Prevention Study in Adult Patients Suffering From Migraine Headaches

Migraine Clinical Trial

Official title:

Study MPX111381: A Dose-ranging Study Evaluating the Efficacy, Safety and Tolerability of GSK1838262 (XP13512) in the Prophylactic Treatment of Migraine Headache

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00742209
• Other study ID #: 111381
• 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

• Migraine
• Migraine Disorders

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