Clinical trial NCT05127564: A Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of Diroximel Fumarate (DRF) in Chinese and Caucasian Adult Healthy Participants
Official title: An Open-Label, Parallel-Group, Phase 1 Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of Diroximel Fumarate (BIIB098) in Chinese and Caucasian Adult Healthy Participants
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Lead sponsor: Biogen
Sponsor class: INDUSTRY
First posted: 2021-11-19
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Key Inclusion Criteria:

* 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.

Key Exclusion Criteria:

* 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.

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Primary outcomes:
measure: Maximum Observed Concentration (Cmax) of Monomethyl Fumarate (MMF)
timeFrame: Pre-dose and at multiple timepoints post-dose on Days 1 and 5 and post-dose on Days 6, 7 and 8
measure: Area Under the Concentration-Time Curve within a Dosing Interval (AUCtau) of MMF
timeFrame: Pre-dose and at multiple timepoints post-dose on Days 1 and 5 and post-dose on Days 6, 7 and 8
Secondary outcomes:
measure: Time to Reach Maximum Observed Concentration (Tmax) of MMF
timeFrame: Pre-dose and at multiple timepoints post-dose on Days 1 and 5 and post-dose on Days 6, 7 and 8
measure: Elimination Half-Life (t½) of MMF
timeFrame: Pre-dose and at multiple timepoints post-dose on Days 1 and 5 and post-dose on Days 6, 7 and 8
measure: Lag Time in Absorption (Tlag) of MMF
timeFrame: Pre-dose and at multiple timepoints post-dose on Days 1 and 5 and post-dose on Days 6, 7 and 8
measure: Apparent Total Body Clearance (CL/F) of MMF
timeFrame: Pre-dose and at multiple timepoints post-dose on Days 1 and 5 and post-dose on Days 6, 7 and 8
measure: Apparent Volume of Distribution (Vz/F) of MMF
timeFrame: Pre-dose and at multiple timepoints post-dose on Days 1 and 5 and post-dose on Days 6, 7 and 8
measure: Accumulation Ratio Following Multiple Dosing (Rac) of MMF
timeFrame: Pre-dose and at multiple timepoints post-dose on Days 1 and 5 and post-dose on Days 6, 7 and 8
measure: Maximum Observed Concentration (Cmax) of 2-Hydroxyethyl Succinimide (HES)
timeFrame: Pre-dose and at multiple timepoints post-dose on Days 1 and 5 and post-dose on Days 6, 7 and 8
measure: Area Under the Concentration-Time Curve within a Dosing Interval (AUCtau) of HES
timeFrame: Pre-dose and at multiple timepoints post-dose on Days 1 and 5 and post-dose on Days 6, 7 and 8
measure: Time to Reach Maximum Observed Concentration (Tmax) of HES
timeFrame: Pre-dose and at multiple timepoints post-dose on Days 1 and 5 and post-dose on Days 6, 7 and 8
measure: Elimination Half-Life (t½) of HES
timeFrame: Pre-dose and at multiple timepoints post-dose on Days 1 and 5 and post-dose on Days 6, 7 and 8
measure: Lag Time in Absorption (Tlag) of HES
timeFrame: Pre-dose and at multiple timepoints post-dose on Days 1 and 5 and post-dose on Days 6, 7 and 8
measure: Apparent Total Body Clearance (CL/F) of HES
timeFrame: Pre-dose and at multiple timepoints post-dose on Days 1 and 5 and post-dose on Days 6, 7 and 8
measure: Apparent Volume of Distribution (Vz/F) of HES
timeFrame: Pre-dose and at multiple timepoints post-dose on Days 1 and 5 and post-dose on Days 6, 7 and 8
measure: Accumulation Ratio Following Multiple Dosing (Rac) of HES
timeFrame: Pre-dose and at multiple timepoints post-dose on Days 1 and 5 and post-dose on Days 6, 7 and 8
measure: Number of Participants with Adverse Events (AEs)
timeFrame: Day 1 to Day 10
measure: Number of Participants with Serious Adverse Events (SAEs)
timeFrame: Screening to Day 10
Other outcomes:
Locations:
city: Sha Tin
country: Hong Kong
facility: Research Site
state: New Territories
city: Christchurch
country: New Zealand
facility: Research Site
Study officials:
affiliation: Biogen
name: Medical Director
role: STUDY_DIRECTOR
References: