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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT00742209
Other study ID # 111381
Secondary ID
Status Completed
Phase Phase 2
First received August 26, 2008
Last updated July 15, 2013
Start date August 2008
Est. completion date June 2010

Study information

Verified date October 2011
Source XenoPort, Inc.
Contact n/a
Is FDA regulated No
Health authority Canada: Health CanadaUnited States: Food and Drug Administration
Study type Interventional

Clinical Trial 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.


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.


Recruitment information / eligibility

Status Completed
Enrollment 526
Est. completion date June 2010
Est. primary completion date June 2010
Accepts healthy volunteers No
Gender Both
Age group 18 Years and older
Eligibility 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.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Prevention


Related Conditions & MeSH terms


Intervention

Drug:
GSK1838262
Flexible dosing: 1200 mg/day, 1800 mg/day, 2400 mg/day and 3000 mg/day
Placebo
Placebo-control

Locations

Country Name City State
Canada GSK Investigational Site Bay Roberts Newfoundland and Labrador
Canada GSK Investigational Site Brampton Ontario
Canada GSK Investigational Site Montreal Quebec
Canada GSK Investigational Site Ottawa Ontario
Canada GSK Investigational Site Ottawa Ontario
Canada GSK Investigational Site Penticton British Columbia
Canada GSK Investigational Site Quebec
Canada GSK Investigational Site Saint Romuald Quebec
Canada GSK Investigational Site Sherbrooke Quebec
Canada GSK Investigational Site Sudbury Ontario
Canada GSK Investigational Site Surrey British Columbia
Canada GSK Investigational Site Toronto Ontario
Canada GSK Investigational Site Toronto Ontario
Canada GSK Investigational Site Toronto Ontario
United States GSK Investigational Site Albany New York
United States GSK Investigational Site Alexandria Virginia
United States GSK Investigational Site Anaheim California
United States GSK Investigational Site Atlanta Georgia
United States GSK Investigational Site Birmingham Alabama
United States GSK Investigational Site Charleston South Carolina
United States GSK Investigational Site Chicago Illinois
United States GSK Investigational Site Cleveland Ohio
United States GSK Investigational Site Colorado Springs Colorado
United States GSK Investigational Site Colorado Springs Colorado
United States GSK Investigational Site Deland Florida
United States GSK Investigational Site Denver Colorado
United States GSK Investigational Site Golden Valley Minnesota
United States GSK Investigational Site Greensboro North Carolina
United States GSK Investigational Site Houston Texas
United States GSK Investigational Site Kalamazoo Michigan
United States GSK Investigational Site Kansas City Missouri
United States GSK Investigational Site Las Vegas Nevada
United States GSK Investigational Site Memphis Tennessee
United States GSK Investigational Site Nashville Tennessee
United States GSK Investigational Site Newport Beach California
United States GSK Investigational Site Philadelphia Pennsylvania
United States GSK Investigational Site Philadelphia Pennsylvania
United States GSK Investigational Site Phoenix Arizona
United States GSK Investigational Site Phoenix Arizona
United States GSK Investigational Site Pittsburgh Pennsylvania
United States GSK Investigational Site Raleigh North Carolina
United States GSK Investigational Site Raleigh North Carolina
United States GSK Investigational Site Redlands California
United States GSK Investigational Site Salt Lake City Utah
United States GSK Investigational Site Salt Lake City Utah
United States GSK Investigational Site San Antonio Texas
United States GSK Investigational Site San Francisco California
United States GSK Investigational Site Santa Monica California
United States GSK Investigational Site Seattle Washington
United States GSK Investigational Site Springfield Missouri
United States GSK Investigational Site St. Louis Missouri
United States GSK Investigational Site Stockbridge Georgia
United States GSK Investigational Site Sunrise Florida
United States GSK Investigational Site Wenatchee Washington
United States GSK Investigational Site West Chester Ohio
United States GSK Investigational Site West Palm Beach Florida
United States GSK Investigational Site Westerville Ohio
United States GSK Investigational Site Westlake Village California
United States GSK Investigational Site Wichita Kansas

Sponsors (2)

Lead Sponsor Collaborator
XenoPort, Inc. GlaxoSmithKline

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type Measure Description Time frame Safety issue
Other 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 The MSQ is a 14-item health-related quality of life (HRQOL) questionnaire. Participants provide responses using a 6-point Likert scale (1=None of the time, 2= A little bit of the time, 3=Some of the time, 4=A good bit of the time, 5=Most of the time, 6=All of the time) that are then recoded with a final item value where 1=6, 2=5, 3=4, 4=3, 5=2, and 6=1. The scale measures 3 independently scored dimensions (Role Function Restrictive, Role Function, Preventive, and Emotional Function) of HRQOL that are affected by migraine. For each dimension, a higher score indicates a better health status. Baseline and Week 17 No
Other Mean Change From Baseline in the Headache Impact Test (HIT-6) Total Scores at Week 17 The HIT is a 6-item, self-administered HRQOL questionnaire used to measure six areas that impact headaches have on participants' ability to function on the job, at school, at home, and in social situations. Participants provide responses to questions using a 5-point Likert-type scale. All item values range from 6 to13.The total scores range from 36 to 78, where higher scores indicate greater impact on a participant's life. Week 17 No
Other 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) Productivity, as measured by LTE, is a metric used to assess productivity loss in migraine. It is a composite measure of presenteeism (continued to work while under the influence of migraine symptoms) and absenteeism (time missed from work due to migraine), and can be applied to productivity for work and non-work activities. Productivity data were collected via an e-diary, and productivity measures were summarized for each study phase by averaging each measure across migraine attacks for each participant. Week 17 No
Other Assessment of Treatment Satisfaction Using the Patient Perception of Migraine Questionnaire (PPMQ-R) at Week 17 Three global treatment satisfaction items from the PPMQ included satisfaction or dissatisfaction with Medication Effectiveness, Medication Side Effects, and Overall Medication. Each item on the PPMQ uses a 7-point satisfaction scale (1 = Very Satisfied to 7 = Very Dissatisfied). Satisfied participants include those reporting "Very Satisfied" (scale value = 1) or "Satisfied" (scale value = 2) on the scale. Week 17 No
Primary Adjusted Mean Change From Baseline in the Number of Migraine Headache Days (MHD) During the Last 4 Weeks of Treatment Prior to Taper A migraine headache day is defined as a calendar day with any occurrence of migraine headache pain of at least 30 minutes in duration. Change from baseline was calculated as the mean number of MHD over the last 4 weeks of treatment prior to taper minus the number at baseline using the Last Observation Carried Forward (LOCF). The last 4-week treatment phase is based on the last 4 weeks prior to taper for each participant. Baseline and last 4 weeks of treatment prior to taper (up to Week 17) No
Secondary Mean Change From Baseline in the Number of MHD in All Study Phases A migraine headache day is defined as a calendar day with any occurrence of migraine headache pain of at least 30 minutes in duration. Change from baseline and the last 4 weeks of treatment prior to taper were calculated means of the number of migraine headache days using the Last Observation Carried Forward (LOCF). Change from baseline is calculated as post-baseline minus baseline. The last 4-week treatment phase is based on the last 4 weeks prior to taper for each participant. Baseline and last 4 weeks of treatment prior to taper (up to Week 17) No
Secondary Adjusted Mean Change From Baseline in the Number of Migraine Attacks A migraine attack is defined as a migraine headache of at least 30 minutes in duration and may also include recurring non-migraine or migraine headaches . Change from baseline and the last 4 weeks of treatment prior to taper were calculated means of the number of migraine attacks using the Last Observation Carried Forward (LOCF). The last 4-week treatment phase is based on the last 4 weeks prior to taper for each participant. Baseline and last 4 weeks of treatment prior to taper (up to Week 17) No
Secondary Mean Change From Baseline in the Number of Migraine Headache Periods (MHP) A migraine headache period is a 24-hour block of time that begins at the onset of a migraine event . The 24-hour period is not linked directly with a calendar day. The change from baseline and the last 4 weeks of treatment prior to taper were calculated means of the number of migraine headache periods using the Last Observation Carried Forward (LOCF). The last 4-week treatment phase is based on the last 4 weeks prior to taper for each participant. Baseline and last 4 weeks of treatment prior to taper (up to Week 17) No
Secondary Change From Baseline in the Mean Migraine Attack Duration The total duration of a migraine attack is measured from migraine attack onset until the resolution of the attack measured in hours and may include more than 1 headache event. The duration is assessed using a Daily Migraine Diary. Change from baseline and the last 4 weeks of treatment prior to taper were calculated means of the number of migraine headache days using the Last Observation Carried Forward (LOCF). Change from baseline is calculated as post-baseline minus baseline. The last 4-week treatment phase is based on the last 4 weeks prior to taper for each participant. Baseline and last 4 weeks of treatment prior to taper (up to Week 17) No
Secondary Change From Baseline in the Mean Peak Migraine Pain Severity Peak Migraine Pain Severity was measured using a 4-point scale (0=none, 1=mild, 2=moderate, or 3=severe) on a participant self assessed Daily Migraine Diary. The scale measured the maximum pain severity across all headache events considered to be one attack.. Change from baseline and the last 4 weeks of treatment prior to taper were calculated means of the number of migraine headache days using the Last Observation Carried Forward (LOCF). The last 4-week treatment phase is based on the last 4 weeks prior to taper for each participant. Baseline and last 4 weeks of treatment prior to taper (up to Week 17) No
Secondary Mean Change From Baseline to the Last 4-Week Treatment Phase in the Number of Days of Acute Migraine Medication Use The Number of Days of Acute Migraine Medication Use was assessed via the participant-assessed Daily Migraine Diary. Baseline and last 4 weeks of treatment prior to taper (up to Week 17) No
Secondary Mean Change From Baseline to the Last 4-Week Treatment Phase in the Number of Acute Migraine Medication Doses Administered The Number of Acute Migraine Medication Doses Administered was captured via the participant-assessed Daily Migraine Diary. Baseline and last 4 weeks of treatment prior to taper (up to Week 17) No
Secondary Mean Change From Baseline to the Last 4-Week Treatment Phase in the Number of Acute Migraine Medication Doses Administered by Triptan Use The Number of Acute Migraine Medication Administered was measured via the participant-assessed Daily Migraine Diary. Baseline and last 4 weeks of treatment prior to taper (up to Week 17) No
Secondary Mean Change From Baseline to the Last 4-Week Treatment Phase in the Number of Acute Migraine Medication Doses Administered by Opioid Use The Number of Acute Migraine Medication Doses Administered by Opioid Use was measured via the participant-assessed Daily Migraine Diary. Baseline and last 4 weeks of treatment prior to taper (up to Week 17) No
Secondary 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 The Number of Acute Migraine Medication Doses Administered by Prescription Headache Medication use was measured via the participant-assessed Daily Migraine Diary. Baseline and last 4 weeks of treatment prior to taper (up to Week 17) No
Secondary Mean Change From Baseline in Percentage of Migraine Attacks With Each of the Following Migraine Symptoms: Aura, Nausea, Vomiting, Photophobia, Phonophobia The endpoint is defined as the percentage of attacks with each symptom (separately) for each study phase. Migraine symptoms aura, nausea, vomiting, photophobia, and phonophobia are defined as the presence of each migraine symptom during any of the headache events within an attack. Baseline and last 4 weeks of treatment prior to taper (up to Week 17) No
Secondary Percentage of Participants Classified as Responders for Each of the Following Measures: Migraine Headache Days, Migraine Attacks, and Migraine Headache Periods A responder is defined as a participant who achieved at least a 50% reduction from baseline for the indicated measures. Baseline to the Last 4 weeks of treatment No
Secondary 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 The PGIC is a single question measured on the 7-point Likert Scale (1 = "very much improved"; 2 = "much improved"; 7 = "very much worse"). A responder is defined as being "very much improved" or "much improved." Week 17 No
Secondary 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 The CGIC is a single question measured on a 7-point Likert Scale. (1 = "very much improved"; 2= "much improved, and 7 = "very much worse") designed to give an assessment of treatment from a clinician's perspective. A responder is defined as being 'Very much improved' or 'much improved'. Week 17 No
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