Multiple Sclerosis
Conditions
Keywords
Gastrointestinal
Brief summary
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
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.
Interventions
DRUGBafiertam
Over-encapsulated capsule to mask treatment
DRUGTecfidera
Over-encapsulated capsule to mask treatment
Sponsors
Banner Life Sciences LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
1. Males or non-pregnant females. 2. Healthy, according to the medical history, ECG, vital signs, laboratory results and physical examination as determined by the PI/Sub-Investigator. 3. Body Mass Index within 18.0 - 34.0 kg/m2, inclusive
Exclusion criteria
1. 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. 2. 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. 3. Presence of any significant physical or organ abnormality as determined by the PI/Sub-Investigator. 4. Subject with abnormal baseline laboratory values deemed to be clinically significant by the Investigator. 5. Lymphocyte count \<1.5x 10\^9/L. 6. 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);
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Curve (AUC) in each of the individual symptoms over the treatment period. | 5 weeks | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Comparison of the Modified Overall Gastrointestinal Symptom Scale (MOGISS) composite score | 5 weeks | 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). |
| The number of days that a subject experiences at least one GI symptom. | 5 weeks | Number of days with at (as reported on the MOGISS) with a severity score of at least 1 |
| AUC in the MOGISS total score within in each subject over the treatment period | 5 weeks | Defined as the daily total of all 8 individual symptom scores within each subject |
| Frequency, severity, and duration of overall GI events using the MOGISS. | 5 weeks | 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. |
| Safety and tolerability outcomes: incidence rates of all non GI-adverse events | 5 weeks | Subject incidence rates of all non GI-adverse events |
Countries
United States
Outcome results
None listed