Alternate Dosing Regimens of BG00012 in Healthy Volunteers (109HV106)

A Randomized, Double-Blind, Placebo-Controlled Study of the Safety, Tolerability, and Pharmacokinetics of BG00012 Administered With and Without 325 mg Aspirin in Healthy Adult Volunteers

The purpose of this study is to evaluate the safety, tolerability, and PK of different doses and dosing regimens of BG00012 administered with and without ASA compared to placebo

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Aspirin; Drug: Dimethyl Fumarate (BG00012); Drug: ASA matching placebo; Drug: BG00012 matching placebo

Detailed Description

Preclinical safety margins for BG00012 allow for a maximum daily dose of 720 mg daily. The study will use a variety of clinical scales, including a flushing scale derived from a validated questionnaire [Norquist 2007], to better understand the safety and tolerability of several doses and dosing regimens of BG00012 up to a total daily dose of 720 mg. The etiology of BG00012-induced flushing will be assessed by collecting relevant biomarker data and the impact of ASA on flushing will be evaluated. Assessments relating to GI symptoms will also be performed.

• Study Type: Interventional
• Enrollment (Actual): 56
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Saint Paul, Minnesota, United States, 55114
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information (PHI) in accordance with national and local subject privacy regulations.
• Aged 18 to 55 years old, inclusive, at the time of informed consent.
• Must be in good health, as determined by the Investigator, based on medical history and screening evaluations.
• Must have a body mass index of 18 to 34 kg/m2, inclusive.
• Subjects of childbearing potential must practice effective contraception during the study and be willing and able to continue contraception for 30 days after their last dose of study treatment.

Exclusion Criteria:

• History of any clinically significant cardiac, endocrinologic, GI, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, neurologic, dermatologic, psychiatric, renal, or other major disease, as determined by the Investigator.
• History of malignant disease, including solid tumors and hematologic malignancies (except basal cell and squamous cell carcinomas of the skin that have been completely excised and are considered cured).
• Serious infection (e.g., pneumonia, septicemia) as determined by the Investigator within the 3 months prior to Day 1.
• Diarrhea, constipation, abdominal pain, flushing, or nausea within 28 days prior to Day 1.
• History of severe allergic or anaphylactic reactions. Additionally, subjects with a history of intolerance to ASA or non-steroidal anti-inflammatory drugs (NSAIDS) must be excluded.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: Double

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BG00012 plus ASA	Drug: Aspirin; Drug: Dimethyl Fumarate (BG00012)
Experimental: BG00012 plus ASA matching placebo	Drug: Dimethyl Fumarate (BG00012); Drug: ASA matching placebo
Placebo Comparator: BG00012 Placebo plus ASA	Drug: Aspirin; Drug: BG00012 matching placebo
Experimental: BG00012 Placebo plus ASA matching placebo	Drug: ASA matching placebo; Drug: BG00012 matching placebo
Experimental: BG00012; modified dose regimen	Drug: Dimethyl Fumarate (BG00012)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
• incidence of treatment emergent AEs	11 days
• incidence of serious AEs (SAEs)	11 days
• clinical laboratory assessments:	11 days
• Concentration versus time data for BG00012 (as measured by monomethyl fumarate (MMF), will be collected for each treatment group. Plasma PK parameters will include AUC, Cmax, time to maximum plasma concentration, half life & lagtime.	11 days

Secondary Outcome Measures

Outcome Measure	Time Frame
• incidence, severity, and duration (time of onset until time of resolution) of flushing based on flushing severity measurements.	11 days
• Incidence, severity, duration, and characteristics of GI events	11 days
• concentrations of PGD2 and/or its metabolites in plasma and/or urine and other prostaglandins, as well as other biomarkers in plasma and/or urine	11 days

Collaborators and Investigators

• Sponsor: Biogen

Publications and helpful links

General Publications

• Sheikh SI, Nestorov I, Russell H, O'Gorman J, Huang R, Milne GL, Scannevin RH, Novas M, Dawson KT. Tolerability and pharmacokinetics of delayed-release dimethyl fumarate administered with and without aspirin in healthy volunteers. Clin Ther. 2013 Oct;35(10):1582-1594.e9. doi: 10.1016/j.clinthera.2013.08.009.

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2011
• Primary Completion (Actual): March 18, 2011
• Study Completion (Actual): March 18, 2011

Study Registration Dates

• First Submitted: January 20, 2011
• First Submitted That Met QC Criteria: January 20, 2011
• First Posted (Estimated): January 21, 2011

Study Record Updates

• Last Update Posted (Actual): August 23, 2023
• Last Update Submitted That Met QC Criteria: August 22, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Fibrinolytic Agents; Fibrin Modulating Agents; Platelet Aggregation Inhibitors; Cyclooxygenase Inhibitors; Antipyretics; Immunosuppressive Agents; Immunologic Factors; Dermatologic Agents; Aspirin; Dimethyl Fumarate
• Other Study ID Numbers: 109HV106