Alternate Dosing Regimens of BG00012 in Healthy Volunteers

Study Overview
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Brief Summary
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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

Detailed Description
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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.

Official Title
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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

Conditions
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Healthy

Intervention / Treatment
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* Drug: Dimethyl Fumarate (BG00012)
* Drug: Aspirin
* Drug: BG00012 matching placebo
* Drug: ASA matching placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 &amp; lagtime. |  | 11 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | 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 |