Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02542605
Recruitment Status : Completed
First Posted : September 7, 2015
Results First Posted : June 3, 2019
Last Update Posted : June 3, 2019
Sponsor:
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Migraine Drug: Erenumab Drug: Placebo Drug: PACAP-38 Challenge Agent Phase 1

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 35 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Prevention
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
Actual Study Start Date : November 11, 2015
Actual Primary Completion Date : September 28, 2017
Actual Study Completion Date : November 8, 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Migraine

Arm Intervention/treatment
PACAP-38 Challenge Agent
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.
Drug: 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.

Other Name: Pituitary adenylate cyclase-activating polypeptide-38 (PACAP-38)

Placebo Comparator: Placebo
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.
Drug: Placebo
Administered once on day 1 of Part B of the study by intravenous infusion.

Drug: 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.

Other Name: Pituitary adenylate cyclase-activating polypeptide-38 (PACAP-38)

Experimental: Erenumab
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.
Drug: Erenumab
Administered once on day 1 of Part B of the study by intravenous infusion.
Other Names:
  • AMG 334
  • Aimovig™

Drug: 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.

Other Name: Pituitary adenylate cyclase-activating polypeptide-38 (PACAP-38)




Primary Outcome Measures :
  1. Number of Participants With a MLA Within 24 Hours of Challenge Agent Infusion [ Time Frame: 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 Outcome Measures :
  1. Number of Participants With a Headache Within 24 Hours of Challenge Agent Infusion [ Time Frame: 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.

  2. Number of Participants With Treatment Emergent Adverse Events (TEAEs) [ Time Frame: 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.

  3. Mean Change From Baseline in Systolic and Diastolic Blood Pressure (BP) at Day 1, Day 8 and EOS [ Time Frame: 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.

  4. Mean Change From Baseline in Heart Rate at Day 1, Day 8 and EOS [ Time Frame: 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.

  5. Mean Change From Baseline in Respiratory Rate at Day 1, Day 8 and EOS [ Time Frame: 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.

  6. Mean Change From Baseline in Temperature at Day 1, Day 8 and EOS [ Time Frame: 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.

  7. Mean Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) at Day 8, Day 9 and EOS [ Time Frame: 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.

  8. Mean Change From Baseline in Total Bilirubin at Day 8, Day 9 and EOS [ Time Frame: 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.

  9. Mean Change From Baseline in Blood Urea at Day 8, Day 9 and EOS [ Time Frame: 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.

  10. Mean Change From Baseline in Creatine Kinase at Day 8, Day 9 and EOS [ Time Frame: 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.

  11. Mean Change From Baseline in Creatinine at Day 8, Day 9 and EOS [ Time Frame: 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.

  12. Mean Change From Baseline in Direct Bilirubin at Day 8, Day 9 and EOS [ Time Frame: 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.

  13. Mean Change From Baseline in Eosinophil Count at Day 8, Day 9 and EOS [ Time Frame: 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.

  14. Mean Change From Baseline in Blood Glucose at Day 8, Day 9 and EOS [ Time Frame: 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.

  15. Mean Change From Baseline in Hemoglobin A1C (Fraction of 1) at Day 8, Day 9 and EOS [ Time Frame: 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.

  16. Pharmacokinetics (PK): Mean Erenumab Serum Concentration at 1 Hour (C1h) [ Time Frame: 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.

  17. PK: Mean Area Under the Concentration-time Curve From Time 0 to 84 Days Post-dose (AUC84d) [ Time Frame: Part B randomization phase baseline and 84 days post-dose. ]
    The mean AUC84d for erenumab for the Part B randomization phase is presented.

  18. Number of Participants With Anti-Erenumab Antibodies [ Time Frame: Part B randomization phase baseline and EOS. ]
    Participants were tested for binding antibodies and neutralizing antibodies at baseline and following treatment with erenumab.

  19. Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Parameters [ Time Frame: 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.

  20. Number of Participants With Clinically Significant Changes in Physical Parameters [ Time Frame: 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.

  21. Number of Participants With Clinically Significant Changes in Neurological Assessments [ Time Frame: 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 45 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02542605


Locations
Layout table for location information
United States, California
Research Site
Anaheim, California, United States, 92801
Belgium
Research Site
Leuven, Belgium, 3000
Netherlands
Research Site
Leiden, Netherlands, 2333 CL
Sponsors and Collaborators
Amgen
Investigators
Layout table for investigator information
Study Director: MD Amgen
  Study Documents (Full-Text)

Documents provided by Amgen:
Study Protocol  [PDF] September 1, 2016
Statistical Analysis Plan  [PDF] May 17, 2017


Additional Information:
Layout table for additonal information
Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT02542605    
Other Study ID Numbers: 20140207
First Posted: September 7, 2015    Key Record Dates
Results First Posted: June 3, 2019
Last Update Posted: June 3, 2019
Last Verified: February 2019
Keywords provided by Amgen:
Migraine
Headache
Migraine Headache
Headache, Migraine
Amgen
Additional relevant MeSH terms:
Layout table for MeSH terms
Migraine Disorders
Calcitonin Gene-Related Peptide Receptor Antagonists
Headache Disorders, Primary
Headache Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Pituitary Adenylate Cyclase-Activating Polypeptide
Erenumab
Molecular Mechanisms of Pharmacological Action
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Growth Substances
Vasodilator Agents
Neurotransmitter Agents