Study of Erenumab (AMG 334) in Women With 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.

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.

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.

Blood samples were analyzed using an enzyme-linked immunosorbent assay (ELISA) following a validated analytical procedure.

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?

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.