A Study in Healthy Volunteers to Evaluate Effects of Pre-Medication or Slow Dose Titration on Flushing and Gastrointestinal Events

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Biogen
ClinicalTrials.gov Identifier:
NCT01568112
First received: March 29, 2012
Last updated: November 3, 2014
Last verified: November 2014
  Purpose

The primary objective of the study is to evaluate whether premedication with 325 mg microcoated aspirin (ASA) tablet or a slow-titration dosing schedule of BG00012 reduces the incidence and severity of flushing and GI events following oral administration of BG00012 dosed at 240 mg twice a day (BID) in healthy volunteers. The secondary objective of this study is to evaluate the safety and tolerability of BG00012 when administered orally as a 240 mg BID dose regimen with and without 325 mg ASA premedication or following a slow-titration dosing schedule in healthy volunteers.


Condition Intervention Phase
Healthy
Drug: BG00012 (dimethyl fumarate)
Drug: BG00012 placebo
Drug: ASA
Drug: ASA placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Supportive Care
Official Title: A Randomized, Double-Blind, Phase 3b Study to Evaluate Effects of Aspirin or Slow Dose Titration on Flushing and Gastrointestinal Events Following Oral Administration of BG00012 Dosed at 240 mg BID

Resource links provided by NLM:


Further study details as provided by Biogen:

Primary Outcome Measures:
  • Incidence and severity of flushing based on the Modified Flushing Severity Scale (MFSS) [ Time Frame: Day 1 to Week 8 ] [ Designated as safety issue: Yes ]
  • Incidence and severity of flushing based on the Modified Global Flushing Severity Scale (MGFSS) [ Time Frame: Day 1 to Week 8 ] [ Designated as safety issue: Yes ]
  • The incidence and severity of gastrointestinal events by using modified acute gastrointestinal scale (MAGISS) [ Time Frame: Day 1 to Week 8 ] [ Designated as safety issue: Yes ]
  • The incidence and severity of gastrointestinal events by using modified overall gastrointestinal scale (MOGISS) [ Time Frame: Day 1 to Week 8 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Number of Participants with Adverse Events as a measure of safety and tolerability [ Time Frame: Day 1 up to week 9 ] [ Designated as safety issue: Yes ]
  • Duration of Flushing side effects based on modified acute flushing scale and the modified global flushing scale [ Time Frame: Day 1 to Week 8 ] [ Designated as safety issue: Yes ]
  • Duration of GI side effects based on modified acute gastrointestinal scale and modified overall gastrointestinal symptom scale [ Time Frame: Day 1 to Week 8 ] [ Designated as safety issue: Yes ]

Enrollment: 173
Study Start Date: April 2012
Study Completion Date: October 2012
Primary Completion Date: October 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Fast Titration of BG00012 and ASA placebo
Participants begin the study with a 1-week fast-titration dosing schedule of a total daily dose of 240 mg BG00012 followed by a total daily dose of 480 mg BG00012 for 7 weeks. Participants receive premedication with ASA placebo for the first 4 weeks only.
Drug: BG00012 (dimethyl fumarate)
Each capsule contains 120 mg dimethyl fumarate (DMF). Fast titration involves taking one 120 mg capsule in the morning and one in the evening (240 mg daily) for one week, and then escalating to a dose of 480 mg daily (two capsules morning and evening) for the remainder of the study.Slow titration expands the dose escalation time to 4 weeks.
Other Names:
  • BG-12
  • oral fumarate
  • DMF
Drug: BG00012 placebo
Placebo matching BG00012
Drug: ASA placebo
Placebo matching aspirin
Placebo Comparator: BG00012 placebo and ASA placebo
Participants receive BG00012 placebo for 8 weeks. Participants receive premedication with ASA placebo for the first 4 weeks only.
Drug: BG00012 placebo
Placebo matching BG00012
Drug: ASA placebo
Placebo matching aspirin
Experimental: Fast Titration of BG00012 and ASA
Participants begin the study with a 1-week fast-titration dosing schedule of a total daily dose of 240 mg BG00012 followed by a total daily dose of 480 mg BG00012 for 7 weeks. Participants receive premedication with 325 mg microcoated aspirin (ASA) for the first 4 weeks only.
Drug: BG00012 (dimethyl fumarate)
Each capsule contains 120 mg dimethyl fumarate (DMF). Fast titration involves taking one 120 mg capsule in the morning and one in the evening (240 mg daily) for one week, and then escalating to a dose of 480 mg daily (two capsules morning and evening) for the remainder of the study.Slow titration expands the dose escalation time to 4 weeks.
Other Names:
  • BG-12
  • oral fumarate
  • DMF
Drug: BG00012 placebo
Placebo matching BG00012
Drug: ASA
325 mg microcoated aspirin (ASA)
Other Names:
  • acetylsalicylic acid
  • Aspirin
Experimental: Slow Titration of BG00012 and ASA placebo
Participants follow a BG00012 slow-titration dosing schedule (4 increasing BG00012 doses over 4 weeks and maintaining the Week 4 dose (480 mg daily) until study completion (four additional weeks)). Participants receive premedication with ASA placebo for the first 4 weeks only.
Drug: BG00012 (dimethyl fumarate)
Each capsule contains 120 mg dimethyl fumarate (DMF). Fast titration involves taking one 120 mg capsule in the morning and one in the evening (240 mg daily) for one week, and then escalating to a dose of 480 mg daily (two capsules morning and evening) for the remainder of the study.Slow titration expands the dose escalation time to 4 weeks.
Other Names:
  • BG-12
  • oral fumarate
  • DMF
Drug: BG00012 placebo
Placebo matching BG00012
Drug: ASA placebo
Placebo matching aspirin

  Eligibility

Ages Eligible for Study:   25 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Key Inclusion Criteria:

  • Must give written informed consent and any authorizations required by local law
  • Must have a body mass index (BMI) of between 18.0 to 34.0 kg/m2,inclusive.
  • Ability to complete the tolerability scales by accurately using the hand-held subject reporting device
  • Subjects of childbearing potential must be willing to practice effective contraception

Key Exclusion Criteria:

  • History of clinically significant diseases
  • History of severe allergic or anaphylactic reactions
  • Intolerance to Aspirin or nonsteroidal anti-inflammatory drugs (NSAIDs)
  • Diarrhea, constipation, abdominal pain, flushing or nausea within 28 days prior to Day 1

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01568112

Locations
United States, Minnesota
Research Site
St Paul, Minnesota, United States
Sponsors and Collaborators
Biogen
Investigators
Study Director: Medical Director Biogen
  More Information

No publications provided

Responsible Party: Biogen
ClinicalTrials.gov Identifier: NCT01568112     History of Changes
Other Study ID Numbers: 109HV321
Study First Received: March 29, 2012
Last Updated: November 3, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Biogen:
BG00012, Aspirin, Pre-medication, dose titration, flushing events, gastrointestinal events

Additional relevant MeSH terms:
Flushing
Signs and Symptoms
Aspirin
Dimethyl fumarate
Analgesics
Analgesics, Non-Narcotic
Anti-Inflammatory Agents
Anti-Inflammatory Agents, Non-Steroidal
Antipyretics
Antirheumatic Agents
Cardiovascular Agents
Central Nervous System Agents
Cyclooxygenase Inhibitors
Dermatologic Agents
Enzyme Inhibitors
Fibrin Modulating Agents
Fibrinolytic Agents
Hematologic Agents
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Platelet Aggregation Inhibitors
Radiation-Sensitizing Agents
Sensory System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 01, 2015