Clinical trial NCT01281111: Alternate Dosing Regimens of BG00012 in Healthy Volunteers
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Biogen
Sponsor class: INDUSTRY
First posted: 2011-01-21
Enrollment: 56
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: BASIC_SCIENCE

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: • incidence of treatment emergent AEs
timeFrame: 11 days
measure: • incidence of serious AEs (SAEs)
timeFrame: 11 days
measure: • clinical laboratory assessments:
timeFrame: 11 days
measure: • 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.
timeFrame: 11 days
Secondary outcomes:
measure: • incidence, severity, and duration (time of onset until time of resolution) of flushing based on flushing severity measurements.
timeFrame: 11 days
measure: • Incidence, severity, duration, and characteristics of GI events
timeFrame: 11 days
measure: • 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
timeFrame: 11 days
Other outcomes:
Locations:
city: Saint Paul
country: United States
facility: Research Site
state: Minnesota
Study officials:
References:
citation: 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.