Comparative Bioavailability of BAFIERTAM™ (Monomethyl Fumarate) and Tecfidera® (Dimethyl Fumarate) in Healthy Subjects
Condition: Relapsing Remitting Multiple Sclerosis
MeSH terms: Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting
Intervention: monomethyl fumarate 190 mg; dimethyl fumarate 240 mg
Intervention MeSH terms: Dimethyl Fumarate
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: Subjects were randomized to 1 of 2 treatment sequences prior to the first dose.
Masking: None (Open Label)
Enrollment: 50.0
Sex: All
Minimum age: 18 Years
Maximum age: 55 Years
Healthy volunteers: Accepts Healthy Volunteers

Summary:

      The primary objective of this study was to assess the bioequivalence of the test product
      (Bafiertam; BLS-11; monomethyl fumarate) 190 mg versus Tecfidera® (dimethyl fumarate) 240 mg
      based on the Cmax and Area Under the Curve (AUC) values of monomethyl fumarate (MMF)
      determined after a single dose under fasting conditions.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Continuous non-smoker who had not used nicotine-containing products for at least 3
             months prior to the first dose and throughout the study.

          2. Body mass index (BMI) ≥ 18.5 and ≤ 29.9 kg/m2 at Screening.

          3. Medically healthy as determined by the Investigator or designee with no clinically
             significant medical history, physical examination, laboratory profiles, vital signs or
             electrocardiograms (ECGs), as deemed by the Investigator or designee.

          4. Females of childbearing potential: not pregnant and either sexually inactive
             (abstinent) for 14 days prior to the first dose and throughout the study or using one
             of the following acceptable birth control methods: hormonal oral contraceptives,
             vaginal ring, transdermal patch, or nonhormone or hormone releasing intrauterine
             device for at least 3 months prior to the first dose with either a physical (e.g.,
             condom, diaphragm, or other) or a chemical (e.g., spermicide) barrier method from the
             time of Screening and throughout the study; depot/implantable hormone (e.g., Depo
             Provera®, Implanon®) for at least 3 months prior to the first dose and throughout the
             study.

             In addition, female subjects of childbearing potential were advised to remain sexually
             inactive or to keep the same birth control method for at least 7 days following the
             last dose.

          5. Females of non-childbearing potential: had undergone one of the following
             sterilization procedures at least 6 months prior to the first dose: hysteroscopic
             sterilization; bilateral tubal ligation or bilateral salpingectomy; hysterectomy;
             bilateral oophorectomy or were postmenopausal with amenorrhea for at least 1 year
             prior to the first dose and follicle-stimulating hormone (FSH) serum levels consistent
             with postmenopausal status as per Investigator's or designee's judgment.

          6. Non-vasectomized male subjects agreed to use a condom with spermicide or abstain from
             sexual intercourse during the study until 90 days beyond the last dose of study drug.
             (No restrictions were required for a vasectomized male provided his vasectomy had been
             performed 4 months or more prior to the first dose of study drug. A male who had been
             vasectomized less than 4 months prior to the first dose of study drug, followed the
             same restrictions as a non-vasectomized male.)

          7. Males agreed not to donate sperm from the first dose until 90 days after dosing.

          8. Understood the study procedures in the Informed Consent Form (ICF), and were willing
             and able to comply with the protocol.

        Exclusion Criteria:

          1. Subject was mentally or legally incapacitated or had significant emotional problems at
             the time of the Screening visit or expected during the conduct of the study.

          2. History or presence of clinically significant medical or psychiatric condition or
             disease in the opinion of the Investigator or designee.

          3. History of any illness that, in the opinion of the Investigator or designee, might
             have confounded the results of the study or posed an additional risk to the subject by
             their participation in the study.

          4. History or presence of alcoholism or drug abuse within the past 2 years prior to the
             first dose.

          5. History or presence of hypersensitivity or idiosyncratic reaction to the study drugs
             or related compounds.

          6. Female subjects with a positive serum pregnancy test at Screening or Check-in, or who
             were lactating.

          7. Positive urine drug, alcohol, or cotinine results at Screening or Check-in.

          8. Positive results at Screening for human immunodeficiency virus (HIV), hepatitis B
             surface antigen (HBsAg) or hepatitis C virus (HCV).

          9. Seated blood pressure was less than 90/40 mmHg or greater than 140/90 mmHg at
             Screening.

         10. Seated heart rate was lower than 40 beats per minute (bpm) or higher than 99 bpm at
             Screening.

         11. Abnormal 12-lead ECG deemed clinically significant by the Investigator or designee at
             Screening or prior to the first dose.

         12. Unable to refrain from or anticipated the use of any drug, including prescription and
             non-prescription medications, or herbal remedies, beginning 14 days prior to the first
             dose and throughout the study. Medication listed as part of acceptable birth control
             methods was allowed. Hormone replacement therapy was also allowed. Acetaminophen (up
             to 2 g per 24-hour period) may have been permitted, as necessary during the study.

         13. Had been on a diet incompatible with the on study diet, in the opinion of the
             Investigator or designee, within the 28 days prior to the first dose and throughout
             the study.

         14. Donation of blood or significant blood loss within 30 days prior to the first dose.

         15. Plasma donation within 7 days prior to the first dose.

         16. Participation in another clinical study within 28 days prior to the first dose. The
             28-day window was derived from the date of the last blood collection or dosing,
             whichever was later, in the previous study to Day 1 of Period 1 of the current study.