Trial Outcomes & Findings for Long-Term Extension of Previous rAvPAL-PEG Protocols in Subjects With PKU (PAL-003) (NCT NCT00924703)

NCT ID: NCT00924703

Last Updated: 2021-10-12

Results Overview

Blood Phe Concentration (Change from Baseline) and Daily Dose in PAL-003 Subjects by Disposition (PAL-003 Population)

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

68 participants

Primary outcome timeframe

At Baseline and Change from Baseline to Week 48, Week 96, Week 144, Week 216, and Week 240

Results posted on

2021-10-12

Participant Flow

This was a multicenter study, conducted in 14 study centers of United States.

Participant milestones

Participant milestones
Measure	rAvPAL-PEG rAvPAL-PEG 0.001 to a maximum dose of 5.0 mg/kg/week or 375 mg/week by subcutaneous injection
Overall Study STARTED	68
Overall Study COMPLETED	46
Overall Study NOT COMPLETED	22

Reasons for withdrawal

Reasons for withdrawal
Measure	rAvPAL-PEG rAvPAL-PEG 0.001 to a maximum dose of 5.0 mg/kg/week or 375 mg/week by subcutaneous injection
Overall Study Withdrawal by Subject	11
Overall Study Physician Decision	5
Overall Study Lost to Follow-up	3
Overall Study Adverse Event	2
Overall Study Withdrawal by Sponsor	1

Baseline Characteristics

Total 5 (7.4%) out of 68 subjects BMI are missing due to missing height

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	rAvPAL-PEG n=68 Participants rAvPAL-PEG 0.001 to a maximum dose of 5.0 mg/kg/week or 375 mg/week by subcutaneous injection
Age, Continuous	28.31 years STANDARD_DEVIATION 8.66 • n=68 Participants
Sex: Female, Male Female	40 Participants n=68 Participants
Sex: Female, Male Male	28 Participants n=68 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=68 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	67 Participants n=68 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=68 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	1 Participants n=68 Participants
Race/Ethnicity, Customized White	66 Participants n=68 Participants
Race/Ethnicity, Customized Asian	1 Participants n=68 Participants
Weight	83.0 kg STANDARD_DEVIATION 26.39 • n=68 Participants
Body mass index (BMI)	29.2 kg/m^2 STANDARD_DEVIATION 8.44 • n=63 Participants • Total 5 (7.4%) out of 68 subjects BMI are missing due to missing height
Baseline blood Phe	1022.4 μmol/L STANDARD_DEVIATION 530.39 • n=68 Participants

PRIMARY outcome

Timeframe: At Baseline and Change from Baseline to Week 48, Week 96, Week 144, Week 216, and Week 240

Population: Efficacy population consisted of all subjects who received at least one dose of study drug and have post-treatment blood Phe concentration measurements.

Blood Phe Concentration (Change from Baseline) and Daily Dose in PAL-003 Subjects by Disposition (PAL-003 Population)

Outcome measures

Outcome measures
Measure	rAvPAL-PEG n=68 Participants rAvPAL-PEG 0.001 to a maximum dose of 5.0 mg/kg/week or 375 mg/week by subcutaneous injection
Change From Baseline in the Blood Phenylalanine (Phe) Concentration Baseline	1022.4 μmol/L Standard Deviation 530.39
Change From Baseline in the Blood Phenylalanine (Phe) Concentration Change from Baseline to Week 48	-553.5 μmol/L Standard Deviation 652.95
Change From Baseline in the Blood Phenylalanine (Phe) Concentration Change from Baseline to Week 96	-653.3 μmol/L Standard Deviation 637.81
Change From Baseline in the Blood Phenylalanine (Phe) Concentration Change from Baseline to Week 144	-672.3 μmol/L Standard Deviation 621.06
Change From Baseline in the Blood Phenylalanine (Phe) Concentration Change from Baseline to Week 216	-535.9 μmol/L Standard Deviation 573.08
Change From Baseline in the Blood Phenylalanine (Phe) Concentration Change from Baseline to Week 240	-574.9 μmol/L Standard Deviation 549.90

SECONDARY outcome

Timeframe: At Baseline, Week 48, Week 96, Week 144, Week 216 and Week 240

Population: As PAL-003 is an extension of parent Phase 2 studies (PAL-002, PAL-004 \& 165-205), the parent Phase 2 treatment naïve baseline data (N=80) was used for the vital signs, immunogenicity \& PK analyses to monitor changes in vital signs mediated by pegvaliase, understand development \& maturation of immune response against pegvaliase, \& the resulting impact on PK. Refer to NCT00925054-PAL-002, NCT01212744-PAL-004 \& NCT01560286-165-205 for parent Ph2 demographic data (N=80).

Steady-state Pharmacokinetics (PK) of pegvaliase was measured in subjects who have achieved and maintained target blood Phe

Outcome measures

Outcome measures
Measure	rAvPAL-PEG n=80 Participants rAvPAL-PEG 0.001 to a maximum dose of 5.0 mg/kg/week or 375 mg/week by subcutaneous injection
Pharmacokinetics-Plasma Pegvaliase Concentration At Baseline	961.5 ng/mL Standard Deviation 3013.43
Pharmacokinetics-Plasma Pegvaliase Concentration Week 48	4127.3 ng/mL Standard Deviation 6116.72
Pharmacokinetics-Plasma Pegvaliase Concentration Week 96	7457.7 ng/mL Standard Deviation 10685.02
Pharmacokinetics-Plasma Pegvaliase Concentration Week 144	7196.1 ng/mL Standard Deviation 11678.89
Pharmacokinetics-Plasma Pegvaliase Concentration Week 216	7764.4 ng/mL Standard Deviation 9292.34
Pharmacokinetics-Plasma Pegvaliase Concentration Week 240	6557.8 ng/mL Standard Deviation 9220.95

SECONDARY outcome

Timeframe: Up to 109 months.

Population: Analysis population consisted of subjects from the study of PAL-003 only

A treatment-emergent AE was defined as any adverse event (AE) newly appearing or worsened in severity following initiation of study drug until 4 weeks after last dose of pegvaliase (PAL-003)

Outcome measures

Outcome measures
Measure	rAvPAL-PEG n=68 Participants rAvPAL-PEG 0.001 to a maximum dose of 5.0 mg/kg/week or 375 mg/week by subcutaneous injection
Number of Subjects With Treatment Emergent Adverse Events (TEAEs) Subjects with any adverse event	68 Participants
Number of Subjects With Treatment Emergent Adverse Events (TEAEs) Subjects with any serious adverse events	12 Participants
Number of Subjects With Treatment Emergent Adverse Events (TEAEs) Subjects with any treatment-related adverse event	65 Participants
Number of Subjects With Treatment Emergent Adverse Events (TEAEs) Any treatment-related serious adverse event	6 Participants
Number of Subjects With Treatment Emergent Adverse Events (TEAEs) Death	0 Participants

SECONDARY outcome

Timeframe: At Baseline and Change from Baseline to Week 24, Week 52, Week 104 and Week 156

The presence of IgG Antibodies against PEG (polyethylene glycol) is measured overtime

Outcome measures

Outcome measures
Measure	rAvPAL-PEG n=80 Participants rAvPAL-PEG 0.001 to a maximum dose of 5.0 mg/kg/week or 375 mg/week by subcutaneous injection
Percentage of Participants With Positive PEG IgG Antibody Baseline	29 Participants
Percentage of Participants With Positive PEG IgG Antibody Change from Baseline to Week 24	24 Participants
Percentage of Participants With Positive PEG IgG Antibody Change from Baseline to Week 52	14 Participants
Percentage of Participants With Positive PEG IgG Antibody Change from Baseline to Week 104	2 Participants
Percentage of Participants With Positive PEG IgG Antibody Change from Baseline to Week 156	7 Participants

SECONDARY outcome

Timeframe: At Baseline and Change from Baseline to Week 24, Week 52, Week 104 and Week 156

The presence of IgG Antibodies against PAL (phenylalanine ammonia lyase) is measured overtime

Outcome measures

Outcome measures
Measure	rAvPAL-PEG n=80 Participants rAvPAL-PEG 0.001 to a maximum dose of 5.0 mg/kg/week or 375 mg/week by subcutaneous injection
Percentage of Participants With Positive PAL IgG Antibody Baseline	10 Participants
Percentage of Participants With Positive PAL IgG Antibody Change from Baseline to Week 24	63 Participants
Percentage of Participants With Positive PAL IgG Antibody Change from Baseline to Week 52	60 Participants
Percentage of Participants With Positive PAL IgG Antibody Change from Baseline to Week 104	48 Participants
Percentage of Participants With Positive PAL IgG Antibody Change from Baseline to Week 156	45 Participants

Adverse Events

rAvPAL-PEG

Serious events: 12 serious events

Other events: 68 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	rAvPAL-PEG n=68 participants at risk rAvPAL-PEG 0.001 to a maximum dose of 5.0 mg/kg/week or 375 mg/week by subcutaneous injection
Respiratory, thoracic and mediastinal disorders Asthma	2.9% 2/68 • Number of events 2 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.
Immune system disorders Hypersensitivity	1.5% 1/68 • Number of events 1 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.
Surgical and medical procedures Abortion induced	1.5% 1/68 • Number of events 1 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.
Immune system disorders Anaphylactic reaction	1.5% 1/68 • Number of events 1 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.
Infections and infestations Appendicitis	1.5% 1/68 • Number of events 1 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.
Musculoskeletal and connective tissue disorders Arthralgia	1.5% 1/68 • Number of events 1 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.
Infections and infestations Bacteraemia	1.5% 1/68 • Number of events 1 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.
Infections and infestations Bacterial infection	1.5% 1/68 • Number of events 1 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.
Blood and lymphatic system disorders Bone marrow failure	1.5% 1/68 • Number of events 1 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.
Infections and infestations Diarrhoea infectious	1.5% 1/68 • Number of events 1 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.
Metabolism and nutrition disorders Hyponatraemia	1.5% 1/68 • Number of events 1 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.
Vascular disorders Hypotension	1.5% 1/68 • Number of events 1 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.
Injury, poisoning and procedural complications Injection related reaction	1.5% 1/68 • Number of events 1 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.
Blood and lymphatic system disorders Lymphadenopathy	1.5% 1/68 • Number of events 1 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.
Nervous system disorders Neuropathy peripheral	1.5% 1/68 • Number of events 1 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.
Blood and lymphatic system disorders Neutropenia	1.5% 1/68 • Number of events 1 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.
Skin and subcutaneous tissue disorders Panniculitis	1.5% 1/68 • Number of events 1 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.
Injury, poisoning and procedural complications Postoperative wound complication	1.5% 1/68 • Number of events 1 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.
Infections and infestations Staphylococcal infection	1.5% 1/68 • Number of events 1 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.
Psychiatric disorders Suicide attempt	1.5% 1/68 • Number of events 1 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.
Skin and subcutaneous tissue disorders Urticaria	1.5% 1/68 • Number of events 1 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.

Other adverse events

Other adverse events
Measure	rAvPAL-PEG n=68 participants at risk rAvPAL-PEG 0.001 to a maximum dose of 5.0 mg/kg/week or 375 mg/week by subcutaneous injection
Blood and lymphatic system disorders Lymphadenopathy	13.2% 9/68 • Number of events 12 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.
General disorders Injection site reaction	52.9% 36/68 • Number of events 114 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.
General disorders Injection site erythema	52.9% 36/68 • Number of events 160 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.
General disorders Injection site bruising	50.0% 34/68 • Number of events 245 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.
General disorders Pyrexia	36.8% 25/68 • Number of events 38 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.
Musculoskeletal and connective tissue disorders Pain in extremity	36.8% 25/68 • Number of events 59 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.
General disorders Injection site rash	16.2% 11/68 • Number of events 24 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.
General disorders Injection site pruritus	32.4% 22/68 • Number of events 83 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.
General disorders Injection site pain	26.5% 18/68 • Number of events 76 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.
General disorders Injection site swelling	23.5% 16/68 • Number of events 25 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.
General disorders Injection site urticaria	26.5% 18/68 • Number of events 66 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.
General disorders Fatigue	25.0% 17/68 • Number of events 24 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.
General disorders Peripheral swelling	13.2% 9/68 • Number of events 18 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.
General disorders Pain	22.1% 15/68 • Number of events 22 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.
Gastrointestinal disorders Toothache	19.1% 13/68 • Number of events 20 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.
Injury, poisoning and procedural complications Fall	10.3% 7/68 • Number of events 7 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.
Injury, poisoning and procedural complications Procedural pain	10.3% 7/68 • Number of events 10 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.
General disorders Injection site mass	7.4% 5/68 • Number of events 9 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.
General disorders Injection site nodule	7.4% 5/68 • Number of events 8 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.
General disorders Injection site discolouration	5.9% 4/68 • Number of events 17 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.
General disorders Injection site haemorrhage	5.9% 4/68 • Number of events 6 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.
Nervous system disorders Headache	63.2% 43/68 • Number of events 253 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.
Nervous system disorders Dizziness	38.2% 26/68 • Number of events 61 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.
Injury, poisoning and procedural complications Contusion	35.3% 24/68 • Number of events 59 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.
Psychiatric disorders Anxiety	17.6% 12/68 • Number of events 17 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.
Nervous system disorders Migraine	20.6% 14/68 • Number of events 41 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.
Vascular disorders Hypertension	13.2% 9/68 • Number of events 9 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.
General disorders Oedema peripheral	5.9% 4/68 • Number of events 10 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.
Ear and labyrinth disorders Vertigo	5.9% 4/68 • Number of events 5 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.
Psychiatric disorders Insomnia	20.6% 14/68 • Number of events 30 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.
Psychiatric disorders Depression	19.1% 13/68 • Number of events 16 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.
Respiratory, thoracic and mediastinal disorders Dyspnoea	8.8% 6/68 • Number of events 11 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.
Psychiatric disorders Irritability	8.8% 6/68 • Number of events 9 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.
Nervous system disorders Disturbance in attention	7.4% 5/68 • Number of events 5 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.
Skin and subcutaneous tissue disorders Rash generalised	8.8% 6/68 • Number of events 17 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.
Injury, poisoning and procedural complications Arthropod bite	16.2% 11/68 • Number of events 14 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.
Nervous system disorders Paraesthesia	11.8% 8/68 • Number of events 12 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.
Immune system disorders Seasonal allergy	7.4% 5/68 • Number of events 9 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.
General disorders Influenza like illness	8.8% 6/68 • Number of events 10 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.
Musculoskeletal and connective tissue disorders Tendonitis	5.9% 4/68 • Number of events 7 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.
Skin and subcutaneous tissue disorders Dermatitis contact	16.2% 11/68 • Number of events 20 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.
Skin and subcutaneous tissue disorders Dry skin	11.8% 8/68 • Number of events 12 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.
Injury, poisoning and procedural complications Thermal burn	13.2% 9/68 • Number of events 11 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.
Injury, poisoning and procedural complications Skin abrasion	10.3% 7/68 • Number of events 9 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.
Skin and subcutaneous tissue disorders Acne	5.9% 4/68 • Number of events 6 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.
Respiratory, thoracic and mediastinal disorders Epistaxis	5.9% 4/68 • Number of events 8 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.
Skin and subcutaneous tissue disorders Rash	55.9% 38/68 • Number of events 124 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.
Skin and subcutaneous tissue disorders Urticaria	48.5% 33/68 • Number of events 294 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.
Skin and subcutaneous tissue disorders Pruritus	39.7% 27/68 • Number of events 69 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.
Skin and subcutaneous tissue disorders Erythema	20.6% 14/68 • Number of events 31 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.
Skin and subcutaneous tissue disorders Rash erythematous	23.5% 16/68 • Number of events 21 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.
Skin and subcutaneous tissue disorders Alopecia	17.6% 12/68 • Number of events 14 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.
Skin and subcutaneous tissue disorders Rash pruritic	7.4% 5/68 • Number of events 6 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.
Infections and infestations Nasopharyngitis	66.2% 45/68 • Number of events 137 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.
Infections and infestations Upper respiratory tract infection	50.0% 34/68 • Number of events 157 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.
Respiratory, thoracic and mediastinal disorders Nasal congestion	32.4% 22/68 • Number of events 43 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.
Infections and infestations Urinary tract infection	20.6% 14/68 • Number of events 21 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.
Infections and infestations Gastroenteritis viral	17.6% 12/68 • Number of events 21 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.
Infections and infestations Influenza	19.1% 13/68 • Number of events 18 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.
Infections and infestations Pharyngitis streptococcal	8.8% 6/68 • Number of events 6 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	8.8% 6/68 • Number of events 8 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.
Infections and infestations Viral infection	11.8% 8/68 • Number of events 14 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.
Infections and infestations Gastroenteritis	10.3% 7/68 • Number of events 16 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.
General disorders Asthenia	5.9% 4/68 • Number of events 5 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.
Infections and infestations Fungal infection	5.9% 4/68 • Number of events 7 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.
Renal and urinary disorders Nephrolithiasis	8.8% 6/68 • Number of events 7 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.
Renal and urinary disorders Microalbuminuria	5.9% 4/68 • Number of events 8 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.
Renal and urinary disorders Proteinuria	5.9% 4/68 • Number of events 4 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.
Investigations Alanine aminotransferase increased	5.9% 4/68 • Number of events 7 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.
Investigations Amino acid level decreased	5.9% 4/68 • Number of events 5 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.
Infections and infestations Ear infection	7.4% 5/68 • Number of events 6 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.
Ear and labyrinth disorders Ear pain	5.9% 4/68 • Number of events 4 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.
Respiratory, thoracic and mediastinal disorders Cough	48.5% 33/68 • Number of events 52 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	48.5% 33/68 • Number of events 82 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.
Infections and infestations Sinusitis	36.8% 25/68 • Number of events 41 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.
Respiratory, thoracic and mediastinal disorders Sinus congestion	22.1% 15/68 • Number of events 33 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.
General disorders Chest discomfort	11.8% 8/68 • Number of events 12 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.
Injury, poisoning and procedural complications Laceration	14.7% 10/68 • Number of events 18 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.
Infections and infestations Bronchitis	13.2% 9/68 • Number of events 12 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.
General disorders Chest pain	7.4% 5/68 • Number of events 6 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.
Respiratory, thoracic and mediastinal disorders Pulmonary congestion	5.9% 4/68 • Number of events 4 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.
Vascular disorders Raynaud's phenomenon	7.4% 5/68 • Number of events 6 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.
Respiratory, thoracic and mediastinal disorders Paranasal sinus discomfort	5.9% 4/68 • Number of events 4 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.
Respiratory, thoracic and mediastinal disorders Pharyngeal oedema	5.9% 4/68 • Number of events 4 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.
Respiratory, thoracic and mediastinal disorders Upper-airway cough syndrome	5.9% 4/68 • Number of events 5 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.
Investigations Complement factor C3 decreased	10.3% 7/68 • Number of events 8 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.
Reproductive system and breast disorders Dysmenorrhoea	13.2% 9/68 • Number of events 42 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.
Investigations Complement factor C4 decreased	10.3% 7/68 • Number of events 9 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.
Nervous system disorders Hypoaesthesia	7.4% 5/68 • Number of events 7 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.
Metabolism and nutrition disorders Dehydration	7.4% 5/68 • Number of events 5 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.
Investigations Blood uric acid increased	7.4% 5/68 • Number of events 6 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.
Renal and urinary disorders Haematuria	8.8% 6/68 • Number of events 8 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.
Investigations Amino acid level increased	7.4% 5/68 • Number of events 5 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.
Investigations Blood bicarbonate decreased	5.9% 4/68 • Number of events 4 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.
Investigations Urobilinogen urine increased	5.9% 4/68 • Number of events 4 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.
Eye disorders Eye swelling	7.4% 5/68 • Number of events 7 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.
Eye disorders Ocular hyperaemia	5.9% 4/68 • Number of events 5 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.
Gastrointestinal disorders Nausea	48.5% 33/68 • Number of events 70 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.
Gastrointestinal disorders Vomiting	44.1% 30/68 • Number of events 64 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.
Gastrointestinal disorders Diarrhoea	39.7% 27/68 • Number of events 79 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.
Gastrointestinal disorders Abdominal pain	29.4% 20/68 • Number of events 42 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.
Gastrointestinal disorders Abdominal pain upper	19.1% 13/68 • Number of events 31 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.
Gastrointestinal disorders Dyspepsia	16.2% 11/68 • Number of events 21 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.
Gastrointestinal disorders Abdominal discomfort	19.1% 13/68 • Number of events 26 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.
Gastrointestinal disorders Constipation	11.8% 8/68 • Number of events 10 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.
Metabolism and nutrition disorders Decreased appetite	7.4% 5/68 • Number of events 5 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.
Gastrointestinal disorders Gastrooesophageal reflux disease	8.8% 6/68 • Number of events 7 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.
Gastrointestinal disorders Food poisoning	7.4% 5/68 • Number of events 8 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.
Gastrointestinal disorders Dental caries	7.4% 5/68 • Number of events 6 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.
Infections and infestations Tooth abscess	5.9% 4/68 • Number of events 4 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.
Musculoskeletal and connective tissue disorders Arthralgia	54.4% 37/68 • Number of events 188 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.
Musculoskeletal and connective tissue disorders Back pain	44.1% 30/68 • Number of events 78 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.
Musculoskeletal and connective tissue disorders Myalgia	32.4% 22/68 • Number of events 67 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.
Musculoskeletal and connective tissue disorders Neck pain	26.5% 18/68 • Number of events 27 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	19.1% 13/68 • Number of events 28 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.
Musculoskeletal and connective tissue disorders Joint stiffness	19.1% 13/68 • Number of events 20 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.
Musculoskeletal and connective tissue disorders Joint swelling	14.7% 10/68 • Number of events 12 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.
Injury, poisoning and procedural complications Ligament sprain	14.7% 10/68 • Number of events 12 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.
Nervous system disorders Tremor	7.4% 5/68 • Number of events 7 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	10.3% 7/68 • Number of events 9 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.
Musculoskeletal and connective tissue disorders Muscle spasms	10.3% 7/68 • Number of events 12 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.
General disorders Non-cardiac chest pain	5.9% 4/68 • Number of events 4 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.
Injury, poisoning and procedural complications Joint dislocation	5.9% 4/68 • Number of events 4 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.
Injury, poisoning and procedural complications Wound	5.9% 4/68 • Number of events 6 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.
Infections and infestations Folliculitis	5.9% 4/68 • Number of events 6 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.
General disorders Vessel puncture site bruise	5.9% 4/68 • Number of events 9 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.
Injury, poisoning and procedural complications Muscle strain	7.4% 5/68 • Number of events 5 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.
General disorders Injection site induration	5.9% 4/68 • Number of events 9 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.
Gastrointestinal disorders Abdominal distension	5.9% 4/68 • Number of events 9 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.
General disorders Adverse drug reaction	7.4% 5/68 • Number of events 10 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.
Immune system disorders Hypersensitivity	5.9% 4/68 • Number of events 5 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.
Injury, poisoning and procedural complications Joint injury	10.3% 7/68 • Number of events 8 • Up to 109 months. Only treatment-emergent AEs that occurred and were reported during the study period were included in AE summaries. The incidence, exposure-adjusted event rate, severity grade (assessed per CTCAE version 4.03), and relationship to study drug (per Investigator) for all treatment-emergent AEs were summarized. For AEs occurring more than once during the study, maximum severity was used to summarize AEs by severity.

Additional Information

Debra Lounsbury/Sr Principle Scientist, Clinical Sciences

BioMarin Pharmaceutical Inc.

Phone: 415-506-6348

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60