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Completed

NCT Number: NCT02542605

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

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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Key information

Conditions

Migraine Brain Diseases Central Nervous System Diseases Headache Headache Disorders Headache Disorders, Primary Migraine Disorders Nervous System Diseases Neurologic Manifestations Pain Pathological Conditions, Signs and Symptoms Signs and Symptoms

Age range

18 year–45 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Research Site, Leuven, Belgium

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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)

Treatment and study plan

Erenumab

Drug

Administered once on day 1 of Part B of the study by intravenous infusion.

Other names: AMG 334, Aimovig™

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.

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

Primary outcomes

  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:

    • 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.

Secondary outcomes

  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.

Sponsors and collaborators

Lead sponsor

Amgen

Industry

Registry information

Official study 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

Important dates

Study start
2015
Primary completion
2017
Study completion
2017
First posted
Sep 7, 2015
Registry last updated
Jun 3, 2019

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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