A Phase 1 interventional study of Erenumab and Placebo in Vasomotor Symptoms; Hot Flashes, sponsored by Amgen. Completed at 7 sites in United States. Open to female participants aged 45 Years to 65 Years. Per ClinicalTrials.gov, last updated 2019-01-14.
Sponsored by Amgen · Phase 1, Interventional, and Prevention
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.
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.
285 studies on the registry are indexed under Hot Flashes; 50 are open to participants now.
This study's enrollment of 103 is above the median of 90 across 255 interventional studies indexed under Hot Flashes.
Browse Hot Flashes studies →Amgen is the lead sponsor of 1,015 studies on the registry; 49 are open to participants now.
Of its 245 completed or terminated interventional studies of FDA-regulated products, 159 (65%) have results posted.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
Participants received a single dose of placebo administered by subcutaneous injection.
Drug: Placebo
Participants received a single dose of 70 mg erenumab administered by subcutaneous injection.
Biological: Erenumab
Administered via subcutaneous injection.
Also known as: AMG 334, Aimovig™
Administered via subcutaneous injection
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.
Time frame: Baseline (days -7 to day 1 predose) and week 4 (days 21 to 27)
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.
Time frame: 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.
Time frame: 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.
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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: 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?
Time frame: 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.
Time frame: 16 weeks
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.
| Milestone | Placebo | Erenumab |
|---|---|---|
| Started | 52 | 51 |
| Received study treatment | 52 | 50 |
| Completed | 51 | 46 |
| Not completed | 1 | 5 |
| Withdrew: Withdrawal by subject | 0 | 3 |
| Withdrew: Lost to follow-up | 1 | 2 |
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.
| ratio | Placebo | Erenumab |
|---|---|---|
| Ratio of Week 4 to Baseline Average Number of Daily Moderate to Severe Hot Flashes | 0.35 (0.24 to 0.50) | 0.38 (0.26 to 0.55) |
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.
| ratio | Placebo | Erenumab |
|---|---|---|
| Ratio of Week 4 to Baseline Daily Hot Flash Severity Score | 0.40 (0.29 to 0.53) | 0.45 (0.33 to 0.61) |
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.
| Participants | Placebo | Erenumab |
|---|---|---|
| Treatment-emergent adverse events (TEAEs) | 23 | 24 |
| Serious adverse events | 0 | 0 |
| TEAE leading to discontinuation of study drug | 0 | 0 |
| TEAE leading to discontinuation of study | 0 | 0 |
| Fatal adverse events | 0 | 0 |
| Treatment-related adverse events (TRAEs) | 5 | 3 |
| Treatment-related serious adverse events | 0 | 0 |
| TRAE leading to discontinuation of study drug | 0 | 0 |
| TRAE leading to discontinuation of study | 0 | 0 |
| Treatment-related fatal adverse events | 0 | 0 |
Blood samples were analyzed using an enzyme-linked immunosorbent assay (ELISA) following a validated analytical procedure.
| μg/mL | Erenumab |
|---|---|
| Maximum Observed Concentration (Cmax) of Erenumab After a Single Dose | 6.13 ± 2.86 |
| days | Erenumab |
|---|---|
| Time to Maximum Observed Concentration (Tmax) of Erunumab After a Single Dose | 7.0 (0.92 to 19) |
| day*μg/mL | Erenumab |
|---|---|
| Area Under the Concentration-time Curve From Time 0 to Time of Last Quantifiable Concentration (AUClast) for Erenumab | 173 ± 84.6 |
| day*μg/mL | Erenumab |
|---|---|
| Area Under the Concentration-time Curve From Time 0 to Infinity (AUCinf) for Erenumab | 190 ± 96.3 |
| days | Erenumab |
|---|---|
| Terminal Half-life (T1/2) of Erenumab | 12.1 ± 3.00 |
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?
| Participants | Placebo | Erenumab |
|---|---|---|
| Number of Participants With Treatment-emergent Suicidal Ideation | 0 | 0 |
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.
| Participants | Placebo | Erenumab |
|---|---|---|
| Binding antibody positive | 0 | 5 |
| Neutralizing antibody positive | 0 | 4 |
Collected over 16 Weeks. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Placebo | — | 0/52 (0%) | 11/52 (21.2%) |
| Erenumab 70 mg | — | 0/50 (0%) | 9/50 (18%) |
| Event | Placebo | Erenumab 70 mg |
|---|---|---|
| ArthralgiaMusculoskeletal and connective tissue disorders | 0/52 | 4/50 |
| HeadacheNervous system disorders | 4/52 | 3/50 |
| Upper respiratory tract infectionInfections and infestations | 2/52 | 3/50 |
| Back painMusculoskeletal and connective tissue disorders | 0/52 | 3/50 |
| Urinary tract infectionInfections and infestations | 3/52 | 0/50 |
| Oropharyngeal painRespiratory, thoracic and mediastinal disorders | 3/52 | 0/50 |
Participants who received study treatment.
| Age, Continuous(years) | Placebo | Erenumab | Total |
|---|---|---|---|
| Mean | 55.5 ± 4.8 | 55.6 ± 3.8 | 55.6 ± 4.3 |
| Sex: Female, Male(Participants) | Placebo | Erenumab | Total |
|---|---|---|---|
| Female | 52 | 50 | 102 |
| Male | 0 | 0 | 0 |
| Ethnicity (NIH/OMB)(Participants) | Placebo | Erenumab | Total |
|---|---|---|---|
| Hispanic or Latino | 6 | 8 | 14 |
| Not Hispanic or Latino | 46 | 42 | 88 |
| Unknown or Not Reported | 0 | 0 | 0 |
| Race/Ethnicity, Customized(Participants) | Placebo | Erenumab | Total |
|---|---|---|---|
| American Indian or Alaska Native | 0 | 1 | 1 |
| Asian | 1 | 0 | 1 |
| Black or African American | 15 | 10 | 25 |
| Mixed Race | 0 | 1 | 1 |
| Native Hawaiian or Other Pacific Islander | 0 | 2 | 2 |
| White | 36 | 36 | 72 |
| Number of Hot Flashes at Baseline(Participants) | Placebo | Erenumab | Total |
|---|---|---|---|
| ≤ 11.5 hot flashes/24 hours | 26 | 25 | 51 |
| > 11.5 hot flashes/24 hours | 26 | 25 | 51 |
This study is completed, as verified in Jan 2019. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Amgen