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

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

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.

Study Overview

• Status: Completed
• Conditions: Multiple Sclerosis
• Intervention / Treatment: Drug: Bafiertam; Drug: Tecfidera

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.

• Study Type: Interventional
• Enrollment (Actual): 210
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Missouri
    • Columbia, Missouri, United States, 65201
      • BioPharma Services, Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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);

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Banner Life Sciences LLC
• Investigators: Principal Investigator: Kathleen Doisy, MD, BioPharma Services, Inc

Study record dates

Study Major Dates

• Study Start (Actual): July 7, 2019
• Primary Completion (Actual): October 19, 2019
• Study Completion (Actual): October 19, 2019

Study Registration Dates

• First Submitted: July 15, 2019
• First Submitted That Met QC Criteria: July 16, 2019
• First Posted (Actual): July 17, 2019

Study Record Updates

• Last Update Posted (Actual): January 18, 2020
• Last Update Submitted That Met QC Criteria: January 13, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Keywords: Gastrointestinal
• Additional Relevant MeSH Terms: Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Multiple Sclerosis; Physiological Effects of Drugs; Immunosuppressive Agents; Immunologic Factors; Dermatologic Agents; Dimethyl Fumarate
• Other Study ID Numbers: BLS-11-109

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures, and appendices).
• IPD Sharing Time Frame: Beginning 6 months and ending 12 months following article publication.

IPD Sharing Access Criteria

Researchers who provide a methodologically sound proposal and whose proposed use of the data has been approved by an independent review committee ("learned intermediary") identified for this purpose.

The stated purpose of the analysis as to be for individual participant data meta-analysis.

• IPD Sharing Supporting Information Type: Study Protocol

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No