Trial Outcomes & Findings for Study to Evaluate the Efficacy and Safety of AMG 301 in Migraine Prevention (NCT NCT03238781)
NCT ID: NCT03238781
Last Updated: 2020-02-07
Results Overview
A migraine day is any calendar day from the eDiary in which the participant experienced a migraine headache. A migraine headache is a headache with or without aura, lasting for \>= 4 hours, and meeting \>=1 of the criteria: 1. \>= 2 pain features (unilateral, throbbing, moderate to severe, exacerbated with exercise/physical activity) 2. \>= 1 symptoms (nausea and/or vomiting, photophobia and phonophobia) If the participant took a migraine-specific medication during aura or to treat headache, it was counted as a migraine day. Days without eDiary data in each monthly interval are handled by proration. Negative change from baseline values indicated improvement (i.e. fewer migraine days after treatment as compared to baseline).
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
343 participants
Primary outcome timeframe
Baseline Day -28 to Day -1; Weeks 9-12
Results posted on
2020-02-07
Participant Flow
A total of 510 subjects were screened.
Participants were randomized 4:3:3 to placebo, AMG 301 210 mg Q4W, or AMG 301 420 mg Q2W, respectively. The randomization was stratified by * chronic migraine versus episodic migraine and * North America versus Rest of World.
Participant milestones
| Measure |
Placebo
Participants randomized to Placebo were administered 6 subcutaneous (SC) injections on day 1 and weeks 2, 4, 6, 8 and 10 during the 12 week double-blind treatment period.
|
AMG 301 210 mg Q4W
Participants randomized to AMG 301 210 mg every fourth week (Q4W) received a total of 3 AMG 301 subcutaneous (SC) injections (70 mg/mL in each injection) plus 3 matching placebo injections on day 1 and weeks 4 and 8. Participants also received 6 SC placebo injections on weeks 2, 6, and 10 during the 12 week double-blind treatment period.
|
AMG 301 420 mg Q2W
Participants randomized to AMG 301 420 mg every second week (Q2W) received a total of 6 AMG 301 subcutaneous (SC) injections (70 mg/mL in each injection) on day 1 and weeks 2, 4, 6, 8, and 10 during the 12 week double-blind treatment period.
|
|---|---|---|---|
|
Overall Study
STARTED
|
137
|
104
|
102
|
|
Overall Study
COMPLETED
|
111
|
87
|
82
|
|
Overall Study
NOT COMPLETED
|
26
|
17
|
20
|
Reasons for withdrawal
| Measure |
Placebo
Participants randomized to Placebo were administered 6 subcutaneous (SC) injections on day 1 and weeks 2, 4, 6, 8 and 10 during the 12 week double-blind treatment period.
|
AMG 301 210 mg Q4W
Participants randomized to AMG 301 210 mg every fourth week (Q4W) received a total of 3 AMG 301 subcutaneous (SC) injections (70 mg/mL in each injection) plus 3 matching placebo injections on day 1 and weeks 4 and 8. Participants also received 6 SC placebo injections on weeks 2, 6, and 10 during the 12 week double-blind treatment period.
|
AMG 301 420 mg Q2W
Participants randomized to AMG 301 420 mg every second week (Q2W) received a total of 6 AMG 301 subcutaneous (SC) injections (70 mg/mL in each injection) on day 1 and weeks 2, 4, 6, 8, and 10 during the 12 week double-blind treatment period.
|
|---|---|---|---|
|
Overall Study
Adverse Event
|
1
|
1
|
2
|
|
Overall Study
Lost to Follow-up
|
2
|
1
|
2
|
|
Overall Study
Withdrawal by Subject
|
23
|
14
|
16
|
|
Overall Study
Decision by sponsor
|
0
|
1
|
0
|
Baseline Characteristics
Study to Evaluate the Efficacy and Safety of AMG 301 in Migraine Prevention
Baseline characteristics by cohort
| Measure |
Placebo
n=137 Participants
Participants randomized to Placebo were administered 6 subcutaneous (SC) injections on day 1 and weeks 2, 4, 6, 8 and 10 during the 12 week double-blind treatment period.
|
AMG 301 210 mg Q4W
n=104 Participants
Participants randomized to AMG 301 210 mg every fourth week (Q4W) received a total of 3 AMG 301 subcutaneous (SC) injections (70 mg/mL in each injection) plus 3 matching placebo injections on day 1 and weeks 4 and 8. Participants also received 6 SC placebo injections on weeks 2, 6, and 10 during the 12 week double-blind treatment period.
|
AMG 301 420 mg Q2W
n=102 Participants
Participants randomized to AMG 301 420 mg every second week (Q2W) received a total of 6 AMG 301 subcutaneous (SC) injections (70 mg/mL in each injection) on day 1 and weeks 2, 4, 6, 8, and 10 during the 12 week double-blind treatment period.
|
Total
n=343 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
41.8 years
STANDARD_DEVIATION 9.9 • n=5 Participants
|
42.3 years
STANDARD_DEVIATION 9.7 • n=7 Participants
|
42.5 years
STANDARD_DEVIATION 9.4 • n=5 Participants
|
42.2 years
STANDARD_DEVIATION 9.7 • n=4 Participants
|
|
Sex: Female, Male
Female
|
117 Participants
n=5 Participants
|
94 Participants
n=7 Participants
|
90 Participants
n=5 Participants
|
301 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
20 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
12 Participants
n=5 Participants
|
42 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
6 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
15 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
131 Participants
n=5 Participants
|
98 Participants
n=7 Participants
|
99 Participants
n=5 Participants
|
328 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Black or African American
|
6 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
12 Participants
n=4 Participants
|
|
Race (NIH/OMB)
White
|
129 Participants
n=5 Participants
|
100 Participants
n=7 Participants
|
96 Participants
n=5 Participants
|
325 Participants
n=4 Participants
|
|
Race (NIH/OMB)
More than one race
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
|
Weight
|
71.8 kg
STANDARD_DEVIATION 15.0 • n=5 Participants
|
73.8 kg
STANDARD_DEVIATION 17.2 • n=7 Participants
|
72.1 kg
STANDARD_DEVIATION 14.9 • n=5 Participants
|
72.5 kg
STANDARD_DEVIATION 15.7 • n=4 Participants
|
|
Height
|
168.27 cm
STANDARD_DEVIATION 7.82 • n=5 Participants
|
167.05 cm
STANDARD_DEVIATION 8.56 • n=7 Participants
|
167.55 cm
STANDARD_DEVIATION 7.72 • n=5 Participants
|
167.69 cm
STANDARD_DEVIATION 8.01 • n=4 Participants
|
|
Body Mass Index
|
25.29 kg/m^2
STANDARD_DEVIATION 4.66 • n=5 Participants
|
26.37 kg/m^2
STANDARD_DEVIATION 5.45 • n=7 Participants
|
25.64 kg/m^2
STANDARD_DEVIATION 4.78 • n=5 Participants
|
25.72 kg/m^2
STANDARD_DEVIATION 4.95 • n=4 Participants
|
|
Monthly Migraine Days
|
12.18 monthly migraine days
STANDARD_DEVIATION 5.14 • n=5 Participants
|
12.47 monthly migraine days
STANDARD_DEVIATION 4.78 • n=7 Participants
|
12.14 monthly migraine days
STANDARD_DEVIATION 5.32 • n=5 Participants
|
12.26 monthly migraine days
STANDARD_DEVIATION 5.08 • n=4 Participants
|
|
Monthly Headache Days
|
13.45 days
STANDARD_DEVIATION 5.27 • n=5 Participants
|
13.85 days
STANDARD_DEVIATION 4.90 • n=7 Participants
|
13.09 days
STANDARD_DEVIATION 5.24 • n=5 Participants
|
13.46 days
STANDARD_DEVIATION 5.15 • n=4 Participants
|
|
Targeted Neurological Disease Diagnosis
Migraine with aura
|
40 participants with diagnosis
n=5 Participants
|
32 participants with diagnosis
n=7 Participants
|
43 participants with diagnosis
n=5 Participants
|
115 participants with diagnosis
n=4 Participants
|
|
Targeted Neurological Disease Diagnosis
Migraine without aura
|
120 participants with diagnosis
n=5 Participants
|
92 participants with diagnosis
n=7 Participants
|
87 participants with diagnosis
n=5 Participants
|
299 participants with diagnosis
n=4 Participants
|
|
Targeted Neurological Disease Diagnosis
Depression
|
24 participants with diagnosis
n=5 Participants
|
25 participants with diagnosis
n=7 Participants
|
18 participants with diagnosis
n=5 Participants
|
67 participants with diagnosis
n=4 Participants
|
|
Targeted Neurological Disease Diagnosis
Anxiety
|
21 participants with diagnosis
n=5 Participants
|
15 participants with diagnosis
n=7 Participants
|
16 participants with diagnosis
n=5 Participants
|
52 participants with diagnosis
n=4 Participants
|
|
Reported Reasons for Prior Migraine Prophylactic Medication Failure
Lack of efficacy
|
110 participants reporting the reason
n=5 Participants
|
88 participants reporting the reason
n=7 Participants
|
77 participants reporting the reason
n=5 Participants
|
275 participants reporting the reason
n=4 Participants
|
|
Reported Reasons for Prior Migraine Prophylactic Medication Failure
Intolerance
|
62 participants reporting the reason
n=5 Participants
|
47 participants reporting the reason
n=7 Participants
|
52 participants reporting the reason
n=5 Participants
|
161 participants reporting the reason
n=4 Participants
|
|
Baseline Migraine Type
Chronic migraine
|
44 Participants
n=5 Participants
|
39 Participants
n=7 Participants
|
36 Participants
n=5 Participants
|
119 Participants
n=4 Participants
|
|
Baseline Migraine Type
Episodic migraine
|
93 Participants
n=5 Participants
|
65 Participants
n=7 Participants
|
66 Participants
n=5 Participants
|
224 Participants
n=4 Participants
|
PRIMARY outcome
Timeframe: Baseline Day -28 to Day -1; Weeks 9-12Population: Efficacy Analysis set consisting of participants who were randomized, received \>=1 dose of investigational product, and have \>=1 postbaseline monthly eDiary measurement. Participants were analyzed according to their randomized treatment group, regardless of treatment received. Participants with both baseline and week 9-12 values are included.
A migraine day is any calendar day from the eDiary in which the participant experienced a migraine headache. A migraine headache is a headache with or without aura, lasting for \>= 4 hours, and meeting \>=1 of the criteria: 1. \>= 2 pain features (unilateral, throbbing, moderate to severe, exacerbated with exercise/physical activity) 2. \>= 1 symptoms (nausea and/or vomiting, photophobia and phonophobia) If the participant took a migraine-specific medication during aura or to treat headache, it was counted as a migraine day. Days without eDiary data in each monthly interval are handled by proration. Negative change from baseline values indicated improvement (i.e. fewer migraine days after treatment as compared to baseline).
Outcome measures
| Measure |
Placebo
n=119 Participants
Participants randomized to Placebo were administered 6 subcutaneous (SC) injections on day 1 and weeks 2, 4, 6, 8 and 10 during the 12 week double-blind treatment period.
|
AMG 301 210 mg Q4W
n=93 Participants
Participants randomized to AMG 301 210 mg every fourth week (Q4W) received a total of 3 AMG 301 subcutaneous (SC) injections (70 mg/mL in each injection) plus 3 matching placebo injections on day 1 and weeks 4 and 8. Participants also received 6 SC placebo injections on weeks 2, 6, and 10 during the 12 week double-blind treatment period.
|
AMG 301 420 mg Q2W
n=85 Participants
Participants randomized to AMG 301 420 mg every second week (Q2W) received a total of 6 AMG 301 subcutaneous (SC) injections (70 mg/mL in each injection) on day 1 and weeks 2, 4, 6, 8, and 10 during the 12 week double-blind treatment period.
|
|---|---|---|---|
|
Change From Baseline in Monthly Migraine Days to the Last 4 Weeks of the 12 Week Double-Blind Treatment Period
|
-2.45 days
Standard Error 0.40
|
-2.20 days
Standard Error 0.45
|
-2.19 days
Standard Error 0.46
|
SECONDARY outcome
Timeframe: Baseline Day -28 to Day -1; Weeks 9-12Population: Efficacy Analysis set consisting of participants who were randomized, received \>=1 dose of investigational product, and have \>=1 postbaseline monthly eDiary measurement. Participants were analyzed according to their randomized treatment group, regardless of treatment received. Participants with both baseline and week 9-12 values are included.
Responders are participants who had at least a 50% reduction from baseline in monthly migraine days during the last 4 weeks of treatment in the 12-week double blind period.
Outcome measures
| Measure |
Placebo
n=119 Participants
Participants randomized to Placebo were administered 6 subcutaneous (SC) injections on day 1 and weeks 2, 4, 6, 8 and 10 during the 12 week double-blind treatment period.
|
AMG 301 210 mg Q4W
n=93 Participants
Participants randomized to AMG 301 210 mg every fourth week (Q4W) received a total of 3 AMG 301 subcutaneous (SC) injections (70 mg/mL in each injection) plus 3 matching placebo injections on day 1 and weeks 4 and 8. Participants also received 6 SC placebo injections on weeks 2, 6, and 10 during the 12 week double-blind treatment period.
|
AMG 301 420 mg Q2W
n=85 Participants
Participants randomized to AMG 301 420 mg every second week (Q2W) received a total of 6 AMG 301 subcutaneous (SC) injections (70 mg/mL in each injection) on day 1 and weeks 2, 4, 6, 8, and 10 during the 12 week double-blind treatment period.
|
|---|---|---|---|
|
Percentage of Participants Who Responded, Defined as At Least a 50% Reduction From the Baseline Period in Monthly Migraine Days in the Last 4 Weeks of the 12-Week Double-Blind Treatment Period
|
22.7 percentage of participants
|
19.4 percentage of participants
|
18.8 percentage of participants
|
SECONDARY outcome
Timeframe: Baseline Day -28 to Day -1; Weeks 9-12Population: Efficacy Analysis set consisting of participants who were randomized, received \>=1 dose of investigational product, and have \>=1 postbaseline monthly eDiary measurement. Participants were analyzed according to their randomized treatment group, regardless of treatment received. Participants with both baseline and week 9-12 values are included.
Number of days on which acute headache medications (triptans and ergotamine-derivatives, alone or in combination) are used as recorded in eDiary. Monthly acute headache medication treatment days at baseline are the number of acute headache medication treatment days in the baseline period. Days without eDiary data are handled by proration. Negative change from baseline values indicate improvement (i.e. fewer days requiring acute migraine-specific medications after treatment as compared to baseline).
Outcome measures
| Measure |
Placebo
n=103 Participants
Participants randomized to Placebo were administered 6 subcutaneous (SC) injections on day 1 and weeks 2, 4, 6, 8 and 10 during the 12 week double-blind treatment period.
|
AMG 301 210 mg Q4W
n=84 Participants
Participants randomized to AMG 301 210 mg every fourth week (Q4W) received a total of 3 AMG 301 subcutaneous (SC) injections (70 mg/mL in each injection) plus 3 matching placebo injections on day 1 and weeks 4 and 8. Participants also received 6 SC placebo injections on weeks 2, 6, and 10 during the 12 week double-blind treatment period.
|
AMG 301 420 mg Q2W
n=76 Participants
Participants randomized to AMG 301 420 mg every second week (Q2W) received a total of 6 AMG 301 subcutaneous (SC) injections (70 mg/mL in each injection) on day 1 and weeks 2, 4, 6, 8, and 10 during the 12 week double-blind treatment period.
|
|---|---|---|---|
|
Change From Baseline Period in Monthly Acute Migraine-Specific Medication Days in the Last 4 Weeks of the 12-Week Double-Blind Treatment Period
|
-1.25 days
Standard Error 0.29
|
-1.28 days
Standard Error 0.33
|
-1.34 days
Standard Error 0.34
|
SECONDARY outcome
Timeframe: Baseline Day -28 to Day -1; Weeks 9-12Population: Efficacy Analysis set consisting of participants who were randomized, received \>=1 dose of investigational product, and have \>=1 postbaseline monthly eDiary measurement. Participants were analyzed according to their randomized treatment group, regardless of treatment received. Participants with both baseline and week 9-12 values are included.
Participants complete the MPFID every day during baseline (Days -28 to Day -1) and the 12-week Double Blind Treatment Period. The MPFID has 2 domains, Impact on Everyday Activities (7 items) and Physical Impairment (5 items), and 1 stand-alone global question that provides an assessment of the overall impact of migraine on participants' everyday activities. The recall period for each item is the past 24 hours. The Physical Impairment Domain Score is reported here. A participant's response to the difficulty of the 5 physical impairment items is measured using a 5-point scale, with difficulty measurements ranging from 1 to 5. The sum was rescaled to a 0 to 100 scale, with 0=no difficulty and 100=unable to do (maximum burden). Negative change from baseline values indicate improvement in migraine impact.
Outcome measures
| Measure |
Placebo
n=119 Participants
Participants randomized to Placebo were administered 6 subcutaneous (SC) injections on day 1 and weeks 2, 4, 6, 8 and 10 during the 12 week double-blind treatment period.
|
AMG 301 210 mg Q4W
n=93 Participants
Participants randomized to AMG 301 210 mg every fourth week (Q4W) received a total of 3 AMG 301 subcutaneous (SC) injections (70 mg/mL in each injection) plus 3 matching placebo injections on day 1 and weeks 4 and 8. Participants also received 6 SC placebo injections on weeks 2, 6, and 10 during the 12 week double-blind treatment period.
|
AMG 301 420 mg Q2W
n=85 Participants
Participants randomized to AMG 301 420 mg every second week (Q2W) received a total of 6 AMG 301 subcutaneous (SC) injections (70 mg/mL in each injection) on day 1 and weeks 2, 4, 6, 8, and 10 during the 12 week double-blind treatment period.
|
|---|---|---|---|
|
Change From Baseline in Mean Physical Impairment Domain Scores as Measured by the Migraine Physical Function Impact Diary (MPFID) Over the Last 4 Weeks of the 12-Week Double-Blind Treatment Period
|
-2.44 units on a scale
Standard Error 0.78
|
-2.72 units on a scale
Standard Error 0.89
|
-2.13 units on a scale
Standard Error 0.91
|
SECONDARY outcome
Timeframe: Baseline Day -28 to Day -1; Weeks 9-12Population: Efficacy Analysis set consisting of participants who were randomized, received \>=1 dose of investigational product, and have \>=1 postbaseline monthly eDiary measurement. Participants were analyzed according to their randomized treatment group, regardless of treatment received. Participants with both baseline and week 9-12 values are included.
Participants complete the MPFID every day during baseline (Days -28 to Day -1) and the 12-week Double Blind Treatment Period. The MPFID has 2 domains, Impact on Everyday Activities (7 items) and Physical Impairment (5 items), and 1 stand-alone global question that provides an assessment of the overall impact of migraine on participants' everyday activities. The recall period for each item is the past 24 hours. The Impact on Everyday Activities Domain Score is reported here. A participant's response to the Impact on Everyday Activities 7 items is measured using a 5-point scale, with difficulty measurements ranging from 1 to 5. The sum was rescaled to a 0 to 100 scale, with 0=no difficulty and 100=unable to do (maximum burden). Negative change from baseline values indicate improvement in migraine impact.
Outcome measures
| Measure |
Placebo
n=119 Participants
Participants randomized to Placebo were administered 6 subcutaneous (SC) injections on day 1 and weeks 2, 4, 6, 8 and 10 during the 12 week double-blind treatment period.
|
AMG 301 210 mg Q4W
n=93 Participants
Participants randomized to AMG 301 210 mg every fourth week (Q4W) received a total of 3 AMG 301 subcutaneous (SC) injections (70 mg/mL in each injection) plus 3 matching placebo injections on day 1 and weeks 4 and 8. Participants also received 6 SC placebo injections on weeks 2, 6, and 10 during the 12 week double-blind treatment period.
|
AMG 301 420 mg Q2W
n=86 Participants
Participants randomized to AMG 301 420 mg every second week (Q2W) received a total of 6 AMG 301 subcutaneous (SC) injections (70 mg/mL in each injection) on day 1 and weeks 2, 4, 6, 8, and 10 during the 12 week double-blind treatment period.
|
|---|---|---|---|
|
Change From Baseline in Mean Impact on Everyday Activity Domain Scores as Measured by the Migraine Physical Function Impact Diary (MPFID) Over the Last 4 Weeks of the 12-Week Double-Blind Treatment Period
|
-3.42 units on a scale
Standard Error 0.79
|
-4.28 units on a scale
Standard Error 0.89
|
-2.86 units on a scale
Standard Error 0.92
|
SECONDARY outcome
Timeframe: Day 1 up to Week 30 (12 weeks of double-blind treatment plus 18 weeks follow-up after last dose of investigational product)Population: The Safety Analysis Set (SAS) consists of all enrolled participants who received \>= 1 dose of investigational product (IP). If a participant received the incorrect dose during the entire double-blind treatment period (DBTP), the participant was analyzed according to treatment received.
Adverse events (AEs) were graded according to the Common Terminology Criteria for Adverse Events (CTCAE), version 4, where: Grade 1 = Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated; Grade 2 = Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living (ADL); Grade 3 = Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL; Grade 4 = Life-threatening consequences; urgent intervention indicated Grade 5 = Death related to AE.
Outcome measures
| Measure |
Placebo
n=137 Participants
Participants randomized to Placebo were administered 6 subcutaneous (SC) injections on day 1 and weeks 2, 4, 6, 8 and 10 during the 12 week double-blind treatment period.
|
AMG 301 210 mg Q4W
n=104 Participants
Participants randomized to AMG 301 210 mg every fourth week (Q4W) received a total of 3 AMG 301 subcutaneous (SC) injections (70 mg/mL in each injection) plus 3 matching placebo injections on day 1 and weeks 4 and 8. Participants also received 6 SC placebo injections on weeks 2, 6, and 10 during the 12 week double-blind treatment period.
|
AMG 301 420 mg Q2W
n=102 Participants
Participants randomized to AMG 301 420 mg every second week (Q2W) received a total of 6 AMG 301 subcutaneous (SC) injections (70 mg/mL in each injection) on day 1 and weeks 2, 4, 6, 8, and 10 during the 12 week double-blind treatment period.
|
|---|---|---|---|
|
Participants With Treatment-Emergent Adverse Events (TEAEs)
>= 1 TEAE
|
90 Participants
|
71 Participants
|
65 Participants
|
|
Participants With Treatment-Emergent Adverse Events (TEAEs)
Severity grade >= 2
|
41 Participants
|
43 Participants
|
39 Participants
|
|
Participants With Treatment-Emergent Adverse Events (TEAEs)
Severity grade >= 3
|
9 Participants
|
5 Participants
|
8 Participants
|
|
Participants With Treatment-Emergent Adverse Events (TEAEs)
Severity grade >= 4
|
0 Participants
|
1 Participants
|
0 Participants
|
|
Participants With Treatment-Emergent Adverse Events (TEAEs)
Serious TEAE
|
3 Participants
|
1 Participants
|
2 Participants
|
|
Participants With Treatment-Emergent Adverse Events (TEAEs)
TEAE leading to discontinuation of IP
|
3 Participants
|
2 Participants
|
5 Participants
|
|
Participants With Treatment-Emergent Adverse Events (TEAEs)
Fatal TEAE
|
0 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Baseline: Day 1 On study: Weeks 4, 6, 12, 20, 28Population: Safety analysis set
Hy's law predicts potential for drug-related hepatotoxicity. Hy's Law cases have three components: * The drug causes hepatocellular injury, generally defined as an elevated alanine aminotransferase (ALT) or aspartate aminotransferase (AST) by 3-fold or greater above the upper limit of normal (ULN). * Among participants showing such aminotransferase elevations, they also have elevation of their serum total bilirubin of greater than 2 times the ULN, without findings of cholestasis (defined as serum alkaline phosphatase activity less than 2 times the upper limit of normal). * No other reason can be found to explain the combination of increased aminotransferase and serum total bilirubin, such as viral hepatitis, alcohol abuse, ischemia, preexisting liver disease, or another drug capable of causing the observed injury.
Outcome measures
| Measure |
Placebo
n=137 Participants
Participants randomized to Placebo were administered 6 subcutaneous (SC) injections on day 1 and weeks 2, 4, 6, 8 and 10 during the 12 week double-blind treatment period.
|
AMG 301 210 mg Q4W
n=104 Participants
Participants randomized to AMG 301 210 mg every fourth week (Q4W) received a total of 3 AMG 301 subcutaneous (SC) injections (70 mg/mL in each injection) plus 3 matching placebo injections on day 1 and weeks 4 and 8. Participants also received 6 SC placebo injections on weeks 2, 6, and 10 during the 12 week double-blind treatment period.
|
AMG 301 420 mg Q2W
n=102 Participants
Participants randomized to AMG 301 420 mg every second week (Q2W) received a total of 6 AMG 301 subcutaneous (SC) injections (70 mg/mL in each injection) on day 1 and weeks 2, 4, 6, 8, and 10 during the 12 week double-blind treatment period.
|
|---|---|---|---|
|
Percentage of Participants Who Met Hy's Law Criteria at Baseline and On Study
Baseline
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
|
Percentage of Participants Who Met Hy's Law Criteria at Baseline and On Study
On study
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
SECONDARY outcome
Timeframe: Baseline: Day 1 On study: Weeks 4, 6, 12, 20, 28Population: Safety analysis set
Aminotransferase tests included alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Percentage of participants with results that were greater than 3 \* ULN for either test are reported.
Outcome measures
| Measure |
Placebo
n=137 Participants
Participants randomized to Placebo were administered 6 subcutaneous (SC) injections on day 1 and weeks 2, 4, 6, 8 and 10 during the 12 week double-blind treatment period.
|
AMG 301 210 mg Q4W
n=104 Participants
Participants randomized to AMG 301 210 mg every fourth week (Q4W) received a total of 3 AMG 301 subcutaneous (SC) injections (70 mg/mL in each injection) plus 3 matching placebo injections on day 1 and weeks 4 and 8. Participants also received 6 SC placebo injections on weeks 2, 6, and 10 during the 12 week double-blind treatment period.
|
AMG 301 420 mg Q2W
n=102 Participants
Participants randomized to AMG 301 420 mg every second week (Q2W) received a total of 6 AMG 301 subcutaneous (SC) injections (70 mg/mL in each injection) on day 1 and weeks 2, 4, 6, 8, and 10 during the 12 week double-blind treatment period.
|
|---|---|---|---|
|
Percentage of Participants With Aminotransferase Test Abnormalities > 3 Times the Upper Limit of Normal (ULN) at Baseline and On Study
Baseline
|
0 percentage of participants
|
1.9 percentage of participants
|
0 percentage of participants
|
|
Percentage of Participants With Aminotransferase Test Abnormalities > 3 Times the Upper Limit of Normal (ULN) at Baseline and On Study
On study
|
0.7 percentage of participants
|
1.9 percentage of participants
|
0 percentage of participants
|
SECONDARY outcome
Timeframe: Baseline: Day 1 On study: Weeks 4, 6, 12, 20, 28Population: Safety analysis set
Percentage of participants with total bilirubin results that were greater than 2 \* ULN are reported.
Outcome measures
| Measure |
Placebo
n=137 Participants
Participants randomized to Placebo were administered 6 subcutaneous (SC) injections on day 1 and weeks 2, 4, 6, 8 and 10 during the 12 week double-blind treatment period.
|
AMG 301 210 mg Q4W
n=104 Participants
Participants randomized to AMG 301 210 mg every fourth week (Q4W) received a total of 3 AMG 301 subcutaneous (SC) injections (70 mg/mL in each injection) plus 3 matching placebo injections on day 1 and weeks 4 and 8. Participants also received 6 SC placebo injections on weeks 2, 6, and 10 during the 12 week double-blind treatment period.
|
AMG 301 420 mg Q2W
n=102 Participants
Participants randomized to AMG 301 420 mg every second week (Q2W) received a total of 6 AMG 301 subcutaneous (SC) injections (70 mg/mL in each injection) on day 1 and weeks 2, 4, 6, 8, and 10 during the 12 week double-blind treatment period.
|
|---|---|---|---|
|
Percentage of Participants With Total Bilirubin Test Abnormalities > 2 Times the Upper Limit of Normal (ULN) at Baseline and On Study
Baseline
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
|
Percentage of Participants With Total Bilirubin Test Abnormalities > 2 Times the Upper Limit of Normal (ULN) at Baseline and On Study
On study
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
SECONDARY outcome
Timeframe: Day 1, Weeks 2, 4, 6, 8, 10, 12,16, 20, 24, 28Population: Safety analysis population of participants with data at that visit.
Participant was expected to be in a supine position (or the most recumbent position possible) in a rested and calm state for at least 5 minutes before blood pressure assessments were conducted. Blood pressure units are millimeters of mercury (mmHg).
Outcome measures
| Measure |
Placebo
n=137 Participants
Participants randomized to Placebo were administered 6 subcutaneous (SC) injections on day 1 and weeks 2, 4, 6, 8 and 10 during the 12 week double-blind treatment period.
|
AMG 301 210 mg Q4W
n=104 Participants
Participants randomized to AMG 301 210 mg every fourth week (Q4W) received a total of 3 AMG 301 subcutaneous (SC) injections (70 mg/mL in each injection) plus 3 matching placebo injections on day 1 and weeks 4 and 8. Participants also received 6 SC placebo injections on weeks 2, 6, and 10 during the 12 week double-blind treatment period.
|
AMG 301 420 mg Q2W
n=102 Participants
Participants randomized to AMG 301 420 mg every second week (Q2W) received a total of 6 AMG 301 subcutaneous (SC) injections (70 mg/mL in each injection) on day 1 and weeks 2, 4, 6, 8, and 10 during the 12 week double-blind treatment period.
|
|---|---|---|---|
|
Percentage of Participants With Systolic Blood Pressure (SBP) in Categories by Visit
Day 1 SBP <90 mmHg
|
0.9 percentage of participants
|
0.0 percentage of participants
|
0.0 percentage of participants
|
|
Percentage of Participants With Systolic Blood Pressure (SBP) in Categories by Visit
Day 1 SBP > 140 mmHg
|
5.5 percentage of participants
|
7.9 percentage of participants
|
4.9 percentage of participants
|
|
Percentage of Participants With Systolic Blood Pressure (SBP) in Categories by Visit
Day 1 SBP > 160 mmHg
|
0.9 percentage of participants
|
0.0 percentage of participants
|
0.0 percentage of participants
|
|
Percentage of Participants With Systolic Blood Pressure (SBP) in Categories by Visit
Week 2 SBP < 90 mmHg
|
1.5 percentage of participants
|
0.0 percentage of participants
|
0.0 percentage of participants
|
|
Percentage of Participants With Systolic Blood Pressure (SBP) in Categories by Visit
Week 2 SBP > 140 mmHg
|
5.2 percentage of participants
|
2.9 percentage of participants
|
8.0 percentage of participants
|
|
Percentage of Participants With Systolic Blood Pressure (SBP) in Categories by Visit
Week 2 SBP > 160 mmHg
|
0.0 percentage of participants
|
0.0 percentage of participants
|
1.0 percentage of participants
|
|
Percentage of Participants With Systolic Blood Pressure (SBP) in Categories by Visit
Week 4 SBP < 90 mmHg
|
0.0 percentage of participants
|
0.0 percentage of participants
|
0.0 percentage of participants
|
|
Percentage of Participants With Systolic Blood Pressure (SBP) in Categories by Visit
Week 4 SBP > 140 mmHg
|
3.0 percentage of participants
|
3.0 percentage of participants
|
6.2 percentage of participants
|
|
Percentage of Participants With Systolic Blood Pressure (SBP) in Categories by Visit
Week 4 SBP > 160 mmHg
|
0.7 percentage of participants
|
0.0 percentage of participants
|
1.0 percentage of participants
|
|
Percentage of Participants With Systolic Blood Pressure (SBP) in Categories by Visit
Week 6 SBP < 90 mmHg
|
0.8 percentage of participants
|
0.0 percentage of participants
|
0.0 percentage of participants
|
|
Percentage of Participants With Systolic Blood Pressure (SBP) in Categories by Visit
Week 6 SBP > 140 mmHg
|
3.1 percentage of participants
|
3.1 percentage of participants
|
3.2 percentage of participants
|
|
Percentage of Participants With Systolic Blood Pressure (SBP) in Categories by Visit
Week 6 SBP > 160 mmHg
|
0.0 percentage of participants
|
0.0 percentage of participants
|
0.0 percentage of participants
|
|
Percentage of Participants With Systolic Blood Pressure (SBP) in Categories by Visit
Week 8 SBP < 90 mmHg
|
0.0 percentage of participants
|
0.0 percentage of participants
|
0.0 percentage of participants
|
|
Percentage of Participants With Systolic Blood Pressure (SBP) in Categories by Visit
Week 8 SBP > 140 mmHg
|
2.3 percentage of participants
|
5.4 percentage of participants
|
8.5 percentage of participants
|
|
Percentage of Participants With Systolic Blood Pressure (SBP) in Categories by Visit
Week 8 SBP > 160 mmHg
|
0.0 percentage of participants
|
0.0 percentage of participants
|
1.1 percentage of participants
|
|
Percentage of Participants With Systolic Blood Pressure (SBP) in Categories by Visit
Week 10 SBP < 90 mmHg
|
0.0 percentage of participants
|
0.0 percentage of participants
|
0.0 percentage of participants
|
|
Percentage of Participants With Systolic Blood Pressure (SBP) in Categories by Visit
Week 10 SBP > 140 mmHg
|
4.1 percentage of participants
|
1.1 percentage of participants
|
2.2 percentage of participants
|
|
Percentage of Participants With Systolic Blood Pressure (SBP) in Categories by Visit
Week 10 SBP > 160 mmHg
|
0.0 percentage of participants
|
0.0 percentage of participants
|
2.2 percentage of participants
|
|
Percentage of Participants With Systolic Blood Pressure (SBP) in Categories by Visit
Week 12 SBP < 90 mmHg
|
0.8 percentage of participants
|
0.0 percentage of participants
|
0.0 percentage of participants
|
|
Percentage of Participants With Systolic Blood Pressure (SBP) in Categories by Visit
Week 12 SBP > 140 mmHg
|
6.4 percentage of participants
|
2.2 percentage of participants
|
5.7 percentage of participants
|
|
Percentage of Participants With Systolic Blood Pressure (SBP) in Categories by Visit
Week 12 SBP > 160 mmHg
|
0.0 percentage of participants
|
0.0 percentage of participants
|
0.0 percentage of participants
|
|
Percentage of Participants With Systolic Blood Pressure (SBP) in Categories by Visit
Week 16 SBP < 90 mmHg
|
0.9 percentage of participants
|
0.0 percentage of participants
|
0.0 percentage of participants
|
|
Percentage of Participants With Systolic Blood Pressure (SBP) in Categories by Visit
Week 16 SBP > 140 mmHg
|
4.4 percentage of participants
|
4.4 percentage of participants
|
5.7 percentage of participants
|
|
Percentage of Participants With Systolic Blood Pressure (SBP) in Categories by Visit
Week 16 SBP > 160 mmHg
|
0.0 percentage of participants
|
0.0 percentage of participants
|
3.4 percentage of participants
|
|
Percentage of Participants With Systolic Blood Pressure (SBP) in Categories by Visit
Week 20 SBP < 90 mmHg
|
0.9 percentage of participants
|
0.0 percentage of participants
|
0.0 percentage of participants
|
|
Percentage of Participants With Systolic Blood Pressure (SBP) in Categories by Visit
Week 20 SBP > 140 mmHg
|
4.4 percentage of participants
|
8.1 percentage of participants
|
7.3 percentage of participants
|
|
Percentage of Participants With Systolic Blood Pressure (SBP) in Categories by Visit
Week 20 SBP > 160 mmHg
|
0.9 percentage of participants
|
0.0 percentage of participants
|
0.0 percentage of participants
|
|
Percentage of Participants With Systolic Blood Pressure (SBP) in Categories by Visit
Week 24 SBP < 90 mmHg
|
0.0 percentage of participants
|
1.2 percentage of participants
|
0.0 percentage of participants
|
|
Percentage of Participants With Systolic Blood Pressure (SBP) in Categories by Visit
Week 24 SBP > 140 mmHg
|
4.7 percentage of participants
|
6.1 percentage of participants
|
8.9 percentage of participants
|
|
Percentage of Participants With Systolic Blood Pressure (SBP) in Categories by Visit
Week 24 SBP > 160 mmHg
|
0.0 percentage of participants
|
0.0 percentage of participants
|
0.0 percentage of participants
|
|
Percentage of Participants With Systolic Blood Pressure (SBP) in Categories by Visit
Week 28 SBP < 90 mmHg
|
0.9 percentage of participants
|
1.2 percentage of participants
|
0.0 percentage of participants
|
|
Percentage of Participants With Systolic Blood Pressure (SBP) in Categories by Visit
Week 28 SBP > 140 mmHg
|
8.3 percentage of participants
|
4.7 percentage of participants
|
6.3 percentage of participants
|
|
Percentage of Participants With Systolic Blood Pressure (SBP) in Categories by Visit
Week 28 SBP > 160 mmHg
|
0.9 percentage of participants
|
1.2 percentage of participants
|
0.0 percentage of participants
|
SECONDARY outcome
Timeframe: Day 1, Weeks 2, 4, 6, 8, 10, 12,16, 20, 24, 28Population: Safety analysis population of participants with data at that visit.
Participant was expected to be in a supine position (or the most recumbent position possible) in a rested and calm state for at least 5 minutes before blood pressure assessments were conducted. Blood pressure units are millimeters of mercury (mmHg).
Outcome measures
| Measure |
Placebo
n=137 Participants
Participants randomized to Placebo were administered 6 subcutaneous (SC) injections on day 1 and weeks 2, 4, 6, 8 and 10 during the 12 week double-blind treatment period.
|
AMG 301 210 mg Q4W
n=104 Participants
Participants randomized to AMG 301 210 mg every fourth week (Q4W) received a total of 3 AMG 301 subcutaneous (SC) injections (70 mg/mL in each injection) plus 3 matching placebo injections on day 1 and weeks 4 and 8. Participants also received 6 SC placebo injections on weeks 2, 6, and 10 during the 12 week double-blind treatment period.
|
AMG 301 420 mg Q2W
n=102 Participants
Participants randomized to AMG 301 420 mg every second week (Q2W) received a total of 6 AMG 301 subcutaneous (SC) injections (70 mg/mL in each injection) on day 1 and weeks 2, 4, 6, 8, and 10 during the 12 week double-blind treatment period.
|
|---|---|---|---|
|
Percentage of Participants With Diastolic Blood Pressure (DBP) in Categories by Visit
Day 1 DBP <50 mmHg
|
0.0 percentage of participants
|
0.0 percentage of participants
|
0.0 percentage of participants
|
|
Percentage of Participants With Diastolic Blood Pressure (DBP) in Categories by Visit
Day 1 DBP > 90 mmHg
|
4.5 percentage of participants
|
6.7 percentage of participants
|
7.4 percentage of participants
|
|
Percentage of Participants With Diastolic Blood Pressure (DBP) in Categories by Visit
Day 1 DBP > 100 mmHg
|
0.0 percentage of participants
|
1.1 percentage of participants
|
0.0 percentage of participants
|
|
Percentage of Participants With Diastolic Blood Pressure (DBP) in Categories by Visit
Week 2 DBP <50 mmHg
|
0.7 percentage of participants
|
0.0 percentage of participants
|
0.0 percentage of participants
|
|
Percentage of Participants With Diastolic Blood Pressure (DBP) in Categories by Visit
Week 2 DBP > 90 mmHg
|
3.7 percentage of participants
|
4.9 percentage of participants
|
11.0 percentage of participants
|
|
Percentage of Participants With Diastolic Blood Pressure (DBP) in Categories by Visit
Week 2 DBP > 100 mmHg
|
0.7 percentage of participants
|
1.0 percentage of participants
|
0.0 percentage of participants
|
|
Percentage of Participants With Diastolic Blood Pressure (DBP) in Categories by Visit
Week 4 DBP <50 mmHg
|
0.7 percentage of participants
|
0.0 percentage of participants
|
0.0 percentage of participants
|
|
Percentage of Participants With Diastolic Blood Pressure (DBP) in Categories by Visit
Week 4 DBP > 90 mmHg
|
5.2 percentage of participants
|
7.0 percentage of participants
|
9.3 percentage of participants
|
|
Percentage of Participants With Diastolic Blood Pressure (DBP) in Categories by Visit
Week 4 DBP > 100 mmHg
|
0.7 percentage of participants
|
2.0 percentage of participants
|
1.0 percentage of participants
|
|
Percentage of Participants With Diastolic Blood Pressure (DBP) in Categories by Visit
Week 6 DBP <50 mmHg
|
0.0 percentage of participants
|
0.0 percentage of participants
|
0.0 percentage of participants
|
|
Percentage of Participants With Diastolic Blood Pressure (DBP) in Categories by Visit
Week 6 DBP > 90 mmHg
|
9.2 percentage of participants
|
3.1 percentage of participants
|
7.4 percentage of participants
|
|
Percentage of Participants With Diastolic Blood Pressure (DBP) in Categories by Visit
Week 6 DBP > 100 mmHg
|
0.0 percentage of participants
|
0.0 percentage of participants
|
1.1 percentage of participants
|
|
Percentage of Participants With Diastolic Blood Pressure (DBP) in Categories by Visit
Week 8 DBP <50 mmHg
|
0.0 percentage of participants
|
0.0 percentage of participants
|
0.0 percentage of participants
|
|
Percentage of Participants With Diastolic Blood Pressure (DBP) in Categories by Visit
Week 8 DBP > 90 mmHg
|
4.6 percentage of participants
|
6.5 percentage of participants
|
9.6 percentage of participants
|
|
Percentage of Participants With Diastolic Blood Pressure (DBP) in Categories by Visit
Week 8 DBP > 100 mmHg
|
0.0 percentage of participants
|
1.1 percentage of participants
|
0.0 percentage of participants
|
|
Percentage of Participants With Diastolic Blood Pressure (DBP) in Categories by Visit
Week 10 DBP <50 mmHg
|
0.0 percentage of participants
|
0.0 percentage of participants
|
0.0 percentage of participants
|
|
Percentage of Participants With Diastolic Blood Pressure (DBP) in Categories by Visit
Week 10 DBP > 90 mmHg
|
6.6 percentage of participants
|
4.3 percentage of participants
|
9.9 percentage of participants
|
|
Percentage of Participants With Diastolic Blood Pressure (DBP) in Categories by Visit
Week 10 DBP > 100 mmHg
|
0.0 percentage of participants
|
0.0 percentage of participants
|
1.1 percentage of participants
|
|
Percentage of Participants With Diastolic Blood Pressure (DBP) in Categories by Visit
Week 12 DBP <50 mmHg
|
0.0 percentage of participants
|
0.0 percentage of participants
|
0.0 percentage of participants
|
|
Percentage of Participants With Diastolic Blood Pressure (DBP) in Categories by Visit
Week 12 DBP > 90 mmHg
|
7.2 percentage of participants
|
3.3 percentage of participants
|
8.0 percentage of participants
|
|
Percentage of Participants With Diastolic Blood Pressure (DBP) in Categories by Visit
Week 12 DBP > 100 mmHg
|
0.0 percentage of participants
|
0.0 percentage of participants
|
1.1 percentage of participants
|
|
Percentage of Participants With Diastolic Blood Pressure (DBP) in Categories by Visit
Week 16 DBP <50 mmHg
|
0.0 percentage of participants
|
0.0 percentage of participants
|
0.0 percentage of participants
|
|
Percentage of Participants With Diastolic Blood Pressure (DBP) in Categories by Visit
Week 16 DBP > 90 mmHg
|
5.3 percentage of participants
|
5.6 percentage of participants
|
12.5 percentage of participants
|
|
Percentage of Participants With Diastolic Blood Pressure (DBP) in Categories by Visit
Week 16 DBP > 100 mmHg
|
0.0 percentage of participants
|
0.0 percentage of participants
|
2.3 percentage of participants
|
|
Percentage of Participants With Diastolic Blood Pressure (DBP) in Categories by Visit
Week 20 DBP <50 mmHg
|
0.0 percentage of participants
|
0.0 percentage of participants
|
0.0 percentage of participants
|
|
Percentage of Participants With Diastolic Blood Pressure (DBP) in Categories by Visit
Week 20 DBP > 90 mmHg
|
8.0 percentage of participants
|
8.1 percentage of participants
|
7.3 percentage of participants
|
|
Percentage of Participants With Diastolic Blood Pressure (DBP) in Categories by Visit
Week 20 DBP > 100 mmHg
|
0.0 percentage of participants
|
1.2 percentage of participants
|
1.2 percentage of participants
|
|
Percentage of Participants With Diastolic Blood Pressure (DBP) in Categories by Visit
Week 24 DBP <50 mmHg
|
0.0 percentage of participants
|
0.0 percentage of participants
|
0.0 percentage of participants
|
|
Percentage of Participants With Diastolic Blood Pressure (DBP) in Categories by Visit
Week 24 DBP > 90 mmHg
|
4.7 percentage of participants
|
7.3 percentage of participants
|
11.4 percentage of participants
|
|
Percentage of Participants With Diastolic Blood Pressure (DBP) in Categories by Visit
Week 24 DBP > 100 mmHg
|
0.0 percentage of participants
|
2.4 percentage of participants
|
1.3 percentage of participants
|
|
Percentage of Participants With Diastolic Blood Pressure (DBP) in Categories by Visit
Week 28 DBP <50 mmHg
|
0.0 percentage of participants
|
0.0 percentage of participants
|
0.0 percentage of participants
|
|
Percentage of Participants With Diastolic Blood Pressure (DBP) in Categories by Visit
Week 28 DBP > 90 mmHg
|
4.6 percentage of participants
|
10.6 percentage of participants
|
10.0 percentage of participants
|
|
Percentage of Participants With Diastolic Blood Pressure (DBP) in Categories by Visit
Week 28 DBP > 100 mmHg
|
0.0 percentage of participants
|
1.2 percentage of participants
|
1.3 percentage of participants
|
SECONDARY outcome
Timeframe: Day 1, Weeks 2, 4, 6, 8, 10, 12,16, 20, 24, 28Population: Safety analysis population of participants with data at that visit.
Participant was expected to be in a supine position (or the most recumbent position possible) in a rested and calm state for at least 5 minutes before pulse assessments were conducted. Pulse rate units are beats per minute (BPM)
Outcome measures
| Measure |
Placebo
n=137 Participants
Participants randomized to Placebo were administered 6 subcutaneous (SC) injections on day 1 and weeks 2, 4, 6, 8 and 10 during the 12 week double-blind treatment period.
|
AMG 301 210 mg Q4W
n=104 Participants
Participants randomized to AMG 301 210 mg every fourth week (Q4W) received a total of 3 AMG 301 subcutaneous (SC) injections (70 mg/mL in each injection) plus 3 matching placebo injections on day 1 and weeks 4 and 8. Participants also received 6 SC placebo injections on weeks 2, 6, and 10 during the 12 week double-blind treatment period.
|
AMG 301 420 mg Q2W
n=102 Participants
Participants randomized to AMG 301 420 mg every second week (Q2W) received a total of 6 AMG 301 subcutaneous (SC) injections (70 mg/mL in each injection) on day 1 and weeks 2, 4, 6, 8, and 10 during the 12 week double-blind treatment period.
|
|---|---|---|---|
|
Percentage of Participants With Pulse Rate in Categories by Visit
Day 1 Pulse rate <60 bpm
|
15.5 percentage of participants
|
13.5 percentage of participants
|
6.2 percentage of participants
|
|
Percentage of Participants With Pulse Rate in Categories by Visit
Day 1 Pulse rate >100 bpm
|
0.0 percentage of participants
|
0.0 percentage of participants
|
0.0 percentage of participants
|
|
Percentage of Participants With Pulse Rate in Categories by Visit
Week 2 Pulse rate <60 bpm
|
11.2 percentage of participants
|
4.9 percentage of participants
|
6.0 percentage of participants
|
|
Percentage of Participants With Pulse Rate in Categories by Visit
Week 2 Pulse rate >100 bpm
|
0.7 percentage of participants
|
1.0 percentage of participants
|
0.0 percentage of participants
|
|
Percentage of Participants With Pulse Rate in Categories by Visit
Week 4 Pulse rate <60 bpm
|
10.4 percentage of participants
|
8.0 percentage of participants
|
6.2 percentage of participants
|
|
Percentage of Participants With Pulse Rate in Categories by Visit
Week 4 Pulse rate >100 bpm
|
0.7 percentage of participants
|
0.0 percentage of participants
|
0.0 percentage of participants
|
|
Percentage of Participants With Pulse Rate in Categories by Visit
Week 6 Pulse rate <60 bpm
|
6.9 percentage of participants
|
8.2 percentage of participants
|
9.6 percentage of participants
|
|
Percentage of Participants With Pulse Rate in Categories by Visit
Week 6 Pulse rate >100 bpm
|
0.8 percentage of participants
|
0.0 percentage of participants
|
1.1 percentage of participants
|
|
Percentage of Participants With Pulse Rate in Categories by Visit
Week 8 Pulse rate <60 bpm
|
9.2 percentage of participants
|
7.6 percentage of participants
|
12.8 percentage of participants
|
|
Percentage of Participants With Pulse Rate in Categories by Visit
Week 8 Pulse rate >100 bpm
|
1.5 percentage of participants
|
0.0 percentage of participants
|
0.0 percentage of participants
|
|
Percentage of Participants With Pulse Rate in Categories by Visit
Week 10 Pulse rate <60 bpm
|
11.5 percentage of participants
|
8.6 percentage of participants
|
6.6 percentage of participants
|
|
Percentage of Participants With Pulse Rate in Categories by Visit
Week 10 Pulse rate >100 bpm
|
0.0 percentage of participants
|
0.0 percentage of participants
|
0.0 percentage of participants
|
|
Percentage of Participants With Pulse Rate in Categories by Visit
Week 12 Pulse rate <60 bpm
|
13.6 percentage of participants
|
13.0 percentage of participants
|
8.0 percentage of participants
|
|
Percentage of Participants With Pulse Rate in Categories by Visit
Week 12 Pulse rate >100 bpm
|
0.0 percentage of participants
|
1.1 percentage of participants
|
1.1 percentage of participants
|
|
Percentage of Participants With Pulse Rate in Categories by Visit
Week 16 Pulse rate <60 bpm
|
10.6 percentage of participants
|
8.9 percentage of participants
|
8.0 percentage of participants
|
|
Percentage of Participants With Pulse Rate in Categories by Visit
Week 16 Pulse rate >100 bpm
|
0.0 percentage of participants
|
0.0 percentage of participants
|
0.0 percentage of participants
|
|
Percentage of Participants With Pulse Rate in Categories by Visit
Week 20 Pulse rate <60 bpm
|
10.6 percentage of participants
|
9.3 percentage of participants
|
9.8 percentage of participants
|
|
Percentage of Participants With Pulse Rate in Categories by Visit
Week 20 Pulse rate >100 bpm
|
0.9 percentage of participants
|
1.2 percentage of participants
|
1.2 percentage of participants
|
|
Percentage of Participants With Pulse Rate in Categories by Visit
Week 24 Pulse rate <60 bpm
|
10.4 percentage of participants
|
8.5 percentage of participants
|
7.6 percentage of participants
|
|
Percentage of Participants With Pulse Rate in Categories by Visit
Week 24 Pulse rate >100 bpm
|
0.0 percentage of participants
|
1.2 percentage of participants
|
1.3 percentage of participants
|
|
Percentage of Participants With Pulse Rate in Categories by Visit
Week 28 Pulse rate <60 bpm
|
8.3 percentage of participants
|
11.8 percentage of participants
|
10.0 percentage of participants
|
|
Percentage of Participants With Pulse Rate in Categories by Visit
Week 28 Pulse rate >100 bpm
|
0.9 percentage of participants
|
1.2 percentage of participants
|
0.0 percentage of participants
|
SECONDARY outcome
Timeframe: Day 1, Weeks 2, 4, 6, 8, 10, 12,16, 20, 24, 28Population: Safety analysis population of participants with data at that visit.
Participant was expected to be in a supine position (or the most recumbent position possible) in a rested and calm state for at least 5 minutes before vital sign assessments were conducted. Temperature units are reported in degrees Celsius (C).
Outcome measures
| Measure |
Placebo
n=137 Participants
Participants randomized to Placebo were administered 6 subcutaneous (SC) injections on day 1 and weeks 2, 4, 6, 8 and 10 during the 12 week double-blind treatment period.
|
AMG 301 210 mg Q4W
n=104 Participants
Participants randomized to AMG 301 210 mg every fourth week (Q4W) received a total of 3 AMG 301 subcutaneous (SC) injections (70 mg/mL in each injection) plus 3 matching placebo injections on day 1 and weeks 4 and 8. Participants also received 6 SC placebo injections on weeks 2, 6, and 10 during the 12 week double-blind treatment period.
|
AMG 301 420 mg Q2W
n=102 Participants
Participants randomized to AMG 301 420 mg every second week (Q2W) received a total of 6 AMG 301 subcutaneous (SC) injections (70 mg/mL in each injection) on day 1 and weeks 2, 4, 6, 8, and 10 during the 12 week double-blind treatment period.
|
|---|---|---|---|
|
Percentage of Participants With Temperature in Categories by Visit
Week 16 Temperature > 38 C
|
0.0 percentage of participants
|
0.0 percentage of participants
|
0.0 percentage of participants
|
|
Percentage of Participants With Temperature in Categories by Visit
Week 20 Temperature < 36 C
|
10.6 percentage of participants
|
7.0 percentage of participants
|
9.8 percentage of participants
|
|
Percentage of Participants With Temperature in Categories by Visit
Day 1 Temperature < 36 C
|
5.5 percentage of participants
|
10.1 percentage of participants
|
7.4 percentage of participants
|
|
Percentage of Participants With Temperature in Categories by Visit
Day 1 Temperature > 38 C
|
0.0 percentage of participants
|
0.0 percentage of participants
|
0.0 percentage of participants
|
|
Percentage of Participants With Temperature in Categories by Visit
Week 2 Temperature < 36 C
|
11.2 percentage of participants
|
9.8 percentage of participants
|
8.0 percentage of participants
|
|
Percentage of Participants With Temperature in Categories by Visit
Week 2 Temperature > 38 C
|
0.0 percentage of participants
|
0.0 percentage of participants
|
0.0 percentage of participants
|
|
Percentage of Participants With Temperature in Categories by Visit
Week 4 Temperature < 36 C
|
8.9 percentage of participants
|
12.0 percentage of participants
|
10.3 percentage of participants
|
|
Percentage of Participants With Temperature in Categories by Visit
Week 4 Temperature > 38 C
|
0.0 percentage of participants
|
0.0 percentage of participants
|
0.0 percentage of participants
|
|
Percentage of Participants With Temperature in Categories by Visit
Week 6 Temperature < 36 C
|
6.1 percentage of participants
|
12.4 percentage of participants
|
8.5 percentage of participants
|
|
Percentage of Participants With Temperature in Categories by Visit
Week 6 Temperature > 38 C
|
0.0 percentage of participants
|
0.0 percentage of participants
|
0.0 percentage of participants
|
|
Percentage of Participants With Temperature in Categories by Visit
Week 8 Temperature < 36 C
|
7.7 percentage of participants
|
7.6 percentage of participants
|
8.5 percentage of participants
|
|
Percentage of Participants With Temperature in Categories by Visit
Week 8 Temperature > 38 C
|
0.0 percentage of participants
|
0.0 percentage of participants
|
0.0 percentage of participants
|
|
Percentage of Participants With Temperature in Categories by Visit
Week 10 Temperature < 36 C
|
9.0 percentage of participants
|
14.0 percentage of participants
|
7.7 percentage of participants
|
|
Percentage of Participants With Temperature in Categories by Visit
Week 10 Temperature > 38 C
|
0.0 percentage of participants
|
0.0 percentage of participants
|
0.0 percentage of participants
|
|
Percentage of Participants With Temperature in Categories by Visit
Week 12 Temperature < 36 C
|
8.0 percentage of participants
|
13.0 percentage of participants
|
12.5 percentage of participants
|
|
Percentage of Participants With Temperature in Categories by Visit
Week 12 Temperature > 38 C
|
0.8 percentage of participants
|
0.0 percentage of participants
|
0.0 percentage of participants
|
|
Percentage of Participants With Temperature in Categories by Visit
Week 20 Temperature > 38 C
|
0.0 percentage of participants
|
0.0 percentage of participants
|
0.0 percentage of participants
|
|
Percentage of Participants With Temperature in Categories by Visit
Week 24 Temperature < 36 C
|
5.7 percentage of participants
|
8.5 percentage of participants
|
11.4 percentage of participants
|
|
Percentage of Participants With Temperature in Categories by Visit
Week 24 Temperature > 38 C
|
0.0 percentage of participants
|
0.0 percentage of participants
|
0.0 percentage of participants
|
|
Percentage of Participants With Temperature in Categories by Visit
Week 28 Temperature < 36 C
|
6.5 percentage of participants
|
9.4 percentage of participants
|
11.3 percentage of participants
|
|
Percentage of Participants With Temperature in Categories by Visit
Week 28 Temperature > 38 C
|
0.0 percentage of participants
|
0.0 percentage of participants
|
0.0 percentage of participants
|
|
Percentage of Participants With Temperature in Categories by Visit
Week 16 Temperature < 36 C
|
6.2 percentage of participants
|
7.8 percentage of participants
|
13.6 percentage of participants
|
SECONDARY outcome
Timeframe: Day 1, Weeks 2, 4, 6, 8, 10, 12,16, 20, 24, 28Population: Safety analysis population of participants with data at that visit.
Participant was expected to be in a supine position (or the most recumbent position possible) in a rested and calm state for at least 5 minutes before vital sign assessments were conducted. Respiratory rate (RR) is reported in breaths/minute.
Outcome measures
| Measure |
Placebo
n=137 Participants
Participants randomized to Placebo were administered 6 subcutaneous (SC) injections on day 1 and weeks 2, 4, 6, 8 and 10 during the 12 week double-blind treatment period.
|
AMG 301 210 mg Q4W
n=104 Participants
Participants randomized to AMG 301 210 mg every fourth week (Q4W) received a total of 3 AMG 301 subcutaneous (SC) injections (70 mg/mL in each injection) plus 3 matching placebo injections on day 1 and weeks 4 and 8. Participants also received 6 SC placebo injections on weeks 2, 6, and 10 during the 12 week double-blind treatment period.
|
AMG 301 420 mg Q2W
n=102 Participants
Participants randomized to AMG 301 420 mg every second week (Q2W) received a total of 6 AMG 301 subcutaneous (SC) injections (70 mg/mL in each injection) on day 1 and weeks 2, 4, 6, 8, and 10 during the 12 week double-blind treatment period.
|
|---|---|---|---|
|
Percentage of Participants With Respiratory Rates in Categories by Visit
Day 1 RR < 12 breaths/min
|
4.6 percentage of participants
|
2.2 percentage of participants
|
3.8 percentage of participants
|
|
Percentage of Participants With Respiratory Rates in Categories by Visit
Day 1 RR > 20 breaths/min
|
0.0 percentage of participants
|
2.2 percentage of participants
|
1.3 percentage of participants
|
|
Percentage of Participants With Respiratory Rates in Categories by Visit
Week 2 RR < 12 breaths/min
|
5.2 percentage of participants
|
2.9 percentage of participants
|
5.0 percentage of participants
|
|
Percentage of Participants With Respiratory Rates in Categories by Visit
Week 2 RR > 20 breaths/min
|
0.0 percentage of participants
|
0.0 percentage of participants
|
0.0 percentage of participants
|
|
Percentage of Participants With Respiratory Rates in Categories by Visit
Week 4 RR < 12 breaths/min
|
2.2 percentage of participants
|
3.0 percentage of participants
|
5.2 percentage of participants
|
|
Percentage of Participants With Respiratory Rates in Categories by Visit
Week 4 RR > 20 breaths/min
|
0.0 percentage of participants
|
0.0 percentage of participants
|
2.1 percentage of participants
|
|
Percentage of Participants With Respiratory Rates in Categories by Visit
Week 6 RR < 12 breaths/min
|
6.1 percentage of participants
|
1.0 percentage of participants
|
4.3 percentage of participants
|
|
Percentage of Participants With Respiratory Rates in Categories by Visit
Week 6 RR > 20 breaths/min
|
0.8 percentage of participants
|
0.0 percentage of participants
|
0.0 percentage of participants
|
|
Percentage of Participants With Respiratory Rates in Categories by Visit
Week 8 RR < 12 breaths/min
|
3.1 percentage of participants
|
2.2 percentage of participants
|
1.1 percentage of participants
|
|
Percentage of Participants With Respiratory Rates in Categories by Visit
Week 8 RR > 20 breaths/min
|
0.0 percentage of participants
|
2.2 percentage of participants
|
0.0 percentage of participants
|
|
Percentage of Participants With Respiratory Rates in Categories by Visit
Week 10 RR < 12 breaths/min
|
5.7 percentage of participants
|
1.1 percentage of participants
|
4.4 percentage of participants
|
|
Percentage of Participants With Respiratory Rates in Categories by Visit
Week 10 RR > 20 breaths/min
|
0.0 percentage of participants
|
2.2 percentage of participants
|
0.0 percentage of participants
|
|
Percentage of Participants With Respiratory Rates in Categories by Visit
Week 12 RR < 12 breaths/min
|
4.0 percentage of participants
|
1.1 percentage of participants
|
0.0 percentage of participants
|
|
Percentage of Participants With Respiratory Rates in Categories by Visit
Week 12 RR > 20 breaths/min
|
0.0 percentage of participants
|
0.0 percentage of participants
|
0.0 percentage of participants
|
|
Percentage of Participants With Respiratory Rates in Categories by Visit
Week 16 RR < 12 breaths/min
|
4.4 percentage of participants
|
2.2 percentage of participants
|
4.5 percentage of participants
|
|
Percentage of Participants With Respiratory Rates in Categories by Visit
Week 16 RR > 20 breaths/min
|
0.0 percentage of participants
|
1.1 percentage of participants
|
0.0 percentage of participants
|
|
Percentage of Participants With Respiratory Rates in Categories by Visit
Week 20 RR < 12 breaths/min
|
5.3 percentage of participants
|
0.0 percentage of participants
|
1.2 percentage of participants
|
|
Percentage of Participants With Respiratory Rates in Categories by Visit
Week 20 RR > 20 breaths/min
|
0.0 percentage of participants
|
1.2 percentage of participants
|
0.0 percentage of participants
|
|
Percentage of Participants With Respiratory Rates in Categories by Visit
Week 24 RR < 12 breaths/min
|
1.9 percentage of participants
|
0.0 percentage of participants
|
0.0 percentage of participants
|
|
Percentage of Participants With Respiratory Rates in Categories by Visit
Week 24 RR > 20 breaths/min
|
0.0 percentage of participants
|
4.9 percentage of participants
|
0.0 percentage of participants
|
|
Percentage of Participants With Respiratory Rates in Categories by Visit
Week 28 RR < 12 breaths/min
|
3.7 percentage of participants
|
1.2 percentage of participants
|
2.5 percentage of participants
|
|
Percentage of Participants With Respiratory Rates in Categories by Visit
Week 28 RR > 20 breaths/min
|
0.9 percentage of participants
|
2.4 percentage of participants
|
1.3 percentage of participants
|
Adverse Events
Placebo
Serious events: 3 serious events
Other events: 32 other events
Deaths: 0 deaths
AMG 301 210 mg Q4W
Serious events: 1 serious events
Other events: 27 other events
Deaths: 0 deaths
AMG 301 420 mg Q2W
Serious events: 2 serious events
Other events: 31 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Placebo
n=137 participants at risk
Participants randomized to Placebo were administered 6 subcutaneous (SC) injections on day 1 and weeks 2, 4, 6, 8 and 10 during the 12 week double-blind treatment period.
|
AMG 301 210 mg Q4W
n=104 participants at risk
Participants randomized to AMG 301 210 mg every fourth week (Q4W) received a total of 3 AMG 301 subcutaneous (SC) injections (70 mg/mL in each injection) plus 3 matching placebo injections on day 1 and weeks 4 and 8. Participants also received 6 SC placebo injections on weeks 2, 6, and 10 during the 12 week double-blind treatment period.
|
AMG 301 420 mg Q2W
n=102 participants at risk
Participants randomized to AMG 301 420 mg every second week (Q2W) received a total of 6 AMG 301 subcutaneous (SC) injections (70 mg/mL in each injection) on day 1 and weeks 2, 4, 6, 8, and 10 during the 12 week double-blind treatment period.
|
|---|---|---|---|
|
Hepatobiliary disorders
Cholelithiasis
|
0.73%
1/137 • All-cause mortality includes time from enrollment (including the 28 days prior to Day 1), 12-week double-blind treatment and 16-week safety follow-up. Serious adverse events and other adverse events include the 12-week double-blind treatment and 16-week safety follow-up.
All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
0.00%
0/104 • All-cause mortality includes time from enrollment (including the 28 days prior to Day 1), 12-week double-blind treatment and 16-week safety follow-up. Serious adverse events and other adverse events include the 12-week double-blind treatment and 16-week safety follow-up.
All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
0.00%
0/102 • All-cause mortality includes time from enrollment (including the 28 days prior to Day 1), 12-week double-blind treatment and 16-week safety follow-up. Serious adverse events and other adverse events include the 12-week double-blind treatment and 16-week safety follow-up.
All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
|
Immune system disorders
Hypersensitivity
|
0.00%
0/137 • All-cause mortality includes time from enrollment (including the 28 days prior to Day 1), 12-week double-blind treatment and 16-week safety follow-up. Serious adverse events and other adverse events include the 12-week double-blind treatment and 16-week safety follow-up.
All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
0.00%
0/104 • All-cause mortality includes time from enrollment (including the 28 days prior to Day 1), 12-week double-blind treatment and 16-week safety follow-up. Serious adverse events and other adverse events include the 12-week double-blind treatment and 16-week safety follow-up.
All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
0.98%
1/102 • All-cause mortality includes time from enrollment (including the 28 days prior to Day 1), 12-week double-blind treatment and 16-week safety follow-up. Serious adverse events and other adverse events include the 12-week double-blind treatment and 16-week safety follow-up.
All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
|
Infections and infestations
Gastroenteritis
|
0.73%
1/137 • All-cause mortality includes time from enrollment (including the 28 days prior to Day 1), 12-week double-blind treatment and 16-week safety follow-up. Serious adverse events and other adverse events include the 12-week double-blind treatment and 16-week safety follow-up.
All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
0.00%
0/104 • All-cause mortality includes time from enrollment (including the 28 days prior to Day 1), 12-week double-blind treatment and 16-week safety follow-up. Serious adverse events and other adverse events include the 12-week double-blind treatment and 16-week safety follow-up.
All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
0.00%
0/102 • All-cause mortality includes time from enrollment (including the 28 days prior to Day 1), 12-week double-blind treatment and 16-week safety follow-up. Serious adverse events and other adverse events include the 12-week double-blind treatment and 16-week safety follow-up.
All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
|
Nervous system disorders
Migraine with aura
|
0.73%
1/137 • All-cause mortality includes time from enrollment (including the 28 days prior to Day 1), 12-week double-blind treatment and 16-week safety follow-up. Serious adverse events and other adverse events include the 12-week double-blind treatment and 16-week safety follow-up.
All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
0.00%
0/104 • All-cause mortality includes time from enrollment (including the 28 days prior to Day 1), 12-week double-blind treatment and 16-week safety follow-up. Serious adverse events and other adverse events include the 12-week double-blind treatment and 16-week safety follow-up.
All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
0.00%
0/102 • All-cause mortality includes time from enrollment (including the 28 days prior to Day 1), 12-week double-blind treatment and 16-week safety follow-up. Serious adverse events and other adverse events include the 12-week double-blind treatment and 16-week safety follow-up.
All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
|
Reproductive system and breast disorders
Polycystic ovaries
|
0.00%
0/137 • All-cause mortality includes time from enrollment (including the 28 days prior to Day 1), 12-week double-blind treatment and 16-week safety follow-up. Serious adverse events and other adverse events include the 12-week double-blind treatment and 16-week safety follow-up.
All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
0.96%
1/104 • All-cause mortality includes time from enrollment (including the 28 days prior to Day 1), 12-week double-blind treatment and 16-week safety follow-up. Serious adverse events and other adverse events include the 12-week double-blind treatment and 16-week safety follow-up.
All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
0.00%
0/102 • All-cause mortality includes time from enrollment (including the 28 days prior to Day 1), 12-week double-blind treatment and 16-week safety follow-up. Serious adverse events and other adverse events include the 12-week double-blind treatment and 16-week safety follow-up.
All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
|
Skin and subcutaneous tissue disorders
Erythema nodosum
|
0.00%
0/137 • All-cause mortality includes time from enrollment (including the 28 days prior to Day 1), 12-week double-blind treatment and 16-week safety follow-up. Serious adverse events and other adverse events include the 12-week double-blind treatment and 16-week safety follow-up.
All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
0.00%
0/104 • All-cause mortality includes time from enrollment (including the 28 days prior to Day 1), 12-week double-blind treatment and 16-week safety follow-up. Serious adverse events and other adverse events include the 12-week double-blind treatment and 16-week safety follow-up.
All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
0.98%
1/102 • All-cause mortality includes time from enrollment (including the 28 days prior to Day 1), 12-week double-blind treatment and 16-week safety follow-up. Serious adverse events and other adverse events include the 12-week double-blind treatment and 16-week safety follow-up.
All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
Other adverse events
| Measure |
Placebo
n=137 participants at risk
Participants randomized to Placebo were administered 6 subcutaneous (SC) injections on day 1 and weeks 2, 4, 6, 8 and 10 during the 12 week double-blind treatment period.
|
AMG 301 210 mg Q4W
n=104 participants at risk
Participants randomized to AMG 301 210 mg every fourth week (Q4W) received a total of 3 AMG 301 subcutaneous (SC) injections (70 mg/mL in each injection) plus 3 matching placebo injections on day 1 and weeks 4 and 8. Participants also received 6 SC placebo injections on weeks 2, 6, and 10 during the 12 week double-blind treatment period.
|
AMG 301 420 mg Q2W
n=102 participants at risk
Participants randomized to AMG 301 420 mg every second week (Q2W) received a total of 6 AMG 301 subcutaneous (SC) injections (70 mg/mL in each injection) on day 1 and weeks 2, 4, 6, 8, and 10 during the 12 week double-blind treatment period.
|
|---|---|---|---|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/137 • All-cause mortality includes time from enrollment (including the 28 days prior to Day 1), 12-week double-blind treatment and 16-week safety follow-up. Serious adverse events and other adverse events include the 12-week double-blind treatment and 16-week safety follow-up.
All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
3.8%
4/104 • All-cause mortality includes time from enrollment (including the 28 days prior to Day 1), 12-week double-blind treatment and 16-week safety follow-up. Serious adverse events and other adverse events include the 12-week double-blind treatment and 16-week safety follow-up.
All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
5.9%
6/102 • All-cause mortality includes time from enrollment (including the 28 days prior to Day 1), 12-week double-blind treatment and 16-week safety follow-up. Serious adverse events and other adverse events include the 12-week double-blind treatment and 16-week safety follow-up.
All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
|
General disorders
Fatigue
|
5.8%
8/137 • All-cause mortality includes time from enrollment (including the 28 days prior to Day 1), 12-week double-blind treatment and 16-week safety follow-up. Serious adverse events and other adverse events include the 12-week double-blind treatment and 16-week safety follow-up.
All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
4.8%
5/104 • All-cause mortality includes time from enrollment (including the 28 days prior to Day 1), 12-week double-blind treatment and 16-week safety follow-up. Serious adverse events and other adverse events include the 12-week double-blind treatment and 16-week safety follow-up.
All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
8.8%
9/102 • All-cause mortality includes time from enrollment (including the 28 days prior to Day 1), 12-week double-blind treatment and 16-week safety follow-up. Serious adverse events and other adverse events include the 12-week double-blind treatment and 16-week safety follow-up.
All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
|
Infections and infestations
Influenza
|
3.6%
5/137 • All-cause mortality includes time from enrollment (including the 28 days prior to Day 1), 12-week double-blind treatment and 16-week safety follow-up. Serious adverse events and other adverse events include the 12-week double-blind treatment and 16-week safety follow-up.
All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
4.8%
5/104 • All-cause mortality includes time from enrollment (including the 28 days prior to Day 1), 12-week double-blind treatment and 16-week safety follow-up. Serious adverse events and other adverse events include the 12-week double-blind treatment and 16-week safety follow-up.
All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
5.9%
6/102 • All-cause mortality includes time from enrollment (including the 28 days prior to Day 1), 12-week double-blind treatment and 16-week safety follow-up. Serious adverse events and other adverse events include the 12-week double-blind treatment and 16-week safety follow-up.
All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
|
Infections and infestations
Nasopharyngitis
|
9.5%
13/137 • All-cause mortality includes time from enrollment (including the 28 days prior to Day 1), 12-week double-blind treatment and 16-week safety follow-up. Serious adverse events and other adverse events include the 12-week double-blind treatment and 16-week safety follow-up.
All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
9.6%
10/104 • All-cause mortality includes time from enrollment (including the 28 days prior to Day 1), 12-week double-blind treatment and 16-week safety follow-up. Serious adverse events and other adverse events include the 12-week double-blind treatment and 16-week safety follow-up.
All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
6.9%
7/102 • All-cause mortality includes time from enrollment (including the 28 days prior to Day 1), 12-week double-blind treatment and 16-week safety follow-up. Serious adverse events and other adverse events include the 12-week double-blind treatment and 16-week safety follow-up.
All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
5.8%
8/137 • All-cause mortality includes time from enrollment (including the 28 days prior to Day 1), 12-week double-blind treatment and 16-week safety follow-up. Serious adverse events and other adverse events include the 12-week double-blind treatment and 16-week safety follow-up.
All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
2.9%
3/104 • All-cause mortality includes time from enrollment (including the 28 days prior to Day 1), 12-week double-blind treatment and 16-week safety follow-up. Serious adverse events and other adverse events include the 12-week double-blind treatment and 16-week safety follow-up.
All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
0.98%
1/102 • All-cause mortality includes time from enrollment (including the 28 days prior to Day 1), 12-week double-blind treatment and 16-week safety follow-up. Serious adverse events and other adverse events include the 12-week double-blind treatment and 16-week safety follow-up.
All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
|
Nervous system disorders
Migraine
|
2.2%
3/137 • All-cause mortality includes time from enrollment (including the 28 days prior to Day 1), 12-week double-blind treatment and 16-week safety follow-up. Serious adverse events and other adverse events include the 12-week double-blind treatment and 16-week safety follow-up.
All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
1.9%
2/104 • All-cause mortality includes time from enrollment (including the 28 days prior to Day 1), 12-week double-blind treatment and 16-week safety follow-up. Serious adverse events and other adverse events include the 12-week double-blind treatment and 16-week safety follow-up.
All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
5.9%
6/102 • All-cause mortality includes time from enrollment (including the 28 days prior to Day 1), 12-week double-blind treatment and 16-week safety follow-up. Serious adverse events and other adverse events include the 12-week double-blind treatment and 16-week safety follow-up.
All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
Additional Information
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