Comparative Bioavailability of BAFIERTAM™ (Monomethyl Fumarate) and Tecfidera® (Dimethyl Fumarate) in Healthy Subjects

NCT04570670 | Completed Phase 1 Results FDA Drug

• 1 other identifier: BLS-11-104
• Study Type: interventional
• Target: 50
• Locations: 0 countries
• Sites: N/A

Brief 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.

Conditions

Relapsing Remitting Multiple Sclerosis

Outcome Measures

Primary Outcomes (2)

• The Bioequivalent (BE) Comparison of AUC0-inf of Monomethyl Fumarate (MMF) Between Treatments

  Pharmacokinetics: Plasma concentrations of MMF will be determined and used to calculate AUC0-inf MMF for each treatment. Venous blood samples were collected immediately prior to dosing (time 0), and then 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 9, 10, 11, 12, and 24 hours postdose.

  24 hours

• The BE Comparison of Cmax of Monomethyl Fumarate (MMF) Between Treatments

  Pharmacokinetics: Plasma concentrations of MMF will be determined and used to calculate the Cmax of MMF for each treatment.Venous blood samples were collected immediately prior to dosing, and then 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 9, 10, 11, 12, and 24 hours postdose.

  24 hours

Study Arms (2)

Test (BLS-11)

EXPERIMENTAL

A single oral dose administration of BLS-11 190 mg (2 × 95 mg monomethyl fumarate delayed-release capsules) at Hour 0 on Day 1

Drug: monomethyl fumarate 190 mg

Reference (Tecfidera)

ACTIVE COMPARATOR

A single oral dose administration of Tecfidera 240 mg (1 × 240 mg dimethyl fumarate delayed-release capsule) at Hour 0 on Day 1

Drug: dimethyl fumarate 240 mg

Interventions

monomethyl fumarate 190 mg DRUG

Also known as: BAFIERTAM, BLS-11

Test (BLS-11)

dimethyl fumarate 240 mg DRUG

Also known as: Tecfidera

Reference (Tecfidera)

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Continuous non-smoker who had not used nicotine-containing products for at least 3 months prior to the first dose and throughout the study.
• Body mass index (BMI) ≥ 18.5 and ≤ 29.9 kg/m2 at Screening.
• 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.
• 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.
• 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.
• 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.)
• Males agreed not to donate sperm from the first dose until 90 days after dosing.
• Understood the study procedures in the Informed Consent Form (ICF), and were willing and able to comply with the protocol.

You may not qualify if:

• 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.
• History or presence of clinically significant medical or psychiatric condition or disease in the opinion of the Investigator or designee.
• 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.
• History or presence of alcoholism or drug abuse within the past 2 years prior to the first dose.
• History or presence of hypersensitivity or idiosyncratic reaction to the study drugs or related compounds.
• Female subjects with a positive serum pregnancy test at Screening or Check-in, or who were lactating.
• Positive urine drug, alcohol, or cotinine results at Screening or Check-in.
• Positive results at Screening for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV).
• Seated blood pressure was less than 90/40 mmHg or greater than 140/90 mmHg at Screening.
• Seated heart rate was lower than 40 beats per minute (bpm) or higher than 99 bpm at Screening.
• Abnormal 12-lead ECG deemed clinically significant by the Investigator or designee at Screening or prior to the first dose.
• 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.
• 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.
• Donation of blood or significant blood loss within 30 days prior to the first dose.
• Plasma donation within 7 days prior to the first dose.

Sponsors & Collaborators

• Banner Life Sciences LLC: lead

Related Publications (1)

• Lategan TW, Wang L, Sprague TN, Rousseau FS. Pharmacokinetics and Bioavailability of Monomethyl Fumarate Following a Single Oral Dose of Bafiertam (Monomethyl Fumarate) or Tecfidera(R) (Dimethyl Fumarate). CNS Drugs. 2021 May;35(5):567-574. doi: 10.1007/s40263-021-00799-9. Epub 2021 Mar 30.

  PMID: 33797063 RESULT

Related Links

• Open Access

MeSH Terms

Conditions

Multiple Sclerosis, Relapsing-Remitting

Interventions

monomethyl fumarate; Dimethyl Fumarate

Condition Hierarchy (Ancestors)

Multiple Sclerosis; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Fumarates; Dicarboxylic Acids; Acids, Acyclic; Carboxylic Acids; Organic Chemicals

Results Point of Contact

• Title: Thomas Lategan, PhD
• Organization: Banner Life Sciences LLC

thomas.lategan@bannerls.com

3368990959

Study Officials

• Franck Rousseau, MD

  Banner Life Sciences LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Subjects were randomized to 1 of 2 treatment sequences prior to the first dose.

Study Record Dates

• First Submitted: September 22, 2020
• First Posted: September 30, 2020
• Study Start: January 6, 2017
• Primary Completion: February 17, 2017
• Study Completion: February 17, 2017
• Last Updated: December 30, 2022
• Results First Posted: July 28, 2021

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will not share