Prevention Study in Adult Patients Suffering From Migraine Headaches

NCT ID: NCT00742209

Last Updated: 2013-07-22

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

526 participants

Study Classification

INTERVENTIONAL

Study Start Date

2008-08-31

Study Completion Date

2010-06-30

Brief Summary

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Purpose of the study is to evaluate dose response relationship, efficacy, safety and tolerability of target doses of GSK1838262 compared to placebo in the prophylactic treatment of migraine headache. Once subjects complete the baseline and meet the randomization criteria, they will complete a 5-wk flexible titration period and then enter the 12 week maintenance period.

Detailed Description

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MPX111381 is a multicenter, randomized, double-blind, placebo-controlled, parallel group, flexible-dose evaluation of GSK1838262 1200 mg/day, 1800 mg/day, 2400 mg/day and 3000 mg/day compared with placebo in the prophylactic treatment of migraine headache.

Subjects 18 years of age must have experienced at least three migraine headache attacks (with or without aura according to 2004 International Headache Society \[IHS\] criteria 1.1 and 1.2.1) per month during the 3 months prior to screening and at least four migraine headache days but less than 15 total headache days (migraine or non-migraine) per month during the 3 months prior to screening and must maintain this requirement throughout the last 4 weeks of the baseline period. Approximately 528 subjects from approximately 53 centers in North America will be randomized in a 2:1:2:2:1 ratio to the following treatment groups: placebo, GSK1838262 1200 mg/day, 1800 mg/day, 2400 mg/day and 3000 mg/day. Investigational product will be administered twice daily (morning and evening) with food (e.g., meal or snack).

The study will consist of six study periods for a total study duration of up to 30 weeks: Screening (2 weeks), baseline (including randomization, 6 weeks), flexible titration (5 weeks), maintenance (12 weeks), taper (3 weeks) and post-treatment (2 weeks). The flexible titration administration of investigational product is designed to allow subjects to reach the target dose for maintenance treatment or, if unable to reach this target dose, to achieve a maximum tolerated dose for maintenance treatment. Subjects will have the opportunity to undergo a single dose (600 mg/day) downward adjustment during the flexible titration period if intolerability at the current dose occurs. Subsequently, if a single dose downward adjustment has occurred, no further dose adjustments in the study (upward or downward) will be permitted.

Conditions

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Migraine Disorders Migraine

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Placebo

PBO

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Placebo-control

GSK 1838262 1200 mg/day

600 or 1200 mg/day

Group Type ACTIVE_COMPARATOR

GSK1838262

Intervention Type DRUG

Flexible dosing: 1200 mg/day, 1800 mg/day, 2400 mg/day and 3000 mg/day

GSK 1838262 1800 mg/day

600 or 1200 or 1800 mg/day

Group Type ACTIVE_COMPARATOR

GSK1838262

Intervention Type DRUG

Flexible dosing: 1200 mg/day, 1800 mg/day, 2400 mg/day and 3000 mg/day

GSK 1838262 2400 mg/day

600 or 1200 or 1800 or 2400 mg/day

Group Type ACTIVE_COMPARATOR

GSK1838262

Intervention Type DRUG

Flexible dosing: 1200 mg/day, 1800 mg/day, 2400 mg/day and 3000 mg/day

GSK 1838262 3000 mg/day

600 or 1200 or 1800 or 2400 or 3000 mg/day

Group Type ACTIVE_COMPARATOR

GSK1838262

Intervention Type DRUG

Flexible dosing: 1200 mg/day, 1800 mg/day, 2400 mg/day and 3000 mg/day

Interventions

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GSK1838262

Flexible dosing: 1200 mg/day, 1800 mg/day, 2400 mg/day and 3000 mg/day

Intervention Type DRUG

Placebo

Placebo-control

Intervention Type DRUG

Other Intervention Names

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XP13512

Eligibility Criteria

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Inclusion Criteria

* Outpatient subjects aged 18 years or older.
* Females of non-childbearing potential. If of child-bearing potential, is not lactating and has a negative pregnancy test 7 days prior to study treatment initiation and agrees to use one of the GlaxoSmithKline (GSK)-specified highly effective methods for avoiding pregnancy.
* Subjects suffering from migraine headache with or without aura, according to 2004 IHS criteria 1.1 and 1.2.1.
* Subject has had a history of migraine headache for at least one year, and the age of onset was prior to 50 years.
* Subject has consistent migraine headache over time (i.e., incidence and severity).
* Subject has had at least three migraine headache attacks per month during the 3 months prior to screening and maintains this requirement during the last 4 weeks of the baseline period
* Subject has had at least four migraine headache days but less than 15 total headache days (migraine or non-migraine) per month during the 3 months prior to screening and maintains this requirement during the last 4 weeks of the baseline period.
* Subject is able to distinguish migraine headache attacks as discrete from other headaches (i.e., tension-type headaches).
* Subject has the ability to read, comprehend and legibly and reliably record information in paper and electronic format as required by the protocol.
* Subject must be able to provide written informed consent prior to participation in the study. The contents and process of obtaining informed consent will be in accordance with all applicable regulatory requirements.

Exclusion Criteria

* Subject has a history of ergotamine, triptan, opioid, and/or combination pain medication use on \>/=10 days per month on a regular basis for \>/= 3 months.
* Subject has failed more than 2 adequate treatments of migraine prophylaxis -where failure is defined as a lack of efficacy with treatment duration of at least 8 weeks.
* Subject has history of simple analgesic use on \>/=15 days per month for \>/=3months.
* Subject is unable to discontinue prohibited medications during the 2-week screening period and throughout the duration of the study including beta-blockers, benzodiazepines, tricyclic antidepressants, calcium channel blockers, antiepileptic drugs, bupropion or serotonergic noradrenergic reuptake inhibitors (SNRIs).
* Subjects who have taken gabapentin or pregabalin previously for the prophylactic treatment of migraine headache. Subjects who have taken gabapentin or pregabalin for treatment of conditions other than migraine are eligible provided, (1) their total exposure to gabapentin and pregabalin is less than 3 months during the preceding 12 months, and (2) the subject stopped taking gabapentin or pregabalin for at least 3 months prior to baseline.
* Subject has a history of cluster headaches or basilar, ophthalmoplegic, hemiplegic, or transformed migraine headaches.
* Subject has a current or past history of seizure disorder.
* Subject has any of the following medical conditions, laboratory abnormalities or disorders:
* Hepatic impairment defined as alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \>2x upper limit of normal (ULN) or alkaline phosphatase or bilirubin \>1.5x ULN
* Chronic hepatitis B or C with a positive Hepatitis B surface antigen (HBsAg) or Hepatitis C Core Antigen Antibody (Hep C antibody)
* Impaired renal function defined as either creatinine clearance \<60 mL/min (estimation of creatinine clearance by Cockroft and Gault Method) or renal dysfunction requiring hemodialysis
* Corrected QT (QTc) interval \>/= 450 msec based on the average QTc value of triplicate electrocardiograms (ECGs) obtained by the central ECG reader over a brief recording period
* QTc interval \>/= 480 msec for subjects with Bundle Branch Block based on the average QTc value of triplicate ECGs obtained by the central ECG reader over a brief recording period
* Uncontrolled hypertension at screen or at time of randomization (sitting systolic blood pressure \[SBP\] \>160 mmHg and/or sitting diastolic blood pressure \[DBP\] \>90 mmHg)
* Medical condition or disorder that would interfere with the action, absorption, distribution, metabolism, or excretion of GSK1838262, or, in the investigator's judgement:
* Is considered to be clinically significant and may pose a safety concern, or,
* Could interfere with the accurate assessment of safety or efficacy, or,
* Could potentially affect a subject's safety or study outcome.
* Subject meets criteria as defined by the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR) for a major depressive episode or for active significant psychiatric disorders within the past year, including dementia, general anxiety disorder, psychotic disorders or bipolar disorder.
* Subjects with a history of depression that is in remission, with or without antidepressant treatment, may participate, unless a stable antidepressant regimen includes a prohibited medication.
* Antidepressant medication may not be changed or discontinued to meet entry criteria and must be stable for at least 3 months prior to screening.
* Subject has a history of clinically significant drug or alcohol abuse as defined by DSM IV TR or is unable to refrain from substance abuse throughout the study.
* Subject is currently participating in another clinical study in which the subject is, or will be exposed to an investigational or non-investigational drug or device.
* Subject has participated in a clinical study in which the subject was exposed to an investigational or non investigational drug or device:
* Within the preceding month for studies unrelated to the current illness (migraine headaches), or
* Within the preceding 3 months for studies related to the current illness (migraine headaches).
* Subjects who have taken botulinum toxin type A (Botox) within the past 6 months.
* Subject has a history of an allergic reaction, or a medically significant adverse reaction to the investigational product or excipients, which, in the opinion of the investigator, makes a subject unsuitable for participation in the study.
* Subject is felt to be at risk of non-compliance (e.g., for taking investigational product or for completing the electronic diary \[e-diary\]), in the investigator's opinion.
* Subject is a pregnant or nursing woman.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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GlaxoSmithKline

INDUSTRY

Sponsor Role collaborator

XenoPort, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline

Locations

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GSK Investigational Site

Birmingham, Alabama, United States

Site Status

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Phoenix, Arizona, United States

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GSK Investigational Site

Phoenix, Arizona, United States

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Anaheim, California, United States

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Newport Beach, California, United States

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Redlands, California, United States

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San Francisco, California, United States

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Santa Monica, California, United States

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Westlake Village, California, United States

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Colorado Springs, Colorado, United States

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Colorado Springs, Colorado, United States

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Denver, Colorado, United States

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DeLand, Florida, United States

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Sunrise, Florida, United States

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West Palm Beach, Florida, United States

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Atlanta, Georgia, United States

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Stockbridge, Georgia, United States

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Chicago, Illinois, United States

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Wichita, Kansas, United States

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Kalamazoo, Michigan, United States

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Golden Valley, Minnesota, United States

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Kansas City, Missouri, United States

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Springfield, Missouri, United States

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St Louis, Missouri, United States

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Las Vegas, Nevada, United States

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Albany, New York, United States

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Greensboro, North Carolina, United States

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Raleigh, North Carolina, United States

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Raleigh, North Carolina, United States

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Cleveland, Ohio, United States

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West Chester, Ohio, United States

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Westerville, Ohio, United States

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Philadelphia, Pennsylvania, United States

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Philadelphia, Pennsylvania, United States

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Pittsburgh, Pennsylvania, United States

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Charleston, South Carolina, United States

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Memphis, Tennessee, United States

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Nashville, Tennessee, United States

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Houston, Texas, United States

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San Antonio, Texas, United States

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Salt Lake City, Utah, United States

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Salt Lake City, Utah, United States

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Alexandria, Virginia, United States

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Seattle, Washington, United States

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Wenatchee, Washington, United States

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Penticton, British Columbia, Canada

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Surrey, British Columbia, Canada

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Bay Roberts, Newfoundland and Labrador, Canada

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Brampton, Ontario, Canada

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Greater Sudbury, Ontario, Canada

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Ottawa, Ontario, Canada

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Ottawa, Ontario, Canada

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Toronto, Ontario, Canada

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Toronto, Ontario, Canada

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Toronto, Ontario, Canada

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Montreal, Quebec, Canada

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Québec, Quebec, Canada

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GSK Investigational Site

Saint Romuald, Quebec, Canada

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GSK Investigational Site

Sherbrooke, Quebec, Canada

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Countries

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United States Canada

References

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Silberstein S, Goode-Sellers S, Twomey C, Saiers J, Ascher J. Randomized, double-blind, placebo-controlled, phase II trial of gabapentin enacarbil for migraine prophylaxis. Cephalalgia. 2013 Jan;33(2):101-11. doi: 10.1177/0333102412466968. Epub 2012 Nov 19.

Reference Type DERIVED
PMID: 23165696 (View on PubMed)

Other Identifiers

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111381

Identifier Type: -

Identifier Source: org_study_id

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