Study to Compare GI Tolerability Following Oral Administration of Bafiertam™ or Tecfidera to Healthy Volunteers

Study Overview
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Brief Summary
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The primary objective of the study is to compare in healthy subjects, the GI tolerability of bioequivalent doses of Bafiertam™(monomethyl fumarate) and its pro-drug Tecfidera® (dimethyl fumarate). Secondary objective of this study is to compare the safety and tolerability of Bafiertam™ and Tecfidera® when administered orally following bioequivalent dose regimens in healthy subjects.

Detailed Description
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Subjects randomized (1:1) to either Bafiertam (monomethyl fumarate) or Tecfidera (dimethyl fumarate) will enter a double-blind titration period where they will receive either Bafiertam 95 mg twice daily (BID) or Tecfidera 120 mg BID for 7 days. Following the titration period, they will enter a maintenance period in which they will receive Bafiertam 190 mg BID or Tecfidera 240 mg BID for 4 weeks.

Official Title
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A Randomized, Double-Blind Study to Compare Gastrointestinal Tolerability Following Oral Administration of Bafiertam™ (Monomethyl Fumarate) or Tecfidera® (Dimethyl Fumarate) to Healthy Male and Female Volunteers

Conditions
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Multiple Sclerosis

Intervention / Treatment
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* Drug: Bafiertam
* Drug: Tecfidera


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males or non-pregnant females. Healthy, according to the medical history, ECG, vital signs, laboratory results and physical examination as determined by the PI/Sub-Investigator. Body Mass Index within 18.0 - 34.0 kg/m2, inclusive Exclusion Criteria: Known history or presence of any clinically significant hepatic, renal/genitourinary, Gastrointestinal (GI), cardiovascular, cerebrovascular, pulmonary, endocrine, immunological, musculoskeletal, neurological, psychiatric, dermatological or hematological disease or condition unless determined as not clinically significant by the PI/Sub-Investigator. Clinically significant history or presence of any clinically significant GI pathology unresolved GI symptoms, or other conditions known to interfere with the absorption, distribution, metabolism or excretion of the drug experienced within 7 days prior to first study drug administration, as determined by the PI/Sub-Investigator. Presence of any significant physical or organ abnormality as determined by the PI/Sub-Investigator. Subject with abnormal baseline laboratory values deemed to be clinically significant by the Investigator. Lymphocyte count <1.5x 10^9/L. Known history or presence of: Alcohol abuse or dependence within one year prior to first study drug administration; Drug abuse or dependence; Hypersensitivity or idiosyncratic reaction to DMF, its excipients, and/or related substances; Progressive multifocal leukoencephalopathy (PML); Fanconi syndrome; Flushing (e.g., warmth, redness, itching, and burning sensation); Low white blood cell count (lymphopenia);

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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Accepts Healthy Volunteers

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Bafiertam<br>oral capsules administered twice daily | Drug: Bafiertam<br>* Over-encapsulated capsule to mask treatment<br>* Other names: monomethyl fumarate;|
| Active Comparator: Tecfidera<br>oral capsules administered twice daily | Drug: Tecfidera<br>* Over-encapsulated capsule to mask treatment<br>* Other names: dimethyl fumarate;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Curve (AUC) in each of the individual symptoms over the treatment period. | The symptoms measured are (1) nausea, (2) vomiting, (3) diarrhea, (4) upper abdominal pain, (5) lower abdominal pain, (6) constipation, (7) bloating, and (8) flatulence | 5 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison of the Modified Overall Gastrointestinal Symptom Scale (MOGISS) composite score | The MOGISS assesses global GI events (defined as one or more of the following symptoms: nausea, diarrhea, upper abdominal pain, lower abdominal pain, vomiting, constipation, bloating, and flatulence) and their effect on the patient during the 24 hours before each morning dose. The events items are rated on a 10-point numerical rating scale, where 0 = no events, 1 to 3 = mild events, 4 to 6 = moderate events, 7 to 9 = severe events, and 10 = extreme events. The MOGISS Total (sum of 8 scores) range is 0 (no symptoms) to 80 (worst possible symptoms) and the MOGISS Composite (average of 8 scores) range is 0 (no symptoms) - 10 (worst possible symptoms). | 5 weeks | 
| The number of days that a subject experiences at least one GI symptom. | Number of days with at (as reported on the MOGISS) with a severity score of at least 1 | 5 weeks | 
| AUC in the MOGISS total score within in each subject over the treatment period | Defined as the daily total of all 8 individual symptom scores within each subject | 5 weeks | 
| Frequency, severity, and duration of overall GI events using the MOGISS. | Frequency, severity and duration of overall GI events will be completed using the MOGISS for each week of study treatment as well as for the overall study treatment period. | 5 weeks | 
| Safety and tolerability outcomes: incidence rates of all non GI-adverse events | Subject incidence rates of all non GI-adverse events | 5 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Gastrointestinal