Migraine
Conditions
Keywords
Migraine, Headache, Migraine Headache, Headache, Migraine, Amgen
Brief summary
Phase I, Randomized, Parallel-group, Double-Blind, Placebo-Controlled, Single Dose Study to Evaluate the Blockade of CGRP Receptor by AMG 334 in Preventing PACAP-38 Induced Migraine-like Attacks in Migraine Patients.
Interventions
DRUGErenumab
Administered once on day 1 of Part B of the study by intravenous infusion.
DRUGPlacebo
Administered once on day 1 of Part B of the study by intravenous infusion.
DRUGPACAP-38 Challenge Agent
Administered by intravenous infusion during Part A of the study for dose selection for Part B. Administered by intravenous infusion on day 8 in Part B as a challenge agent to induce a migraine-like attack.
Sponsors
Amgen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
No
Inclusion criteria
* Adults ≥ 18 to ≤ 45 years of age upon entry into screening * History of migraine headaches without aura for ≥ 6 months prior to screening according to the International Headache Society (IHS) International Classification of Headache Disorders (ICHD-II) (Headache Classification Committee of the International Headache Society, 2004) based on medical records and/or patient self-report * Migraine frequency: ≥ 1 and ≤ 5 migraine days per month in each of the 3 months prior to screening
Exclusion criteria
* History of migraine with aura, cluster headache or hemiplegic migraine headache according to the IHS Classification ICHD-II (Headache Classification Committee of the International Headache Society, 2004) based on medical records and/or patient self-report * ≥ 6 migraine days per month in the last 3 months prior to study enrollment and during screening period * Other headache disorders (except for episodic tension-type headache \<5 days/month)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With a MLA Within 24 Hours of Challenge Agent Infusion | Part B randomization phase day 8 plus 24 hours. | On day 1 of the double-blind randomization phase participants received 140 mg intravenous erenumab over 30 minutes or matching placebo. On day 8, participants received 10 mol/kg/minute PACAP-38 over 10 minutes and were observed for 24 hours after PACAP-38 infusion. A MLA was defined as fulfilling 1 of the 2 criteria: 1. Headache with at least 2 of the following characteristics: unilateral location, pulsating quality, moderate or severe pain intensity, aggravated by/causing avoidance of routine physical activity. Additionally, during the headache at least 1 of the following: nausea and/or vomiting, photophobia or phonophobia. 2. Headache described as mimicking usual migraine attack treated with triptan. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Part B randomization phase day 1 until EOS (up to 12 weeks). | TEAEs were summarised for days 1 to 7 after the participants received placebo or erenumab infusion on day 1 of the Part B randomization phase. TEAEs were also summarized from day 8 to end of study (EOS) after participants had received both investigational product (placebo or erenumab) and the second dose of PACAP-38 on day 8. |
| Mean Change From Baseline in Systolic and Diastolic Blood Pressure (BP) at Day 1, Day 8 and EOS | Part B randomization phase baseline and day 1, day 8 and EOS (week 12). | Systolic and diastolic BP was assessed during Part B of the study, and the mean change from baseline is presented for the last measurements taken following administration of placebo or erenumab on day 1 (1 hour post-dose), and following administration of PACAP-38 on day 8 (8 hours post-dose). The mean change from baseline is also presented for the EOS assessment. |
| Mean Change From Baseline in Heart Rate at Day 1, Day 8 and EOS | Part B randomization phase baseline and day 1, day 8 and EOS (week 12). | Heart rate was assessed during Part B of the study, and the mean change from baseline is presented for the last measurements taken following administration of placebo or erenumab on day 1 (1 hour post-dose), and following administration of PACAP-38 on day 8 (8 hours post-dose). The mean change from baseline is also presented for the EOS assessment. |
| Mean Change From Baseline in Respiratory Rate at Day 1, Day 8 and EOS | Part B randomization phase baseline and day 1, day 8 and EOS (week 12). | Respiratory rate was assessed during Part B of the study, and the mean change from baseline is presented for the last measurements taken following administration of placebo or erenumab on day 1 (1 hour post-dose), and following administration of PACAP-38 on day 8 (8 hours post-dose). The mean change from baseline is also presented for the EOS assessment. |
| Mean Change From Baseline in Temperature at Day 1, Day 8 and EOS | Part B randomization phase baseline and day 1, day 8 and EOS (week 12). | Temperature was assessed during Part B of the study, and the mean change from baseline is presented for the last measurements taken following administration of placebo or erenumab on day 1 (1 hour post-dose), and following administration of PACAP-38 on day 8 (8 hours post-dose). The mean change from baseline is also presented for the EOS assessment. |
| Mean Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) at Day 8, Day 9 and EOS | Part B randomization phase baseline and day 8, day 9 and EOS (week 12). | ALP, ALT and AST were assessed during Part B of the study, and the mean change from baseline is presented for samples taken prior to administration of PACAP-38 on day 8 (pre-PACAP-38 dose), and following administration of PACAP-38 on day 9. The mean change from baseline is also presented for the EOS assessment. |
| Mean Change From Baseline in Total Bilirubin at Day 8, Day 9 and EOS | Part B randomization baseline and day 8, day 9 and EOS (week 12). | Total bilirubin was assessed during Part B of the study, and the mean change from baseline is presented for samples taken prior to administration of PACAP-38 on day 8 (pre-PACAP-38 dose), and following administration of PACAP-38 on day 9. The mean change from baseline is also presented for the EOS assessment. |
| Mean Change From Baseline in Blood Urea at Day 8, Day 9 and EOS | Part B randomization baseline and day 8, day 9 and EOS (week 12). | Blood urea was assessed during Part B of the study, and the mean change from baseline is presented for samples taken prior to administration of PACAP-38 on day 8 (pre-PACAP-38 dose), and following administration of PACAP-38 on day 9. The mean change from baseline is also presented for the EOS assessment. |
| Mean Change From Baseline in Creatine Kinase at Day 8, Day 9 and EOS | Part B randomization baseline and day 8, day 9 and EOS (week 12). | Creatine Kinase was assessed during Part B of the study, and the mean change from baseline is presented for samples taken prior to administration of PACAP-38 on day 8 (pre-PACAP-38 dose), and following administration of PACAP-38 on day 9. The mean change from baseline is also presented for the EOS assessment. |
| Mean Change From Baseline in Creatinine at Day 8, Day 9 and EOS | Part B randomization baseline and day 8, day 9 and EOS (week 12). | Creatinine was assessed during Part B of the study, and the mean change from baseline is presented for samples taken prior to administration of PACAP-38 on day 8 (pre-PACAP-38 dose), and following administration of PACAP-38 on day 9. The mean change from baseline is also presented for the EOS assessment. |
| Number of Participants With a Headache Within 24 Hours of Challenge Agent Infusion | Part B randomization phase day 8 plus 24 hours. | On day 1 of the double-blind randomization phase participants received 140 mg intravenous erenumab over 30 minutes or matching placebo. On day 8, participants received 10 mol/kg/minute PACAP-38 over 10 minutes and were observed for 24 hours after PACAP-38 infusion. |
| Mean Change From Baseline in Eosinophil Count at Day 8, Day 9 and EOS | Part B randomization baseline and day 8, day 9 and EOS (week 12). | Eosinophil count was assessed during Part B of the study, and the mean change from baseline is presented for samples taken prior to administration of PACAP-38 on day 8 (pre-PACAP-38 dose), and following administration of PACAP-38 on day 9. The mean change from baseline is also presented for the EOS assessment. |
| Mean Change From Baseline in Blood Glucose at Day 8, Day 9 and EOS | Part B randomization baseline and day 8, day 9 and EOS (week 12). | Blood glucose was assessed during Part B of the study, and the mean change from baseline is presented for samples taken prior to administration of PACAP-38 on day 8 (pre-PACAP-38 dose), and following administration of PACAP-38 on day 9. The mean change from baseline is also presented for the EOS assessment. |
| Mean Change From Baseline in Hemoglobin A1C (Fraction of 1) at Day 8, Day 9 and EOS | Part B randomization baseline and day 8, day 9 and EOS (week 12). | Hemoglobin A1C was assessed during Part B of the study, and the mean change from baseline is presented for samples taken prior to administration of PACAP-38 on day 8 (pre-PACAP-38 dose), and following administration of PACAP-38 on day 9. The mean change from baseline is also presented for the EOS assessment. |
| Pharmacokinetics (PK): Mean Erenumab Serum Concentration at 1 Hour (C1h) | Part B randomization phase 1 hour post-dose day 1. | The mean serum erenumab concentration at 1 hour post-dose on day 1 of Part B randomization phase is presented. |
| PK: Mean Area Under the Concentration-time Curve From Time 0 to 84 Days Post-dose (AUC84d) | Part B randomization phase baseline and 84 days post-dose. | The mean AUC84d for erenumab for the Part B randomization phase is presented. |
| Number of Participants With Anti-Erenumab Antibodies | Part B randomization phase baseline and EOS. | Participants were tested for binding antibodies and neutralizing antibodies at baseline and following treatment with erenumab. |
| Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Parameters | Part B randomization phase baseline and EOS. | At baseline, 12-lead ECGs were performed in a standardized method, in triplicate, and approximately 30 seconds apart, prior to blood draws or other invasive procedures. Single ECGs were performed from Day 1 to EOS. ECG results were reviewed by the investigator and classified as: normal, abnormal not clinically significant or abnormal, clinically significant. The number of participants with abnormal, clinically significant changes in ECG results at EOS are presented. |
| Number of Participants With Clinically Significant Changes in Physical Parameters | Part B randomization phase baseline and EOS. | Physical examinations were performed by an investigator and any abnormal findings, judged to be clinically significant were recorded as an AE. The number of participants with clinically significant changes in physical parameters at EOS are presented. |
| Number of Participants With Clinically Significant Changes in Neurological Assessments | Part B randomization phase baseline and EOS. | Neurological examinations including assessment of cranial nerves, motor system, sensory system (including testing for pain sensation \[pin prick\], light touch sensation \[brush\], von Frey, and vibratory sense), reflexes, and cerebellar function were performed by the investigator and classified as normal or abnormal. Any abnormal findings, judged by the investigator to be clinically significant, were recorded as an AE. The number of participants with clinically significant changes in neurological assessments at EOS are presented. |
| Mean Change From Baseline in Direct Bilirubin at Day 8, Day 9 and EOS | Part B randomization baseline and day 8, day 9 and EOS (week 12). | Direct bilirubin was assessed during Part B of the study, and the mean change from baseline is presented for samples taken prior to administration of PACAP-38 on day 8 (pre-PACAP-38 dose), and following administration of PACAP-38 on day 9. The mean change from baseline is also presented for the EOS assessment. |
Countries
Belgium, Netherlands, United States
Participant flow
Recruitment details
Participants were enrolled in 2 centers in Belgium and the Netherlands from November 2015 until November 2017 when the study was terminated early due to slow recruitment rate. Additionally, 2 participants were enrolled at a center in the United States for Part A prior to this study site being closed.
Pre-assignment details
12 participants received treatment in Part A to determine the lowest pituitary adenylate cyclase-activating polypeptide-38 (PACAP-38) dose that triggered a migraine-like attack (MLA). PACAP-38 responders from Part A and PACAP-38 naïve participants were randomized in Part B (17 in total). 35 participants were enrolled in the study (Parts A and B).
Participants by arm
| Arm | Count |
|---|---|
| PACAP-38 Challenge Agent In Part A, cohorts 1 to 4 (of 2 to 5 participants each) sequentially received an intravenous infusion of 10 pmol/kg/minute PACAP-38 over 2.5, 5, 7.5 and 10 minutes, respectively. Dose selection in Part A enabled the dose for Part B to be determined.
PACAP-38 naïve participants entered the study at Part B. On day 1 of the Part B challenge phase participants received the dose of PACAP-38 determined from Part A of the study: 100 pmol/kg (administered as 10 pmol/kg/minute PACAP-38 over 10 minutes). Responders who experienced a MLA within 24 hours were screened for the randomization phase. | 35 |
| Total | 35 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Part B: Challenge Phase | Sponsor decision | 1 | 0 | 0 |
| Part B: Randomization Phase | Withdrawal by Subject | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | PACAP-38 Challenge Agent |
|---|---|
| Age, Continuous | 27.5 Years STANDARD_DEVIATION 6.2 |
| Age, Customized 18 - 64 years | 35 Participants |
| Body Mass Index | 24.4738 kg/m^2 STANDARD_DEVIATION 4.2926 |
| Height | 168.13 centimeters STANDARD_DEVIATION 7.72 |
| Race/Ethnicity, Customized Asian | 3 Participants |
| Race/Ethnicity, Customized Black (or African American) | 2 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 1 Participants |
| Race/Ethnicity, Customized Multiple (Asian-White) | 1 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 34 Participants |
| Race/Ethnicity, Customized Other | 1 Participants |
| Race/Ethnicity, Customized White | 28 Participants |
| Sex: Female, Male Female | 30 Participants |
| Sex: Female, Male Male | 5 Participants |
| Weight | 69.433 kg STANDARD_DEVIATION 14.656 |
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 / 9 | 0 / 7 | 0 / 9 | 0 / 7 |
| other Total, other adverse events | 6 / 9 | 0 / 7 | 9 / 9 | 7 / 7 |
| serious Total, serious adverse events | 0 / 9 | 0 / 7 | 0 / 9 | 0 / 7 |
Outcome results
Primary
Number of Participants With a MLA Within 24 Hours of Challenge Agent Infusion
On day 1 of the double-blind randomization phase participants received 140 mg intravenous erenumab over 30 minutes or matching placebo. On day 8, participants received 10 mol/kg/minute PACAP-38 over 10 minutes and were observed for 24 hours after PACAP-38 infusion. A MLA was defined as fulfilling 1 of the 2 criteria: 1. Headache with at least 2 of the following characteristics: unilateral location, pulsating quality, moderate or severe pain intensity, aggravated by/causing avoidance of routine physical activity. Additionally, during the headache at least 1 of the following: nausea and/or vomiting, photophobia or phonophobia. 2. Headache described as mimicking usual migraine attack treated with triptan.
Time frame: Part B randomization phase day 8 plus 24 hours.
Population: The Safety Analysis Set consisted of all randomized participants who received at least 1 dose of investigational product (placebo or erenumab) in Part B.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With a MLA Within 24 Hours of Challenge Agent Infusion | Participants with MLA | 1 Participants |
| Placebo | Number of Participants With a MLA Within 24 Hours of Challenge Agent Infusion | Participants without MLA | 8 Participants |
| Erenumab | Number of Participants With a MLA Within 24 Hours of Challenge Agent Infusion | Participants with MLA | 1 Participants |
| Erenumab | Number of Participants With a MLA Within 24 Hours of Challenge Agent Infusion | Participants without MLA | 6 Participants |
Secondary
Mean Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) at Day 8, Day 9 and EOS
ALP, ALT and AST were assessed during Part B of the study, and the mean change from baseline is presented for samples taken prior to administration of PACAP-38 on day 8 (pre-PACAP-38 dose), and following administration of PACAP-38 on day 9. The mean change from baseline is also presented for the EOS assessment.
Time frame: Part B randomization phase baseline and day 8, day 9 and EOS (week 12).
Population: The Safety Analysis Set consisted of all randomized participants who received at least 1 dose of investigational product (placebo or erenumab) in Part B. Only participants with data available for analysis at each time point are presented.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Mean Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) at Day 8, Day 9 and EOS | Day 9 (Post-PACAP-38 dose): ALP | -1.6 Units/Liter | Standard Deviation 4.1 |
| Placebo | Mean Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) at Day 8, Day 9 and EOS | EOS: ALT | -2.0 Units/Liter | Standard Deviation 4.7 |
| Placebo | Mean Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) at Day 8, Day 9 and EOS | Day 8 (Pre-PACAP-38 dose): ALT | -1.4 Units/Liter | Standard Deviation 3.5 |
| Placebo | Mean Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) at Day 8, Day 9 and EOS | Day 8 (Pre-PACAP-38 dose): AST | 0.3 Units/Liter | Standard Deviation 3 |
| Placebo | Mean Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) at Day 8, Day 9 and EOS | EOS: ALP | 1.0 Units/Liter | Standard Deviation 12.3 |
| Placebo | Mean Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) at Day 8, Day 9 and EOS | Day 9 (Post-PACAP-38 dose): AST | -0.8 Units/Liter | Standard Deviation 2.7 |
| Placebo | Mean Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) at Day 8, Day 9 and EOS | Day 9 (Post-PACAP-38 dose): ALT | -2.1 Units/Liter | Standard Deviation 3.5 |
| Placebo | Mean Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) at Day 8, Day 9 and EOS | EOS: AST | 0.3 Units/Liter | Standard Deviation 5.1 |
| Placebo | Mean Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) at Day 8, Day 9 and EOS | Day 8 (Pre-PACAP-38 dose): ALP | -2.0 Units/Liter | Standard Deviation 5.6 |
| Erenumab | Mean Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) at Day 8, Day 9 and EOS | EOS: AST | -0.4 Units/Liter | Standard Deviation 3.6 |
| Erenumab | Mean Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) at Day 8, Day 9 and EOS | Day 8 (Pre-PACAP-38 dose): ALP | 0.0 Units/Liter | Standard Deviation 4.8 |
| Erenumab | Mean Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) at Day 8, Day 9 and EOS | Day 9 (Post-PACAP-38 dose): ALP | -0.3 Units/Liter | Standard Deviation 2.3 |
| Erenumab | Mean Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) at Day 8, Day 9 and EOS | EOS: ALP | 6.1 Units/Liter | Standard Deviation 9.6 |
| Erenumab | Mean Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) at Day 8, Day 9 and EOS | Day 8 (Pre-PACAP-38 dose): ALT | -3.0 Units/Liter | Standard Deviation 4.2 |
| Erenumab | Mean Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) at Day 8, Day 9 and EOS | Day 9 (Post-PACAP-38 dose): ALT | -4.5 Units/Liter | Standard Deviation 4.2 |
| Erenumab | Mean Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) at Day 8, Day 9 and EOS | EOS: ALT | 3.1 Units/Liter | Standard Deviation 9.4 |
| Erenumab | Mean Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) at Day 8, Day 9 and EOS | Day 8 (Pre-PACAP-38 dose): AST | 2.4 Units/Liter | Standard Deviation 4 |
| Erenumab | Mean Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) at Day 8, Day 9 and EOS | Day 9 (Post-PACAP-38 dose): AST | -4.2 Units/Liter | Standard Deviation 2.3 |
Secondary
Mean Change From Baseline in Blood Glucose at Day 8, Day 9 and EOS
Blood glucose was assessed during Part B of the study, and the mean change from baseline is presented for samples taken prior to administration of PACAP-38 on day 8 (pre-PACAP-38 dose), and following administration of PACAP-38 on day 9. The mean change from baseline is also presented for the EOS assessment.
Time frame: Part B randomization baseline and day 8, day 9 and EOS (week 12).
Population: The Safety Analysis Set consisted of all randomized participants who received at least 1 dose of investigational product (placebo or erenumab) in Part B. Only participants with data available for analysis at each time point are presented.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Mean Change From Baseline in Blood Glucose at Day 8, Day 9 and EOS | Day 8 (Pre-PACAP-38 dose) | -0.1360 mmol/L | Standard Deviation 0.3103 |
| Placebo | Mean Change From Baseline in Blood Glucose at Day 8, Day 9 and EOS | Day 9 (Post-PACAP-38 dose) | -0.2290 mmol/L | Standard Deviation 0.235 |
| Placebo | Mean Change From Baseline in Blood Glucose at Day 8, Day 9 and EOS | EOS | -0.3183 mmol/L | Standard Deviation 0.3395 |
| Erenumab | Mean Change From Baseline in Blood Glucose at Day 8, Day 9 and EOS | Day 8 (Pre-PACAP-38 dose) | -0.2761 mmol/L | Standard Deviation 0.5961 |
| Erenumab | Mean Change From Baseline in Blood Glucose at Day 8, Day 9 and EOS | Day 9 (Post-PACAP-38 dose) | 0.0427 mmol/L | Standard Deviation 0.2432 |
| Erenumab | Mean Change From Baseline in Blood Glucose at Day 8, Day 9 and EOS | EOS | -0.1237 mmol/L | Standard Deviation 0.3645 |
Secondary
Mean Change From Baseline in Blood Urea at Day 8, Day 9 and EOS
Blood urea was assessed during Part B of the study, and the mean change from baseline is presented for samples taken prior to administration of PACAP-38 on day 8 (pre-PACAP-38 dose), and following administration of PACAP-38 on day 9. The mean change from baseline is also presented for the EOS assessment.
Time frame: Part B randomization baseline and day 8, day 9 and EOS (week 12).
Population: The Safety Analysis Set consisted of all randomized participants who received at least 1 dose of investigational product (placebo or erenumab) in Part B. Only participants with data available for analysis at each time point are presented.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Mean Change From Baseline in Blood Urea at Day 8, Day 9 and EOS | Day 8 (Pre-PACAP-38 dose) | 0.0629 millimol/L (mmol/L) | Standard Deviation 0.9274 |
| Placebo | Mean Change From Baseline in Blood Urea at Day 8, Day 9 and EOS | Day 9 (Post-PACAP-38 dose) | 0.1501 millimol/L (mmol/L) | Standard Deviation 0.7552 |
| Placebo | Mean Change From Baseline in Blood Urea at Day 8, Day 9 and EOS | EOS | -0.1961 millimol/L (mmol/L) | Standard Deviation 0.7673 |
| Erenumab | Mean Change From Baseline in Blood Urea at Day 8, Day 9 and EOS | Day 8 (Pre-PACAP-38 dose) | -0.0524 millimol/L (mmol/L) | Standard Deviation 0.527 |
| Erenumab | Mean Change From Baseline in Blood Urea at Day 8, Day 9 and EOS | Day 9 (Post-PACAP-38 dose) | -0.5278 millimol/L (mmol/L) | Standard Deviation 1.2592 |
| Erenumab | Mean Change From Baseline in Blood Urea at Day 8, Day 9 and EOS | EOS | 0.0570 millimol/L (mmol/L) | Standard Deviation 1.1286 |
Secondary
Mean Change From Baseline in Creatine Kinase at Day 8, Day 9 and EOS
Creatine Kinase was assessed during Part B of the study, and the mean change from baseline is presented for samples taken prior to administration of PACAP-38 on day 8 (pre-PACAP-38 dose), and following administration of PACAP-38 on day 9. The mean change from baseline is also presented for the EOS assessment.
Time frame: Part B randomization baseline and day 8, day 9 and EOS (week 12).
Population: The Safety Analysis Set consisted of all randomized participants who received at least 1 dose of investigational product (placebo or erenumab) in Part B. Only participants with data available for analysis at each time point are presented.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Mean Change From Baseline in Creatine Kinase at Day 8, Day 9 and EOS | EOS | 8.1 U/L | Standard Deviation 25.3 |
| Placebo | Mean Change From Baseline in Creatine Kinase at Day 8, Day 9 and EOS | Day 8 (Pre-PACAP-38 dose) | 5.8 U/L | Standard Deviation 21 |
| Placebo | Mean Change From Baseline in Creatine Kinase at Day 8, Day 9 and EOS | Day 9 (Post-PACAP-38 dose) | -16.8 U/L | Standard Deviation 9.1 |
| Erenumab | Mean Change From Baseline in Creatine Kinase at Day 8, Day 9 and EOS | EOS | -24.9 U/L | Standard Deviation 79.9 |
| Erenumab | Mean Change From Baseline in Creatine Kinase at Day 8, Day 9 and EOS | Day 8 (Pre-PACAP-38 dose) | -22.4 U/L | Standard Deviation 51.5 |
| Erenumab | Mean Change From Baseline in Creatine Kinase at Day 8, Day 9 and EOS | Day 9 (Post-PACAP-38 dose) | -59.3 U/L | Standard Deviation 65.7 |
Secondary
Mean Change From Baseline in Creatinine at Day 8, Day 9 and EOS
Creatinine was assessed during Part B of the study, and the mean change from baseline is presented for samples taken prior to administration of PACAP-38 on day 8 (pre-PACAP-38 dose), and following administration of PACAP-38 on day 9. The mean change from baseline is also presented for the EOS assessment.
Time frame: Part B randomization baseline and day 8, day 9 and EOS (week 12).
Population: The Safety Analysis Set consisted of all randomized participants who received at least 1 dose of investigational product (placebo or erenumab) in Part B. Only participants with data available for analysis at each time point are presented.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Mean Change From Baseline in Creatinine at Day 8, Day 9 and EOS | Day 8 (Pre-PACAP-38 dose) | -1.9890 micromol/L | Standard Deviation 6.0835 |
| Placebo | Mean Change From Baseline in Creatinine at Day 8, Day 9 and EOS | Day 9 (Post-PACAP-38 dose) | 0.1450 micromol/L | Standard Deviation 7.3859 |
| Placebo | Mean Change From Baseline in Creatinine at Day 8, Day 9 and EOS | EOS | 3.5151 micromol/L | Standard Deviation 7.8109 |
| Erenumab | Mean Change From Baseline in Creatinine at Day 8, Day 9 and EOS | Day 8 (Pre-PACAP-38 dose) | -2.2526 micromol/L | Standard Deviation 3.1121 |
| Erenumab | Mean Change From Baseline in Creatinine at Day 8, Day 9 and EOS | Day 9 (Post-PACAP-38 dose) | -1.4733 micromol/L | Standard Deviation 3.4367 |
| Erenumab | Mean Change From Baseline in Creatinine at Day 8, Day 9 and EOS | EOS | -0.3457 micromol/L | Standard Deviation 2.6598 |
Secondary
Mean Change From Baseline in Direct Bilirubin at Day 8, Day 9 and EOS
Direct bilirubin was assessed during Part B of the study, and the mean change from baseline is presented for samples taken prior to administration of PACAP-38 on day 8 (pre-PACAP-38 dose), and following administration of PACAP-38 on day 9. The mean change from baseline is also presented for the EOS assessment.
Time frame: Part B randomization baseline and day 8, day 9 and EOS (week 12).
Population: The Safety Analysis Set consisted of all randomized participants who received at least 1 dose of investigational product (placebo or erenumab) in Part B. Only participants with data available for analysis at each time point are presented.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Mean Change From Baseline in Direct Bilirubin at Day 8, Day 9 and EOS | Day 8 (Pre-PACAP-38 dose) | -0.0570 micromol/L | Standard Deviation 1.2948 |
| Placebo | Mean Change From Baseline in Direct Bilirubin at Day 8, Day 9 and EOS | Day 9 (Post-PACAP-38 dose) | 0.6270 micromol/L | Standard Deviation 0.5497 |
| Placebo | Mean Change From Baseline in Direct Bilirubin at Day 8, Day 9 and EOS | EOS | 0.1710 micromol/L | Standard Deviation 0.171 |
| Erenumab | Mean Change From Baseline in Direct Bilirubin at Day 8, Day 9 and EOS | Day 8 (Pre-PACAP-38 dose) | -1.0260 micromol/L | — |
| Erenumab | Mean Change From Baseline in Direct Bilirubin at Day 8, Day 9 and EOS | Day 9 (Post-PACAP-38 dose) | -1.1115 micromol/L | Standard Deviation 0.1209 |
| Erenumab | Mean Change From Baseline in Direct Bilirubin at Day 8, Day 9 and EOS | EOS | 1.1970 micromol/L | Standard Deviation 0 |
Secondary
Mean Change From Baseline in Eosinophil Count at Day 8, Day 9 and EOS
Eosinophil count was assessed during Part B of the study, and the mean change from baseline is presented for samples taken prior to administration of PACAP-38 on day 8 (pre-PACAP-38 dose), and following administration of PACAP-38 on day 9. The mean change from baseline is also presented for the EOS assessment.
Time frame: Part B randomization baseline and day 8, day 9 and EOS (week 12).
Population: The Safety Analysis Set consisted of all randomized participants who received at least 1 dose of investigational product (placebo or erenumab) in Part B. Only participants with data available for analysis at each time point are presented.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Mean Change From Baseline in Eosinophil Count at Day 8, Day 9 and EOS | Day 8 (Pre-PACAP-38 dose) | -0.013 10^9/L | Standard Deviation 0.067 |
| Placebo | Mean Change From Baseline in Eosinophil Count at Day 8, Day 9 and EOS | Day 9 (Post-PACAP-38 dose) | -0.035 10^9/L | Standard Deviation 0.076 |
| Placebo | Mean Change From Baseline in Eosinophil Count at Day 8, Day 9 and EOS | EOS | -0.041 10^9/L | Standard Deviation 0.06 |
| Erenumab | Mean Change From Baseline in Eosinophil Count at Day 8, Day 9 and EOS | Day 8 (Pre-PACAP-38 dose) | -0.004 10^9/L | Standard Deviation 0.046 |
| Erenumab | Mean Change From Baseline in Eosinophil Count at Day 8, Day 9 and EOS | Day 9 (Post-PACAP-38 dose) | -0.002 10^9/L | Standard Deviation 0.066 |
| Erenumab | Mean Change From Baseline in Eosinophil Count at Day 8, Day 9 and EOS | EOS | 0.033 10^9/L | Standard Deviation 0.061 |
Secondary
Mean Change From Baseline in Heart Rate at Day 1, Day 8 and EOS
Heart rate was assessed during Part B of the study, and the mean change from baseline is presented for the last measurements taken following administration of placebo or erenumab on day 1 (1 hour post-dose), and following administration of PACAP-38 on day 8 (8 hours post-dose). The mean change from baseline is also presented for the EOS assessment.
Time frame: Part B randomization phase baseline and day 1, day 8 and EOS (week 12).
Population: The Safety Analysis Set consisted of all randomized participants who received at least 1 dose of investigational product (placebo or erenumab) in Part B. Only participants with data available for analysis at each time point are presented.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Mean Change From Baseline in Heart Rate at Day 1, Day 8 and EOS | 1 hour post-dose day 1 | -5.0 beats/minute | Standard Deviation 8.2 |
| Placebo | Mean Change From Baseline in Heart Rate at Day 1, Day 8 and EOS | 8 hours post-dose day 8 | 2.6 beats/minute | Standard Deviation 11.5 |
| Placebo | Mean Change From Baseline in Heart Rate at Day 1, Day 8 and EOS | EOS | -0.9 beats/minute | Standard Deviation 8.6 |
| Erenumab | Mean Change From Baseline in Heart Rate at Day 1, Day 8 and EOS | 1 hour post-dose day 1 | 1.7 beats/minute | Standard Deviation 5.7 |
| Erenumab | Mean Change From Baseline in Heart Rate at Day 1, Day 8 and EOS | 8 hours post-dose day 8 | 8.7 beats/minute | Standard Deviation 4.6 |
| Erenumab | Mean Change From Baseline in Heart Rate at Day 1, Day 8 and EOS | EOS | 2.4 beats/minute | Standard Deviation 5.5 |
Secondary
Mean Change From Baseline in Hemoglobin A1C (Fraction of 1) at Day 8, Day 9 and EOS
Hemoglobin A1C was assessed during Part B of the study, and the mean change from baseline is presented for samples taken prior to administration of PACAP-38 on day 8 (pre-PACAP-38 dose), and following administration of PACAP-38 on day 9. The mean change from baseline is also presented for the EOS assessment.
Time frame: Part B randomization baseline and day 8, day 9 and EOS (week 12).
Population: The Safety Analysis Set consisted of all randomized participants who received at least 1 dose of investigational product (placebo or erenumab) in Part B. Only participants with data available for analysis at each time point are presented.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Mean Change From Baseline in Hemoglobin A1C (Fraction of 1) at Day 8, Day 9 and EOS | Day 8 (Pre-PACAP-38 dose) | 0.0003 fraction of 1 | Standard Deviation 0.0007 |
| Placebo | Mean Change From Baseline in Hemoglobin A1C (Fraction of 1) at Day 8, Day 9 and EOS | Day 9 (Post-PACAP-38 dose) | 0.0000 fraction of 1 | Standard Deviation 0.0005 |
| Placebo | Mean Change From Baseline in Hemoglobin A1C (Fraction of 1) at Day 8, Day 9 and EOS | EOS | 0.0003 fraction of 1 | Standard Deviation 0.0012 |
| Erenumab | Mean Change From Baseline in Hemoglobin A1C (Fraction of 1) at Day 8, Day 9 and EOS | Day 8 (Pre-PACAP-38 dose) | 0.0001 fraction of 1 | Standard Deviation 0.0007 |
| Erenumab | Mean Change From Baseline in Hemoglobin A1C (Fraction of 1) at Day 8, Day 9 and EOS | Day 9 (Post-PACAP-38 dose) | 0.0002 fraction of 1 | Standard Deviation 0.001 |
| Erenumab | Mean Change From Baseline in Hemoglobin A1C (Fraction of 1) at Day 8, Day 9 and EOS | EOS | 0.0002 fraction of 1 | Standard Deviation 0.0012 |
Secondary
Mean Change From Baseline in Respiratory Rate at Day 1, Day 8 and EOS
Respiratory rate was assessed during Part B of the study, and the mean change from baseline is presented for the last measurements taken following administration of placebo or erenumab on day 1 (1 hour post-dose), and following administration of PACAP-38 on day 8 (8 hours post-dose). The mean change from baseline is also presented for the EOS assessment.
Time frame: Part B randomization phase baseline and day 1, day 8 and EOS (week 12).
Population: The Safety Analysis Set consisted of all randomized participants who received at least 1 dose of investigational product (placebo or erenumab) in Part B. Only participants with data available for analysis at each time point are presented.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Mean Change From Baseline in Respiratory Rate at Day 1, Day 8 and EOS | 1 hour post-dose day 1 | 0.8 breaths/minute | Standard Deviation 2.2 |
| Placebo | Mean Change From Baseline in Respiratory Rate at Day 1, Day 8 and EOS | 8 hours post-dose day 8 | 1.0 breaths/minute | Standard Deviation 2.1 |
| Placebo | Mean Change From Baseline in Respiratory Rate at Day 1, Day 8 and EOS | EOS | 1.7 breaths/minute | Standard Deviation 4 |
| Erenumab | Mean Change From Baseline in Respiratory Rate at Day 1, Day 8 and EOS | 1 hour post-dose day 1 | -1.4 breaths/minute | Standard Deviation 2.6 |
| Erenumab | Mean Change From Baseline in Respiratory Rate at Day 1, Day 8 and EOS | 8 hours post-dose day 8 | -1.0 breaths/minute | Standard Deviation 3.5 |
| Erenumab | Mean Change From Baseline in Respiratory Rate at Day 1, Day 8 and EOS | EOS | 1.1 breaths/minute | Standard Deviation 3.7 |
Secondary
Mean Change From Baseline in Systolic and Diastolic Blood Pressure (BP) at Day 1, Day 8 and EOS
Systolic and diastolic BP was assessed during Part B of the study, and the mean change from baseline is presented for the last measurements taken following administration of placebo or erenumab on day 1 (1 hour post-dose), and following administration of PACAP-38 on day 8 (8 hours post-dose). The mean change from baseline is also presented for the EOS assessment.
Time frame: Part B randomization phase baseline and day 1, day 8 and EOS (week 12).
Population: The Safety Analysis Set consisted of all randomized participants who received at least 1 dose of investigational product (placebo or erenumab) in Part B. Only participants with data available for analysis at each time point are presented.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Mean Change From Baseline in Systolic and Diastolic Blood Pressure (BP) at Day 1, Day 8 and EOS | 1 hour post-dose day 1: systolic BP | -0.7 millimeters of mercury | Standard Deviation 7.9 |
| Placebo | Mean Change From Baseline in Systolic and Diastolic Blood Pressure (BP) at Day 1, Day 8 and EOS | 1 hour post-dose day 1: diastolic BP | 1.2 millimeters of mercury | Standard Deviation 5.7 |
| Placebo | Mean Change From Baseline in Systolic and Diastolic Blood Pressure (BP) at Day 1, Day 8 and EOS | 8 hours post-dose day 8: systolic BP | -3.1 millimeters of mercury | Standard Deviation 5.7 |
| Placebo | Mean Change From Baseline in Systolic and Diastolic Blood Pressure (BP) at Day 1, Day 8 and EOS | 8 hours post-dose day 8: diastolic BP | -3.6 millimeters of mercury | Standard Deviation 2.9 |
| Placebo | Mean Change From Baseline in Systolic and Diastolic Blood Pressure (BP) at Day 1, Day 8 and EOS | EOS: systolic BP | -2.6 millimeters of mercury | Standard Deviation 9.2 |
| Placebo | Mean Change From Baseline in Systolic and Diastolic Blood Pressure (BP) at Day 1, Day 8 and EOS | EOS: diastolic BP | -0.1 millimeters of mercury | Standard Deviation 6.4 |
| Erenumab | Mean Change From Baseline in Systolic and Diastolic Blood Pressure (BP) at Day 1, Day 8 and EOS | EOS: systolic BP | 2.6 millimeters of mercury | Standard Deviation 3.8 |
| Erenumab | Mean Change From Baseline in Systolic and Diastolic Blood Pressure (BP) at Day 1, Day 8 and EOS | 1 hour post-dose day 1: systolic BP | 2.4 millimeters of mercury | Standard Deviation 5.2 |
| Erenumab | Mean Change From Baseline in Systolic and Diastolic Blood Pressure (BP) at Day 1, Day 8 and EOS | 8 hours post-dose day 8: diastolic BP | -9.6 millimeters of mercury | Standard Deviation 6.8 |
| Erenumab | Mean Change From Baseline in Systolic and Diastolic Blood Pressure (BP) at Day 1, Day 8 and EOS | 1 hour post-dose day 1: diastolic BP | 0.7 millimeters of mercury | Standard Deviation 6.4 |
| Erenumab | Mean Change From Baseline in Systolic and Diastolic Blood Pressure (BP) at Day 1, Day 8 and EOS | EOS: diastolic BP | 1.7 millimeters of mercury | Standard Deviation 5.9 |
| Erenumab | Mean Change From Baseline in Systolic and Diastolic Blood Pressure (BP) at Day 1, Day 8 and EOS | 8 hours post-dose day 8: systolic BP | -3.7 millimeters of mercury | Standard Deviation 6.2 |
Secondary
Mean Change From Baseline in Temperature at Day 1, Day 8 and EOS
Temperature was assessed during Part B of the study, and the mean change from baseline is presented for the last measurements taken following administration of placebo or erenumab on day 1 (1 hour post-dose), and following administration of PACAP-38 on day 8 (8 hours post-dose). The mean change from baseline is also presented for the EOS assessment.
Time frame: Part B randomization phase baseline and day 1, day 8 and EOS (week 12).
Population: The Safety Analysis Set consisted of all randomized participants who received at least 1 dose of investigational product (placebo or erenumab) in Part B. Only participants with data available for analysis at each time point are presented.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Mean Change From Baseline in Temperature at Day 1, Day 8 and EOS | 1 hour post-dose day 1 | 0.18 degrees Celsius | Standard Deviation 0.39 |
| Placebo | Mean Change From Baseline in Temperature at Day 1, Day 8 and EOS | 8 hours post-dose day 8 | 0.60 degrees Celsius | Standard Deviation 0.48 |
| Placebo | Mean Change From Baseline in Temperature at Day 1, Day 8 and EOS | EOS | -0.34 degrees Celsius | Standard Deviation 0.47 |
| Erenumab | Mean Change From Baseline in Temperature at Day 1, Day 8 and EOS | 1 hour post-dose day 1 | 0.34 degrees Celsius | Standard Deviation 0.36 |
| Erenumab | Mean Change From Baseline in Temperature at Day 1, Day 8 and EOS | 8 hours post-dose day 8 | 0.63 degrees Celsius | Standard Deviation 0.56 |
| Erenumab | Mean Change From Baseline in Temperature at Day 1, Day 8 and EOS | EOS | 0.16 degrees Celsius | Standard Deviation 0.41 |
Secondary
Mean Change From Baseline in Total Bilirubin at Day 8, Day 9 and EOS
Total bilirubin was assessed during Part B of the study, and the mean change from baseline is presented for samples taken prior to administration of PACAP-38 on day 8 (pre-PACAP-38 dose), and following administration of PACAP-38 on day 9. The mean change from baseline is also presented for the EOS assessment.
Time frame: Part B randomization baseline and day 8, day 9 and EOS (week 12).
Population: The Safety Analysis Set consisted of all randomized participants who received at least 1 dose of investigational product (placebo or erenumab) in Part B. Only participants with data available for analysis at each time point are presented.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Mean Change From Baseline in Total Bilirubin at Day 8, Day 9 and EOS | Day 8 (Pre-PACAP-38 dose) | -0.4211 micromol/L | Standard Deviation 3.6356 |
| Placebo | Mean Change From Baseline in Total Bilirubin at Day 8, Day 9 and EOS | Day 9 (Post-PACAP-38 dose) | 3.3229 micromol/L | Standard Deviation 1.3971 |
| Placebo | Mean Change From Baseline in Total Bilirubin at Day 8, Day 9 and EOS | EOS | 0.0804 micromol/L | Standard Deviation 3.027 |
| Erenumab | Mean Change From Baseline in Total Bilirubin at Day 8, Day 9 and EOS | Day 8 (Pre-PACAP-38 dose) | -1.4849 micromol/L | Standard Deviation 0.8532 |
| Erenumab | Mean Change From Baseline in Total Bilirubin at Day 8, Day 9 and EOS | Day 9 (Post-PACAP-38 dose) | -2.2980 micromol/L | Standard Deviation 1.03 |
| Erenumab | Mean Change From Baseline in Total Bilirubin at Day 8, Day 9 and EOS | EOS | 1.3191 micromol/L | Standard Deviation 3.5099 |
Secondary
Number of Participants With a Headache Within 24 Hours of Challenge Agent Infusion
On day 1 of the double-blind randomization phase participants received 140 mg intravenous erenumab over 30 minutes or matching placebo. On day 8, participants received 10 mol/kg/minute PACAP-38 over 10 minutes and were observed for 24 hours after PACAP-38 infusion.
Time frame: Part B randomization phase day 8 plus 24 hours.
Population: The Safety Analysis Set consisted of all randomized participants who received at least 1 dose of investigational product (placebo or erenumab) in Part B.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With a Headache Within 24 Hours of Challenge Agent Infusion | Participants with headaches | 3 Participants |
| Placebo | Number of Participants With a Headache Within 24 Hours of Challenge Agent Infusion | Participants without headaches | 6 Participants |
| Erenumab | Number of Participants With a Headache Within 24 Hours of Challenge Agent Infusion | Participants with headaches | 3 Participants |
| Erenumab | Number of Participants With a Headache Within 24 Hours of Challenge Agent Infusion | Participants without headaches | 4 Participants |
Secondary
Number of Participants With Anti-Erenumab Antibodies
Participants were tested for binding antibodies and neutralizing antibodies at baseline and following treatment with erenumab.
Time frame: Part B randomization phase baseline and EOS.
Population: The Safety Analysis Set for erenumab consisted of all randomized participants who received at least 1 dose of erenumab in Part B.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Anti-Erenumab Antibodies | Neutralizing antibody positive post-baseline | 0 Participants |
| Placebo | Number of Participants With Anti-Erenumab Antibodies | Binding antibody positive at/before baseline | 0 Participants |
| Placebo | Number of Participants With Anti-Erenumab Antibodies | Neutralizing antibody positive at/before baseline | 0 Participants |
| Placebo | Number of Participants With Anti-Erenumab Antibodies | Binding antibody positive post-baseline | 0 Participants |
Secondary
Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Parameters
At baseline, 12-lead ECGs were performed in a standardized method, in triplicate, and approximately 30 seconds apart, prior to blood draws or other invasive procedures. Single ECGs were performed from Day 1 to EOS. ECG results were reviewed by the investigator and classified as: normal, abnormal not clinically significant or abnormal, clinically significant. The number of participants with abnormal, clinically significant changes in ECG results at EOS are presented.
Time frame: Part B randomization phase baseline and EOS.
Population: The Safety Analysis Set consisted of all randomized participants who received at least 1 dose of investigational product (placebo or erenumab) in Part B.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Parameters | 0 Participants |
| Erenumab | Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Parameters | 0 Participants |
Secondary
Number of Participants With Clinically Significant Changes in Neurological Assessments
Neurological examinations including assessment of cranial nerves, motor system, sensory system (including testing for pain sensation \[pin prick\], light touch sensation \[brush\], von Frey, and vibratory sense), reflexes, and cerebellar function were performed by the investigator and classified as normal or abnormal. Any abnormal findings, judged by the investigator to be clinically significant, were recorded as an AE. The number of participants with clinically significant changes in neurological assessments at EOS are presented.
Time frame: Part B randomization phase baseline and EOS.
Population: The Safety Analysis Set consisted of all randomized participants who received at least 1 dose of investigational product (placebo or erenumab) in Part B.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Clinically Significant Changes in Neurological Assessments | 0 Participants |
| Erenumab | Number of Participants With Clinically Significant Changes in Neurological Assessments | 0 Participants |
Secondary
Number of Participants With Clinically Significant Changes in Physical Parameters
Physical examinations were performed by an investigator and any abnormal findings, judged to be clinically significant were recorded as an AE. The number of participants with clinically significant changes in physical parameters at EOS are presented.
Time frame: Part B randomization phase baseline and EOS.
Population: The Safety Analysis Set consisted of all randomized participants who received at least 1 dose of investigational product (placebo or erenumab) in Part B.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Clinically Significant Changes in Physical Parameters | 0 Participants |
| Erenumab | Number of Participants With Clinically Significant Changes in Physical Parameters | 0 Participants |
Secondary
Number of Participants With Treatment Emergent Adverse Events (TEAEs)
TEAEs were summarised for days 1 to 7 after the participants received placebo or erenumab infusion on day 1 of the Part B randomization phase. TEAEs were also summarized from day 8 to end of study (EOS) after participants had received both investigational product (placebo or erenumab) and the second dose of PACAP-38 on day 8.
Time frame: Part B randomization phase day 1 until EOS (up to 12 weeks).
Population: The Safety Analysis Set consisted of all randomized participants who received at least 1 dose of investigational product (placebo or erenumab) in Part B.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Participants with TEAEs from day 8 to EOS | 9 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Serious AEs | 0 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | AEs with fatal outcome | 0 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Participants with TEAEs from day 1 to 7 | 6 Participants |
| Erenumab | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Participants with TEAEs from day 1 to 7 | 0 Participants |
| Erenumab | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Participants with TEAEs from day 8 to EOS | 7 Participants |
| Erenumab | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | AEs with fatal outcome | 0 Participants |
| Erenumab | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Serious AEs | 0 Participants |
Secondary
Pharmacokinetics (PK): Mean Erenumab Serum Concentration at 1 Hour (C1h)
The mean serum erenumab concentration at 1 hour post-dose on day 1 of Part B randomization phase is presented.
Time frame: Part B randomization phase 1 hour post-dose day 1.
Population: The PK Analysis Set consisted of all randomized participants who received erenumab and have at least 1 PK concentration result.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Pharmacokinetics (PK): Mean Erenumab Serum Concentration at 1 Hour (C1h) | 51.2 micrograms per milliliter (mcg/mL) | Standard Deviation 9.72 |
Secondary
PK: Mean Area Under the Concentration-time Curve From Time 0 to 84 Days Post-dose (AUC84d)
The mean AUC84d for erenumab for the Part B randomization phase is presented.
Time frame: Part B randomization phase baseline and 84 days post-dose.
Population: The PK Analysis Set consisted of all randomized participants who received erenumab and have at least 1 PK concentration result.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | PK: Mean Area Under the Concentration-time Curve From Time 0 to 84 Days Post-dose (AUC84d) | 877 day*mcg/mL | Standard Deviation 131 |