Ascending Multiple-Doses of Erenumab (AMG 334) in Healthy Adults and in Migraine Patients

Migraine Clinical Trial

Official title:

Phase 1, Randomized, Double-Blind, Placebo-Controlled, Ascending Multiple-Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of AMG 334 in Healthy Subjects and in Migraine Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01723514
• Other study ID #: 20101268
• Secondary ID: 2012-003594-26
• Status: Completed
• Phase: Phase 1
• Start date: November 14, 2012
• Est. completion date: July 10, 2014

Study information

• Verified date: August 2018
• Source: Amgen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The primary purpose of this study is to determine whether erenumab is safe and well tolerated in healthy adults and migraine patients. As part of the secondary objectives, this study will be conducted to characterize the pharmacokinetic (PK) profile of erenumab after multiple subcutaneous (SC) doses in healthy adults and migraine patients, as well as to characterize the effect of erenumab on the capsaicin induced increase in dermal blood flow after multiple SC doses in healthy adults and migraine patients.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 48
• Est. completion date: July 10, 2014
• Est. primary completion date: July 10, 2014
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

Inclusion Criteria:

Healthy male and female subjects, as well as male or female subjects with migraines between 18 and 55 years of age, inclusive, with no history or evidence of clinically relevant medical disorders as determined by the investigator in consultation with the Amgen physician;

Exclusion Criteria:

• History or evidence of clinically significant disorder (including psychiatric), condition or disease that, in the opinion of the Investigator or Amgen physician would pose a risk to subject safety or interfere with the study evaluation, procedures, or completion;

Related Conditions & MeSH terms

• Migraine
• Migraine Disorders

Intervention

Drug:
• Erenumab
Administered by subcutaneous injection once a month
• Placebo
Administered by subcutaneous injection once a month

Locations

Country	Name	City	State
Belgium	Research Site	Leuven

Sponsors (1)

Lead Sponsor	Collaborator
Amgen

Country where clinical trial is conducted

Belgium, 

References & Publications (1)

de Hoon J, Van Hecken A, Vandermeulen C, Yan L, Smith B, Chen JS, Bautista E, Hamilton L, Waksman J, Vu T, Vargas G. Phase I, Randomized, Double-blind, Placebo-controlled, Single-dose, and Multiple-dose Studies of Erenumab in Healthy Subjects and Patients With Migraine. Clin Pharmacol Ther. 2018 May;103(5):815-825. doi: 10.1002/cpt.799. Epub 2017 Oct 24. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Adverse Events	An adverse event (AE) is defined as any untoward medical occurrence in a clinical trial participant. The event does not necessarily have a causal relationship with study treatment. The definition of adverse events includes worsening of a pre-existing medical condition. Laboratory value changes that require treatment or adjustment in current therapy are considered adverse events.; Teatment-related adverse events (TRAEs) are those assessed by the investigator as being possibly related to study drug.; A serious adverse event is defined as an adverse event that meets at least 1 of the following serious criteria: fatal; life-threatening (places the subject at immediate risk of death); requires in-patient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; congenital anomaly/birth defect; other medically important serious event.	From first dose of study drug until a maximum of 168 days after last dose (225 days)
Primary	Number of Participants With Suicidal Ideation and Behavior as Assessed by the Columbia Suicide Severity Rating Scale (C-SSRS)	The C-SSRS is a measure of suicidal ideation and behavior. Ideation includes a wish to be dead or nonspecific thoughts about wanting to end life. Suicidal behavior includes actual attempts, interrupted or aborted attempts, and any preparatory acts.	From first dose of study drug until a maximum of 168 days after last dose (225 days)
Primary	Number of Participants Who Developed Anti-erenumab Antibodies	Participants who had a negative or no result at baseline and were antibody positive postbaseline.; Blood samples were first tested for anti-erenumab binding antibodies, samples testing positive for binding antibodies were also tested for neutralizing antibodies.	From first dose of study drug until a maximum of 168 days after last dose (225 days)
Secondary	Maximum Observed Serum Concentration (Cmax) of Erenumab	Serum concentration of erenumab was analyzed using an enzyme-linked immunosorbent assay (ELISA).	Day 1 (assessed from predose to day 28) and day 57 (assessed from predose up to day 225)
Secondary	Time to Maximum Observed Concentration (Tmax) of Erenumab	Serum concentration of erenumab was analyzed using an enzyme-linked immunosorbent assay (ELISA).	Day 1 (assessed from predose to day 28) and day 57 (assessed from predose up to day 225)
Secondary	Area Under the Serum Concentration-Time Curve From 0 to 28 Days (AUC0-28day)	Serum concentration of erenumab was analyzed using an enzyme-linked immunosorbent assay (ELISA).	Day 1 (assessed from predose to day 28) and day 57 (assessed from predose up to day 225)
Secondary	Area Under the Serum Curve From Time Zero to Time of Last Quantifiable Concentration (AUClast)	Serum concentration of erenumab was analyzed using an enzyme-linked immunosorbent assay (ELISA).	Day 57 (assessed from predose to day 225))
Secondary	Ratio of Post-capsaicin Dermal Blood Flow to Pre-capsaicin Dermal Blood Flow	Inhibition of capsaicin-induced dermal blood flow (DBF) by erenumab was used to measure calcitonin gene-related peptide (CGRP) receptor antagonism. Capsaicin was applied at 2 sites on the volar surface of the participants' left or right forearms and a control mixture was applied to 1 site on the volar surface of either the participants' left or right forearm. Dermal blood flow was assessed by laser Doppler perfusion imaging and was done immediately before ('baseline') and 0.5 hours post-capsaicin on the surface of these 3 sites.; Data reported are the least square geometric mean ratios for the post-capsaicin dermal blood flow to pre-capsaicin dermal blood flow.; According to the protocol, not all cohorts had dermal blood flow measurements at all time points.	Baseline, Days 8, 57, 85, 113, 169 and 197

External Links

•   AmgenTrials clinical trials website