A Tolerability Study of ALKS 8700 in Subjects With Relapsing Remitting Multiple Sclerosis (RRMS) EVOLVE-MS-2

Study Overview
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Brief Summary
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The objectives of this study are to evaluate the utility of two gastrointestinal (GI) symptom scales (Individual GI Symptom and Impact Scale {IGISIS} and Global GI Symptom and Impact Scale {GGISIS}) in assessing GI tolerability in adult subjects with RRMS after administration of ALKS 8700 or Dimethyl Fumarate (DMF) in Part A, to compare the GI tolerability of ALKS 8700 and DMF in adult subjects with RRMS using IGISIS and GGISIS in Part B, and to Evaluate the safety and tolerability of ALKS 8700 in adult subjects with RRMS in Parts A and B.

Official Title
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A Phase 3 Study in Subjects With Relapsing Remitting Multiple Sclerosis to Evaluate the Tolerability of ALKS 8700 and Dimethyl Fumarate

Conditions
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Relapsing Remitting Multiple Sclerosis

Intervention / Treatment
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* Drug: ALKS 8700
* Drug: Dimethyl Fumarate


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Capable of understanding and complying with the protocol Has a confirmed diagnosis of RRMS Neurologically stable with no evidence of relapse within 30 days prior to randomization Agrees to use an acceptable method of contraception for the duration of the study and for 30 days after any study drug administration, or is surgically sterile or post-menopausal Key Exclusion Criteria: Have any finding(s) that would compromise the safety of the subject, affect the subject's ability to adhere to the protocol visit schedule or to fulfill visit requirements, or would make the subject unsuitable for participation in the study Diagnosis of primary progressive, secondary progressive, or progressive relapsing MS History of clinically significant cardiovascular, pulmonary, GI, dermatologic, psychiatric, neurologic (other than MS), endocrine, renal, and/or other major disease that would preclude participation in a clinical trial History of GI surgery (except appendectomy that occurred more than 6 months prior to screening History of clinically significant recurring or active gastrointestinal symptoms (eg, nausea, diarrhea, dyspepsia, constipation) within 3 months of screening Chronic use (7 days) of medical therapy to treat any GI symptoms within 1 month of screening Has a clinically significant medical condition or observed abnormality at screening History of a myocardial infarction, including a silent myocardial infarction or unstable angina History of clinically significant drug or alcohol abuse within the past year prior to screening Clinically significant history of suicidal ideation or suicidal behavior in the last 12 months Subject is pregnant or breastfeeding or plans to become pregnant or begin breastfeeding at any point during the study and for 30 days after any study drug administration Prior use of Dimethyl Fumarate (DMF) NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ALKS 8700<br>Oral capsules, administered orally twice daily. | Drug: ALKS 8700<br>* Administered as specified in the treatment arm.<br>|
| Active Comparator: Dimethyl Fumarate<br>Oral capsules, administered orally twice daily. | Drug: Dimethyl Fumarate<br>* Administered as specified in the treatment arm.<br>* Other names: Tecfidera;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Days With Any Individual Gastrointestinal Symptom and Impact Scale (IGISIS) Individual Symptom Intensity Score ≥2 Relative to Exposure Days in Parts A and B | IGISIS assessed the intensity of five individual GI symptoms: nausea, vomiting, upper abdominal pain, lower abdominal pain, and diarrhea. Participants rated the intensity of each individual symptom via an 11-point numeric rating scale ranging from 0 (did not have) to 10 (extreme). IGISIS was completed by the participants using e-diaries. | End of treatment (up to Week 6) for both Parts A and B | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Days With Any IGISIS Individual Symptom Intensity Score ≥2 Relative to Exposure Days in Part B | IGISIS assessed the intensity of five individual GI symptoms: nausea, vomiting, upper abdominal pain, lower abdominal pain, and diarrhea. Participants rated the intensity of each individual symptom via an 11-point numeric rating scale ranging from 0 (did not have) to 10 (extreme). IGISIS was completed by the participants using e-diaries. | End of treatment (up to Week 6) for Part B | 
| Number of Days With Any IGISIS Individual Symptom Intensity Score ≥1 Relative to Exposure Days in Parts A and B | IGISIS assessed the intensity of five individual GI symptoms: nausea, vomiting, upper abdominal pain, lower abdominal pain, and diarrhea. Participants rated the intensity of each individual symptom via an 11-point numeric rating scale ranging from 0 (did not have) to 10 (extreme). IGISIS was completed by the participants using e-diaries. | End of treatment (up to Week 6) for both Parts A and B | 
| Number of Days With Any IGISIS Individual Symptom Intensity Score ≥3 Relative to Exposure Days in Parts A and B | IGISIS assessed the intensity of five individual GI symptoms: nausea, vomiting, upper abdominal pain, lower abdominal pain, and diarrhea. Participants rated the intensity of each individual symptom via an 11-point numeric rating scale ranging from 0 (did not have) to 10 (extreme). IGISIS was completed by the participants using e-diaries. | End of treatment (up to Week 6) for both Parts A and B | 
| Number of Days With a Global GI Symptom and Impact Scale (GGISIS) Symptom Intensity Score ≥1 Relative to Exposure Days in Parts A and B | GGISIS is a global scale to assess the overall intensity of GI symptoms (nausea, vomiting, upper abdominal pain, lower abdominal pain, and diarrhea). Participants rated the intensity of GI symptoms via an 11-point numeric rating scale ranging from 0 (did not have) to 10 (extreme). GGISIS was completed by the participants using e-diaries. | End of treatment (up to Week 6) for both Parts A and B | 
| Number of Days With a GGISIS Symptom Intensity Score ≥2 Relative to Exposure Days in Parts A and B | GGISIS is a global scale to assess the overall intensity of GI symptoms (nausea, vomiting, upper abdominal pain, lower abdominal pain, and diarrhea). Participants rated the intensity of GI symptoms via an 11-point numeric rating scale ranging from 0 (did not have) to 10 (extreme). GGISIS was completed by the participants using e-diaries. | End of treatment (up to Week 6) for both Parts A and B | 
| Number of Days With a GGISIS Symptom Intensity Score ≥3 Relative to Exposure Days in Parts A and B | GGISIS is a global scale to assess the overall intensity of GI symptoms (nausea, vomiting, upper abdominal pain, lower abdominal pain, and diarrhea). Participants rated the intensity of GI symptoms via an 11-point numeric rating scale ranging from 0 (did not have) to 10 (extreme). GGISIS was completed by the participants using e-diaries. | End of treatment (up to Week 6) for both Parts A and B | 
| Worst IGISIS Individual Symptom Intensity Score During the 5-Week Treatment Period in Parts A and B | IGISIS assessed the intensity of five individual GI symptoms: nausea, vomiting, upper abdominal pain, lower abdominal pain, and diarrhea. Participants rated the intensity of each individual symptom via an 11-point numeric rating scale ranging from 0 (did not have) to 10 (extreme). IGISIS was completed by the participants using e-diaries. Scores were averaged for 5-week treatment period. | End of treatment (up to Week 6) for both Parts A and B | 
| Number of Participants With Adverse Events (AEs) | 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 laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. | End of study (up to Week 10) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MS, Alkermes, ALKS 8700, Dimethyl Fumarate, DMF, Tecfidera, RRMS, Multiple Sclerosis