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

Healthy Volunteers Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05127564
• Other study ID #: 272HV111
• Status: Completed
• Phase: Phase 1
• Start date: December 3, 2021
• Est. completion date: June 29, 2022

Study information

• Verified date: June 2022
• Source: Biogen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 32
• Est. completion date: June 29, 2022
• Est. primary completion date: June 9, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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.

Related Conditions & MeSH terms

• Healthy Volunteers

Intervention

Drug:
• Diroximel fumarate
Administered as specified in the treatment arm

Locations

Country	Name	City	State
Hong Kong	Research Site	Sha Tin	New Territories
New Zealand	Research Site	Christchurch

Sponsors (1)

Lead Sponsor	Collaborator
Biogen

Countries where clinical trial is conducted

Hong Kong,  New Zealand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Number of Participants with Adverse Events (AEs)	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.	Day 1 to Day 10
Secondary	Number of Participants with Serious Adverse Events (SAEs)	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.	Screening to Day 10