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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| PACAP-38 Challenge Agent | Other | In Part A, 4 cohorts of 2 to 5 participants sequentially received an intravenous infusion of 10 picomol/kilogram/minute (pmol/kg/minute) PACAP-38 for 2.5, 5, 7.5 and 10 minutes each in order to determine the dose for Part B. |
|
| Placebo | Placebo Comparator | Participants were randomized to receive matching erenumab placebo by intravenous administration over 30 minutes on day 1. On day 8 participants were administered the dose of PACAP-38 determined from Part A of the study (100 pmol/kg) and were followed up for 11 weeks. |
|
| Erenumab | Experimental | Participants were randomized to receive 140 milligrams (mg) erenumab by intravenous administration over 30 minutes on day 1 in Part B. On day 8 participants were administered the dose of PACAP-38 determined from Part A of the study (100 pmol/kg) and were followed up for 11 weeks. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Erenumab | Drug | Administered once on day 1 of Part B of the study by intravenous infusion. |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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:
| Part B randomization phase day 8 plus 24 hours. |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Part B randomization phase day 8 plus 24 hours. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| MD | Amgen | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Research Site | Anaheim | California | 92801 | United States | ||
| Research Site |
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| Label | URL |
|---|---|
| AmgenTrials clinical trials website | View source |
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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 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.
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| ID | Title | Description |
|---|---|---|
| FG000 | PACAP-38 Challenge Agent | In Part A, cohorts 1 to 4 (of 2 to 5 participants each) sequentially received an intravenous infusion of 10 picomol/kilogram/minute (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. |
| FG001 | Placebo | Participants were randomized to receive matching erenumab placebo by intravenous administration over 30 minutes on day 1 of Part B randomization phase. On day 8, participants were administered the dose of PACAP-38 determined from Part A of the study (100 pmol/kg) and were followed up for 11 weeks. |
| FG002 | Erenumab | Participants were randomized to receive 140 milligrams (mg) erenumab by intravenous administration over 30 minutes on day 1 of Part B randomization phase. On day 8, participants were administered the dose of PACAP-38 determined from Part A of the study (100 pmol/kg) and were followed up for 11 weeks. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Part A: PACAP-38 Dose Selection Phase |
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| Part B: Challenge Phase |
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| Part B: Randomization Phase |
|
The overall baseline population consists of all participants who received at least 1 dose of PACAP-38 in either Part A or Part B of the study.
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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:
| The Safety Analysis Set consisted of all randomized participants who received at least 1 dose of investigational product (placebo or erenumab) in Part B. | Posted | Count of Participants | Participants | Part B randomization phase day 8 plus 24 hours. |
|
From first dose of investigational product (placebo or erenumab) up to 85 days (up to 12 weeks).
Other Adverse Events summarizes the non-serious occurrences of AEs that exceed the indicated frequency threshold.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Placebo Day 1-7 | Participants were randomized to receive matching erenumab placebo intravenously over 30 minutes on study day 1 of Part B randomization phase. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Leukocytosis | Blood and lymphatic system disorders | MedDRA 20.1 | Systematic Assessment |
The study was terminated early due to slow recruitment rate.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Study Director | Amgen Inc. | 866-572-6436 | medinfo@amgen.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Sep 1, 2016 | Sep 20, 2018 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | May 17, 2017 | Sep 20, 2018 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D008881 | Migraine Disorders |
| D006261 | Headache |
| ID | Term |
|---|---|
| D051270 | Headache Disorders, Primary |
| D020773 | Headache Disorders |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
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| ID | Term |
|---|---|
| C000605816 | erenumab |
| D051219 | Pituitary Adenylate Cyclase-Activating Polypeptide |
| ID | Term |
|---|---|
| D009414 | Nerve Growth Factors |
| D036341 | Intercellular Signaling Peptides and Proteins |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
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| Placebo | Drug | Administered once on day 1 of Part B of the study by intravenous infusion. |
|
| PACAP-38 Challenge Agent | Drug | 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. |
|
|
| 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. | Part B randomization phase day 1 until EOS (up to 12 weeks). |
| 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. | Part B randomization phase baseline and day 1, day 8 and EOS (week 12). |
| 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. | Part B randomization phase baseline and day 1, day 8 and EOS (week 12). |
| 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. | Part B randomization phase baseline and day 1, day 8 and EOS (week 12). |
| 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. | Part B randomization phase baseline and day 1, day 8 and EOS (week 12). |
| 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. | Part B randomization phase baseline and day 8, day 9 and EOS (week 12). |
| 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. | Part B randomization baseline and day 8, day 9 and EOS (week 12). |
| 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. | Part B randomization baseline and day 8, day 9 and EOS (week 12). |
| 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. | Part B randomization baseline and day 8, day 9 and EOS (week 12). |
| 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. | Part B randomization baseline and day 8, day 9 and EOS (week 12). |
| 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. | Part B randomization baseline and day 8, day 9 and EOS (week 12). |
| 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. | Part B randomization baseline and day 8, day 9 and EOS (week 12). |
| 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. | Part B randomization baseline and day 8, day 9 and EOS (week 12). |
| 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. | Part B randomization baseline and day 8, day 9 and EOS (week 12). |
| 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. | Part B randomization phase 1 hour post-dose day 1. |
| 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. | Part B randomization phase baseline and 84 days post-dose. |
| Number of Participants With Anti-Erenumab Antibodies | Participants were tested for binding antibodies and neutralizing antibodies at baseline and following treatment with erenumab. | Part B randomization phase baseline and EOS. |
| 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. | Part B randomization phase baseline and EOS. |
| 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. | Part B randomization phase baseline and EOS. |
| 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. | Part B randomization phase baseline and EOS. |
| Leuven |
| 3000 |
| Belgium |
| Research Site | Leiden | 2333 CL | Netherlands |
| Proceeded to Randomization Phase |
|
| COMPLETED |
|
| NOT COMPLETED |
|
|
| PACAP-38 naïve Participants | Participants joined the study at Part B and did not receive PACAP-38 in Part A. |
|
| Received Placebo/Erenumab |
|
| COMPLETED |
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| NOT COMPLETED |
|
|
| Years |
|
| Age, Customized | Number | Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Number | Participants |
|
| Race/Ethnicity, Customized | Number | Participants |
|
| Height | Mean | Standard Deviation | centimeters |
|
| Weight | Mean | Standard Deviation | kg |
|
| Body Mass Index | Mean | Standard Deviation | kg/m^2 |
|
| OG000 |
| Placebo |
Participants were randomized to receive matching erenumab placebo by intravenous administration over 30 minutes on day 1 of Part B randomization phase. On day 8, participants were administered the dose of PACAP-38 determined from Part A of the study (100 pmol/kg) and were followed up for 11 weeks. |
| OG001 | Erenumab | Participants were randomized to receive 140 mg erenumab by intravenous administration over 30 minutes on day 1 of Part B randomization phase. On day 8, participants were administered the dose of PACAP-38 determined from Part A of the study (100 pmol/kg) and were followed up for 11 weeks. |
|
|
| 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. | The Safety Analysis Set consisted of all randomized participants who received at least 1 dose of investigational product (placebo or erenumab) in Part B. | Posted | Count of Participants | Participants | Part B randomization phase day 8 plus 24 hours. |
|
|
|
| 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. | The Safety Analysis Set consisted of all randomized participants who received at least 1 dose of investigational product (placebo or erenumab) in Part B. | Posted | Count of Participants | Participants | Part B randomization phase day 1 until EOS (up to 12 weeks). |
|
|
|
| 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. | 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. | Posted | Mean | Standard Deviation | millimeters of mercury | Part B randomization phase baseline and day 1, day 8 and EOS (week 12). |
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|
| 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. | 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. | Posted | Mean | Standard Deviation | beats/minute | Part B randomization phase baseline and day 1, day 8 and EOS (week 12). |
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| 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. | 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. | Posted | Mean | Standard Deviation | breaths/minute | Part B randomization phase baseline and day 1, day 8 and EOS (week 12). |
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| 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. | 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. | Posted | Mean | Standard Deviation | degrees Celsius | Part B randomization phase baseline and day 1, day 8 and EOS (week 12). |
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| 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. | 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. | Posted | Mean | Standard Deviation | Units/Liter | Part B randomization phase baseline and day 8, day 9 and EOS (week 12). |
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| 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. | 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. | Posted | Mean | Standard Deviation | micromol/L | Part B randomization baseline and day 8, day 9 and EOS (week 12). |
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| 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. | 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. | Posted | Mean | Standard Deviation | millimol/L (mmol/L) | Part B randomization baseline and day 8, day 9 and EOS (week 12). |
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| 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. | 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. | Posted | Mean | Standard Deviation | U/L | Part B randomization baseline and day 8, day 9 and EOS (week 12). |
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| 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. | 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. | Posted | Mean | Standard Deviation | micromol/L | Part B randomization baseline and day 8, day 9 and EOS (week 12). |
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| 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. | 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. | Posted | Mean | Standard Deviation | micromol/L | Part B randomization baseline and day 8, day 9 and EOS (week 12). |
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| 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. | 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. | Posted | Mean | Standard Deviation | 10^9/L | Part B randomization baseline and day 8, day 9 and EOS (week 12). |
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| 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. | 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. | Posted | Mean | Standard Deviation | mmol/L | Part B randomization baseline and day 8, day 9 and EOS (week 12). |
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| 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. | 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. | Posted | Mean | Standard Deviation | fraction of 1 | Part B randomization baseline and day 8, day 9 and EOS (week 12). |
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| 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. | The PK Analysis Set consisted of all randomized participants who received erenumab and have at least 1 PK concentration result. | Posted | Mean | Standard Deviation | micrograms per milliliter (mcg/mL) | Part B randomization phase 1 hour post-dose day 1. |
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| 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. | The PK Analysis Set consisted of all randomized participants who received erenumab and have at least 1 PK concentration result. | Posted | Mean | Standard Deviation | day*mcg/mL | Part B randomization phase baseline and 84 days post-dose. |
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| Secondary | Number of Participants With Anti-Erenumab Antibodies | Participants were tested for binding antibodies and neutralizing antibodies at baseline and following treatment with erenumab. | The Safety Analysis Set for erenumab consisted of all randomized participants who received at least 1 dose of erenumab in Part B. | Posted | Count of Participants | Participants | Part B randomization phase baseline and EOS. |
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| 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. | The Safety Analysis Set consisted of all randomized participants who received at least 1 dose of investigational product (placebo or erenumab) in Part B. | Posted | Count of Participants | Participants | Part B randomization phase baseline and EOS. |
|
|
|
| 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. | The Safety Analysis Set consisted of all randomized participants who received at least 1 dose of investigational product (placebo or erenumab) in Part B. | Posted | Count of Participants | Participants | Part B randomization phase baseline and EOS. |
|
|
|
| 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. | The Safety Analysis Set consisted of all randomized participants who received at least 1 dose of investigational product (placebo or erenumab) in Part B. | Posted | Count of Participants | Participants | Part B randomization phase baseline and EOS. |
|
|
|
| 0 |
| 9 |
| 0 |
| 9 |
| 6 |
| 9 |
| EG001 | Erenumab Day 1-7 | Participants were randomized to receive 140 mg erenumab intravenously over 30 minutes on study day 1 of Part B randomization phase. | 0 | 7 | 0 | 7 | 0 | 7 |
| EG002 | Placebo Day 8-EOS | On day 8 of Part B randomization phase, participants were administered 100 pmol/kg of PACAP-38, having received matching erenumab placebo on day 1. Participants were followed up for 11 weeks to EOS. | 0 | 9 | 0 | 9 | 9 | 9 |
| EG003 | Erenumab Day 8-EOS | On day 8 of Part B randomization phase, participants were administered 100 pmol/kg of PACAP-38, having received 140 mg erenumab intravenously on day 1. Participants were followed up for 11 weeks to EOS. | 0 | 7 | 0 | 7 | 7 | 7 |
| Cardiac discomfort | Cardiac disorders | MedDRA 20.1 | Systematic Assessment |
|
| Palpitations | Cardiac disorders | MedDRA 20.1 | Systematic Assessment |
|
| Hyperacusis | Ear and labyrinth disorders | MedDRA 20.1 | Systematic Assessment |
|
| Eye irritation | Eye disorders | MedDRA 20.1 | Systematic Assessment |
|
| Lacrimation increased | Eye disorders | MedDRA 20.1 | Systematic Assessment |
|
| Ocular discomfort | Eye disorders | MedDRA 20.1 | Systematic Assessment |
|
| Photophobia | Eye disorders | MedDRA 20.1 | Systematic Assessment |
|
| Abdominal pain upper | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Gastritis | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Hypoaesthesia oral | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Catheter site pain | General disorders | MedDRA 20.1 | Systematic Assessment |
|
| Chest discomfort | General disorders | MedDRA 20.1 | Systematic Assessment |
|
| Discomfort | General disorders | MedDRA 20.1 | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA 20.1 | Systematic Assessment |
|
| Feeling cold | General disorders | MedDRA 20.1 | Systematic Assessment |
|
| Feeling hot | General disorders | MedDRA 20.1 | Systematic Assessment |
|
| Hunger | General disorders | MedDRA 20.1 | Systematic Assessment |
|
| Malaise | General disorders | MedDRA 20.1 | Systematic Assessment |
|
| Pain | General disorders | MedDRA 20.1 | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA 20.1 | Systematic Assessment |
|
| Thirst decreased | General disorders | MedDRA 20.1 | Systematic Assessment |
|
| Bacterial infection | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
|
| Cystitis | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
|
| Gastroenteritis | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
|
| Upper respiratory tract infection | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
|
| Urinary tract infection | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
|
| Concussion | Injury, poisoning and procedural complications | MedDRA 20.1 | Systematic Assessment |
|
| Contusion | Injury, poisoning and procedural complications | MedDRA 20.1 | Systematic Assessment |
|
| Joint lock | Musculoskeletal and connective tissue disorders | MedDRA 20.1 | Systematic Assessment |
|
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA 20.1 | Systematic Assessment |
|
| Musculoskeletal stiffness | Musculoskeletal and connective tissue disorders | MedDRA 20.1 | Systematic Assessment |
|
| Disturbance in attention | Nervous system disorders | MedDRA 20.1 | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA 20.1 | Systematic Assessment |
|
| Head discomfort | Nervous system disorders | MedDRA 20.1 | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA 20.1 | Systematic Assessment |
|
| Hypoaesthesia | Nervous system disorders | MedDRA 20.1 | Systematic Assessment |
|
| Migraine | Nervous system disorders | MedDRA 20.1 | Systematic Assessment |
|
| Paraesthesia | Nervous system disorders | MedDRA 20.1 | Systematic Assessment |
|
| Leukocyturia | Renal and urinary disorders | MedDRA 20.1 | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Photosensitivity reaction | Skin and subcutaneous tissue disorders | MedDRA 20.1 | Systematic Assessment |
|
| Swelling face | Skin and subcutaneous tissue disorders | MedDRA 20.1 | Systematic Assessment |
|
| Flushing | Vascular disorders | MedDRA 20.1 | Systematic Assessment |
|
The Clinical Trial Agreement generally does not restrict an investigator's discussion of trial results after completion. The Agreement permits Amgen a limited period of time to review material discussing trial results (typically up to 45 days and possible extension). Amgen may remove confidential information, but authors have final control and approval of publication content. For multicenter studies, the investigator agrees not to publish any results before the first multi-center publication.
| D009422 | Nervous System Diseases |
| D010146 | Pain |
| D009461 | Neurologic Manifestations |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D009479 | Neuropeptides |
| D011506 | Proteins |
| D009419 | Nerve Tissue Proteins |
| D001685 | Biological Factors |
| Serious AEs |
|
| AEs with fatal outcome |
|
| 1 hour post-dose day 1: diastolic BP |
|
|
| 8 hours post-dose day 8: systolic BP |
|
|
| 8 hours post-dose day 8: diastolic BP |
|
|
| EOS: systolic BP |
|
|
| EOS: diastolic BP |
|
|
| 8 hours post-dose day 8 |
|
|
| EOS |
|
|
| 8 hours post-dose day 8 |
|
|
| EOS |
|
|
| 8 hours post-dose day 8 |
|
|
| EOS |
|
|
| Day 9 (Post-PACAP-38 dose): ALP |
|
|
| EOS: ALP |
|
|
| Day 8 (Pre-PACAP-38 dose): ALT |
|
|
| Day 9 (Post-PACAP-38 dose): ALT |
|
|
| EOS: ALT |
|
|
| Day 8 (Pre-PACAP-38 dose): AST |
|
|
| Day 9 (Post-PACAP-38 dose): AST |
|
|
| EOS: AST |
|
|
| Day 9 (Post-PACAP-38 dose) |
|
|
| EOS |
|
|
| Day 9 (Post-PACAP-38 dose) |
|
|
| EOS |
|
|
| Day 9 (Post-PACAP-38 dose) |
|
|
| EOS |
|
|
| Day 9 (Post-PACAP-38 dose) |
|
|
| EOS |
|
|
| Day 9 (Post-PACAP-38 dose) |
|
|
| EOS |
|
|
| Day 9 (Post-PACAP-38 dose) |
|
|
| EOS |
|
|
| Day 9 (Post-PACAP-38 dose) |
|
|
| EOS |
|
|
| Day 9 (Post-PACAP-38 dose) |
|
|
| EOS |
|
|
| Title | Measurements |
|---|---|
|
| Neutralizing antibody positive post-baseline |
|