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

Sponsor
Biogen (Industry)
Overall Status
Not yet recruiting
CT.gov ID
NCT05127564
Collaborator
(none)
32
Enrollment
2
Arms
5.4
Anticipated Duration (Months)

Study Details

Study Description

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.

Condition or DiseaseIntervention/TreatmentPhase
  • Drug: Diroximel fumarate
Phase 1

Study Design

Study Type:
Interventional
Anticipated Enrollment :
32 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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
Anticipated Study Start Date :
Jan 31, 2022
Anticipated Primary Completion Date :
Jul 15, 2022
Anticipated Study Completion Date :
Jul 15, 2022

Arms and Interventions

ArmIntervention/Treatment
Experimental: DRF: Chinese Participants

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
Administered as specified in the treatment arm
Other Names:
  • Vumerity
  • BIIB098
  • Experimental: DRF: Caucasian Participants

    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
    Administered as specified in the treatment arm
    Other Names:
  • Vumerity
  • BIIB098
  • Outcome Measures

    Primary Outcome Measures

    1. 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]

    2. 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 Outcome Measures

    1. 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]

    2. 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]

    3. 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]

    4. 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]

    5. 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]

    6. Accumulation Ratio Following Multiple Dosing (Rac) of MMF [Pre-dose and at multiple timepoints post-dose on Days 1 and 5 and post-dose on Days 6, 7 and 8]

    7. Maximum Observed Concentration (Cmax) of 2-Hydroxyethyl Succinimide (HES) [Pre-dose and at multiple timepoints post-dose on Days 1 and 5 and post-dose on Days 6, 7 and 8]

    8. Area Under the Concentration-Time Curve within a Dosing Interval (AUCtau) of HES [Pre-dose and at multiple timepoints post-dose on Days 1 and 5 and post-dose on Days 6, 7 and 8]

    9. Time to Reach Maximum Observed Concentration (Tmax) of HES [Pre-dose and at multiple timepoints post-dose on Days 1 and 5 and post-dose on Days 6, 7 and 8]

    10. Elimination Half-Life (t½) of HES [Pre-dose and at multiple timepoints post-dose on Days 1 and 5 and post-dose on Days 6, 7 and 8]

    11. Lag Time in Absorption (Tlag) of HES [Pre-dose and at multiple timepoints post-dose on Days 1 and 5 and post-dose on Days 6, 7 and 8]

    12. Apparent Total Body Clearance (CL/F) of HES [Pre-dose and at multiple timepoints post-dose on Days 1 and 5 and post-dose on Days 6, 7 and 8]

    13. Apparent Volume of Distribution (Vz/F) of HES [Pre-dose and at multiple timepoints post-dose on Days 1 and 5 and post-dose on Days 6, 7 and 8]

    14. Accumulation Ratio Following Multiple Dosing (Rac) of HES [Pre-dose and at multiple timepoints post-dose on Days 1 and 5 and post-dose on Days 6, 7 and 8]

    15. Number of Participants with Adverse Events (AEs) [Day 1 to Day 10]

      An adverse event (AE) is any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product.

    16. Number of Participants with Serious Adverse Events (SAEs) [Screening to Day 10]

      A serious adverse event (SAE) is any untoward medical occurrence that at any dose results in death, in the view of the investigator, places the participant at immediate risk of death (a life-threatening event), requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, results in a congenital anomaly/birth defect or is a medically important event.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 55 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    Yes
    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.

    Contacts and Locations

    Locations

    No locations specified.

    Sponsors and Collaborators

    • Biogen

    Investigators

    • Study Director: Medical Director, Biogen

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Biogen
    ClinicalTrials.gov Identifier:
    NCT05127564
    Other Study ID Numbers:
    • 272HV111
    First Posted:
    Nov 19, 2021
    Last Update Posted:
    Nov 19, 2021
    Last Verified:
    Jul 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No

    Study Results

    No Results Posted as of Nov 19, 2021