Migraine
Conditions
Keywords
prevention, prophylaxis, headache
Brief summary
The main purpose of this study is to evaluate the efficacy and safety of the study drug known as galcanezumab in participants with episodic migraine.
Interventions
DRUGGalcanezumab
Administered SC
DRUGPlacebo
Administered SC
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
Sponsor is also masked.
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Have a diagnosis of migraine as defined by International Headache Society (IHS) International Classification of Headache Disorders (ICHD)-3 beta version (1.1 or 1.2) (ICHD-3 2013), with a history of migraine headaches of at least 1 year prior to screening, migraine onset prior to age 50 and MONTHLY frequency of 4-14 MHD.
Exclusion criteria
* Are currently enrolled in or have participated within the last 30 days or within 5 half-lives (whichever is longer) in a clinical trial involving an investigational product. * Current use or prior exposure to galcanezumab or another Calcitonin Gene-Related Peptide (CGRP) antibody. * Known hypersensitivity to multiple drugs, monoclonal antibodies or other therapeutic proteins, or to galcanezumab. * History of persistent daily headache, cluster headache or migraine subtypes including hemiplegic (sporadic or familial) migraine, ophthalmoplegic migraine, and migraine with brainstem aura (basilar-type migraine) defined by IHS ICHD-3 beta.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Mean Change From Baseline in the Number of Monthly Migraine Headache Days | Baseline, Month 1 through Month 6 | Migraine Headache Day (MHD):A calendar day on which a migraine headache or probable migraine headache occurred. Migraine Headache : A headache, with or without aura, of ≥30 minutes duration with both of the following required features (A and B): A) At least 2 of the following headache characteristics: Unilateral location; Pulsatile quality; Moderate or severe pain intensity; Aggravation by or causing avoidance of routine physical activity; AND B) During headache at least one of the following: Nausea and/or vomiting; Photophobia and phonophobia; Overall mean is derived from the average of months 1 to 6 from mixed model repeated measures (MMRM) model. Least Square (LS) mean was calculated using mixed model repeated measures (MMRM) model with treatment, pooled country, month, and treatment by month, baseline, and baseline by month as fixed effects. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline in the Migraine-Specific Quality of Life Questionnaire (MSQ) Version 2.1 Role Function Restrictive Domain | Baseline, Month 4 through Month 6 | MSQ v2.1 was developed to address physical & emotional limitations of specific concern to individuals with migraine. It consists of 14 items that address 3 domains:(1) Role Function-Restrictive (items 1-7);(2) Role Function- Preventive (items 8-11);&(3) Emotional Function (items 12-14).Response options range from none of the time (value 1) to all of the time (value 6), & are reverse-recoded (value 6 to 1) before the domain scores are calculated.Total raw scores for each domain is the sum of the final item value for all of the items in that domain.After the total raw score is computed for each domain, they are transformed to a 0-100 scale with higher scores indicating a better health status & a positive change in scores reflecting functional improvement. Mean is derived from the average of months 4 to 6 from MMRM model. LSMean was calculated using MMRM model with treatment, pooled country, month, treatment by month, baseline by month & baseline MHD category as fixed factors. |
| Overall Mean Change From Baseline in the Number of Monthly Migraine Headache Days Requiring Medication for the Acute Treatment of Migraine or Headache | Baseline, Month 1 through Month 6 | Migraine Headache Day (MHD):A calendar day on which a migraine headache or probable migraine headache occurred. Overall mean is derived from the average of months 1 to 6 from MMRM model.LSMean was calculated using MMRM model with treatment, pooled country, month, treatment by month, baseline, baseline by month, and baseline MHD category as fixed effects. |
| Mean Change From Baseline in Patient Global Impression of Severity (PGI-S) Rating | Baseline, Month 4 through Month 6 | The PGI-S scale is a participant-rated instrument that measures patients own global impression of their illness severity. The participant was instructed as follows: Considering migraine as a chronic condition, how would you rate your level of illness? Response options were from 1 (normal, not at all ill) to 7 (extremely ill). Mean is derived from the average of months 4 to 6 from MMRM model. LSMean was calculated using MMRM model with treatment, pooled country, month, treatment by month, baseline, baseline by month, and baseline MHD category as fixed factors. |
| Overall Mean Change From Baseline in Headache Hours | Baseline, Month 1 through Month 6 | Headache Hours is calculated as the total number of headache hours on which a headache occurred. Overall mean is derived from the average of months 1 to 6 from MMRM model. LSMean was calculated using MMRM model with treatment, pooled country, month, treatment by month, baseline, baseline by month and baseline MHD category. |
| Mean Percentage of Participants With Reduction From Baseline ≥50%, ≥75%, and 100% in Monthly Migraine Headache Days | Baseline, Month 1 through Month 6 | Migraine Headache Day (MHD): A calendar day on which a migraine headache or probable migraine headache occurred. Mean is derived from the average of months 1 to 6 from generalized linear mixed model repeated measures. Mean percentages of participants were calculated with a generalized linear mixed model repeated measures method with treatment, month and treatment by month, baseline. |
| Percentage of Participants Developing Anti-drug Antibodies (ADA) to Galcanezumab | Month 1 through Month 6 | Treatment emergent (TE) ADA evaluable participant is considered to be TE ADA+ if the subject has at least one post-baseline titer that is a 4-fold or greater increase in titer from baseline measurement. If baseline result is ADA Not Present, then the participant is TE ADA+ if there is at least one post-baseline result of ADA present with titer \>= 1: 20. |
| Pharmacokinetics (PK): Serum Concentrations of Galcanezumab | Month 6 | Pharmacokinetics (PK): Serum Concentrations of Galcanezumab. |
| Plasma Concentration of Calcitonin Gene-Related Peptide (CGRP) | Month 6 | Plasma Concentration of Calcitonin Gene-Related Peptide (CGRP). |
| Mean Change From Baseline in the Migraine Disability Assessment Test (MIDAS) Total Score | Baseline, Month 6 | The MIDAS is a participant-rated scale which was designed to quantify headache-related disability over a 3-month period. This instrument consists of five items that reflect the number of days reported as missing or with reduced productivity at work or home, and the number of days of missed social events. Each item has a numeric response range from 0 to 90 days, if days are missed from work or home they are not counted as days with reduced productivity at work or home. The numeric responses are summed to produce a total score ranging from 0 to 270, in which a higher value is indicative of more disability. LSMean was calculated using MMRM model with treatment, pooled country, month, treatment by month, baseline, baseline by month, and baseline MHD category as fixed factors. |
Countries
Argentina, Czechia, Germany, Israel, Mexico, Netherlands, Puerto Rico, South Korea, Spain, Taiwan, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received placebo by subcutaneous injection once a month for 6 months during double blind treatment phase. Participants did not receive any intervention during post-treatment follow-up phase. | 461 |
| Galcanezumab 120mg Participants received loading dose of 240mg galcanezumab at 1st dosing visit followed by 120mg galcanezumab once a month for 5 months by subcutaneous injection during double blind treatment phase. Participants did not receive any intervention during post-treatment follow-up phase. | 231 |
| Galcanezumab 240mg Participants received 240mg galcanezumab by subcutaneous injection once a month for 6 months during double blind treatment phase. Participants did not receive any intervention during post-treatment follow-up phase. | 223 |
| Placebo Maximum Extended Enrollment Cohort Participants received placebo by subcutaneous injection once a month for 6 months during double blind treatment phase. Participants did not receive any intervention during post-treatment follow-up phase. | 30 |
| Galcanezumab 120mg Maximum Extended Enrollment Cohort Participants received loading dose of 240mg galcanezumab at 1st dosing visit followed by 120mg galcanezumab once a month for 5 months by subcutaneous injection during double blind treatment phase. Participants did not receive any intervention during post-treatment follow-up phase. | 15 |
| Galcanezumab 240mg Maximum Extended Enrollment Cohort Participants received 240mg galcanezumab by subcutaneous injection once a month for 6 months during double blind treatment phase. Participants did not receive any intervention during post-treatment follow-up phase. | 19 |
| Total | 979 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Double Blind Treatment Phase | Adverse Event | 8 | 5 | 9 | 0 | 0 | 0 |
| Double Blind Treatment Phase | Did not receive study drug | 2 | 2 | 3 | 0 | 0 | 0 |
| Double Blind Treatment Phase | Lack of Efficacy | 6 | 1 | 1 | 0 | 0 | 0 |
| Double Blind Treatment Phase | Lost to Follow-up | 10 | 7 | 1 | 0 | 0 | 0 |
| Double Blind Treatment Phase | Physician Decision | 4 | 0 | 2 | 0 | 0 | 0 |
| Double Blind Treatment Phase | Pregnancy | 1 | 2 | 0 | 0 | 0 | 0 |
| Double Blind Treatment Phase | Protocol Violation | 5 | 2 | 1 | 0 | 1 | 0 |
| Double Blind Treatment Phase | Terminated by sponsor | 1 | 0 | 0 | 0 | 0 | 0 |
| Double Blind Treatment Phase | Withdrawal by Subject | 39 | 11 | 14 | 4 | 0 | 0 |
| Post Treatment Follow-up Phase | Lost to Follow-up | 8 | 3 | 3 | 0 | 1 | 0 |
| Post Treatment Follow-up Phase | Pregnancy | 2 | 0 | 0 | 0 | 0 | 0 |
| Post Treatment Follow-up Phase | Protocol Violation | 0 | 1 | 0 | 0 | 1 | 0 |
| Post Treatment Follow-up Phase | Withdrawal by Subject | 10 | 1 | 5 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Galcanezumab 120mg | Placebo | Total | Galcanezumab 240mg Maximum Extended Enrollment Cohort | Galcanezumab 120mg Maximum Extended Enrollment Cohort | Placebo Maximum Extended Enrollment Cohort | Galcanezumab 240mg |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 40.91 years STANDARD_DEVIATION 11.15 | 42.33 years STANDARD_DEVIATION 11.3 | 41.95 years STANDARD_DEVIATION 11.12 | 42.58 years STANDARD_DEVIATION 11.13 | 39.40 years STANDARD_DEVIATION 11.58 | 45.37 years STANDARD_DEVIATION 10.3 | 41.91 years STANDARD_DEVIATION 10.77 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 58 Participants | 118 Participants | 246 Participants | 3 Participants | 2 Participants | 4 Participants | 61 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 162 Participants | 318 Participants | 674 Participants | 12 Participants | 10 Participants | 21 Participants | 151 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 11 Participants | 25 Participants | 59 Participants | 4 Participants | 3 Participants | 5 Participants | 11 Participants |
| Migraine Headache Days (MHD) per month | 9.07 Days per Month STANDARD_DEVIATION 2.87 | 9.19 Days per Month STANDARD_DEVIATION 2.99 | 9.10 Days per Month STANDARD_DEVIATION 2.93 | 9.01 Days per Month STANDARD_DEVIATION 2.9 | 9.06 Days per Month STANDARD_DEVIATION 2.86 | 9.16 Days per Month STANDARD_DEVIATION 2.98 | 9.06 Days per Month STANDARD_DEVIATION 2.92 |
| Race (NIH/OMB) American Indian or Alaska Native | 8 Participants | 20 Participants | 41 Participants | 0 Participants | 0 Participants | 0 Participants | 13 Participants |
| Race (NIH/OMB) Asian | 28 Participants | 50 Participants | 166 Participants | 19 Participants | 15 Participants | 30 Participants | 24 Participants |
| Race (NIH/OMB) Black or African American | 11 Participants | 36 Participants | 63 Participants | 0 Participants | 0 Participants | 0 Participants | 16 Participants |
| Race (NIH/OMB) More than one race | 18 Participants | 30 Participants | 64 Participants | 0 Participants | 0 Participants | 0 Participants | 16 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 166 Participants | 325 Participants | 643 Participants | 0 Participants | 0 Participants | 0 Participants | 152 Participants |
| Region of Enrollment Argentina | 12 Participants | 22 Participants | 44 Participants | 0 Participants | 0 Participants | 0 Participants | 10 Participants |
| Region of Enrollment Czechia | 19 Participants | 39 Participants | 77 Participants | 0 Participants | 0 Participants | 0 Participants | 19 Participants |
| Region of Enrollment Germany | 19 Participants | 37 Participants | 75 Participants | 0 Participants | 0 Participants | 0 Participants | 19 Participants |
| Region of Enrollment Israel | 5 Participants | 11 Participants | 21 Participants | 0 Participants | 0 Participants | 0 Participants | 5 Participants |
| Region of Enrollment Mexico | 18 Participants | 36 Participants | 71 Participants | 0 Participants | 0 Participants | 0 Participants | 17 Participants |
| Region of Enrollment Netherlands | 11 Participants | 24 Participants | 46 Participants | 0 Participants | 0 Participants | 0 Participants | 11 Participants |
| Region of Enrollment South Korea | 17 Participants | 34 Participants | 98 Participants | 9 Participants | 7 Participants | 14 Participants | 17 Participants |
| Region of Enrollment Spain | 7 Participants | 14 Participants | 28 Participants | 0 Participants | 0 Participants | 0 Participants | 7 Participants |
| Region of Enrollment Taiwan | 7 Participants | 12 Participants | 58 Participants | 10 Participants | 8 Participants | 16 Participants | 5 Participants |
| Region of Enrollment United Kingdom | 4 Participants | 8 Participants | 15 Participants | 0 Participants | 0 Participants | 0 Participants | 3 Participants |
| Region of Enrollment United States | 112 Participants | 224 Participants | 446 Participants | 0 Participants | 0 Participants | 0 Participants | 110 Participants |
| Sex: Female, Male Female | 197 Participants | 393 Participants | 830 Participants | 14 Participants | 13 Participants | 22 Participants | 191 Participants |
| Sex: Female, Male Male | 34 Participants | 68 Participants | 149 Participants | 5 Participants | 2 Participants | 8 Participants | 32 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 461 | 0 / 226 | 0 / 228 | 0 / 410 | 0 / 212 | 0 / 208 | 0 / 30 | 0 / 14 | 0 / 20 | 0 / 25 | 0 / 14 | 0 / 20 |
| other Total, other adverse events | 150 / 461 | 78 / 226 | 87 / 228 | 40 / 410 | 16 / 212 | 13 / 208 | 10 / 30 | 9 / 14 | 9 / 20 | 3 / 25 | 6 / 14 | 0 / 20 |
| serious Total, serious adverse events | 5 / 461 | 5 / 226 | 7 / 228 | 3 / 410 | 1 / 212 | 3 / 208 | 1 / 30 | 1 / 14 | 0 / 20 | 2 / 25 | 0 / 14 | 0 / 20 |
Outcome results
Primary
Overall Mean Change From Baseline in the Number of Monthly Migraine Headache Days
Migraine Headache Day (MHD):A calendar day on which a migraine headache or probable migraine headache occurred. Migraine Headache : A headache, with or without aura, of ≥30 minutes duration with both of the following required features (A and B): A) At least 2 of the following headache characteristics: Unilateral location; Pulsatile quality; Moderate or severe pain intensity; Aggravation by or causing avoidance of routine physical activity; AND B) During headache at least one of the following: Nausea and/or vomiting; Photophobia and phonophobia; Overall mean is derived from the average of months 1 to 6 from mixed model repeated measures (MMRM) model. Least Square (LS) mean was calculated using mixed model repeated measures (MMRM) model with treatment, pooled country, month, and treatment by month, baseline, and baseline by month as fixed effects.
Time frame: Baseline, Month 1 through Month 6
Population: All randomized participants who received at least one dose of study drug and had baseline and at least one post baseline value.~As pre-specified in the analysis plan, outcome measures will not be reported for the Maximum Extended Enrollment (ME2) arms/groups but only for the main global study arms/groups
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Overall Mean Change From Baseline in the Number of Monthly Migraine Headache Days | -2.28 Migraine Headache Days per Month | Standard Error 0.2 |
| Galcanezumab 120mg | Overall Mean Change From Baseline in the Number of Monthly Migraine Headache Days | -4.29 Migraine Headache Days per Month | Standard Error 0.25 |
| Galcanezumab 240mg | Overall Mean Change From Baseline in the Number of Monthly Migraine Headache Days | -4.18 Migraine Headache Days per Month | Standard Error 0.26 |
p-value: <0.00195% CI: [-2.55, -1.48]Mixed Models Analysis
p-value: <0.00195% CI: [-2.44, -1.36]Mixed Models Analysis
Secondary
Mean Change From Baseline in Patient Global Impression of Severity (PGI-S) Rating
The PGI-S scale is a participant-rated instrument that measures patients own global impression of their illness severity. The participant was instructed as follows: Considering migraine as a chronic condition, how would you rate your level of illness? Response options were from 1 (normal, not at all ill) to 7 (extremely ill). Mean is derived from the average of months 4 to 6 from MMRM model. LSMean was calculated using MMRM model with treatment, pooled country, month, treatment by month, baseline, baseline by month, and baseline MHD category as fixed factors.
Time frame: Baseline, Month 4 through Month 6
Population: All randomized participants who received at least one dose of study drug and had baseline and post baseline value.~As pre-specified in the analysis plan, outcome measures will not be reported for the Maximum Extended Enrollment (ME2) arms/groups but only for the main global study arms/groups.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mean Change From Baseline in Patient Global Impression of Severity (PGI-S) Rating | -0.94 units on a scale | Standard Error 0.07 |
| Galcanezumab 120mg | Mean Change From Baseline in Patient Global Impression of Severity (PGI-S) Rating | -1.22 units on a scale | Standard Error 0.08 |
| Galcanezumab 240mg | Mean Change From Baseline in Patient Global Impression of Severity (PGI-S) Rating | -1.17 units on a scale | Standard Error 0.08 |
p-value: 0.00295% CI: [-0.47, -0.11]Mixed Models Analysis
p-value: 0.01295% CI: [-0.41, -0.05]Mixed Models Analysis
Secondary
Mean Change From Baseline in the Migraine Disability Assessment Test (MIDAS) Total Score
The MIDAS is a participant-rated scale which was designed to quantify headache-related disability over a 3-month period. This instrument consists of five items that reflect the number of days reported as missing or with reduced productivity at work or home, and the number of days of missed social events. Each item has a numeric response range from 0 to 90 days, if days are missed from work or home they are not counted as days with reduced productivity at work or home. The numeric responses are summed to produce a total score ranging from 0 to 270, in which a higher value is indicative of more disability. LSMean was calculated using MMRM model with treatment, pooled country, month, treatment by month, baseline, baseline by month, and baseline MHD category as fixed factors.
Time frame: Baseline, Month 6
Population: All randomized participants who received at least one dose of study drug and had baseline and at least one post baseline value.~As pre-specified in the analysis plan, outcome measures will not be reported for the Maximum Extended Enrollment (ME2) arms/groups but only for the main global study arms/groups.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mean Change From Baseline in the Migraine Disability Assessment Test (MIDAS) Total Score | -12.02 units on a scale | Standard Error 1.27 |
| Galcanezumab 120mg | Mean Change From Baseline in the Migraine Disability Assessment Test (MIDAS) Total Score | -21.17 units on a scale | Standard Error 1.58 |
| Galcanezumab 240mg | Mean Change From Baseline in the Migraine Disability Assessment Test (MIDAS) Total Score | -20.24 units on a scale | Standard Error 1.62 |
p-value: <0.00195% CI: [-12.61, -5.69]Mixed Models Analysis
p-value: <0.00195% CI: [-11.71, -4.72]Mixed Models Analysis
Secondary
Mean Change From Baseline in the Migraine-Specific Quality of Life Questionnaire (MSQ) Version 2.1 Role Function Restrictive Domain
MSQ v2.1 was developed to address physical & emotional limitations of specific concern to individuals with migraine. It consists of 14 items that address 3 domains:(1) Role Function-Restrictive (items 1-7);(2) Role Function- Preventive (items 8-11);&(3) Emotional Function (items 12-14).Response options range from none of the time (value 1) to all of the time (value 6), & are reverse-recoded (value 6 to 1) before the domain scores are calculated.Total raw scores for each domain is the sum of the final item value for all of the items in that domain.After the total raw score is computed for each domain, they are transformed to a 0-100 scale with higher scores indicating a better health status & a positive change in scores reflecting functional improvement. Mean is derived from the average of months 4 to 6 from MMRM model. LSMean was calculated using MMRM model with treatment, pooled country, month, treatment by month, baseline by month & baseline MHD category as fixed factors.
Time frame: Baseline, Month 4 through Month 6
Population: All randomized participants who received at least one dose of study drug and had baseline \& at least one post baseline value.~As pre-specified in the analysis plan, outcome measures will not be reported for the Maximum Extended Enrollment (ME2) arms/groups but only for the main global study arms/groups.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mean Change From Baseline in the Migraine-Specific Quality of Life Questionnaire (MSQ) Version 2.1 Role Function Restrictive Domain | 19.65 units on a scale | Standard Error 0.92 |
| Galcanezumab 120mg | Mean Change From Baseline in the Migraine-Specific Quality of Life Questionnaire (MSQ) Version 2.1 Role Function Restrictive Domain | 28.47 units on a scale | Standard Error 1.15 |
| Galcanezumab 240mg | Mean Change From Baseline in the Migraine-Specific Quality of Life Questionnaire (MSQ) Version 2.1 Role Function Restrictive Domain | 27.04 units on a scale | Standard Error 1.17 |
p-value: <0.00195% CI: [6.33, 11.31]Mixed Models Analysis
p-value: <0.00195% CI: [4.88, 9.9]Mixed Models Analysis
Secondary
Mean Percentage of Participants With Reduction From Baseline ≥50%, ≥75%, and 100% in Monthly Migraine Headache Days
Migraine Headache Day (MHD): A calendar day on which a migraine headache or probable migraine headache occurred. Mean is derived from the average of months 1 to 6 from generalized linear mixed model repeated measures. Mean percentages of participants were calculated with a generalized linear mixed model repeated measures method with treatment, month and treatment by month, baseline.
Time frame: Baseline, Month 1 through Month 6
Population: All randomized participants who received at least one dose of study drug and had baseline and at least one post baseline value.~As pre-specified in the analysis plan, outcome measures will not be reported for the Maximum Extended Enrollment (ME2) arms/groups but only for the main global study arms/groups.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Mean Percentage of Participants With Reduction From Baseline ≥50%, ≥75%, and 100% in Monthly Migraine Headache Days | ≥75% | 17.8 percentage of participants | Standard Error 1.3 |
| Placebo | Mean Percentage of Participants With Reduction From Baseline ≥50%, ≥75%, and 100% in Monthly Migraine Headache Days | ≥50% | 36 percentage of participants | Standard Error 1.7 |
| Placebo | Mean Percentage of Participants With Reduction From Baseline ≥50%, ≥75%, and 100% in Monthly Migraine Headache Days | 100% | 5.7 percentage of participants | Standard Error 0.7 |
| Galcanezumab 120mg | Mean Percentage of Participants With Reduction From Baseline ≥50%, ≥75%, and 100% in Monthly Migraine Headache Days | ≥75% | 33.5 percentage of participants | Standard Error 2.3 |
| Galcanezumab 120mg | Mean Percentage of Participants With Reduction From Baseline ≥50%, ≥75%, and 100% in Monthly Migraine Headache Days | ≥50% | 59.3 percentage of participants | Standard Error 2.4 |
| Galcanezumab 120mg | Mean Percentage of Participants With Reduction From Baseline ≥50%, ≥75%, and 100% in Monthly Migraine Headache Days | 100% | 11.5 percentage of participants | Standard Error 1.4 |
| Galcanezumab 240mg | Mean Percentage of Participants With Reduction From Baseline ≥50%, ≥75%, and 100% in Monthly Migraine Headache Days | ≥50% | 56.5 percentage of participants | Standard Error 2.5 |
| Galcanezumab 240mg | Mean Percentage of Participants With Reduction From Baseline ≥50%, ≥75%, and 100% in Monthly Migraine Headache Days | 100% | 13.8 percentage of participants | Standard Error 1.5 |
| Galcanezumab 240mg | Mean Percentage of Participants With Reduction From Baseline ≥50%, ≥75%, and 100% in Monthly Migraine Headache Days | ≥75% | 34.3 percentage of participants | Standard Error 2.3 |
Comparison: Reduction from Baseline ≥50%95% CI: [2.03, 3.32]
Comparison: Reduction from Baseline ≥50%95% CI: [1.81, 2.96]
Comparison: Reduction from Baseline ≥75%95% CI: [1.78, 3.06]
Comparison: Reduction from Baseline ≥75%95% CI: [1.84, 3.17]
Comparison: Reduction from Baseline ≥100%95% CI: [1.5, 3.12]
Comparison: Reduction from Baseline ≥100%95% CI: [1.87, 3.81]
Secondary
Overall Mean Change From Baseline in Headache Hours
Headache Hours is calculated as the total number of headache hours on which a headache occurred. Overall mean is derived from the average of months 1 to 6 from MMRM model. LSMean was calculated using MMRM model with treatment, pooled country, month, treatment by month, baseline, baseline by month and baseline MHD category.
Time frame: Baseline, Month 1 through Month 6
Population: All randomized participants who received at least one dose of study drug and had baseline and at least one post baseline value.~As pre-specified in the analysis plan, outcome measures will not be reported for the Maximum Extended Enrollment (ME2) arms/groups but only for the main global study arms/groups.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Overall Mean Change From Baseline in Headache Hours | -10.89 Headache Hours per Month | Standard Error 1.92 |
| Galcanezumab 120mg | Overall Mean Change From Baseline in Headache Hours | -26.07 Headache Hours per Month | Standard Error 2.41 |
| Galcanezumab 240mg | Overall Mean Change From Baseline in Headache Hours | -24.44 Headache Hours per Month | Standard Error 2.44 |
p-value: <0.00195% CI: [-20.27, -10.11]Mixed Models Analysis
p-value: <0.00195% CI: [-18.67, -8.44]Mixed Models Analysis
Secondary
Overall Mean Change From Baseline in the Number of Monthly Migraine Headache Days Requiring Medication for the Acute Treatment of Migraine or Headache
Migraine Headache Day (MHD):A calendar day on which a migraine headache or probable migraine headache occurred. Overall mean is derived from the average of months 1 to 6 from MMRM model.LSMean was calculated using MMRM model with treatment, pooled country, month, treatment by month, baseline, baseline by month, and baseline MHD category as fixed effects.
Time frame: Baseline, Month 1 through Month 6
Population: All randomized participants who received at least one dose of study drug and had baseline and post baseline value.~As pre-specified in the analysis plan, outcome measures will not be reported for the Maximum Extended Enrollment (ME2) arms/groups but only for the main global study arms/groups.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Overall Mean Change From Baseline in the Number of Monthly Migraine Headache Days Requiring Medication for the Acute Treatment of Migraine or Headache | -1.85 Days per Month | Standard Error 0.18 |
| Galcanezumab 120mg | Overall Mean Change From Baseline in the Number of Monthly Migraine Headache Days Requiring Medication for the Acute Treatment of Migraine or Headache | -3.67 Days per Month | Standard Error 0.22 |
| Galcanezumab 240mg | Overall Mean Change From Baseline in the Number of Monthly Migraine Headache Days Requiring Medication for the Acute Treatment of Migraine or Headache | -3.63 Days per Month | Standard Error 0.23 |
p-value: <0.00195% CI: [-2.29, -1.36]Mixed Models Analysis
p-value: <0.00195% CI: [-2.25, -1.31]Mixed Models Analysis
Secondary
Percentage of Participants Developing Anti-drug Antibodies (ADA) to Galcanezumab
Treatment emergent (TE) ADA evaluable participant is considered to be TE ADA+ if the subject has at least one post-baseline titer that is a 4-fold or greater increase in titer from baseline measurement. If baseline result is ADA Not Present, then the participant is TE ADA+ if there is at least one post-baseline result of ADA present with titer \>= 1: 20.
Time frame: Month 1 through Month 6
Population: All randomized participants who received at least one dose of study drug \& had least one non-missing test result for ADA for each of the baseline period and the post-baseline period. As pre-specified in the analysis plan, outcome measures will not be reported for the ME2 arms/groups but only for the main global study arms/groups.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Developing Anti-drug Antibodies (ADA) to Galcanezumab | 0.45 percentage of participants |
| Galcanezumab 120mg | Percentage of Participants Developing Anti-drug Antibodies (ADA) to Galcanezumab | 8.56 percentage of participants |
| Galcanezumab 240mg | Percentage of Participants Developing Anti-drug Antibodies (ADA) to Galcanezumab | 5.14 percentage of participants |
Comparison: TE ADA Positive.p-value: <0.001Fisher Exact
Comparison: TE ADA Positivep-value: <0.001Fisher Exact
Secondary
Pharmacokinetics (PK): Serum Concentrations of Galcanezumab
Pharmacokinetics (PK): Serum Concentrations of Galcanezumab.
Time frame: Month 6
Population: All randomized participants who received at least one dose of study drug and had measurable serum concentrations.~As pre-specified in the analysis plan, outcome measures will not be reported for the Maximum Extended Enrollment (ME2) arms/groups but only for the main global study arms/groups.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Pharmacokinetics (PK): Serum Concentrations of Galcanezumab | 17400 Nanogram per milliliter (ng/mL) | Standard Deviation 8820 |
| Galcanezumab 120mg | Pharmacokinetics (PK): Serum Concentrations of Galcanezumab | 32200 Nanogram per milliliter (ng/mL) | Standard Deviation 12600 |
Secondary
Plasma Concentration of Calcitonin Gene-Related Peptide (CGRP)
Plasma Concentration of Calcitonin Gene-Related Peptide (CGRP).
Time frame: Month 6
Population: All randomized participants who had received at least one dose of study drug and had measurable plasma concentration.~As pre-specified in the analysis plan, outcome measures will not be reported for the Maximum Extended Enrollment (ME2) arms/groups but only for the main global study arms/groups.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Plasma Concentration of Calcitonin Gene-Related Peptide (CGRP) | 0.541 ng/mL | Standard Deviation 1.11 |
| Galcanezumab 120mg | Plasma Concentration of Calcitonin Gene-Related Peptide (CGRP) | 3.93 ng/mL | Standard Deviation 1.83 |
| Galcanezumab 240mg | Plasma Concentration of Calcitonin Gene-Related Peptide (CGRP) | 4.98 ng/mL | Standard Deviation 1.6 |