We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
Try the New Site
We're building a modernized ClinicalTrials.gov! Visit Beta.ClinicalTrials.gov to try the new functionality.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02634307
Recruitment Status : Completed
First Posted : December 18, 2015
Results First Posted : June 24, 2022
Last Update Posted : July 26, 2022
Sponsor:
Collaborator:
Alkermes, Inc.
Information provided by (Responsible Party):
Biogen

Study Type Interventional
Study Design Allocation: N/A;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Multiple Sclerosis
Intervention Drug: ALKS 8700
Enrollment 1057
Recruitment Details Participants were enrolled at investigational sites in North America and Europe from 10 December 2015 to 11 November 2021.
Pre-assignment Details 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.
Arm/Group Title De Novo Rollover: ALKS 8700 Rollover: DMF
Hide Arm/Group Description 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. 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. 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.
Period Title: Overall Study
Started 593 239 225
Safety Population 593 239 225
Full Analysis Set (FAS) Population 582 235 224
Completed 468 168 164
Not Completed 125 71 61
Reason Not Completed
Adverse Event             50             24             14
Lost to Follow-up             21             5             6
Pregnancy             5             1             3
Withdrawal by Subject             38             24             18
Non-Compliance with Study Drug             0             2             2
Lack of Efficacy             1             5             3
Physician Decision             7             5             5
Reason not Specified             3             5             10
Arm/Group Title De Novo Rollover: ALKS 8700 Rollover: DMF Total
Hide Arm/Group Description 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. 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. 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 of all reporting groups
Overall Number of Baseline Participants 593 239 225 1057
Hide Baseline Analysis Population Description
Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 593 participants 239 participants 225 participants 1057 participants
41.5  (10.96) 44.0  (11.00) 43.7  (9.77) 42.5  (10.78)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 593 participants 239 participants 225 participants 1057 participants
Female
427
  72.0%
165
  69.0%
170
  75.6%
762
  72.1%
Male
166
  28.0%
74
  31.0%
55
  24.4%
295
  27.9%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 593 participants 239 participants 225 participants 1057 participants
Hispanic or Latino
25
   4.2%
5
   2.1%
10
   4.4%
40
   3.8%
Not Hispanic or Latino
568
  95.8%
234
  97.9%
215
  95.6%
1017
  96.2%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Race Number Analyzed 593 participants 239 participants 225 participants 1057 participants
White
547
  92.2%
220
  92.1%
205
  91.1%
972
  92.0%
Black or African American
37
   6.2%
19
   7.9%
16
   7.1%
72
   6.8%
Asian
4
   0.7%
0
   0.0%
1
   0.4%
5
   0.5%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
1
   0.4%
1
   0.1%
Other
5
   0.8%
0
   0.0%
2
   0.9%
7
   0.7%
1.Primary Outcome
Title Number of Participants Experiencing Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Hide Description 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.
Time Frame From first dose to two weeks after last dose of study drug (Up to 98 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.
Arm/Group Title De Novo Rollover: ALKS 8700 Rollover: DMF
Hide Arm/Group Description:
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.
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.
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 Number of Participants Analyzed 593 239 225
Measure Type: Count of Participants
Unit of Measure: Participants
TEAEs
519
  87.5%
212
  88.7%
207
  92.0%
SAEs
69
  11.6%
29
  12.1%
25
  11.1%
2.Primary Outcome
Title Number of Participants With Potentially Clinically Significant Vital Sign Abnormalities
Hide Description 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).
Time Frame From first dose to two weeks after last dose of study drug (Up to 98 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title De Novo Rollover: ALKS 8700 Rollover: DMF
Hide Arm/Group Description:
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.
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.
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 Number of Participants Analyzed 582 238 225
Measure Type: Count of Participants
Unit of Measure: Participants
Systolic BP (Low: <=90 mmHg and decrease >=20 mmHg) Number Analyzed 581 participants 237 participants 224 participants
15
   2.6%
4
   1.7%
2
   0.9%
Systolic BP (High: >=180 mmHg and increase >=20 mmHg) Number Analyzed 582 participants 238 participants 225 participants
3
   0.5%
2
   0.8%
1
   0.4%
Diastolic BP (Low: <=50 mmHg and decrease >=15 mmHg) Number Analyzed 580 participants 238 participants 224 participants
10
   1.7%
2
   0.8%
4
   1.8%
Diastolic BP (High: >=105 mmHg and increase >=15 mmHg) Number Analyzed 581 participants 238 participants 225 participants
6
   1.0%
2
   0.8%
2
   0.9%
Heart Rate (Low: <=50 bpm and decrease >=15 bpm) Number Analyzed 579 participants 235 participants 225 participants
5
   0.9%
1
   0.4%
2
   0.9%
Heart Rate (High: >=120 bpm and increase >=15 bpm) Number Analyzed 582 participants 238 participants 225 participants
1
   0.2%
1
   0.4%
2
   0.9%
3.Primary Outcome
Title Number of Participants With Potentially Clinically Significant 12-Lead Electrocardiogram (ECG) Abnormalities
Hide Description Potentially clinically significant QTcF values (>450 to <=480 millisecond [msec], >480 to <=500 msec) at any post-baseline visit during treatment period were reported.
Time Frame From first dose to two weeks after last dose of study drug (Up to 98 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title De Novo Rollover: ALKS 8700 Rollover: DMF
Hide Arm/Group Description:
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.
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.
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 Number of Participants Analyzed 576 237 223
Measure Type: Count of Participants
Unit of Measure: Participants
>450 - <=480 msec
15
   2.6%
5
   2.1%
6
   2.7%
>480 - <=500 msec
0
   0.0%
0
   0.0%
1
   0.4%
4.Primary Outcome
Title Number of Participants With Columbia Suicide Severity Rating Scale (C-SSRS) Score at Any Post-Baseline Visit
Hide Description 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.
Time Frame Up to 98 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.
Arm/Group Title De Novo Rollover: ALKS 8700 Rollover: DMF
Hide Arm/Group Description:
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.
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.
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 Number of Participants Analyzed 593 239 225
Measure Type: Count of Participants
Unit of Measure: Participants
Suicidal Behavior: Preparatory acts or behavior
0
   0.0%
0
   0.0%
0
   0.0%
Suicidal Behavior: Aborted attempt
0
   0.0%
0
   0.0%
0
   0.0%
Suicidal Behavior: Interrupted attempt
0
   0.0%
0
   0.0%
0
   0.0%
Suicidal Behavior: Actual attempt
1
   0.2%
0
   0.0%
0
   0.0%
Suicidal Behavior: Completed suicide
0
   0.0%
0
   0.0%
0
   0.0%
Suicidal Ideation: Wish to be dead
12
   2.0%
2
   0.8%
4
   1.8%
Suicidal Ideation: Non-specific active suicidal thoughts
8
   1.3%
2
   0.8%
2
   0.9%
Suicidal Ideation: Active ideation without intention to act
2
   0.3%
0
   0.0%
1
   0.4%
Suicidal Ideation: Active ideation with some intent to act without a plan
1
   0.2%
0
   0.0%
0
   0.0%
Suicidal Ideation: Active ideation with a specific plan and intent
1
   0.2%
0
   0.0%
0
   0.0%
Non-Suicidal Self-Injurious Behavior
0
   0.0%
0
   0.0%
0
   0.0%
5.Primary Outcome
Title Number of Participants With Potentially Clinically Significant Laboratory Abnormalities
Hide Description 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+.
Time Frame From first dose to two weeks after last dose of study drug (Up to 98 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title De Novo Rollover: ALKS 8700 Rollover: DMF
Hide Arm/Group Description:
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.
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.
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 Number of Participants Analyzed 582 238 225
Measure Type: Count of Participants
Unit of Measure: Participants
Alanine Aminotransferase (U/L) >=3 x ULN Number Analyzed 581 participants 237 participants 223 participants
13
   2.2%
6
   2.5%
1
   0.4%
Aspartate Aminotransferase (U/L) >=3 x ULN Number Analyzed 581 participants 237 participants 223 participants
8
   1.4%
3
   1.3%
1
   0.4%
Bicarbonate <15 mmol/L Number Analyzed 582 participants 237 participants 225 participants
3
   0.5%
0
   0.0%
0
   0.0%
Bicarbonate >31 mmol/L Number Analyzed 582 participants 237 participants 224 participants
13
   2.2%
1
   0.4%
3
   1.3%
Bilirubin, Total >=2.0 mg/dL Number Analyzed 582 participants 238 participants 224 participants
2
   0.3%
1
   0.4%
0
   0.0%
Calcium <8.2 mg/dL Number Analyzed 580 participants 238 participants 225 participants
2
   0.3%
0
   0.0%
0
   0.0%
Calcium >12 mg/dL Number Analyzed 582 participants 238 participants 225 participants
0
   0.0%
1
   0.4%
0
   0.0%
Cholesterol, Total >300 mg/dL Number Analyzed 574 participants 237 participants 223 participants
23
   4.0%
8
   3.4%
8
   3.6%
Creatine Kinase (U/L) >3 x ULN Number Analyzed 582 participants 235 participants 224 participants
26
   4.5%
11
   4.7%
8
   3.6%
Chloride <=90 mmol/L Number Analyzed 582 participants 237 participants 225 participants
1
   0.2%
0
   0.0%
0
   0.0%
Creatinine >=2.0 mg/dL Number Analyzed 581 participants 238 participants 225 participants
1
   0.2%
0
   0.0%
2
   0.9%
Glucose <50 mg/dL Number Analyzed 579 participants 237 participants 225 participants
4
   0.7%
6
   2.5%
4
   1.8%
Glucose >200 mg/dL Number Analyzed 581 participants 237 participants 224 participants
6
   1.0%
5
   2.1%
4
   1.8%
HDL Cholesterol <=30 mg/dL Number Analyzed 575 participants 238 participants 221 participants
13
   2.3%
6
   2.5%
3
   1.4%
Potassium <3 mmol/L Number Analyzed 582 participants 238 participants 225 participants
1
   0.2%
0
   0.0%
0
   0.0%
Potassium >5.5 mmol/L Number Analyzed 577 participants 237 participants 225 participants
39
   6.8%
8
   3.4%
16
   7.1%
Lactate Dehydrogenase (U/L) >3 x ULN Number Analyzed 579 participants 238 participants 225 participants
1
   0.2%
0
   0.0%
0
   0.0%
LDL Cholesterol >=160 mg/dL Number Analyzed 521 participants 226 participants 207 participants
69
  13.2%
27
  11.9%
29
  14.0%
Sodium <130 mmol/L Number Analyzed 581 participants 238 participants 225 participants
1
   0.2%
0
   0.0%
0
   0.0%
Sodium >150 mmol/L Number Analyzed 582 participants 238 participants 225 participants
3
   0.5%
0
   0.0%
0
   0.0%
Triglycerides >=120 mg/dL (Female) Number Analyzed 270 participants 102 participants 111 participants
123
  45.6%
45
  44.1%
61
  55.0%
Triglycerides >=160 mg/dL (Male) Number Analyzed 116 participants 60 participants 41 participants
54
  46.6%
32
  53.3%
24
  58.5%
Urate >9 mg/dL Number Analyzed 580 participants 236 participants 225 participants
10
   1.7%
5
   2.1%
2
   0.9%
Urate >8 mg/dL (Female) Number Analyzed 415 participants 164 participants 168 participants
8
   1.9%
3
   1.8%
4
   2.4%
Blood Urea Nitrogen >30 mg/dL Number Analyzed 582 participants 237 participants 225 participants
5
   0.9%
3
   1.3%
2
   0.9%
Eosinophils >1x10^3/uL Number Analyzed 581 participants 236 participants 211 participants
8
   1.4%
3
   1.3%
1
   0.5%
Hematocrit <=32% and 3 point decrease from baseline (Female) Number Analyzed 410 participants 160 participants 165 participants
18
   4.4%
5
   3.1%
8
   4.8%
Hematocrit <=37% and 3 point decrease from baseline (Male) Number Analyzed 163 participants 72 participants 53 participants
6
   3.7%
4
   5.6%
3
   5.7%
Hemoglobin <=9.5 g/dL (Female) Number Analyzed 414 participants 164 participants 169 participants
5
   1.2%
1
   0.6%
3
   1.8%
Hemoglobin <=11.5 g/dL (Male) Number Analyzed 164 participants 72 participants 55 participants
2
   1.2%
1
   1.4%
0
   0.0%
Lymphocytes <0.5x10^9/L Number Analyzed 582 participants 238 participants 225 participants
47
   8.1%
25
  10.5%
24
  10.7%
Neutrophils, Absolute <1.5x10^3/uL Number Analyzed 580 participants 236 participants 224 participants
39
   6.7%
10
   4.2%
13
   5.8%
Platelets <75.1x10^3/uL Number Analyzed 581 participants 238 participants 225 participants
2
   0.3%
0
   0.0%
1
   0.4%
Platelets >=700x10^3/uL Number Analyzed 581 participants 238 participants 225 participants
0
   0.0%
0
   0.0%
0
   0.0%
Leukocytes <=2.8x10^3/uL Number Analyzed 581 participants 238 participants 225 participants
45
   7.7%
17
   7.1%
15
   6.7%
Leukocytes >=16x10^3/uL Number Analyzed 581 participants 238 participants 224 participants
4
   0.7%
5
   2.1%
5
   2.2%
Albumin/Creatinine >200 g/kg Number Analyzed 581 participants 237 participants 225 participants
15
   2.6%
8
   3.4%
5
   2.2%
Beta-2 Microglobulin >0.300 mg/L Number Analyzed 568 participants 228 participants 214 participants
95
  16.7%
32
  14.0%
31
  14.5%
Glucose at least 2+ Number Analyzed 579 participants 237 participants 223 participants
10
   1.7%
4
   1.7%
3
   1.3%
Protein at least 2+ Number Analyzed 581 participants 238 participants 223 participants
15
   2.6%
4
   1.7%
9
   4.0%
6.Other Pre-specified Outcome
Title Annualized Relapse Rate (ARR)
Hide Description 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.
Time Frame Up to 96 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.
Arm/Group Title De Novo Rollover: ALKS 8700 Rollover: DMF
Hide Arm/Group Description:
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.
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.
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 Number of Participants Analyzed 593 239 225
Measure Type: Number
Unit of Measure: relapses per participant year
0.14 0.11 0.13
7.Other Pre-specified Outcome
Title Percentage of Participants With Multiple Sclerosis (MS) Relapse
Hide Description 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.
Time Frame Up to 96 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.
Arm/Group Title De Novo Rollover: ALKS 8700 Rollover: DMF
Hide Arm/Group Description:
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.
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.
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 Number of Participants Analyzed 593 239 225
Measure Type: Number
Unit of Measure: percentage of participants
17.66 16.66 18.30
8.Other Pre-specified Outcome
Title Change From Baseline in Expanded Disability Status Scale (EDSS) Score
Hide Description 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.
Time Frame Baseline up to Week 96
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title De Novo Rollover: ALKS 8700 Rollover: DMF
Hide Arm/Group Description:
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.
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.
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 Number of Participants Analyzed 582 235 224
Mean (Standard Deviation)
Unit of Measure: score on a scale
Baseline Number Analyzed 582 participants 235 participants 224 participants
2.71  (1.457) 2.64  (1.481) 2.71  (1.445)
Change From Baseline at Week 12 Number Analyzed 576 participants 232 participants 224 participants
-0.01  (0.490) -0.03  (0.548) 0.05  (0.557)
Change From Baseline at Week 24 Number Analyzed 549 participants 217 participants 214 participants
0.00  (0.518) -0.02  (0.603) -0.01  (0.696)
Change From Baseline at Week 36 Number Analyzed 531 participants 212 participants 209 participants
0.01  (0.558) -0.01  (0.597) -0.03  (0.733)
Change From Baseline at Week 48 Number Analyzed 521 participants 203 participants 202 participants
0.03  (0.614) -0.01  (0.579) 0.00  (0.702)
Change From Baseline at Week 60 Number Analyzed 511 participants 192 participants 190 participants
0.04  (0.617) -0.02  (0.643) -0.02  (0.633)
Change From Baseline at Week 72 Number Analyzed 498 participants 189 participants 184 participants
0.05  (0.617) -0.04  (0.639) 0.08  (0.713)
Change From Baseline at Week 84 Number Analyzed 486 participants 174 participants 177 participants
0.07  (0.641) -0.03  (0.616) -0.02  (0.759)
Change From Baseline at Week 96 Number Analyzed 478 participants 172 participants 166 participants
0.07  (0.631) -0.01  (0.775) 0.03  (0.735)
9.Other Pre-specified Outcome
Title Change From Baseline in Timed 25-Foot Walk Test (T25-FW) Score
Hide Description 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.
Time Frame Baseline up to Week 96
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title De Novo Rollover: ALKS 8700 Rollover: DMF
Hide Arm/Group Description:
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.
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.
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 Number of Participants Analyzed 582 235 224
Median (Inter-Quartile Range)
Unit of Measure: seconds
Baseline Number Analyzed 582 participants 235 participants 224 participants
5.875
(4.900 to 7.500)
5.350
(4.500 to 6.850)
5.635
(4.575 to 7.020)
Change From Baseline at Week 12 Number Analyzed 579 participants 232 participants 224 participants
-0.050
(-0.450 to 0.250)
0.000
(-0.250 to 0.350)
0.000
(-0.425 to 0.375)
Change From Baseline at Week 24 Number Analyzed 551 participants 218 participants 214 participants
0.000
(-0.450 to 0.300)
-0.050
(-0.350 to 0.400)
0.000
(-0.450 to 0.400)
Change From Baseline at Week 36 Number Analyzed 526 participants 213 participants 209 participants
-0.050
(-0.500 to 0.300)
-0.100
(-0.450 to 0.350)
0.000
(-0.500 to 0.500)
Change From Baseline at Week 48 Number Analyzed 517 participants 199 participants 201 participants
0.000
(-0.450 to 0.400)
0.000
(-0.450 to 0.350)
-0.050
(-0.450 to 0.550)
Change From Baseline at Week 60 Number Analyzed 511 participants 194 participants 191 participants
-0.050
(-0.600 to 0.400)
-0.090
(-0.550 to 0.300)
0.000
(-0.550 to 0.550)
Change From Baseline at Week 72 Number Analyzed 499 participants 185 participants 183 participants
0.000
(-0.550 to 0.500)
-0.050
(-0.600 to 0.350)
0.000
(-0.550 to 0.600)
Change From Baseline at Week 84 Number Analyzed 486 participants 174 participants 173 participants
-0.050
(-0.600 to 0.450)
-0.075
(-0.500 to 0.300)
0.000
(-0.500 to 0.700)
Change From Baseline at Week 96 Number Analyzed 476 participants 169 participants 165 participants
-0.050
(-0.550 to 0.400)
-0.050
(-0.500 to 0.400)
0.000
(-0.450 to 0.650)
10.Other Pre-specified Outcome
Title Change From Baseline in the EuroQol 5-Dimension 5-Level Visual Analog Scale (EQ-5D-5L VAS) Score
Hide Description 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.
Time Frame Baseline up to Week 96
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title De Novo Rollover: ALKS 8700 Rollover: DMF
Hide Arm/Group Description:
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.
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.
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 Number of Participants Analyzed 581 232 221
Mean (Standard Deviation)
Unit of Measure: score on a scale
Baseline Number Analyzed 581 participants 232 participants 221 participants
73.7  (17.48) 80.3  (14.65) 80.0  (16.26)
Change From Baseline at Week 24 Number Analyzed 560 participants 222 participants 216 participants
1.0  (15.30) -1.6  (12.24) -1.6  (12.31)
Change From Baseline at Week 48 Number Analyzed 523 participants 204 participants 202 participants
0.3  (15.27) -2.8  (10.68) -1.9  (12.48)
Change From Baseline at Week 72 Number Analyzed 498 participants 192 participants 187 participants
1.3  (14.85) -2.8  (11.97) -2.1  (12.50)
Change From Baseline at Week 96 Number Analyzed 481 participants 173 participants 169 participants
0.6  (14.59) -4.2  (12.35) -3.7  (14.71)
11.Other Pre-specified Outcome
Title Change From Baseline in the EQ-5D-5L Index Score
Hide Description 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.
Time Frame Baseline up to Week 96
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title De Novo Rollover: ALKS 8700 Rollover: DMF
Hide Arm/Group Description:
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.
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.
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 Number of Participants Analyzed 581 232 221
Mean (Standard Deviation)
Unit of Measure: score on a scale
Baseline Number Analyzed 581 participants 232 participants 221 participants
0.793  (0.137) 0.841  (0.128) 0.837  (0.128)
Change From Baseline at Week 24 Number Analyzed 560 participants 222 participants 216 participants
-0.002  (0.110) -0.018  (0.085) -0.035  (0.096)
Change From Baseline at Week 48 Number Analyzed 522 participants 203 participants 202 participants
-0.006  (0.108) -0.026  (0.086) -0.037  (0.101)
Change From Baseline at Week 72 Number Analyzed 498 participants 192 participants 187 participants
-0.010  (0.109) -0.030  (0.108) -0.036  (0.110)
Change From Baseline at Week 96 Number Analyzed 481 participants 173 participants 168 participants
-0.009  (0.114) -0.042  (0.109) -0.057  (0.117)
12.Other Pre-specified Outcome
Title Change From Baseline in the 12-item Short Form Health Survey (SF-12) Score
Hide Description 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.
Time Frame Baseline up to Week 96
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title De Novo Rollover: ALKS 8700 Rollover: DMF
Hide Arm/Group Description:
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.
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.
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 Number of Participants Analyzed 582 235 224
Mean (Standard Deviation)
Unit of Measure: score on a scale
PCS: Baseline Number Analyzed 578 participants 235 participants 224 participants
42.90  (10.662) 44.68  (10.629) 45.03  (10.720)
PCS: Change From Baseline at Week 24 Number Analyzed 555 participants 221 participants 216 participants
0.35  (7.329) -0.28  (6.893) -1.00  (6.248)
PCS: Change From Baseline at Week 48 Number Analyzed 523 participants 203 participants 200 participants
0.22  (6.804) -0.04  (7.428) -1.62  (6.546)
PCS: Change From Baseline at Week 72 Number Analyzed 491 participants 192 participants 185 participants
0.04  (7.341) -0.27  (7.902) -1.25  (6.849)
PCS: Change From Baseline at Week 96 Number Analyzed 476 participants 173 participants 169 participants
0.48  (7.154) -0.28  (7.095) -1.44  (7.191)
MCS: Baseline Number Analyzed 578 participants 235 participants 224 participants
47.75  (10.345) 50.90  (8.926) 51.14  (9.299)
MCS: Change From Baseline at Week 24 Number Analyzed 555 participants 221 participants 216 participants
0.29  (8.745) -2.12  (7.962) -1.69  (8.415)
MCS: Change From Baseline at Week 48 Number Analyzed 523 participants 203 participants 200 participants
-0.62  (9.412) -2.57  (8.059) -2.20  (9.386)
MCS: Change From Baseline at Week 72 Number Analyzed 491 participants 192 participants 185 participants
-0.34  (9.866) -2.63  (7.786) -3.50  (9.663)
MCS: Change From Baseline at Week 96 Number Analyzed 476 participants 173 participants 169 participants
-0.35  (9.517) -2.93  (8.681) -3.57  (10.582)
13.Other Pre-specified Outcome
Title Time to Onset of 12-week Confirmed Disability Progression
Hide Description 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.
Time Frame Up to Week 96
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title De Novo Rollover: ALKS 8700 Rollover: DMF
Hide Arm/Group Description:
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.
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.
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 Number of Participants Analyzed 47 22 23
Median (Inter-Quartile Range)
Unit of Measure: days
250.0
(91.0 to 420.0)
254.5
(89.0 to 419.0)
176.0
(89.0 to 333.0)
14.Other Pre-specified Outcome
Title Percentage of Participants With No Evidence of Disease Activity (NEDA) at Week 96
Hide Description 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.
Time Frame Week 96
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title De Novo Rollover: ALKS 8700 Rollover: DMF
Hide Arm/Group Description:
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.
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.
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 Number of Participants Analyzed 487 185 185
Measure Type: Number
Unit of Measure: percentage of participants
NEDA-3 Number Analyzed 487 participants 185 participants 185 participants
24.8 34.6 28.6
NEDA-4 Number Analyzed 419 participants 158 participants 160 participants
14.3 15.2 11.9
Time Frame From first dose to two weeks after last dose of study drug (Up to 98 weeks)
Adverse Event Reporting Description Safety Analysis Set included all enrolled participants who received at least one dose of ALKS 8700.
 
Arm/Group Title De Novo Rollover: ALKS 8700 Rollover: DMF
Hide Arm/Group Description 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. 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. 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.
All-Cause Mortality
De Novo Rollover: ALKS 8700 Rollover: DMF
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   3/593 (0.51%)   1/239 (0.42%)   0/225 (0.00%) 
Hide Serious Adverse Events
De Novo Rollover: ALKS 8700 Rollover: DMF
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   69/593 (11.64%)   29/239 (12.13%)   25/225 (11.11%) 
Cardiac disorders       
Cardiac arrest † 1  0/593 (0.00%)  1/239 (0.42%)  0/225 (0.00%) 
Cardiac failure † 1  1/593 (0.17%)  0/239 (0.00%)  0/225 (0.00%) 
Hypertensive heart disease † 1  1/593 (0.17%)  0/239 (0.00%)  0/225 (0.00%) 
Myocardial infarction † 1  0/593 (0.00%)  0/239 (0.00%)  1/225 (0.44%) 
Stress cardiomyopathy † 1  0/593 (0.00%)  1/239 (0.42%)  0/225 (0.00%) 
Ventricular extrasystoles † 1  1/593 (0.17%)  0/239 (0.00%)  0/225 (0.00%) 
Eye disorders       
Chorioretinopathy † 1  0/593 (0.00%)  0/239 (0.00%)  1/225 (0.44%) 
Gastrointestinal disorders       
Abdominal pain † 1  1/593 (0.17%)  0/239 (0.00%)  2/225 (0.89%) 
Chronic gastritis † 1  0/593 (0.00%)  1/239 (0.42%)  0/225 (0.00%) 
Colitis ischaemic † 1  1/593 (0.17%)  0/239 (0.00%)  0/225 (0.00%) 
Eosinophilic oesophagitis † 1  0/593 (0.00%)  1/239 (0.42%)  0/225 (0.00%) 
Gastritis † 1  0/593 (0.00%)  1/239 (0.42%)  1/225 (0.44%) 
Inguinal hernia † 1  1/593 (0.17%)  1/239 (0.42%)  0/225 (0.00%) 
Mechanical ileus † 1  1/593 (0.17%)  0/239 (0.00%)  0/225 (0.00%) 
Peptic ulcer † 1  1/593 (0.17%)  0/239 (0.00%)  0/225 (0.00%) 
Vomiting † 1  0/593 (0.00%)  0/239 (0.00%)  1/225 (0.44%) 
General disorders       
Pyrexia † 1  0/593 (0.00%)  1/239 (0.42%)  0/225 (0.00%) 
Hepatobiliary disorders       
Cholecystitis † 1  0/593 (0.00%)  1/239 (0.42%)  1/225 (0.44%) 
Cholelithiasis † 1  0/593 (0.00%)  1/239 (0.42%)  0/225 (0.00%) 
Cholestatic liver injury † 1  0/593 (0.00%)  0/239 (0.00%)  1/225 (0.44%) 
Immune system disorders       
Drug hypersensitivity † 1  1/593 (0.17%)  0/239 (0.00%)  0/225 (0.00%) 
Infections and infestations       
Appendicitis † 1  1/593 (0.17%)  1/239 (0.42%)  0/225 (0.00%) 
Cellulitis † 1  0/593 (0.00%)  0/239 (0.00%)  1/225 (0.44%) 
Pharyngeal abscess † 1  0/593 (0.00%)  0/239 (0.00%)  1/225 (0.44%) 
Pharyngitis † 1  0/593 (0.00%)  1/239 (0.42%)  0/225 (0.00%) 
Pneumonia † 1  1/593 (0.17%)  0/239 (0.00%)  0/225 (0.00%) 
Pneumonia bacterial † 1  1/593 (0.17%)  0/239 (0.00%)  0/225 (0.00%) 
Sepsis † 1  1/593 (0.17%)  0/239 (0.00%)  0/225 (0.00%) 
Urinary tract infection † 1  0/593 (0.00%)  0/239 (0.00%)  1/225 (0.44%) 
Injury, poisoning and procedural complications       
Accidental overdose † 1  0/593 (0.00%)  0/239 (0.00%)  1/225 (0.44%) 
Fall † 1  1/593 (0.17%)  0/239 (0.00%)  1/225 (0.44%) 
Femoral neck fracture † 1  1/593 (0.17%)  0/239 (0.00%)  0/225 (0.00%) 
Humerus fracture † 1  1/593 (0.17%)  0/239 (0.00%)  0/225 (0.00%) 
Incarcerated incisional hernia † 1  1/593 (0.17%)  0/239 (0.00%)  0/225 (0.00%) 
Joint injury † 1  0/593 (0.00%)  0/239 (0.00%)  1/225 (0.44%) 
Laceration † 1  0/593 (0.00%)  0/239 (0.00%)  1/225 (0.44%) 
Limb traumatic amputation † 1  0/593 (0.00%)  0/239 (0.00%)  1/225 (0.44%) 
Lower limb fracture † 1  1/593 (0.17%)  0/239 (0.00%)  0/225 (0.00%) 
Road traffic accident † 1  1/593 (0.17%)  0/239 (0.00%)  0/225 (0.00%) 
VIIIth nerve injury † 1  1/593 (0.17%)  0/239 (0.00%)  0/225 (0.00%) 
Investigations       
Alanine aminotransferase increased † 1  0/593 (0.00%)  1/239 (0.42%)  0/225 (0.00%) 
Liver function test increased † 1  1/593 (0.17%)  0/239 (0.00%)  0/225 (0.00%) 
Metabolism and nutrition disorders       
Hyperglycaemia † 1  1/593 (0.17%)  0/239 (0.00%)  0/225 (0.00%) 
Musculoskeletal and connective tissue disorders       
Back pain † 1  0/593 (0.00%)  0/239 (0.00%)  1/225 (0.44%) 
Flank pain † 1  0/593 (0.00%)  0/239 (0.00%)  1/225 (0.44%) 
Intervertebral disc disorder † 1  1/593 (0.17%)  0/239 (0.00%)  0/225 (0.00%) 
Intervertebral disc protrusion † 1  1/593 (0.17%)  0/239 (0.00%)  0/225 (0.00%) 
Osteoarthritis † 1  1/593 (0.17%)  0/239 (0.00%)  0/225 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Diffuse large b-cell lymphoma † 1  0/593 (0.00%)  0/239 (0.00%)  1/225 (0.44%) 
Invasive ductal breast carcinoma † 1  1/593 (0.17%)  0/239 (0.00%)  0/225 (0.00%) 
Parathyroid tumour benign † 1  0/593 (0.00%)  1/239 (0.42%)  0/225 (0.00%) 
Uterine leiomyoma † 1  2/593 (0.34%)  0/239 (0.00%)  0/225 (0.00%) 
Nervous system disorders       
Cerebellar embolism † 1  0/593 (0.00%)  0/239 (0.00%)  1/225 (0.44%) 
Idiopathic intracranial hypertension † 1  0/593 (0.00%)  0/239 (0.00%)  1/225 (0.44%) 
Lumbar radiculopathy † 1  1/593 (0.17%)  0/239 (0.00%)  0/225 (0.00%) 
Multiple sclerosis † 1  1/593 (0.17%)  0/239 (0.00%)  0/225 (0.00%) 
Multiple sclerosis relapse † 1  32/593 (5.40%)  19/239 (7.95%)  10/225 (4.44%) 
Partial seizures † 1  0/593 (0.00%)  1/239 (0.42%)  0/225 (0.00%) 
Sciatica † 1  1/593 (0.17%)  0/239 (0.00%)  0/225 (0.00%) 
Seizure † 1  0/593 (0.00%)  0/239 (0.00%)  1/225 (0.44%) 
Uhthoff's phenomenon † 1  1/593 (0.17%)  0/239 (0.00%)  0/225 (0.00%) 
Pregnancy, puerperium and perinatal conditions       
Abortion spontaneous † 1  1/593 (0.17%)  0/239 (0.00%)  0/225 (0.00%) 
Psychiatric disorders       
Bipolar I disorder † 1  0/593 (0.00%)  0/239 (0.00%)  1/225 (0.44%) 
Drug abuse † 1  1/593 (0.17%)  0/239 (0.00%)  0/225 (0.00%) 
Substance-induced psychotic disorder † 1  1/593 (0.17%)  0/239 (0.00%)  0/225 (0.00%) 
Suicidal ideation † 1  2/593 (0.34%)  0/239 (0.00%)  0/225 (0.00%) 
Suicide attempt † 1  1/593 (0.17%)  0/239 (0.00%)  0/225 (0.00%) 
Renal and urinary disorders       
Ureterolithiasis † 1  1/593 (0.17%)  0/239 (0.00%)  0/225 (0.00%) 
Reproductive system and breast disorders       
Benign prostatic hyperplasia † 1  0/593 (0.00%)  0/239 (0.00%)  1/225 (0.44%) 
Cervical dysplasia † 1  1/593 (0.17%)  0/239 (0.00%)  0/225 (0.00%) 
Cervical polyp † 1  1/593 (0.17%)  0/239 (0.00%)  0/225 (0.00%) 
Endometrial hyperplasia † 1  0/593 (0.00%)  1/239 (0.42%)  0/225 (0.00%) 
Fallopian tube cyst † 1  1/593 (0.17%)  0/239 (0.00%)  0/225 (0.00%) 
Ovarian disorder † 1  1/593 (0.17%)  0/239 (0.00%)  0/225 (0.00%) 
Pelvic prolapse † 1  1/593 (0.17%)  0/239 (0.00%)  0/225 (0.00%) 
Uterine haemorrhage † 1  1/593 (0.17%)  0/239 (0.00%)  0/225 (0.00%) 
Uterine polyp † 1  1/593 (0.17%)  0/239 (0.00%)  0/225 (0.00%) 
Vaginal prolapse † 1  0/593 (0.00%)  1/239 (0.42%)  0/225 (0.00%) 
Respiratory, thoracic and mediastinal disorders       
Pulmonary embolism † 1  0/593 (0.00%)  0/239 (0.00%)  1/225 (0.44%) 
Respiratory failure † 1  2/593 (0.34%)  0/239 (0.00%)  0/225 (0.00%) 
Status asthmaticus † 1  1/593 (0.17%)  0/239 (0.00%)  0/225 (0.00%) 
Vascular disorders       
Flushing † 1  1/593 (0.17%)  0/239 (0.00%)  0/225 (0.00%) 
1
Term from vocabulary, MedDRA 20.1
†
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
De Novo Rollover: ALKS 8700 Rollover: DMF
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   461/593 (77.74%)   186/239 (77.82%)   189/225 (84.00%) 
Blood and lymphatic system disorders       
Lymphopenia † 1  51/593 (8.60%)  35/239 (14.64%)  38/225 (16.89%) 
Gastrointestinal disorders       
Abdominal pain upper † 1  30/593 (5.06%)  5/239 (2.09%)  5/225 (2.22%) 
Constipation † 1  26/593 (4.38%)  10/239 (4.18%)  13/225 (5.78%) 
Diarrhoea † 1  66/593 (11.13%)  18/239 (7.53%)  25/225 (11.11%) 
Nausea † 1  45/593 (7.59%)  12/239 (5.02%)  15/225 (6.67%) 
General disorders       
Fatigue † 1  39/593 (6.58%)  26/239 (10.88%)  22/225 (9.78%) 
Infections and infestations       
Nasopharyngitis † 1  86/593 (14.50%)  24/239 (10.04%)  27/225 (12.00%) 
Sinusitis † 1  34/593 (5.73%)  17/239 (7.11%)  14/225 (6.22%) 
Upper respiratory tract infection † 1  76/593 (12.82%)  42/239 (17.57%)  35/225 (15.56%) 
Urinary tract infection † 1  55/593 (9.27%)  25/239 (10.46%)  24/225 (10.67%) 
Investigations       
Alanine aminotransferase increased † 1  30/593 (5.06%)  17/239 (7.11%)  11/225 (4.89%) 
Lymphocyte count decreased † 1  21/593 (3.54%)  13/239 (5.44%)  12/225 (5.33%) 
Urine albumin/creatinine ratio increased † 1  13/593 (2.19%)  6/239 (2.51%)  13/225 (5.78%) 
Musculoskeletal and connective tissue disorders       
Arthralgia † 1  32/593 (5.40%)  18/239 (7.53%)  20/225 (8.89%) 
Back pain † 1  24/593 (4.05%)  18/239 (7.53%)  17/225 (7.56%) 
Muscle spasms † 1  20/593 (3.37%)  11/239 (4.60%)  18/225 (8.00%) 
Pain in extremity † 1  29/593 (4.89%)  12/239 (5.02%)  12/225 (5.33%) 
Nervous system disorders       
Dizziness † 1  31/593 (5.23%)  12/239 (5.02%)  14/225 (6.22%) 
Headache † 1  49/593 (8.26%)  23/239 (9.62%)  24/225 (10.67%) 
Hypoaesthesia † 1  19/593 (3.20%)  13/239 (5.44%)  11/225 (4.89%) 
Multiple sclerosis relapse † 1  93/593 (15.68%)  47/239 (19.67%)  44/225 (19.56%) 
Psychiatric disorders       
Depression † 1  23/593 (3.88%)  14/239 (5.86%)  13/225 (5.78%) 
Skin and subcutaneous tissue disorders       
Erythema † 1  38/593 (6.41%)  8/239 (3.35%)  5/225 (2.22%) 
Pruritus † 1  52/593 (8.77%)  8/239 (3.35%)  10/225 (4.44%) 
Vascular disorders       
Flushing † 1  226/593 (38.11%)  33/239 (13.81%)  29/225 (12.89%) 
Hypertension † 1  13/593 (2.19%)  8/239 (3.35%)  12/225 (5.33%) 
1
Term from vocabulary, MedDRA 20.1
†
Indicates events were collected by systematic assessment
[Not Specified]
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: US Biogen Clinical Trial Center
Organization: Biogen
Phone: 866-633-4636
EMail: clinicaltrials@biogen.com
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Biogen
ClinicalTrials.gov Identifier: NCT02634307    
Other Study ID Numbers: ALK8700-A301
2015-005160-41 ( EudraCT Number )
First Submitted: December 16, 2015
First Posted: December 18, 2015
Results First Submitted: May 30, 2022
Results First Posted: June 24, 2022
Last Update Posted: July 26, 2022