Clinical trial NCT00742209: Prevention Study in Adult Patients Suffering From Migraine Headaches
Official title: Study MPX111381: A Dose-ranging Study Evaluating the Efficacy, Safety and Tolerability of GSK1838262 (XP13512) in the Prophylactic Treatment of Migraine Headache
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Migraine Disorders
Migraine
Keywords: migraine
prophylaxis
prevention
Lead sponsor: XenoPort, Inc.
Sponsor class: INDUSTRY
Collaborators: name: GlaxoSmithKline
First posted: 2008-08-27
Enrollment: 526
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Adjusted Mean Change From Baseline in the Number of Migraine Headache Days (MHD) During the Last 4 Weeks of Treatment Prior to Taper
timeFrame: Baseline and last 4 weeks of treatment prior to taper (up to Week 17)
Secondary outcomes:
measure: Mean Change From Baseline in the Number of MHD in All Study Phases
timeFrame: Baseline and last 4 weeks of treatment prior to taper (up to Week 17)
measure: Adjusted Mean Change From Baseline in the Number of Migraine Attacks
timeFrame: Baseline and last 4 weeks of treatment prior to taper (up to Week 17)
measure: Mean Change From Baseline in the Number of Migraine Headache Periods (MHP)
timeFrame: Baseline and last 4 weeks of treatment prior to taper (up to Week 17)
measure: Change From Baseline in the Mean Migraine Attack Duration
timeFrame: Baseline and last 4 weeks of treatment prior to taper (up to Week 17)
measure: Change From Baseline in the Mean Peak Migraine Pain Severity
timeFrame: Baseline and last 4 weeks of treatment prior to taper (up to Week 17)
measure: Mean Change From Baseline to the Last 4-Week Treatment Phase in the Number of Days of Acute Migraine Medication Use
timeFrame: Baseline and last 4 weeks of treatment prior to taper (up to Week 17)
measure: Mean Change From Baseline to the Last 4-Week Treatment Phase in the Number of Acute Migraine Medication Doses Administered
timeFrame: Baseline and last 4 weeks of treatment prior to taper (up to Week 17)
measure: Mean Change From Baseline to the Last 4-Week Treatment Phase in the Number of Acute Migraine Medication Doses Administered by Triptan Use
timeFrame: Baseline and last 4 weeks of treatment prior to taper (up to Week 17)
measure: Mean Change From Baseline to the Last 4-Week Treatment Phase in the Number of Acute Migraine Medication Doses Administered by Opioid Use
timeFrame: Baseline and last 4 weeks of treatment prior to taper (up to Week 17)
measure: Mean Change From Baseline to the Last 4-Week Treatment Phase in the Number of Acute Migraine Medication Doses Administered by Prescription Headache Medication Use
timeFrame: Baseline and last 4 weeks of treatment prior to taper (up to Week 17)
measure: Mean Change From Baseline in Percentage of Migraine Attacks With Each of the Following Migraine Symptoms: Aura, Nausea, Vomiting, Photophobia, Phonophobia
timeFrame: Baseline and last 4 weeks of treatment prior to taper (up to Week 17)
measure: Percentage of Participants Classified as Responders for Each of the Following Measures: Migraine Headache Days, Migraine Attacks, and Migraine Headache Periods
timeFrame: Baseline to the Last 4 weeks of treatment
measure: Number of Participants Who Were "Much Improved" or "Very Much Improved" on the 7-point Likert Patient Global Impression of Change (PGIC) Scale Using LOCF at Week 17
timeFrame: Week 17
measure: Number of Participants Who Were "Much Improved" or "Very Much Improved" (Responders) on the 7-point Likert Clinical Global Impression of Change (CGIC) Scale Using LOCF at Week 17
timeFrame: Week 17
Other outcomes:
measure: Mean Change From Baseline in Migraine Specific Quality of Life Questionnaire (MSQ v2.1) Composite Score and Subscales (Role Function Restrictive, Role Function, Preventive, & Emotional Function) at Week 17
timeFrame: Baseline and Week 17
measure: Mean Change From Baseline in the Headache Impact Test (HIT-6) Total Scores at Week 17
timeFrame: Week 17
measure: Mean Change From Baseline in Productivity as Measured by Lost Time Equivalents (LTE) - (Work Activities, Non-work Activities, and Combination of Work and Non-work Activities)
timeFrame: Week 17
measure: Assessment of Treatment Satisfaction Using the Patient Perception of Migraine Questionnaire (PPMQ-R) at Week 17
timeFrame: Week 17
Locations:
city: Birmingham
country: United States
facility: GSK Investigational Site
state: Alabama
city: Phoenix
country: United States
facility: GSK Investigational Site
state: Arizona
city: Phoenix
country: United States
facility: GSK Investigational Site
state: Arizona
city: Anaheim
country: United States
facility: GSK Investigational Site
state: California
city: Newport Beach
country: United States
facility: GSK Investigational Site
state: California
city: Redlands
country: United States
facility: GSK Investigational Site
state: California
city: San Francisco
country: United States
facility: GSK Investigational Site
state: California
city: Santa Monica
country: United States
facility: GSK Investigational Site
state: California
city: Westlake Village
country: United States
facility: GSK Investigational Site
state: California
city: Colorado Springs
country: United States
facility: GSK Investigational Site
state: Colorado
city: Colorado Springs
country: United States
facility: GSK Investigational Site
state: Colorado
city: Denver
country: United States
facility: GSK Investigational Site
state: Colorado
city: Deland
country: United States
facility: GSK Investigational Site
state: Florida
city: Sunrise
country: United States
facility: GSK Investigational Site
state: Florida
city: West Palm Beach
country: United States
facility: GSK Investigational Site
state: Florida
city: Atlanta
country: United States
facility: GSK Investigational Site
state: Georgia
city: Stockbridge
country: United States
facility: GSK Investigational Site
state: Georgia
city: Chicago
country: United States
facility: GSK Investigational Site
state: Illinois
city: Wichita
country: United States
facility: GSK Investigational Site
state: Kansas
city: Kalamazoo
country: United States
facility: GSK Investigational Site
state: Michigan
city: Golden Valley
country: United States
facility: GSK Investigational Site
state: Minnesota
city: Kansas City
country: United States
facility: GSK Investigational Site
state: Missouri
city: Springfield
country: United States
facility: GSK Investigational Site
state: Missouri
city: St. Louis
country: United States
facility: GSK Investigational Site
state: Missouri
city: Las Vegas
country: United States
facility: GSK Investigational Site
state: Nevada
city: Albany
country: United States
facility: GSK Investigational Site
state: New York
city: Greensboro
country: United States
facility: GSK Investigational Site
state: North Carolina
city: Raleigh
country: United States
facility: GSK Investigational Site
state: North Carolina
city: Raleigh
country: United States
facility: GSK Investigational Site
state: North Carolina
city: Cleveland
country: United States
facility: GSK Investigational Site
state: Ohio
city: West Chester
country: United States
facility: GSK Investigational Site
state: Ohio
city: Westerville
country: United States
facility: GSK Investigational Site
state: Ohio
city: Philadelphia
country: United States
facility: GSK Investigational Site
state: Pennsylvania
city: Philadelphia
country: United States
facility: GSK Investigational Site
state: Pennsylvania
city: Pittsburgh
country: United States
facility: GSK Investigational Site
state: Pennsylvania
city: Charleston
country: United States
facility: GSK Investigational Site
state: South Carolina
city: Memphis
country: United States
facility: GSK Investigational Site
state: Tennessee
city: Nashville
country: United States
facility: GSK Investigational Site
state: Tennessee
city: Houston
country: United States
facility: GSK Investigational Site
state: Texas
city: San Antonio
country: United States
facility: GSK Investigational Site
state: Texas
city: Salt Lake City
country: United States
facility: GSK Investigational Site
state: Utah
city: Salt Lake City
country: United States
facility: GSK Investigational Site
state: Utah
city: Alexandria
country: United States
facility: GSK Investigational Site
state: Virginia
city: Seattle
country: United States
facility: GSK Investigational Site
state: Washington
city: Wenatchee
country: United States
facility: GSK Investigational Site
state: Washington
city: Penticton
country: Canada
facility: GSK Investigational Site
state: British Columbia
city: Surrey
country: Canada
facility: GSK Investigational Site
state: British Columbia
city: Bay Roberts
country: Canada
facility: GSK Investigational Site
state: Newfoundland and Labrador
city: Brampton
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Ottawa
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Ottawa
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Sudbury
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Toronto
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Toronto
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Toronto
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Montreal
country: Canada
facility: GSK Investigational Site
state: Quebec
city: Saint Romuald
country: Canada
facility: GSK Investigational Site
state: Quebec
city: Sherbrooke
country: Canada
facility: GSK Investigational Site
state: Quebec
city: Quebec
country: Canada
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: 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.