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

Migraine Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01688739
• Other study ID #: 20101267
• Secondary ID: 2011-005600-15
• Status: Completed
• Phase: Phase 1
• Start date: March 13, 2012
• Est. completion date: March 27, 2013

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 single subcutaneous (SC) or intravenous (IV) doses in healthy participants and migraine patients as well as to characterize the effect of erenumab on the capsaicin-induced increase in dermal blood flow after single SC or IV doses in healthy participants and migraine patients.

Description:

This study was a single-dose, double-blind, placebo-controlled, sequential dose escalation study in which participants were to be enrolled into 8 cohorts.

In Part 1 healthy participants were randomized in a 3:1 ratio (erenumab:placebo) into 6 cohorts: 5 cohorts received the investigational product (IP) as an SC administration and 1 cohort received it as an IV administration. In Part 2 a total of 12 migraine patients were randomized in a 1:1 ratio (erenumab:placebo) in cohort 7. An additional 8 migraine patients could have been enrolled and randomized in a 3:1 ratio in the optional cohort 8, however this cohort was not enrolled.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 61
• Est. completion date: March 27, 2013
• Est. primary completion date: March 27, 2013
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

Inclusion Criteria:

• Healthy male and female subjects between 18 and 45 years of age, or 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 or intravenous injection
• Placebo
Administered by subcutaneous injection or intravenous injection

Locations

Country	Name	City	State
Belgium	Research Site	Leuven

Sponsors (1)

Lead Sponsor	Collaborator
Amgen

Country where clinical trial is conducted

Belgium, 

References & Publications (2)

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

Vu T, Ma P, Chen JS, de Hoon J, Van Hecken A, Yan L, Wu LS, Hamilton L, Vargas G. Pharmacokinetic-Pharmacodynamic Relationship of Erenumab (AMG 334) and Capsaicin-Induced Dermal Blood Flow in Healthy and Migraine Subjects. Pharm Res. 2017 Sep;34(9):1784-1795. doi: 10.1007/s11095-017-2183-6. Epub 2017 Jun 7. — 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 the initial dose of study drug up to 155 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.	Baseline and up to 155 days postdose
Secondary	Maximum Observed Concentration (Cmax) of Erenumab		Predose to 155 days postdose
Secondary	Time to Maximum Observed Concentration (Tmax) of Erenumab		Predose to 155 days postdose
Secondary	Area Under the Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration (AUClast) of Erenumab		Predose to 155 days postdose
Secondary	Area Under the Concentration-time Curve From Time Zero to Infinity (AUCinf) of Erenumab		Predose to 155 days postdose
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.	Days 4, 15, 29, 43, 64, 85, 99, 127, and end of study (defined as day 43 for the 1 mg, 7 mg and 21 mg erenumab cohorts, day 99 for the 70 mg erenumab cohort, day 127 for the 140 mg erenumab cohorts and day 155 for the 210 mg erenumab cohort).

External Links

•   AmgenTrials clinical trials website