Migraine
Conditions
Keywords
Migraine Prevention, Headache, Prophylaxis
Brief summary
Randomized, double-blind, placebo-controlled, parallel-group, multicenter study followed by an open-label treatment phase (OLTP). To evaluate the effect of erenumab (AMG 334) compared to placebo on the change from baseline in monthly migraine days.
Detailed description
This is a Phase 2, randomized, double-blind, placebo-controlled study in participants with episodic migraine. The study's double blind treatment phase (DBTP) is designed to evaluate if treatment with erenumab once a month for 6 months compared with placebo is effective in reducing the mean monthly migraine days. Additionally, this study will continue to evaluate the efficacy and safety of erenumab during the OLTP where participants will continue to receive active treatment monthly. The study also includes a clinical home use (CHU) sub-study to assess a participant's ability to self-administer 140 mg of erenumab. Participants will be randomized 1:1 to use either 2 pre-filled 70 mg/mL autoinjector (AI)/pens or 1 pre-filled 140 mg/mL AI/pen. Participation in the substudy is optional, and no additional samples will be collected for the sub-study. After implementation of Protocol Amendment 2, the dose of erenumab in the OLTP increased from 70 mg to 140 mg QM. Participants who had already completed week 48 remain on 70 mg QM, participants not yet starting the OLTP, or not yet completing the week 48 visit receive erenumab 140 mg QM for the remainder of the OLTP.
Interventions
DRUGPlacebo
placebo via subcutaneous injection
DRUGErenumab
erenumab via subcutaneous injection
Sponsors
Amgen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
20 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
to be assessed prior to entering the subject into the initial screening and/or baseline phase: * Provided informed consent prior to initiation of any study-specific activities/procedures * History of migraine (with or without aura) for ≥ 12 months prior to screening according to the International Headache Society (IHS) Classification The International Classification of Headache Disorders (ICHD)-3 (Headache Classification Committee of the IHS, 2013), * Migraine frequency: ≥ 4 and \< 15 migraine days per month on average across the 3 months prior to screening, * Headache frequency: \< 15 headache days per month on average across the 3 months prior to screening. Inclusion Criteria to be assessed during the baseline phase and confirmed prior to randomizing the subject into the double-blind treatment phase: * Demonstrated at least 80% compliance with the electronic Diary (eDiary), * Migraine frequency: ≥ 4 and \< 15 migraine days during the baseline phase based on the eDiary calculations, * Headache frequency: \< 15 headache days during the baseline phase based on the eDiary calculations. Inclusion Criteria for the Clinical Home Use (CHU) Substudy: \- Subjects must have provided informed consent for the substudy. Subjects enrolling in the CHU substudy must have received open-label 140 mg erenumab for at least 1 dose.
Exclusion criteria
* Older than 50 years of age at migraine onset, * History of cluster headache or hemiplegic migraine headache, * Unable to differentiate migraine from other headaches, * No therapeutic response with \> 2 of the following 7 medication categories for prophylactic treatment of migraine after an adequate therapeutic trial: Category 1: Divalproex sodium, sodium valproate, Category 2: Topiramate, Category 3: Beta blockers (for example: atenolol, bisoprolol, metoprolol, nadolol, nebivolol, pindolol, propranolol, timolol), Category 4: Tricyclic antidepressants (for example: amitriptyline, nortriptyline, protriptyline),Category 5: Serotonin-norepinephrine reuptake inhibitors (for example: venlafaxine, desvenlafaxine, duloxetine, milnacipran), Category 6: Flunarizine, verapamil, lomerizine, Category 7: Lisinopril, candesartan, * Used a prohibited medication, device or procedure within 2 months prior to the start of the baseline phase or during the baseline phase, * Received botulinum toxin in the head and/or neck region within 4 months prior to the start of the baseline phase or during the baseline phase, * Taken the following for any indication in any month during the 2 months prior to the start of the baseline phase: Ergotamines or triptans on ≥ 10 days per month, or Simple analgesics (nonsteroidal anti-inflammatory drugs \[NSAIDs\], acetaminophen) on ≥ 15 days per month, or Opioid- or butalbital-containing analgesics on ≥ 4 days per month, * Anticipated to require any excluded medication, device or procedure during the study, * Active chronic pain syndromes (such as fibromyalgia and chronic pelvic pain), * History of major psychiatric disorder (such as schizophrenia and bipolar disorder), or current evidence of depression based on a Beck Depression Inventory (BDI)-II total score \> 19 at screening. Subjects with anxiety disorder and/or major depressive disorder are permitted in the study if they are considered by the investigator to be stable and are taking no more than 1 medication for each disorder. Subjects must have been on a stable dose within the 3 months prior to the start of the baseline phase, * History of seizure disorder or other significant neurological conditions other than migraine. Note: A single childhood febrile seizure is not exclusionary, * Malignancy within the 5 years prior to screening, except non melanoma skin cancers, cervical or breast ductal carcinoma in situ, * Human immunodeficiency virus (HIV) infection by history, * Hepatic disease by history, or total bilirubin (TBL) ≥ 2.0 x upper limit of normal (ULN) or alanine transaminase (ALT) or aspartate aminotransferase (AST) ≥ 3.0 x ULN, as assessed by the central laboratory at initial screening, or evidence of acute or chronic hepatitis B or hepatitis C virus. Hepatitis status will be evaluated by testing for hepatitis B surface antigen (HepBsAg), total hepatitis B core antibody (HepBcAb) and hepatitis C antibody by the central laboratory at initial screening. Polymerase chain reaction (PCR) should be performed to confirm active disease only if total HepBcAb is positive and HepBsAg is negative or if C antibody is positive, * Myocardial infarction, stroke, transient ischemic attack (TIA), unstable angina, or coronary artery bypass surgery or other revascularization procedure within 12 months prior to screening, * History or evidence of any other unstable or clinically significant medical condition that, in the opinion of the investigator, would pose a risk to subject safety or interfere with the study evaluation, procedures or completion, * Subject has any clinically significant vital sign, laboratory, or electrocardiogram (ECG) abnormality during screening that, in the opinion of the investigator, could pose a risk to subject safety or interfere with the study evaluation, * The subject is at risk of self-harm or harm to others as evidenced by past suicidal behavior or endorsing items 4 or 5 on the Columbia-Suicide Severity Rating Scale (C-SSRS) assessed at screening, * Evidence of drug or alcohol abuse or dependence within 12 months prior to screening, based on medical records, patient self-report, or positive urine drug test performed during screening (with the exception of prescribed medications such as opioids or barbiturates), * Pregnant or breastfeeding, or is a female expecting to conceive during the study, including through 16 weeks after the last dose of investigational product, * Female subject of childbearing potential who is unwilling to use an acceptable method of effective contraception during treatment with investigational product through 16 weeks after the last dose of investigational product, * Currently receiving treatment in another investigational device or drug study, or less than 90 days prior to screening since ending treatment on another investigational device or drug study(-ies), * Known sensitivity to any component of the investigational product (Refer to the Investigational Product Instruction Manual \[IPIM\] for details), * Previously randomized into an erenumab study, * Member of investigational site staff or relative of the investigator, * Unlikely to be able to complete all protocol-required study visits or procedures, and/or to comply with all required study procedures (eg, independent completion of eDiary items) to the best of the subject's and investigator's knowledge.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Mean Monthly Migraine Days at Months 4, 5 and 6 | 4-week baseline phase and months 4, 5 and 6 of DBTP. | A migraine day was defined as any calendar day in which the participant experienced a qualified migraine headache (onset, continuation or recurrence of the migraine headache). A qualified migraine headache was a migraine with or without aura, lasting for ≥ 30 minutes, and meeting at least one of the following criteria: a) ≥ 2 of the following pain features: unilateral, throbbing, moderate to severe, exacerbated with exercise/physical activity; b) ≥ 1 of the following associated symptoms: nausea and/or vomiting, photophobia and phonophobia. Change from baseline was calculated using the mean monthly migraine days from months 4, 5 and 6 of the DBTP minus the number of migraine days during the 4-week baseline phase. Least squares (LS) mean was estimated using a generalized linear mixed model which included treatment, visit, treatment by visit interaction, stratification factor (current, prior only, or no prior/current treatment), and baseline value as covariates. |
| CHU Sub-Study: Participant-Reported Outcome of Attempted Full-Dose Administration at Day 29 (Week 4) and Day 57 (Week 8) | CHU day 29 (week 4) and day 57 (week 8) | On CHU day 29 and day 57, site staff interviewed sub-study participants and asked if they administered a full, partial, or no dose of erenumab (after explaining that a full dose means that the entire volume of the AI/pen was injected) and documented the participant's response in the electronic case report form. Data presented are the percentage of participants who reported full administration, not full administration, or discontinued investigational product (ie, no dose). (Day 1 of the CHU substudy occurred at any OLTP study visit \[up to week 88\] as long as the participant had previously received at least 1 OL dose of erenumab 140 mg.) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, Discontinuations Due to TEAEs, and Fatal TEAEs During the DBTP | From first dose of IP up to week 24 | An adverse event (AE) is defined as any untoward medical occurrence in a clinical trial participant. A serious adverse event (SAE) is defined as an adverse event that meets at least 1 of the following serious criteria: fatal; life threatening; requires in-patient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; congenital anomaly/birth defect; other medically important serious event. Events were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03 (grade 1=mild, grade 2=moderate, grade 3=severe, grade 4= life-threatening, grade 5=death). |
| Number of Participants With TEAEs, Serious TEAEs, Discontinuations Due to TEAEs, and Fatal TEAEs During the OLTP | From first dose of IP in the OLTP (week 24) through the end of the OLTP (week 100) plus 12 weeks | An AE is defined as any untoward medical occurrence in a clinical trial participant. An SAE is defined as an adverse event that meets at least 1 of the following serious criteria: fatal; life threatening; requires in-patient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; congenital anomaly/birth defect; other medically important serious event. Events were graded according to the NCI CTCAE version 4.03 (grade 1=mild, grade 2=moderate, grade 3=severe, grade 4= life-threatening, grade 5=death). |
| Number of Participants With TEAEs, Serious TEAEs, Discotninuations Due to TEAEs, Fatal TEAEs, and Adverse Device Effects During the CHU Sub-Study | CHU sub-study day 1 through day 85 (end of CHU sub-study). Day 1 of the CHU substudy occurred at any OLTP study visit (up to week 88) as long as the participant had previously received at least 1 OL dose of erenumab 140 mg. | An AE is defined as any untoward medical occurrence in a clinical trial participant. An SAE is defined as an adverse event that meets at least 1 of the following serious criteria: fatal; life threatening; requires in-patient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; congenital anomaly/birth defect; other medically important serious event. Events were graded according to the NCI CTCAE version 4.03 (grade 1=mild, grade 2=moderate, grade 3=severe, grade 4= life-threatening, grade 5=death). TEAEs leading to discontinuation of IP are TEAEs leading to complete discontinuation of erenumab regardless of CHU IP or parent study IP. |
| Number of Participants With Post-Baseline Liver Function Test Abnormalities During the DBTP | From the first dose of study IP through the end of the DBTP (up to week 24) | Post-baseline is defined as any assessment done after the first dose of IP. Liver Function tests included alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin (TBL). ULN=upper limit of normal. |
| Percentage of Participants With at Least a 50% Reduction From Baseline in Mean Monthly Migraine Days at Months 4, 5 and 6 | 4-week baseline phase and months 4, 5 and 6 of DBTP. | A migraine day was defined as any calendar day in which the participant experienced a qualified migraine headache (onset, continuation or recurrence of the migraine headache). A qualified migraine headache was a migraine with or without aura, lasting for ≥ 30 minutes, and meeting at least one of the following criteria: a) ≥ 2 of the following pain features: unilateral, throbbing, moderate to severe, exacerbated with exercise/physical activity; b) ≥ 1 of the following associated symptoms: nausea and/or vomiting, photophobia and phonophobia. At least a 50% reduction from baseline in monthly migraine days was determined if: (mean monthly migraine days over the last three months of the DBTP minus baseline monthly migraine days) \* 100 / baseline monthly migraine days, was less than or equal to -50%. |
| Number of Participants With Blood Pressure Changes From Baseline in Categories at Week 24 During the DBTP | Baseline (last assessment prior to first dose of IP), week 24 | Participants with increases (↑) from baseline (BL) in diastolic blood pressure (DBP) and systolic blood pressure (SBP) at week 24 (Wk24) are presented. |
| Number of Participants With Blood Pressure Changes From Pre-OLTP Baseline in Categories at Week 100 During the OLTP | Pre-OLTP Baseline (last assessment prior to first dose of IP in OLTP), week 100 | Participants with increases (↑) from baseline (BL) in diastolic blood pressure (DBP) and systolic blood pressure (SBP) at week 100 (Wk100) are presented. |
| Number of Participants With Anti-Erenumab Antibodies During the Entire Study for Participants Who Received ≥ 1 Dose of Erenumab | Baseline (first dose of erenumab) up to end of study (week 100) plus 12 weeks | Data are summarized by the treatment participants received during the double-blind treatment phase. Placebo participants may have received erenumab 70 mg or 140 mg during the OLTP. Baseline is defined as the last antibody assessment on or prior to the first dose of erenumab. Transient binding/neutralizing antibody responses are defined as a negative (neg) result at the participant's last timepoint tested among participants who developed binding/neutralizing antibodies post-baseline. |
| Number of Participants With Post-Baseline Liver Function Test Abnormalities During the OLTP | From the first dose of OLTP IP (week 24) through the end of the OLTP (up to week 100) | Post-baseline is defined as any assessment done after the first dose of OLTP IP. Liver Function tests included alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin (TBL). ULN=upper limit of normal. |
| Change From Baseline in Mean Monthly Acute Migraine-Specific Medication Treatment Days at Months 4, 5 and 6 | 4-week baseline phase and months 4, 5 and 6 of DBTP. | An acute migraine-specific medication treatment day was defined as any calendar day during which the participant took a migraine-specific medication (ie, triptan or ergotamine-derivatives). The change from baseline was calculated using the mean monthly acute migraine-specific medication treatment days over the last three months (months 4, 5 and 6) of the DBTP minus the baseline monthly acute migraine-specific medication treatment days. LS mean was estimated using a generalized linear mixed model which included treatment, visit, treatment by visit interaction, stratification factor (prior/current treatment), and baseline value as covariates. |
Countries
Japan
Participant flow
Recruitment details
The study, initiated on 06 January 2016 at 43 centers in Japan, included a 24-week double-blind treatment phase (DBTP) followed by a 76-week open-label (OL) treatment phase (OLTP). DBTP: participants were randomized 2:1:2:2 to receive placebo, erenumab 28 mg, erenumab 70 mg, or erenumab 140 mg once monthly (QM) subcutaneously (SC).
Pre-assignment details
OLTP: participants received erenumab 70 mg and/or 140 mg QM SC (depending on the participant's visit completion status after a protocol amendment). Optional 85-day clinical home use (CHU) sub-study during the OLTP: participants randomized 1:1 to erenumab using two 70 mg/mL or one 140 mg/mL autoinjector (AI)/pen(s).
Participants by arm
| Arm | Count |
|---|---|
| DBTP: Placebo Placebo SC on day 1 and at weeks 4, 8, 12, 16, and 20 in the DBTP. | 136 |
| DBTP: Erenumab 28 mg QM Erenumab 28 mg SC on day 1 and at weeks 4, 8, 12, 16, and 20 in the DBTP. | 67 |
| DPTP: Erenumab 70 mg QM Erenumab 70 mg SC on day 1 and at weeks 4, 8, 12, 16, and 20 in the DBTP. | 135 |
| DBTP: Erenumab 140 mg QM Erenumab 140 mg SC on day 1 and at weeks 4, 8, 12, 16, and 20 in the DBTP. | 137 |
| Total | 475 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 |
|---|---|---|---|---|---|---|---|---|---|
| Double-Blind Treatment Phase (DBTP) | Protocol-specified criteria | 0 | 1 | 0 | 2 | 0 | 0 | 0 | 0 |
| Double-Blind Treatment Phase (DBTP) | Sponsor decision | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Double-Blind Treatment Phase (DBTP) | Subject missed week 24 assessment | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Double-Blind Treatment Phase (DBTP) | Withdrawal by Subject | 2 | 1 | 4 | 1 | 0 | 0 | 0 | 0 |
| Open-Label Treatment Phase (OLTP) | Decision by Sponsor | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
| Open-Label Treatment Phase (OLTP) | Protocol-Specified Criteria | 0 | 0 | 0 | 0 | 4 | 1 | 0 | 0 |
| Open-Label Treatment Phase (OLTP) | Subject Request | 0 | 0 | 0 | 0 | 24 | 3 | 0 | 0 |
Baseline characteristics
| Characteristic | DPTP: Erenumab 70 mg QM | DBTP: Placebo | DBTP: Erenumab 140 mg QM | Total | DBTP: Erenumab 28 mg QM |
|---|---|---|---|---|---|
| Age, Continuous | 43.8 Years STANDARD_DEVIATION 9 | 43.7 Years STANDARD_DEVIATION 9.1 | 45.0 Years STANDARD_DEVIATION 8.3 | 44.0 Years STANDARD_DEVIATION 8.6 | 42.8 Years STANDARD_DEVIATION 6.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 135 Participants | 136 Participants | 137 Participants | 475 Participants | 67 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Monthly Migraine Days at Baseline | 7.84 Days STANDARD_DEVIATION 2.31 | 7.67 Days STANDARD_DEVIATION 2.34 | 8.14 Days STANDARD_DEVIATION 2.43 | 7.86 Days STANDARD_DEVIATION 2.33 | 7.68 Days STANDARD_DEVIATION 2.14 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 135 Participants | 136 Participants | 137 Participants | 475 Participants | 67 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 115 Participants | 118 Participants | 112 Participants | 400 Participants | 55 Participants |
| Sex: Female, Male Male | 20 Participants | 18 Participants | 25 Participants | 75 Participants | 12 Participants |
| Treatment Status with Migraine Prophylactic Medication Current treatment | 13 Participants | 14 Participants | 15 Participants | 49 Participants | 7 Participants |
| Treatment Status with Migraine Prophylactic Medication No prior or current treatment | 47 Participants | 47 Participants | 47 Participants | 163 Participants | 22 Participants |
| Treatment Status with Migraine Prophylactic Medication Prior treatment only | 75 Participants | 75 Participants | 75 Participants | 263 Participants | 38 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 |
|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 136 | 0 / 67 | 0 / 135 | 0 / 137 | 0 / 386 | 0 / 189 | 0 / 459 | 0 / 24 | 0 / 25 | 0 / 49 |
| other Total, other adverse events | 55 / 136 | 28 / 66 | 67 / 135 | 58 / 137 | 231 / 386 | 133 / 189 | 343 / 459 | 7 / 24 | 7 / 25 | 14 / 49 |
| serious Total, serious adverse events | 4 / 136 | 1 / 66 | 1 / 135 | 1 / 137 | 18 / 386 | 9 / 189 | 27 / 459 | 1 / 24 | 0 / 25 | 1 / 49 |
Outcome results
Primary
Change From Baseline in Mean Monthly Migraine Days at Months 4, 5 and 6
A migraine day was defined as any calendar day in which the participant experienced a qualified migraine headache (onset, continuation or recurrence of the migraine headache). A qualified migraine headache was a migraine with or without aura, lasting for ≥ 30 minutes, and meeting at least one of the following criteria: a) ≥ 2 of the following pain features: unilateral, throbbing, moderate to severe, exacerbated with exercise/physical activity; b) ≥ 1 of the following associated symptoms: nausea and/or vomiting, photophobia and phonophobia. Change from baseline was calculated using the mean monthly migraine days from months 4, 5 and 6 of the DBTP minus the number of migraine days during the 4-week baseline phase. Least squares (LS) mean was estimated using a generalized linear mixed model which included treatment, visit, treatment by visit interaction, stratification factor (current, prior only, or no prior/current treatment), and baseline value as covariates.
Time frame: 4-week baseline phase and months 4, 5 and 6 of DBTP.
Population: Efficacy Analysis Set: Participants who received at least 1 dose of the investigational product (IP) and had at least 1 change from baseline measurement in monthly migraine days during the DBTP.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| DBTP: Placebo | Change From Baseline in Mean Monthly Migraine Days at Months 4, 5 and 6 | 0.06 Days |
| DBTP: Erenumab 28 mg QM | Change From Baseline in Mean Monthly Migraine Days at Months 4, 5 and 6 | -1.19 Days |
| DPTP: Erenumab 70 mg QM | Change From Baseline in Mean Monthly Migraine Days at Months 4, 5 and 6 | -2.25 Days |
| DBTP: Erenumab 140 mg QM | Change From Baseline in Mean Monthly Migraine Days at Months 4, 5 and 6 | -1.83 Days |
Comparison: The primary analysis utilized a generalized linear mixed model which included treatment, visit, treatment by visit interaction, stratification factor (prior/current treatment with migraine prophylactic medication status), and baseline value as covariates and assumed a first-order autoregressive covariance structurep-value: <0.00195% CI: [-2.58, -1.2]Generalized Linear Mixed Model
Comparison: The primary analysis utilized a generalized linear mixed model which included treatment, visit, treatment by visit interaction, stratification factor (prior/current treatment with migraine prophylactic medication status), and baseline value as covariates and assumed a first-order autoregressive covariance structurep-value: <0.00195% CI: [-3, -1.62]Generalized Linear Mixed Model
Comparison: The primary analysis utilized a generalized linear mixed model which included treatment, visit, treatment by visit interaction, stratification factor (prior/current treatment with migraine prophylactic medication status), and baseline value as covariates and assumed a first-order autoregressive covariance structurep-value: 0.00495% CI: [-2.1, -0.41]Generalized Linear Mixed Model
Primary
CHU Sub-Study: Participant-Reported Outcome of Attempted Full-Dose Administration at Day 29 (Week 4) and Day 57 (Week 8)
On CHU day 29 and day 57, site staff interviewed sub-study participants and asked if they administered a full, partial, or no dose of erenumab (after explaining that a full dose means that the entire volume of the AI/pen was injected) and documented the participant's response in the electronic case report form. Data presented are the percentage of participants who reported full administration, not full administration, or discontinued investigational product (ie, no dose). (Day 1 of the CHU substudy occurred at any OLTP study visit \[up to week 88\] as long as the participant had previously received at least 1 OL dose of erenumab 140 mg.)
Time frame: CHU day 29 (week 4) and day 57 (week 8)
Population: CHU Sub-Study Analysis Set: all participants randomized into the CHU substudy who received at least one dose of CHU investigational product (IP).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| DBTP: Placebo | CHU Sub-Study: Participant-Reported Outcome of Attempted Full-Dose Administration at Day 29 (Week 4) and Day 57 (Week 8) | Week 4: Full Administration | 100.0 percentage of participants |
| DBTP: Placebo | CHU Sub-Study: Participant-Reported Outcome of Attempted Full-Dose Administration at Day 29 (Week 4) and Day 57 (Week 8) | Week 4: Not Full Administration | 0.0 percentage of participants |
| DBTP: Placebo | CHU Sub-Study: Participant-Reported Outcome of Attempted Full-Dose Administration at Day 29 (Week 4) and Day 57 (Week 8) | Week 4: Discontinued Investigational Product | 0.0 percentage of participants |
| DBTP: Placebo | CHU Sub-Study: Participant-Reported Outcome of Attempted Full-Dose Administration at Day 29 (Week 4) and Day 57 (Week 8) | Week 8: Full Administration | 100.0 percentage of participants |
| DBTP: Placebo | CHU Sub-Study: Participant-Reported Outcome of Attempted Full-Dose Administration at Day 29 (Week 4) and Day 57 (Week 8) | Week 8: Not Full Administration | 0.0 percentage of participants |
| DBTP: Placebo | CHU Sub-Study: Participant-Reported Outcome of Attempted Full-Dose Administration at Day 29 (Week 4) and Day 57 (Week 8) | Week 8: Discontinued Investigational Product | 0.0 percentage of participants |
| DBTP: Erenumab 28 mg QM | CHU Sub-Study: Participant-Reported Outcome of Attempted Full-Dose Administration at Day 29 (Week 4) and Day 57 (Week 8) | Week 8: Not Full Administration | 0.0 percentage of participants |
| DBTP: Erenumab 28 mg QM | CHU Sub-Study: Participant-Reported Outcome of Attempted Full-Dose Administration at Day 29 (Week 4) and Day 57 (Week 8) | Week 4: Full Administration | 100.0 percentage of participants |
| DBTP: Erenumab 28 mg QM | CHU Sub-Study: Participant-Reported Outcome of Attempted Full-Dose Administration at Day 29 (Week 4) and Day 57 (Week 8) | Week 8: Full Administration | 100.0 percentage of participants |
| DBTP: Erenumab 28 mg QM | CHU Sub-Study: Participant-Reported Outcome of Attempted Full-Dose Administration at Day 29 (Week 4) and Day 57 (Week 8) | Week 4: Not Full Administration | 0.0 percentage of participants |
| DBTP: Erenumab 28 mg QM | CHU Sub-Study: Participant-Reported Outcome of Attempted Full-Dose Administration at Day 29 (Week 4) and Day 57 (Week 8) | Week 8: Discontinued Investigational Product | 0.0 percentage of participants |
| DBTP: Erenumab 28 mg QM | CHU Sub-Study: Participant-Reported Outcome of Attempted Full-Dose Administration at Day 29 (Week 4) and Day 57 (Week 8) | Week 4: Discontinued Investigational Product | 0.0 percentage of participants |
Comparison: Week 4: Full Administration95% CI: [-13.3, 13.8]
Comparison: Week 4: Not Full Administration95% CI: [-13.8, 13.3]
Comparison: Week 4: Discontinued Investigational Product95% CI: [-13.8, 13.3]
Comparison: Week 8: Full Administration95% CI: [-13.3, 13.8]
Comparison: Week 8: Not Full Administration95% CI: [-13.8, 13.3]
Comparison: Week 8: Discontinued Investigational Product95% CI: [-13.8, 13.3]
Secondary
Change From Baseline in Mean Monthly Acute Migraine-Specific Medication Treatment Days at Months 4, 5 and 6
An acute migraine-specific medication treatment day was defined as any calendar day during which the participant took a migraine-specific medication (ie, triptan or ergotamine-derivatives). The change from baseline was calculated using the mean monthly acute migraine-specific medication treatment days over the last three months (months 4, 5 and 6) of the DBTP minus the baseline monthly acute migraine-specific medication treatment days. LS mean was estimated using a generalized linear mixed model which included treatment, visit, treatment by visit interaction, stratification factor (prior/current treatment), and baseline value as covariates.
Time frame: 4-week baseline phase and months 4, 5 and 6 of DBTP.
Population: Efficacy Analysis Set: Participants who received at least 1 dose of IP and had at least 1 change from baseline measurement in monthly migraine days during the DBTP.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| DBTP: Placebo | Change From Baseline in Mean Monthly Acute Migraine-Specific Medication Treatment Days at Months 4, 5 and 6 | 0.88 Days |
| DBTP: Erenumab 28 mg QM | Change From Baseline in Mean Monthly Acute Migraine-Specific Medication Treatment Days at Months 4, 5 and 6 | -0.19 Days |
| DPTP: Erenumab 70 mg QM | Change From Baseline in Mean Monthly Acute Migraine-Specific Medication Treatment Days at Months 4, 5 and 6 | -1.19 Days |
| DBTP: Erenumab 140 mg QM | Change From Baseline in Mean Monthly Acute Migraine-Specific Medication Treatment Days at Months 4, 5 and 6 | -1.16 Days |
Comparison: The primary analysis utilized a generalized linear mixed model which included treatment, visit, treatment by visit interaction, stratification factor (prior/current treatment with migraine prophylactic medication status), and baseline value as covariates and assumed a first-order autoregressive covariance structurep-value: <0.00195% CI: [-2.63, -1.45]Generalized Linear Mixed Model
Comparison: The primary analysis utilized a generalized linear mixed model which included treatment, visit, treatment by visit interaction, stratification factor (prior/current treatment with migraine prophylactic medication status), and baseline value as covariates and assumed a first-order autoregressive covariance structurep-value: <0.00195% CI: [-2.66, -1.49]Generalized Linear Mixed Model
Comparison: The primary analysis utilized a generalized linear mixed model which included treatment, visit, treatment by visit interaction, stratification factor (prior/current treatment with migraine prophylactic medication status), and baseline value as covariates and assumed a first-order autoregressive covariance structurep-value: 0.00495% CI: [-1.8, -0.35]Generalized Linear Mixed Model
Secondary
Number of Participants With Anti-Erenumab Antibodies During the Entire Study for Participants Who Received ≥ 1 Dose of Erenumab
Data are summarized by the treatment participants received during the double-blind treatment phase. Placebo participants may have received erenumab 70 mg or 140 mg during the OLTP. Baseline is defined as the last antibody assessment on or prior to the first dose of erenumab. Transient binding/neutralizing antibody responses are defined as a negative (neg) result at the participant's last timepoint tested among participants who developed binding/neutralizing antibodies post-baseline.
Time frame: Baseline (first dose of erenumab) up to end of study (week 100) plus 12 weeks
Population: Safety Analysis Set: all randomized participants who received at least one dose of IP. Participants who received at least one dose of erenumab (during the DBTP and/or OLTP).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| DBTP: Placebo | Number of Participants With Anti-Erenumab Antibodies During the Entire Study for Participants Who Received ≥ 1 Dose of Erenumab | Binding Antibody Positive (BAb+) at Baseline (BL) | 0 Participants |
| DBTP: Placebo | Number of Participants With Anti-Erenumab Antibodies During the Entire Study for Participants Who Received ≥ 1 Dose of Erenumab | Neutralizing Antibody Positive (NAb+) at BL | 0 Participants |
| DBTP: Placebo | Number of Participants With Anti-Erenumab Antibodies During the Entire Study for Participants Who Received ≥ 1 Dose of Erenumab | BAb+ Post-BL With a Neg/No Result at BL | 4 Participants |
| DBTP: Placebo | Number of Participants With Anti-Erenumab Antibodies During the Entire Study for Participants Who Received ≥ 1 Dose of Erenumab | Transient BAb+ Post-BL With a Neg/No Result at BL | 2 Participants |
| DBTP: Placebo | Number of Participants With Anti-Erenumab Antibodies During the Entire Study for Participants Who Received ≥ 1 Dose of Erenumab | NAb+ Post-BL With a Neg/No Result at BL | 0 Participants |
| DBTP: Placebo | Number of Participants With Anti-Erenumab Antibodies During the Entire Study for Participants Who Received ≥ 1 Dose of Erenumab | Transient NAb+ Post-BL With a Neg/No Result at BL | 0 Participants |
| DBTP: Erenumab 28 mg QM | Number of Participants With Anti-Erenumab Antibodies During the Entire Study for Participants Who Received ≥ 1 Dose of Erenumab | Transient NAb+ Post-BL With a Neg/No Result at BL | 0 Participants |
| DBTP: Erenumab 28 mg QM | Number of Participants With Anti-Erenumab Antibodies During the Entire Study for Participants Who Received ≥ 1 Dose of Erenumab | Transient BAb+ Post-BL With a Neg/No Result at BL | 4 Participants |
| DBTP: Erenumab 28 mg QM | Number of Participants With Anti-Erenumab Antibodies During the Entire Study for Participants Who Received ≥ 1 Dose of Erenumab | Binding Antibody Positive (BAb+) at Baseline (BL) | 0 Participants |
| DBTP: Erenumab 28 mg QM | Number of Participants With Anti-Erenumab Antibodies During the Entire Study for Participants Who Received ≥ 1 Dose of Erenumab | BAb+ Post-BL With a Neg/No Result at BL | 5 Participants |
| DBTP: Erenumab 28 mg QM | Number of Participants With Anti-Erenumab Antibodies During the Entire Study for Participants Who Received ≥ 1 Dose of Erenumab | Neutralizing Antibody Positive (NAb+) at BL | 0 Participants |
| DBTP: Erenumab 28 mg QM | Number of Participants With Anti-Erenumab Antibodies During the Entire Study for Participants Who Received ≥ 1 Dose of Erenumab | NAb+ Post-BL With a Neg/No Result at BL | 0 Participants |
| DPTP: Erenumab 70 mg QM | Number of Participants With Anti-Erenumab Antibodies During the Entire Study for Participants Who Received ≥ 1 Dose of Erenumab | Neutralizing Antibody Positive (NAb+) at BL | 0 Participants |
| DPTP: Erenumab 70 mg QM | Number of Participants With Anti-Erenumab Antibodies During the Entire Study for Participants Who Received ≥ 1 Dose of Erenumab | BAb+ Post-BL With a Neg/No Result at BL | 6 Participants |
| DPTP: Erenumab 70 mg QM | Number of Participants With Anti-Erenumab Antibodies During the Entire Study for Participants Who Received ≥ 1 Dose of Erenumab | Transient BAb+ Post-BL With a Neg/No Result at BL | 5 Participants |
| DPTP: Erenumab 70 mg QM | Number of Participants With Anti-Erenumab Antibodies During the Entire Study for Participants Who Received ≥ 1 Dose of Erenumab | Transient NAb+ Post-BL With a Neg/No Result at BL | 0 Participants |
| DPTP: Erenumab 70 mg QM | Number of Participants With Anti-Erenumab Antibodies During the Entire Study for Participants Who Received ≥ 1 Dose of Erenumab | NAb+ Post-BL With a Neg/No Result at BL | 0 Participants |
| DPTP: Erenumab 70 mg QM | Number of Participants With Anti-Erenumab Antibodies During the Entire Study for Participants Who Received ≥ 1 Dose of Erenumab | Binding Antibody Positive (BAb+) at Baseline (BL) | 0 Participants |
| DBTP: Erenumab 140 mg QM | Number of Participants With Anti-Erenumab Antibodies During the Entire Study for Participants Who Received ≥ 1 Dose of Erenumab | NAb+ Post-BL With a Neg/No Result at BL | 0 Participants |
| DBTP: Erenumab 140 mg QM | Number of Participants With Anti-Erenumab Antibodies During the Entire Study for Participants Who Received ≥ 1 Dose of Erenumab | Transient NAb+ Post-BL With a Neg/No Result at BL | 0 Participants |
| DBTP: Erenumab 140 mg QM | Number of Participants With Anti-Erenumab Antibodies During the Entire Study for Participants Who Received ≥ 1 Dose of Erenumab | Neutralizing Antibody Positive (NAb+) at BL | 0 Participants |
| DBTP: Erenumab 140 mg QM | Number of Participants With Anti-Erenumab Antibodies During the Entire Study for Participants Who Received ≥ 1 Dose of Erenumab | Transient BAb+ Post-BL With a Neg/No Result at BL | 0 Participants |
| DBTP: Erenumab 140 mg QM | Number of Participants With Anti-Erenumab Antibodies During the Entire Study for Participants Who Received ≥ 1 Dose of Erenumab | Binding Antibody Positive (BAb+) at Baseline (BL) | 0 Participants |
| DBTP: Erenumab 140 mg QM | Number of Participants With Anti-Erenumab Antibodies During the Entire Study for Participants Who Received ≥ 1 Dose of Erenumab | BAb+ Post-BL With a Neg/No Result at BL | 0 Participants |
Secondary
Number of Participants With Blood Pressure Changes From Baseline in Categories at Week 24 During the DBTP
Participants with increases (↑) from baseline (BL) in diastolic blood pressure (DBP) and systolic blood pressure (SBP) at week 24 (Wk24) are presented.
Time frame: Baseline (last assessment prior to first dose of IP), week 24
Population: Safety Analysis Set: all randomized participants who received at least one dose of IP. Participants with an assessment at week 24.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| DBTP: Placebo | Number of Participants With Blood Pressure Changes From Baseline in Categories at Week 24 During the DBTP | ↑ from BL ≥10 mmHg in DBP w/DBP >90 mmHg at Wk24 | 3 Participants |
| DBTP: Placebo | Number of Participants With Blood Pressure Changes From Baseline in Categories at Week 24 During the DBTP | ↑ from BL ≥10 mmHg in DBP w/DBP ≤90 mmHg at Wk24 | 14 Participants |
| DBTP: Placebo | Number of Participants With Blood Pressure Changes From Baseline in Categories at Week 24 During the DBTP | ↑ from BL ≥20 mmHg in SBP w/SBP >140 mmHg at Wk24 | 1 Participants |
| DBTP: Placebo | Number of Participants With Blood Pressure Changes From Baseline in Categories at Week 24 During the DBTP | ↑ from BL ≥20 mmHg in SBP w/SBP ≤140 mmHg at Wk24 | 0 Participants |
| DBTP: Erenumab 28 mg QM | Number of Participants With Blood Pressure Changes From Baseline in Categories at Week 24 During the DBTP | ↑ from BL ≥10 mmHg in DBP w/DBP ≤90 mmHg at Wk24 | 6 Participants |
| DBTP: Erenumab 28 mg QM | Number of Participants With Blood Pressure Changes From Baseline in Categories at Week 24 During the DBTP | ↑ from BL ≥20 mmHg in SBP w/SBP >140 mmHg at Wk24 | 1 Participants |
| DBTP: Erenumab 28 mg QM | Number of Participants With Blood Pressure Changes From Baseline in Categories at Week 24 During the DBTP | ↑ from BL ≥20 mmHg in SBP w/SBP ≤140 mmHg at Wk24 | 2 Participants |
| DBTP: Erenumab 28 mg QM | Number of Participants With Blood Pressure Changes From Baseline in Categories at Week 24 During the DBTP | ↑ from BL ≥10 mmHg in DBP w/DBP >90 mmHg at Wk24 | 2 Participants |
| DPTP: Erenumab 70 mg QM | Number of Participants With Blood Pressure Changes From Baseline in Categories at Week 24 During the DBTP | ↑ from BL ≥20 mmHg in SBP w/SBP >140 mmHg at Wk24 | 0 Participants |
| DPTP: Erenumab 70 mg QM | Number of Participants With Blood Pressure Changes From Baseline in Categories at Week 24 During the DBTP | ↑ from BL ≥10 mmHg in DBP w/DBP ≤90 mmHg at Wk24 | 14 Participants |
| DPTP: Erenumab 70 mg QM | Number of Participants With Blood Pressure Changes From Baseline in Categories at Week 24 During the DBTP | ↑ from BL ≥20 mmHg in SBP w/SBP ≤140 mmHg at Wk24 | 0 Participants |
| DPTP: Erenumab 70 mg QM | Number of Participants With Blood Pressure Changes From Baseline in Categories at Week 24 During the DBTP | ↑ from BL ≥10 mmHg in DBP w/DBP >90 mmHg at Wk24 | 1 Participants |
| DBTP: Erenumab 140 mg QM | Number of Participants With Blood Pressure Changes From Baseline in Categories at Week 24 During the DBTP | ↑ from BL ≥20 mmHg in SBP w/SBP ≤140 mmHg at Wk24 | 3 Participants |
| DBTP: Erenumab 140 mg QM | Number of Participants With Blood Pressure Changes From Baseline in Categories at Week 24 During the DBTP | ↑ from BL ≥10 mmHg in DBP w/DBP ≤90 mmHg at Wk24 | 8 Participants |
| DBTP: Erenumab 140 mg QM | Number of Participants With Blood Pressure Changes From Baseline in Categories at Week 24 During the DBTP | ↑ from BL ≥10 mmHg in DBP w/DBP >90 mmHg at Wk24 | 3 Participants |
| DBTP: Erenumab 140 mg QM | Number of Participants With Blood Pressure Changes From Baseline in Categories at Week 24 During the DBTP | ↑ from BL ≥20 mmHg in SBP w/SBP >140 mmHg at Wk24 | 2 Participants |
Secondary
Number of Participants With Blood Pressure Changes From Pre-OLTP Baseline in Categories at Week 100 During the OLTP
Participants with increases (↑) from baseline (BL) in diastolic blood pressure (DBP) and systolic blood pressure (SBP) at week 100 (Wk100) are presented.
Time frame: Pre-OLTP Baseline (last assessment prior to first dose of IP in OLTP), week 100
Population: Safety Analysis Set: all randomized participants who received at least one dose of IP in the OLTP. Participants with an assessment at week 100.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| DBTP: Placebo | Number of Participants With Blood Pressure Changes From Pre-OLTP Baseline in Categories at Week 100 During the OLTP | ↑ from BL ≥10 mmHg in DBP w/DBP >90 mmHg at Wk100 | 8 Participants |
| DBTP: Placebo | Number of Participants With Blood Pressure Changes From Pre-OLTP Baseline in Categories at Week 100 During the OLTP | ↑ from BL ≥10 mmHg in DBP w/DBP ≤90 mmHg at Wk100 | 25 Participants |
| DBTP: Placebo | Number of Participants With Blood Pressure Changes From Pre-OLTP Baseline in Categories at Week 100 During the OLTP | ↑ from BL ≥20 mmHg in SBP w/SBP >140 mmHg at Wk100 | 4 Participants |
| DBTP: Placebo | Number of Participants With Blood Pressure Changes From Pre-OLTP Baseline in Categories at Week 100 During the OLTP | ↑ from BL ≥20 mmHg in SBP w/SBP ≤140 mmHg at Wk100 | 7 Participants |
| DBTP: Erenumab 28 mg QM | Number of Participants With Blood Pressure Changes From Pre-OLTP Baseline in Categories at Week 100 During the OLTP | ↑ from BL ≥10 mmHg in DBP w/DBP ≤90 mmHg at Wk100 | 10 Participants |
| DBTP: Erenumab 28 mg QM | Number of Participants With Blood Pressure Changes From Pre-OLTP Baseline in Categories at Week 100 During the OLTP | ↑ from BL ≥20 mmHg in SBP w/SBP >140 mmHg at Wk100 | 0 Participants |
| DBTP: Erenumab 28 mg QM | Number of Participants With Blood Pressure Changes From Pre-OLTP Baseline in Categories at Week 100 During the OLTP | ↑ from BL ≥20 mmHg in SBP w/SBP ≤140 mmHg at Wk100 | 2 Participants |
| DBTP: Erenumab 28 mg QM | Number of Participants With Blood Pressure Changes From Pre-OLTP Baseline in Categories at Week 100 During the OLTP | ↑ from BL ≥10 mmHg in DBP w/DBP >90 mmHg at Wk100 | 0 Participants |
| DPTP: Erenumab 70 mg QM | Number of Participants With Blood Pressure Changes From Pre-OLTP Baseline in Categories at Week 100 During the OLTP | ↑ from BL ≥20 mmHg in SBP w/SBP >140 mmHg at Wk100 | 1 Participants |
| DPTP: Erenumab 70 mg QM | Number of Participants With Blood Pressure Changes From Pre-OLTP Baseline in Categories at Week 100 During the OLTP | ↑ from BL ≥10 mmHg in DBP w/DBP ≤90 mmHg at Wk100 | 10 Participants |
| DPTP: Erenumab 70 mg QM | Number of Participants With Blood Pressure Changes From Pre-OLTP Baseline in Categories at Week 100 During the OLTP | ↑ from BL ≥20 mmHg in SBP w/SBP ≤140 mmHg at Wk100 | 0 Participants |
| DPTP: Erenumab 70 mg QM | Number of Participants With Blood Pressure Changes From Pre-OLTP Baseline in Categories at Week 100 During the OLTP | ↑ from BL ≥10 mmHg in DBP w/DBP >90 mmHg at Wk100 | 2 Participants |
| DBTP: Erenumab 140 mg QM | Number of Participants With Blood Pressure Changes From Pre-OLTP Baseline in Categories at Week 100 During the OLTP | ↑ from BL ≥20 mmHg in SBP w/SBP ≤140 mmHg at Wk100 | 9 Participants |
| DBTP: Erenumab 140 mg QM | Number of Participants With Blood Pressure Changes From Pre-OLTP Baseline in Categories at Week 100 During the OLTP | ↑ from BL ≥10 mmHg in DBP w/DBP ≤90 mmHg at Wk100 | 45 Participants |
| DBTP: Erenumab 140 mg QM | Number of Participants With Blood Pressure Changes From Pre-OLTP Baseline in Categories at Week 100 During the OLTP | ↑ from BL ≥10 mmHg in DBP w/DBP >90 mmHg at Wk100 | 10 Participants |
| DBTP: Erenumab 140 mg QM | Number of Participants With Blood Pressure Changes From Pre-OLTP Baseline in Categories at Week 100 During the OLTP | ↑ from BL ≥20 mmHg in SBP w/SBP >140 mmHg at Wk100 | 5 Participants |
Secondary
Number of Participants With Post-Baseline Liver Function Test Abnormalities During the DBTP
Post-baseline is defined as any assessment done after the first dose of IP. Liver Function tests included alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin (TBL). ULN=upper limit of normal.
Time frame: From the first dose of study IP through the end of the DBTP (up to week 24)
Population: Safety Analysis Set: all randomized participants who received at least one dose of IP.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| DBTP: Placebo | Number of Participants With Post-Baseline Liver Function Test Abnormalities During the DBTP | Post-Baseline ALT or AST > 3 x ULN | 0 Participants |
| DBTP: Placebo | Number of Participants With Post-Baseline Liver Function Test Abnormalities During the DBTP | Post-Baseline ALT or AST > 5 x ULN | 0 Participants |
| DBTP: Placebo | Number of Participants With Post-Baseline Liver Function Test Abnormalities During the DBTP | Post-Baseline TBL > 1 x ULN | 6 Participants |
| DBTP: Placebo | Number of Participants With Post-Baseline Liver Function Test Abnormalities During the DBTP | Post-Baseline TBL > 1.5 x ULN | 0 Participants |
| DBTP: Placebo | Number of Participants With Post-Baseline Liver Function Test Abnormalities During the DBTP | Post-Baseline TBL > 2 x ULN | 0 Participants |
| DBTP: Placebo | Number of Participants With Post-Baseline Liver Function Test Abnormalities During the DBTP | Post-Baseline ALP > 1.5 x ULN | 0 Participants |
| DBTP: Erenumab 28 mg QM | Number of Participants With Post-Baseline Liver Function Test Abnormalities During the DBTP | Post-Baseline ALP > 1.5 x ULN | 0 Participants |
| DBTP: Erenumab 28 mg QM | Number of Participants With Post-Baseline Liver Function Test Abnormalities During the DBTP | Post-Baseline TBL > 1.5 x ULN | 1 Participants |
| DBTP: Erenumab 28 mg QM | Number of Participants With Post-Baseline Liver Function Test Abnormalities During the DBTP | Post-Baseline ALT or AST > 3 x ULN | 0 Participants |
| DBTP: Erenumab 28 mg QM | Number of Participants With Post-Baseline Liver Function Test Abnormalities During the DBTP | Post-Baseline TBL > 1 x ULN | 3 Participants |
| DBTP: Erenumab 28 mg QM | Number of Participants With Post-Baseline Liver Function Test Abnormalities During the DBTP | Post-Baseline ALT or AST > 5 x ULN | 0 Participants |
| DBTP: Erenumab 28 mg QM | Number of Participants With Post-Baseline Liver Function Test Abnormalities During the DBTP | Post-Baseline TBL > 2 x ULN | 0 Participants |
| DPTP: Erenumab 70 mg QM | Number of Participants With Post-Baseline Liver Function Test Abnormalities During the DBTP | Post-Baseline ALT or AST > 5 x ULN | 0 Participants |
| DPTP: Erenumab 70 mg QM | Number of Participants With Post-Baseline Liver Function Test Abnormalities During the DBTP | Post-Baseline TBL > 1 x ULN | 4 Participants |
| DPTP: Erenumab 70 mg QM | Number of Participants With Post-Baseline Liver Function Test Abnormalities During the DBTP | Post-Baseline TBL > 1.5 x ULN | 0 Participants |
| DPTP: Erenumab 70 mg QM | Number of Participants With Post-Baseline Liver Function Test Abnormalities During the DBTP | Post-Baseline ALP > 1.5 x ULN | 0 Participants |
| DPTP: Erenumab 70 mg QM | Number of Participants With Post-Baseline Liver Function Test Abnormalities During the DBTP | Post-Baseline TBL > 2 x ULN | 0 Participants |
| DPTP: Erenumab 70 mg QM | Number of Participants With Post-Baseline Liver Function Test Abnormalities During the DBTP | Post-Baseline ALT or AST > 3 x ULN | 3 Participants |
| DBTP: Erenumab 140 mg QM | Number of Participants With Post-Baseline Liver Function Test Abnormalities During the DBTP | Post-Baseline TBL > 2 x ULN | 0 Participants |
| DBTP: Erenumab 140 mg QM | Number of Participants With Post-Baseline Liver Function Test Abnormalities During the DBTP | Post-Baseline ALP > 1.5 x ULN | 0 Participants |
| DBTP: Erenumab 140 mg QM | Number of Participants With Post-Baseline Liver Function Test Abnormalities During the DBTP | Post-Baseline ALT or AST > 5 x ULN | 1 Participants |
| DBTP: Erenumab 140 mg QM | Number of Participants With Post-Baseline Liver Function Test Abnormalities During the DBTP | Post-Baseline TBL > 1.5 x ULN | 1 Participants |
| DBTP: Erenumab 140 mg QM | Number of Participants With Post-Baseline Liver Function Test Abnormalities During the DBTP | Post-Baseline ALT or AST > 3 x ULN | 1 Participants |
| DBTP: Erenumab 140 mg QM | Number of Participants With Post-Baseline Liver Function Test Abnormalities During the DBTP | Post-Baseline TBL > 1 x ULN | 4 Participants |
Secondary
Number of Participants With Post-Baseline Liver Function Test Abnormalities During the OLTP
Post-baseline is defined as any assessment done after the first dose of OLTP IP. Liver Function tests included alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin (TBL). ULN=upper limit of normal.
Time frame: From the first dose of OLTP IP (week 24) through the end of the OLTP (up to week 100)
Population: Safety Analysis Set: all randomized participants who received at least one dose of OLTP erenumab.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| DBTP: Placebo | Number of Participants With Post-Baseline Liver Function Test Abnormalities During the OLTP | Post-Baseline ALT or AST > 3 x ULN | 4 Participants |
| DBTP: Placebo | Number of Participants With Post-Baseline Liver Function Test Abnormalities During the OLTP | Post-Baseline ALT or AST > 5 x ULN | 0 Participants |
| DBTP: Placebo | Number of Participants With Post-Baseline Liver Function Test Abnormalities During the OLTP | Post-Baseline TBL > 1 x ULN | 12 Participants |
| DBTP: Placebo | Number of Participants With Post-Baseline Liver Function Test Abnormalities During the OLTP | Post-Baseline TBL > 1.5 x ULN | 0 Participants |
| DBTP: Placebo | Number of Participants With Post-Baseline Liver Function Test Abnormalities During the OLTP | Post-Baseline TBL > 2 x ULN | 0 Participants |
| DBTP: Placebo | Number of Participants With Post-Baseline Liver Function Test Abnormalities During the OLTP | Post-Baseline ALP > 1.5 x ULN | 0 Participants |
| DBTP: Erenumab 28 mg QM | Number of Participants With Post-Baseline Liver Function Test Abnormalities During the OLTP | Post-Baseline ALP > 1.5 x ULN | 0 Participants |
| DBTP: Erenumab 28 mg QM | Number of Participants With Post-Baseline Liver Function Test Abnormalities During the OLTP | Post-Baseline TBL > 1.5 x ULN | 0 Participants |
| DBTP: Erenumab 28 mg QM | Number of Participants With Post-Baseline Liver Function Test Abnormalities During the OLTP | Post-Baseline ALT or AST > 3 x ULN | 2 Participants |
| DBTP: Erenumab 28 mg QM | Number of Participants With Post-Baseline Liver Function Test Abnormalities During the OLTP | Post-Baseline TBL > 1 x ULN | 3 Participants |
| DBTP: Erenumab 28 mg QM | Number of Participants With Post-Baseline Liver Function Test Abnormalities During the OLTP | Post-Baseline ALT or AST > 5 x ULN | 0 Participants |
| DBTP: Erenumab 28 mg QM | Number of Participants With Post-Baseline Liver Function Test Abnormalities During the OLTP | Post-Baseline TBL > 2 x ULN | 0 Participants |
| DPTP: Erenumab 70 mg QM | Number of Participants With Post-Baseline Liver Function Test Abnormalities During the OLTP | Post-Baseline ALT or AST > 5 x ULN | 0 Participants |
| DPTP: Erenumab 70 mg QM | Number of Participants With Post-Baseline Liver Function Test Abnormalities During the OLTP | Post-Baseline TBL > 1 x ULN | 6 Participants |
| DPTP: Erenumab 70 mg QM | Number of Participants With Post-Baseline Liver Function Test Abnormalities During the OLTP | Post-Baseline TBL > 1.5 x ULN | 0 Participants |
| DPTP: Erenumab 70 mg QM | Number of Participants With Post-Baseline Liver Function Test Abnormalities During the OLTP | Post-Baseline ALP > 1.5 x ULN | 0 Participants |
| DPTP: Erenumab 70 mg QM | Number of Participants With Post-Baseline Liver Function Test Abnormalities During the OLTP | Post-Baseline TBL > 2 x ULN | 0 Participants |
| DPTP: Erenumab 70 mg QM | Number of Participants With Post-Baseline Liver Function Test Abnormalities During the OLTP | Post-Baseline ALT or AST > 3 x ULN | 0 Participants |
| DBTP: Erenumab 140 mg QM | Number of Participants With Post-Baseline Liver Function Test Abnormalities During the OLTP | Post-Baseline TBL > 2 x ULN | 0 Participants |
| DBTP: Erenumab 140 mg QM | Number of Participants With Post-Baseline Liver Function Test Abnormalities During the OLTP | Post-Baseline ALP > 1.5 x ULN | 0 Participants |
| DBTP: Erenumab 140 mg QM | Number of Participants With Post-Baseline Liver Function Test Abnormalities During the OLTP | Post-Baseline ALT or AST > 5 x ULN | 0 Participants |
| DBTP: Erenumab 140 mg QM | Number of Participants With Post-Baseline Liver Function Test Abnormalities During the OLTP | Post-Baseline TBL > 1.5 x ULN | 0 Participants |
| DBTP: Erenumab 140 mg QM | Number of Participants With Post-Baseline Liver Function Test Abnormalities During the OLTP | Post-Baseline ALT or AST > 3 x ULN | 6 Participants |
| DBTP: Erenumab 140 mg QM | Number of Participants With Post-Baseline Liver Function Test Abnormalities During the OLTP | Post-Baseline TBL > 1 x ULN | 21 Participants |
Secondary
Number of Participants With TEAEs, Serious TEAEs, Discontinuations Due to TEAEs, and Fatal TEAEs During the OLTP
An AE is defined as any untoward medical occurrence in a clinical trial participant. An SAE is defined as an adverse event that meets at least 1 of the following serious criteria: fatal; life threatening; requires in-patient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; congenital anomaly/birth defect; other medically important serious event. Events were graded according to the NCI CTCAE version 4.03 (grade 1=mild, grade 2=moderate, grade 3=severe, grade 4= life-threatening, grade 5=death).
Time frame: From first dose of IP in the OLTP (week 24) through the end of the OLTP (week 100) plus 12 weeks
Population: Open-Label Treatment Phase Set: all participants receiving at least one dose of IP in the OLTP, by dose received at the time of the event, and overall (total participants in the OLTP).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| DBTP: Placebo | Number of Participants With TEAEs, Serious TEAEs, Discontinuations Due to TEAEs, and Fatal TEAEs During the OLTP | Grade ≥ 2 TEAEs | 238 Participants |
| DBTP: Placebo | Number of Participants With TEAEs, Serious TEAEs, Discontinuations Due to TEAEs, and Fatal TEAEs During the OLTP | Serious TEAEs | 18 Participants |
| DBTP: Placebo | Number of Participants With TEAEs, Serious TEAEs, Discontinuations Due to TEAEs, and Fatal TEAEs During the OLTP | Grade ≥ 4 TEAEs | 0 Participants |
| DBTP: Placebo | Number of Participants With TEAEs, Serious TEAEs, Discontinuations Due to TEAEs, and Fatal TEAEs During the OLTP | All TEAEs | 292 Participants |
| DBTP: Placebo | Number of Participants With TEAEs, Serious TEAEs, Discontinuations Due to TEAEs, and Fatal TEAEs During the OLTP | Fatal TEAEs | 0 Participants |
| DBTP: Placebo | Number of Participants With TEAEs, Serious TEAEs, Discontinuations Due to TEAEs, and Fatal TEAEs During the OLTP | TEAEs Leading to Discontinuation of IP | 4 Participants |
| DBTP: Placebo | Number of Participants With TEAEs, Serious TEAEs, Discontinuations Due to TEAEs, and Fatal TEAEs During the OLTP | Grade ≥ 3 TEAEs | 19 Participants |
| DBTP: Erenumab 28 mg QM | Number of Participants With TEAEs, Serious TEAEs, Discontinuations Due to TEAEs, and Fatal TEAEs During the OLTP | Grade ≥ 4 TEAEs | 0 Participants |
| DBTP: Erenumab 28 mg QM | Number of Participants With TEAEs, Serious TEAEs, Discontinuations Due to TEAEs, and Fatal TEAEs During the OLTP | All TEAEs | 173 Participants |
| DBTP: Erenumab 28 mg QM | Number of Participants With TEAEs, Serious TEAEs, Discontinuations Due to TEAEs, and Fatal TEAEs During the OLTP | Grade ≥ 2 TEAEs | 147 Participants |
| DBTP: Erenumab 28 mg QM | Number of Participants With TEAEs, Serious TEAEs, Discontinuations Due to TEAEs, and Fatal TEAEs During the OLTP | Grade ≥ 3 TEAEs | 9 Participants |
| DBTP: Erenumab 28 mg QM | Number of Participants With TEAEs, Serious TEAEs, Discontinuations Due to TEAEs, and Fatal TEAEs During the OLTP | Serious TEAEs | 9 Participants |
| DBTP: Erenumab 28 mg QM | Number of Participants With TEAEs, Serious TEAEs, Discontinuations Due to TEAEs, and Fatal TEAEs During the OLTP | TEAEs Leading to Discontinuation of IP | 2 Participants |
| DBTP: Erenumab 28 mg QM | Number of Participants With TEAEs, Serious TEAEs, Discontinuations Due to TEAEs, and Fatal TEAEs During the OLTP | Fatal TEAEs | 0 Participants |
| DPTP: Erenumab 70 mg QM | Number of Participants With TEAEs, Serious TEAEs, Discontinuations Due to TEAEs, and Fatal TEAEs During the OLTP | Serious TEAEs | 27 Participants |
| DPTP: Erenumab 70 mg QM | Number of Participants With TEAEs, Serious TEAEs, Discontinuations Due to TEAEs, and Fatal TEAEs During the OLTP | Grade ≥ 2 TEAEs | 358 Participants |
| DPTP: Erenumab 70 mg QM | Number of Participants With TEAEs, Serious TEAEs, Discontinuations Due to TEAEs, and Fatal TEAEs During the OLTP | Fatal TEAEs | 0 Participants |
| DPTP: Erenumab 70 mg QM | Number of Participants With TEAEs, Serious TEAEs, Discontinuations Due to TEAEs, and Fatal TEAEs During the OLTP | TEAEs Leading to Discontinuation of IP | 6 Participants |
| DPTP: Erenumab 70 mg QM | Number of Participants With TEAEs, Serious TEAEs, Discontinuations Due to TEAEs, and Fatal TEAEs During the OLTP | Grade ≥ 4 TEAEs | 0 Participants |
| DPTP: Erenumab 70 mg QM | Number of Participants With TEAEs, Serious TEAEs, Discontinuations Due to TEAEs, and Fatal TEAEs During the OLTP | Grade ≥ 3 TEAEs | 28 Participants |
| DPTP: Erenumab 70 mg QM | Number of Participants With TEAEs, Serious TEAEs, Discontinuations Due to TEAEs, and Fatal TEAEs During the OLTP | All TEAEs | 422 Participants |
Secondary
Number of Participants With TEAEs, Serious TEAEs, Discotninuations Due to TEAEs, Fatal TEAEs, and Adverse Device Effects During the CHU Sub-Study
An AE is defined as any untoward medical occurrence in a clinical trial participant. An SAE is defined as an adverse event that meets at least 1 of the following serious criteria: fatal; life threatening; requires in-patient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; congenital anomaly/birth defect; other medically important serious event. Events were graded according to the NCI CTCAE version 4.03 (grade 1=mild, grade 2=moderate, grade 3=severe, grade 4= life-threatening, grade 5=death). TEAEs leading to discontinuation of IP are TEAEs leading to complete discontinuation of erenumab regardless of CHU IP or parent study IP.
Time frame: CHU sub-study day 1 through day 85 (end of CHU sub-study). Day 1 of the CHU substudy occurred at any OLTP study visit (up to week 88) as long as the participant had previously received at least 1 OL dose of erenumab 140 mg.
Population: CHU Sub-Study Analysis Set: all participants randomized into the CHU substudy who received at least one dose of CHU IP.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| DBTP: Placebo | Number of Participants With TEAEs, Serious TEAEs, Discotninuations Due to TEAEs, Fatal TEAEs, and Adverse Device Effects During the CHU Sub-Study | All TEAEs | 11 Participants |
| DBTP: Placebo | Number of Participants With TEAEs, Serious TEAEs, Discotninuations Due to TEAEs, Fatal TEAEs, and Adverse Device Effects During the CHU Sub-Study | Grade ≥ 2 TEAEs | 9 Participants |
| DBTP: Placebo | Number of Participants With TEAEs, Serious TEAEs, Discotninuations Due to TEAEs, Fatal TEAEs, and Adverse Device Effects During the CHU Sub-Study | Grade ≥ 3 TEAEs | 0 Participants |
| DBTP: Placebo | Number of Participants With TEAEs, Serious TEAEs, Discotninuations Due to TEAEs, Fatal TEAEs, and Adverse Device Effects During the CHU Sub-Study | Grade ≥ 4 TEAEs | 0 Participants |
| DBTP: Placebo | Number of Participants With TEAEs, Serious TEAEs, Discotninuations Due to TEAEs, Fatal TEAEs, and Adverse Device Effects During the CHU Sub-Study | Serious TEAEs | 1 Participants |
| DBTP: Placebo | Number of Participants With TEAEs, Serious TEAEs, Discotninuations Due to TEAEs, Fatal TEAEs, and Adverse Device Effects During the CHU Sub-Study | TEAEs Leading to Discontinuation of IP | 0 Participants |
| DBTP: Placebo | Number of Participants With TEAEs, Serious TEAEs, Discotninuations Due to TEAEs, Fatal TEAEs, and Adverse Device Effects During the CHU Sub-Study | Fatal TEAEs | 0 Participants |
| DBTP: Placebo | Number of Participants With TEAEs, Serious TEAEs, Discotninuations Due to TEAEs, Fatal TEAEs, and Adverse Device Effects During the CHU Sub-Study | Adverse Device Effects | 2 Participants |
| DBTP: Erenumab 28 mg QM | Number of Participants With TEAEs, Serious TEAEs, Discotninuations Due to TEAEs, Fatal TEAEs, and Adverse Device Effects During the CHU Sub-Study | Adverse Device Effects | 1 Participants |
| DBTP: Erenumab 28 mg QM | Number of Participants With TEAEs, Serious TEAEs, Discotninuations Due to TEAEs, Fatal TEAEs, and Adverse Device Effects During the CHU Sub-Study | All TEAEs | 14 Participants |
| DBTP: Erenumab 28 mg QM | Number of Participants With TEAEs, Serious TEAEs, Discotninuations Due to TEAEs, Fatal TEAEs, and Adverse Device Effects During the CHU Sub-Study | Serious TEAEs | 0 Participants |
| DBTP: Erenumab 28 mg QM | Number of Participants With TEAEs, Serious TEAEs, Discotninuations Due to TEAEs, Fatal TEAEs, and Adverse Device Effects During the CHU Sub-Study | Grade ≥ 2 TEAEs | 9 Participants |
| DBTP: Erenumab 28 mg QM | Number of Participants With TEAEs, Serious TEAEs, Discotninuations Due to TEAEs, Fatal TEAEs, and Adverse Device Effects During the CHU Sub-Study | Fatal TEAEs | 0 Participants |
| DBTP: Erenumab 28 mg QM | Number of Participants With TEAEs, Serious TEAEs, Discotninuations Due to TEAEs, Fatal TEAEs, and Adverse Device Effects During the CHU Sub-Study | Grade ≥ 3 TEAEs | 0 Participants |
| DBTP: Erenumab 28 mg QM | Number of Participants With TEAEs, Serious TEAEs, Discotninuations Due to TEAEs, Fatal TEAEs, and Adverse Device Effects During the CHU Sub-Study | TEAEs Leading to Discontinuation of IP | 0 Participants |
| DBTP: Erenumab 28 mg QM | Number of Participants With TEAEs, Serious TEAEs, Discotninuations Due to TEAEs, Fatal TEAEs, and Adverse Device Effects During the CHU Sub-Study | Grade ≥ 4 TEAEs | 0 Participants |
Secondary
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, Discontinuations Due to TEAEs, and Fatal TEAEs During the DBTP
An adverse event (AE) is defined as any untoward medical occurrence in a clinical trial participant. A serious adverse event (SAE) is defined as an adverse event that meets at least 1 of the following serious criteria: fatal; life threatening; requires in-patient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; congenital anomaly/birth defect; other medically important serious event. Events were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03 (grade 1=mild, grade 2=moderate, grade 3=severe, grade 4= life-threatening, grade 5=death).
Time frame: From first dose of IP up to week 24
Population: Safety Analysis Set: all randomized participants who received at least one dose of IP in the DBTP.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| DBTP: Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, Discontinuations Due to TEAEs, and Fatal TEAEs During the DBTP | All TEAEs | 92 Participants |
| DBTP: Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, Discontinuations Due to TEAEs, and Fatal TEAEs During the DBTP | TEAEs Leading to Discontinuation of IP | 1 Participants |
| DBTP: Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, Discontinuations Due to TEAEs, and Fatal TEAEs During the DBTP | Serious TEAEs | 4 Participants |
| DBTP: Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, Discontinuations Due to TEAEs, and Fatal TEAEs During the DBTP | Grade ≥ 2 TEAEs | 60 Participants |
| DBTP: Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, Discontinuations Due to TEAEs, and Fatal TEAEs During the DBTP | Fatal TEAEs | 0 Participants |
| DBTP: Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, Discontinuations Due to TEAEs, and Fatal TEAEs During the DBTP | Grade ≥ 3 TEAEs | 4 Participants |
| DBTP: Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, Discontinuations Due to TEAEs, and Fatal TEAEs During the DBTP | Grade ≥ 4 TEAEs | 0 Participants |
| DBTP: Erenumab 28 mg QM | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, Discontinuations Due to TEAEs, and Fatal TEAEs During the DBTP | TEAEs Leading to Discontinuation of IP | 0 Participants |
| DBTP: Erenumab 28 mg QM | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, Discontinuations Due to TEAEs, and Fatal TEAEs During the DBTP | Grade ≥ 4 TEAEs | 0 Participants |
| DBTP: Erenumab 28 mg QM | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, Discontinuations Due to TEAEs, and Fatal TEAEs During the DBTP | Grade ≥ 3 TEAEs | 1 Participants |
| DBTP: Erenumab 28 mg QM | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, Discontinuations Due to TEAEs, and Fatal TEAEs During the DBTP | Serious TEAEs | 1 Participants |
| DBTP: Erenumab 28 mg QM | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, Discontinuations Due to TEAEs, and Fatal TEAEs During the DBTP | Fatal TEAEs | 0 Participants |
| DBTP: Erenumab 28 mg QM | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, Discontinuations Due to TEAEs, and Fatal TEAEs During the DBTP | Grade ≥ 2 TEAEs | 33 Participants |
| DBTP: Erenumab 28 mg QM | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, Discontinuations Due to TEAEs, and Fatal TEAEs During the DBTP | All TEAEs | 40 Participants |
| DPTP: Erenumab 70 mg QM | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, Discontinuations Due to TEAEs, and Fatal TEAEs During the DBTP | Grade ≥ 4 TEAEs | 1 Participants |
| DPTP: Erenumab 70 mg QM | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, Discontinuations Due to TEAEs, and Fatal TEAEs During the DBTP | All TEAEs | 95 Participants |
| DPTP: Erenumab 70 mg QM | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, Discontinuations Due to TEAEs, and Fatal TEAEs During the DBTP | Grade ≥ 2 TEAEs | 66 Participants |
| DPTP: Erenumab 70 mg QM | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, Discontinuations Due to TEAEs, and Fatal TEAEs During the DBTP | Grade ≥ 3 TEAEs | 3 Participants |
| DPTP: Erenumab 70 mg QM | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, Discontinuations Due to TEAEs, and Fatal TEAEs During the DBTP | Serious TEAEs | 1 Participants |
| DPTP: Erenumab 70 mg QM | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, Discontinuations Due to TEAEs, and Fatal TEAEs During the DBTP | TEAEs Leading to Discontinuation of IP | 2 Participants |
| DPTP: Erenumab 70 mg QM | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, Discontinuations Due to TEAEs, and Fatal TEAEs During the DBTP | Fatal TEAEs | 0 Participants |
| DBTP: Erenumab 140 mg QM | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, Discontinuations Due to TEAEs, and Fatal TEAEs During the DBTP | Grade ≥ 3 TEAEs | 0 Participants |
| DBTP: Erenumab 140 mg QM | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, Discontinuations Due to TEAEs, and Fatal TEAEs During the DBTP | Fatal TEAEs | 0 Participants |
| DBTP: Erenumab 140 mg QM | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, Discontinuations Due to TEAEs, and Fatal TEAEs During the DBTP | TEAEs Leading to Discontinuation of IP | 0 Participants |
| DBTP: Erenumab 140 mg QM | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, Discontinuations Due to TEAEs, and Fatal TEAEs During the DBTP | Grade ≥ 2 TEAEs | 65 Participants |
| DBTP: Erenumab 140 mg QM | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, Discontinuations Due to TEAEs, and Fatal TEAEs During the DBTP | All TEAEs | 95 Participants |
| DBTP: Erenumab 140 mg QM | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, Discontinuations Due to TEAEs, and Fatal TEAEs During the DBTP | Serious TEAEs | 1 Participants |
| DBTP: Erenumab 140 mg QM | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, Discontinuations Due to TEAEs, and Fatal TEAEs During the DBTP | Grade ≥ 4 TEAEs | 0 Participants |
Secondary
Percentage of Participants With at Least a 50% Reduction From Baseline in Mean Monthly Migraine Days at Months 4, 5 and 6
A migraine day was defined as any calendar day in which the participant experienced a qualified migraine headache (onset, continuation or recurrence of the migraine headache). A qualified migraine headache was a migraine with or without aura, lasting for ≥ 30 minutes, and meeting at least one of the following criteria: a) ≥ 2 of the following pain features: unilateral, throbbing, moderate to severe, exacerbated with exercise/physical activity; b) ≥ 1 of the following associated symptoms: nausea and/or vomiting, photophobia and phonophobia. At least a 50% reduction from baseline in monthly migraine days was determined if: (mean monthly migraine days over the last three months of the DBTP minus baseline monthly migraine days) \* 100 / baseline monthly migraine days, was less than or equal to -50%.
Time frame: 4-week baseline phase and months 4, 5 and 6 of DBTP.
Population: Efficacy Analysis Set: Participants who received at least 1 dose of IP and had at least 1 change from baseline measurement in monthly migraine days during the DBTP.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| DBTP: Placebo | Percentage of Participants With at Least a 50% Reduction From Baseline in Mean Monthly Migraine Days at Months 4, 5 and 6 | 7.4 Percentage of participants |
| DBTP: Erenumab 28 mg QM | Percentage of Participants With at Least a 50% Reduction From Baseline in Mean Monthly Migraine Days at Months 4, 5 and 6 | 19.7 Percentage of participants |
| DPTP: Erenumab 70 mg QM | Percentage of Participants With at Least a 50% Reduction From Baseline in Mean Monthly Migraine Days at Months 4, 5 and 6 | 28.9 Percentage of participants |
| DBTP: Erenumab 140 mg QM | Percentage of Participants With at Least a 50% Reduction From Baseline in Mean Monthly Migraine Days at Months 4, 5 and 6 | 27.2 Percentage of participants |
Comparison: The common odds ratios and p-values were obtained from a Cochran-Mantel-Haenszel (CMH) test, stratified by stratification factor prior/current treatment with migraine prophylactic medication status.p-value: <0.00195% CI: [2.24, 9.99]Cochran-Mantel-Haenszel
Comparison: The common odds ratios and p-values were obtained from a CMH test, stratified by stratification factor prior/current treatment with migraine prophylactic medication status.p-value: <0.00195% CI: [2.6, 12.06]Cochran-Mantel-Haenszel
Comparison: The common odds ratios and p-values were obtained from a CMH test, stratified by stratification factor prior/current treatment with migraine prophylactic medication status.p-value: 0.00995% CI: [1.3, 7.88]Cochran-Mantel-Haenszel