Migraine Headache
Conditions
Brief summary
To assess the efficacy and safety of LY2951742 in the prevention of migraine headache in migraineurs with or without aura during 3 months of treatment.
Detailed description
The study is comprised of 4 trial periods: 1. Screening and washout (5-45 days) 2. Baseline for assessment of the type, frequency, and severity of headaches (28-38 days) 3. Treatment (12 weeks) 4. Follow-up (12 weeks)
Interventions
DRUGLY2951742
DRUGPlacebo
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Have a history of migraine as defined by the International Headache Society (IHS) International Classification of Headache Disorders II guidelines 1.1 and 1.2 (ICHD-II, Cephalgia 2004) of at least 1 year prior to enrollment, migraine onset prior to age 50, and a moderate frequency of migraine headaches * Women of child-bearing potential (not surgically sterile or at least 1 year post-menopause) must test negative for pregnancy at the time of screening based on a serum pregnancy test and must agree to use a reliable method of birth control during the study and for 3 months following completion of participation in the study * Have clinical laboratory test results within normal reference ranges or, if outside the normal range, judged not clinically significant by the Investigator * Must not be on any migraine prevention therapy, including botulinum toxin (Botox) * Agree not to post any personal medical data related to the study or information related to the study on any website or social media site (for example, Facebook, Twitter, et cetera) until the trial has completed
Exclusion criteria
* Current enrollment in, or discontinuation within the last 30 days from, a clinical trial involving any investigational drug or device, or concurrent enrollment in any other type of medical research judged not to be scientifically or medically compatible with this study * Previous completion or withdrawal from this study or any other study investigating LY2951742 or other therapeutic antibodies that target calcitonin gene-related peptide (CGRP) * History of chronic migraine or migraine subtypes including hemiplegic (sporadic or familial) migraine, ophthalmoplegic migraine, and basilar-type migraine * History of headache (for example, cluster headache or Medication Overuse Headache \[MOH\]) other than migraine or tension type headache as defined by IHS ICHD-II within 12 months prior to randomization * Evidence of significant active psychiatric disease including, but not limited to, manic depressive illness, schizophrenia, generalized anxiety disorder, obsessive compulsive disorder, personality disorders, or other serious mood, anxiety, depression, or substance use disorders * Have a history or presence of any other medical illness that in the judgment of the Investigator, indicates a medical problem that would preclude study participation * Women who are pregnant or nursing * Confirmed corrected QT (QTc) interval \>470 milliseconds (msec) for women and \>450 for men * Excessive alcohol, opiate, or barbiturate use; history of drug abuse or dependence * In the opinion of the Investigator, have no other issues that would interfere with compliance with the study requirements and completion of evaluations required for this study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline in the Number of Migraine Headache Days in the Last 28-day Period of the 12-week Treatment Phase | Baseline, 12 weeks | The criteria for a migraine headache was adapted from the standard International Headache Society (IHS) International Classification of Headache Disorders II guidelines 1.1 and 1.2 (ICHD-II, Cephalgia 2004). The definition of a migraine headache was a headache with or without aura, of ≥30 minutes (min) duration, and with both (A and B) required features from the IHS ICHD-II definition. Required feature A includes at least 2 of the following headache characteristics: unilateral location, pulsatile quality, moderate or severe pain intensity, or aggravation by or causing avoidance of routine physical activity. Required feature B includes at least 1 of the following during the headache: nausea and/or vomiting, or photophobia and phonophobia. Least square (LS) means were calculated using mixed model repeated measures (MMRM) with baseline value, treatment, month, and treatment-by-month interaction as fixed effects and participant as random effect. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline in the Number of Headache Days in the Last 28-day Period of the 12-week Treatment Phase | Baseline, 12 weeks | Number of calendar days on which a headache lasts ≥4 hours which includes migraines, probable migraines (PM) and nonmigraines. Criteria for migraine headache (MH) was adapted from standard IHS ICHD-II guidelines 1.1 and 1.2 (Cephalgia 2004). Definition of MH was headache with or without aura, of ≥30 min duration, and with both (A and B) required features from IHS ICHD-II definition. Required feature A includes ≥2 of following headache characteristics: unilateral location, pulsatile quality, moderate or severe pain intensity, or aggravation by or causing avoidance of routine physical activity. Required feature B includes at least 1 of following during headache: nausea and/or vomiting, or photophobia and phonophobia. PM is headache with or without aura, but missing 1 feature needed to fulfill all criteria for MH. LS means were calculated using MMRM with baseline value, gender, treatment, month, and treatment-by-month interaction as fixed effects and participant as random effect. |
| Mean Change From Baseline in the Number of Migraine Attacks in the Last 28-day Period of the 12-week Treatment Phase | Baseline, 12 weeks | A migraine attack was defined as beginning on any day a migraine headache day was recorded and ending when a migraine headache-free day occurred. The criteria for a migraine headache was adapted from the standard IHS ICHD-II guidelines 1.1 and 1.2 (Cephalgia 2004). The definition of a migraine headache was a headache with or without aura, of ≥30 minutes duration, and with both (A and B) required features from the IHS ICHD-II definition. Required feature A includes at least 2 of the following headache characteristics: unilateral location, pulsatile quality, moderate or severe pain intensity, or aggravation by or causing avoidance of routine physical activity. Required feature B includes at least 1 of the following during the headache: nausea and/or vomiting, or photophobia and phonophobia. LS means were calculated using MMRM with baseline value, gender, treatment, month, and treatment-by-month interaction as fixed effects and participant as random effect. |
| Percentage of Responders | Baseline, 4, 8, and 12 weeks | Percentage of participants with greater than 50% reduction in the number of migraine headache days in a 28-day period. The criteria for a migraine headache was adapted from the standard International Headache Society (IHS) International Classification of Headache Disorders II guidelines 1.1 and 1.2 (ICHD-II, Cephalgia 2004). The definition of a migraine headache was a headache with or without aura, of ≥30 minutes duration, and with both (A and B) required features from the IHS ICHD-II definition. Required feature A includes at least 2 of the following headache characteristics: unilateral location, pulsatile quality, moderate or severe pain intensity, or aggravation by or causing avoidance of routine physical activity. Required feature B includes at least 1 of the following during the headache: nausea and/or vomiting, or photophobia and phonophobia. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| LY2951742 LY2951742: 150 milligrams (mg), subcutaneous (SC) injection on Day 1 and then once every other week for a total of 6 doses during the 12-week Treatment Period. | 107 |
| Placebo Placebo: 0.9% Sodium Chloride, USP, SC injection on Day 1 and then once every other week for a total of 6 doses during the 12-week Treatment Period. | 110 |
| Total | 217 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 |
| Overall Study | Lack of Efficacy | 0 | 1 |
| Overall Study | Lost to Follow-up | 5 | 6 |
| Overall Study | Protocol Violation | 0 | 2 |
| Overall Study | Randomized Inappropriately | 1 | 0 |
| Overall Study | Withdrawal by Subject | 8 | 3 |
Baseline characteristics
| Characteristic | LY2951742 | Total | Placebo |
|---|---|---|---|
| Age, Continuous | 40.9 years STANDARD_DEVIATION 11.4 | 41.4 years STANDARD_DEVIATION 11.5 | 41.9 years STANDARD_DEVIATION 11.7 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 11 Participants | 24 Participants | 13 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 96 Participants | 193 Participants | 97 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 4 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 25 Participants | 51 Participants | 26 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 4 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 5 Participants | 3 Participants |
| Race (NIH/OMB) White | 76 Participants | 150 Participants | 74 Participants |
| Region of Enrollment United States | 107 participants | 217 participants | 110 participants |
| Sex: Female, Male Female | 88 Participants | 184 Participants | 96 Participants |
| Sex: Female, Male Male | 19 Participants | 33 Participants | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 36 / 107 | 30 / 110 | 6 / 98 | 2 / 103 |
| serious Total, serious adverse events | 0 / 107 | 1 / 110 | 2 / 98 | 3 / 103 |
Outcome results
Primary
Mean Change From Baseline in the Number of Migraine Headache Days in the Last 28-day Period of the 12-week Treatment Phase
The criteria for a migraine headache was adapted from the standard International Headache Society (IHS) International Classification of Headache Disorders II guidelines 1.1 and 1.2 (ICHD-II, Cephalgia 2004). The definition of a migraine headache was a headache with or without aura, of ≥30 minutes (min) duration, and with both (A and B) required features from the IHS ICHD-II definition. Required feature A includes at least 2 of the following headache characteristics: unilateral location, pulsatile quality, moderate or severe pain intensity, or aggravation by or causing avoidance of routine physical activity. Required feature B includes at least 1 of the following during the headache: nausea and/or vomiting, or photophobia and phonophobia. Least square (LS) means were calculated using mixed model repeated measures (MMRM) with baseline value, treatment, month, and treatment-by-month interaction as fixed effects and participant as random effect.
Time frame: Baseline, 12 weeks
Population: All participants with a valid 28-day baseline assessment of migraine headache days who received at least 1 dose of study treatment and had evaluable postbaseline headache data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| LY2951742 | Mean Change From Baseline in the Number of Migraine Headache Days in the Last 28-day Period of the 12-week Treatment Phase | -4.2 Migraine headache days | Standard Error 0.3 |
| Placebo | Mean Change From Baseline in the Number of Migraine Headache Days in the Last 28-day Period of the 12-week Treatment Phase | -3.0 Migraine headache days | Standard Error 0.29 |
Secondary
Mean Change From Baseline in the Number of Headache Days in the Last 28-day Period of the 12-week Treatment Phase
Number of calendar days on which a headache lasts ≥4 hours which includes migraines, probable migraines (PM) and nonmigraines. Criteria for migraine headache (MH) was adapted from standard IHS ICHD-II guidelines 1.1 and 1.2 (Cephalgia 2004). Definition of MH was headache with or without aura, of ≥30 min duration, and with both (A and B) required features from IHS ICHD-II definition. Required feature A includes ≥2 of following headache characteristics: unilateral location, pulsatile quality, moderate or severe pain intensity, or aggravation by or causing avoidance of routine physical activity. Required feature B includes at least 1 of following during headache: nausea and/or vomiting, or photophobia and phonophobia. PM is headache with or without aura, but missing 1 feature needed to fulfill all criteria for MH. LS means were calculated using MMRM with baseline value, gender, treatment, month, and treatment-by-month interaction as fixed effects and participant as random effect.
Time frame: Baseline, 12 weeks
Population: All participants with a valid 28-day baseline assessment of migraine headache days who received at least 1 dose of study treatment and had evaluable postbaseline headache data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| LY2951742 | Mean Change From Baseline in the Number of Headache Days in the Last 28-day Period of the 12-week Treatment Phase | -4.9 Headache days | Standard Error 0.4 |
| Placebo | Mean Change From Baseline in the Number of Headache Days in the Last 28-day Period of the 12-week Treatment Phase | -3.7 Headache days | Standard Error 0.4 |
Secondary
Mean Change From Baseline in the Number of Migraine Attacks in the Last 28-day Period of the 12-week Treatment Phase
A migraine attack was defined as beginning on any day a migraine headache day was recorded and ending when a migraine headache-free day occurred. The criteria for a migraine headache was adapted from the standard IHS ICHD-II guidelines 1.1 and 1.2 (Cephalgia 2004). The definition of a migraine headache was a headache with or without aura, of ≥30 minutes duration, and with both (A and B) required features from the IHS ICHD-II definition. Required feature A includes at least 2 of the following headache characteristics: unilateral location, pulsatile quality, moderate or severe pain intensity, or aggravation by or causing avoidance of routine physical activity. Required feature B includes at least 1 of the following during the headache: nausea and/or vomiting, or photophobia and phonophobia. LS means were calculated using MMRM with baseline value, gender, treatment, month, and treatment-by-month interaction as fixed effects and participant as random effect.
Time frame: Baseline, 12 weeks
Population: All participants with a valid 28-day baseline assessment of migraine headache days who received at least 1 dose of study treatment and had evaluable postbaseline headache data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| LY2951742 | Mean Change From Baseline in the Number of Migraine Attacks in the Last 28-day Period of the 12-week Treatment Phase | -3.1 Migraine attacks | Standard Error 0.23 |
| Placebo | Mean Change From Baseline in the Number of Migraine Attacks in the Last 28-day Period of the 12-week Treatment Phase | -2.3 Migraine attacks | Standard Error 0.24 |
Secondary
Percentage of Responders
Percentage of participants with greater than 50% reduction in the number of migraine headache days in a 28-day period. The criteria for a migraine headache was adapted from the standard International Headache Society (IHS) International Classification of Headache Disorders II guidelines 1.1 and 1.2 (ICHD-II, Cephalgia 2004). The definition of a migraine headache was a headache with or without aura, of ≥30 minutes duration, and with both (A and B) required features from the IHS ICHD-II definition. Required feature A includes at least 2 of the following headache characteristics: unilateral location, pulsatile quality, moderate or severe pain intensity, or aggravation by or causing avoidance of routine physical activity. Required feature B includes at least 1 of the following during the headache: nausea and/or vomiting, or photophobia and phonophobia.
Time frame: Baseline, 4, 8, and 12 weeks
Population: All participants with a valid 28-day baseline assessment of migraine headache days who received at least 1 dose of study treatment and had evaluable postbaseline headache data during the time period of analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| LY2951742 | Percentage of Responders | Week 4 | 57.9 Percentage of participants |
| LY2951742 | Percentage of Responders | Week 8 | 61.7 Percentage of participants |
| LY2951742 | Percentage of Responders | Week 12 | 64.5 Percentage of participants |
| Placebo | Percentage of Responders | Week 4 | 37.3 Percentage of participants |
| Placebo | Percentage of Responders | Week 8 | 42.7 Percentage of participants |
| Placebo | Percentage of Responders | Week 12 | 42.7 Percentage of participants |