Trial Outcomes & Findings for A Study of ALKS 8700 in Adults With Relapsing Remitting Multiple Sclerosis (MS) EVOLVE-MS-1 (NCT NCT02634307)

NCT ID: NCT02634307

Last Updated: 2022-07-26

Results Overview

An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal assessment such as an abnormal laboratory value), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. TEAE is any AE that start or worsen on or after the date of first dose of study treatment. An SAE is any untoward medical occurrence that at any dose, results in death; in the view of the investigator places the participant at immediate risk of death; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; results in a congenital anomaly/birth defect; is a medically important event.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 1057 participants
• Primary outcome timeframe: From first dose to two weeks after last dose of study drug (Up to 98 weeks)
• Results posted on: 2022-07-26

Participant Flow

Participants were enrolled at investigational sites in North America and Europe from 10 December 2015 to 11 November 2021.

De Novo (who had not participated in any prior study of ALKS 8700) and Rollover participants (who had completed the Treatment Period of Study ALK8700-A302) were enrolled in this study.

Participant milestones

Measure	De Novo Participants who had not received ALKS 8700 or dimethyl fumarate (DMF) were administered ALKS 8700 231 milligrams (mg) capsules orally, twice daily (BID) on Days 1 to 7 followed by ALKS 8700 462 mg (as two 231 mg capsules) orally, BID from Day 8 up to Week 96.	Rollover: ALKS 8700 Participants rolled over from study ALK870-A302 who had already received ALKS 8700 prior to Day 1 were administered ALKS 8700 462 mg (as two 231 mg capsules) orally, BID from Day 1 up to Week 96.	Rollover: DMF Participants rolled over from study ALK870-A302 who had already received DMF prior to Day 1 were administered ALKS 8700 462 mg (as two 231 mg capsules) orally, BID from Day 1 up to Week 96.
Overall Study STARTED	593	239	225
Overall Study Safety Population	593	239	225
Overall Study Full Analysis Set (FAS) Population	582	235	224
Overall Study COMPLETED	468	168	164
Overall Study NOT COMPLETED	125	71	61

Reasons for withdrawal

Measure	De Novo Participants who had not received ALKS 8700 or dimethyl fumarate (DMF) were administered ALKS 8700 231 milligrams (mg) capsules orally, twice daily (BID) on Days 1 to 7 followed by ALKS 8700 462 mg (as two 231 mg capsules) orally, BID from Day 8 up to Week 96.	Rollover: ALKS 8700 Participants rolled over from study ALK870-A302 who had already received ALKS 8700 prior to Day 1 were administered ALKS 8700 462 mg (as two 231 mg capsules) orally, BID from Day 1 up to Week 96.	Rollover: DMF Participants rolled over from study ALK870-A302 who had already received DMF prior to Day 1 were administered ALKS 8700 462 mg (as two 231 mg capsules) orally, BID from Day 1 up to Week 96.
Overall Study Adverse Event	50	24	14
Overall Study Lost to Follow-up	21	5	6
Overall Study Pregnancy	5	1	3
Overall Study Withdrawal by Subject	38	24	18
Overall Study Non-Compliance with Study Drug	0	2	2
Overall Study Lack of Efficacy	1	5	3
Overall Study Physician Decision	7	5	5
Overall Study Reason not Specified	3	5	10

Baseline Characteristics

A Study of ALKS 8700 in Adults With Relapsing Remitting Multiple Sclerosis (MS) EVOLVE-MS-1

Baseline characteristics by cohort

Measure	De Novo n=593 Participants Participants who had not received ALKS 8700 or DMF were administered ALKS 8700 231 mg capsules orally, BID on Days 1 to 7 followed by ALKS 8700 462 mg (as two 231 mg capsules) orally, BID from Day 8 up to Week 96.	Rollover: ALKS 8700 n=239 Participants Participants rolled over from study ALK870-A302 who had already received ALKS 8700 prior to Day 1 were administered ALKS 8700 462 mg (as two 231 mg capsules) orally, BID from Day 1 up to Week 96.	Rollover: DMF n=225 Participants Participants rolled over from study ALK870-A302 who had already received DMF prior to Day 1 were administered ALKS 8700 462 mg (as two 231 mg capsules) orally, BID from Day 1 up to Week 96.	Total n=1057 Participants Total of all reporting groups
Age, Continuous	41.5 years STANDARD_DEVIATION 10.96 • n=5 Participants	44.0 years STANDARD_DEVIATION 11.00 • n=7 Participants	43.7 years STANDARD_DEVIATION 9.77 • n=5 Participants	42.5 years STANDARD_DEVIATION 10.78 • n=4 Participants
Sex: Female, Male Female	427 Participants n=5 Participants	165 Participants n=7 Participants	170 Participants n=5 Participants	762 Participants n=4 Participants
Sex: Female, Male Male	166 Participants n=5 Participants	74 Participants n=7 Participants	55 Participants n=5 Participants	295 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	25 Participants n=5 Participants	5 Participants n=7 Participants	10 Participants n=5 Participants	40 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	568 Participants n=5 Participants	234 Participants n=7 Participants	215 Participants n=5 Participants	1017 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race/Ethnicity, Customized Race · White	547 Participants n=5 Participants	220 Participants n=7 Participants	205 Participants n=5 Participants	972 Participants n=4 Participants
Race/Ethnicity, Customized Race · Black or African American	37 Participants n=5 Participants	19 Participants n=7 Participants	16 Participants n=5 Participants	72 Participants n=4 Participants
Race/Ethnicity, Customized Race · Asian	4 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	5 Participants n=4 Participants
Race/Ethnicity, Customized Race · Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants
Race/Ethnicity, Customized Race · Other	5 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants	7 Participants n=4 Participants

PRIMARY outcome

Timeframe: From first dose to two weeks after last dose of study drug (Up to 98 weeks)

Population: Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.

An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal assessment such as an abnormal laboratory value), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. TEAE is any AE that start or worsen on or after the date of first dose of study treatment. An SAE is any untoward medical occurrence that at any dose, results in death; in the view of the investigator places the participant at immediate risk of death; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; results in a congenital anomaly/birth defect; is a medically important event.

Outcome measures

Measure	De Novo n=593 Participants Participants who had not received ALKS 8700 or DMF were administered ALKS 8700 231 mg capsules orally, BID on Days 1 to 7 followed by ALKS 8700 462 mg (as two 231 mg capsules) orally, BID from Day 8 up to Week 96.	Rollover: ALKS 8700 n=239 Participants Participants rolled over from study ALK870-A302 who had already received ALKS 8700 prior to Day 1 were administered ALKS 8700 462 mg (as two 231 mg capsules) orally, BID from Day 1 up to Week 96.	Rollover: DMF n=225 Participants Participants rolled over from study ALK870-A302 who had already received DMF prior to Day 1 were administered ALKS 8700 462 mg (as two 231 mg capsules) orally, BID from Day 1 up to Week 96.
Number of Participants Experiencing Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) TEAEs	519 Participants	212 Participants	207 Participants
Number of Participants Experiencing Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) SAEs	69 Participants	29 Participants	25 Participants

PRIMARY outcome

Timeframe: From first dose to two weeks after last dose of study drug (Up to 98 weeks)

Population: Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700. 'Number of Participants Analyzed' signifies number of participants analyzed for this outcome measure. 'Number Analyzed' signifies number of participants analyzed for the specified measurement.

Vital sign measurements included heart rate (low: <=50 beats per minute [bpm] and decrease >=15 bpm; High: >=120 bpm and increase >=15 bpm), systolic blood pressure (BP) (low: <=90 millimeters of mercury [mmHg] and decrease >=20 mmHg; High: >=180 mmHg and increase >=20 mmHg) and diastolic BP (low: <=50 mmHg and decrease >=15 mmHg; High: >=105 mmHg and increase >=15 mmHg).

Outcome measures

Measure	De Novo n=582 Participants Participants who had not received ALKS 8700 or DMF were administered ALKS 8700 231 mg capsules orally, BID on Days 1 to 7 followed by ALKS 8700 462 mg (as two 231 mg capsules) orally, BID from Day 8 up to Week 96.	Rollover: ALKS 8700 n=238 Participants Participants rolled over from study ALK870-A302 who had already received ALKS 8700 prior to Day 1 were administered ALKS 8700 462 mg (as two 231 mg capsules) orally, BID from Day 1 up to Week 96.	Rollover: DMF n=225 Participants Participants rolled over from study ALK870-A302 who had already received DMF prior to Day 1 were administered ALKS 8700 462 mg (as two 231 mg capsules) orally, BID from Day 1 up to Week 96.
Number of Participants With Potentially Clinically Significant Vital Sign Abnormalities Heart Rate (Low: <=50 bpm and decrease >=15 bpm)	5 Participants	1 Participants	2 Participants
Number of Participants With Potentially Clinically Significant Vital Sign Abnormalities Systolic BP (Low: <=90 mmHg and decrease >=20 mmHg)	15 Participants	4 Participants	2 Participants
Number of Participants With Potentially Clinically Significant Vital Sign Abnormalities Systolic BP (High: >=180 mmHg and increase >=20 mmHg)	3 Participants	2 Participants	1 Participants
Number of Participants With Potentially Clinically Significant Vital Sign Abnormalities Diastolic BP (Low: <=50 mmHg and decrease >=15 mmHg)	10 Participants	2 Participants	4 Participants
Number of Participants With Potentially Clinically Significant Vital Sign Abnormalities Diastolic BP (High: >=105 mmHg and increase >=15 mmHg)	6 Participants	2 Participants	2 Participants
Number of Participants With Potentially Clinically Significant Vital Sign Abnormalities Heart Rate (High: >=120 bpm and increase >=15 bpm)	1 Participants	1 Participants	2 Participants

PRIMARY outcome

Timeframe: From first dose to two weeks after last dose of study drug (Up to 98 weeks)

Population: Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700. 'Number of Participants Analyzed' signifies number of participants analyzed in this outcome measure.

Potentially clinically significant QTcF values (>450 to <=480 millisecond [msec], >480 to <=500 msec) at any post-baseline visit during treatment period were reported.

Outcome measures

Measure	De Novo n=576 Participants Participants who had not received ALKS 8700 or DMF were administered ALKS 8700 231 mg capsules orally, BID on Days 1 to 7 followed by ALKS 8700 462 mg (as two 231 mg capsules) orally, BID from Day 8 up to Week 96.	Rollover: ALKS 8700 n=237 Participants Participants rolled over from study ALK870-A302 who had already received ALKS 8700 prior to Day 1 were administered ALKS 8700 462 mg (as two 231 mg capsules) orally, BID from Day 1 up to Week 96.	Rollover: DMF n=223 Participants Participants rolled over from study ALK870-A302 who had already received DMF prior to Day 1 were administered ALKS 8700 462 mg (as two 231 mg capsules) orally, BID from Day 1 up to Week 96.
Number of Participants With Potentially Clinically Significant 12-Lead Electrocardiogram (ECG) Abnormalities >450 - <=480 msec	15 Participants	5 Participants	6 Participants
Number of Participants With Potentially Clinically Significant 12-Lead Electrocardiogram (ECG) Abnormalities >480 - <=500 msec	0 Participants	0 Participants	1 Participants

PRIMARY outcome

Timeframe: Up to 98 weeks

Population: Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.

The C-SSRS is a clinician-administered instrument that systematically assess suicidal ideation and behavior rating scale. It rates an individual's degree of suicidal ideation (SI) on a scale, ranging from "wish to be dead" to "active suicidal ideation with specific plan and intent." The scale identifies SI severity and intensity, which may be indicative of an individual's intent to commit suicide. C-SSRS SI severity subscale ranges from 0 (no SI) to 5 (active SI with plan and intent). The scale identifies specific behaviors ranging from "preparatory acts or behavior" to "suicide" which may be indicative of an individual's intent to complete suicide.

Outcome measures

Measure	De Novo n=593 Participants Participants who had not received ALKS 8700 or DMF were administered ALKS 8700 231 mg capsules orally, BID on Days 1 to 7 followed by ALKS 8700 462 mg (as two 231 mg capsules) orally, BID from Day 8 up to Week 96.	Rollover: ALKS 8700 n=239 Participants Participants rolled over from study ALK870-A302 who had already received ALKS 8700 prior to Day 1 were administered ALKS 8700 462 mg (as two 231 mg capsules) orally, BID from Day 1 up to Week 96.	Rollover: DMF n=225 Participants Participants rolled over from study ALK870-A302 who had already received DMF prior to Day 1 were administered ALKS 8700 462 mg (as two 231 mg capsules) orally, BID from Day 1 up to Week 96.
Number of Participants With Columbia Suicide Severity Rating Scale (C-SSRS) Score at Any Post-Baseline Visit Suicidal Behavior: Preparatory acts or behavior	0 Participants	0 Participants	0 Participants
Number of Participants With Columbia Suicide Severity Rating Scale (C-SSRS) Score at Any Post-Baseline Visit Suicidal Behavior: Aborted attempt	0 Participants	0 Participants	0 Participants
Number of Participants With Columbia Suicide Severity Rating Scale (C-SSRS) Score at Any Post-Baseline Visit Suicidal Behavior: Interrupted attempt	0 Participants	0 Participants	0 Participants
Number of Participants With Columbia Suicide Severity Rating Scale (C-SSRS) Score at Any Post-Baseline Visit Suicidal Behavior: Actual attempt	1 Participants	0 Participants	0 Participants
Number of Participants With Columbia Suicide Severity Rating Scale (C-SSRS) Score at Any Post-Baseline Visit Suicidal Behavior: Completed suicide	0 Participants	0 Participants	0 Participants
Number of Participants With Columbia Suicide Severity Rating Scale (C-SSRS) Score at Any Post-Baseline Visit Suicidal Ideation: Wish to be dead	12 Participants	2 Participants	4 Participants
Number of Participants With Columbia Suicide Severity Rating Scale (C-SSRS) Score at Any Post-Baseline Visit Suicidal Ideation: Non-specific active suicidal thoughts	8 Participants	2 Participants	2 Participants
Number of Participants With Columbia Suicide Severity Rating Scale (C-SSRS) Score at Any Post-Baseline Visit Suicidal Ideation: Active ideation without intention to act	2 Participants	0 Participants	1 Participants
Number of Participants With Columbia Suicide Severity Rating Scale (C-SSRS) Score at Any Post-Baseline Visit Suicidal Ideation: Active ideation with some intent to act without a plan	1 Participants	0 Participants	0 Participants
Number of Participants With Columbia Suicide Severity Rating Scale (C-SSRS) Score at Any Post-Baseline Visit Suicidal Ideation: Active ideation with a specific plan and intent	1 Participants	0 Participants	0 Participants
Number of Participants With Columbia Suicide Severity Rating Scale (C-SSRS) Score at Any Post-Baseline Visit Non-Suicidal Self-Injurious Behavior	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: From first dose to two weeks after last dose of study drug (Up to 98 weeks)

Population: Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700. 'Number of Participants Analyzed' signifies number of participants analyzed for this outcome measure. 'Number Analyzed' signifies number of participants analyzed for the specified measurement.

Laboratory assessments included hematology, biochemistry, and urinalysis. Abnormality criteria: >=3xupper limit of normal (ULN) in alanine aminotransferase, aspartate aminotransferase; In millimoles per liter (mmol/L) [bicarbonate<15/>31, chloride<=90, potassium<3/>5.5, sodium<130/>150]; In mg per decilitre(mg/dL) {total bilirubin>=2.0, calcium<8.2/>12, total cholesterol>300, creatinine>=2.0, glucose<50/>200, cholesterol: High density lipoprotein (HDL)<=30, low density lipoprotein (LDL)>=160, triglycerides>=120 [female(F)]/>=160 [male(M)], urate>9/>8(F), blood urea nitrogen>30}; >3xULN in creatine kinase, lactate dehydrogenase; Hematocrit <=32(F)/<=37(M) percentage(%),3 point decrease from baseline; Hemoglobin<=9.5(F)/<=11.5(M)g/dL; Lymphocytes<0.5x10^9/L; In 10^3/microliter(uL) [Eosinophils>1; Absolute neutrophils<1.5; Platelets<75.1/>=700; Leukocytes<=2.8/>=16]; Albumin/creatinine>200g/kilograms(kg); Beta-2 microglobulin >0.3milligrams/liter(mg/L); Glucose/protein at least 2+.

Outcome measures

Measure	De Novo n=582 Participants Participants who had not received ALKS 8700 or DMF were administered ALKS 8700 231 mg capsules orally, BID on Days 1 to 7 followed by ALKS 8700 462 mg (as two 231 mg capsules) orally, BID from Day 8 up to Week 96.	Rollover: ALKS 8700 n=238 Participants Participants rolled over from study ALK870-A302 who had already received ALKS 8700 prior to Day 1 were administered ALKS 8700 462 mg (as two 231 mg capsules) orally, BID from Day 1 up to Week 96.	Rollover: DMF n=225 Participants Participants rolled over from study ALK870-A302 who had already received DMF prior to Day 1 were administered ALKS 8700 462 mg (as two 231 mg capsules) orally, BID from Day 1 up to Week 96.
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities Alanine Aminotransferase (U/L) >=3 x ULN	13 Participants	6 Participants	1 Participants
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities Aspartate Aminotransferase (U/L) >=3 x ULN	8 Participants	3 Participants	1 Participants
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities Bicarbonate <15 mmol/L	3 Participants	0 Participants	0 Participants
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities Bicarbonate >31 mmol/L	13 Participants	1 Participants	3 Participants
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities Bilirubin, Total >=2.0 mg/dL	2 Participants	1 Participants	0 Participants
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities Calcium <8.2 mg/dL	2 Participants	0 Participants	0 Participants
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities Calcium >12 mg/dL	0 Participants	1 Participants	0 Participants
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities Cholesterol, Total >300 mg/dL	23 Participants	8 Participants	8 Participants
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities Creatine Kinase (U/L) >3 x ULN	26 Participants	11 Participants	8 Participants
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities Chloride <=90 mmol/L	1 Participants	0 Participants	0 Participants
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities Creatinine >=2.0 mg/dL	1 Participants	0 Participants	2 Participants
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities Glucose <50 mg/dL	4 Participants	6 Participants	4 Participants
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities Glucose >200 mg/dL	6 Participants	5 Participants	4 Participants
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities HDL Cholesterol <=30 mg/dL	13 Participants	6 Participants	3 Participants
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities Potassium <3 mmol/L	1 Participants	0 Participants	0 Participants
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities Potassium >5.5 mmol/L	39 Participants	8 Participants	16 Participants
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities Lactate Dehydrogenase (U/L) >3 x ULN	1 Participants	0 Participants	0 Participants
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities LDL Cholesterol >=160 mg/dL	69 Participants	27 Participants	29 Participants
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities Sodium <130 mmol/L	1 Participants	0 Participants	0 Participants
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities Sodium >150 mmol/L	3 Participants	0 Participants	0 Participants
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities Triglycerides >=120 mg/dL (Female)	123 Participants	45 Participants	61 Participants
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities Urate >8 mg/dL (Female)	8 Participants	3 Participants	4 Participants
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities Blood Urea Nitrogen >30 mg/dL	5 Participants	3 Participants	2 Participants
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities Eosinophils >1x10^3/uL	8 Participants	3 Participants	1 Participants
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities Hematocrit <=32% and 3 point decrease from baseline (Female)	18 Participants	5 Participants	8 Participants
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities Hematocrit <=37% and 3 point decrease from baseline (Male)	6 Participants	4 Participants	3 Participants
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities Hemoglobin <=9.5 g/dL (Female)	5 Participants	1 Participants	3 Participants
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities Hemoglobin <=11.5 g/dL (Male)	2 Participants	1 Participants	0 Participants
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities Lymphocytes <0.5x10^9/L	47 Participants	25 Participants	24 Participants
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities Neutrophils, Absolute <1.5x10^3/uL	39 Participants	10 Participants	13 Participants
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities Platelets <75.1x10^3/uL	2 Participants	0 Participants	1 Participants
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities Platelets >=700x10^3/uL	0 Participants	0 Participants	0 Participants
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities Leukocytes <=2.8x10^3/uL	45 Participants	17 Participants	15 Participants
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities Leukocytes >=16x10^3/uL	4 Participants	5 Participants	5 Participants
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities Albumin/Creatinine >200 g/kg	15 Participants	8 Participants	5 Participants
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities Beta-2 Microglobulin >0.300 mg/L	95 Participants	32 Participants	31 Participants
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities Glucose at least 2+	10 Participants	4 Participants	3 Participants
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities Protein at least 2+	15 Participants	4 Participants	9 Participants
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities Triglycerides >=160 mg/dL (Male)	54 Participants	32 Participants	24 Participants
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities Urate >9 mg/dL	10 Participants	5 Participants	2 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 96 weeks

Population: Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.

Relapse was defined as new or recurrent neurologic symptoms, not associated with fever or infection, lasting for at least 24 hours, accompanied by one or more of the following: New objective neurological findings upon examination by the treating neurologist that are functionally consistent with findings on the Expanded Disability Status Scale [EDSS] (performed within 7 days of onset of symptoms) with an increase over the prior visit of ≥ 0.5 for the total score, an increase of ≥ 2 in 1 functional system (FS), except bladder/cognitive changes, and/or, an increase of ≥ 1 in 2 FS, except bladder/cognitive changes. The relapse rate for an individual participant was calculated as the number of relapses for that participant divided by the number of participant-years followed. The ARR for each enrollment group was calculated as the total number of relapses experienced in the group divided by the total number of participant-years on study.

Outcome measures

Measure	De Novo n=593 Participants Participants who had not received ALKS 8700 or DMF were administered ALKS 8700 231 mg capsules orally, BID on Days 1 to 7 followed by ALKS 8700 462 mg (as two 231 mg capsules) orally, BID from Day 8 up to Week 96.	Rollover: ALKS 8700 n=239 Participants Participants rolled over from study ALK870-A302 who had already received ALKS 8700 prior to Day 1 were administered ALKS 8700 462 mg (as two 231 mg capsules) orally, BID from Day 1 up to Week 96.	Rollover: DMF n=225 Participants Participants rolled over from study ALK870-A302 who had already received DMF prior to Day 1 were administered ALKS 8700 462 mg (as two 231 mg capsules) orally, BID from Day 1 up to Week 96.
Annualized Relapse Rate (ARR)	0.14 relapses per participant year	0.11 relapses per participant year	0.13 relapses per participant year

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 96 weeks

Population: Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.

Relapse was defined as new or recurrent neurologic symptoms, not associated with fever or infection, lasting for at least 24 hours, accompanied by one or more of the following: New objective neurological findings upon examination by the treating neurologist that are functionally consistent with findings on the EDSS (performed within 7 days of onset of symptoms) with an increase over the prior visit of ≥ 0.5 for the total score, an increase of ≥ 2 in 1 FS, except bladder/cognitive changes, and/or, an increase of ≥ 1 in 2 FS, except bladder/cognitive changes.

Outcome measures

Measure	De Novo n=593 Participants Participants who had not received ALKS 8700 or DMF were administered ALKS 8700 231 mg capsules orally, BID on Days 1 to 7 followed by ALKS 8700 462 mg (as two 231 mg capsules) orally, BID from Day 8 up to Week 96.	Rollover: ALKS 8700 n=239 Participants Participants rolled over from study ALK870-A302 who had already received ALKS 8700 prior to Day 1 were administered ALKS 8700 462 mg (as two 231 mg capsules) orally, BID from Day 1 up to Week 96.	Rollover: DMF n=225 Participants Participants rolled over from study ALK870-A302 who had already received DMF prior to Day 1 were administered ALKS 8700 462 mg (as two 231 mg capsules) orally, BID from Day 1 up to Week 96.
Percentage of Participants With Multiple Sclerosis (MS) Relapse	17.66 percentage of participants	16.66 percentage of participants	18.30 percentage of participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline up to Week 96

Population: FAS included all participants who received at least one dose of ALKS 8700 and had at least one post-baseline efficacy assessment. 'Number Analyzed' signifies number of participants analyzed for this outcome measure at the specified timepoint.

The EDSS is used to measure and evaluate MS participants' level of functioning. The EDSS provides a total score on a scale that ranges from 0 to 10. The first levels 1.0 to 4.5 refer to people with a high degree of ambulatory ability and the subsequent levels 5.0 to 9.5 refer to the loss of ambulatory ability. The range of main categories include (0) = normal neurologic examination; to (5) = ambulatory without aid or rest for 200 meters; disability severe enough to impair full daily activities; to (10) = death due to MS. Higher scores indicate more disability. Positive change from baseline indicates more disability.

Outcome measures

Measure	De Novo n=582 Participants Participants who had not received ALKS 8700 or DMF were administered ALKS 8700 231 mg capsules orally, BID on Days 1 to 7 followed by ALKS 8700 462 mg (as two 231 mg capsules) orally, BID from Day 8 up to Week 96.	Rollover: ALKS 8700 n=235 Participants Participants rolled over from study ALK870-A302 who had already received ALKS 8700 prior to Day 1 were administered ALKS 8700 462 mg (as two 231 mg capsules) orally, BID from Day 1 up to Week 96.	Rollover: DMF n=224 Participants Participants rolled over from study ALK870-A302 who had already received DMF prior to Day 1 were administered ALKS 8700 462 mg (as two 231 mg capsules) orally, BID from Day 1 up to Week 96.
Change From Baseline in Expanded Disability Status Scale (EDSS) Score Change From Baseline at Week 12	-0.01 score on a scale Standard Deviation 0.490	-0.03 score on a scale Standard Deviation 0.548	0.05 score on a scale Standard Deviation 0.557
Change From Baseline in Expanded Disability Status Scale (EDSS) Score Change From Baseline at Week 24	0.00 score on a scale Standard Deviation 0.518	-0.02 score on a scale Standard Deviation 0.603	-0.01 score on a scale Standard Deviation 0.696
Change From Baseline in Expanded Disability Status Scale (EDSS) Score Change From Baseline at Week 36	0.01 score on a scale Standard Deviation 0.558	-0.01 score on a scale Standard Deviation 0.597	-0.03 score on a scale Standard Deviation 0.733
Change From Baseline in Expanded Disability Status Scale (EDSS) Score Change From Baseline at Week 48	0.03 score on a scale Standard Deviation 0.614	-0.01 score on a scale Standard Deviation 0.579	0.00 score on a scale Standard Deviation 0.702
Change From Baseline in Expanded Disability Status Scale (EDSS) Score Change From Baseline at Week 60	0.04 score on a scale Standard Deviation 0.617	-0.02 score on a scale Standard Deviation 0.643	-0.02 score on a scale Standard Deviation 0.633
Change From Baseline in Expanded Disability Status Scale (EDSS) Score Change From Baseline at Week 72	0.05 score on a scale Standard Deviation 0.617	-0.04 score on a scale Standard Deviation 0.639	0.08 score on a scale Standard Deviation 0.713
Change From Baseline in Expanded Disability Status Scale (EDSS) Score Change From Baseline at Week 96	0.07 score on a scale Standard Deviation 0.631	-0.01 score on a scale Standard Deviation 0.775	0.03 score on a scale Standard Deviation 0.735
Change From Baseline in Expanded Disability Status Scale (EDSS) Score Baseline	2.71 score on a scale Standard Deviation 1.457	2.64 score on a scale Standard Deviation 1.481	2.71 score on a scale Standard Deviation 1.445
Change From Baseline in Expanded Disability Status Scale (EDSS) Score Change From Baseline at Week 84	0.07 score on a scale Standard Deviation 0.641	-0.03 score on a scale Standard Deviation 0.616	-0.02 score on a scale Standard Deviation 0.759

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline up to Week 96

Population: FAS included all participants who received at least one dose of ALKS 8700 and had at least one post-baseline efficacy assessment. 'Number Analyzed' signifies number of participants analyzed for this outcome measure at the specified timepoint.

The T25-FW is a reliable quantitative mobility and leg function performance test based on a timed 25-foot walk. The participant was directed to one end of a clearly marked 25-foot course and was instructed to walk 25 feet as quickly as possible, but safely. Participants were allowed to use assistive devices (canes, crutches, walkers) as needed. The time was calculated from when the lead foot crosses the start point to when the participant had reached the 25-foot mark. The task was immediately administered again by having the participant walk back the same distance. The score for the T25-FW was calculated as the average of the 2 completed trials. A negative change from Baseline indicates improvement.

Outcome measures

Measure	De Novo n=582 Participants Participants who had not received ALKS 8700 or DMF were administered ALKS 8700 231 mg capsules orally, BID on Days 1 to 7 followed by ALKS 8700 462 mg (as two 231 mg capsules) orally, BID from Day 8 up to Week 96.	Rollover: ALKS 8700 n=235 Participants Participants rolled over from study ALK870-A302 who had already received ALKS 8700 prior to Day 1 were administered ALKS 8700 462 mg (as two 231 mg capsules) orally, BID from Day 1 up to Week 96.	Rollover: DMF n=224 Participants Participants rolled over from study ALK870-A302 who had already received DMF prior to Day 1 were administered ALKS 8700 462 mg (as two 231 mg capsules) orally, BID from Day 1 up to Week 96.
Change From Baseline in Timed 25-Foot Walk Test (T25-FW) Score Baseline	5.875 seconds Interval 4.9 to 7.5	5.350 seconds Interval 4.5 to 6.85	5.635 seconds Interval 4.575 to 7.02
Change From Baseline in Timed 25-Foot Walk Test (T25-FW) Score Change From Baseline at Week 12	-0.050 seconds Interval -0.45 to 0.25	0.000 seconds Interval -0.25 to 0.35	0.000 seconds Interval -0.425 to 0.375
Change From Baseline in Timed 25-Foot Walk Test (T25-FW) Score Change From Baseline at Week 24	0.000 seconds Interval -0.45 to 0.3	-0.050 seconds Interval -0.35 to 0.4	0.000 seconds Interval -0.45 to 0.4
Change From Baseline in Timed 25-Foot Walk Test (T25-FW) Score Change From Baseline at Week 36	-0.050 seconds Interval -0.5 to 0.3	-0.100 seconds Interval -0.45 to 0.35	0.000 seconds Interval -0.5 to 0.5
Change From Baseline in Timed 25-Foot Walk Test (T25-FW) Score Change From Baseline at Week 48	0.000 seconds Interval -0.45 to 0.4	0.000 seconds Interval -0.45 to 0.35	-0.050 seconds Interval -0.45 to 0.55
Change From Baseline in Timed 25-Foot Walk Test (T25-FW) Score Change From Baseline at Week 60	-0.050 seconds Interval -0.6 to 0.4	-0.090 seconds Interval -0.55 to 0.3	0.000 seconds Interval -0.55 to 0.55
Change From Baseline in Timed 25-Foot Walk Test (T25-FW) Score Change From Baseline at Week 72	0.000 seconds Interval -0.55 to 0.5	-0.050 seconds Interval -0.6 to 0.35	0.000 seconds Interval -0.55 to 0.6
Change From Baseline in Timed 25-Foot Walk Test (T25-FW) Score Change From Baseline at Week 84	-0.050 seconds Interval -0.6 to 0.45	-0.075 seconds Interval -0.5 to 0.3	0.000 seconds Interval -0.5 to 0.7
Change From Baseline in Timed 25-Foot Walk Test (T25-FW) Score Change From Baseline at Week 96	-0.050 seconds Interval -0.55 to 0.4	-0.050 seconds Interval -0.5 to 0.4	0.000 seconds Interval -0.45 to 0.65

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline up to Week 96

Population: FAS included all participants who received at least one dose of ALKS 8700 and had at least one post-baseline efficacy assessment. 'Number of Participants Analyzed' signifies number of participants analyzed for this outcome measure. 'Number Analyzed' signifies number of participants analyzed for this outcome measure at the specified timepoint.

The EQ-5D-5L is an instrument designed to assess decrements in health. The EQ-5D-5L includes a VAS and a descriptive system that defines health in terms of 5 dimensions: Mobility, Self-Care, Usual Activities, Pain/Discomfort, and Anxiety/Depression. Each dimension has 5 response categories corresponding to the level of severity (i.e., no problems, slight problems, moderate problems, severe problems, and unable to/extreme problems). The EQ-5D-5L VAS records the participant's self-rated health on a vertical visual analogue scale numbered from 100 (best health imagined) to 0 (worst health imagined). Higher scores indicate good health. Positive change from baseline indicates improved health.

Outcome measures

Measure	De Novo n=581 Participants Participants who had not received ALKS 8700 or DMF were administered ALKS 8700 231 mg capsules orally, BID on Days 1 to 7 followed by ALKS 8700 462 mg (as two 231 mg capsules) orally, BID from Day 8 up to Week 96.	Rollover: ALKS 8700 n=232 Participants Participants rolled over from study ALK870-A302 who had already received ALKS 8700 prior to Day 1 were administered ALKS 8700 462 mg (as two 231 mg capsules) orally, BID from Day 1 up to Week 96.	Rollover: DMF n=221 Participants Participants rolled over from study ALK870-A302 who had already received DMF prior to Day 1 were administered ALKS 8700 462 mg (as two 231 mg capsules) orally, BID from Day 1 up to Week 96.
Change From Baseline in the EuroQol 5-Dimension 5-Level Visual Analog Scale (EQ-5D-5L VAS) Score Baseline	73.7 score on a scale Standard Deviation 17.48	80.3 score on a scale Standard Deviation 14.65	80.0 score on a scale Standard Deviation 16.26
Change From Baseline in the EuroQol 5-Dimension 5-Level Visual Analog Scale (EQ-5D-5L VAS) Score Change From Baseline at Week 24	1.0 score on a scale Standard Deviation 15.30	-1.6 score on a scale Standard Deviation 12.24	-1.6 score on a scale Standard Deviation 12.31
Change From Baseline in the EuroQol 5-Dimension 5-Level Visual Analog Scale (EQ-5D-5L VAS) Score Change From Baseline at Week 48	0.3 score on a scale Standard Deviation 15.27	-2.8 score on a scale Standard Deviation 10.68	-1.9 score on a scale Standard Deviation 12.48
Change From Baseline in the EuroQol 5-Dimension 5-Level Visual Analog Scale (EQ-5D-5L VAS) Score Change From Baseline at Week 72	1.3 score on a scale Standard Deviation 14.85	-2.8 score on a scale Standard Deviation 11.97	-2.1 score on a scale Standard Deviation 12.50
Change From Baseline in the EuroQol 5-Dimension 5-Level Visual Analog Scale (EQ-5D-5L VAS) Score Change From Baseline at Week 96	0.6 score on a scale Standard Deviation 14.59	-4.2 score on a scale Standard Deviation 12.35	-3.7 score on a scale Standard Deviation 14.71

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline up to Week 96

Population: FAS included all participants who received at least one dose of ALKS 8700 and had at least one post-baseline efficacy assessment. 'Number of Participants Analyzed' signifies number of participants analyzed for this outcome measure. 'Number Analyzed' signifies number of participants analyzed for this outcome measure at the specified timepoint.

The EQ-5D-5L is an instrument designed to assess decrements in health. The EQ-5D-5L includes a VAS and a descriptive system that defines health in terms of 5 dimensions: Mobility, Self-Care, Usual Activities, Pain/Discomfort, and Anxiety/Depression. Each dimension has 5 response categories corresponding to the level of severity (i.e., no problems, slight problems, moderate problems, severe problems, and unable to/extreme problems). The 5-item index score is transformed into a utility score between 0 (worst health state) and 1 (best health state). Higher scores indicate good health. Positive change from baseline indicates improved health.

Outcome measures

Measure	De Novo n=581 Participants Participants who had not received ALKS 8700 or DMF were administered ALKS 8700 231 mg capsules orally, BID on Days 1 to 7 followed by ALKS 8700 462 mg (as two 231 mg capsules) orally, BID from Day 8 up to Week 96.	Rollover: ALKS 8700 n=232 Participants Participants rolled over from study ALK870-A302 who had already received ALKS 8700 prior to Day 1 were administered ALKS 8700 462 mg (as two 231 mg capsules) orally, BID from Day 1 up to Week 96.	Rollover: DMF n=221 Participants Participants rolled over from study ALK870-A302 who had already received DMF prior to Day 1 were administered ALKS 8700 462 mg (as two 231 mg capsules) orally, BID from Day 1 up to Week 96.
Change From Baseline in the EQ-5D-5L Index Score Baseline	0.793 score on a scale Standard Deviation 0.137	0.841 score on a scale Standard Deviation 0.128	0.837 score on a scale Standard Deviation 0.128
Change From Baseline in the EQ-5D-5L Index Score Change From Baseline at Week 24	-0.002 score on a scale Standard Deviation 0.110	-0.018 score on a scale Standard Deviation 0.085	-0.035 score on a scale Standard Deviation 0.096
Change From Baseline in the EQ-5D-5L Index Score Change From Baseline at Week 48	-0.006 score on a scale Standard Deviation 0.108	-0.026 score on a scale Standard Deviation 0.086	-0.037 score on a scale Standard Deviation 0.101
Change From Baseline in the EQ-5D-5L Index Score Change From Baseline at Week 72	-0.010 score on a scale Standard Deviation 0.109	-0.030 score on a scale Standard Deviation 0.108	-0.036 score on a scale Standard Deviation 0.110
Change From Baseline in the EQ-5D-5L Index Score Change From Baseline at Week 96	-0.009 score on a scale Standard Deviation 0.114	-0.042 score on a scale Standard Deviation 0.109	-0.057 score on a scale Standard Deviation 0.117

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline up to Week 96

Population: FAS included all participants who received at least one dose of ALKS 8700 and had at least one post-baseline efficacy assessment. 'Number Analyzed' signifies number of participants analyzed for this outcome measure at the specified timepoint.

The SF-12 uses 12 questions to measure functional health and well-being from the study participant's perspective across eight domains: physical functioning, role, bodily pain, general health perceptions, vitality, social functioning, emotional role, and mental health. Mental and physical composite scores (MCS & PCS) are computed using the scores of twelve questions and range from 0 to 100, where a higher score indicates better health. Positive change from baseline indicates improved health.

Outcome measures

Measure	De Novo n=582 Participants Participants who had not received ALKS 8700 or DMF were administered ALKS 8700 231 mg capsules orally, BID on Days 1 to 7 followed by ALKS 8700 462 mg (as two 231 mg capsules) orally, BID from Day 8 up to Week 96.	Rollover: ALKS 8700 n=235 Participants Participants rolled over from study ALK870-A302 who had already received ALKS 8700 prior to Day 1 were administered ALKS 8700 462 mg (as two 231 mg capsules) orally, BID from Day 1 up to Week 96.	Rollover: DMF n=224 Participants Participants rolled over from study ALK870-A302 who had already received DMF prior to Day 1 were administered ALKS 8700 462 mg (as two 231 mg capsules) orally, BID from Day 1 up to Week 96.
Change From Baseline in the 12-item Short Form Health Survey (SF-12) Score PCS: Baseline	42.90 score on a scale Standard Deviation 10.662	44.68 score on a scale Standard Deviation 10.629	45.03 score on a scale Standard Deviation 10.720
Change From Baseline in the 12-item Short Form Health Survey (SF-12) Score PCS: Change From Baseline at Week 24	0.35 score on a scale Standard Deviation 7.329	-0.28 score on a scale Standard Deviation 6.893	-1.00 score on a scale Standard Deviation 6.248
Change From Baseline in the 12-item Short Form Health Survey (SF-12) Score PCS: Change From Baseline at Week 48	0.22 score on a scale Standard Deviation 6.804	-0.04 score on a scale Standard Deviation 7.428	-1.62 score on a scale Standard Deviation 6.546
Change From Baseline in the 12-item Short Form Health Survey (SF-12) Score PCS: Change From Baseline at Week 72	0.04 score on a scale Standard Deviation 7.341	-0.27 score on a scale Standard Deviation 7.902	-1.25 score on a scale Standard Deviation 6.849
Change From Baseline in the 12-item Short Form Health Survey (SF-12) Score MCS: Change From Baseline at Week 48	-0.62 score on a scale Standard Deviation 9.412	-2.57 score on a scale Standard Deviation 8.059	-2.20 score on a scale Standard Deviation 9.386
Change From Baseline in the 12-item Short Form Health Survey (SF-12) Score MCS: Change From Baseline at Week 96	-0.35 score on a scale Standard Deviation 9.517	-2.93 score on a scale Standard Deviation 8.681	-3.57 score on a scale Standard Deviation 10.582
Change From Baseline in the 12-item Short Form Health Survey (SF-12) Score PCS: Change From Baseline at Week 96	0.48 score on a scale Standard Deviation 7.154	-0.28 score on a scale Standard Deviation 7.095	-1.44 score on a scale Standard Deviation 7.191
Change From Baseline in the 12-item Short Form Health Survey (SF-12) Score MCS: Baseline	47.75 score on a scale Standard Deviation 10.345	50.90 score on a scale Standard Deviation 8.926	51.14 score on a scale Standard Deviation 9.299
Change From Baseline in the 12-item Short Form Health Survey (SF-12) Score MCS: Change From Baseline at Week 24	0.29 score on a scale Standard Deviation 8.745	-2.12 score on a scale Standard Deviation 7.962	-1.69 score on a scale Standard Deviation 8.415
Change From Baseline in the 12-item Short Form Health Survey (SF-12) Score MCS: Change From Baseline at Week 72	-0.34 score on a scale Standard Deviation 9.866	-2.63 score on a scale Standard Deviation 7.786	-3.50 score on a scale Standard Deviation 9.663

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to Week 96

Population: FAS included all participants who received at least one dose of ALKS 8700 and had at least one post-baseline efficacy assessment. 'Number of Participants Analyzed' signifies number of participants analyzed for this outcome measure.

The time to onset of 12-week confirmed disability progression is defined as the time from baseline to the first disability progression that is confirmed at the next regularly scheduled visit ≥ 12 weeks after the initial disability progression. Disability progression is defined by one of the following: an EDSS increase of at least 1.5 points from baseline EDSS = 0, an EDSS increase of at least a 1.0 point from baseline EDSS between 1.0 and 5.5 (inclusive), or an EDSS increase of at least 0.5 points from baseline EDSS = 6.0.

Outcome measures

Measure	De Novo n=47 Participants Participants who had not received ALKS 8700 or DMF were administered ALKS 8700 231 mg capsules orally, BID on Days 1 to 7 followed by ALKS 8700 462 mg (as two 231 mg capsules) orally, BID from Day 8 up to Week 96.	Rollover: ALKS 8700 n=22 Participants Participants rolled over from study ALK870-A302 who had already received ALKS 8700 prior to Day 1 were administered ALKS 8700 462 mg (as two 231 mg capsules) orally, BID from Day 1 up to Week 96.	Rollover: DMF n=23 Participants Participants rolled over from study ALK870-A302 who had already received DMF prior to Day 1 were administered ALKS 8700 462 mg (as two 231 mg capsules) orally, BID from Day 1 up to Week 96.
Time to Onset of 12-week Confirmed Disability Progression	250.0 days Interval 91.0 to 420.0	254.5 days Interval 89.0 to 419.0	176.0 days Interval 89.0 to 333.0

OTHER_PRE_SPECIFIED outcome

Timeframe: Week 96

Population: Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700. 'Number Analyzed' signifies number of participants analyzed for this outcome measure at the specified timepoint.

The definition of NEDA-3 encompasses a combination of the following 3 related measures of disease activity: No relapses, no confirmed disability progression sustained for 12 weeks as measured on EDSS, and no magnetic resonance imaging (MRI) disease activity, defined as no gadolinium-enhancing (GdE) lesions and no new or enlarging T2 lesions. The definition of NEDA-4 was the above definition of NEDA-3 with the addition of a mean annualized rate of brain volume loss of less than 0.4% where annualized rate of brain volume loss was derived from percentage brain volume change (PBVC) from baseline and was calculated as ([PBVC/100+1]^[365.25/days]-1) × 100.

Outcome measures

Measure	De Novo n=487 Participants Participants who had not received ALKS 8700 or DMF were administered ALKS 8700 231 mg capsules orally, BID on Days 1 to 7 followed by ALKS 8700 462 mg (as two 231 mg capsules) orally, BID from Day 8 up to Week 96.	Rollover: ALKS 8700 n=185 Participants Participants rolled over from study ALK870-A302 who had already received ALKS 8700 prior to Day 1 were administered ALKS 8700 462 mg (as two 231 mg capsules) orally, BID from Day 1 up to Week 96.	Rollover: DMF n=185 Participants Participants rolled over from study ALK870-A302 who had already received DMF prior to Day 1 were administered ALKS 8700 462 mg (as two 231 mg capsules) orally, BID from Day 1 up to Week 96.
Percentage of Participants With No Evidence of Disease Activity (NEDA) at Week 96 NEDA-3	24.8 percentage of participants	34.6 percentage of participants	28.6 percentage of participants
Percentage of Participants With No Evidence of Disease Activity (NEDA) at Week 96 NEDA-4	14.3 percentage of participants	15.2 percentage of participants	11.9 percentage of participants

Adverse Events

De Novo

Serious events: 69 serious events

Other events: 461 other events

Deaths: 3 deaths

Rollover: ALKS 8700

Serious events: 29 serious events

Other events: 186 other events

Deaths: 1 deaths

Rollover: DMF

Serious events: 25 serious events

Other events: 189 other events

Deaths: 0 deaths

Serious adverse events

Measure	De Novo n=593 participants at risk Participants who had not received ALKS 8700 or DMF were administered ALKS 8700 231 mg capsules orally, BID on Days 1 to 7 followed by ALKS 8700 462 mg (as two 231 mg capsules) orally, BID from Day 8 up to Week 96.	Rollover: ALKS 8700 n=239 participants at risk Participants rolled over from study ALK870-A302 who had already received ALKS 8700 prior to Day 1 were administered ALKS 8700 462 mg (as two 231 mg capsules) orally, BID from Day 1 up to Week 96.	Rollover: DMF n=225 participants at risk Participants rolled over from study ALK870-A302 who had already received DMF prior to Day 1 were administered ALKS 8700 462 mg (as two 231 mg capsules) orally, BID from Day 1 up to Week 96.
Injury, poisoning and procedural complications Incarcerated incisional hernia	0.17% 1/593 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.00% 0/239 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.00% 0/225 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.
Injury, poisoning and procedural complications Joint injury	0.00% 0/593 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.00% 0/239 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.44% 1/225 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.
Injury, poisoning and procedural complications Laceration	0.00% 0/593 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.00% 0/239 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.44% 1/225 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.
Cardiac disorders Cardiac arrest	0.00% 0/593 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.42% 1/239 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.00% 0/225 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.
Cardiac disorders Cardiac failure	0.17% 1/593 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.00% 0/239 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.00% 0/225 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.
Cardiac disorders Hypertensive heart disease	0.17% 1/593 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.00% 0/239 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.00% 0/225 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.
Cardiac disorders Myocardial infarction	0.00% 0/593 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.00% 0/239 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.44% 1/225 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.
Cardiac disorders Stress cardiomyopathy	0.00% 0/593 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.42% 1/239 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.00% 0/225 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.
Cardiac disorders Ventricular extrasystoles	0.17% 1/593 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.00% 0/239 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.00% 0/225 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.
Eye disorders Chorioretinopathy	0.00% 0/593 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.00% 0/239 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.44% 1/225 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.
Gastrointestinal disorders Abdominal pain	0.17% 1/593 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.00% 0/239 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.89% 2/225 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.
Gastrointestinal disorders Chronic gastritis	0.00% 0/593 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.42% 1/239 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.00% 0/225 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.
Gastrointestinal disorders Colitis ischaemic	0.17% 1/593 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.00% 0/239 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.00% 0/225 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.
Gastrointestinal disorders Eosinophilic oesophagitis	0.00% 0/593 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.42% 1/239 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.00% 0/225 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.
Gastrointestinal disorders Gastritis	0.00% 0/593 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.42% 1/239 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.44% 1/225 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.
Gastrointestinal disorders Inguinal hernia	0.17% 1/593 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.42% 1/239 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.00% 0/225 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.
Gastrointestinal disorders Mechanical ileus	0.17% 1/593 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.00% 0/239 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.00% 0/225 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.
Gastrointestinal disorders Peptic ulcer	0.17% 1/593 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.00% 0/239 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.00% 0/225 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.
Gastrointestinal disorders Vomiting	0.00% 0/593 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.00% 0/239 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.44% 1/225 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.
General disorders Pyrexia	0.00% 0/593 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.42% 1/239 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.00% 0/225 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.
Hepatobiliary disorders Cholecystitis	0.00% 0/593 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.42% 1/239 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.44% 1/225 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.
Hepatobiliary disorders Cholelithiasis	0.00% 0/593 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.42% 1/239 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.00% 0/225 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.
Hepatobiliary disorders Cholestatic liver injury	0.00% 0/593 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.00% 0/239 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.44% 1/225 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.
Immune system disorders Drug hypersensitivity	0.17% 1/593 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.00% 0/239 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.00% 0/225 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.
Infections and infestations Appendicitis	0.17% 1/593 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.42% 1/239 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.00% 0/225 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.
Infections and infestations Cellulitis	0.00% 0/593 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.00% 0/239 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.44% 1/225 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.
Infections and infestations Pharyngeal abscess	0.00% 0/593 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.00% 0/239 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.44% 1/225 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.
Infections and infestations Pharyngitis	0.00% 0/593 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.42% 1/239 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.00% 0/225 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.
Infections and infestations Pneumonia	0.17% 1/593 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.00% 0/239 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.00% 0/225 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.
Infections and infestations Pneumonia bacterial	0.17% 1/593 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.00% 0/239 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.00% 0/225 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.
Infections and infestations Sepsis	0.17% 1/593 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.00% 0/239 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.00% 0/225 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.
Infections and infestations Urinary tract infection	0.00% 0/593 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.00% 0/239 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.44% 1/225 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.
Injury, poisoning and procedural complications Accidental overdose	0.00% 0/593 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.00% 0/239 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.44% 1/225 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.
Injury, poisoning and procedural complications Fall	0.17% 1/593 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.00% 0/239 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.44% 1/225 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.
Injury, poisoning and procedural complications Femoral neck fracture	0.17% 1/593 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.00% 0/239 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.00% 0/225 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.
Injury, poisoning and procedural complications Humerus fracture	0.17% 1/593 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.00% 0/239 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.00% 0/225 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.
Injury, poisoning and procedural complications Limb traumatic amputation	0.00% 0/593 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.00% 0/239 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.44% 1/225 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.
Injury, poisoning and procedural complications Lower limb fracture	0.17% 1/593 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.00% 0/239 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.00% 0/225 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.
Injury, poisoning and procedural complications Road traffic accident	0.17% 1/593 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.00% 0/239 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.00% 0/225 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.
Injury, poisoning and procedural complications VIIIth nerve injury	0.17% 1/593 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.00% 0/239 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.00% 0/225 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.
Investigations Alanine aminotransferase increased	0.00% 0/593 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.42% 1/239 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.00% 0/225 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.
Investigations Liver function test increased	0.17% 1/593 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.00% 0/239 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.00% 0/225 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.
Metabolism and nutrition disorders Hyperglycaemia	0.17% 1/593 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.00% 0/239 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.00% 0/225 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/593 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.00% 0/239 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.44% 1/225 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.
Musculoskeletal and connective tissue disorders Flank pain	0.00% 0/593 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.00% 0/239 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.44% 1/225 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.
Musculoskeletal and connective tissue disorders Intervertebral disc disorder	0.17% 1/593 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.00% 0/239 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.00% 0/225 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	0.17% 1/593 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.00% 0/239 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.00% 0/225 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.
Musculoskeletal and connective tissue disorders Osteoarthritis	0.17% 1/593 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.00% 0/239 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.00% 0/225 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Diffuse large b-cell lymphoma	0.00% 0/593 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.00% 0/239 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.44% 1/225 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Invasive ductal breast carcinoma	0.17% 1/593 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.00% 0/239 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.00% 0/225 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Parathyroid tumour benign	0.00% 0/593 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.42% 1/239 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.00% 0/225 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Uterine leiomyoma	0.34% 2/593 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.00% 0/239 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.00% 0/225 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.
Nervous system disorders Cerebellar embolism	0.00% 0/593 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.00% 0/239 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.44% 1/225 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.
Nervous system disorders Idiopathic intracranial hypertension	0.00% 0/593 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.00% 0/239 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.44% 1/225 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.
Nervous system disorders Lumbar radiculopathy	0.17% 1/593 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.00% 0/239 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.00% 0/225 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.
Nervous system disorders Multiple sclerosis	0.17% 1/593 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.00% 0/239 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.00% 0/225 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.
Nervous system disorders Multiple sclerosis relapse	5.4% 32/593 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	7.9% 19/239 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	4.4% 10/225 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.
Nervous system disorders Partial seizures	0.00% 0/593 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.42% 1/239 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.00% 0/225 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.
Nervous system disorders Sciatica	0.17% 1/593 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.00% 0/239 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.00% 0/225 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.
Nervous system disorders Seizure	0.00% 0/593 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.00% 0/239 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.44% 1/225 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.
Nervous system disorders Uhthoff's phenomenon	0.17% 1/593 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.00% 0/239 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.00% 0/225 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.
Pregnancy, puerperium and perinatal conditions Abortion spontaneous	0.17% 1/593 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.00% 0/239 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.00% 0/225 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.
Psychiatric disorders Bipolar I disorder	0.00% 0/593 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.00% 0/239 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.44% 1/225 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.
Psychiatric disorders Drug abuse	0.17% 1/593 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.00% 0/239 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.00% 0/225 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.
Psychiatric disorders Substance-induced psychotic disorder	0.17% 1/593 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.00% 0/239 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.00% 0/225 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.
Psychiatric disorders Suicidal ideation	0.34% 2/593 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.00% 0/239 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.00% 0/225 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.
Psychiatric disorders Suicide attempt	0.17% 1/593 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.00% 0/239 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.00% 0/225 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.
Renal and urinary disorders Ureterolithiasis	0.17% 1/593 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.00% 0/239 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.00% 0/225 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.
Reproductive system and breast disorders Benign prostatic hyperplasia	0.00% 0/593 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.00% 0/239 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.44% 1/225 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.
Reproductive system and breast disorders Cervical dysplasia	0.17% 1/593 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.00% 0/239 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.00% 0/225 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.
Reproductive system and breast disorders Cervical polyp	0.17% 1/593 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.00% 0/239 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.00% 0/225 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.
Reproductive system and breast disorders Endometrial hyperplasia	0.00% 0/593 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.42% 1/239 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.00% 0/225 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.
Reproductive system and breast disorders Fallopian tube cyst	0.17% 1/593 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.00% 0/239 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.00% 0/225 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.
Reproductive system and breast disorders Ovarian disorder	0.17% 1/593 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.00% 0/239 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.00% 0/225 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.
Reproductive system and breast disorders Pelvic prolapse	0.17% 1/593 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.00% 0/239 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.00% 0/225 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.
Reproductive system and breast disorders Uterine haemorrhage	0.17% 1/593 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.00% 0/239 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.00% 0/225 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.
Reproductive system and breast disorders Uterine polyp	0.17% 1/593 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.00% 0/239 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.00% 0/225 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.
Reproductive system and breast disorders Vaginal prolapse	0.00% 0/593 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.42% 1/239 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.00% 0/225 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.00% 0/593 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.00% 0/239 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.44% 1/225 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.34% 2/593 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.00% 0/239 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.00% 0/225 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.
Respiratory, thoracic and mediastinal disorders Status asthmaticus	0.17% 1/593 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.00% 0/239 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.00% 0/225 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.
Vascular disorders Flushing	0.17% 1/593 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.00% 0/239 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	0.00% 0/225 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.

Other adverse events

Measure	De Novo n=593 participants at risk Participants who had not received ALKS 8700 or DMF were administered ALKS 8700 231 mg capsules orally, BID on Days 1 to 7 followed by ALKS 8700 462 mg (as two 231 mg capsules) orally, BID from Day 8 up to Week 96.	Rollover: ALKS 8700 n=239 participants at risk Participants rolled over from study ALK870-A302 who had already received ALKS 8700 prior to Day 1 were administered ALKS 8700 462 mg (as two 231 mg capsules) orally, BID from Day 1 up to Week 96.	Rollover: DMF n=225 participants at risk Participants rolled over from study ALK870-A302 who had already received DMF prior to Day 1 were administered ALKS 8700 462 mg (as two 231 mg capsules) orally, BID from Day 1 up to Week 96.
Blood and lymphatic system disorders Lymphopenia	8.6% 51/593 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	14.6% 35/239 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	16.9% 38/225 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.
Gastrointestinal disorders Abdominal pain upper	5.1% 30/593 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	2.1% 5/239 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	2.2% 5/225 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.
Gastrointestinal disorders Constipation	4.4% 26/593 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	4.2% 10/239 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	5.8% 13/225 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.
Gastrointestinal disorders Diarrhoea	11.1% 66/593 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	7.5% 18/239 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	11.1% 25/225 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.
Gastrointestinal disorders Nausea	7.6% 45/593 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	5.0% 12/239 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	6.7% 15/225 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.
General disorders Fatigue	6.6% 39/593 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	10.9% 26/239 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	9.8% 22/225 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.
Infections and infestations Nasopharyngitis	14.5% 86/593 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	10.0% 24/239 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	12.0% 27/225 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.
Infections and infestations Sinusitis	5.7% 34/593 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	7.1% 17/239 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	6.2% 14/225 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.
Infections and infestations Upper respiratory tract infection	12.8% 76/593 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	17.6% 42/239 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	15.6% 35/225 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.
Infections and infestations Urinary tract infection	9.3% 55/593 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	10.5% 25/239 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	10.7% 24/225 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.
Investigations Alanine aminotransferase increased	5.1% 30/593 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	7.1% 17/239 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	4.9% 11/225 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.
Investigations Lymphocyte count decreased	3.5% 21/593 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	5.4% 13/239 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	5.3% 12/225 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.
Investigations Urine albumin/creatinine ratio increased	2.2% 13/593 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	2.5% 6/239 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	5.8% 13/225 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.
Musculoskeletal and connective tissue disorders Arthralgia	5.4% 32/593 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	7.5% 18/239 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	8.9% 20/225 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.
Musculoskeletal and connective tissue disorders Back pain	4.0% 24/593 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	7.5% 18/239 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	7.6% 17/225 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.
Musculoskeletal and connective tissue disorders Muscle spasms	3.4% 20/593 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	4.6% 11/239 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	8.0% 18/225 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.
Musculoskeletal and connective tissue disorders Pain in extremity	4.9% 29/593 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	5.0% 12/239 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	5.3% 12/225 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.
Nervous system disorders Dizziness	5.2% 31/593 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	5.0% 12/239 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	6.2% 14/225 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.
Nervous system disorders Headache	8.3% 49/593 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	9.6% 23/239 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	10.7% 24/225 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.
Nervous system disorders Hypoaesthesia	3.2% 19/593 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	5.4% 13/239 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	4.9% 11/225 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.
Nervous system disorders Multiple sclerosis relapse	15.7% 93/593 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	19.7% 47/239 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	19.6% 44/225 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.
Psychiatric disorders Depression	3.9% 23/593 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	5.9% 14/239 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	5.8% 13/225 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.
Skin and subcutaneous tissue disorders Erythema	6.4% 38/593 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	3.3% 8/239 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	2.2% 5/225 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.
Skin and subcutaneous tissue disorders Pruritus	8.8% 52/593 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	3.3% 8/239 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	4.4% 10/225 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.
Vascular disorders Flushing	38.1% 226/593 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	13.8% 33/239 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	12.9% 29/225 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.
Vascular disorders Hypertension	2.2% 13/593 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	3.3% 8/239 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.	5.3% 12/225 • From first dose to two weeks after last dose of study drug (Up to 98 weeks) Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.

Additional Information

US Biogen Clinical Trial Center

Biogen

Phone: 866-633-4636

Email: clinicaltrials@biogen.com

Results disclosure agreements

• Principal investigator is a sponsor employee Our agreement is subject to confidentiality but generally the PI can publish, for non-commercial 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