Trial Outcomes & Findings for Study to Evaluate the Efficacy and Safety of Erenumab (AMG 334) in Migraine Prevention (NCT NCT02456740)

NCT ID: NCT02456740

Last Updated: 2022-10-12

Results Overview

A migraine day was any calendar day in which the participant experienced a qualified migraine headache (onset, continuation, or recurrence of the migraine headache). A qualified migraine headache was defined either as a migraine with or without aura. The change from baseline in monthly migraine days was calculated as the average number of migraine days per month during the last 3 months (months 4, 5, and 6) of the 24-week double-blind treatment phase - the number of migraine days during the 4-week baseline phase.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 955 participants
• Primary outcome timeframe: 4-week baseline phase and the last 3 months (months 4, 5, and 6) of the 24-week double-blind treatment phase
• Results posted on: 2022-10-12

Participant Flow

This study was conducted at 121 centers in Canada, Austria, Belgium, Czech Republic, Finland, Germany, Poland, Slovakia, Sweden, the United Kingdom, Turkey, the Netherlands and USA. The study consisted of a 24-week double-blind treatment phase and a 28-week active treatment phase.

At the end of the baseline phase, participants were randomized 1:1:1 to receive placebo, erenumab 70 mg, or erenumab 140 mg monthly for 24 weeks. Randomization was stratified by region and treatment status with migraine prophylactic medication. Participants were re-randomized at week 24 to erenumab 70 mg or 140 mg for 28 weeks.

Participant milestones

Measure	Placebo Participants received placebo once a month (QM) by subcutaneous injection on day 1 and weeks 4, 8, 12, 16, and 20 in the 24-week double-blind treatment phase.	Erenumab 70 mg QM Participants received erenumab 70 mg QM by subcutaneous injection on day 1 and weeks 4, 8, 12, 16, and 20 in the 24-week double-blind treatment phase.	Erenumab 140 mg QM Participants received erenumab 140 mg QM by subcutaneous injection on day 1 and weeks 4, 8, 12, 16, and 20 in the 24-week double-blind treatment phase.	Placebo / Erenumab 70 mg Participants originally randomized to receive placebo in the 24-week double-blind treatment phase were re-randomized at week 24 to receive erenumab 70 mg subcutaneously at weeks 24, 28, 32, 36, 40, 44, and 48 in the active treatment phase.	Erenumab 70 mg / Erenumab 70 mg Participants originally randomized to receive erenumab 70 mg QM in the 24-week double-blind treatment phase were re-randomized at week 24 to receive erenumab 70 mg subcutaneously at weeks 24, 28, 32, 36, 40, 44, and 48 in the active treatment phase.	Erenumab 140 mg / Erenumab 70 mg Participants originally randomized to receive erenumab 140 mg QM in the 24-week double-blind treatment phase were re-randomized at week 24 to receive erenumab 70 mg subcutaneously at weeks 24, 28, 32, 36, 40, 44, and 48 in the active treatment phase.	Placebo / Erenumab 140 mg Participants originally randomized to receive placebo QM in the 24-week double-blind treatment phase were re-randomized at week 24 to receive erenumab 140 mg subcutaneously at weeks 24, 28, 32, 36, 40, 44, and 48 in the active treatment phase.	Erenumab 70 mg / Erenumab 140 mg Participants originally randomized to receive erenumab 70 mg QM in the 24-week double-blind treatment phase were re-randomized at week 24 to receive erenumab 140 mg subcutaneously at weeks 24, 28, 32, 36, 40, 44, and 48 in the active treatment phase.	Erenumab 140 mg / Erenumab 140 mg Participants originally randomized to receive erenumab 140 mg QM in the 24-week double-blind treatment phase were re-randomized at week 24 to receive erenumab 140 mg subcutaneously at weeks 24, 28, 32, 36, 40, 44, and 48 in the active treatment phase.
Double-blind Treatment Phase (24 Weeks) STARTED	319	317	319	0	0	0	0	0	0
Double-blind Treatment Phase (24 Weeks) Received Study Drug	319	314	319	0	0	0	0	0	0
Double-blind Treatment Phase (24 Weeks) COMPLETED	282	284	292	0	0	0	0	0	0
Double-blind Treatment Phase (24 Weeks) NOT COMPLETED	37	33	27	0	0	0	0	0	0
Active Treatment Phase (Weeks 24 - 52) STARTED	0	0	0	138	140	143	140	140	144
Active Treatment Phase (Weeks 24 - 52) COMPLETED	0	0	0	124	123	130	131	128	126
Active Treatment Phase (Weeks 24 - 52) NOT COMPLETED	0	0	0	14	17	13	9	12	18

Reasons for withdrawal

Measure	Placebo Participants received placebo once a month (QM) by subcutaneous injection on day 1 and weeks 4, 8, 12, 16, and 20 in the 24-week double-blind treatment phase.	Erenumab 70 mg QM Participants received erenumab 70 mg QM by subcutaneous injection on day 1 and weeks 4, 8, 12, 16, and 20 in the 24-week double-blind treatment phase.	Erenumab 140 mg QM Participants received erenumab 140 mg QM by subcutaneous injection on day 1 and weeks 4, 8, 12, 16, and 20 in the 24-week double-blind treatment phase.	Placebo / Erenumab 70 mg Participants originally randomized to receive placebo in the 24-week double-blind treatment phase were re-randomized at week 24 to receive erenumab 70 mg subcutaneously at weeks 24, 28, 32, 36, 40, 44, and 48 in the active treatment phase.	Erenumab 70 mg / Erenumab 70 mg Participants originally randomized to receive erenumab 70 mg QM in the 24-week double-blind treatment phase were re-randomized at week 24 to receive erenumab 70 mg subcutaneously at weeks 24, 28, 32, 36, 40, 44, and 48 in the active treatment phase.	Erenumab 140 mg / Erenumab 70 mg Participants originally randomized to receive erenumab 140 mg QM in the 24-week double-blind treatment phase were re-randomized at week 24 to receive erenumab 70 mg subcutaneously at weeks 24, 28, 32, 36, 40, 44, and 48 in the active treatment phase.	Placebo / Erenumab 140 mg Participants originally randomized to receive placebo QM in the 24-week double-blind treatment phase were re-randomized at week 24 to receive erenumab 140 mg subcutaneously at weeks 24, 28, 32, 36, 40, 44, and 48 in the active treatment phase.	Erenumab 70 mg / Erenumab 140 mg Participants originally randomized to receive erenumab 70 mg QM in the 24-week double-blind treatment phase were re-randomized at week 24 to receive erenumab 140 mg subcutaneously at weeks 24, 28, 32, 36, 40, 44, and 48 in the active treatment phase.	Erenumab 140 mg / Erenumab 140 mg Participants originally randomized to receive erenumab 140 mg QM in the 24-week double-blind treatment phase were re-randomized at week 24 to receive erenumab 140 mg subcutaneously at weeks 24, 28, 32, 36, 40, 44, and 48 in the active treatment phase.
Double-blind Treatment Phase (24 Weeks) Decision by Sponsor	1	1	1	0	0	0	0	0	0
Double-blind Treatment Phase (24 Weeks) Withdrawal by Subject	27	28	21	0	0	0	0	0	0
Double-blind Treatment Phase (24 Weeks) Lost to Follow-up	9	4	5	0	0	0	0	0	0
Active Treatment Phase (Weeks 24 - 52) Protocol Specified Criteria	0	0	0	1	4	0	0	0	5
Active Treatment Phase (Weeks 24 - 52) Withdrawal by Subject	0	0	0	10	11	9	8	8	9
Active Treatment Phase (Weeks 24 - 52) Death	0	0	0	0	0	0	0	1	0
Active Treatment Phase (Weeks 24 - 52) Lost to Follow-up	0	0	0	3	2	4	1	3	4

Baseline Characteristics

Participants with non-missing values

Baseline characteristics by cohort

Measure	Placebo n=319 Participants Participants received placebo once a month (QM) by subcutaneous injection on day 1 and weeks 4, 8, 12, 16, and 20 in the 24-week double-blind treatment phase.	Erenumab 70 mg QM n=317 Participants Participants received erenumab 70 mg QM by subcutaneous injection on day 1 and weeks 4, 8, 12, 16, and 20 in the 24-week double-blind treatment phase.	Erenumab 140 mg QM n=319 Participants Participants received erenumab 140 mg QM by subcutaneous injection on day 1 and weeks 4, 8, 12, 16, and 20 in the 24-week double-blind treatment phase.	Total n=955 Participants Total of all reporting groups
Age, Continuous	41.3 years STANDARD_DEVIATION 11.2 • n=319 Participants	41.1 years STANDARD_DEVIATION 11.3 • n=317 Participants	40.4 years STANDARD_DEVIATION 11.1 • n=319 Participants	40.9 years STANDARD_DEVIATION 11.2 • n=955 Participants
Age, Customized 18 - 64 years	317 Participants n=319 Participants	317 Participants n=317 Participants	317 Participants n=319 Participants	951 Participants n=955 Participants
Age, Customized 65 - 74 years	2 Participants n=319 Participants	0 Participants n=317 Participants	2 Participants n=319 Participants	4 Participants n=955 Participants
Sex: Female, Male Female	274 Participants n=319 Participants	268 Participants n=317 Participants	272 Participants n=319 Participants	814 Participants n=955 Participants
Sex: Female, Male Male	45 Participants n=319 Participants	49 Participants n=317 Participants	47 Participants n=319 Participants	141 Participants n=955 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	32 Participants n=319 Participants	26 Participants n=317 Participants	22 Participants n=319 Participants	80 Participants n=955 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	287 Participants n=319 Participants	291 Participants n=317 Participants	297 Participants n=319 Participants	875 Participants n=955 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=319 Participants	0 Participants n=317 Participants	0 Participants n=319 Participants	0 Participants n=955 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	2 Participants n=319 Participants	0 Participants n=317 Participants	1 Participants n=319 Participants	3 Participants n=955 Participants
Race/Ethnicity, Customized Asian	8 Participants n=319 Participants	5 Participants n=317 Participants	4 Participants n=319 Participants	17 Participants n=955 Participants
Race/Ethnicity, Customized Black or African American	24 Participants n=319 Participants	24 Participants n=317 Participants	18 Participants n=319 Participants	66 Participants n=955 Participants
Race/Ethnicity, Customized Multiple	2 Participants n=319 Participants	1 Participants n=317 Participants	0 Participants n=319 Participants	3 Participants n=955 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	0 Participants n=319 Participants	0 Participants n=317 Participants	1 Participants n=319 Participants	1 Participants n=955 Participants
Race/Ethnicity, Customized White	277 Participants n=319 Participants	281 Participants n=317 Participants	293 Participants n=319 Participants	851 Participants n=955 Participants
Race/Ethnicity, Customized Other	6 Participants n=319 Participants	6 Participants n=317 Participants	2 Participants n=319 Participants	14 Participants n=955 Participants
Region North America	158 Participants n=319 Participants	159 Participants n=317 Participants	160 Participants n=319 Participants	477 Participants n=955 Participants
Region Other	161 Participants n=319 Participants	158 Participants n=317 Participants	159 Participants n=319 Participants	478 Participants n=955 Participants
Treatment Status with Migraine Prophylactic Medication Current migraine prophylactic treatment	8 Participants n=319 Participants	6 Participants n=317 Participants	7 Participants n=319 Participants	21 Participants n=955 Participants
Treatment Status with Migraine Prophylactic Medication Prior migraine prophylactic treatment only	119 Participants n=319 Participants	119 Participants n=317 Participants	120 Participants n=319 Participants	358 Participants n=955 Participants
Treatment Status with Migraine Prophylactic Medication No prior / current migraine prophylactic treatment	192 Participants n=319 Participants	192 Participants n=317 Participants	192 Participants n=319 Participants	576 Participants n=955 Participants
Monthly Migraine Days	8.23 migraine days/month STANDARD_DEVIATION 2.51 • n=318 Participants • Participants with non-missing values	8.29 migraine days/month STANDARD_DEVIATION 2.47 • n=316 Participants • Participants with non-missing values	8.34 migraine days/month STANDARD_DEVIATION 2.48 • n=319 Participants • Participants with non-missing values	8.29 migraine days/month STANDARD_DEVIATION 2.48 • n=953 Participants • Participants with non-missing values

PRIMARY outcome

Timeframe: 4-week baseline phase and the last 3 months (months 4, 5, and 6) of the 24-week double-blind treatment phase

Population: The analysis was conducted in the efficacy analysis set which includes participants who received at least 1 dose of study drug and had at least 1 change from baseline measurement in monthly migraine days in the double-blind treatment phase.

A migraine day was any calendar day in which the participant experienced a qualified migraine headache (onset, continuation, or recurrence of the migraine headache). A qualified migraine headache was defined either as a migraine with or without aura.

The change from baseline in monthly migraine days was calculated as the average number of migraine days per month during the last 3 months (months 4, 5, and 6) of the 24-week double-blind treatment phase - the number of migraine days during the 4-week baseline phase.

Outcome measures

Measure	Placebo n=316 Participants Participants received placebo once a month (QM) by subcutaneous injection on day 1 and weeks 4, 8, 12, 16, and 20 in the 24-week double-blind treatment phase.	Erenumab 70 mg QM n=312 Participants Participants received erenumab 70 mg QM by subcutaneous injection on day 1 and weeks 4, 8, 12, 16, and 20 in the 24-week double-blind treatment phase.	Erenumab 140 mg QM n=318 Participants Participants received erenumab 140 mg QM by subcutaneous injection on day 1 and weeks 4, 8, 12, 16, and 20 in the 24-week double-blind treatment phase.
Change From Baseline in Mean Monthly Migraine Days to the Last 3 Months of the Double-blind Treatment Period	-1.83 migraine days / month Standard Error 0.18	-3.23 migraine days / month Standard Error 0.18	-3.67 migraine days / month Standard Error 0.18

SECONDARY outcome

Timeframe: 4-week baseline phase and the last 3 months (months 4, 5, and 6) of the 24-week double-blind treatment phase

Population: The analysis was conducted in the efficacy analysis set which includes participants who received at least 1 dose of study drug and had at least 1 change from baseline measurement in monthly migraine days in the double-blind treatment phase. Participants with missing data at months 4, 5, and 6 were counted as non-responders.

A migraine day was any calendar day in which the participant experienced a qualified migraine headache (onset, continuation, or recurrence of the migraine headache). A qualified migraine headache was defined either as a migraine without aura or a migraine with aura.

At least a 50% reduction from baseline in monthly migraine days was determined if the change in monthly migraine days from the 4-week baseline phase to the last 3 months (mean of months 4, 5 and 6) of the 24-week double-blind treatment phase * 100 / baseline monthly migraine days was less than or equal to -50%.

Outcome measures

Measure	Placebo n=316 Participants Participants received placebo once a month (QM) by subcutaneous injection on day 1 and weeks 4, 8, 12, 16, and 20 in the 24-week double-blind treatment phase.	Erenumab 70 mg QM n=312 Participants Participants received erenumab 70 mg QM by subcutaneous injection on day 1 and weeks 4, 8, 12, 16, and 20 in the 24-week double-blind treatment phase.	Erenumab 140 mg QM n=318 Participants Participants received erenumab 140 mg QM by subcutaneous injection on day 1 and weeks 4, 8, 12, 16, and 20 in the 24-week double-blind treatment phase.
Percentage of Participants With at Least a 50% Reduction From Baseline in Monthly Migraine Days in the Last 3 Months of the Double-blind Treatment Phase	26.6 percentage of participants	43.3 percentage of participants	50.0 percentage of participants

SECONDARY outcome

Timeframe: 4-week baseline phase and the last 3 months (months 4, 5, and 6) of the 24-week double-blind treatment phase

Population: The analysis was conducted in the efficacy analysis set which includes participants who received at least 1 dose of study drug and had at least 1 change from baseline measurement in monthly acute migraine-specific treatment days in the double-blind treatment phase.

Monthly acute migraine-specific medication treatment days is the number of days on which migraine specific medications were used between monthly doses of study drug. Migraine-specific medications includes two categories of medications: triptan-based migraine medications and ergotamine-based migraine medications.

The change from baseline in monthly acute migraine-specific treatment days was calculated as the average number of migraine-specific treatment days per month during the last 3 months of the 24-week double-blind treatment phase - the number of migraine-specific treatment days during the 4-week baseline phase.

Outcome measures

Measure	Placebo n=316 Participants Participants received placebo once a month (QM) by subcutaneous injection on day 1 and weeks 4, 8, 12, 16, and 20 in the 24-week double-blind treatment phase.	Erenumab 70 mg QM n=312 Participants Participants received erenumab 70 mg QM by subcutaneous injection on day 1 and weeks 4, 8, 12, 16, and 20 in the 24-week double-blind treatment phase.	Erenumab 140 mg QM n=318 Participants Participants received erenumab 140 mg QM by subcutaneous injection on day 1 and weeks 4, 8, 12, 16, and 20 in the 24-week double-blind treatment phase.
Change From Baseline in Monthly Acute Migraine-specific Medication Treatment Days to the Last 3 Months of the Double-blind Treatment Period	-0.20 Acute migraine-specific med days/mo Standard Error 0.11	-1.13 Acute migraine-specific med days/mo Standard Error 0.11	-1.61 Acute migraine-specific med days/mo Standard Error 0.11

SECONDARY outcome

Timeframe: 4-week baseline phase and the last 3 months (months 4, 5, and 6) of the 24-week double-blind treatment phase

Population: The analysis was conducted in the efficacy analysis set including participants who received at least 1 dose of study drug and had at least 1 change from baseline measurement in MPFID average physical impairment domain score in the double-blind treatment phase.

The Migraine Physical Function Impact Diary (MPFID) is a self-administered 13-item instrument measuring physical functioning. It has two domains, Impact on Everyday Activities (7 items) and Physical Impairment (5 items), and one stand-alone global question. Participants completed the MPFID daily in an electronic diary based on the past 24 hours. Participants responded to each item on a 5-point scale, with difficulty items ranging from "Without any difficulty" (1) to "Unable to do" (5) and frequency items ranging from "None of the time" (1) to "All of the time" (5). For each domain, the scores were calculated as the sum of the responses and rescaled to 0 - 100, with higher scores representing greater impact of migraine.

Change from baseline was calculated as (mean monthly average physical impairment scores as measured by the MPFID over the last 3 months of the double-blind treatment period) - (baseline monthly average physical impairment scores as measured by the MPFID).

Outcome measures

Measure	Placebo n=316 Participants Participants received placebo once a month (QM) by subcutaneous injection on day 1 and weeks 4, 8, 12, 16, and 20 in the 24-week double-blind treatment phase.	Erenumab 70 mg QM n=312 Participants Participants received erenumab 70 mg QM by subcutaneous injection on day 1 and weeks 4, 8, 12, 16, and 20 in the 24-week double-blind treatment phase.	Erenumab 140 mg QM n=318 Participants Participants received erenumab 140 mg QM by subcutaneous injection on day 1 and weeks 4, 8, 12, 16, and 20 in the 24-week double-blind treatment phase.
Change From Baseline in Mean Monthly Average Physical Impairment Domain Score Measured by MPFID in the Last 3 Months of the Double-blind Treatment Phase	-2.38 units on a scale Standard Error 0.40	-4.24 units on a scale Standard Error 0.40	-4.81 units on a scale Standard Error 0.40

SECONDARY outcome

Timeframe: 4-week baseline phase and the last 3 months (months 4, 5, and 6) of the 24-week double-blind treatment phase

Population: The analysis was conducted in the efficacy analysis set including participants who received at least 1 dose of study drug and had at least 1 change from baseline measurement in MPFID average impact on everyday activities domain score in the double-blind treatment phase.

The Migraine Physical Function Impact Diary (MPFID) is a self-administered 13-item instrument measuring physical functioning. It has two domains, Impact on Everyday Activities (7 items) and Physical Impairment (5 items), and one stand-alone global question. Participants completed the MPFID daily in an electronic diary based on the past 24 hours. Participants responded to each item on a 5-point scale, with difficulty items ranging from "Without any difficulty" (1) to "Unable to do" (5) and frequency items ranging from "None of the time" (1) to "All of the time" (5). For each domain, the scores were calculated as the sum of the responses and rescaled to 0 - 100, with higher scores representing greater impact of migraine.

Change from baseline was calculated as (mean monthly impact on everyday activities scores as measured by the MPFID over the last 3 months of the double-blind treatment period) - (baseline monthly impact on everyday activities scores as measured by the MPFID).

Outcome measures

Measure	Placebo n=316 Participants Participants received placebo once a month (QM) by subcutaneous injection on day 1 and weeks 4, 8, 12, 16, and 20 in the 24-week double-blind treatment phase.	Erenumab 70 mg QM n=312 Participants Participants received erenumab 70 mg QM by subcutaneous injection on day 1 and weeks 4, 8, 12, 16, and 20 in the 24-week double-blind treatment phase.	Erenumab 140 mg QM n=318 Participants Participants received erenumab 140 mg QM by subcutaneous injection on day 1 and weeks 4, 8, 12, 16, and 20 in the 24-week double-blind treatment phase.
Change From Baseline in Mean Monthly Average Impact on Everyday Activities Score Measured by MPFID in the Last 3 Months of the Double-blind Treatment Phase	-3.30 units on a scale Standard Error 0.39	-5.52 units on a scale Standard Error 0.39	-5.86 units on a scale Standard Error 0.39

Adverse Events

Double-blind Treatment Phase: Placebo

Serious events: 7 serious events

Other events: 53 other events

Deaths: 0 deaths

Double-blind Treatment Phase: Erenumab 70 mg

Serious events: 8 serious events

Other events: 53 other events

Deaths: 0 deaths

Double-blind Treatment Phase: Erenumab 140 mg

Serious events: 8 serious events

Other events: 54 other events

Deaths: 0 deaths

Active Treatment Phase: Erenumab 70 mg

Serious events: 14 serious events

Other events: 83 other events

Deaths: 0 deaths

Active Treatment Phase: Erenumab 140 mg

Serious events: 14 serious events

Other events: 63 other events

Deaths: 0 deaths

Serious adverse events

Measure	Double-blind Treatment Phase: Placebo n=319 participants at risk Participants received placebo once a month (QM) by subcutaneous injection on day 1 and weeks 4, 8, 12, 16, and 20 in the 24-week double-blind treatment phase.	Double-blind Treatment Phase: Erenumab 70 mg n=314 participants at risk Participants received erenumab 70 mg QM by subcutaneous injection on day 1 and weeks 4, 8, 12, 16, and 20 in the 24-week double-blind treatment phase.	Double-blind Treatment Phase: Erenumab 140 mg n=319 participants at risk Participants received erenumab 140 mg QM by subcutaneous injection on day 1 and weeks 4, 8, 12, 16, and 20 in the 24-week double-blind treatment phase.	Active Treatment Phase: Erenumab 70 mg n=421 participants at risk Participants received erenumab 70 mg subcutaneously at weeks 24, 28, 32, 36, 40, 44, and 48 in the active treatment phase.	Active Treatment Phase: Erenumab 140 mg n=424 participants at risk Participants received erenumab 140 mg subcutaneously at weeks 24, 28, 32, 36, 40, 44, and 48 in the active treatment phase.
Cardiac disorders Pericarditis	0.00% 0/319 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/314 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/319 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/421 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.24% 1/424 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Congenital, familial and genetic disorders Arrhythmogenic right ventricular dysplasia	0.00% 0/319 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/314 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/319 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/421 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.24% 1/424 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Eye disorders Idiopathic orbital inflammation	0.00% 0/319 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/314 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/319 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.24% 1/421 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/424 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Gastrointestinal disorders Dyspepsia	0.00% 0/319 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/314 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/319 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.24% 1/421 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/424 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Gastrointestinal disorders Gastritis	0.00% 0/319 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/314 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/319 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.24% 1/421 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/424 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Gastrointestinal disorders Gastrooesophageal reflux disease	0.00% 0/319 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/314 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/319 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.24% 1/421 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/424 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
General disorders Non-cardiac chest pain	0.31% 1/319 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.32% 1/314 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.31% 1/319 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/421 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/424 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Hepatobiliary disorders Cholelithiasis	0.00% 0/319 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.64% 2/314 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/319 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/421 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/424 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Immune system disorders Hypersensitivity	0.31% 1/319 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/314 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/319 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/421 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/424 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Appendicitis	0.00% 0/319 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/314 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/319 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/421 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.24% 1/424 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Clostridium difficile colitis	0.00% 0/319 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/314 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.31% 1/319 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/421 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/424 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Diverticulitis	0.00% 0/319 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/314 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/319 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/421 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.47% 2/424 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Erysipelas	0.00% 0/319 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/314 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/319 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/421 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.24% 1/424 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Gastroenteritis viral	0.00% 0/319 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/314 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.31% 1/319 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/421 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/424 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Kidney infection	0.00% 0/319 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/314 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.31% 1/319 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/421 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/424 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Postoperative abscess	0.00% 0/319 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/314 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/319 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.24% 1/421 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/424 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Pyelonephritis	0.00% 0/319 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/314 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.31% 1/319 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/421 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/424 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Pyelonephritis acute	0.00% 0/319 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.32% 1/314 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/319 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/421 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/424 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Sepsis	0.00% 0/319 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/314 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.31% 1/319 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/421 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/424 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Vestibular neuronitis	0.00% 0/319 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/314 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.31% 1/319 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/421 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/424 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Injury, poisoning and procedural complications Ankle fracture	0.00% 0/319 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/314 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.31% 1/319 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/421 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/424 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Injury, poisoning and procedural complications Fall	0.31% 1/319 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/314 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/319 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/421 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/424 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Injury, poisoning and procedural complications Femur fracture	0.00% 0/319 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/314 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/319 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.24% 1/421 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/424 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Injury, poisoning and procedural complications Intentional overdose	0.31% 1/319 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/314 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/319 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/421 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/424 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Injury, poisoning and procedural complications Post-traumatic neck syndrome	0.00% 0/319 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.32% 1/314 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/319 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/421 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/424 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Injury, poisoning and procedural complications Radius fracture	0.00% 0/319 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/314 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/319 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/421 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.24% 1/424 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Injury, poisoning and procedural complications Subdural haematoma	0.00% 0/319 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/314 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/319 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/421 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.24% 1/424 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Injury, poisoning and procedural complications Wound	0.00% 0/319 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/314 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/319 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.24% 1/421 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/424 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Metabolism and nutrition disorders Dehydration	0.00% 0/319 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/314 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/319 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/421 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.24% 1/424 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Musculoskeletal and connective tissue disorders Arthralgia	0.31% 1/319 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/314 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/319 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/421 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/424 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/319 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.32% 1/314 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/319 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/421 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/424 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Musculoskeletal and connective tissue disorders Osteoarthritis	0.31% 1/319 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/314 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/319 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/421 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/424 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Musculoskeletal and connective tissue disorders Spinal pain	0.00% 0/319 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/314 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.31% 1/319 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/421 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/424 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer	0.00% 0/319 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/314 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/319 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/421 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.24% 1/424 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast fibroma	0.00% 0/319 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/314 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/319 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/421 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.24% 1/424 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prolactin-producing pituitary tumour	0.00% 0/319 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/314 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/319 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/421 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.24% 1/424 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Uterine leiomyoma	0.00% 0/319 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/314 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.31% 1/319 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/421 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.24% 1/424 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Nervous system disorders Cerebral venous thrombosis	0.00% 0/319 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/314 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.31% 1/319 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/421 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/424 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Nervous system disorders Idiopathic intracranial hypertension	0.00% 0/319 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/314 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/319 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.24% 1/421 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/424 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Nervous system disorders Migraine	0.00% 0/319 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.32% 1/314 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/319 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/421 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/424 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Nervous system disorders Migraine with aura	0.00% 0/319 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/314 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/319 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.24% 1/421 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/424 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Nervous system disorders Syncope	0.00% 0/319 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/314 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.31% 1/319 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.24% 1/421 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/424 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Nervous system disorders Toxic encephalopathy	0.00% 0/319 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/314 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/319 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.24% 1/421 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/424 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Psychiatric disorders Depression	0.00% 0/319 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/314 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/319 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.24% 1/421 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/424 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Reproductive system and breast disorders Breast cyst	0.00% 0/319 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/314 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/319 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/421 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.24% 1/424 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Reproductive system and breast disorders Endometriosis	0.31% 1/319 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/314 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/319 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/421 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/424 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Reproductive system and breast disorders Ovarian cyst	0.00% 0/319 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.32% 1/314 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/319 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/421 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/424 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Respiratory, thoracic and mediastinal disorders Nasal septum deviation	0.00% 0/319 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/314 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/319 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.24% 1/421 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/424 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Vascular disorders Deep vein thrombosis	0.00% 0/319 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/314 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/319 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.24% 1/421 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/424 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.

Other adverse events

Measure	Double-blind Treatment Phase: Placebo n=319 participants at risk Participants received placebo once a month (QM) by subcutaneous injection on day 1 and weeks 4, 8, 12, 16, and 20 in the 24-week double-blind treatment phase.	Double-blind Treatment Phase: Erenumab 70 mg n=314 participants at risk Participants received erenumab 70 mg QM by subcutaneous injection on day 1 and weeks 4, 8, 12, 16, and 20 in the 24-week double-blind treatment phase.	Double-blind Treatment Phase: Erenumab 140 mg n=319 participants at risk Participants received erenumab 140 mg QM by subcutaneous injection on day 1 and weeks 4, 8, 12, 16, and 20 in the 24-week double-blind treatment phase.	Active Treatment Phase: Erenumab 70 mg n=421 participants at risk Participants received erenumab 70 mg subcutaneously at weeks 24, 28, 32, 36, 40, 44, and 48 in the active treatment phase.	Active Treatment Phase: Erenumab 140 mg n=424 participants at risk Participants received erenumab 140 mg subcutaneously at weeks 24, 28, 32, 36, 40, 44, and 48 in the active treatment phase.
Infections and infestations Upper respiratory tract infection	6.0% 19/319 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	6.7% 21/314 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	4.7% 15/319 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	5.9% 25/421 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	4.5% 19/424 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Viral upper respiratory tract infection	10.7% 34/319 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	10.2% 32/314 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	12.2% 39/319 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	13.8% 58/421 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	10.4% 44/424 • From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.

Additional Information

Study Director

Amgen Inc.

Phone: 866-572-6436

Results disclosure agreements

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

Restriction type: OTHER