Migraine
Conditions
Keywords
prevention, prophylaxis, headache
Brief summary
The main purpose of this study is to evaluate the longer term safety of the study drug known as galcanezumab in participants with episodic or chronic migraine.
Interventions
DRUGGalcanezumab
Administered SC
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Have a diagnosis of episodic or chronic migraine as defined by International Headache Society (IHS) International Classification of Headache Disorders (ICHD)-3 beta guidelines (1.1, 1.2 or 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. * Prior to baseline, a history of 4 or more migraine headache days per month on average for the past 3 months.
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 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 |
|---|---|---|
| Percentage of Participants Who Discontinued Due to Adverse Event | Baseline through Month 12 | Adverse Event: Any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product that does not necessarily have a causal relationship with this treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. A summary of other non-serious AEs, and all SAE's, regardless of causality, is reported in the Adverse Events section. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics (PK): Area Under the Concentration Time Curve (AUC) of Galcanezumab | Baseline through Month 12 | Pharmacokinetics (PK): Area Under the Concentration Time Curve (AUC) of Galcanezumab |
| Serum Concentrations of Galcanezumab | Month 12 | Serum Concentrations of Galcanezumab. |
| Plasma Concentration of Calcitonin Gene-Related Peptide (CGRP) | Month 12 | Plasma Concentration of Calcitonin Gene-Related Peptide (CGRP) |
| Percentage of Participants Developing Anti-Drug Antibodies to Galcanezumab | Month 1 through Month 12 | A Treatment Emergent Anti-drug Antibody (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 \>= 1: 20 (treatment-induced). There were 6 participants in the 120 mg arm who discontinued after receiving loading dose of 240mg, these participants were moved to 240mg arm for safety analysis. |
| Overall Mean Change From Baseline in the Number of Migraine Headache Days (MHD) | Baseline, Month 1 through Month 12 | 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 12 from MMRM model. Least squares mean (LSMean) was calculated using mixed model repeated measures (MMRM) model with treatment, pooled investigative site, month, and treatment by month, baseline, and baseline by month as fixed effects. |
| Overall Mean Change From Baseline in the Number of Headache Days | Baseline, Month 1 through Month 12 | Headache Day: A calendar day on which any type of headache occurred (including migraine, probable migraine, and non-migraine headache). Overall mean is derived from the average of months 1 to 12 from MMRM model. LSMean was calculated using MMRM model with treatment, pooled investigative site, month, and treatment by month, baseline, and baseline by month as fixed effects. |
| Percentage of Participants With Overall Reduction From Baseline ≥50% in Monthly Migraine Headache Days | Baseline, Month 1 through Month 12 | Migraine Headache Day: A calendar day on which a migraine headache or probable migraine headache occurred. Overall percentage of participants with a given response rate were estimated from the generalized linear mixed models (GLIMMIX) model. |
| Overall Mean Change From Baseline in the Frequency of Medication Use for the Acute Treatment of Migraines or Headaches | Baseline, Month 1 through Month 12 | Overall mean is derived from the average of months 1 to 12 from MMRM model. LSMean was calculated using MMRM model with treatment, pooled investigative site, month, and treatment by month, baseline, and baseline by month as fixed effects. |
| Overall Mean Patient Global Impression-Improvement (PGI-I) Score | Month 1 through Month 12 | The Patient Global Impression of Improvement (PGI -I) scale is a participant-rated instrument that measures the participants own global impression of their symptom improvement. The participant was instructed as follows: Mark the box that best describes your migraine headache condition since you started taking this medicine. Response options were on a 7-point scale in which a score of 1 indicates that the participant's condition is very much better, a score of 4 indicates that the participant has experienced no change, and a score of 7 indicates that the participant is very much worse. Overall mean is derived from the average of months 1 to 12 from MMRM model. LSMean was calculated using MMRM model with treatment, pooled investigative site, month, and treatment by month, baseline PGI-S, and baseline PGI-S by month as fixed effects. |
| Overall Mean Change From Baseline on the Migraine Disability Assessment Test (MIDAS) Total Score | Baseline, Month 1 through Month 12 | 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. Overall mean is derived from the average of months 1 to 12 from MMRM model. LSMean was calculated using MMRM model with treatment, pooled investigative site, month, and treatment by month, baseline, and baseline by month. |
| Overall Mean Change From Baseline on the Migraine-Specific Quality of Life Questionnaire (MSQ) Version 2.1 | Baseline, Month 1 through Month 12 | MSQv2.1 is a health status instrument,with a 4-week recall period, developed to address physical & 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 addressing 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 total raw score is computed for each domain & total score, they are transformed to a 0-100 scale with higher scores indicating a better health status & a positive change in scores reflecting functional improvement. |
| Percentage of Participants With Positive Responses on Patient Satisfaction With Medication Questionnaire-Modified (PSMQ-M) | Baseline through Month 12 | The PSMQ-M is a self-rated scale which measures participants level of satisfaction with study medication.The scale has been modified for use in this study, assessing 3 items related to the clinical trial treatment over the past 4 weeks: satisfaction, preference, and side effects. Satisfaction responses range from very unsatisfied to very satisfied with the current treatment. Preference compares the current study medication to previous medications, with responses from much rather prefer my previous medication to much rather prefer the medication administered to me during the study. |
| Number of Participant Visits With Positive Reponses by Device Type Subcutaneous Administration Assessment Questionnaire Q1, Q3-Q12 | Baseline through Month 12 | The SQAAQ is a self-administered questionnaire that provides an assessment of ease of use and confidence with using a device to administer a subcutaneous injection of study drug. Participants will respond to questionnaire items using a 7-point Likert scale (from Strongly Disagree to Strongly Agree) shortly after the injection. If a caregiver administers the injection, the participants should be prepared to provide the caregiver's ratings of the questions.strongly agree & agree are considered as positive responses. |
Countries
Belgium, Canada, France, Hungary, Puerto Rico, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Galcanezumab 120 mg Participants received a loading dose of 240 mg galcanezumab at first dosing visit followed by 120 mg galcanezumab once a month by subcutaneous injection during open label treatment phase & participants did not receive any intervention during post treatment follow-up phase. | 135 |
| Galcanezumab 240 mg Participants received 240 mg galcanezumab once a month by subcutaneous injection during open label treatment phase & participants did not receive any intervention during post treatment follow-up phase. | 135 |
| Total | 270 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Open Label (OL) Treatment Phase | Adverse Event | 7 | 6 |
| Open Label (OL) Treatment Phase | Lack of Efficacy | 13 | 5 |
| Open Label (OL) Treatment Phase | Lost to Follow-up | 7 | 4 |
| Open Label (OL) Treatment Phase | Physician Decision | 1 | 0 |
| Open Label (OL) Treatment Phase | Withdrawal by Subject | 10 | 7 |
| Post Treatment Follow-up Phase | Adverse Event | 1 | 0 |
| Post Treatment Follow-up Phase | Lost to Follow-up | 2 | 2 |
| Post Treatment Follow-up Phase | Withdrawal by Subject | 6 | 3 |
Baseline characteristics
| Characteristic | Galcanezumab 240 mg | Total | Galcanezumab 120 mg |
|---|---|---|---|
| Age, Continuous | 43.69 years STANDARD_DEVIATION 10.99 | 41.95 years STANDARD_DEVIATION 11.45 | 40.21 years STANDARD_DEVIATION 11.68 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 20 Participants | 32 Participants | 12 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 108 Participants | 223 Participants | 115 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 8 Participants | 14 Participants | 6 Participants |
| Race (NIH/OMB) More than one race | 19 Participants | 42 Participants | 23 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 108 Participants | 211 Participants | 103 Participants |
| Sex: Female, Male Female | 113 Participants | 223 Participants | 110 Participants |
| Sex: Female, Male Male | 22 Participants | 47 Participants | 25 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 | 0 / 129 | 0 / 141 | 0 / 112 | 0 / 124 |
| other Total, other adverse events | 76 / 129 | 83 / 141 | 6 / 112 | 8 / 124 |
| serious Total, serious adverse events | 3 / 129 | 7 / 141 | 3 / 112 | 2 / 124 |
Outcome results
Primary
Percentage of Participants Who Discontinued Due to Adverse Event
Adverse Event: Any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product that does not necessarily have a causal relationship with this treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. A summary of other non-serious AEs, and all SAE's, regardless of causality, is reported in the Adverse Events section.
Time frame: Baseline through Month 12
Population: All randomized participants who received at least one dose of study drug. There were 6 participants in the 120 mg group who discontinued after receiving loading dose of 240mg, these participants were moved to 240mg group for AE analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Galcanezumab 120 mg | Percentage of Participants Who Discontinued Due to Adverse Event | 4.65 Percentage of Participants |
| Galcanezumab 240 mg | Percentage of Participants Who Discontinued Due to Adverse Event | 4.96 Percentage of Participants |
p-value: 1Fisher Exact
Secondary
Number of Participant Visits With Positive Reponses by Device Type Subcutaneous Administration Assessment Questionnaire Q1, Q3-Q12
The SQAAQ is a self-administered questionnaire that provides an assessment of ease of use and confidence with using a device to administer a subcutaneous injection of study drug. Participants will respond to questionnaire items using a 7-point Likert scale (from Strongly Disagree to Strongly Agree) shortly after the injection. If a caregiver administers the injection, the participants should be prepared to provide the caregiver's ratings of the questions.strongly agree & agree are considered as positive responses.
Time frame: Baseline through Month 12
Population: All randomized participants who switched from pre-filled syringe and received at least one dose of study drug by autoinjector.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Galcanezumab 120 mg | Number of Participant Visits With Positive Reponses by Device Type Subcutaneous Administration Assessment Questionnaire Q1, Q3-Q12 | Autoinjector : Easy to learn how to use | 250 participants |
| Galcanezumab 120 mg | Number of Participant Visits With Positive Reponses by Device Type Subcutaneous Administration Assessment Questionnaire Q1, Q3-Q12 | Pre-filled Syringe : Easy to pickup | 610 participants |
| Galcanezumab 120 mg | Number of Participant Visits With Positive Reponses by Device Type Subcutaneous Administration Assessment Questionnaire Q1, Q3-Q12 | Autoinjector : Easy to hold in hand | 247 participants |
| Galcanezumab 120 mg | Number of Participant Visits With Positive Reponses by Device Type Subcutaneous Administration Assessment Questionnaire Q1, Q3-Q12 | Pre-filled Syringe : Easy to inject my dose | 580 participants |
| Galcanezumab 120 mg | Number of Participant Visits With Positive Reponses by Device Type Subcutaneous Administration Assessment Questionnaire Q1, Q3-Q12 | Autoinjector : Easy to inject my dose | 245 participants |
| Galcanezumab 120 mg | Number of Participant Visits With Positive Reponses by Device Type Subcutaneous Administration Assessment Questionnaire Q1, Q3-Q12 | Pre-filled Syringe : overall, easy to use | 600 participants |
| Galcanezumab 120 mg | Number of Participant Visits With Positive Reponses by Device Type Subcutaneous Administration Assessment Questionnaire Q1, Q3-Q12 | Autoinjector : Easy to know dose is complete | 241 participants |
| Galcanezumab 120 mg | Number of Participant Visits With Positive Reponses by Device Type Subcutaneous Administration Assessment Questionnaire Q1, Q3-Q12 | Pre-filled Syringe: Easy to store device in fridge | 536 participants |
| Galcanezumab 120 mg | Number of Participant Visits With Positive Reponses by Device Type Subcutaneous Administration Assessment Questionnaire Q1, Q3-Q12 | Autoinjector : Easy store device in fridge | 230 participants |
| Galcanezumab 120 mg | Number of Participant Visits With Positive Reponses by Device Type Subcutaneous Administration Assessment Questionnaire Q1, Q3-Q12 | Pre-filled Syringe:Dvc is stable against skin | 590 participants |
| Galcanezumab 120 mg | Number of Participant Visits With Positive Reponses by Device Type Subcutaneous Administration Assessment Questionnaire Q1, Q3-Q12 | Autoinjector : Easy to remove needle shield | 250 participants |
| Galcanezumab 120 mg | Number of Participant Visits With Positive Reponses by Device Type Subcutaneous Administration Assessment Questionnaire Q1, Q3-Q12 | Pre-filled Syringe : Easy to hold in hand | 589 participants |
| Galcanezumab 120 mg | Number of Participant Visits With Positive Reponses by Device Type Subcutaneous Administration Assessment Questionnaire Q1, Q3-Q12 | Autoinjector : Easy to pickup | 251 participants |
| Galcanezumab 120 mg | Number of Participant Visits With Positive Reponses by Device Type Subcutaneous Administration Assessment Questionnaire Q1, Q3-Q12 | Pre-filled Syringe:Confident in ability to use | 580 participants |
| Galcanezumab 120 mg | Number of Participant Visits With Positive Reponses by Device Type Subcutaneous Administration Assessment Questionnaire Q1, Q3-Q12 | Autoinjector : Overall, easy to use | 251 participants |
| Galcanezumab 120 mg | Number of Participant Visits With Positive Reponses by Device Type Subcutaneous Administration Assessment Questionnaire Q1, Q3-Q12 | Pre-filled Syringe : Easy to remove needle shield | 610 participants |
| Galcanezumab 120 mg | Number of Participant Visits With Positive Reponses by Device Type Subcutaneous Administration Assessment Questionnaire Q1, Q3-Q12 | Autoinjector : Dvc is stable against skin | 244 participants |
| Galcanezumab 120 mg | Number of Participant Visits With Positive Reponses by Device Type Subcutaneous Administration Assessment Questionnaire Q1, Q3-Q12 | Pre-filled Syringe : Confident my dose is complete | 618 participants |
| Galcanezumab 120 mg | Number of Participant Visits With Positive Reponses by Device Type Subcutaneous Administration Assessment Questionnaire Q1, Q3-Q12 | Autoinjector : Confident in ability to use | 247 participants |
| Galcanezumab 120 mg | Number of Participant Visits With Positive Reponses by Device Type Subcutaneous Administration Assessment Questionnaire Q1, Q3-Q12 | Pre-filled Syringe : Easy to know dose is complete | 615 participants |
| Galcanezumab 120 mg | Number of Participant Visits With Positive Reponses by Device Type Subcutaneous Administration Assessment Questionnaire Q1, Q3-Q12 | Autoinjector : Confident my dose is complete | 244 participants |
| Galcanezumab 120 mg | Number of Participant Visits With Positive Reponses by Device Type Subcutaneous Administration Assessment Questionnaire Q1, Q3-Q12 | Pre-filled Syringe : Easy to learn how to use | 611 participants |
| Galcanezumab 240 mg | Number of Participant Visits With Positive Reponses by Device Type Subcutaneous Administration Assessment Questionnaire Q1, Q3-Q12 | Autoinjector : Confident my dose is complete | 263 participants |
| Galcanezumab 240 mg | Number of Participant Visits With Positive Reponses by Device Type Subcutaneous Administration Assessment Questionnaire Q1, Q3-Q12 | Pre-filled Syringe : Easy to learn how to use | 688 participants |
| Galcanezumab 240 mg | Number of Participant Visits With Positive Reponses by Device Type Subcutaneous Administration Assessment Questionnaire Q1, Q3-Q12 | Pre-filled Syringe : Easy to hold in hand | 660 participants |
| Galcanezumab 240 mg | Number of Participant Visits With Positive Reponses by Device Type Subcutaneous Administration Assessment Questionnaire Q1, Q3-Q12 | Pre-filled Syringe : Easy to inject my dose | 659 participants |
| Galcanezumab 240 mg | Number of Participant Visits With Positive Reponses by Device Type Subcutaneous Administration Assessment Questionnaire Q1, Q3-Q12 | Pre-filled Syringe : Easy to know dose is complete | 703 participants |
| Galcanezumab 240 mg | Number of Participant Visits With Positive Reponses by Device Type Subcutaneous Administration Assessment Questionnaire Q1, Q3-Q12 | Pre-filled Syringe: Easy to store device in fridge | 630 participants |
| Galcanezumab 240 mg | Number of Participant Visits With Positive Reponses by Device Type Subcutaneous Administration Assessment Questionnaire Q1, Q3-Q12 | Pre-filled Syringe : Easy to remove needle shield | 699 participants |
| Galcanezumab 240 mg | Number of Participant Visits With Positive Reponses by Device Type Subcutaneous Administration Assessment Questionnaire Q1, Q3-Q12 | Pre-filled Syringe : Easy to pickup | 693 participants |
| Galcanezumab 240 mg | Number of Participant Visits With Positive Reponses by Device Type Subcutaneous Administration Assessment Questionnaire Q1, Q3-Q12 | Pre-filled Syringe : overall, easy to use | 663 participants |
| Galcanezumab 240 mg | Number of Participant Visits With Positive Reponses by Device Type Subcutaneous Administration Assessment Questionnaire Q1, Q3-Q12 | Pre-filled Syringe:Dvc is stable against skin | 652 participants |
| Galcanezumab 240 mg | Number of Participant Visits With Positive Reponses by Device Type Subcutaneous Administration Assessment Questionnaire Q1, Q3-Q12 | Pre-filled Syringe:Confident in ability to use | 654 participants |
| Galcanezumab 240 mg | Number of Participant Visits With Positive Reponses by Device Type Subcutaneous Administration Assessment Questionnaire Q1, Q3-Q12 | Pre-filled Syringe : Confident my dose is complete | 708 participants |
| Galcanezumab 240 mg | Number of Participant Visits With Positive Reponses by Device Type Subcutaneous Administration Assessment Questionnaire Q1, Q3-Q12 | Autoinjector : Easy to learn how to use | 265 participants |
| Galcanezumab 240 mg | Number of Participant Visits With Positive Reponses by Device Type Subcutaneous Administration Assessment Questionnaire Q1, Q3-Q12 | Autoinjector : Easy to hold in hand | 267 participants |
| Galcanezumab 240 mg | Number of Participant Visits With Positive Reponses by Device Type Subcutaneous Administration Assessment Questionnaire Q1, Q3-Q12 | Autoinjector : Easy to inject my dose | 265 participants |
| Galcanezumab 240 mg | Number of Participant Visits With Positive Reponses by Device Type Subcutaneous Administration Assessment Questionnaire Q1, Q3-Q12 | Autoinjector : Easy to know dose is complete | 261 participants |
| Galcanezumab 240 mg | Number of Participant Visits With Positive Reponses by Device Type Subcutaneous Administration Assessment Questionnaire Q1, Q3-Q12 | Autoinjector : Easy store device in fridge | 256 participants |
| Galcanezumab 240 mg | Number of Participant Visits With Positive Reponses by Device Type Subcutaneous Administration Assessment Questionnaire Q1, Q3-Q12 | Autoinjector : Easy to remove needle shield | 268 participants |
| Galcanezumab 240 mg | Number of Participant Visits With Positive Reponses by Device Type Subcutaneous Administration Assessment Questionnaire Q1, Q3-Q12 | Autoinjector : Easy to pickup | 271 participants |
| Galcanezumab 240 mg | Number of Participant Visits With Positive Reponses by Device Type Subcutaneous Administration Assessment Questionnaire Q1, Q3-Q12 | Autoinjector : Overall, easy to use | 262 participants |
| Galcanezumab 240 mg | Number of Participant Visits With Positive Reponses by Device Type Subcutaneous Administration Assessment Questionnaire Q1, Q3-Q12 | Autoinjector : Dvc is stable against skin | 264 participants |
| Galcanezumab 240 mg | Number of Participant Visits With Positive Reponses by Device Type Subcutaneous Administration Assessment Questionnaire Q1, Q3-Q12 | Autoinjector : Confident in ability to use | 260 participants |
Secondary
Overall Mean Change From Baseline in the Frequency of Medication Use for the Acute Treatment of Migraines or Headaches
Overall mean is derived from the average of months 1 to 12 from MMRM model. LSMean was calculated using MMRM model with treatment, pooled investigative site, month, and treatment by month, baseline, and baseline by month as fixed effects.
Time frame: Baseline, Month 1 through Month 12
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 |
|---|---|---|---|
| Galcanezumab 120 mg | Overall Mean Change From Baseline in the Frequency of Medication Use for the Acute Treatment of Migraines or Headaches | -5.09 Medication Used Days per Month | Standard Error 0.38 |
| Galcanezumab 240 mg | Overall Mean Change From Baseline in the Frequency of Medication Use for the Acute Treatment of Migraines or Headaches | -5.05 Medication Used Days per Month | Standard Error 0.37 |
p-value: 0.93795% CI: [-0.96, 1.04]Mixed Models Analysis
Secondary
Overall Mean Change From Baseline in the Number of Headache Days
Headache Day: A calendar day on which any type of headache occurred (including migraine, probable migraine, and non-migraine headache). Overall mean is derived from the average of months 1 to 12 from MMRM model. LSMean was calculated using MMRM model with treatment, pooled investigative site, month, and treatment by month, baseline, and baseline by month as fixed effects.
Time frame: Baseline, Month 1 through Month 12
Population: All randomized participants who received at least one dose of study drug and had baseline \& at least one post baseline Value.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Galcanezumab 120 mg | Overall Mean Change From Baseline in the Number of Headache Days | -2.17 Headache Days per Month | Standard Error 0.3 |
| Galcanezumab 240 mg | Overall Mean Change From Baseline in the Number of Headache Days | -2.09 Headache Days per Month | Standard Error 0.3 |
p-value: 0.83595% CI: [-0.72, 0.89]Mixed Models Analysis
Secondary
Overall Mean Change From Baseline in the Number of 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 12 from MMRM model. Least squares mean (LSMean) was calculated using mixed model repeated measures (MMRM) model with treatment, pooled investigative site, month, and treatment by month, baseline, and baseline by month as fixed effects.
Time frame: Baseline, Month 1 through Month 12
Population: All randomized participants who received at least one dose of study drug and had baseline \& at least one post baseline value.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Galcanezumab 120 mg | Overall Mean Change From Baseline in the Number of Migraine Headache Days (MHD) | -5.61 Migraine Headache Days per Month | Standard Error 0.34 |
| Galcanezumab 240 mg | Overall Mean Change From Baseline in the Number of Migraine Headache Days (MHD) | -6.47 Migraine Headache Days per Month | Standard Error 0.33 |
p-value: 0.695% CI: [-1.76, 0.04]Mixed Models Analysis
Secondary
Overall 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. Overall mean is derived from the average of months 1 to 12 from MMRM model. LSMean was calculated using MMRM model with treatment, pooled investigative site, month, and treatment by month, baseline, and baseline by month.
Time frame: Baseline, Month 1 through Month 12
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 |
|---|---|---|---|
| Galcanezumab 120 mg | Overall Mean Change From Baseline on the Migraine Disability Assessment Test (MIDAS) Total Score | -33.58 units on a scale | Standard Error 2.11 |
| Galcanezumab 240 mg | Overall Mean Change From Baseline on the Migraine Disability Assessment Test (MIDAS) Total Score | -32.67 units on a scale | Standard Error 2.04 |
p-value: 0.74795% CI: [-4.65, 6.47]Mixed Models Analysis
Secondary
Overall Mean Change From Baseline on the Migraine-Specific Quality of Life Questionnaire (MSQ) Version 2.1
MSQv2.1 is a health status instrument,with a 4-week recall period, developed to address physical & 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 addressing 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 total raw score is computed for each domain & total score, 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 1 through Month 12
Population: All randomized participants who received at least one dose of study drug and had baseline and at least one post baseline value.~Overall mean is derived from the average of months 1 to 12.LSMean was calculated using MMRM model with treatment, pooled investigative site, month, and treatment by month, baseline, and baseline by month as fixed effects.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Galcanezumab 120 mg | Overall Mean Change From Baseline on the Migraine-Specific Quality of Life Questionnaire (MSQ) Version 2.1 | Total Score | 28.27 units on a scale | Standard Error 1.16 |
| Galcanezumab 120 mg | Overall Mean Change From Baseline on the Migraine-Specific Quality of Life Questionnaire (MSQ) Version 2.1 | Role Function-Restrictive Domain | 31.55 units on a scale | Standard Error 1.2 |
| Galcanezumab 120 mg | Overall Mean Change From Baseline on the Migraine-Specific Quality of Life Questionnaire (MSQ) Version 2.1 | Role Function-Preventive Domain | 22.08 units on a scale | Standard Error 1.11 |
| Galcanezumab 120 mg | Overall Mean Change From Baseline on the Migraine-Specific Quality of Life Questionnaire (MSQ) Version 2.1 | Emotional Function Domain | 28.92 units on a scale | Standard Error 1.35 |
| Galcanezumab 240 mg | Overall Mean Change From Baseline on the Migraine-Specific Quality of Life Questionnaire (MSQ) Version 2.1 | Emotional Function Domain | 32.01 units on a scale | Standard Error 1.31 |
| Galcanezumab 240 mg | Overall Mean Change From Baseline on the Migraine-Specific Quality of Life Questionnaire (MSQ) Version 2.1 | Total Score | 30.25 units on a scale | Standard Error 1.13 |
| Galcanezumab 240 mg | Overall Mean Change From Baseline on the Migraine-Specific Quality of Life Questionnaire (MSQ) Version 2.1 | Role Function-Preventive Domain | 23.33 units on a scale | Standard Error 1.08 |
| Galcanezumab 240 mg | Overall Mean Change From Baseline on the Migraine-Specific Quality of Life Questionnaire (MSQ) Version 2.1 | Role Function-Restrictive Domain | 33.40 units on a scale | Standard Error 1.16 |
Comparison: Total Scorep-value: 0.20395% CI: [-1.07, 5.03]Mixed Models Analysis
Comparison: Role Function-Restrictive Domain Scorep-value: 0.24795% CI: [-1.29, 4.98]Mixed Models Analysis
Comparison: Role Function-Preventive Domain Scorep-value: 0.39995% CI: [-1.67, 4.19]Mixed Models Analysis
Comparison: Emotional Function Domain Scorep-value: 0.8895% CI: [-0.46, 6.64]Mixed Models Analysis
Secondary
Overall Mean Patient Global Impression-Improvement (PGI-I) Score
The Patient Global Impression of Improvement (PGI -I) scale is a participant-rated instrument that measures the participants own global impression of their symptom improvement. The participant was instructed as follows: Mark the box that best describes your migraine headache condition since you started taking this medicine. Response options were on a 7-point scale in which a score of 1 indicates that the participant's condition is very much better, a score of 4 indicates that the participant has experienced no change, and a score of 7 indicates that the participant is very much worse. Overall mean is derived from the average of months 1 to 12 from MMRM model. LSMean was calculated using MMRM model with treatment, pooled investigative site, month, and treatment by month, baseline PGI-S, and baseline PGI-S by month as fixed effects.
Time frame: Month 1 through Month 12
Population: All randomized participants who received at least one dose of study drug and had at least one post baseline value.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Galcanezumab 120 mg | Overall Mean Patient Global Impression-Improvement (PGI-I) Score | 2.18 units on a scale | Standard Error 0.08 |
| Galcanezumab 240 mg | Overall Mean Patient Global Impression-Improvement (PGI-I) Score | 1.99 units on a scale | Standard Error 0.08 |
p-value: 0.07395% CI: [-0.4, 0.02]Mixed Models Analysis
Secondary
Percentage of Participants Developing Anti-Drug Antibodies to Galcanezumab
A Treatment Emergent Anti-drug Antibody (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 \>= 1: 20 (treatment-induced). There were 6 participants in the 120 mg arm who discontinued after receiving loading dose of 240mg, these participants were moved to 240mg arm for safety analysis.
Time frame: Month 1 through Month 12
Population: All randomized participants who received at least one dose of study drug and had baseline and at least one post baseline evaluable data for TE ADA.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Galcanezumab 120 mg | Percentage of Participants Developing Anti-Drug Antibodies to Galcanezumab | 12.40 Percentage of Participants |
| Galcanezumab 240 mg | Percentage of Participants Developing Anti-Drug Antibodies to Galcanezumab | 7.30 Percentage of Participants |
Comparison: TE ADA Positive (TE ADA+)p-value: 0.215Fisher Exact
Secondary
Percentage of Participants With Overall Reduction From Baseline ≥50% in Monthly Migraine Headache Days
Migraine Headache Day: A calendar day on which a migraine headache or probable migraine headache occurred. Overall percentage of participants with a given response rate were estimated from the generalized linear mixed models (GLIMMIX) model.
Time frame: Baseline, Month 1 through Month 12
Population: All randomized participants who received at least one dose of study drug and had baseline \& at least one post baseline value.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Galcanezumab 120 mg | Percentage of Participants With Overall Reduction From Baseline ≥50% in Monthly Migraine Headache Days | 65.6 percentage of Participants |
| Galcanezumab 240 mg | Percentage of Participants With Overall Reduction From Baseline ≥50% in Monthly Migraine Headache Days | 73.7 percentage of Participants |
p-value: 0.06395% CI: [0.979, 2.197]CPLRM
Secondary
Percentage of Participants With Positive Responses on Patient Satisfaction With Medication Questionnaire-Modified (PSMQ-M)
The PSMQ-M is a self-rated scale which measures participants level of satisfaction with study medication.The scale has been modified for use in this study, assessing 3 items related to the clinical trial treatment over the past 4 weeks: satisfaction, preference, and side effects. Satisfaction responses range from very unsatisfied to very satisfied with the current treatment. Preference compares the current study medication to previous medications, with responses from much rather prefer my previous medication to much rather prefer the medication administered to me during the study.
Time frame: Baseline through Month 12
Population: All randomized participants who received at least one dose of study drug and had month 12 PSMQ-M measurement.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Galcanezumab 120 mg | Percentage of Participants With Positive Responses on Patient Satisfaction With Medication Questionnaire-Modified (PSMQ-M) | Satisfaction: Very satisfied | 57.78 percentage of Participants |
| Galcanezumab 120 mg | Percentage of Participants With Positive Responses on Patient Satisfaction With Medication Questionnaire-Modified (PSMQ-M) | Satisfaction: Somewhat satisfied | 18.89 percentage of Participants |
| Galcanezumab 120 mg | Percentage of Participants With Positive Responses on Patient Satisfaction With Medication Questionnaire-Modified (PSMQ-M) | Preference: Much prefer study medication | 66.67 percentage of Participants |
| Galcanezumab 120 mg | Percentage of Participants With Positive Responses on Patient Satisfaction With Medication Questionnaire-Modified (PSMQ-M) | Preference: Prefer study medication | 22.22 percentage of Participants |
| Galcanezumab 120 mg | Percentage of Participants With Positive Responses on Patient Satisfaction With Medication Questionnaire-Modified (PSMQ-M) | Side effects: Much less side effects | 66.67 percentage of Participants |
| Galcanezumab 120 mg | Percentage of Participants With Positive Responses on Patient Satisfaction With Medication Questionnaire-Modified (PSMQ-M) | Side effects: Less side effects | 14.44 percentage of Participants |
| Galcanezumab 240 mg | Percentage of Participants With Positive Responses on Patient Satisfaction With Medication Questionnaire-Modified (PSMQ-M) | Side effects: Much less side effects | 50.89 percentage of Participants |
| Galcanezumab 240 mg | Percentage of Participants With Positive Responses on Patient Satisfaction With Medication Questionnaire-Modified (PSMQ-M) | Satisfaction: Very satisfied | 58.04 percentage of Participants |
| Galcanezumab 240 mg | Percentage of Participants With Positive Responses on Patient Satisfaction With Medication Questionnaire-Modified (PSMQ-M) | Preference: Prefer study medication | 17.86 percentage of Participants |
| Galcanezumab 240 mg | Percentage of Participants With Positive Responses on Patient Satisfaction With Medication Questionnaire-Modified (PSMQ-M) | Satisfaction: Somewhat satisfied | 15.18 percentage of Participants |
| Galcanezumab 240 mg | Percentage of Participants With Positive Responses on Patient Satisfaction With Medication Questionnaire-Modified (PSMQ-M) | Side effects: Less side effects | 30.36 percentage of Participants |
| Galcanezumab 240 mg | Percentage of Participants With Positive Responses on Patient Satisfaction With Medication Questionnaire-Modified (PSMQ-M) | Preference: Much prefer study medication | 63.39 percentage of Participants |
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 12
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 12
Population: All randomized participants with measurable plasma concentration.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Galcanezumab 120 mg | Plasma Concentration of Calcitonin Gene-Related Peptide (CGRP) | 2.74 ng/mL | Standard Deviation 1.07 |
| Galcanezumab 240 mg | Plasma Concentration of Calcitonin Gene-Related Peptide (CGRP) | 3.85 ng/mL | Standard Deviation 1.85 |
Secondary
Serum Concentrations of Galcanezumab
Serum Concentrations of Galcanezumab.
Time frame: Month 12
Population: All randomized participants with measurable serum concentrations at month 12.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Galcanezumab 120 mg | Serum Concentrations of Galcanezumab | 16500 Nanogram per milliliter (ng/mL) | Standard Deviation 8370 |
| Galcanezumab 240 mg | Serum Concentrations of Galcanezumab | 31600 Nanogram per milliliter (ng/mL) | Standard Deviation 15900 |