Trial Outcomes & Findings for Effects of Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Inhibition on Arterial Wall Inflammation in Patients With Elevated Lipoprotein(a) (Lp(a)) (NCT NCT02729025)

NCT ID: NCT02729025

Last Updated: 2022-09-23

Results Overview

Arterial inflammation was assessed using 18F-fluoro-deoxyglucose positron-emission tomography/computed tomography (18F-FDG PET/CT). Arterial 18F-FDG uptake is correlated with arterial macrophage content and predicts cardiovascular events. Images were analyzed by an experienced radiologist blinded to all patient characteristics. The maximum standardized uptake value was calculated as a time- and dose- corrected tissue radioactivity divided by body weight in the index and the target-to-background ratio (TBR) was calculated from the ratio of the standardized uptake value of the artery compared to mean background venous activity. The average maximum TBR for the most diseased segment (MDS) was calculated from a group of 3 contiguous slices (approximately 1.5 cm), centered on the slice with the highest maximum TBR in the index vessel. The index vessel was defined as the vessel (either the right or left carotid or aorta) with the highest mean TBR at baseline.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 129 participants
• Primary outcome timeframe: Baseline and week 16
• Results posted on: 2022-09-23

Participant Flow

This study was conducted at 14 centers in Canada, the Netherlands, and the United States. Participants were enrolled from 14 April 2016 to 07 December 2017.

Eligible participants were randomized in a 1:1 ratio to receive either evolocumab or placebo. Randomization was stratified by baseline background statin therapy (on statin versus not on statin) and by screening lipoprotein(a) (Lp[a]) (< 175 mg/dL or ≥ 175 mg/dL).

Participant milestones

Measure	Placebo Participants received placebo to evolocumab by subcutaneous injection once a month (QM) for 12 weeks.	Evolocumab 420 mg QM Participants received 420 mg evolocumab by subcutaneous injection once a month (QM) for 12 weeks.
Overall Study STARTED	64	65
Overall Study COMPLETED	64	64
Overall Study NOT COMPLETED	0	1

Reasons for withdrawal

Measure	Placebo Participants received placebo to evolocumab by subcutaneous injection once a month (QM) for 12 weeks.	Evolocumab 420 mg QM Participants received 420 mg evolocumab by subcutaneous injection once a month (QM) for 12 weeks.
Overall Study Sponsor Decision	0	1

Baseline Characteristics

Participants with available data

Baseline characteristics by cohort

Measure	Placebo n=64 Participants Participants received placebo to evolocumab by subcutaneous injection once a month (QM) for 12 weeks.	Evolocumab 420 mg QM n=65 Participants Participants received 420 mg evolocumab by subcutaneous injection once a month (QM) for 12 weeks.	Total n=129 Participants Total of all reporting groups
Age, Continuous	60.7 years STANDARD_DEVIATION 7.6 • n=64 Participants	60.0 years STANDARD_DEVIATION 6.8 • n=65 Participants	60.3 years STANDARD_DEVIATION 7.2 • n=129 Participants
Age, Customized 18 - 64 years	41 Participants n=64 Participants	48 Participants n=65 Participants	89 Participants n=129 Participants
Age, Customized ≥ 65 years	23 Participants n=64 Participants	17 Participants n=65 Participants	40 Participants n=129 Participants
Sex: Female, Male Female	30 Participants n=64 Participants	39 Participants n=65 Participants	69 Participants n=129 Participants
Sex: Female, Male Male	34 Participants n=64 Participants	26 Participants n=65 Participants	60 Participants n=129 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=64 Participants	1 Participants n=65 Participants	1 Participants n=129 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	64 Participants n=64 Participants	64 Participants n=65 Participants	128 Participants n=129 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=64 Participants	0 Participants n=65 Participants	0 Participants n=129 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 Participants n=64 Participants	0 Participants n=65 Participants	0 Participants n=129 Participants
Race/Ethnicity, Customized Asian	3 Participants n=64 Participants	2 Participants n=65 Participants	5 Participants n=129 Participants
Race/Ethnicity, Customized Black or African American	2 Participants n=64 Participants	4 Participants n=65 Participants	6 Participants n=129 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	1 Participants n=64 Participants	0 Participants n=65 Participants	1 Participants n=129 Participants
Race/Ethnicity, Customized White	58 Participants n=64 Participants	58 Participants n=65 Participants	116 Participants n=129 Participants
Race/Ethnicity, Customized Other	0 Participants n=64 Participants	1 Participants n=65 Participants	1 Participants n=129 Participants
Location of the Index Vessel Used for Calculation of Maximum Target-to-background Ratio Ascending thoracic aorta	54 Participants n=64 Participants	49 Participants n=65 Participants	103 Participants n=129 Participants
Location of the Index Vessel Used for Calculation of Maximum Target-to-background Ratio Left common carotid	1 Participants n=64 Participants	3 Participants n=65 Participants	4 Participants n=129 Participants
Location of the Index Vessel Used for Calculation of Maximum Target-to-background Ratio Right common carotid	8 Participants n=64 Participants	11 Participants n=65 Participants	19 Participants n=129 Participants
Location of the Index Vessel Used for Calculation of Maximum Target-to-background Ratio Missing	1 Participants n=64 Participants	2 Participants n=65 Participants	3 Participants n=129 Participants
Maximum Target-to-background Ratio (TBR) in the Most Diseased Section of the Index Vessel	2.28765 ratio STANDARD_DEVIATION 0.41284 • n=63 Participants • Participants with available data	2.29667 ratio STANDARD_DEVIATION 0.46063 • n=63 Participants • Participants with available data	2.29216 ratio STANDARD_DEVIATION 0.43566 • n=126 Participants • Participants with available data
Stratification Factor: Baseline Statin Therapy Yes	33 Participants n=64 Participants	34 Participants n=65 Participants	67 Participants n=129 Participants
Stratification Factor: Baseline Statin Therapy No	31 Participants n=64 Participants	31 Participants n=65 Participants	62 Participants n=129 Participants
Stratification Factor: Screening Lipoprotein(a) (Lp[a]) Level < 175 mg/dL	60 Participants n=64 Participants	61 Participants n=65 Participants	121 Participants n=129 Participants
Stratification Factor: Screening Lipoprotein(a) (Lp[a]) Level ≥ 175 mg/dL	4 Participants n=64 Participants	4 Participants n=65 Participants	8 Participants n=129 Participants
Lipoprotein(a) Concentration	198.0 nmol/L n=64 Participants	203.0 nmol/L n=65 Participants	200.0 nmol/L n=129 Participants
Low-density Lipoprotein Cholesterol (LDL-C) Concentration	141.7 mg/dL STANDARD_DEVIATION 35.7 • n=64 Participants	146.2 mg/dL STANDARD_DEVIATION 43.5 • n=65 Participants	144.0 mg/dL STANDARD_DEVIATION 39.7 • n=129 Participants
Apolipoprotein B Concentration	108.0 mg/dL STANDARD_DEVIATION 22.9 • n=64 Participants	109.9 mg/dL STANDARD_DEVIATION 23.7 • n=65 Participants	108.9 mg/dL STANDARD_DEVIATION 23.2 • n=129 Participants

PRIMARY outcome

Timeframe: Baseline and week 16

Population: Participants who received at least 1 dose of study drug with available data

Arterial inflammation was assessed using 18F-fluoro-deoxyglucose positron-emission tomography/computed tomography (18F-FDG PET/CT). Arterial 18F-FDG uptake is correlated with arterial macrophage content and predicts cardiovascular events. Images were analyzed by an experienced radiologist blinded to all patient characteristics.

The maximum standardized uptake value was calculated as a time- and dose- corrected tissue radioactivity divided by body weight in the index and the target-to-background ratio (TBR) was calculated from the ratio of the standardized uptake value of the artery compared to mean background venous activity. The average maximum TBR for the most diseased segment (MDS) was calculated from a group of 3 contiguous slices (approximately 1.5 cm), centered on the slice with the highest maximum TBR in the index vessel. The index vessel was defined as the vessel (either the right or left carotid or aorta) with the highest mean TBR at baseline.

Outcome measures

Measure	Placebo n=63 Participants Participants received placebo to evolocumab by subcutaneous injection once a month (QM) for 12 weeks.	Evolocumab 420 mg QM n=63 Participants Participants received 420 mg evolocumab by subcutaneous injection once a month (QM) for 12 weeks.
Percent Change From Baseline in Maximum Target-to-background Ratio in the Most Diseased Segment of the Index Vessel at Week 16	-5.31 percent change Standard Error 1.67	-8.31 percent change Standard Error 1.67

SECONDARY outcome

Timeframe: Baseline and week 16

Population: Participants who received at least 1 dose of study drug with available data

Outcome measures

Measure	Placebo n=61 Participants Participants received placebo to evolocumab by subcutaneous injection once a month (QM) for 12 weeks.	Evolocumab 420 mg QM n=63 Participants Participants received 420 mg evolocumab by subcutaneous injection once a month (QM) for 12 weeks.
Percent Change From Baseline in Lipoprotein(a) Concentration at Week 16	1.06 percent change Standard Error 1.94	-12.83 percent change Standard Error 1.92

SECONDARY outcome

Timeframe: Baseline and week 16

Population: Participants who received at least 1 dose of study drug with available data

Outcome measures

Measure	Placebo n=59 Participants Participants received placebo to evolocumab by subcutaneous injection once a month (QM) for 12 weeks.	Evolocumab 420 mg QM n=62 Participants Participants received 420 mg evolocumab by subcutaneous injection once a month (QM) for 12 weeks.
Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) Concentration at Week 16	1.64 percent change Standard Error 1.86	-59.02 percent change Standard Error 1.82

SECONDARY outcome

Timeframe: Baseline and week 16

Population: Participants who received at least 1 dose of study drug with available data

Outcome measures

Measure	Placebo n=61 Participants Participants received placebo to evolocumab by subcutaneous injection once a month (QM) for 12 weeks.	Evolocumab 420 mg QM n=63 Participants Participants received 420 mg evolocumab by subcutaneous injection once a month (QM) for 12 weeks.
Percent Change From Baseline in Apolipoprotein B Concentration at Week 16	3.29 percent change Standard Error 1.53	-48.30 percent change Standard Error 1.51

Adverse Events

Placebo QM

Serious events: 0 serious events

Other events: 47 other events

Deaths: 0 deaths

Evolocumab 420 mg QM

Serious events: 2 serious events

Other events: 49 other events

Deaths: 0 deaths

Serious adverse events

Measure	Placebo QM n=64 participants at risk Participants received placebo to evolocumab by subcutaneous injection once a month (QM) for 12 weeks.	Evolocumab 420 mg QM n=65 participants at risk Participants received 420 mg evolocumab by subcutaneous injection once a month (QM) for 12 weeks.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Diffuse large B-cell lymphoma	0.00% 0/64 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	1.5% 1/65 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Renal and urinary disorders Nephrolithiasis	0.00% 0/64 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	1.5% 1/65 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.

Other adverse events

Measure	Placebo QM n=64 participants at risk Participants received placebo to evolocumab by subcutaneous injection once a month (QM) for 12 weeks.	Evolocumab 420 mg QM n=65 participants at risk Participants received 420 mg evolocumab by subcutaneous injection once a month (QM) for 12 weeks.
Cardiac disorders Palpitations	0.00% 0/64 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	1.5% 1/65 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Congenital, familial and genetic disorders Dermoid cyst	1.6% 1/64 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/65 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Congenital, familial and genetic disorders Muscular dystrophy	1.6% 1/64 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/65 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Ear and labyrinth disorders Excessive cerumen production	1.6% 1/64 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/65 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Eye disorders Keratitis	0.00% 0/64 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	1.5% 1/65 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Eye disorders Lacrimation increased	1.6% 1/64 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/65 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Eye disorders Visual impairment	0.00% 0/64 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	1.5% 1/65 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Gastrointestinal disorders Abdominal discomfort	3.1% 2/64 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/65 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Gastrointestinal disorders Abdominal pain	0.00% 0/64 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	1.5% 1/65 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Gastrointestinal disorders Abdominal pain lower	0.00% 0/64 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	1.5% 1/65 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Gastrointestinal disorders Dental caries	0.00% 0/64 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	1.5% 1/65 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Gastrointestinal disorders Diarrhoea	7.8% 5/64 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	1.5% 1/65 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Gastrointestinal disorders Dyspepsia	1.6% 1/64 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/65 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Gastrointestinal disorders Food poisoning	0.00% 0/64 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	3.1% 2/65 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Gastrointestinal disorders Gastrooesophageal reflux disease	0.00% 0/64 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	3.1% 2/65 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Gastrointestinal disorders Nausea	7.8% 5/64 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	1.5% 1/65 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Gastrointestinal disorders Oesophageal pain	1.6% 1/64 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/65 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Gastrointestinal disorders Peptic ulcer	1.6% 1/64 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/65 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Gastrointestinal disorders Toothache	0.00% 0/64 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	1.5% 1/65 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
General disorders Chest pain	4.7% 3/64 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/65 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
General disorders Chills	0.00% 0/64 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	1.5% 1/65 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
General disorders Drug intolerance	1.6% 1/64 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/65 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
General disorders Fatigue	1.6% 1/64 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	3.1% 2/65 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
General disorders Influenza like illness	6.2% 4/64 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	6.2% 4/65 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
General disorders Injection site hypersensitivity	1.6% 1/64 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/65 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
General disorders Injection site pain	1.6% 1/64 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	1.5% 1/65 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
General disorders Injection site rash	1.6% 1/64 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/65 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
General disorders Nodule	0.00% 0/64 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	1.5% 1/65 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
General disorders Non-cardiac chest pain	0.00% 0/64 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	3.1% 2/65 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
General disorders Oedema peripheral	1.6% 1/64 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/65 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
General disorders Pain	0.00% 0/64 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	1.5% 1/65 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Immune system disorders Drug hypersensitivity	1.6% 1/64 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	1.5% 1/65 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Immune system disorders Hypersensitivity	0.00% 0/64 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	1.5% 1/65 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Immune system disorders Seasonal allergy	1.6% 1/64 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	1.5% 1/65 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Bronchitis	3.1% 2/64 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/65 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Cellulitis	0.00% 0/64 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	1.5% 1/65 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Erysipelas	1.6% 1/64 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/65 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Eye infection	1.6% 1/64 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/65 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Folliculitis	0.00% 0/64 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	1.5% 1/65 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations H1N1 influenza	0.00% 0/64 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	1.5% 1/65 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Herpes zoster	0.00% 0/64 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	1.5% 1/65 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Heterophyiasis	0.00% 0/64 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	1.5% 1/65 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Influenza	4.7% 3/64 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	10.8% 7/65 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Nail infection	0.00% 0/64 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	1.5% 1/65 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Nasopharyngitis	20.3% 13/64 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	9.2% 6/65 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Otitis externa	0.00% 0/64 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	1.5% 1/65 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Root canal infection	1.6% 1/64 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/65 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Sinusitis	0.00% 0/64 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	1.5% 1/65 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Upper respiratory tract infection	3.1% 2/64 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	3.1% 2/65 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Urinary tract infection	4.7% 3/64 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	1.5% 1/65 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Vulvovaginal mycotic infection	1.6% 1/64 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/65 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Injury, poisoning and procedural complications Arthropod bite	0.00% 0/64 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	1.5% 1/65 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Injury, poisoning and procedural complications Bone contusion	0.00% 0/64 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	1.5% 1/65 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Injury, poisoning and procedural complications Contusion	0.00% 0/64 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	1.5% 1/65 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Injury, poisoning and procedural complications Epicondylitis	1.6% 1/64 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/65 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Injury, poisoning and procedural complications Fall	0.00% 0/64 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	1.5% 1/65 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Injury, poisoning and procedural complications Ligament sprain	1.6% 1/64 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	1.5% 1/65 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Injury, poisoning and procedural complications Post-traumatic pain	1.6% 1/64 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/65 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Injury, poisoning and procedural complications Procedural pain	1.6% 1/64 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	1.5% 1/65 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Injury, poisoning and procedural complications Vaccination complication	1.6% 1/64 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/65 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Investigations Weight decreased	1.6% 1/64 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	1.5% 1/65 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Investigations Weight increased	1.6% 1/64 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/65 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/64 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	1.5% 1/65 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Musculoskeletal and connective tissue disorders Arthritis	1.6% 1/64 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/65 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Musculoskeletal and connective tissue disorders Back pain	4.7% 3/64 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	1.5% 1/65 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Musculoskeletal and connective tissue disorders Bursitis	3.1% 2/64 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	1.5% 1/65 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	1.6% 1/64 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/65 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Musculoskeletal and connective tissue disorders Lumbar spinal stenosis	0.00% 0/64 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	1.5% 1/65 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Musculoskeletal and connective tissue disorders Muscle spasms	0.00% 0/64 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	4.6% 3/65 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Musculoskeletal and connective tissue disorders Muscle twitching	0.00% 0/64 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	1.5% 1/65 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	3.1% 2/64 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	4.6% 3/65 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Musculoskeletal and connective tissue disorders Musculoskeletal stiffness	1.6% 1/64 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/65 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Musculoskeletal and connective tissue disorders Myalgia	1.6% 1/64 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	7.7% 5/65 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Musculoskeletal and connective tissue disorders Osteoarthritis	1.6% 1/64 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/65 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Musculoskeletal and connective tissue disorders Pain in extremity	1.6% 1/64 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	3.1% 2/65 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Musculoskeletal and connective tissue disorders Rotator cuff syndrome	0.00% 0/64 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	1.5% 1/65 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Musculoskeletal and connective tissue disorders Tendonitis	1.6% 1/64 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	1.5% 1/65 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. 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) Dysplastic naevus	1.6% 1/64 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/65 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Nervous system disorders Carpal tunnel syndrome	0.00% 0/64 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	1.5% 1/65 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Nervous system disorders Cervical radiculopathy	0.00% 0/64 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	1.5% 1/65 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Nervous system disorders Dizziness	1.6% 1/64 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	4.6% 3/65 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Nervous system disorders Headache	10.9% 7/64 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	6.2% 4/65 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Nervous system disorders Hypoaesthesia	0.00% 0/64 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	1.5% 1/65 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Nervous system disorders Lethargy	1.6% 1/64 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	1.5% 1/65 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Nervous system disorders Memory impairment	1.6% 1/64 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/65 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Nervous system disorders Migraine	1.6% 1/64 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	1.5% 1/65 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Nervous system disorders Paraesthesia	3.1% 2/64 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	1.5% 1/65 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Nervous system disorders Retinal migraine	1.6% 1/64 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/65 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Nervous system disorders Speech disorder	0.00% 0/64 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	1.5% 1/65 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Psychiatric disorders Insomnia	0.00% 0/64 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	6.2% 4/65 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Psychiatric disorders Irritability	0.00% 0/64 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	1.5% 1/65 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Reproductive system and breast disorders Menopausal symptoms	0.00% 0/64 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	1.5% 1/65 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Respiratory, thoracic and mediastinal disorders Cough	3.1% 2/64 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	1.5% 1/65 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Respiratory, thoracic and mediastinal disorders Epistaxis	1.6% 1/64 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/65 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Respiratory, thoracic and mediastinal disorders Nasal congestion	1.6% 1/64 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/65 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	0.00% 0/64 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	3.1% 2/65 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Respiratory, thoracic and mediastinal disorders Pharyngeal inflammation	1.6% 1/64 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/65 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	1.6% 1/64 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	1.5% 1/65 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Respiratory, thoracic and mediastinal disorders Upper-airway cough syndrome	0.00% 0/64 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	1.5% 1/65 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Skin and subcutaneous tissue disorders Dermatitis allergic	0.00% 0/64 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	1.5% 1/65 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Skin and subcutaneous tissue disorders Dry skin	0.00% 0/64 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	1.5% 1/65 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Skin and subcutaneous tissue disorders Eczema	3.1% 2/64 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/65 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Skin and subcutaneous tissue disorders Erythema	0.00% 0/64 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	1.5% 1/65 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Skin and subcutaneous tissue disorders Hyperhidrosis	1.6% 1/64 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/65 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Skin and subcutaneous tissue disorders Hyperkeratosis	0.00% 0/64 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	1.5% 1/65 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Skin and subcutaneous tissue disorders Pruritus	0.00% 0/64 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	1.5% 1/65 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Skin and subcutaneous tissue disorders Psoriasis	1.6% 1/64 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/65 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Skin and subcutaneous tissue disorders Rash erythematous	0.00% 0/64 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	1.5% 1/65 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Skin and subcutaneous tissue disorders Rosacea	0.00% 0/64 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	1.5% 1/65 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Surgical and medical procedures Bunion operation	1.6% 1/64 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/65 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Vascular disorders Flushing	1.6% 1/64 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/65 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Vascular disorders Hot flush	0.00% 0/64 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	1.5% 1/65 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Vascular disorders Hypertension	0.00% 0/64 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	4.6% 3/65 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Vascular disorders Peripheral coldness	0.00% 0/64 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	1.5% 1/65 • From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months. 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

Email: medinfo@amgen.com

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