Trial Outcomes & Findings for Study of Erenumab (AMG 334) in Women With Hot Flashes (NCT NCT01890109)

NCT ID: NCT01890109

Last Updated: 2019-01-14

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 103 participants
• Primary outcome timeframe: Baseline (days -7 to day 1 predose) and week 4 (days 21 to 27)
• Results posted on: 2019-01-14

Participant Flow

This study was conducted at 6 centers in the United States from 13 May 2013 to 11 March 2014. Screening included completion of a 7-day diary to record hot flashes.

Participants meeting the eligibility criteria were randomized in a 1:1 ratio to erenumab or placebo. Participants were stratified based on the average number of hot flashes per 24 hours during the screening period (≤ 11.5 or > 11.5).

Participant milestones

Measure	Placebo Participants received a single dose of placebo administered by subcutaneous injection.	Erenumab Participants received a single dose of 70 mg erenumab administered by subcutaneous injection.
Overall Study STARTED	52	51
Overall Study Received Study Treatment	52	50
Overall Study COMPLETED	51	46
Overall Study NOT COMPLETED	1	5

Reasons for withdrawal

Measure	Placebo Participants received a single dose of placebo administered by subcutaneous injection.	Erenumab Participants received a single dose of 70 mg erenumab administered by subcutaneous injection.
Overall Study Withdrawal by Subject	0	3
Overall Study Lost to Follow-up	1	2

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Placebo n=52 Participants Participants received a single dose of placebo administered by subcutaneous injection.	Erenumab n=50 Participants Participants received a single dose of 70 mg erenumab administered by subcutaneous injection.	Total n=102 Participants Total of all reporting groups
Age, Continuous	55.5 years STANDARD_DEVIATION 4.8 • n=5 Participants	55.6 years STANDARD_DEVIATION 3.8 • n=7 Participants	55.6 years STANDARD_DEVIATION 4.3 • n=5 Participants
Sex: Female, Male Female	52 Participants n=5 Participants	50 Participants n=7 Participants	102 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	6 Participants n=5 Participants	8 Participants n=7 Participants	14 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	46 Participants n=5 Participants	42 Participants n=7 Participants	88 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Asian	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	15 Participants n=5 Participants	10 Participants n=7 Participants	25 Participants n=5 Participants
Race/Ethnicity, Customized Mixed Race	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized White	36 Participants n=5 Participants	36 Participants n=7 Participants	72 Participants n=5 Participants
Number of Hot Flashes at Baseline ≤ 11.5 hot flashes/24 hours	26 Participants n=5 Participants	25 Participants n=7 Participants	51 Participants n=5 Participants
Number of Hot Flashes at Baseline > 11.5 hot flashes/24 hours	26 Participants n=5 Participants	25 Participants n=7 Participants	51 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline (days -7 to day 1 predose) and week 4 (days 21 to 27)

Population: All participants for whom at least 1 postdose hot flash response measure was recorded.

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.

Outcome measures

Measure	Placebo n=52 Participants Participants received a single dose of placebo administered by subcutaneous injection.	Erenumab n=50 Participants Participants received a single dose of 70 mg erenumab administered by subcutaneous injection.
Ratio of Week 4 to Baseline Average Number of Daily Moderate to Severe Hot Flashes	0.35 ratio Interval 0.24 to 0.5	0.38 ratio Interval 0.26 to 0.55

SECONDARY outcome

Timeframe: Baseline (days -7 to day 1 predose) and week 4 (days 21 to 27)

Population: All participants for whom at least 1 postdose hot flash response measure was recorded.

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.

Outcome measures

Measure	Placebo n=52 Participants Participants received a single dose of placebo administered by subcutaneous injection.	Erenumab n=50 Participants Participants received a single dose of 70 mg erenumab administered by subcutaneous injection.
Ratio of Week 4 to Baseline Daily Hot Flash Severity Score	0.40 ratio Interval 0.29 to 0.53	0.45 ratio Interval 0.33 to 0.61

SECONDARY outcome

Timeframe: 16 weeks

Population: All participants who received study drug

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.

Outcome measures

Measure	Placebo n=52 Participants Participants received a single dose of placebo administered by subcutaneous injection.	Erenumab n=50 Participants Participants received a single dose of 70 mg erenumab administered by subcutaneous injection.
Number of Participants With Treatment-emergent Adverse Events Treatment-emergent adverse events (TEAEs)	23 Participants	24 Participants
Number of Participants With Treatment-emergent Adverse Events Fatal adverse events	0 Participants	0 Participants
Number of Participants With Treatment-emergent Adverse Events Treatment-related serious adverse events	0 Participants	0 Participants
Number of Participants With Treatment-emergent Adverse Events TRAE leading to discontinuation of study drug	0 Participants	0 Participants
Number of Participants With Treatment-emergent Adverse Events Serious adverse events	0 Participants	0 Participants
Number of Participants With Treatment-emergent Adverse Events TEAE leading to discontinuation of study drug	0 Participants	0 Participants
Number of Participants With Treatment-emergent Adverse Events TEAE leading to discontinuation of study	0 Participants	0 Participants
Number of Participants With Treatment-emergent Adverse Events Treatment-related adverse events (TRAEs)	5 Participants	3 Participants
Number of Participants With Treatment-emergent Adverse Events TRAE leading to discontinuation of study	0 Participants	0 Participants
Number of Participants With Treatment-emergent Adverse Events Treatment-related fatal adverse events	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Predose and 4 hours, 2, 3, 4, 8, 12, 15, 22, 29, 43, 50, 57, 64, 78, 85, and 113 days post-dose

Population: All participants who received erenumab and for whom at least 1 pharmacokinetic (PK) parameter or endpoint could be adequately estimated.

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

Outcome measures

Measure	Placebo n=50 Participants Participants received a single dose of placebo administered by subcutaneous injection.	Erenumab Participants received a single dose of 70 mg erenumab administered by subcutaneous injection.
Maximum Observed Concentration (Cmax) of Erenumab After a Single Dose	6.13 μg/mL Standard Deviation 2.86	—

SECONDARY outcome

Timeframe: Predose and 4 hours, 2, 3, 4, 8, 12, 15, 22, 29, 43, 50, 57, 64, 78, 85, and 113 days post-dose

Population: All participants who received erenumab and for whom at least 1 pharmacokinetic (PK) parameter or endpoint could be adequately estimated.

Outcome measures

Measure	Placebo n=50 Participants Participants received a single dose of placebo administered by subcutaneous injection.	Erenumab Participants received a single dose of 70 mg erenumab administered by subcutaneous injection.
Time to Maximum Observed Concentration (Tmax) of Erunumab After a Single Dose	7.0 days Interval 0.92 to 19.0	—

SECONDARY outcome

Timeframe: Predose and 4 hours, 2, 3, 4, 8, 12, 15, 22, 29, 43, 50, 57, 64, 78, 85, and 113 days post-dose

Population: All participants who received erenumab and for whom at least 1 pharmacokinetic (PK) parameter or endpoint could be adequately estimated.

Outcome measures

Measure	Placebo n=50 Participants Participants received a single dose of placebo administered by subcutaneous injection.	Erenumab Participants received a single dose of 70 mg erenumab administered by subcutaneous injection.
Area Under the Concentration-time Curve From Time 0 to Time of Last Quantifiable Concentration (AUClast) for Erenumab	173 day*μg/mL Standard Deviation 84.6	—

SECONDARY outcome

Timeframe: Predose and 4 hours, 2, 3, 4, 8, 12, 15, 22, 29, 43, 50, 57, 64, 78, 85, and 113 days post-dose

Population: All participants who received erenumab and for whom at least 1 pharmacokinetic (PK) parameter or endpoint could be adequately estimated. AUCinf could not be accurately estimated for 23 participants who are excluded from the analysis.

Outcome measures

Measure	Placebo n=27 Participants Participants received a single dose of placebo administered by subcutaneous injection.	Erenumab Participants received a single dose of 70 mg erenumab administered by subcutaneous injection.
Area Under the Concentration-time Curve From Time 0 to Infinity (AUCinf) for Erenumab	190 day*μg/mL Standard Deviation 96.3	—

SECONDARY outcome

Timeframe: Predose and 4 hours, 2, 3, 4, 8, 12, 15, 22, 29, 43, 50, 57, 64, 78, 85, and 113 days post-dose

Population: All participants who received erenumab and for whom at least 1 PK parameter or endpoint could be adequately estimated. T1/2 could not be accurately estimated for 23 participants who are excluded from the analysis. The terminal half-life calculated from this single dose study may not be representative of a clinically relevant half-life of erenumab.

Outcome measures

Measure	Placebo n=27 Participants Participants received a single dose of placebo administered by subcutaneous injection.	Erenumab Participants received a single dose of 70 mg erenumab administered by subcutaneous injection.
Terminal Half-life (T1/2) of Erenumab	12.1 days Standard Deviation 3.00	—

SECONDARY outcome

Timeframe: 16 weeks

Population: All participants who received study drug

The Columbia Suicide Severity Rating Scale (C-SSRS) was used to assess suicidal ideation during the study based on the following Yes/No questions:

1. Have you wished you were dead or wished you could go to sleep and not wake up?

2. Have you actually had any thoughts of killing yourself?

Outcome measures

Measure	Placebo n=52 Participants Participants received a single dose of placebo administered by subcutaneous injection.	Erenumab n=50 Participants Participants received a single dose of 70 mg erenumab administered by subcutaneous injection.
Number of Participants With Treatment-emergent Suicidal Ideation	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 16 weeks

Population: All participants who received study drug.

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.

Outcome measures

Measure	Placebo n=52 Participants Participants received a single dose of placebo administered by subcutaneous injection.	Erenumab n=50 Participants Participants received a single dose of 70 mg erenumab administered by subcutaneous injection.
Number of Participants Who Developed Anti-erenumab Antibodies After a Single Dose Binding antibody positive	0 Participants	5 Participants
Number of Participants Who Developed Anti-erenumab Antibodies After a Single Dose Neutralizing antibody positive	0 Participants	4 Participants

Adverse Events

Placebo

Serious events: 0 serious events

Other events: 11 other events

Deaths: 0 deaths

Erenumab 70 mg

Serious events: 0 serious events

Other events: 9 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Placebo n=52 participants at risk Participants received a single dose of placebo administered by subcutaneous injection.	Erenumab 70 mg n=50 participants at risk Participants received a single dose of 70 mg erenumab administered by subcutaneous injection.
Infections and infestations Upper respiratory tract infection	3.8% 2/52 • 16 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	6.0% 3/50 • 16 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Urinary tract infection	5.8% 3/52 • 16 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/50 • 16 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/52 • 16 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	8.0% 4/50 • 16 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/52 • 16 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	6.0% 3/50 • 16 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Nervous system disorders Headache	7.7% 4/52 • 16 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	6.0% 3/50 • 16 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	5.8% 3/52 • 16 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/50 • 16 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.

Additional Information

Study Director

Amgen Inc.

Phone: 866-572-6436

Email: medinfo@amgen.com

Results disclosure agreements

• Principal investigator is a sponsor employee The Clinical Trial Agreement generally does not restrict an investigator's discussion of trial results after completion. The Agreement permits Amgen a limited period of time to review material discussing trial results (typically up to 45 days and possible extension). Amgen may remove confidential information, but authors have final control and approval of publication content. For multicenter studies, the investigator agrees not to publish any results before the first multi-center publication.
• Publication restrictions are in place

Restriction type: OTHER