Trial Outcomes & Findings for Efficacy, Safety, and Tolerability Rollover Study of Eteplirsen in Subjects With Duchenne Muscular Dystrophy (NCT NCT01540409)

NCT ID: NCT01540409

Last Updated: 2020-03-30

Results Overview

This study used a modified version of the 6MWT test procedure described in American Thoracic Society (ATS) 2002 guidelines, specifically adapted for patients with Duchenne muscular dystrophy. The participant was asked to walk a set course of 25 meters for 6 minutes (timed) and the distance walked in meters was recorded. Increases from baseline in 6MWT distance are indicative of improvement and decreases from baseline indicate worsening. Baseline here corresponds to the baseline in the parent study (4658-us-201, NCT01396239).

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 12 participants
• Primary outcome timeframe: Parent Baseline and Week 240
• Results posted on: 2020-03-30

Participant Flow

The study was conducted at 12 centers in the United States. Overall, 12 participants who completed parent study 4658-us-201 (NCT01396239) were enrolled between July 2011 and February 2012 in this extension study (4658-us-202; NCT01540409). A 4-week open label period (Week 24-28) was observed between the parent and extension study.

Participants who received placebo in 4658-us-201 study were randomized in 1:1 ratio in this extension study to receive either eteplirsen 30 or 50 milligram per kilogram (mg/kg) and, those who received eteplirsen 30 or 50 mg/kg in 4658-us-201 received same treatment in this extension study.

Participant milestones

Measure	Eteplirsen 30 mg/kg Participants who received 30 milligram per kilogram (mg/kg) eteplirsen or placebo once weekly, intravenous (IV) infusion for 24 weeks in the parent study 4658-us-201 (NCT01396239), continued the same treatment with 30 mg/kg eteplirsen once weekly for 212 weeks (up to Week 240) in this extension study.	Eteplirsen 50 mg/kg Participants who received 50 mg/kg eteplirsen or placebo once weekly, IV infusion for 24 weeks in the parent study 4658-us-201 (NCT01396239), continued the same treatment with 50 mg/kg eteplirsen once weekly for 212 weeks (up to Week 240) in this extension study.
Overall Study STARTED	6	6
Overall Study COMPLETED	6	6
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Efficacy, Safety, and Tolerability Rollover Study of Eteplirsen in Subjects With Duchenne Muscular Dystrophy

Baseline characteristics by cohort

Measure	Eteplirsen 30 mg/kg n=6 Participants Participants who received 30 mg/kg eteplirsen or placebo once weekly, IV infusion for 24 weeks in the parent study 4658-us-201 (NCT01396239), continued the same treatment with 30 mg/kg eteplirsen once weekly for 212 weeks (up to Week 240) in this extension study.	Eteplirsen 50 mg/kg n=6 Participants Participants who received 50 mg/kg eteplirsen or placebo once weekly, IV infusion for 24 weeks in the parent study 4658-us-201 (NCT01396239), continued the same treatment with 50 mg/kg eteplirsen once weekly for 212 weeks (up to Week 240) in this extension study.	Total n=12 Participants Total of all reporting groups
Age, Continuous	9.2 years STANDARD_DEVIATION 0.75 • n=5 Participants	8.8 years STANDARD_DEVIATION 1.47 • n=7 Participants	9.0 years STANDARD_DEVIATION 1.13 • n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Male	6 Participants n=5 Participants	6 Participants n=7 Participants	12 Participants n=5 Participants
Region of Enrollment United States	6 Participants n=5 Participants	6 Participants n=7 Participants	12 Participants n=5 Participants

PRIMARY outcome

Timeframe: Parent Baseline and Week 240

Population: The Intent-to-Treat Population (ITT) population included all participants randomized into parent study 4658-us-201. Here, "Overall Number of Participants Analyzed" signifies participants evaluable for this outcome measure. Results are reported below in 2 reporting groups based on evaluation period (Week 240) as applicable for this outcome measure.

This study used a modified version of the 6MWT test procedure described in American Thoracic Society (ATS) 2002 guidelines, specifically adapted for patients with Duchenne muscular dystrophy. The participant was asked to walk a set course of 25 meters for 6 minutes (timed) and the distance walked in meters was recorded. Increases from baseline in 6MWT distance are indicative of improvement and decreases from baseline indicate worsening. Baseline here corresponds to the baseline in the parent study (4658-us-201, NCT01396239).

Outcome measures

Measure	Eteplirsen 30 mg/kg n=4 Participants Participants who received 30 mg/kg eteplirsen or placebo once weekly, IV infusion for 24 weeks in the parent study 4658-us-201 (NCT01396239), continued the same treatment with 30 mg/kg eteplirsen once weekly for 212 weeks (up to Week 240) in this extension study.	Eteplirsen 50 mg/kg n=3 Participants Participants who received 50 mg/kg eteplirsen or placebo once weekly, IV infusion for 24 weeks in the parent study 4658-us-201 (NCT01396239), continued the same treatment with 50 mg/kg eteplirsen once weekly for 212 weeks (up to Week 240) in this extension study.	Eteplirsen 50 mg/kg Participants who received 50 mg/kg eteplirsen once weekly, IV infusion for 24 weeks in the parent study 4658-us-201 (NCT01396239), continued the same treatment with 50 mg/kg eteplirsen once weekly for 212 weeks (up to Week 240) in this extension study.
Change From Baseline in the 6 Minute Walk Test (6MWT) at Week 240	-199.0 Meters Standard Deviation 113.25	-258.0 Meters Standard Deviation 175.65	—

PRIMARY outcome

Timeframe: Parent Baseline and Week 48

Population: The ITT population included all participants randomized into parent study 4658-us-201. Results are reported below in 3 reporting groups of placebo to eteplirsen, eteplirsen 30 mg/kg, and eteplirsen 50 mg/kg, respectively, based on evaluation period (Week 48) as applicable for this outcome measure.

Dystrophin expression as assessed by percent dystrophin positive fibers was measured by immunohistochemistry (IHC) technique using primary anti-dystrophin antibody. Percent change from baseline is the arithmetic difference of the treatment time point minus baseline divided by baseline calculated for individual subjects. Baseline here corresponds to the baseline in the parent study (4658-us-201, NCT01396239).

Outcome measures

Measure	Eteplirsen 30 mg/kg n=4 Participants Participants who received 30 mg/kg eteplirsen or placebo once weekly, IV infusion for 24 weeks in the parent study 4658-us-201 (NCT01396239), continued the same treatment with 30 mg/kg eteplirsen once weekly for 212 weeks (up to Week 240) in this extension study.	Eteplirsen 50 mg/kg n=4 Participants Participants who received 50 mg/kg eteplirsen or placebo once weekly, IV infusion for 24 weeks in the parent study 4658-us-201 (NCT01396239), continued the same treatment with 50 mg/kg eteplirsen once weekly for 212 weeks (up to Week 240) in this extension study.	Eteplirsen 50 mg/kg n=4 Participants Participants who received 50 mg/kg eteplirsen once weekly, IV infusion for 24 weeks in the parent study 4658-us-201 (NCT01396239), continued the same treatment with 50 mg/kg eteplirsen once weekly for 212 weeks (up to Week 240) in this extension study.
Change From Baseline in the Percentage of Dystrophin Positive Fibers (PDPF) at Week 48	37.70 Percentage of Dystrophin Positive Fibers Standard Deviation 12.602	51.69 Percentage of Dystrophin Positive Fibers Standard Deviation 7.089	42.93 Percentage of Dystrophin Positive Fibers Standard Deviation 13.433

Adverse Events

Eteplirsen 30 mg/kg

Serious events: 4 serious events

Other events: 6 other events

Deaths: 0 deaths

Eteplirsen 50 mg/kg

Serious events: 2 serious events

Other events: 6 other events

Deaths: 0 deaths

Serious adverse events

Measure	Eteplirsen 30 mg/kg n=6 participants at risk Participants who received 30 mg/kg eteplirsen or placebo once weekly, IV infusion for 24 weeks in the parent study 4658-us-201 (NCT01396239), continued the same treatment with 30 mg/kg eteplirsen once weekly for 212 weeks (up to Week 240) in this extension study.	Eteplirsen 50 mg/kg n=6 participants at risk Participants who received 50 mg/kg eteplirsen or placebo once weekly, IV infusion for 24 weeks in the parent study 4658-us-201 (NCT01396239), continued the same treatment with 50 mg/kg eteplirsen once weekly for 212 weeks (up to Week 240) in this extension study.
Injury, poisoning and procedural complications Tibia Fracture	0.00% 0/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Injury, poisoning and procedural complications Femur Fracture	50.0% 3/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Musculoskeletal and connective tissue disorders Scoliosis	33.3% 2/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	0.00% 0/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	0.00% 0/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.

Other adverse events

Measure	Eteplirsen 30 mg/kg n=6 participants at risk Participants who received 30 mg/kg eteplirsen or placebo once weekly, IV infusion for 24 weeks in the parent study 4658-us-201 (NCT01396239), continued the same treatment with 30 mg/kg eteplirsen once weekly for 212 weeks (up to Week 240) in this extension study.	Eteplirsen 50 mg/kg n=6 participants at risk Participants who received 50 mg/kg eteplirsen or placebo once weekly, IV infusion for 24 weeks in the parent study 4658-us-201 (NCT01396239), continued the same treatment with 50 mg/kg eteplirsen once weekly for 212 weeks (up to Week 240) in this extension study.
Endocrine disorders Cushingoid	0.00% 0/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	33.3% 2/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Gastrointestinal disorders Gastritis	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	0.00% 0/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Gastrointestinal disorders Tooth disorder	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	0.00% 0/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Injury, poisoning and procedural complications Procedural pain	83.3% 5/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	100.0% 6/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Injury, poisoning and procedural complications Contusion	66.7% 4/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	66.7% 4/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Injury, poisoning and procedural complications Arthropod bite	50.0% 3/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	33.3% 2/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Injury, poisoning and procedural complications Excoriation	33.3% 2/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	50.0% 3/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Injury, poisoning and procedural complications Joint injury	33.3% 2/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Injury, poisoning and procedural complications Joint sprain	0.00% 0/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	50.0% 3/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Injury, poisoning and procedural complications Muscle strain	33.3% 2/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	33.3% 2/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Injury, poisoning and procedural complications Fall	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	0.00% 0/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Injury, poisoning and procedural complications Foot fracture	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Injury, poisoning and procedural complications Incision site haemorrhage	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Injury, poisoning and procedural complications Incision site pain	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	0.00% 0/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Injury, poisoning and procedural complications Arthropod sting	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	0.00% 0/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Injury, poisoning and procedural complications Back injury	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	0.00% 0/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Injury, poisoning and procedural complications Burns first degree	0.00% 0/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Injury, poisoning and procedural complications Cardiac function disturbance postoperative	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	0.00% 0/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Injury, poisoning and procedural complications Compression fracture	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	0.00% 0/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Injury, poisoning and procedural complications Concussion	0.00% 0/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Injury, poisoning and procedural complications Head injury	0.00% 0/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Injury, poisoning and procedural complications Laceration	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Injury, poisoning and procedural complications Limb injury	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Injury, poisoning and procedural complications Lip injury	0.00% 0/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Injury, poisoning and procedural complications Lower limb fracture	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	0.00% 0/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Injury, poisoning and procedural complications Nail injury	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	0.00% 0/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Injury, poisoning and procedural complications Post procedural haematoma	0.00% 0/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Injury, poisoning and procedural complications Postoperative respiratory distress	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	0.00% 0/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Injury, poisoning and procedural complications Radius fracture	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	0.00% 0/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Injury, poisoning and procedural complications Sunburn	0.00% 0/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Injury, poisoning and procedural complications Thermal burn	0.00% 0/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Injury, poisoning and procedural complications Tibia fracture	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Investigations Activated partial thromboplastin time prolonged	0.00% 0/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	66.7% 4/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Investigations C-reactive protein increased	33.3% 2/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	33.3% 2/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Investigations Blood glucose increased	33.3% 2/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Investigations Blood creatine phosphokinase increased	33.3% 2/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	0.00% 0/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Investigations Body height below normal	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Investigations Activated partial thromboplastin time abnormal	0.00% 0/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Investigations Blood creatinine increased	0.00% 0/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Investigations Blood urea increased	0.00% 0/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Investigations Lymphocyte count decreased	0.00% 0/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Investigations Neutrophil count increased	0.00% 0/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Investigations Red blood cells urine positive	0.00% 0/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Investigations White blood cell count decreased	0.00% 0/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Investigations Wound healing normal	0.00% 0/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Nervous system disorders Headache	66.7% 4/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	83.3% 5/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Nervous system disorders Balance disorder	33.3% 2/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	50.0% 3/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Nervous system disorders Dizziness	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Nervous system disorders Psychomotor hyperactivity	0.00% 0/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Nervous system disorders Sinus headache	0.00% 0/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Nervous system disorders Somnolence	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	0.00% 0/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	66.7% 4/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	66.7% 4/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Respiratory, thoracic and mediastinal disorders Nasal congestion	83.3% 5/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	33.3% 2/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Respiratory, thoracic and mediastinal disorders Cough	33.3% 2/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	66.7% 4/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Respiratory, thoracic and mediastinal disorders Epistaxis	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	33.3% 2/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Respiratory, thoracic and mediastinal disorders Pharyngeal erythema	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	0.00% 0/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	50.0% 3/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Respiratory, thoracic and mediastinal disorders Sleep apnoea syndrome	50.0% 3/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	0.00% 0/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Respiratory, thoracic and mediastinal disorders Upper respiratory tract congestion	33.3% 2/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	0.00% 0/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Respiratory, thoracic and mediastinal disorders Productive cough	0.00% 0/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Respiratory, thoracic and mediastinal disorders Respiratory disorder	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	0.00% 0/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Respiratory, thoracic and mediastinal disorders Sinus congestion	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	0.00% 0/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Respiratory, thoracic and mediastinal disorders Sneezing	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	0.00% 0/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Respiratory, thoracic and mediastinal disorders Upper-airway cough syndrome	0.00% 0/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Gastrointestinal disorders Vomiting	83.3% 5/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	66.7% 4/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Gastrointestinal disorders Abdominal pain upper	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	50.0% 3/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Gastrointestinal disorders Dyspepsia	50.0% 3/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Gastrointestinal disorders Abdominal pain	0.00% 0/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	33.3% 2/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Gastrointestinal disorders Constipation	33.3% 2/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	33.3% 2/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Gastrointestinal disorders Diarrhoea	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	33.3% 2/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Gastrointestinal disorders Nausea	33.3% 2/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	50.0% 3/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Gastrointestinal disorders Oral pain	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	33.3% 2/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Gastrointestinal disorders Abdominal discomfort	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Gastrointestinal disorders Dental caries	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	0.00% 0/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Gastrointestinal disorders Dysphagia	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	0.00% 0/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Gastrointestinal disorders Flatulence	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	0.00% 0/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Gastrointestinal disorders Food poisoning	0.00% 0/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Gastrointestinal disorders Haemorrhoids	0.00% 0/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Gastrointestinal disorders Lip swelling	0.00% 0/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Gastrointestinal disorders Retained deciduous tooth	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	0.00% 0/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Gastrointestinal disorders Tooth impacted	0.00% 0/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Gastrointestinal disorders Toothache	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	0.00% 0/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
General disorders Pyrexia	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	33.3% 2/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
General disorders Catheter site pain	33.3% 2/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	33.3% 2/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
General disorders Infusion site extravasation	33.3% 2/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	33.3% 2/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
General disorders Device occlusion	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
General disorders Infusion site haematoma	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
General disorders Oedema peripheral	33.3% 2/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	0.00% 0/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
General disorders Thrombosis in device	33.3% 2/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
General disorders Application site erythema	0.00% 0/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
General disorders Application site pruritus	0.00% 0/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
General disorders Catheter site haematoma	0.00% 0/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	33.3% 2/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
General disorders Catheter site haemorrhage	0.00% 0/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
General disorders Catheter site inflammation	0.00% 0/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
General disorders Catheter site related reaction	0.00% 0/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
General disorders Chest pain	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	0.00% 0/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
General disorders Influenza like illness	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	0.00% 0/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
General disorders Infusion site pain	0.00% 0/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
General disorders Infusion site rash	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	0.00% 0/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
General disorders Injection site pain	0.00% 0/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
General disorders Irritability	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	0.00% 0/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
General disorders Malaise	0.00% 0/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
General disorders Non-cardiac chest pain	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	0.00% 0/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
General disorders Pain	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	33.3% 2/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
General disorders Swelling	0.00% 0/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Musculoskeletal and connective tissue disorders Pain in extremity	66.7% 4/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	66.7% 4/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Musculoskeletal and connective tissue disorders Arthralgia	83.3% 5/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	66.7% 4/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Musculoskeletal and connective tissue disorders Back pain	100.0% 6/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	50.0% 3/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Musculoskeletal and connective tissue disorders Muscle spasms	33.3% 2/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	33.3% 2/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	33.3% 2/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	33.3% 2/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Musculoskeletal and connective tissue disorders Myalgia	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	33.3% 2/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Musculoskeletal and connective tissue disorders Muscular weakness	0.00% 0/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	50.0% 3/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Musculoskeletal and connective tissue disorders Bone pain	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	0.00% 0/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	0.00% 0/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Musculoskeletal and connective tissue disorders Neck pain	0.00% 0/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Musculoskeletal and connective tissue disorders Scoliosis	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	0.00% 0/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Musculoskeletal and connective tissue disorders Tendon disorder	0.00% 0/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Musculoskeletal and connective tissue disorders Tendonitis	0.00% 0/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Skin and subcutaneous tissue disorders Dermatitis contact	33.3% 2/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Skin and subcutaneous tissue disorders Rash	50.0% 3/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Skin and subcutaneous tissue disorders Ecchymosis	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	33.3% 2/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Skin and subcutaneous tissue disorders Erythema	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	33.3% 2/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Skin and subcutaneous tissue disorders Papule	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Skin and subcutaneous tissue disorders Alopecia	0.00% 0/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Skin and subcutaneous tissue disorders Dermatitis bullous	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	0.00% 0/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Skin and subcutaneous tissue disorders Ingrowing nail	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Skin and subcutaneous tissue disorders Intertrigo	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	0.00% 0/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Skin and subcutaneous tissue disorders Keloid scar	0.00% 0/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Skin and subcutaneous tissue disorders Nail discolouration	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	0.00% 0/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Skin and subcutaneous tissue disorders Nail dystrophy	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	0.00% 0/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Skin and subcutaneous tissue disorders Petechiae	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	0.00% 0/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Skin and subcutaneous tissue disorders Pruritus	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Skin and subcutaneous tissue disorders Rash papular	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	0.00% 0/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Skin and subcutaneous tissue disorders Skin erosion	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	0.00% 0/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Skin and subcutaneous tissue disorders Urticaria	0.00% 0/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Skin and subcutaneous tissue disorders Urticaria thermal	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	0.00% 0/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Infections and infestations Nasopharyngitis	66.7% 4/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	83.3% 5/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Infections and infestations Upper respiratory tract infection	33.3% 2/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	66.7% 4/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Infections and infestations Gastroenteritis viral	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	33.3% 2/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Infections and infestations Hordeolum	0.00% 0/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	50.0% 3/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Infections and infestations Influenza	0.00% 0/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	50.0% 3/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Infections and infestations Post procedural cellulitis	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Infections and infestations Rhinitis	0.00% 0/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Infections and infestations Viral infection	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	33.3% 2/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Infections and infestations Candidiasis	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	0.00% 0/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Infections and infestations Folliculitis	0.00% 0/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Infections and infestations Gastroenteritis	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	0.00% 0/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Infections and infestations Incision site infection	0.00% 0/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Infections and infestations Pharyngitis streptococcal	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	0.00% 0/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Infections and infestations Pneumonia	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	0.00% 0/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Infections and infestations Sinusitis	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	0.00% 0/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Infections and infestations Tinea capitis	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	0.00% 0/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Infections and infestations Tinea pedis	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	0.00% 0/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Infections and infestations Viral upper respiratory tract infection	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	0.00% 0/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Metabolism and nutrition disorders Hypokalaemia	33.3% 2/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	33.3% 2/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Metabolism and nutrition disorders Dehydration	33.3% 2/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Metabolism and nutrition disorders Obesity	33.3% 2/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	0.00% 0/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Metabolism and nutrition disorders Vitamin D deficiency	33.3% 2/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	0.00% 0/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Renal and urinary disorders Proteinuria	33.3% 2/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	66.7% 4/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Renal and urinary disorders Glycosuria	0.00% 0/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Renal and urinary disorders Hypercalciuria	0.00% 0/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Renal and urinary disorders Polyuria	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	0.00% 0/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Ear and labyrinth disorders Cerumen impaction	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	0.00% 0/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Ear and labyrinth disorders Motion sickness	0.00% 0/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Ear and labyrinth disorders Tympanic membrane disorder	0.00% 0/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Eye disorders Cataract	0.00% 0/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	33.3% 2/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Eye disorders Cataract subcapsular	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	0.00% 0/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Eye disorders Conjunctivitis	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	0.00% 0/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Eye disorders Erythema of eyelid	0.00% 0/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Eye disorders Hypermetropia	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	0.00% 0/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Vascular disorders Haematoma	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Endocrine disorders Goitre	0.00% 0/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Endocrine disorders Growth hormone deficiency	0.00% 0/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Psychiatric disorders Anxiety disorder	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	0.00% 0/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Psychiatric disorders Insomnia	0.00% 0/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Reproductive system and breast disorders Pelvic pain	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	0.00% 0/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Reproductive system and breast disorders Testicular pain	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	0.00% 0/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Blood and lymphatic system disorders Anaemia	33.3% 2/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	0.00% 0/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Cardiac disorders Tachycardia	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	0.00% 0/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Congenital, familial and genetic disorders Cryptorchism	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	0.00% 0/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Immune system disorders Hypersensitivity	0.00% 0/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Skin papilloma	0.00% 0/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
General disorders Disease progression	0.00% 0/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
General disorders Infusion site urticaria	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	0.00% 0/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Immune system disorders Seasonal allergy	0.00% 0/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Infections and infestations Abscess	0.00% 0/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Infections and infestations Abscess limb	0.00% 0/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Infections and infestations Bacterial disease carrier	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	0.00% 0/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Infections and infestations Localised infection	0.00% 0/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Infections and infestations Paraspinal abscess	0.00% 0/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Infections and infestations Pharyngitis	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	0.00% 0/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Injury, poisoning and procedural complications Humerus fracture	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	0.00% 0/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Injury, poisoning and procedural complications Scratch	0.00% 0/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Injury, poisoning and procedural complications Torus fracture	0.00% 0/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Injury, poisoning and procedural complications Ulna fracture	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	0.00% 0/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Musculoskeletal and connective tissue disorders Foot deformity	0.00% 0/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Nervous system disorders Syncope	0.00% 0/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Psychiatric disorders Agitation	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	0.00% 0/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Renal and urinary disorders Pollakiuria	0.00% 0/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.
Vascular disorders Flushing	0.00% 0/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.	16.7% 1/6 • Parent Baseline up to 240 weeks (cumulative Study 4658-us-201 + 4658-us-202) Only treatment-emergent adverse events with an onset date on or after the date of first dose of study drug were reported. Relatedness of Serious Adverse Events (SAEs) to study medication was determined by the Investigator.

Additional Information

Medical Director

Sarepta Therapeutics, Inc.

Phone: +1-888-727-3782

Email: clinicaltrials@sarepta.com

Results disclosure agreements

• Principal investigator is a sponsor employee There is an agreement between the Principal Investigators and the Sponsor (or its agents) that restricts the PIs' rights to discuss or publish trial results after the trial is completed.
• Publication restrictions are in place

Restriction type: OTHER