Trial Outcomes & Findings for A Study Evaluating the Effectiveness of AMG 334 Injection in Preventing Migraines in Adults Having Failed Other Therapies (NCT NCT03096834)

NCT ID: NCT03096834

Last Updated: 2022-03-23

Results Overview

A migraine day was defined as any calendar day in which the subject experienced a qualified migraine headache defined as: with/without aura, lasting ≥ 30 minutes with at least 1 criteria: 1. ≥ 2 of following pain features: unilateral, throbbing, moderate to severe or exacerbated with exercise/physical activity, 2. ≥ 1 of the following symptoms: nausea and/or vomiting, photophobia and phonophobia. If a migraine-specific medication (ie, triptan or ergotamine) was taken during aura, or a headache, it was counted as a migraine day regardless of duration and pain features/associated symptoms.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 246 participants
• Primary outcome timeframe: Baseline, Month 3 (last 4 weeks of treatment)
• Results posted on: 2022-03-23

Participant Flow

333 participants were screened for the trial

Participant milestones

Measure	AMG334 140 mg DB AMG334 140 mg subcutaneous injections administered every 4 weeks during Double-Blind Epoch	Placebo DB Matching placebo subcutaneous injections administered every 4 weeks during Double-Blind Epoch	AMG334 140 mg DB Cont on AMG334 140 mg AMG334 140 mg subcutaneous injections during DB continued on AMG334 140 mg in Open-Label Epoch	Placebo DB to AMG334 140 mg Placebo in Double-Blind Epoch (DB) switched to AMG334 140 mg in Open-Label Epoch
Double-Blind Treatment Epoch STARTED	121	125	0	0
Double-Blind Treatment Epoch COMPLETED	118	122	0	0
Double-Blind Treatment Epoch NOT COMPLETED	3	3	0	0
Open-Label Treatment Epoch STARTED	0	0	118	122
Open-Label Treatment Epoch COMPLETED	0	0	86	83
Open-Label Treatment Epoch NOT COMPLETED	0	0	32	39
Safety Follow-Up Epoch STARTED	0	0	66	61
Safety Follow-Up Epoch COMPLETED	0	0	65	59
Safety Follow-Up Epoch NOT COMPLETED	0	0	1	2
Post-Trial Access Epoch STARTED	0	0	21	15
Post-Trial Access Epoch COMPLETED	0	0	21	15
Post-Trial Access Epoch NOT COMPLETED	0	0	0	0

Reasons for withdrawal

Measure	AMG334 140 mg DB AMG334 140 mg subcutaneous injections administered every 4 weeks during Double-Blind Epoch	Placebo DB Matching placebo subcutaneous injections administered every 4 weeks during Double-Blind Epoch	AMG334 140 mg DB Cont on AMG334 140 mg AMG334 140 mg subcutaneous injections during DB continued on AMG334 140 mg in Open-Label Epoch	Placebo DB to AMG334 140 mg Placebo in Double-Blind Epoch (DB) switched to AMG334 140 mg in Open-Label Epoch
Double-Blind Treatment Epoch Protocol deviation	2	1	0	0
Double-Blind Treatment Epoch Pregnancy	0	1	0	0
Double-Blind Treatment Epoch Subject/guardian decision	1	1	0	0
Open-Label Treatment Epoch Lack of Efficacy	0	0	15	15
Open-Label Treatment Epoch Adverse Event	0	0	5	6
Open-Label Treatment Epoch New therapy for study indication	0	0	1	1
Open-Label Treatment Epoch Physician Decision	0	0	1	0
Open-Label Treatment Epoch Pregnancy	0	0	1	0
Open-Label Treatment Epoch Subject/guardian decision	0	0	9	17
Safety Follow-Up Epoch New therapy for study indication	0	0	0	1
Safety Follow-Up Epoch Protocol deviation	0	0	0	1
Safety Follow-Up Epoch Lost to Follow-up	0	0	1	0

Baseline Characteristics

A Study Evaluating the Effectiveness of AMG 334 Injection in Preventing Migraines in Adults Having Failed Other Therapies

Baseline characteristics by cohort

Measure	AMG334 140 mg DB n=121 Participants AMG334 140 mg subcutaneous injections administered every 4 weeks during Double-Blind Epoch	Placebo DB n=125 Participants Matching placebo subcutaneous injections administered every 4 weeks during Double-Blind Epoch	Total n=246 Participants Total of all reporting groups
Age, Customized Between 18 and 65 years	121 Participants n=5 Participants	125 Participants n=7 Participants	246 Participants n=5 Participants
Sex: Female, Male Female	97 Participants n=5 Participants	103 Participants n=7 Participants	200 Participants n=5 Participants
Sex: Female, Male Male	24 Participants n=5 Participants	22 Participants n=7 Participants	46 Participants n=5 Participants
Race/Ethnicity, Customized Caucasian	112 Participants n=5 Participants	115 Participants n=7 Participants	227 Participants n=5 Participants
Race/Ethnicity, Customized Asian	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Unknown	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Other	9 Participants n=5 Participants	8 Participants n=7 Participants	17 Participants n=5 Participants
Monthly Migraine Days at Baseline	9.2 Migraine days/month STANDARD_DEVIATION 2.56 • n=5 Participants	9.3 Migraine days/month STANDARD_DEVIATION 2.72 • n=7 Participants	9.3 Migraine days/month STANDARD_DEVIATION 2.63 • n=5 Participants

PRIMARY outcome

Timeframe: Baseline, Month 3 (last 4 weeks of treatment)

Population: Full analysis set

A migraine day was defined as any calendar day in which the subject experienced a qualified migraine headache defined as: with/without aura, lasting ≥ 30 minutes with at least 1 criteria: 1. ≥ 2 of following pain features: unilateral, throbbing, moderate to severe or exacerbated with exercise/physical activity, 2. ≥ 1 of the following symptoms: nausea and/or vomiting, photophobia and phonophobia. If a migraine-specific medication (ie, triptan or ergotamine) was taken during aura, or a headache, it was counted as a migraine day regardless of duration and pain features/associated symptoms.

Outcome measures

Measure	AMG334 140 mg DB n=119 Participants AMG334 140 mg subcutaneous injections administered every 4 weeks during Double-Blind Epoch	Placebo DB n=124 Participants Matching placebo subcutaneous injections administered every 4 weeks during Double-Blind Epoch
Percentage of Participants With at Least 50% Reduction From Baseline of Monthly Migraine Days (MMD) in the Last Month (Last 4 Weeks of Treatment)	30.3 Percentage of participants	13.7 Percentage of participants

SECONDARY outcome

Timeframe: Baseline, Month 3 (last 4 weeks of treatment)

Population: Number of participants with both baseline and valid post baseline value from the Full Analysis Set

A migraine day was defined as any calendar day in which the subject experienced a qualified migraine headache defined as: with/without aura, lasting ≥ 30 minutes with at least 1 criteria: 1. ≥ 2 of following pain features: unilateral, throbbing, moderate to severe or exacerbated with exercise/physical activity, 2. ≥ 1 of the following symptoms: nausea and/or vomiting, photophobia and phonophobia. If a migraine-specific medication (ie, triptan or ergotamine) was taken during aura, or a headache, it was counted as a migraine day regardless of duration and pain features/associated symptoms.

Outcome measures

Measure	AMG334 140 mg DB n=118 Participants AMG334 140 mg subcutaneous injections administered every 4 weeks during Double-Blind Epoch	Placebo DB n=120 Participants Matching placebo subcutaneous injections administered every 4 weeks during Double-Blind Epoch
Change From Baseline in Monthly Migraine Days (MMD) in the Last Month (Last 4 Weeks of Treatment)	-1.75 Monthly migraine days Standard Error 0.43	-0.16 Monthly migraine days Standard Error 0.41

SECONDARY outcome

Timeframe: Baseline, Month 3 (last 4 weeks of treatment)

Population: Number of participants with both baseline and valid post baseline value from the Full Analysis Set

MPFID has 2 domains: Everyday Activities, which consisted of 7 items and Physical Impairment with 5 items using a 5-point scale. Scores were summed across each domain and were then transformed and used for analyses. Transforming MPFID domain scores ranged from 0-100, where higher scores were indicative of greater migraine impact (ie, higher burden)

Outcome measures

Measure	AMG334 140 mg DB n=118 Participants AMG334 140 mg subcutaneous injections administered every 4 weeks during Double-Blind Epoch	Placebo DB n=120 Participants Matching placebo subcutaneous injections administered every 4 weeks during Double-Blind Epoch
Change From Baseline in Physical Impairment and Everyday Activities as Measured by the Migraine Physical Function Impact Diary (MPFID) at Month 3 Physical impairment domain	-1.85 scores on a scale Standard Error 0.84	1.61 scores on a scale Standard Error 0.80
Change From Baseline in Physical Impairment and Everyday Activities as Measured by the Migraine Physical Function Impact Diary (MPFID) at Month 3 Everyday activities domain	-3.36 scores on a scale Standard Error 0.83	0.55 scores on a scale Standard Error 0.81

SECONDARY outcome

Timeframe: Baseline, Month 3 (last 4 weeks of treatment)

Population: Number of participants with both baseline and valid post baseline value from the Full Analysis Set

Number of days on which acute migraine-specific medications were used were recorded in eDiary between each monthly IP dose. Migraine-Specific medications included two categories of medications: triptan-based migraine medications and ergotamine-based migraine medications. Monthly migraine-specific medication use at baseline was the number of migraine-specific medication treatment days in the baseline period.

Outcome measures

Measure	AMG334 140 mg DB n=118 Participants AMG334 140 mg subcutaneous injections administered every 4 weeks during Double-Blind Epoch	Placebo DB n=120 Participants Matching placebo subcutaneous injections administered every 4 weeks during Double-Blind Epoch
Change in the Number of Monthly Acute Migraine-specific Medication Treatment Days at Month 3	-1.25 Migraine treatment specific days/month Standard Error 0.24	0.46 Migraine treatment specific days/month Standard Error 0.28

SECONDARY outcome

Timeframe: Baseline, Month 3 (last 4 weeks of treatment)

Population: Full analysis set

A migraine day was defined as any calendar day in which the subject experienced a qualified migraine headache defined as: with/without aura, lasting ≥ 30 minutes with at least 1 criteria: 1. ≥ 2 of following pain features: unilateral, throbbing, moderate to severe or exacerbated with exercise/physical activity, 2. ≥ 1 of the following symptoms: nausea and/or vomiting, photophobia and phonophobia. If a migraine-specific medication (ie, triptan or ergotamine) was taken during aura, or a headache, it was counted as a migraine day regardless of duration and pain features/associated symptoms.

Outcome measures

Measure	AMG334 140 mg DB n=119 Participants AMG334 140 mg subcutaneous injections administered every 4 weeks during Double-Blind Epoch	Placebo DB n=124 Participants Matching placebo subcutaneous injections administered every 4 weeks during Double-Blind Epoch
Percentage of Participants With a 75% Reduction From Baseline of Monthly Migraine Days (MMD) in the Last Month (Last 4 Weeks of Treatment)	11.8 Percentage of participants	4.0 Percentage of participants

SECONDARY outcome

Timeframe: Baseline, Month 3 (last 4 weeks of treatment)

Population: Full analysis set

A migraine day was defined as any calendar day in which the subject experienced a qualified migraine headache defined as: with/without aura, lasting ≥ 30 minutes with at least 1 criteria: 1. ≥ 2 of following pain features: unilateral, throbbing, moderate to severe or exacerbated with exercise/physical activity, 2. ≥ 1 of the following symptoms: nausea and/or vomiting, photophobia and phonophobia. If a migraine-specific medication (ie, triptan or ergotamine) was taken during aura, or a headache, it was counted as a migraine day regardless of duration and pain features/associated symptoms.

Outcome measures

Measure	AMG334 140 mg DB n=119 Participants AMG334 140 mg subcutaneous injections administered every 4 weeks during Double-Blind Epoch	Placebo DB n=124 Participants Matching placebo subcutaneous injections administered every 4 weeks during Double-Blind Epoch
Percentage of Participants With a 100% Reduction From Baseline of Monthly Migraine Days (MMD) in the Last Month (Last 4 Weeks of Treatment)	5.9 Percentage of participants	0 Percentage of participants

SECONDARY outcome

Timeframe: Baseline up to approximately 180 weeks

Blood samples for immunogenicity testing were collected for the measurement of anti-AMG334 binding antibodies.

Outcome measures

Measure	AMG334 140 mg DB n=238 Participants AMG334 140 mg subcutaneous injections administered every 4 weeks during Double-Blind Epoch	Placebo DB Matching placebo subcutaneous injections administered every 4 weeks during Double-Blind Epoch
Number of Participants Who Developed Anti-AMG334 Antibodies	0 participants	—

Adverse Events

AMG334 140 mg DB

Serious events: 2 serious events

Other events: 44 other events

Deaths: 0 deaths

Placebo DB

Serious events: 1 serious events

Other events: 43 other events

Deaths: 0 deaths

AMG334 140 mg DB Cont on AMG334 140 mg

Serious events: 16 serious events

Other events: 94 other events

Deaths: 0 deaths

Placebo DB to AMG334 140 mg

Serious events: 18 serious events

Other events: 101 other events

Deaths: 0 deaths

Serious adverse events

Measure	AMG334 140 mg DB n=119 participants at risk AMG334 140 mg subcutaneous injections administered every 4 weeks during Double-Blind Epoch	Placebo DB n=124 participants at risk Matching placebo subcutaneous injections administered every 4 weeks during Double-Blind Epoch	AMG334 140 mg DB Cont on AMG334 140 mg n=118 participants at risk AMG334 140 mg subcutaneous injections during DB continued on AMG334 140 mg in Open-Label Epoch	Placebo DB to AMG334 140 mg n=122 participants at risk Placebo in Double-Blind Epoch (DB) switched to AMG334 140 mg in Open-Label Epoch
Gastrointestinal disorders Colitis ischaemic	0.00% 0/119 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	0.00% 0/124 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	0.00% 0/118 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	0.82% 1/122 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.
Gastrointestinal disorders Gastritis	0.00% 0/119 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	0.00% 0/124 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	0.00% 0/118 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	0.82% 1/122 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.
Cardiac disorders Extrasystoles	0.00% 0/119 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	0.00% 0/124 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	0.00% 0/118 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	0.82% 1/122 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.
Eye disorders Dacryostenosis acquired	0.00% 0/119 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	0.00% 0/124 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	0.85% 1/118 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	0.00% 0/122 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.
Eye disorders Inflammation of lacrimal passage	0.00% 0/119 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	0.00% 0/124 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	0.85% 1/118 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	0.00% 0/122 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.
Eye disorders Retinal vein thrombosis	0.00% 0/119 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	0.00% 0/124 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	0.85% 1/118 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	0.00% 0/122 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.
Gastrointestinal disorders Anal fissure	0.00% 0/119 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	0.00% 0/124 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	0.00% 0/118 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	0.82% 1/122 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.
Gastrointestinal disorders Umbilical hernia	0.00% 0/119 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	0.00% 0/124 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	0.00% 0/118 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	0.82% 1/122 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.
Hepatobiliary disorders Biliary colic	0.00% 0/119 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	0.00% 0/124 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	0.85% 1/118 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	0.82% 1/122 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.
Immune system disorders Allergy to arthropod sting	0.00% 0/119 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	0.00% 0/124 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	0.85% 1/118 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	0.00% 0/122 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.
Infections and infestations Appendicitis	0.00% 0/119 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	0.00% 0/124 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	0.00% 0/118 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	0.82% 1/122 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.
Infections and infestations Cellulitis	0.00% 0/119 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	0.00% 0/124 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	0.00% 0/118 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	0.82% 1/122 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.
Infections and infestations Chronic sinusitis	0.00% 0/119 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	0.00% 0/124 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	0.00% 0/118 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	0.82% 1/122 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.
Infections and infestations Gastrointestinal infection	0.00% 0/119 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	0.81% 1/124 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	0.00% 0/118 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	0.00% 0/122 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.
Infections and infestations Herpes simplex hepatitis	0.00% 0/119 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	0.00% 0/124 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	0.85% 1/118 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	0.00% 0/122 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.
Infections and infestations Pneumonia	0.00% 0/119 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	0.00% 0/124 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	0.00% 0/118 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	0.82% 1/122 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.
Infections and infestations Pyelonephritis	0.00% 0/119 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	0.00% 0/124 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	0.85% 1/118 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	0.00% 0/122 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.
Injury, poisoning and procedural complications Femoral neck fracture	0.00% 0/119 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	0.00% 0/124 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	0.85% 1/118 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	0.00% 0/122 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.
Injury, poisoning and procedural complications Tibia fracture	0.00% 0/119 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	0.00% 0/124 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	0.85% 1/118 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	0.00% 0/122 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.
Injury, poisoning and procedural complications Traumatic fracture	0.84% 1/119 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	0.00% 0/124 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	0.00% 0/118 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	0.00% 0/122 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	0.00% 0/119 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	0.00% 0/124 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	0.85% 1/118 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	0.00% 0/122 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cervix carcinoma stage 0	0.00% 0/119 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	0.00% 0/124 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	0.85% 1/118 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	0.00% 0/122 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Myelofibrosis	0.00% 0/119 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	0.00% 0/124 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	0.85% 1/118 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	0.00% 0/122 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Pituitary tumour benign	0.00% 0/119 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	0.00% 0/124 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	0.00% 0/118 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	0.82% 1/122 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.
Nervous system disorders Aura	0.00% 0/119 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	0.00% 0/124 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	0.85% 1/118 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	0.00% 0/122 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.
Nervous system disorders Cerebral haemorrhage	0.00% 0/119 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	0.00% 0/124 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	0.85% 1/118 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	0.00% 0/122 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.
Nervous system disorders Medication overuse headache	0.00% 0/119 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	0.00% 0/124 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	0.85% 1/118 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	0.00% 0/122 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.
Nervous system disorders Migraine	0.84% 1/119 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	0.00% 0/124 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	1.7% 2/118 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	1.6% 2/122 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.
Nervous system disorders Status migrainosus	0.00% 0/119 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	0.00% 0/124 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	0.00% 0/118 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	0.82% 1/122 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.
Nervous system disorders Syncope	0.00% 0/119 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	0.00% 0/124 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	0.00% 0/118 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	0.82% 1/122 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.
Psychiatric disorders Depression	0.00% 0/119 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	0.00% 0/124 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	0.00% 0/118 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	1.6% 2/122 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.
Renal and urinary disorders Calculus urinary	0.00% 0/119 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	0.00% 0/124 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	0.00% 0/118 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	0.82% 1/122 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.
Renal and urinary disorders Renal colic	0.00% 0/119 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	0.00% 0/124 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	0.85% 1/118 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	0.00% 0/122 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.
Reproductive system and breast disorders Ovarian cyst	0.00% 0/119 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	0.00% 0/124 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	0.00% 0/118 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	0.82% 1/122 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.
Reproductive system and breast disorders Postmenopausal haemorrhage	0.00% 0/119 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	0.00% 0/124 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	0.00% 0/118 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	0.82% 1/122 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.
Respiratory, thoracic and mediastinal disorders Asthma	0.00% 0/119 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	0.00% 0/124 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	0.00% 0/118 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	0.82% 1/122 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.00% 0/119 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	0.00% 0/124 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	0.00% 0/118 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	0.82% 1/122 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.

Other adverse events

Measure	AMG334 140 mg DB n=119 participants at risk AMG334 140 mg subcutaneous injections administered every 4 weeks during Double-Blind Epoch	Placebo DB n=124 participants at risk Matching placebo subcutaneous injections administered every 4 weeks during Double-Blind Epoch	AMG334 140 mg DB Cont on AMG334 140 mg n=118 participants at risk AMG334 140 mg subcutaneous injections during DB continued on AMG334 140 mg in Open-Label Epoch	Placebo DB to AMG334 140 mg n=122 participants at risk Placebo in Double-Blind Epoch (DB) switched to AMG334 140 mg in Open-Label Epoch
Ear and labyrinth disorders Vertigo	0.00% 0/119 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	0.00% 0/124 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	6.8% 8/118 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	4.9% 6/122 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.
Gastrointestinal disorders Constipation	1.7% 2/119 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	1.6% 2/124 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	9.3% 11/118 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	4.1% 5/122 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.
Gastrointestinal disorders Diarrhoea	1.7% 2/119 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	0.81% 1/124 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	6.8% 8/118 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	5.7% 7/122 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.
Gastrointestinal disorders Nausea	2.5% 3/119 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	1.6% 2/124 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	5.1% 6/118 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	7.4% 9/122 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.
General disorders Fatigue	2.5% 3/119 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	1.6% 2/124 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	7.6% 9/118 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	6.6% 8/122 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.
General disorders Influenza like illness	0.00% 0/119 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	0.00% 0/124 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	9.3% 11/118 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	4.9% 6/122 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.
General disorders Injection site haematoma	0.84% 1/119 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	1.6% 2/124 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	1.7% 2/118 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	5.7% 7/122 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.
General disorders Injection site pain	5.9% 7/119 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	5.6% 7/124 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	6.8% 8/118 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	6.6% 8/122 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.
General disorders Pyrexia	0.84% 1/119 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	0.00% 0/124 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	6.8% 8/118 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	5.7% 7/122 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.
Infections and infestations Bronchitis	1.7% 2/119 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	0.81% 1/124 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	6.8% 8/118 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	7.4% 9/122 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.
Infections and infestations Cystitis	0.84% 1/119 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	1.6% 2/124 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	5.9% 7/118 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	6.6% 8/122 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.
Infections and infestations Gastroenteritis	0.84% 1/119 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	0.00% 0/124 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	11.0% 13/118 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	8.2% 10/122 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.
Infections and infestations Influenza	0.00% 0/119 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	0.00% 0/124 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	12.7% 15/118 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	21.3% 26/122 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.
Infections and infestations Nasopharyngitis	5.0% 6/119 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	9.7% 12/124 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	38.1% 45/118 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	55.7% 68/122 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.
Infections and infestations Rhinitis	0.00% 0/119 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	0.00% 0/124 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	5.1% 6/118 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	4.1% 5/122 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.
Infections and infestations Sinusitis	0.84% 1/119 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	0.81% 1/124 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	8.5% 10/118 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	10.7% 13/122 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.
Infections and infestations Tonsillitis	0.84% 1/119 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	0.81% 1/124 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	5.1% 6/118 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	1.6% 2/122 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.
Infections and infestations Upper respiratory tract infection	3.4% 4/119 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	0.00% 0/124 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	7.6% 9/118 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	5.7% 7/122 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.
Infections and infestations Urinary tract infection	0.00% 0/119 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	0.81% 1/124 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	6.8% 8/118 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	13.1% 16/122 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.
Musculoskeletal and connective tissue disorders Arthralgia	1.7% 2/119 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	3.2% 4/124 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	7.6% 9/118 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	9.8% 12/122 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.
Musculoskeletal and connective tissue disorders Back pain	4.2% 5/119 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	1.6% 2/124 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	12.7% 15/118 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	14.8% 18/122 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.
Musculoskeletal and connective tissue disorders Neck pain	2.5% 3/119 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	0.00% 0/124 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	7.6% 9/118 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	4.9% 6/122 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/119 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	2.4% 3/124 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	4.2% 5/118 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	5.7% 7/122 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.
Nervous system disorders Dizziness	2.5% 3/119 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	1.6% 2/124 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	4.2% 5/118 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	5.7% 7/122 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.
Nervous system disorders Headache	0.00% 0/119 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	0.00% 0/124 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	4.2% 5/118 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	5.7% 7/122 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.
Nervous system disorders Migraine	0.00% 0/119 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	1.6% 2/124 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	8.5% 10/118 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	8.2% 10/122 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.
Psychiatric disorders Insomnia	1.7% 2/119 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	0.81% 1/124 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	2.5% 3/118 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	7.4% 9/122 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.
Respiratory, thoracic and mediastinal disorders Cough	0.84% 1/119 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	0.81% 1/124 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	8.5% 10/118 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	8.2% 10/122 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	0.84% 1/119 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	0.00% 0/124 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	11.0% 13/118 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	4.9% 6/122 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.
Vascular disorders Hypertension	0.84% 1/119 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	0.81% 1/124 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	11.9% 14/118 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.	7.4% 9/122 • Adverse events were reported from the first dose of study treatment through the completion of the up to 196-week trial for a maximum treatment exposure of 199 weeks (includes 4 week follow-up). Safety dataset included only those patients, who received at least one dose of study drug. Among 246 patients randomized, two patients in AMG334 and one in Placebo groups were not dosed and were not included.

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: + 1 862 778 8300

Email: Novartis.email@Novartis.com

Results disclosure agreements

• Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial.
• Publication restrictions are in place

Restriction type: OTHER