Ascending Single Doses of Erenumab (AMG 334) in Healthy Adults and Migraine Patients
Sponsor
Amgen (Industry)
Overall Status
Completed
CT.gov ID
NCT01688739
Collaborator
(none)
61
1
2
12.5
4.9
Study Details
Study Description
Brief Summary
The primary purpose of this study is to determine whether erenumab is safe and well tolerated in healthy adults and migraine patients. As part of the secondary objectives, this study will be conducted to characterize the pharmacokinetic (PK) profile of erenumab after single subcutaneous (SC) or intravenous (IV) doses in healthy participants and migraine patients as well as to characterize the effect of erenumab on the capsaicin-induced increase in dermal blood flow after single SC or IV doses in healthy participants and migraine patients.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Detailed Description
This study was a single-dose, double-blind, placebo-controlled, sequential dose escalation study in which participants were to be enrolled into 8 cohorts.
In Part 1 healthy participants were randomized in a 3:1 ratio (erenumab:placebo) into 6 cohorts: 5 cohorts received the investigational product (IP) as an SC administration and 1 cohort received it as an IV administration. In Part 2 a total of 12 migraine patients were randomized in a 1:1 ratio (erenumab:placebo) in cohort 7. An additional 8 migraine patients could have been enrolled and randomized in a 3:1 ratio in the optional cohort 8, however this cohort was not enrolled.
Study Design
Study Type:
Interventional
Actual Enrollment
:
61 participants
Allocation:
Randomized
Intervention Model:
Sequential Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Prevention
Official Title:
A Phase I, Randomized, Double-Blind, Placebo-Controlled, Ascending Single Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of AMG 334 in Healthy Subjects and Migraine Patients
Actual Study Start Date
:
Mar 13, 2012
Actual Primary Completion Date
:
Mar 27, 2013
Actual Study Completion Date
:
Mar 27, 2013
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Erenumab Participants received a single dose of erenumab by subcutaneous injection at doses of 1 mg, 7 mg, 21 mg, 70 mg, 140 mg, and 210 mg or by IV injection at a dose of 140 mg. |
Drug: Erenumab
Administered by subcutaneous injection or intravenous injection
Other Names:
|
| Placebo Comparator: Placebo Participants received a single dose of matching placebo administered by SC or IV injection. |
Drug: Placebo
Administered by subcutaneous injection or intravenous injection
|
Outcome Measures
Primary Outcome Measures
- Number of Participants With Adverse Events [From the initial dose of study drug up to 155 days.]
An adverse event (AE) is defined as any untoward medical occurrence in a clinical trial participant. The event does not necessarily have a causal relationship with study treatment. The definition of adverse events includes worsening of a pre-existing medical condition. Laboratory value changes that require treatment or adjustment in current therapy are considered adverse events. Teatment-related adverse events (TRAEs) are those assessed by the investigator as being possibly related to study drug. A serious adverse event is defined as an adverse event that meets at least 1 of the following serious criteria: fatal life-threatening (places the subject at immediate risk of death) requires in-patient hospitalization or prolongation of existing hospitalization results in persistent or significant disability/incapacity congenital anomaly/birth defect other medically important serious event.
- Number of Participants Who Developed Anti-erenumab Antibodies [Baseline and up to 155 days postdose]
Participants who had a negative or no result at baseline and were antibody positive postbaseline. Blood samples were first tested for anti-erenumab binding antibodies, samples testing positive for binding antibodies were also tested for neutralizing antibodies.
Secondary Outcome Measures
- Maximum Observed Concentration (Cmax) of Erenumab [Predose to 155 days postdose]
- Time to Maximum Observed Concentration (Tmax) of Erenumab [Predose to 155 days postdose]
- Area Under the Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration (AUClast) of Erenumab [Predose to 155 days postdose]
- Area Under the Concentration-time Curve From Time Zero to Infinity (AUCinf) of Erenumab [Predose to 155 days postdose]
- Ratio of Post-capsaicin Dermal Blood Flow to Pre-capsaicin Dermal Blood Flow [Days 4, 15, 29, 43, 64, 85, 99, 127, and end of study (defined as day 43 for the 1 mg, 7 mg and 21 mg erenumab cohorts, day 99 for the 70 mg erenumab cohort, day 127 for the 140 mg erenumab cohorts and day 155 for the 210 mg erenumab cohort).]
Inhibition of capsaicin-induced dermal blood flow (DBF) by erenumab was used to measure calcitonin gene-related peptide (CGRP) receptor antagonism. Capsaicin was applied at 2 sites on the volar surface of the participants' left or right forearms and a control mixture was applied to 1 site on the volar surface of either the participants' left or right forearm. Dermal blood flow was assessed by laser Doppler perfusion imaging and was done immediately before ('baseline') and 0.5 hours post-capsaicin on the surface of these 3 sites. Data reported are the least square geometric mean ratios for the post-capsaicin dermal blood flow to pre-capsaicin dermal blood flow. According to the protocol, not all cohorts had dermal blood flow measurements at all time points.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
to 55 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
Yes
Inclusion Criteria:
- Healthy male and female subjects between 18 and 45 years of age, or male or female subjects with migraines between 18 and 55 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;
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Research Site | Leuven | Belgium | 3000 |
Sponsors and Collaborators
- Amgen
Investigators
- Study Director: MD, Amgen
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
- de Hoon J, Van Hecken A, Vandermeulen C, Yan L, Smith B, Chen JS, Bautista E, Hamilton L, Waksman J, Vu T, Vargas G. Phase I, Randomized, Double-blind, Placebo-controlled, Single-dose, and Multiple-dose Studies of Erenumab in Healthy Subjects and Patients With Migraine. Clin Pharmacol Ther. 2018 May;103(5):815-825. doi: 10.1002/cpt.799. Epub 2017 Oct 24.
- Vu T, Ma P, Chen JS, de Hoon J, Van Hecken A, Yan L, Wu LS, Hamilton L, Vargas G. Pharmacokinetic-Pharmacodynamic Relationship of Erenumab (AMG 334) and Capsaicin-Induced Dermal Blood Flow in Healthy and Migraine Subjects. Pharm Res. 2017 Sep;34(9):1784-1795. doi: 10.1007/s11095-017-2183-6. Epub 2017 Jun 7.
Responsible Party:
Amgen
ClinicalTrials.gov Identifier:
NCT01688739
Other Study ID Numbers:
- 20101267
- 2011-005600-15
First Posted:
Sep 20, 2012
Last Update Posted:
Jan 18, 2019
Last Verified:
Aug 1, 2018
Study Results
Participant Flow
| Recruitment Details | This study was conducted at a single center in Belgium from March 2012 to March 2013. The study enrolled healthy participants (Part 1) and participants who had migraines for at least 6 months and at least 3 migraine attacks per month in the last 3 months (Part 2). |
|---|---|
| Pre-assignment Detail | Healthy participants were randomized in a 3:1 ratio to erenumab or placebo within each dose cohort. Migraine participants were randomized in a 1:1 ratio to erenumab or placebo. |
| Arm/Group Title | Healthy: Placebo | Healthy: Erenumab 1 mg SC | Healthy: Erenumab 7 mg SC | Healthy: Erenumab 21 mg SC | Healthy: Erenumab 70 mg SC | Healthy: Erenumab 140 mg SC | Healthy: Erenumab 140 mg IV | Healthy: Erenumab 210 mg SC | Migraine: Placebo | Migraine: Erenumab 140 mg SC |
|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Healthy participants received a single dose of matching placebo administered by subcutaneous (SC) or intravenous (IV) injection. | Healthy participants received a single dose of erenumab 1 mg administered by subcutaneous injection. | Healthy participants received a single dose of erenumab 7 mg administered by subcutaneous injection. | Healthy participants received a single dose of erenumab 21 mg administered by subcutaneous injection. | Healthy participants received a single dose of erenumab 70 mg administered by subcutaneous injection. | Healthy participants received a single dose of erenumab 140 mg administered by subcutaneous injection. | Healthy participants received a single dose of erenumab 140 mg administered by intravenous injection. | Healthy participants received a single dose of erenumab 210 mg administered by subcutaneous injection. | Participants with migraine received a single dose of placebo administered by subcutaneous injection. | Participants with migraine received a single dose of erenumab 140 mg administered by subcutaneous injection. |
| Period Title: Overall Study | ||||||||||
| STARTED | 13 | 3 | 3 | 6 | 6 | 6 | 6 | 6 | 6 | 6 |
| Received Study Drug | 12 | 3 | 3 | 6 | 6 | 6 | 6 | 6 | 6 | 6 |
| COMPLETED | 12 | 3 | 3 | 6 | 6 | 6 | 6 | 6 | 6 | 6 |
| NOT COMPLETED | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Baseline Characteristics
| Arm/Group Title | Healthy: Placebo | Healthy: Erenumab 1 mg SC | Healthy: Erenumab 7 mg SC | Healthy: Erenumab 21 mg SC | Healthy: Erenumab 70 mg SC | Healthy: Erenumab 140 mg SC | Healthy: Erenumab 140 mg IV | Healthy: Erenumab 210 mg SC | Migraine: Placebo | Migraine: Erenumab 140 mg SC | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Healthy participants received a single dose of matching placebo administered by subcutaneous (SC) or intravenous (IV) injection. | Healthy participants received a single dose of erenumab 1 mg administered by subcutaneous injection. | Healthy participants received a single dose of erenumab 7 mg administered by subcutaneous injection. | Healthy participants received a single dose of erenumab 21 mg administered by subcutaneous injection. | Healthy participants received a single dose of erenumab 70 mg administered by subcutaneous injection. | Healthy participants received a single dose of erenumab 140 mg administered by subcutaneous injection. | Healthy participants received a single dose of erenumab 140 mg administered by intravenous injection. | Healthy participants received a single dose of erenumab 210 mg administered by subcutaneous injection. | Participants with migraine received a single dose of placebo administered by subcutaneous injection. | Participants with migraine received a single dose of erenumab 140 mg administered by subcutaneous injection. | Total of all reporting groups |
| Overall Participants | 12 | 3 | 3 | 6 | 6 | 6 | 6 | 6 | 6 | 6 | 60 |
| Age (years) [Mean (Standard Deviation) ] | |||||||||||
| Healthy Participants |
28.6
(6.1)
|
22.0
(1.7)
|
26.0
(7.9)
|
25.7
(6.9)
|
27.5
(6.6)
|
28.0
(8.5)
|
31.0
(8.1)
|
26.2
(7.0)
|
27.4
(6.8)
|
||
| Migraine Participants |
28.5
(12.6)
|
23.8
(5.4)
|
26.2
(9.6)
|
||||||||
| Sex: Female, Male (Count of Participants) | |||||||||||
| Female |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
4
66.7%
|
5
83.3%
|
9
15%
|
| Male |
12
100%
|
3
100%
|
3
100%
|
6
100%
|
6
100%
|
6
100%
|
6
100%
|
6
100%
|
2
33.3%
|
1
16.7%
|
51
85%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |||||||||||
| Hispanic or Latino |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
16.7%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
1.7%
|
| Not Hispanic or Latino |
12
100%
|
3
100%
|
3
100%
|
6
100%
|
5
83.3%
|
6
100%
|
6
100%
|
6
100%
|
6
100%
|
6
100%
|
59
98.3%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Race/Ethnicity, Customized (Count of Participants) | |||||||||||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Asian |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Mixed race |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
16.7%
|
0
0%
|
0
0%
|
0
0%
|
1
1.7%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| White |
12
100%
|
3
100%
|
3
100%
|
6
100%
|
6
100%
|
6
100%
|
5
83.3%
|
6
100%
|
6
100%
|
6
100%
|
59
98.3%
|
Outcome Measures
| Title | Number of Participants With Adverse Events |
|---|---|
| Description | An adverse event (AE) is defined as any untoward medical occurrence in a clinical trial participant. The event does not necessarily have a causal relationship with study treatment. The definition of adverse events includes worsening of a pre-existing medical condition. Laboratory value changes that require treatment or adjustment in current therapy are considered adverse events. Teatment-related adverse events (TRAEs) are those assessed by the investigator as being possibly related to study drug. A serious adverse event is defined as an adverse event that meets at least 1 of the following serious criteria: fatal life-threatening (places the subject at immediate risk of death) requires in-patient hospitalization or prolongation of existing hospitalization results in persistent or significant disability/incapacity congenital anomaly/birth defect other medically important serious event. |
| Time Frame | From the initial dose of study drug up to 155 days. |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received study drug. |
| Arm/Group Title | Healthy: Placebo | Healthy: Erenumab 1 mg SC | Healthy: Erenumab 7 mg SC | Healthy: Erenumab 21 mg SC | Healthy: Erenumab 70 mg SC | Healthy: Erenumab 140 mg SC | Healthy: Erenumab 140 mg IV | Healthy: Erenumab 210 mg SC | Migraine: Placebo | Migraine: Erenumab 140 mg SC |
|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Healthy participants received a single dose of matching placebo administered by subcutaneous (SC) or intravenous (IV) injection. | Healthy participants received a single dose of erenumab 1 mg administered by subcutaneous injection. | Healthy participants received a single dose of erenumab 7 mg administered by subcutaneous injection. | Healthy participants received a single dose of erenumab 21 mg administered by subcutaneous injection. | Healthy participants received a single dose of erenumab 70 mg administered by subcutaneous injection. | Healthy participants received a single dose of erenumab 140 mg administered by subcutaneous injection. | Healthy participants received a single dose of erenumab 140 mg administered by intravenous injection. | Healthy participants received a single dose of erenumab 210 mg administered by subcutaneous injection. | Participants with migraine received a single dose of placebo administered by subcutaneous injection. | Participants with migraine received a single dose of erenumab 140 mg administered by subcutaneous injection. |
| Measure Participants | 12 | 3 | 3 | 6 | 6 | 6 | 6 | 6 | 6 | 6 |
| Any adverse event |
10
83.3%
|
2
66.7%
|
1
33.3%
|
6
100%
|
5
83.3%
|
5
83.3%
|
5
83.3%
|
6
100%
|
5
83.3%
|
6
100%
|
| Serious adverse event |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| AE leading to discontinuation of study drug |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| AE leading to discontinuation from study |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Fatal adverse events |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Treatment-related adverse events |
4
33.3%
|
0
0%
|
0
0%
|
0
0%
|
1
16.7%
|
1
16.7%
|
2
33.3%
|
4
66.7%
|
0
0%
|
0
0%
|
| Title | Number of Participants Who Developed Anti-erenumab Antibodies |
|---|---|
| Description | Participants who had a negative or no result at baseline and were antibody positive postbaseline. Blood samples were first tested for anti-erenumab binding antibodies, samples testing positive for binding antibodies were also tested for neutralizing antibodies. |
| Time Frame | Baseline and up to 155 days postdose |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received study drug |
| Arm/Group Title | Healthy: Placebo | Healthy: Erenumab 1 mg SC | Healthy: Erenumab 7 mg SC | Healthy: Erenumab 21 mg SC | Healthy: Erenumab 70 mg SC | Healthy: Erenumab 140 mg SC | Healthy: Erenumab 140 mg IV | Healthy: Erenumab 210 mg SC | Migraine: Placebo | Migraine: Erenumab 140 mg SC |
|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Healthy participants received a single dose of matching placebo administered by subcutaneous (SC) or intravenous (IV) injection. | Healthy participants received a single dose of erenumab 1 mg administered by subcutaneous injection. | Healthy participants received a single dose of erenumab 7 mg administered by subcutaneous injection. | Healthy participants received a single dose of erenumab 21 mg administered by subcutaneous injection. | Healthy participants received a single dose of erenumab 70 mg administered by subcutaneous injection. | Healthy participants received a single dose of erenumab 140 mg administered by subcutaneous injection. | Healthy participants received a single dose of erenumab 140 mg administered by intravenous injection. | Healthy participants received a single dose of erenumab 210 mg administered by subcutaneous injection. | Participants with migraine received a single dose of placebo administered by subcutaneous injection. | Participants with migraine received a single dose of erenumab 140 mg administered by subcutaneous injection. |
| Measure Participants | 12 | 3 | 3 | 6 | 6 | 6 | 6 | 6 | 6 | 6 |
| Binding antibody positive |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
16.7%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Neutralizing antibody positive |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Title | Maximum Observed Concentration (Cmax) of Erenumab |
|---|---|
| Description | |
| Time Frame | Predose to 155 days postdose |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received erenumab |
| Arm/Group Title | Healthy: Erenumab 1 mg SC | Healthy: Erenumab 7 mg SC | Healthy: Erenumab 21 mg SC | Healthy: Erenumab 70 mg SC | Healthy: Erenumab 140 mg SC | Healthy: Erenumab 140 mg IV | Healthy: Erenumab 210 mg SC | Migraine: Erenumab 140 mg SC |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Healthy participants received a single dose of erenumab 1 mg administered by subcutaneous injection. | Healthy participants received a single dose of erenumab 7 mg administered by subcutaneous injection. | Healthy participants received a single dose of erenumab 21 mg administered by subcutaneous injection. | Healthy participants received a single dose of erenumab 70 mg administered by subcutaneous injection. | Healthy participants received a single dose of erenumab 140 mg administered by subcutaneous injection. | Healthy participants received a single dose of erenumab 140 mg administered by intravenous injection. | Healthy participants received a single dose of erenumab 210 mg administered by subcutaneous injection. | Participants with migraine received a single dose of erenumab 140 mg administered by subcutaneous injection. |
| Measure Participants | 3 | 3 | 6 | 6 | 6 | 6 | 6 | 6 |
| Mean (Standard Deviation) [µg/mL] |
0.0077
(0.00395)
|
0.302
(0.145)
|
1.17
(0.646)
|
6.25
(2.03)
|
9.18
(1.97)
|
47.8
(4.09)
|
15.2
(4.78)
|
9.93
(3.42)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Healthy: Erenumab 70 mg SC, Healthy: Erenumab 210 mg SC |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.7595 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Ratio of Geometric Means |
| Estimated Value | 1.1 | |
| Confidence Interval |
(2-Sided) 90% 0.8 to 1.4 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Migraine participants / Healthy Participants | |
| Title | Time to Maximum Observed Concentration (Tmax) of Erenumab |
|---|---|
| Description | |
| Time Frame | Predose to 155 days postdose |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received erenumab |
| Arm/Group Title | Healthy: Erenumab 1 mg SC | Healthy: Erenumab 7 mg SC | Healthy: Erenumab 21 mg SC | Healthy: Erenumab 70 mg SC | Healthy: Erenumab 140 mg SC | Healthy: Erenumab 140 mg IV | Healthy: Erenumab 210 mg SC | Migraine: Erenumab 140 mg SC |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Healthy participants received a single dose of erenumab 1 mg administered by subcutaneous injection. | Healthy participants received a single dose of erenumab 7 mg administered by subcutaneous injection. | Healthy participants received a single dose of erenumab 21 mg administered by subcutaneous injection. | Healthy participants received a single dose of erenumab 70 mg administered by subcutaneous injection. | Healthy participants received a single dose of erenumab 140 mg administered by subcutaneous injection. | Healthy participants received a single dose of erenumab 140 mg administered by intravenous injection. | Healthy participants received a single dose of erenumab 210 mg administered by subcutaneous injection. | Participants with migraine received a single dose of erenumab 140 mg administered by subcutaneous injection. |
| Measure Participants | 3 | 3 | 6 | 6 | 6 | 6 | 6 | 6 |
| Median (Full Range) [days] |
4.0
|
7.0
|
7.0
|
6.0
|
5.5
|
0.069
|
8.5
|
11
|
| Title | Area Under the Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration (AUClast) of Erenumab |
|---|---|
| Description | |
| Time Frame | Predose to 155 days postdose |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received erenumab |
| Arm/Group Title | Healthy: Erenumab 1 mg SC | Healthy: Erenumab 7 mg SC | Healthy: Erenumab 21 mg SC | Healthy: Erenumab 70 mg SC | Healthy: Erenumab 140 mg SC | Healthy: Erenumab 140 mg IV | Healthy: Erenumab 210 mg SC | Migraine: Erenumab 140 mg SC |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Healthy participants received a single dose of erenumab 1 mg administered by subcutaneous injection. | Healthy participants received a single dose of erenumab 7 mg administered by subcutaneous injection. | Healthy participants received a single dose of erenumab 21 mg administered by subcutaneous injection. | Healthy participants received a single dose of erenumab 70 mg administered by subcutaneous injection. | Healthy participants received a single dose of erenumab 140 mg administered by subcutaneous injection. | Healthy participants received a single dose of erenumab 140 mg administered by intravenous injection. | Healthy participants received a single dose of erenumab 210 mg administered by subcutaneous injection. | Participants with migraine received a single dose of erenumab 140 mg administered by subcutaneous injection. |
| Measure Participants | 3 | 3 | 6 | 6 | 6 | 6 | 6 | 6 |
| Mean (Standard Deviation) [days*µg/mL] |
0.0851
(0.0169)
|
4.01
(2.07)
|
23.5
(15.5)
|
171
(60.9)
|
332
(57.9)
|
614
(112)
|
652
(221)
|
367
(102)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Healthy: Erenumab 70 mg SC, Healthy: Erenumab 210 mg SC |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5481 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Ratio of Geometric Means |
| Estimated Value | 1.1 | |
| Confidence Interval |
(2-Sided) 90% 0.9 to 1.4 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Migraine participants / Healthy participants | |
| Title | Area Under the Concentration-time Curve From Time Zero to Infinity (AUCinf) of Erenumab |
|---|---|
| Description | |
| Time Frame | Predose to 155 days postdose |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received erenumab |
| Arm/Group Title | Healthy: Erenumab 1 mg SC | Healthy: Erenumab 7 mg SC | Healthy: Erenumab 21 mg SC | Healthy: Erenumab 70 mg SC | Healthy: Erenumab 140 mg SC | Healthy: Erenumab 140 mg IV | Healthy: Erenumab 210 mg SC | Migraine: Erenumab 140 mg SC |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Healthy participants received a single dose of erenumab 1 mg administered by subcutaneous injection. | Healthy participants received a single dose of erenumab 7 mg administered by subcutaneous injection. | Healthy participants received a single dose of erenumab 21 mg administered by subcutaneous injection. | Healthy participants received a single dose of erenumab 70 mg administered by subcutaneous injection. | Healthy participants received a single dose of erenumab 140 mg administered by subcutaneous injection. | Healthy participants received a single dose of erenumab 140 mg administered by intravenous injection. | Healthy participants received a single dose of erenumab 210 mg administered by subcutaneous injection. | Participants with migraine received a single dose of erenumab 140 mg administered by subcutaneous injection. |
| Measure Participants | 0 | 3 | 6 | 6 | 6 | 6 | 6 | 6 |
| Mean (Standard Deviation) [days*µg/mL] |
4.13
(2.04)
|
24.5
(17.0)
|
174
(78.6)
|
333
(57.9)
|
615
(112)
|
653
(222)
|
367
(103)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Healthy: Erenumab 70 mg SC, Healthy: Erenumab 210 mg SC |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5506 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Ratio of Geometric Means |
| Estimated Value | 1.1 | |
| Confidence Interval |
(2-Sided) 90% 0.9 to 1.4 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Migraine participants / Healthy participants | |
| Title | Ratio of Post-capsaicin Dermal Blood Flow to Pre-capsaicin Dermal Blood Flow |
|---|---|
| Description | Inhibition of capsaicin-induced dermal blood flow (DBF) by erenumab was used to measure calcitonin gene-related peptide (CGRP) receptor antagonism. Capsaicin was applied at 2 sites on the volar surface of the participants' left or right forearms and a control mixture was applied to 1 site on the volar surface of either the participants' left or right forearm. Dermal blood flow was assessed by laser Doppler perfusion imaging and was done immediately before ('baseline') and 0.5 hours post-capsaicin on the surface of these 3 sites. Data reported are the least square geometric mean ratios for the post-capsaicin dermal blood flow to pre-capsaicin dermal blood flow. According to the protocol, not all cohorts had dermal blood flow measurements at all time points. |
| Time Frame | Days 4, 15, 29, 43, 64, 85, 99, 127, and end of study (defined as day 43 for the 1 mg, 7 mg and 21 mg erenumab cohorts, day 99 for the 70 mg erenumab cohort, day 127 for the 140 mg erenumab cohorts and day 155 for the 210 mg erenumab cohort). |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants for whom at least one post-dose capsaicin response measure was recorded. |
| Arm/Group Title | Healthy: Placebo | Healthy: Erenumab 1 mg SC | Healthy: Erenumab 7 mg SC | Healthy: Erenumab 21 mg SC | Healthy: Erenumab 70 mg SC | Healthy: Erenumab 140 mg SC | Healthy: Erenumab 140 mg IV | Healthy: Erenumab 210 mg SC | Migraine: Placebo | Migraine: Erenumab 140 mg SC |
|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Healthy participants received a single dose of matching placebo administered by subcutaneous (SC) or intravenous (IV) injection. | Healthy participants received a single dose of erenumab 1 mg administered by subcutaneous injection. | Healthy participants received a single dose of erenumab 7 mg administered by subcutaneous injection. | Healthy participants received a single dose of erenumab 21 mg administered by subcutaneous injection. | Healthy participants received a single dose of erenumab 70 mg administered by subcutaneous injection. | Healthy participants received a single dose of erenumab 140 mg administered by subcutaneous injection. | Healthy participants received a single dose of erenumab 140 mg administered by intravenous injection. | Healthy participants received a single dose of erenumab 210 mg administered by subcutaneous injection. | Participants with migraine received a single dose of placebo administered by subcutaneous injection. | Participants with migraine received a single dose of erenumab 140 mg administered by subcutaneous injection. |
| Measure Participants | 12 | 3 | 3 | 6 | 6 | 6 | 6 | 6 | 6 | 6 |
| Day 4 |
8.6
(1.15)
|
9.9
(1.32)
|
5.6
(1.32)
|
2.9
(1.22)
|
1.7
(1.22)
|
1.4
(1.22)
|
1.4
(1.22)
|
1.9
(1.22)
|
11.9
(1.20)
|
2.0
(1.20)
|
| Day 15 |
8.6
(1.15)
|
9.0
(1.32)
|
3.6
(1.32)
|
1.4
(1.22)
|
2.2
(1.22)
|
1.3
(1.22)
|
1.7
(1.22)
|
2.2
(1.22)
|
12.4
(1.20)
|
2.1
(1.20)
|
| Day 29 |
7.2
(1.15)
|
8.3
(1.32)
|
10.8
(1.32)
|
3.0
(1.22)
|
2.0
(1.22)
|
1.1
(1.22)
|
1.6
(1.22)
|
1.9
(1.22)
|
13.1
(1.20)
|
1.8
(1.20)
|
| Day 43 |
8.4
(1.19)
|
1.2
(1.26)
|
1.8
(1.22)
|
2.0
(1.22)
|
2.1
(1.22)
|
12.0
(1.20)
|
2.1
(1.20)
|
|||
| Day 64 |
8.3
(1.21)
|
1.5
(1.22)
|
2.2
(1.22)
|
2.3
(1.22)
|
12.4
(1.20)
|
2.0
(1.20)
|
||||
| Day 85 |
10.7
(1.21)
|
4.6
(1.26)
|
3.9
(1.22)
|
2.6
(1.22)
|
12.0
(1.20)
|
7.4
(1.20)
|
||||
| Day 99 |
7.6
(1.21)
|
5.1
(1.22)
|
5.9
(1.22)
|
4.3
(1.22)
|
12.2
(1.20)
|
10.2
(1.20)
|
||||
| Day 127 |
11.4
(1.36)
|
9.1
(1.22)
|
||||||||
| End of study |
9.6
(1.15)
|
8.2
(1.32)
|
10.5
(1.32)
|
9.0
(1.22)
|
3.6
(1.22)
|
7.6
(1.22)
|
8.3
(1.22)
|
8.8
(1.22)
|
12.0
(1.20)
|
9.8
(1.20)
|
Adverse Events
| Time Frame | From the initial dose of study drug up to 155 days. | |||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold. | |||||||||||||||||||
| Arm/Group Title | Healthy: Placebo | Healthy: Erenumab 1 mg SC | Healthy: Erenumab 7 mg SC | Healthy: Erenumab 21 mg SC | Healthy: Erenumab 70 mg SC | Healthy: Erenumab 140 mg SC | Healthy: Erenumab 140 mg IV | Healthy: Erenumab 210 mg SC | Migraine: Placebo | Migraine: Erenumab 140 mg SC | ||||||||||
| Arm/Group Description | Healthy participants received a single dose of matching placebo administered by subcutaneous (SC) or intravenous (IV) injection. | Healthy participants received a single dose of erenumab 1 mg administered by subcutaneous injection. | Healthy participants received a single dose of erenumab 7 mg administered by subcutaneous injection. | Healthy participants received a single dose of erenumab 21 mg administered by subcutaneous injection. | Healthy participants received a single dose of erenumab 70 mg administered by subcutaneous injection. | Healthy participants received a single dose of erenumab 140 mg administered by subcutaneous injection. | Healthy participants received a single dose of erenumab 140 mg administered by intravenous injection. | Healthy participants received a single dose of erenumab 210 mg administered by subcutaneous injection. | Participants with migraine received a single dose of placebo administered by subcutaneous injection. | Participants with migraine received a single dose of erenumab 140 mg administered by subcutaneous injection. | ||||||||||
All Cause Mortality |
||||||||||||||||||||
| Healthy: Placebo | Healthy: Erenumab 1 mg SC | Healthy: Erenumab 7 mg SC | Healthy: Erenumab 21 mg SC | Healthy: Erenumab 70 mg SC | Healthy: Erenumab 140 mg SC | Healthy: Erenumab 140 mg IV | Healthy: Erenumab 210 mg SC | Migraine: Placebo | Migraine: Erenumab 140 mg SC | |||||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | ||||||||||
Serious Adverse Events |
||||||||||||||||||||
| Healthy: Placebo | Healthy: Erenumab 1 mg SC | Healthy: Erenumab 7 mg SC | Healthy: Erenumab 21 mg SC | Healthy: Erenumab 70 mg SC | Healthy: Erenumab 140 mg SC | Healthy: Erenumab 140 mg IV | Healthy: Erenumab 210 mg SC | Migraine: Placebo | Migraine: Erenumab 140 mg SC | |||||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/12 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | ||||||||||
Other (Not Including Serious) Adverse Events |
||||||||||||||||||||
| Healthy: Placebo | Healthy: Erenumab 1 mg SC | Healthy: Erenumab 7 mg SC | Healthy: Erenumab 21 mg SC | Healthy: Erenumab 70 mg SC | Healthy: Erenumab 140 mg SC | Healthy: Erenumab 140 mg IV | Healthy: Erenumab 210 mg SC | Migraine: Placebo | Migraine: Erenumab 140 mg SC | |||||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 10/12 (83.3%) | 2/3 (66.7%) | 1/3 (33.3%) | 6/6 (100%) | 5/6 (83.3%) | 5/6 (83.3%) | 5/6 (83.3%) | 6/6 (100%) | 5/6 (83.3%) | 6/6 (100%) | ||||||||||
| Blood and lymphatic system disorders | ||||||||||||||||||||
| Eosinophilia | 1/12 (8.3%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | ||||||||||
| Neutropenia | 0/12 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | ||||||||||
| Ear and labyrinth disorders | ||||||||||||||||||||
| Ear haemorrhage | 0/12 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | ||||||||||
| Ear pain | 0/12 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | ||||||||||
| Eye disorders | ||||||||||||||||||||
| Conjunctivitis | 0/12 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 1/6 (16.7%) | 2/6 (33.3%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | ||||||||||
| Gastrointestinal disorders | ||||||||||||||||||||
| Abdominal pain | 0/12 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 1/6 (16.7%) | ||||||||||
| Abdominal pain upper | 0/12 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | ||||||||||
| Aphthous stomatitis | 0/12 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 1/6 (16.7%) | 0/6 (0%) | ||||||||||
| Diarrhoea | 1/12 (8.3%) | 1/3 (33.3%) | 0/3 (0%) | 0/6 (0%) | 1/6 (16.7%) | 1/6 (16.7%) | 0/6 (0%) | 1/6 (16.7%) | 2/6 (33.3%) | 0/6 (0%) | ||||||||||
| Dry mouth | 0/12 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | ||||||||||
| Dyspepsia | 0/12 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | ||||||||||
| Gastrooesophageal reflux disease | 0/12 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | ||||||||||
| Nausea | 1/12 (8.3%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | ||||||||||
| Toothache | 0/12 (0%) | 0/3 (0%) | 0/3 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | ||||||||||
| Vomiting | 0/12 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | ||||||||||
| General disorders | ||||||||||||||||||||
| Asthenia | 0/12 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | ||||||||||
| Fatigue | 0/12 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | ||||||||||
| Influenza like illness | 0/12 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 1/6 (16.7%) | 2/6 (33.3%) | ||||||||||
| Injection site erythema | 0/12 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | ||||||||||
| Injection site haemorrhage | 2/12 (16.7%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | ||||||||||
| Malaise | 1/12 (8.3%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | ||||||||||
| Pyrexia | 0/12 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | ||||||||||
| Infections and infestations | ||||||||||||||||||||
| Gastroenteritis | 1/12 (8.3%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 1/6 (16.7%) | 0/6 (0%) | ||||||||||
| Genital infection fungal | 1/12 (8.3%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | ||||||||||
| Nasopharyngitis | 1/12 (8.3%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 2/6 (33.3%) | 2/6 (33.3%) | 1/6 (16.7%) | 3/6 (50%) | 3/6 (50%) | ||||||||||
| Oral herpes | 1/12 (8.3%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | ||||||||||
| Rhinitis | 0/12 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | ||||||||||
| Upper respiratory tract infection | 1/12 (8.3%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 1/6 (16.7%) | 0/6 (0%) | ||||||||||
| Viral infection | 0/12 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | ||||||||||
| Injury, poisoning and procedural complications | ||||||||||||||||||||
| Contusion | 1/12 (8.3%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | ||||||||||
| Fall | 1/12 (8.3%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | ||||||||||
| Limb injury | 0/12 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | ||||||||||
| Thermal burn | 0/12 (0%) | 0/3 (0%) | 0/3 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | ||||||||||
| Investigations | ||||||||||||||||||||
| Alanine aminotransferase increased | 0/12 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | ||||||||||
| Aspartate aminotransferase increased | 0/12 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | ||||||||||
| Electrocardiogram PR prolongation | 0/12 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | ||||||||||
| Musculoskeletal and connective tissue disorders | ||||||||||||||||||||
| Arthralgia | 1/12 (8.3%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 2/6 (33.3%) | ||||||||||
| Back pain | 0/12 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | ||||||||||
| Joint stiffness | 1/12 (8.3%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | ||||||||||
| Joint swelling | 0/12 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | ||||||||||
| Muscular weakness | 0/12 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | ||||||||||
| Tendonitis | 0/12 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | ||||||||||
| Nervous system disorders | ||||||||||||||||||||
| Dizziness | 0/12 (0%) | 0/3 (0%) | 0/3 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | ||||||||||
| Dizziness postural | 0/12 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | ||||||||||
| Dysaesthesia | 0/12 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | ||||||||||
| Headache | 3/12 (25%) | 0/3 (0%) | 0/3 (0%) | 1/6 (16.7%) | 1/6 (16.7%) | 1/6 (16.7%) | 2/6 (33.3%) | 4/6 (66.7%) | 0/6 (0%) | 0/6 (0%) | ||||||||||
| Hypoaesthesia | 0/12 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 2/6 (33.3%) | 0/6 (0%) | 0/6 (0%) | ||||||||||
| Paraesthesia | 0/12 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | ||||||||||
| Renal and urinary disorders | ||||||||||||||||||||
| Dysuria | 0/12 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | ||||||||||
| Haematuria | 0/12 (0%) | 0/3 (0%) | 0/3 (0%) | 2/6 (33.3%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | ||||||||||
| Leukocyturia | 0/12 (0%) | 0/3 (0%) | 0/3 (0%) | 1/6 (16.7%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 1/6 (16.7%) | ||||||||||
| Pyuria | 0/12 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 2/6 (33.3%) | 0/6 (0%) | ||||||||||
| Reproductive system and breast disorders | ||||||||||||||||||||
| Breast cyst | 0/12 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | ||||||||||
| Dysmenorrhoea | 0/12 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | ||||||||||
| Respiratory, thoracic and mediastinal disorders | ||||||||||||||||||||
| Cough | 0/12 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | ||||||||||
| Epistaxis | 0/12 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 2/6 (33.3%) | 0/6 (0%) | ||||||||||
| Oropharyngeal pain | 2/12 (16.7%) | 1/3 (33.3%) | 0/3 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | ||||||||||
| Pharyngeal erythema | 0/12 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | ||||||||||
| Pharyngeal oedema | 0/12 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | ||||||||||
| Rhinitis allergic | 1/12 (8.3%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | ||||||||||
| Rhinorrhoea | 0/12 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | ||||||||||
| Skin and subcutaneous tissue disorders | ||||||||||||||||||||
| Dermatitis allergic | 0/12 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | ||||||||||
| Ecchymosis | 0/12 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | ||||||||||
| Pruritus generalised | 1/12 (8.3%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | ||||||||||
| Rash papular | 0/12 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | ||||||||||
| Swelling face | 0/12 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | ||||||||||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
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.
Results Point of Contact
| Name/Title | Study Director |
|---|---|
| Organization | Amgen Inc. |
| Phone | 866-572-6436 |
Responsible Party:
Amgen
ClinicalTrials.gov Identifier:
NCT01688739
Other Study ID Numbers:
- 20101267
- 2011-005600-15
First Posted:
Sep 20, 2012
Last Update Posted:
Jan 18, 2019
Last Verified:
Aug 1, 2018