Phase I, Double-Blind,Placebo, MAD Study to Evaluate the Safety, Tolerability, PK, and PD of AMG 333 in Healthy Subjects and Migraine Subjects

Phase I, Randomized, Double-Blind, Placebo-Controlled, Ascending Multiple-Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of AMG 333 in Healthy Subjects and Migraine Subjects

The primary purpose of this study is to evaluate the safety and tolerability of multiple oral doses of AMG 333 for 14 days in healthy subjects and migraine subjects. As part of the secondary objectives, the study will characterize the pharmacokinetic (PK) profile of AMG 333 after multiple oral doses in healthy subjects and migraine subjects, as well as characterize the effect of multiple doses of AMG 333 on increases in blood pressure (BP) induced by the cold pressor test (CPT) in healthy subjects.

Study Overview

• Status: Terminated
• Conditions: Migraine
• Intervention / Treatment: Drug: AMG 333; Drug: Placebo

Detailed Description

This is a randomized, double-blind, placebo-controlled, ascending multiple-dose study evaluating AMG 333 in healthy subjects and subjects with migraines. Eight healthy subjects will be enrolled in each of cohorts 1 through 5. Study subjects will be randomized such that 6 subjects will receive AMG 333 and 2 subjects will receive placebo (3:1 ratio) per cohort. Likewise, 8 migraine subjects will be enrolled in cohort 6 and randomized to receive AMG 333 or placebo (3:1 ratio). All subjects will be housed for 15 days then allowed to return home. Migraine subjects will self-administer the headache diary at least once daily during the screening and out-patient portions of the study, and site personnel will administer the headache diary during the in-house period of the study. Healthy subjects will not keep the headache diary during screening and will have the headache diary administered by site personnel at least once daily starting on day 1 through day 14, and will then self administer throughout their participation in the study.

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Utah
    • Salt Lake City, Utah, United States, 84106
      • CRI Lifetree

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy male and female subjects (cohorts 1 through 5) and male and female subjects with migraines (cohort 6), who are ≥ 18 and ≤ 55 years of age at the time of screening, and have 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 a clinically significant disorder, condition, or disease that in the opinion of the investigator and Amgen physician, would significantly impair pain perception (eg, history of stroke, history of neuropathy), would pose a risk to subject safety or interfere with evaluation, procedures, or study completion.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: FACTORIAL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: AMG 333; Subjects will receive a single oral dose of AMG 333 daily for 14 days.	Drug: AMG 333; Oral administration available in varying dose strength.
PLACEBO_COMPARATOR: Placebo; Subjects will receive a single oral dose of placebo daily for 14 days.	Drug: Placebo; Placebo containing no active drug

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment-emergent AEs	Treatment-emergent adverse events, including changes in vital signs, 12-lead ECGs, clinical laboratory safety tests, and physical and neurological assessments	Up to 29 Days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma PK Parameter	Plasma PK parameters of AMG 333: time to maximum concentration (tmax)	Up to 29 Days
Plasma PK Parameter	Maximum observed concentration (Cmax)	Up to 29 Days
Plasma PK Parameter	Area Under the Concentration Time-Curve from time 0 to 24 hours postdose (AUC0-24) and Days 1 and 14	Up to 29 Days
Blood Pressure response to CPT	Change in systolic and diastolic BP in response to the CPT in healthy subjects.	Up to 29 Days

Collaborators and Investigators

• Sponsor: Amgen

Publications and helpful links

Helpful Links

• AmgenTrials clinical trials website

Study record dates

Study Major Dates

• Study Start: May 1, 2014
• Primary Completion (ACTUAL): October 1, 2014
• Study Completion (ACTUAL): December 1, 2014

Study Registration Dates

• First Submitted: May 5, 2014
• First Submitted That Met QC Criteria: May 5, 2014
• First Posted (ESTIMATE): May 7, 2014

Study Record Updates

• Last Update Posted (ESTIMATE): April 1, 2015
• Last Update Submitted That Met QC Criteria: March 30, 2015
• Last Verified: March 1, 2015

More Information

Terms related to this study

• Keywords: Migraine
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Headache Disorders, Primary; Headache Disorders; Migraine Disorders
• Other Study ID Numbers: 20130246