- ICH GCP
- US Clinical Trials Registry
- Clinical Trial 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
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
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Leuven, Belgium, 3000
- Research Site
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Leiden, Netherlands, 2333 CL
- Research Site
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California
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Anaheim, California, United States, 92801
- Research Site
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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)
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Prevention
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Other: 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.
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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:
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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.
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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:
Administered once on day 1 of Part B of the study by intravenous infusion.
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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.
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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:
Administered once on day 1 of Part B of the study by intravenous infusion.
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Number of Participants With a MLA Within 24 Hours of Challenge Agent Infusion
Time Frame: Part B randomization phase day 8 plus 24 hours.
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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:
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Part B randomization phase day 8 plus 24 hours.
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Number of Participants With a Headache Within 24 Hours of Challenge Agent Infusion
Time Frame: Part B randomization phase day 8 plus 24 hours.
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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.
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Part B randomization phase day 8 plus 24 hours.
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Number of Participants With Treatment Emergent Adverse Events (TEAEs)
Time Frame: Part B randomization phase day 1 until EOS (up to 12 weeks).
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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.
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Part B randomization phase day 1 until EOS (up to 12 weeks).
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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).
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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.
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Part B randomization phase baseline and day 1, day 8 and EOS (week 12).
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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).
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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.
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Part B randomization phase baseline and day 1, day 8 and EOS (week 12).
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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).
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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.
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Part B randomization phase baseline and day 1, day 8 and EOS (week 12).
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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).
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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.
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Part B randomization phase baseline and day 1, day 8 and EOS (week 12).
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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).
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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.
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Part B randomization phase baseline and day 8, day 9 and EOS (week 12).
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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).
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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.
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Part B randomization baseline and day 8, day 9 and EOS (week 12).
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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).
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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.
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Part B randomization baseline and day 8, day 9 and EOS (week 12).
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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).
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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.
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Part B randomization baseline and day 8, day 9 and EOS (week 12).
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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).
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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.
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Part B randomization baseline and day 8, day 9 and EOS (week 12).
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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).
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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.
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Part B randomization baseline and day 8, day 9 and EOS (week 12).
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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).
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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.
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Part B randomization baseline and day 8, day 9 and EOS (week 12).
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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).
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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.
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Part B randomization baseline and day 8, day 9 and EOS (week 12).
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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).
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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.
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Part B randomization baseline and day 8, day 9 and EOS (week 12).
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Pharmacokinetics (PK): Mean Erenumab Serum Concentration at 1 Hour (C1h)
Time Frame: Part B randomization phase 1 hour post-dose day 1.
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The mean serum erenumab concentration at 1 hour post-dose on day 1 of Part B randomization phase is presented.
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Part B randomization phase 1 hour post-dose day 1.
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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.
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The mean AUC84d for erenumab for the Part B randomization phase is presented.
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Part B randomization phase baseline and 84 days post-dose.
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Number of Participants With Anti-Erenumab Antibodies
Time Frame: Part B randomization phase baseline and EOS.
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Participants were tested for binding antibodies and neutralizing antibodies at baseline and following treatment with erenumab.
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Part B randomization phase baseline and EOS.
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Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Parameters
Time Frame: Part B randomization phase baseline and EOS.
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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.
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Part B randomization phase baseline and EOS.
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Number of Participants With Clinically Significant Changes in Physical Parameters
Time Frame: Part B randomization phase baseline and EOS.
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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.
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Part B randomization phase baseline and EOS.
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Number of Participants With Clinically Significant Changes in Neurological Assessments
Time Frame: Part B randomization phase baseline and EOS.
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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.
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Part B randomization phase baseline and EOS.
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Collaborators and Investigators
Sponsor
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Brain Diseases
- Central Nervous System Diseases
- Nervous System Diseases
- Headache Disorders, Primary
- Headache Disorders
- Migraine Disorders
- Physiological Effects of Drugs
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Vasodilator Agents
- Peripheral Nervous System Agents
- Analgesics
- Sensory System Agents
- Growth Substances
- Calcitonin Gene-Related Peptide Receptor Antagonists
- Erenumab
- Pituitary Adenylate Cyclase-Activating Polypeptide
Other Study ID Numbers
- 20140207
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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