Study of Erenumab (AMG 334) in Women With Hot Flashes

Randomized, Stratified, Parallel-group, Double-blind, Placebo-controlled, Study to Evaluate the Efficacy, Safety, Tolerability, and Pharmacokinetics of AMG 334 in Women With Hot Flashes Associated With Menopause

The primary objective of this study was to evaluate the frequency of moderate to severe daily hot flashes 4 weeks after a single dose of erenumab (AMG 334) in women with hot flashes associated with menopause.

Study Overview

• Status: Completed
• Conditions: Vasomotor Symptoms; Hot Flashes
• Intervention / Treatment: Drug: Placebo; Biological: Erenumab

Detailed Description

This study will test the hypothesis that the vasodilation associated with capsaicin-induced dermal blood flow (DBF) provides a good model for the vasodilation associated with hot flashes; therefore erenumab doses that cause DBF inhibition will be safe and well tolerated, and will be effective in the reduction of the frequency and/or severity of HFs.

• Study Type: Interventional
• Enrollment (Actual): 103
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • San Diego, California, United States, 92108
      • Research Site
  • Florida
    • Miami, Florida, United States, 33186
      • Research Site
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27103
      • Research Site
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19114
      • Eugene Andruczyk
    • Philadelphia, Pennsylvania, United States, 19114
      • Research Site
  • South Carolina
    • Mount Pleasant, South Carolina, United States, 29464
      • Research Site
  • Washington
    • Seattle, Washington, United States, 98105
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 45 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• female subjects with hot flashes associated with menopause between 45 and 65 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Participants received a single dose of placebo administered by subcutaneous injection.	Drug: Placebo; Administered via subcutaneous injection
Experimental: Erenumab; Participants received a single dose of 70 mg erenumab administered by subcutaneous injection.	Biological: Erenumab; Administered via subcutaneous injection.; Other Names: AMG 334; Aimovig™

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ratio of Week 4 to Baseline Average Number of Daily Moderate to Severe Hot Flashes	The severity of hot flashes was assessed by participants based on the following categories: Mild: sensation of heat without sweating, mild flushing;; Moderate: sensation of heat, face flushed, slightly clammy, some sweating, able to continue activity, may want to remove layers of clothing or covers at night;; Severe: sensation of heat with more severe sweating, have to stop current activity, may have to change clothing. Baseline (BL) number of hot flashes is the average number of moderate or severe hot flashes per 24 hours from day -7 to day 1 predose based on geometric mean, and the week 4 number of hot flashes is the average number of moderate or severe hot flashes per 24 hours from day 21 to day 27 based on geometric mean. The ratio of week 4 to BL was used to assess change from BL to week 4 via a log transformation (log[week4/BL] = log[week4] - log[BL]), which was estimated using a repeated measures analysis. The ratio was obtained via an exponential back-transformation.	Baseline (days -7 to day 1 predose) and week 4 (days 21 to 27)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ratio of Week 4 to Baseline Daily Hot Flash Severity Score	The daily severity score was calculated according to the following: (Number of mild hot flashes * 1) + (number of moderate hot flashes * 2) + (number of severe hot flashes * 3). The baseline daily hot flash severity score is the geometric mean daily hot flash severity score from day -7 to day 1 predose, and the week 4 daily hot flash severity score is the geometric mean daily hot flash severity score from day 21 to day 27. The ratio of week 4 to baseline (week 4 / baseline) was used to assess change from baseline to week 4 via a log transformation (log[week4/BL] = log[week4] - log[baseline]), which was estimated using a repeated measures analysis. The ratio was obtained via an exponential back-transformation.	Baseline (days -7 to day 1 predose) and week 4 (days 21 to 27)
Number of Participants With Treatment-emergent Adverse Events	A treatment-emergent adverse event is any adverse event that began or worsened after the initial dose of study drug and before the end of study. A serious adverse event is an adverse event that met at least 1 of the following serious criteria: fatal; life threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; congenital anomaly/birth defect.; other medically important serious event A treatment-related adverse event (TRAE) is any treatment-emergent adverse event that per investigator review had a reasonable possibility of being caused by the study drug.	16 weeks
Maximum Observed Concentration (Cmax) of Erenumab After a Single Dose	Blood samples were analyzed using an enzyme-linked immunosorbent assay (ELISA) following a validated analytical procedure.	Predose and 4 hours, 2, 3, 4, 8, 12, 15, 22, 29, 43, 50, 57, 64, 78, 85, and 113 days post-dose
Time to Maximum Observed Concentration (Tmax) of Erunumab After a Single Dose		Predose and 4 hours, 2, 3, 4, 8, 12, 15, 22, 29, 43, 50, 57, 64, 78, 85, and 113 days post-dose
Area Under the Concentration-time Curve From Time 0 to Time of Last Quantifiable Concentration (AUClast) for Erenumab		Predose and 4 hours, 2, 3, 4, 8, 12, 15, 22, 29, 43, 50, 57, 64, 78, 85, and 113 days post-dose
Area Under the Concentration-time Curve From Time 0 to Infinity (AUCinf) for Erenumab		Predose and 4 hours, 2, 3, 4, 8, 12, 15, 22, 29, 43, 50, 57, 64, 78, 85, and 113 days post-dose
Terminal Half-life (T1/2) of Erenumab		Predose and 4 hours, 2, 3, 4, 8, 12, 15, 22, 29, 43, 50, 57, 64, 78, 85, and 113 days post-dose
Number of Participants With Treatment-emergent Suicidal Ideation	The Columbia Suicide Severity Rating Scale (C-SSRS) was used to assess suicidal ideation during the study based on the following Yes/No questions: Have you wished you were dead or wished you could go to sleep and not wake up?; Have you actually had any thoughts of killing yourself?	16 weeks
Number of Participants Who Developed Anti-erenumab Antibodies After a Single Dose	Two validated assays were used to detect the presence of anti-erenumab antibodies. First, an electrochemiluminescent (ECL) bridging immunoassay was used to detect antibodies capable of binding erenumab. Second, a cell based bioassay was used to test positive binding antibody samples for neutralizing activity against erenumab. A participant was defined as positive for developing anti-erenumab antibodies if they were binding antibody positive postbaseline with a negative or no result at baseline. If a sample was positive for binding antibodies and demonstrated neutralizing activity at the same time point, the participant was defined as positive for neutralizing antibodies.	16 weeks

Collaborators and Investigators

• Sponsor: Amgen

Publications and helpful links

Helpful Links

• AmgenTrials clinical trials website

Study record dates

Study Major Dates

• Study Start (Actual): May 13, 2013
• Primary Completion (Actual): March 11, 2014
• Study Completion (Actual): March 11, 2014

Study Registration Dates

• First Submitted: May 13, 2013
• First Submitted That Met QC Criteria: June 27, 2013
• First Posted (Estimate): July 1, 2013

Study Record Updates

• Last Update Posted (Actual): January 14, 2019
• Last Update Submitted That Met QC Criteria: January 11, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Keywords: Vasomotor symptoms; Hot Flashes; Menopause
• Additional Relevant MeSH Terms: Hot Flashes; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Calcitonin Gene-Related Peptide Receptor Antagonists; Erenumab
• Other Study ID Numbers: 20120180