Migraine
Conditions
Keywords
Lacosamide, migraine prophylaxis, Vimpat
Brief summary
The purpose of this study is to see how safe and effective Lacosamide (LCM) is when taken by mouth, twice a day for up to 18 weeks to prevent migraines.
Detailed description
This study is for subjects who have been diagnosed with migraine for at least one year and who are currently taking an effective abortive medication(s).
Interventions
DRUGLacosamide
Lacosamide 100mg immediate-release film-coated tablet (white,oval) oral administration twice daily 12 hours apart
OTHERPlacebo
Immediate-release film coated tablet (white, oval), oral administration twice daily 12 hours apart
Sponsors
UCB Pharma
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* History of migraines headaches for 1 year and well documented 3 month retrospective history of migraines. * Experience 2-8 migraines per month but not more than 15 headache days per month. There should be at least 48 hours of freedom between headaches. * On effective stable abortive medication(s) for the acute treatment of migraine.
Exclusion criteria
* Subject in another investigational drug or device study within the last 30 days or is currently in another investigational drug trial. * Use of triptans or ergots for migraine abortive treatment \> 2-3 days per calendar week 2 months prior to screening. * Experience 15 or more headache days per month of any kind 2 months prior to screening. * Has another consistent or chronic form of headache. * Unable to stop medications, herbs, vitamins, or minerals used to prevent a migraine from occurring. * Pregnant or nursing women and those of child bearing potential who are not surgically sterile, or 2 years post menopausal, or do not practice 2 combined methods of birth control, unless sexually abstinent, during the trial. * Significant laboratory or electrocardiograms (ECG) abnormalities * Significant medical history including cardiovascular abnormalities.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change From Baseline in Mean Migraine Headache Rates During the Entire 14-week Maintenance Period | Baseline, Entire 14-week Maintenance Period |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Mean Migraine Headache Rates During the Last 4 Weeks of the Maintenance Period | Baseline, last 4 weeks of the 14-week Maintenance Period | — |
| Number of Subjects Who Experience a 50 Percent or Greater Reduction From Baseline in Migraine Frequency During the Entire 14-week Maintenance Period. | Baseline, Entire 14-week Maintenance Period | — |
| Number of Subjects Who Experience a 50 Percent or Greater Reduction From Baseline in Migraine Frequency During the Last 4 Weeks of the Maintenance Period. | Baseline, last 4 weeks of the 14-week Maintenance Period | — |
| Changes From Baseline in Improvement of Function and Reduction of Disability Using the Headache Impact Test (HIT-6) | Baseline, last visit in the 17-week Trial Period | Headache Impact Test (HIT-6™) consists of 6 items designed to measure the impact headaches have on a person's ability to function. Scores from the 6 questions will be added to create a total score. Range of the total score is 36 to 78. Higher scores indicate a greater impact on the subject's quality of life. |
Countries
United States
Participant flow
Recruitment details
A multicenter trial with 24 sites with enrolled subjects and 23 sites with randomized subjects from 15 Feb 2007 to 17 Jul 2008.
Pre-assignment details
Subjects on stable dose of prophylactic medication entered a 2-week Wash-Out Period followed by a 4-week Baseline Period without any prophylactic medication. Subjects not taking prophylactic medication entered the Baseline Period directly for 6 weeks. Subjects entered a 3-week Titration Period and if completed entered a 14-week Maintenance Period.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo immediate-release film coated tablet, oral administration twice daily 12 hours apart | 72 |
| Lacosamide 100mg Lacosamide 100mg immediate-release film coated tablet, oral administration twice daily 12 hours apart | 72 |
| Lacosamide 300mg Lacosamide 300mg immediate-release film coated tablet, oral administration twice daily 12 hours apart | 74 |
| Total | 218 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Maintenance and Safety Follow-up Periods | Adverse Event | 3 | 4 | 2 |
| Maintenance and Safety Follow-up Periods | Lack of Efficacy | 0 | 1 | 1 |
| Maintenance and Safety Follow-up Periods | Lost to Follow-up | 1 | 2 | 0 |
| Maintenance and Safety Follow-up Periods | Other | 0 | 0 | 2 |
| Maintenance and Safety Follow-up Periods | Subject Withdrew Consent | 3 | 2 | 4 |
| Maintenance and Safety Follow-up Periods | Unsatisfactory Compliance | 0 | 3 | 6 |
| Randomized /Titration Period | Adverse Event | 2 | 3 | 0 |
| Randomized /Titration Period | Lack of Efficacy | 1 | 0 | 1 |
| Randomized /Titration Period | Lost to Follow-up | 2 | 2 | 1 |
| Randomized /Titration Period | Other | 1 | 0 | 0 |
| Randomized /Titration Period | Protocol Deviation | 1 | 0 | 0 |
| Randomized /Titration Period | Subject Withdrew Consent | 4 | 1 | 0 |
| Randomized /Titration Period | Unsatisfactory Compliance | 2 | 3 | 2 |
Baseline characteristics
| Characteristic | Lacosamide 100mg | Lacosamide 300mg | Placebo | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 72 Participants | 74 Participants | 72 Participants | 218 Participants |
| Age, Continuous | 40.1 years STANDARD_DEVIATION 11.86 | 40.2 years STANDARD_DEVIATION 11.4 | 39.3 years STANDARD_DEVIATION 12.23 | 39.9 years STANDARD_DEVIATION 11.78 |
| Region of Enrollment United States | 72 participants | 74 participants | 72 participants | 218 participants |
| Sex: Female, Male Female | 62 Participants | 63 Participants | 62 Participants | 187 Participants |
| Sex: Female, Male Male | 10 Participants | 11 Participants | 10 Participants | 31 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 30 / 72 | 36 / 72 | 33 / 74 |
| serious Total, serious adverse events | 3 / 72 | 2 / 72 | 2 / 74 |
Outcome results
Primary
Change From Baseline in Mean Migraine Headache Rates During the Entire 14-week Maintenance Period
Time frame: Baseline, Entire 14-week Maintenance Period
Population: Of the 72 (Placebo), 72 (Lacosamide 100mg) and 74 (Lacosamide 300mg) subjects randomized, 71, 70, and 74 subjects respectively are included in this summary based on the Full Analysis Set (must have Baseline and at least one post-Baseline efficacy value). This summary uses a Last Observation Carried Forward (LOCF) approach.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Mean Migraine Headache Rates During the Entire 14-week Maintenance Period | -1.4 Number of migraine headaches | Standard Deviation 3.12 |
| Lacosamide 100mg | Change From Baseline in Mean Migraine Headache Rates During the Entire 14-week Maintenance Period | -1.4 Number of migraine headaches | Standard Deviation 2.68 |
| Lacosamide 300mg | Change From Baseline in Mean Migraine Headache Rates During the Entire 14-week Maintenance Period | -1.6 Number of migraine headaches | Standard Deviation 2.1 |
Secondary
Change From Baseline in Mean Migraine Headache Rates During the Last 4 Weeks of the Maintenance Period
Time frame: Baseline, last 4 weeks of the 14-week Maintenance Period
Population: Of the 72 (Placebo), 72 (Lacosamide 100mg) and 74 (Lacosamide 300mg) subjects randomized, 71, 70, and 74 subjects respectively are included in this summary based on the Full Analysis Set (must have Baseline and at least one post-Baseline efficacy value). This summary uses a Last Observation Carried Forward (LOCF) approach.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Mean Migraine Headache Rates During the Last 4 Weeks of the Maintenance Period | -1.3 Number of migraine headaches | Standard Deviation 3.45 |
| Lacosamide 100mg | Change From Baseline in Mean Migraine Headache Rates During the Last 4 Weeks of the Maintenance Period | -1.3 Number of migraine headaches | Standard Deviation 2.82 |
| Lacosamide 300mg | Change From Baseline in Mean Migraine Headache Rates During the Last 4 Weeks of the Maintenance Period | -1.7 Number of migraine headaches | Standard Deviation 2.44 |
Secondary
Changes From Baseline in Improvement of Function and Reduction of Disability Using the Headache Impact Test (HIT-6)
Headache Impact Test (HIT-6™) consists of 6 items designed to measure the impact headaches have on a person's ability to function. Scores from the 6 questions will be added to create a total score. Range of the total score is 36 to 78. Higher scores indicate a greater impact on the subject's quality of life.
Time frame: Baseline, last visit in the 17-week Trial Period
Population: Of the 71 (Placebo), 70 (Lacosamide 100mg) and 74 (Lacosamide 300mg) subjects in the Full Analysis Set (must have Baseline and at least one post-Baseline efficacy value), 64, 66, and 66 subjects respectively are included in this summary.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Changes From Baseline in Improvement of Function and Reduction of Disability Using the Headache Impact Test (HIT-6) | -3.8 Scores on a scale | Standard Deviation 7.78 |
| Lacosamide 100mg | Changes From Baseline in Improvement of Function and Reduction of Disability Using the Headache Impact Test (HIT-6) | -4.3 Scores on a scale | Standard Deviation 8.67 |
| Lacosamide 300mg | Changes From Baseline in Improvement of Function and Reduction of Disability Using the Headache Impact Test (HIT-6) | -3.5 Scores on a scale | Standard Deviation 8.03 |
Secondary
Number of Subjects Who Experience a 50 Percent or Greater Reduction From Baseline in Migraine Frequency During the Entire 14-week Maintenance Period.
Time frame: Baseline, Entire 14-week Maintenance Period
Population: Of the 72 (Placebo), 72 (Lacosamide 100mg) and 74 (Lacosamide 300mg) subjects randomized, 71, 70, and 74 subjects respectively are included in this summary based on the Full Analysis Set (must have Baseline and at least one post-Baseline efficacy value). This summary uses a Last Observation Carried Forward (LOCF) approach.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Subjects Who Experience a 50 Percent or Greater Reduction From Baseline in Migraine Frequency During the Entire 14-week Maintenance Period. | 26 Participants |
| Lacosamide 100mg | Number of Subjects Who Experience a 50 Percent or Greater Reduction From Baseline in Migraine Frequency During the Entire 14-week Maintenance Period. | 32 Participants |
| Lacosamide 300mg | Number of Subjects Who Experience a 50 Percent or Greater Reduction From Baseline in Migraine Frequency During the Entire 14-week Maintenance Period. | 29 Participants |
Secondary
Number of Subjects Who Experience a 50 Percent or Greater Reduction From Baseline in Migraine Frequency During the Last 4 Weeks of the Maintenance Period.
Time frame: Baseline, last 4 weeks of the 14-week Maintenance Period
Population: Of the 72 (Placebo), 72 (Lacosamide 100mg) and 74 (Lacosamide 300mg) subjects randomized, 71, 70, and 74 subjects respectively are included in this summary based on the Full Analysis Set (must have Baseline and at least one post-Baseline efficacy value). This summary uses a Last Observation Carried Forward (LOCF) approach.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Subjects Who Experience a 50 Percent or Greater Reduction From Baseline in Migraine Frequency During the Last 4 Weeks of the Maintenance Period. | 27 Participants |
| Lacosamide 100mg | Number of Subjects Who Experience a 50 Percent or Greater Reduction From Baseline in Migraine Frequency During the Last 4 Weeks of the Maintenance Period. | 27 Participants |
| Lacosamide 300mg | Number of Subjects Who Experience a 50 Percent or Greater Reduction From Baseline in Migraine Frequency During the Last 4 Weeks of the Maintenance Period. | 33 Participants |