A Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of Diroximel Fumarate (DRF) in Chinese and Caucasian Adult Healthy Participants

NCT05127564 | Completed Phase 1

• 1 other identifier: 272HV111
• Study Type: interventional
• Target: 32
• Locations: 2 countries
• Sites: 2

Brief Summary

The primary objective is to evaluate the primary pharmacokinetic (PK) parameters of DRF active metabolite monomethyl fumarate (MMF) following multiple doses of DRF in Chinese and Caucasian adult healthy participants. The secondary objectives are to evaluate the secondary PK parameters of DRF active metabolite MMF following multiple doses of DRF in Chinese and Caucasian adult healthy participants, to evaluate the PK of DRF inactive major metabolite 2-hydroxyethyl succinimide (HES) following multiple doses of DRF in Chinese and Caucasian adult healthy participants and to evaluate the safety and tolerability of multiple oral doses of DRF in Chinese and Caucasian adult healthy participants.

Conditions

Healthy Volunteers

Outcome Measures

Primary Outcomes (2)

• Maximum Observed Concentration (Cmax) of Monomethyl Fumarate (MMF)

  Pre-dose and at multiple timepoints post-dose on Days 1 and 5 and post-dose on Days 6, 7 and 8

• Area Under the Concentration-Time Curve within a Dosing Interval (AUCtau) of MMF

  Pre-dose and at multiple timepoints post-dose on Days 1 and 5 and post-dose on Days 6, 7 and 8

Secondary Outcomes (16)

• Time to Reach Maximum Observed Concentration (Tmax) of MMF

  Pre-dose and at multiple timepoints post-dose on Days 1 and 5 and post-dose on Days 6, 7 and 8

• Elimination Half-Life (t½) of MMF

  Pre-dose and at multiple timepoints post-dose on Days 1 and 5 and post-dose on Days 6, 7 and 8

• Lag Time in Absorption (Tlag) of MMF

  Pre-dose and at multiple timepoints post-dose on Days 1 and 5 and post-dose on Days 6, 7 and 8

• Apparent Total Body Clearance (CL/F) of MMF

  Pre-dose and at multiple timepoints post-dose on Days 1 and 5 and post-dose on Days 6, 7 and 8

• Apparent Volume of Distribution (Vz/F) of MMF

  Pre-dose and at multiple timepoints post-dose on Days 1 and 5 and post-dose on Days 6, 7 and 8

Study Arms (2)

DRF: Chinese Participants

EXPERIMENTAL

Chinese participants will receive DRF Dose 1, oral capsules, twice daily (BID), from Day 1 to Day 4 and DRF Dose 1, oral capsules, once daily (QD), on Day 5.

Drug: Diroximel fumarate

DRF: Caucasian Participants

EXPERIMENTAL

Caucasian participants will receive DRF Dose 1, oral capsules, BID, from Day 1 to Day 4 and DRF Dose 1, oral capsules, QD, on Day 5.

Drug: Diroximel fumarate

Interventions

Diroximel fumarate DRUG

Administered as specified in the treatment arm

Also known as: Vumerity, BIIB098

DRF: Caucasian Participants; DRF: Chinese Participants

Eligibility Criteria

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

You may qualify if:

• Have a body mass index (BMI) between 18 and 30 kilograms per meter square (kg/m\^2), inclusive.
• Negative polymerase chain reaction (PCR) test result for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at screening and Day -1.
• For Chinese participants: was born in China, and biological parents and grandparents were of Chinese origin. If living outside China for more than 5 years, must not have had a significantly modified diet since leaving China.

You may not qualify if:

• History of severe allergic or anaphylactic reactions or of any allergic reactions that, in the opinion of the investigator, are likely to be exacerbated by any component of the study treatment; or systemic hypersensitivity reactions to DRF, dimethyl fumarate (DMF), MMF, other fumaric esters, excipients in the formulation, or diagnostic agents to be administered during the study.
• Confirmed demonstration of corrected QT interval, using Fridericia's correction method, of \>450 milliseconds (ms) for males and \>460 ms for females.
• Has a history of gastrointestinal (GI) surgery (except appendectomy or cholecystectomy that occurred more than 6 months prior to screening), irritable bowel syndrome, inflammatory bowel disease (Crohn's disease, ulcerative colitis), or other clinically significant and active GI condition, per the investigator's discretion.
• Has experienced clinically significant acute GI symptoms in the judgment of the investigator within 30 days prior to admission.
• History or positive test result at screening for human immunodeficiency virus (HIV).
• Chronic, recurrent, or serious infection, as determined by the investigator, within 90 days prior to screening and between screening and Day -1.
• Current enrollment in any other drug, biological, device, or clinical study or treatment with an investigational drug or approved therapy for investigational use within 30 days prior to Day -1, or 5 half-lives, whichever is longer.
• Previous participation in this study or previous studies with DRF or DMF.

Sponsors & Collaborators

• Biogen: lead

Study Sites (2)

Research Site

Shatin, New Territories, Hong Kong

Location

Research Site

Christchurch, 8011, New Zealand

Location

MeSH Terms

Interventions

diroximel fumarate

Study Officials

• Medical Director

  Biogen

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: November 9, 2021
• First Posted: November 19, 2021
• Study Start: December 3, 2021
• Primary Completion: June 9, 2022
• Study Completion: June 29, 2022
• Last Updated: July 5, 2022

Record last verified: 2022-06

Data Sharing

• IPD Sharing: Will share

Locations

HK (1); NZ (1)