To Evaluate the Blockade of CGRP in Preventing PACAP-38 Induced Migraine-like Attacks With AMG 334 in Migraine Patients

Migraine Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02542605
• Other study ID #: 20140207
• Status: Completed
• Phase: Phase 1
• Start date: November 11, 2015
• Est. completion date: November 8, 2017

Study information

• Verified date: February 2019
• Source: Amgen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 35
• Est. completion date: November 8, 2017
• Est. primary completion date: September 28, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 45 Years

Eligibility

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)

Related Conditions & MeSH terms

• Migraine
• Migraine Disorders

Intervention

Drug:
• Erenumab
Administered once on day 1 of Part B of the study by intravenous infusion.
• Placebo
Administered once on day 1 of Part B of the study by intravenous infusion.
• PACAP-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.

Locations

Country	Name	City	State
Belgium	Research Site	Leuven
Netherlands	Research Site	Leiden
United States	Research Site	Anaheim	California

Sponsors (1)

Lead Sponsor	Collaborator
Amgen

Countries where clinical trial is conducted

United States,  Belgium,  Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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: 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.; Headache described as mimicking usual migraine attack treated with triptan.	Part B randomization phase day 8 plus 24 hours.
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.	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.	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.	Part B randomization phase baseline and day 1, day 8 and EOS (week 12).
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.	Part B randomization phase baseline and day 1, day 8 and EOS (week 12).
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.	Part B randomization phase baseline and day 1, day 8 and EOS (week 12).
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.	Part B randomization phase baseline and day 1, day 8 and EOS (week 12).
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.	Part B randomization phase baseline and day 8, day 9 and EOS (week 12).
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.	Part B randomization baseline and day 8, day 9 and EOS (week 12).
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.	Part B randomization baseline and day 8, day 9 and EOS (week 12).
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.	Part B randomization baseline and day 8, day 9 and EOS (week 12).
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.	Part B randomization baseline and day 8, day 9 and EOS (week 12).
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.	Part B randomization baseline and day 8, day 9 and EOS (week 12).
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.	Part B randomization baseline and day 8, day 9 and EOS (week 12).
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.	Part B randomization baseline and day 8, day 9 and EOS (week 12).
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.	Part B randomization baseline and day 8, day 9 and EOS (week 12).
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.	Part B randomization phase 1 hour post-dose day 1.
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.	Part B randomization phase baseline and 84 days post-dose.
Secondary	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.
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.	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.	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.	Part B randomization phase baseline and EOS.

External Links

•   AmgenTrials clinical trials website