Chronic Migraine
Conditions
Keywords
prevention, prophylaxis, headache
Brief summary
The main purpose of this study is to evaluate the efficacy of the study drug known as galcanezumab in participants with chronic 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)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
Main Study: * Have a diagnosis of chronic migraine as defined by International Headache Society (IHS) International Classification of Headache Disorders (ICHD)-3 beta guidelines (1.3) (ICHD-3 2013), with a history of migraine headaches of at least 1 year prior to screening, and migraine onset prior to age 50. Israel addendum: * Participants must have completed all phases of main study, including the 4-month post-treatment follow-up phase, during which no investigational product was administered. * Participants also must be considered by the investigator to have benefited from galcanezumab treatment and must have exhausted alternative therapies for the prevention of migraine.
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 (MHD) | Baseline, Month 1 through Month 3 | 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 3 from mixed model repeated measures (MMRM) model. Least square(LS) Mean was calculated using MMRM model with treatment, pooled country, baseline medication overuse, concurrent prophylaxis use, month, 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) Role-function Restrictive Domain | Baseline, Month 3 | MSQ v2.1 is a health status instrument, with a 4-week recall period, developed to address physical and emotional limitations of specific concern to individuals with migraine. Addressing the impact of migraine on work or daily activities, relationships with family & friends, leisure time, productivity, concentration, energy, tiredness & feelings. 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. |
| 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 3 | 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 3 from MMRM model. LSMean was calculated using MMRM model with treatment, pooled country, baseline medication overuse, concurrent prophylaxis use, month, treatment by month,baseline, and baseline by month as fixed effects. |
| Mean Change From Baseline in the Patient Global Impression of Severity (PGI-S) Score | Baseline, Month 3 | PGI-S scale is a participant-rated instrument that measures participants 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). LSMean was calculated using MMRM model with treatment, pooled country, baseline medication overuse, concurrent prophylaxis use, month, treatment by month, baseline, and baseline by month as fixed effects. |
| Overall Mean Change From Baseline in Headache Hours | Baseline, Month 1 through Month 3 | Overall mean is derived from the average of months 1 to 3 from MMRM model. LSMean was calculated using MMRM model with treatment, pooled country, baseline medication overuse, concurrent prophylaxis use, month, treatment by month,baseline, and baseline by month as fixed effects. |
| Number of Participants With Reduction From Baseline ≥50%, ≥75% and 100% in Monthly Migraine Headache Days | Baseline, Month 1 through Month 3 | MHD: A calendar day on which a migraine headache or probable migraine headache occurred. |
| Percentage of Participants Developing Treatment Emergent Anti-drug Antibodies (ADA) to Galcanezumab | Month 1 through Month 3 | A Treatment Emergent Anti-Drug Antibodies (TE ADA) evaluable participant is considered to be TE ADA+ if the participant 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 \>= 20. |
| Pharmacokinetics (PK): Area Under the Concentration Time Curve (AUC) of Galcanezumab | Baseline through Month 3 | Pharmacokinetics (PK): Area Under the Concentration Time Curve (AUC) of Galcanezumab. |
| Plasma Concentration of Calcitonin Gene-Related Peptide (CGRP) | Month 3 | Plasma Concentration of Calcitonin Gene-Related Peptide (CGRP). |
| Serum Concentrations of Galcanezumab | Month 3 | Serum concentrations of Galcanezumab |
| Mean Change From Baseline on the Migraine Disability Assessment Test (MIDAS) Total Score | Baseline, Month 3 | 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 Analysis of covariance (ANCOVA) model with last observation carried forward (LOCF) with treatment, pooled country, baseline medication overuse, concurrent prophylaxis use, and baseline value as fixed effects. |
Countries
Argentina, Canada, Czechia, Germany, Israel, Italy, Mexico, Netherlands, Puerto Rico, Spain, Taiwan, United Kingdom, United States
Participant flow
Pre-assignment details
1. Main study: This randomised part of study was conducted in 3 phases * a 3-month double-blind treatment phase * an optional 9-month open-label extension phase * a 4-month follow-up phase 2. Israel addendum: Participants in Israel who completed all phases in main study, benefited from galcanezumab and had no other suitable alternative treatment options available were provided continued-access to galcanezumab where safety was monitored.
Participants by arm
| Arm | Count |
|---|---|
| Placebo * Double-blind treatment phase: Participants received placebo once a month by subcutaneous injection for 3 months.
* Open-label extension phase: After completion of double-blind phase, participants had an option to enter open-label extension phase where they receive 240 mg galcanezumab SC at first month, 120mg at second month followed by 120mg or 240mg once a month (at the discretion of the investigator) for the remaining 7 months.
* Follow-up phase: After completion or discontinuation from double-blind or open-label extension phases, participants entered follow-up phase where they were observed for 4 months. No treatments administered. | 559 |
| Galcanezumab 120mg * Double-blind treatment phase: Participants received loading dose of 240 mg of galcanezumab at first dosing visit followed 120 mg galcanezumab once a month by subcutaneous injection for 2 months.
* Open-label extension phase: After completion of double-blind phase, participants had an option to enter open-label extension phase where they received 240mg galcanezumab SC at first month, 120mg at second month followed by 120mg or 240mg once a month (at the discretion of the investigator) for the remaining 7 months.
* Follow-up phase: After completion or discontinuation from double-blind or open-label extension phases, participants entered follow-up phase where they were observed for 4 months. No treatments administered. | 279 |
| Galcanezumab 240mg * Double-blind treatment phase: Participants received 240 mg of galcanezumab once a month by subcutaneous injection for 3 months.
* Open-label extension phase: After completion of double-blind phase, participants had an option to enter open-label extension phase where they received 240mg galcanezumab SC at first month, 120mg at second month followed by 120mg or 240mg once a month (at the discretion of the investigator) for the remaining 7 months.
* Follow-up phase: After completion or discontinuation from double-blind or open-label extension phases, participants entered follow-up phase where they were observed for 4 months. No treatments administered. | 279 |
| Total | 1,117 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Double-Blind Treatment Phase | Adverse Event | 7 | 3 | 2 | 0 |
| Double-Blind Treatment Phase | Lack of Efficacy | 4 | 0 | 0 | 0 |
| Double-Blind Treatment Phase | Lost to Follow-up | 9 | 4 | 1 | 0 |
| Double-Blind Treatment Phase | Physician Decision | 2 | 1 | 1 | 0 |
| Double-Blind Treatment Phase | Pregnancy | 2 | 2 | 0 | 0 |
| Double-Blind Treatment Phase | Protocol Violation | 6 | 1 | 0 | 0 |
| Double-Blind Treatment Phase | Screen failure | 0 | 1 | 2 | 0 |
| Double-Blind Treatment Phase | Withdrawal by Subject | 20 | 5 | 7 | 0 |
| Follow-up Phase | Adverse Event | 2 | 0 | 1 | 0 |
| Follow-up Phase | Lost to Follow-up | 12 | 5 | 2 | 0 |
| Follow-up Phase | Physician Decision | 5 | 1 | 0 | 0 |
| Follow-up Phase | Pregnancy | 0 | 1 | 0 | 0 |
| Follow-up Phase | Protocol Violation | 1 | 0 | 0 | 0 |
| Follow-up Phase | Withdrawal by Subject | 12 | 4 | 11 | 0 |
| Israel Addendum | Withdrawal by Subject | 0 | 0 | 0 | 4 |
| Open-Label Extension Phase | Adverse Event | 23 | 12 | 11 | 0 |
| Open-Label Extension Phase | Lack of Efficacy | 14 | 12 | 14 | 0 |
| Open-Label Extension Phase | Lost to Follow-up | 15 | 7 | 9 | 0 |
| Open-Label Extension Phase | Physician Decision | 2 | 0 | 0 | 0 |
| Open-Label Extension Phase | Pregnancy | 1 | 2 | 1 | 0 |
| Open-Label Extension Phase | Protocol Violation | 3 | 4 | 1 | 0 |
| Open-Label Extension Phase | Withdrawal by Subject | 30 | 18 | 18 | 0 |
Baseline characteristics
| Characteristic | Total | Galcanezumab 240mg | Galcanezumab 120mg | Placebo |
|---|---|---|---|---|
| Age, Continuous | 40.98 years STANDARD_DEVIATION 12.11 | 41.06 years STANDARD_DEVIATION 12.36 | 39.66 years STANDARD_DEVIATION 11.86 | 41.61 years STANDARD_DEVIATION 12.07 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 256 Participants | 69 Participants | 65 Participants | 122 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 792 Participants | 194 Participants | 196 Participants | 402 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 69 Participants | 16 Participants | 18 Participants | 35 Participants |
| Migraine Headache Days (MHD) | 19.41 Days per Month STANDARD_DEVIATION 4.52 | 19.17 Days per Month STANDARD_DEVIATION 4.6 | 19.36 Days per Month STANDARD_DEVIATION 4.27 | 19.55 Days per Month STANDARD_DEVIATION 4.59 |
| Race (NIH/OMB) American Indian or Alaska Native | 6 Participants | 0 Participants | 2 Participants | 4 Participants |
| Race (NIH/OMB) Asian | 54 Participants | 15 Participants | 13 Participants | 26 Participants |
| Race (NIH/OMB) Black or African American | 72 Participants | 17 Participants | 16 Participants | 39 Participants |
| Race (NIH/OMB) More than one race | 101 Participants | 21 Participants | 24 Participants | 56 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 882 Participants | 225 Participants | 224 Participants | 433 Participants |
| Region of Enrollment Argentina | 82 Participants | 21 Participants | 20 Participants | 41 Participants |
| Region of Enrollment Canada | 15 Participants | 3 Participants | 4 Participants | 8 Participants |
| Region of Enrollment Czechia | 45 Participants | 10 Participants | 10 Participants | 25 Participants |
| Region of Enrollment Germany | 54 Participants | 13 Participants | 13 Participants | 28 Participants |
| Region of Enrollment Israel | 40 Participants | 10 Participants | 10 Participants | 20 Participants |
| Region of Enrollment Italy | 56 Participants | 15 Participants | 14 Participants | 27 Participants |
| Region of Enrollment Mexico | 24 Participants | 5 Participants | 7 Participants | 12 Participants |
| Region of Enrollment Netherlands | 43 Participants | 11 Participants | 11 Participants | 21 Participants |
| Region of Enrollment Spain | 50 Participants | 12 Participants | 14 Participants | 24 Participants |
| Region of Enrollment Taiwan | 48 Participants | 12 Participants | 12 Participants | 24 Participants |
| Region of Enrollment United Kingdom | 31 Participants | 9 Participants | 7 Participants | 15 Participants |
| Region of Enrollment United States | 629 Participants | 158 Participants | 157 Participants | 314 Participants |
| Sex: Female, Male Female | 950 Participants | 228 Participants | 238 Participants | 484 Participants |
| Sex: Female, Male Male | 167 Participants | 51 Participants | 41 Participants | 75 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 | EG012 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 558 | 0 / 273 | 0 / 282 | 0 / 501 | 0 / 259 | 0 / 262 | 0 / 15 | 0 / 4 | 0 / 4 | 0 / 438 | 0 / 223 | 0 / 228 | 0 / 29 |
| other Total, other adverse events | 170 / 558 | 98 / 273 | 105 / 282 | 223 / 501 | 117 / 259 | 120 / 262 | 0 / 15 | 0 / 4 | 2 / 4 | 57 / 438 | 19 / 223 | 27 / 228 | 26 / 29 |
| serious Total, serious adverse events | 5 / 558 | 2 / 273 | 4 / 282 | 16 / 501 | 6 / 259 | 9 / 262 | 0 / 15 | 0 / 4 | 0 / 4 | 5 / 438 | 3 / 223 | 1 / 228 | 6 / 29 |
Outcome results
Primary
Overall Mean Change From Baseline in the Number of Monthly Migraine Headache Days (MHD)
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 3 from mixed model repeated measures (MMRM) model. Least square(LS) Mean was calculated using MMRM model with treatment, pooled country, baseline medication overuse, concurrent prophylaxis use, month, treatment by month, baseline, and baseline by month as fixed effects.
Time frame: Baseline, Month 1 through Month 3
Population: All randomized participants who received at least one dose of study drug and had baseline and at least one post baseline value.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Overall Mean Change From Baseline in the Number of Monthly Migraine Headache Days (MHD) | -2.74 Migraine Headache Days per Month | Standard Error 0.36 |
| Galcanezumab 120mg | Overall Mean Change From Baseline in the Number of Monthly Migraine Headache Days (MHD) | -4.83 Migraine Headache Days per Month | Standard Error 0.44 |
| Galcanezumab 240mg | Overall Mean Change From Baseline in the Number of Monthly Migraine Headache Days (MHD) | -4.62 Migraine Headache Days per Month | Standard Error 0.43 |
p-value: <0.00195% CI: [-2.92, -1.26]Mixed Models Analysis
p-value: <0.00195% CI: [-2.71, -1.05]Mixed Models Analysis
Secondary
Mean Change From Baseline in the Migraine-Specific Quality of Life Questionnaire (MSQ) Role-function Restrictive Domain
MSQ v2.1 is a health status instrument, with a 4-week recall period, developed to address physical and emotional limitations of specific concern to individuals with migraine. Addressing the impact of migraine on work or daily activities, relationships with family & friends, leisure time, productivity, concentration, energy, tiredness & feelings. 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.
Time frame: Baseline, Month 3
Population: All randomized participants who received at least one dose of study drug and had baseline and month 3 measurement.~LSMean was calculated using MMRM model with treatment, pooled country, baseline medication overuse, concurrent prophylaxis use, month, treatment by month, baseline, and baseline by month as fixed effects.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mean Change From Baseline in the Migraine-Specific Quality of Life Questionnaire (MSQ) Role-function Restrictive Domain | 16.76 units on a scale | Standard Error 1.18 |
| Galcanezumab 120mg | Mean Change From Baseline in the Migraine-Specific Quality of Life Questionnaire (MSQ) Role-function Restrictive Domain | 21.81 units on a scale | Standard Error 1.41 |
| Galcanezumab 240mg | Mean Change From Baseline in the Migraine-Specific Quality of Life Questionnaire (MSQ) Role-function Restrictive Domain | 23.05 units on a scale | Standard Error 1.63 |
p-value: <0.00195% CI: [2.12, 7.99]Mixed Models Analysis
p-value: <0.00195% CI: [3.03, 9.55]Mixed Models Analysis
Secondary
Mean Change From Baseline in the Patient Global Impression of Severity (PGI-S) Score
PGI-S scale is a participant-rated instrument that measures participants 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). LSMean was calculated using MMRM model with treatment, pooled country, baseline medication overuse, concurrent prophylaxis use, month, treatment by month, baseline, and baseline by month as fixed effects.
Time frame: Baseline, Month 3
Population: All randomized participants who received at least one dose of study drug and had baseline and month 3 measurement.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mean Change From Baseline in the Patient Global Impression of Severity (PGI-S) Score | -0.62 units on a scale | Standard Error 0.08 |
| Galcanezumab 120mg | Mean Change From Baseline in the Patient Global Impression of Severity (PGI-S) Score | -0.76 units on a scale | Standard Error 0.1 |
| Galcanezumab 240mg | Mean Change From Baseline in the Patient Global Impression of Severity (PGI-S) Score | -0.91 units on a scale | Standard Error 0.1 |
p-value: 0.18195% CI: [-0.34, 0.06]Mixed Models Analysis
p-value: 0.00695% CI: [-0.48, -0.08]Mixed Models Analysis
Secondary
Mean Change From Baseline on 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 Analysis of covariance (ANCOVA) model with last observation carried forward (LOCF) with treatment, pooled country, baseline medication overuse, concurrent prophylaxis use, and baseline value as fixed effects.
Time frame: Baseline, Month 3
Population: All randomized participants who received at least one dose of study drug and had baseline and at least one post baseline measurement.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mean Change From Baseline on the Migraine Disability Assessment Test (MIDAS) Total Score | -11.53 units on a scale | Standard Error 3.38 |
| Galcanezumab 120mg | Mean Change From Baseline on the Migraine Disability Assessment Test (MIDAS) Total Score | -20.27 units on a scale | Standard Error 4.07 |
| Galcanezumab 240mg | Mean Change From Baseline on the Migraine Disability Assessment Test (MIDAS) Total Score | -17.02 units on a scale | Standard Error 4.05 |
p-value: 0.02595% CI: [-16.39, -1.08]ANCOVA
p-value: 0.15795% CI: [-13.1, 2.12]ANCOVA
Secondary
Number of Participants With Reduction From Baseline ≥50%, ≥75% and 100% in Monthly Migraine Headache Days
MHD: A calendar day on which a migraine headache or probable migraine headache occurred.
Time frame: Baseline, Month 1 through Month 3
Population: All randomized participants who received at least one dose of study drug and had baseline and month 3 measurement.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Reduction From Baseline ≥50%, ≥75% and 100% in Monthly Migraine Headache Days | ≥75% | 44 Participants |
| Placebo | Number of Participants With Reduction From Baseline ≥50%, ≥75% and 100% in Monthly Migraine Headache Days | ≥50% | 123 Participants |
| Placebo | Number of Participants With Reduction From Baseline ≥50%, ≥75% and 100% in Monthly Migraine Headache Days | ≥100% | 8 Participants |
| Galcanezumab 120mg | Number of Participants With Reduction From Baseline ≥50%, ≥75% and 100% in Monthly Migraine Headache Days | ≥75% | 34 Participants |
| Galcanezumab 120mg | Number of Participants With Reduction From Baseline ≥50%, ≥75% and 100% in Monthly Migraine Headache Days | ≥50% | 90 Participants |
| Galcanezumab 120mg | Number of Participants With Reduction From Baseline ≥50%, ≥75% and 100% in Monthly Migraine Headache Days | ≥100% | 4 Participants |
| Galcanezumab 240mg | Number of Participants With Reduction From Baseline ≥50%, ≥75% and 100% in Monthly Migraine Headache Days | ≥50% | 97 Participants |
| Galcanezumab 240mg | Number of Participants With Reduction From Baseline ≥50%, ≥75% and 100% in Monthly Migraine Headache Days | ≥100% | 8 Participants |
| Galcanezumab 240mg | Number of Participants With Reduction From Baseline ≥50%, ≥75% and 100% in Monthly Migraine Headache Days | ≥75% | 40 Participants |
Comparison: Reduction from Baseline ≥50%,p-value: 0.00495% CI: [1.167, 2.256]CPRMM
Comparison: Reduction from Baseline ≥50%p-value: <0.00195% CI: [1.291, 2.474]CPRMM
Comparison: Reduction from Baseline ≥75%p-value: 0.10295% CI: [0.923, 2.43]CPRMM
Comparison: Reduction from Baseline ≥75%p-value: 0.01195% CI: [1.146, 2.888]CPRMM
Comparison: Reduction from Baseline ≥100%p-value: 0.72995% CI: [0.163, 3.563]CPRMM
Comparison: Reduction from Baseline ≥100%p-value: 0.27695% CI: [0.6, 5.998]CPRMM
Secondary
Overall Mean Change From Baseline in Headache Hours
Overall mean is derived from the average of months 1 to 3 from MMRM model. LSMean was calculated using MMRM model with treatment, pooled country, baseline medication overuse, concurrent prophylaxis use, month, treatment by month,baseline, and baseline by month as fixed effects.
Time frame: Baseline, Month 1 through Month 3
Population: All randomized participants who received at least one dose of study drug and had baseline \& at least one post baseline measurement.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Overall Mean Change From Baseline in Headache Hours | -13.44 Headache Hours per Month | Standard Error 3.91 |
| Galcanezumab 120mg | Overall Mean Change From Baseline in Headache Hours | -36.15 Headache Hours per Month | Standard Error 4.74 |
| Galcanezumab 240mg | Overall Mean Change From Baseline in Headache Hours | -31.53 Headache Hours per Month | Standard Error 4.7 |
p-value: <0.00195% CI: [-31.74, -13.69]Mixed Models Analysis
p-value: <0.00195% CI: [-27.09, -9.09]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 3 from MMRM model. LSMean was calculated using MMRM model with treatment, pooled country, baseline medication overuse, concurrent prophylaxis use, month, treatment by month,baseline, and baseline by month as fixed effects.
Time frame: Baseline, Month 1 through Month 3
Population: All randomized participants who received at least one dose of study drug and had baseline and at least one post baseline measurement.
| 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 | -2.23 Days Per Month | Standard Error 0.33 |
| 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 | -4.74 Days Per Month | Standard Error 0.4 |
| 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 | -4.25 Days Per Month | Standard Error 0.4 |
p-value: <0.00195% CI: [-3.27, -1.76]Mixed Models Analysis
p-value: <0.00195% CI: [-2.77, -1.26]Mixed Models Analysis
Secondary
Percentage of Participants Developing Treatment Emergent Anti-drug Antibodies (ADA) to Galcanezumab
A Treatment Emergent Anti-Drug Antibodies (TE ADA) evaluable participant is considered to be TE ADA+ if the participant 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 \>= 20.
Time frame: Month 1 through Month 3
Population: All randomized participants who received at least one dose of study drug and had at least one non-missing test result for ADA for each of the baseline period and the post baseline period.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Percentage of Participants Developing Treatment Emergent Anti-drug Antibodies (ADA) to Galcanezumab | 8 Participants |
| Galcanezumab 120mg | Percentage of Participants Developing Treatment Emergent Anti-drug Antibodies (ADA) to Galcanezumab | 7 Participants |
| Galcanezumab 240mg | Percentage of Participants Developing Treatment Emergent Anti-drug Antibodies (ADA) to Galcanezumab | 7 Participants |
p-value: 0.263Cochran-Mantel-Haenszel
p-value: 0.29Cochran-Mantel-Haenszel
Secondary
Pharmacokinetics (PK): Area Under the Concentration Time Curve (AUC) of Galcanezumab
Pharmacokinetics (PK): Area Under the Concentration Time Curve (AUC) of Galcanezumab.
Time frame: Baseline through Month 3
Population: Zero participants analyzed. AUC data was not collected as AUC was not pre-specified in protocol.
Secondary
Plasma Concentration of Calcitonin Gene-Related Peptide (CGRP)
Plasma Concentration of Calcitonin Gene-Related Peptide (CGRP).
Time frame: Month 3
Population: All randomized participants who received at least one dose of study drug and had measurable plasma concentrations.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Plasma Concentration of Calcitonin Gene-Related Peptide (CGRP) | 0.529 Nanogram per milliliter (ng/mL) | Standard Deviation 0.612 |
| Galcanezumab 120mg | Plasma Concentration of Calcitonin Gene-Related Peptide (CGRP) | 4.02 Nanogram per milliliter (ng/mL) | Standard Deviation 1.7 |
| Galcanezumab 240mg | Plasma Concentration of Calcitonin Gene-Related Peptide (CGRP) | 4.85 Nanogram per milliliter (ng/mL) | Standard Deviation 1.76 |
Secondary
Serum Concentrations of Galcanezumab
Serum concentrations of Galcanezumab
Time frame: Month 3
Population: All randomized participants who received at least one dose of Galcanezumab and had measurable serum concentrations.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Serum Concentrations of Galcanezumab | 16900 Nanogram per milliliter (ng/mL) | Standard Deviation 7140 |
| Galcanezumab 120mg | Serum Concentrations of Galcanezumab | 29000 Nanogram per milliliter (ng/mL) | Standard Deviation 11300 |