 Participants
Part 2: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters Bilirubin >2 x ULN	0 Participants	0 Participants
Part 2: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters Urea Nitrogen >10.71 mmol/L	0 Participants	0 Participants
Part 2: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters Creatinine >=176.8 umol/L	0 Participants	0 Participants
Part 2: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters Bicarbonate <15 mmol/L	0 Participants	0 Participants
Part 2: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters Bicarbonate >31 mmol/L	0 Participants	0 Participants
Part 2: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters Ketones >=4+	1 Participants	0 Participants
Part 2: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters Protein >=2+	3 Participants	0 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Cohort 1: Japanese Participants n=49 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.	Cohort 2: Chinese Participants n=48 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.
Part 2: Number of Participants With Abnormal Shift in 12-Lead ECG Values	7 Participants	5 Participants

PRIMARY outcome

Timeframe: Baseline (Day 1) to Week 48

Population: Safety analysis set included all participants who had received at least 1 dose of study treatment.

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.

Outcome measures

Outcome measures
Measure	Cohort 1: Japanese Participants n=52 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.	Cohort 2: Chinese Participants n=50 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.
Part 2: Number of Participants With Clinically Relevant Abnormalities in Vital Sign Parameters Diastolic Blood Pressure >100 mmHg	4 Participants	0 Participants
Part 2: Number of Participants With Clinically Relevant Abnormalities in Vital Sign Parameters Respiratory Rate >20 breaths/min	13 Participants	1 Participants
Part 2: Number of Participants With Clinically Relevant Abnormalities in Vital Sign Parameters Temperature <36 degrees C	12 Participants	2 Participants
Part 2: Number of Participants With Clinically Relevant Abnormalities in Vital Sign Parameters Temperature >38 degrees C	1 Participants	0 Participants
Part 2: Number of Participants With Clinically Relevant Abnormalities in Vital Sign Parameters Pulse Rate <60 bpm	9 Participants	7 Participants
Part 2: Number of Participants With Clinically Relevant Abnormalities in Vital Sign Parameters Pulse Rate >100 bpm	6 Participants	3 Participants
Part 2: Number of Participants With Clinically Relevant Abnormalities in Vital Sign Parameters Systolic Blood Pressure <90 mmHg	7 Participants	2 Participants
Part 2: Number of Participants With Clinically Relevant Abnormalities in Vital Sign Parameters Systolic Blood Pressure >140 mmHg	3 Participants	1 Participants
Part 2: Number of Participants With Clinically Relevant Abnormalities in Vital Sign Parameters Systolic Blood Pressure >160 mmHg	0 Participants	1 Participants
Part 2: Number of Participants With Clinically Relevant Abnormalities in Vital Sign Parameters Diastolic Blood Pressure <50 mmHg	3 Participants	1 Participants
Part 2: Number of Participants With Clinically Relevant Abnormalities in Vital Sign Parameters Diastolic Blood Pressure >90 mmHg	14 Participants	5 Participants
Part 2: Number of Participants With Clinically Relevant Abnormalities in Vital Sign Parameters Weight 7% or more increase from baseline	3 Participants	6 Participants
Part 2: Number of Participants With Clinically Relevant Abnormalities in Vital Sign Parameters Weight 7% or more decrease from baseline	5 Participants	7 Participants
Part 2: Number of Participants With Clinically Relevant Abnormalities in Vital Sign Parameters Respiratory Rate <12 breaths/min	6 Participants	0 Participants

PRIMARY outcome

Timeframe: Baseline (Day 1) to Week 48

Population: Safety analysis set included all participants who had received at least 1 dose of study treatment.

Outcome measures

Outcome measures
Measure	Cohort 1: Japanese Participants n=52 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.	Cohort 2: Chinese Participants n=50 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.
Part 2: Number of Participants With C-SSRS Events Suicidal Ideation	0 Participants	2 Participants
Part 2: Number of Participants With C-SSRS Events Suicidal Behavior	0 Participants	0 Participants
Part 2: Number of Participants With C-SSRS Events Non-suicidal Self-injurious Behavior	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 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.

Summarized data for plasma concentration of MMF at all timepoints is reported.

Outcome measures

Outcome measures
Measure	Cohort 1: Japanese Participants n=7 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.	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.
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	—
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	—
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 73.60	—
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	—
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	—
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	—
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	—
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 outcome

Timeframe: 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.

Summarized data for plasma concentration of HES at all timepoints is reported.

Outcome measures

Outcome measures
Measure	Cohort 1: Japanese Participants n=7 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.	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.
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Cohort 1: Japanese Participants n=49 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.	Cohort 2: Chinese Participants n=48 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.
Part 1: Plasma Concentrations of MMF-Sparse PK Analysis Set Day 29 (Pre-dose)	0.1 ug/mL Geometric Coefficient of Variation 79.06	0.1 ug/mL Geometric Coefficient of Variation 144.66
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	0.8 ug/mL Geometric Coefficient of Variation 223.71
Part 1: Plasma Concentrations of MMF-Sparse PK Analysis Set Day 57 (Pre-dose)	0.1 ug/mL Geometric Coefficient of Variation 90.08	0.1 ug/mL Geometric Coefficient of Variation 91.21
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 234.80	1.1 ug/mL Geometric Coefficient of Variation 131.05

SECONDARY outcome

Timeframe: Pre-dose and 2 to 3 hours post-dose on Day 29 and Day 57

Outcome measures

Outcome measures
Measure	Cohort 1: Japanese Participants n=49 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.	Cohort 2: Chinese Participants n=48 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.
Part 1: Plasma Concentrations of HES-Sparse PK Analysis Set Day 29 (Pre-dose)	8.2 ug/mL Geometric Coefficient of Variation 28.13	8.0 ug/mL Geometric Coefficient of Variation 32.54
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	9.7 ug/mL Geometric Coefficient of Variation 38.05
Part 1: Plasma Concentrations of HES-Sparse PK Analysis Set Day 57 (Pre-dose)	8.4 ug/mL Geometric Coefficient of Variation 40.45	8.3 ug/mL Geometric Coefficient of Variation 34.97
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	9.7 ug/mL Geometric Coefficient of Variation 31.27

SECONDARY outcome

Timeframe: 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.

Summarized data for Cmax at all timepoints is reported.

Outcome measures

Outcome measures
Measure	Cohort 1: Japanese Participants n=7 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.	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.
Part 1: Maximum Observed Concentration (Cmax) of MMF-Intensive PK Analysis Set	1.2 ug/mL Geometric Coefficient of Variation 56.85	—

SECONDARY outcome

Timeframe: 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.

Summarized data for Cmax at all timepoints is reported.

Outcome measures

Outcome measures
Measure	Cohort 1: Japanese Participants n=7 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.	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.
Part 1: Cmax of HES-Intensive PK Analysis Set	11.6 ug/mL Geometric Coefficient of Variation 26.49	—

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Cohort 1: Japanese Participants n=7 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.	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.
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 hourmicrogram per milliliter (hug/mL) Geometric Coefficient of Variation 36.34	—

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Cohort 1: Japanese Participants n=7 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.	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.
Part 1: AUClast of HES-Intensive PK Analysis Set	75.3 h*ug/mL Geometric Coefficient of Variation 29.31	—

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Cohort 1: Japanese Participants n=7 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.	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.
Part 1: Time to Reach Cmax (Tmax) of MMF-Intensive PK Analysis Set	3.8 hours Interval 2.0 to 6.0	—

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Cohort 1: Japanese Participants n=7 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.	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.
Part 1: Tmax of HES-Intensive PK Analysis Set	5.80 hours Interval 0.5 to 7.9	—

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Cohort 1: Japanese Participants n=7 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.	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.
Part 1: Elimination Half-Life (t½) of MMF-Intensive PK Analysis Set	1.3 hours Interval 0.8 to 1.3	—

Adverse Events

Cohort 1: Japanese Participants

Serious events: 6 serious events

Other events: 50 other events

Deaths: 0 deaths

Cohort 2: Chinese Participants

Serious events: 6 serious events

Other events: 42 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Cohort 1: Japanese Participants n=52 participants at risk 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.	Cohort 2: Chinese Participants n=50 participants at risk 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.
Blood and lymphatic system disorders Iron deficiency anaemia	0.00% 0/52 • From Day 1 up to the end of the study (up to Week 50) Safety analysis set included all participants who had received at least 1 dose of study treatment. TEAEs and TESAEs for participants were collected cumulatively for Parts 1 and 2.	2.0% 1/50 • From Day 1 up to the end of the study (up to Week 50) Safety analysis set included all participants who had received at least 1 dose of study treatment. TEAEs and TESAEs for participants were collected cumulatively for Parts 1 and 2.
Infections and infestations Staphylococcal bacteraemia	1.9% 1/52 • From Day 1 up to the end of the study (up to Week 50) Safety analysis set included all participants who had received at least 1 dose of study treatment. TEAEs and TESAEs for participants were collected cumulatively for Parts 1 and 2.	0.00% 0/50 • From Day 1 up to the end of the study (up to Week 50) Safety analysis set included all participants who had received at least 1 dose of study treatment. TEAEs and TESAEs for participants were collected cumulatively for Parts 1 and 2.
Injury, poisoning and procedural complications Fall	1.9% 1/52 • From Day 1 up to the end of the study (up to Week 50) Safety analysis set included all participants who had received at least 1 dose of study treatment. TEAEs and TESAEs for participants were collected cumulatively for Parts 1 and 2.	0.00% 0/50 • From Day 1 up to the end of the study (up to Week 50) Safety analysis set included all participants who had received at least 1 dose of study treatment. TEAEs and TESAEs for participants were collected cumulatively for Parts 1 and 2.
Injury, poisoning and procedural complications Humerus fracture	1.9% 1/52 • From Day 1 up to the end of the study (up to Week 50) Safety analysis set included all participants who had received at least 1 dose of study treatment. TEAEs and TESAEs for participants were collected cumulatively for Parts 1 and 2.	0.00% 0/50 • From Day 1 up to the end of the study (up to Week 50) Safety analysis set included all participants who had received at least 1 dose of study treatment. TEAEs and TESAEs for participants were collected cumulatively for Parts 1 and 2.
Musculoskeletal and connective tissue disorders Foot deformity	1.9% 1/52 • From Day 1 up to the end of the study (up to Week 50) Safety analysis set included all participants who had received at least 1 dose of study treatment. TEAEs and TESAEs for participants were collected cumulatively for Parts 1 and 2.	0.00% 0/50 • From Day 1 up to the end of the study (up to Week 50) Safety analysis set included all participants who had received at least 1 dose of study treatment. TEAEs and TESAEs for participants were collected cumulatively for Parts 1 and 2.
Musculoskeletal and connective tissue disorders Osteoarthritis	1.9% 1/52 • From Day 1 up to the end of the study (up to Week 50) Safety analysis set included all participants who had received at least 1 dose of study treatment. TEAEs and TESAEs for participants were collected cumulatively for Parts 1 and 2.	0.00% 0/50 • From Day 1 up to the end of the study (up to Week 50) Safety analysis set included all participants who had received at least 1 dose of study treatment. TEAEs and TESAEs for participants were collected cumulatively for Parts 1 and 2.
Nervous system disorders Demyelination	0.00% 0/52 • From Day 1 up to the end of the study (up to Week 50) Safety analysis set included all participants who had received at least 1 dose of study treatment. TEAEs and TESAEs for participants were collected cumulatively for Parts 1 and 2.	2.0% 1/50 • From Day 1 up to the end of the study (up to Week 50) Safety analysis set included all participants who had received at least 1 dose of study treatment. TEAEs and TESAEs for participants were collected cumulatively for Parts 1 and 2.
Nervous system disorders Multiple sclerosis relapse	5.8% 3/52 • From Day 1 up to the end of the study (up to Week 50) Safety analysis set included all participants who had received at least 1 dose of study treatment. TEAEs and TESAEs for participants were collected cumulatively for Parts 1 and 2.	6.0% 3/50 • From Day 1 up to the end of the study (up to Week 50) Safety analysis set included all participants who had received at least 1 dose of study treatment. TEAEs and TESAEs for participants were collected cumulatively for Parts 1 and 2.
Nervous system disorders Relapsing-remitting multiple sclerosis	0.00% 0/52 • From Day 1 up to the end of the study (up to Week 50) Safety analysis set included all participants who had received at least 1 dose of study treatment. TEAEs and TESAEs for participants were collected cumulatively for Parts 1 and 2.	2.0% 1/50 • From Day 1 up to the end of the study (up to Week 50) Safety analysis set included all participants who had received at least 1 dose of study treatment. TEAEs and TESAEs for participants were collected cumulatively for Parts 1 and 2.

Other adverse events

Additional Information

US Biogen Clinical Trial Center

Biogen

Phone: 866-633-4636

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Our agreement is subject to confidentiality but generally the PI can publish, for noncommercial purposes only, results and methods of the trial, but no other Sponsor Confidential Information. PI must give Sponsor no less than 60 days to review any manuscript for a proposed publication and must delay publication for up to an additional 90 days thereafter if Sponsor needs to file any patent application to protect any of Sponsor's intellectual property contained in the proposed publication.
Publication restrictions are in place

Restriction type: OTHER