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

• ClinicalTrials.gov Identifier: NCT04022473
• Recruitment Status: Completed
• First Posted: July 17, 2019
• Last Update Posted: January 18, 2020
• Sponsor: Banner Life Sciences LLC
• Information provided by (Responsible Party): Banner Life Sciences LLC

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Multiple Sclerosis	Drug: Bafiertam; Drug: Tecfidera	Phase 1

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 210 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: July 7, 2019
• Actual Primary Completion Date: October 19, 2019
• Actual Study Completion Date: October 19, 2019

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Area Under the Curve (AUC) in each of the individual symptoms over the treatment period. [ Time Frame: 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 Outcome Measures :

1. Comparison of the Modified Overall Gastrointestinal Symptom Scale (MOGISS) composite score [ Time Frame: 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).
2. The number of days that a subject experiences at least one GI symptom. [ Time Frame: 5 weeks ]
   Number of days with at (as reported on the MOGISS) with a severity score of at least 1
3. AUC in the MOGISS total score within in each subject over the treatment period [ Time Frame: 5 weeks ]
   Defined as the daily total of all 8 individual symptom scores within each subject
4. Frequency, severity, and duration of overall GI events using the MOGISS. [ Time Frame: 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.
5. Safety and tolerability outcomes: incidence rates of all non GI-adverse events [ Time Frame: 5 weeks ]
   Subject incidence rates of all non GI-adverse events

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

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);

Contacts and Locations

Locations

United States, Missouri

BioPharma Services, Inc.

Columbia, Missouri, United States, 65201

Sponsors and Collaborators

Banner Life Sciences LLC

Investigators

• Principal Investigator: Kathleen Doisy, MD; BioPharma Services, Inc

More Information

• Responsible Party: Banner Life Sciences LLC
• ClinicalTrials.gov Identifier: NCT04022473
• Other Study ID Numbers: BLS-11-109
• First Posted: July 17, 2019
• Last Update Posted: January 18, 2020
• Last Verified: January 2020

Individual Participant Data (IPD) Sharing Statement:

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

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.

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Banner Life Sciences LLC:

Gastrointestinal

Additional relevant MeSH terms:

Multiple Sclerosis; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases; Dimethyl Fumarate; Dermatologic Agents; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs