Trial Outcomes & Findings for A Study to Evaluate the Efficacy and Safety of CNTO328 Plus Best Supportive Care in Multicentric Castleman's Disease (NCT NCT01024036)

NCT ID: NCT01024036

Last Updated: 2018-03-21

Results Overview

Durable tumor and symptomatic response is complete response (CR) + partial response (PR). CR: complete disappearance of all measurable and evaluable disease (eg, pleural effusion) and resolution of baseline symptoms attributed to multicentric Castleman's disease, sustained for at least 18 weeks. PR: \>=50 percent decrease in sum of the product of the diameters of indicator lesion(s), with at least stable disease in all other evaluable disease in the absence of treatment failure sustained for at least 18 weeks. The statistical analysis shows difference in symptomatic response rate (siltuximab+best supportive care \[BSC\] minus Placebo+BSC).

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 79 participants
• Primary outcome timeframe: From Day 1 of Cycle 1 of treatment with study medication until treatment failure or discontinuation of treatment or withdrawal from study, or up to 48 weeks after last participant started study medication(approximately 3 years), whichever occurred earlier
• Results posted on: 2018-03-21

Participant Flow

79 participants were enrolled at 38 study centers in 19 countries. The first participant signed the informed consent on 09 Feb 2010, and the last participant's last visit for the primary analysis was 28 Feb 2013. The data until the end of study is presented here.

79 participants were enrolled, randomized and treated during the blinded treatment period. 53 received siltuximab+best supportive care (BSC) and 26 received placebo+BSC.13 participants who did not respond to placebo+BSC during the blinded treatment period, received siltuximab+BSC during the unblinded treatment period.

Participant milestones

Measure	Siltuximab + Best Supportive Care (BSC) Participants received siltuximab 11 milligram per kilogram (mg/kg) as a 1 hour intravenous (IV) infusion every 3 weeks along with BSC until treatment failure, discontinuation of treatment, withdrawal from study, or until 48 weeks after last participant started study treatment, whichever occurred earlier. Participants who discontinued treatment for any reason, completed End-of-Treatment (EOT) visit and entered Follow-up period. If a participant had documented treatment failure and wished to continue treatment, participant's treatment assignment was unblinded. Upon unblinding, if participant was assigned to siltuximab, study treatment was discontinued, and the participant completed EOT Visit and enter Follow up period (up to 3 months after last study drug intake) wherein participants were followed until death, lost to follow-up, withdrawal of consent, death of 50 percent (%) of participants, or end of the study, whichever occurred earlier.	Placebo + Best Supportive Care (BSC) Participants received placebo as a 1-hour IV infusion every 3 weeks along with BSC until treatment failure, discontinuation of treatment, withdrawal from study, or until 48 weeks after last participant started study treatment, whichever occurred earlier. If a participant had documented treatment failure and wished to continue treatment, the participant's treatment assignment was unblinded. Upon unblinding placebo participants who received blinded treatment had an option to receive unblinded treatment with siltuximab. Participants who discontinued or completed treatment period up to Week 48 and who consented to enter follow-up period were continued to be followed up during the course of follow-up period (up to 3 months after last study drug intake) wherein participants were followed until death, lost to follow-up, withdrawal of consent, death of 50% of participants, or end of the study, whichever occurred earlier.
Blinded Treatment STARTED	53	26
Blinded Treatment COMPLETED	31	6
Blinded Treatment NOT COMPLETED	22	20
Unblinded Treatment STARTED	0	13
Unblinded Treatment COMPLETED	0	10
Unblinded Treatment NOT COMPLETED	0	3
Follow-Up Period STARTED	14	6
Follow-Up Period COMPLETED	9	3
Follow-Up Period NOT COMPLETED	5	3

Reasons for withdrawal

Measure	Siltuximab + Best Supportive Care (BSC) Participants received siltuximab 11 milligram per kilogram (mg/kg) as a 1 hour intravenous (IV) infusion every 3 weeks along with BSC until treatment failure, discontinuation of treatment, withdrawal from study, or until 48 weeks after last participant started study treatment, whichever occurred earlier. Participants who discontinued treatment for any reason, completed End-of-Treatment (EOT) visit and entered Follow-up period. If a participant had documented treatment failure and wished to continue treatment, participant's treatment assignment was unblinded. Upon unblinding, if participant was assigned to siltuximab, study treatment was discontinued, and the participant completed EOT Visit and enter Follow up period (up to 3 months after last study drug intake) wherein participants were followed until death, lost to follow-up, withdrawal of consent, death of 50 percent (%) of participants, or end of the study, whichever occurred earlier.	Placebo + Best Supportive Care (BSC) Participants received placebo as a 1-hour IV infusion every 3 weeks along with BSC until treatment failure, discontinuation of treatment, withdrawal from study, or until 48 weeks after last participant started study treatment, whichever occurred earlier. If a participant had documented treatment failure and wished to continue treatment, the participant's treatment assignment was unblinded. Upon unblinding placebo participants who received blinded treatment had an option to receive unblinded treatment with siltuximab. Participants who discontinued or completed treatment period up to Week 48 and who consented to enter follow-up period were continued to be followed up during the course of follow-up period (up to 3 months after last study drug intake) wherein participants were followed until death, lost to follow-up, withdrawal of consent, death of 50% of participants, or end of the study, whichever occurred earlier.
Blinded Treatment Adverse Event	1	1
Blinded Treatment Lack of Efficacy	16	14
Blinded Treatment Physician Decision	1	0
Blinded Treatment Death	0	2
Blinded Treatment Withdrawal by Subject	4	3
Unblinded Treatment Adverse Event	0	1
Unblinded Treatment Lack of Efficacy	0	2
Follow-Up Period Lost to Follow-up	1	1
Follow-Up Period Withdrawal by Subject	0	1
Follow-Up Period Adverse Event	4	1

Baseline Characteristics

A Study to Evaluate the Efficacy and Safety of CNTO328 Plus Best Supportive Care in Multicentric Castleman's Disease

Baseline characteristics by cohort

Measure	Placebo + Best Supportive Care (BSC) n=26 Participants Participants received placebo as a 1-hour IV infusion every 3 weeks along with BSC until treatment failure, discontinuation of treatment, withdrawal from study, or until 48 weeks after last participant started study treatment, whichever occurred earlier. If a participant had documented treatment failure and wished to continue treatment, the participant's treatment assignment was unblinded. Upon unblinding placebo participants who received blinded treatment had an option to receive unblinded treatment with siltuximab. Participants who discontinued or completed treatment period up to Week 48 and who consented to enter follow-up period were continued to be followed up during the course of follow-up period (up to 3 months after last study drug intake) wherein participants were followed until death, lost to follow-up, withdrawal of consent, death of 50% of participants, or end of the study, whichever occurred earlier.	Siltuximab + Best Supportive Care (BSC) n=53 Participants Participants received siltuximab 11 milligram per kilogram (mg/kg) as a 1 hour intravenous (IV) infusion every 3 weeks along with BSC until treatment failure, discontinuation of treatment, withdrawal from study, or until 48 weeks after last participant started study treatment, whichever occurred earlier. Participants who discontinued treatment for any reason, completed End-of-Treatment (EOT) visit and entered Follow-up period. If a participant had documented treatment failure and wished to continue treatment, participant's treatment assignment was unblinded. Upon unblinding, if participant was assigned to siltuximab, study treatment was discontinued, and the participant completed EOT Visit and enter Follow up period (up to 3 months after last study drug intake) wherein participants were followed until death, lost to follow-up, withdrawal of consent, death of 50 percent (%) of participants, or end of the study, whichever occurred earlier.	Total n=79 Participants Total of all reporting groups
Age, Continuous	47.7 years STANDARD_DEVIATION 13.4 • n=5 Participants	44.4 years STANDARD_DEVIATION 13.32 • n=7 Participants	45.5 years STANDARD_DEVIATION 13.35 • n=5 Participants
Sex: Female, Male Female	4 Participants n=5 Participants	23 Participants n=7 Participants	27 Participants n=5 Participants
Sex: Female, Male Male	22 Participants n=5 Participants	30 Participants n=7 Participants	52 Participants n=5 Participants
Region of Enrollment AUSTRALIA	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Region of Enrollment BELGIUM	0 Participants n=5 Participants	3 Participants n=7 Participants	3 Participants n=5 Participants
Region of Enrollment BRAZIL	2 Participants n=5 Participants	4 Participants n=7 Participants	6 Participants n=5 Participants
Region of Enrollment CANADA	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Region of Enrollment CHINA	5 Participants n=5 Participants	11 Participants n=7 Participants	16 Participants n=5 Participants
Region of Enrollment EGYPT	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Region of Enrollment FRANCE	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Region of Enrollment GERMANY	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Region of Enrollment HONG KONG	2 Participants n=5 Participants	3 Participants n=7 Participants	5 Participants n=5 Participants
Region of Enrollment ISRAEL	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Region of Enrollment NEW ZEALAND	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Region of Enrollment NORWAY	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Region of Enrollment RUSSIAN FEDERATION	0 Participants n=5 Participants	3 Participants n=7 Participants	3 Participants n=5 Participants
Region of Enrollment SINGAPORE	0 Participants n=5 Participants	3 Participants n=7 Participants	3 Participants n=5 Participants
Region of Enrollment SOUTH KOREA	2 Participants n=5 Participants	4 Participants n=7 Participants	6 Participants n=5 Participants
Region of Enrollment SPAIN	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Region of Enrollment TAIWAN	1 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants
Region of Enrollment UNITED KINGDOM	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Region of Enrollment UNITED STATES	4 Participants n=5 Participants	10 Participants n=7 Participants	14 Participants n=5 Participants

PRIMARY outcome

Timeframe: From Day 1 of Cycle 1 of treatment with study medication until treatment failure or discontinuation of treatment or withdrawal from study, or up to 48 weeks after last participant started study medication(approximately 3 years), whichever occurred earlier

Population: Intent-to-treat (ITT) population: all randomized participants.

Durable tumor and symptomatic response is complete response (CR) + partial response (PR). CR: complete disappearance of all measurable and evaluable disease (eg, pleural effusion) and resolution of baseline symptoms attributed to multicentric Castleman's disease, sustained for at least 18 weeks. PR: >=50 percent decrease in sum of the product of the diameters of indicator lesion(s), with at least stable disease in all other evaluable disease in the absence of treatment failure sustained for at least 18 weeks. The statistical analysis shows difference in symptomatic response rate (siltuximab+best supportive care [BSC] minus Placebo+BSC).

Outcome measures

Measure	Placebo + Best Supportive Care (BSC) n=26 Participants Participants received placebo as a 1-hour IV infusion every 3 weeks along with BSC until treatment failure, discontinuation of treatment, withdrawal from study, or until 48 weeks after last participant started study treatment, whichever occurred earlier. If a participant had documented treatment failure and wished to continue treatment, the participant's treatment assignment was unblinded. Upon unblinding placebo participants who received blinded treatment had an option to receive unblinded treatment with siltuximab. Participants who discontinued or completed treatment period up to Week 48 and who consented to enter follow-up period were continued to be followed up during the course of follow-up period (up to 3 months after last study drug intake) wherein participants were followed until death, lost to follow-up, withdrawal of consent, death of 50% of participants, or end of the study, whichever occurred earlier.	Siltuximab + Best Supportive Care (BSC) n=53 Participants Participants received siltuximab 11 milligram per kilogram (mg/kg) as a 1 hour intravenous (IV) infusion every 3 weeks along with BSC until treatment failure, discontinuation of treatment, withdrawal from study, or until 48 weeks after last participant started study treatment, whichever occurred earlier. Participants who discontinued treatment for any reason, completed End-of-Treatment (EOT) visit and entered Follow-up period. If a participant had documented treatment failure and wished to continue treatment, participant's treatment assignment was unblinded. Upon unblinding, if participant was assigned to siltuximab, study treatment was discontinued, and the participant completed EOT Visit and enter Follow up period (up to 3 months after last study drug intake) wherein participants were followed until death, lost to follow-up, withdrawal of consent, death of 50 percent (%) of participants, or end of the study, whichever occurred earlier.
Percentage of Participants Who Achieved Durable Tumor and Symptomatic Response - by Independent Radiology Review	0 Percentage of participants	34 Percentage of participants

SECONDARY outcome

Timeframe: From the date when durable tumour and symptomatic response is achieved until treatment failure, as assessed until 48 weeks after the last participant started study treatment (approximately 3 years)

Population: All randomized participants who achieved durable tumor and symptomatic response during blinded treatment period as per independent review.

Duration of tumor and symptomatic response is defined as time from first documentation of tumor and symptomatic response (CR or PR) to treatment failure. Whenever possible, treatment failure documented by the appearance of new lesions should be confirmed by histologic examination of the new lesions. Symptomatic response is complete response (CR) + partial response (PR). CR: complete disappearance of all measurable and evaluable disease (eg, pleural effusion) and resolution of baseline symptoms attributed to multicentric Castleman's disease, sustained for at least 18 weeks. PR: >=50 percent decrease in sum of the product of the diameters of indicator lesion(s), with at least stable disease in all other evaluable disease in the absence of treatment failure sustained for at least 18 weeks.

Outcome measures

Measure	Placebo + Best Supportive Care (BSC) Participants received placebo as a 1-hour IV infusion every 3 weeks along with BSC until treatment failure, discontinuation of treatment, withdrawal from study, or until 48 weeks after last participant started study treatment, whichever occurred earlier. If a participant had documented treatment failure and wished to continue treatment, the participant's treatment assignment was unblinded. Upon unblinding placebo participants who received blinded treatment had an option to receive unblinded treatment with siltuximab. Participants who discontinued or completed treatment period up to Week 48 and who consented to enter follow-up period were continued to be followed up during the course of follow-up period (up to 3 months after last study drug intake) wherein participants were followed until death, lost to follow-up, withdrawal of consent, death of 50% of participants, or end of the study, whichever occurred earlier.	Siltuximab + Best Supportive Care (BSC) n=18 Participants Participants received siltuximab 11 milligram per kilogram (mg/kg) as a 1 hour intravenous (IV) infusion every 3 weeks along with BSC until treatment failure, discontinuation of treatment, withdrawal from study, or until 48 weeks after last participant started study treatment, whichever occurred earlier. Participants who discontinued treatment for any reason, completed End-of-Treatment (EOT) visit and entered Follow-up period. If a participant had documented treatment failure and wished to continue treatment, participant's treatment assignment was unblinded. Upon unblinding, if participant was assigned to siltuximab, study treatment was discontinued, and the participant completed EOT Visit and enter Follow up period (up to 3 months after last study drug intake) wherein participants were followed until death, lost to follow-up, withdrawal of consent, death of 50 percent (%) of participants, or end of the study, whichever occurred earlier.
Median Duration of Tumor and Symptomatic Response - by Independent Radiology Review	—	383.0 Days Interval 232.0 to 676.0

SECONDARY outcome

Timeframe: From Day 1 of Cycle 1 until the date when durable tumour and symptomatic response is achieved, as assessed up to 48 weeks after the last participant started study treatment (approximately 3 years)

Population: Response-evaluable Population: included participants who received at least 1 administration of siltuximab/placebo and had at least 1 post-baseline radiologic disease evaluation.

Overall tumor response is CR + PR assessed according to Cheson criteria. CR: complete disappearance of all measurable and evaluable disease (eg, pleural effusion). PR: a >=50 percent decrease in sum of the product of the diameters of index lesion(s), with at least stable disease in all other evaluable disease. Statistical analysis shows difference of overall response rates (siltuximab+best supportive care [BSC] minus Placebo+BSC).

Outcome measures

Measure	Placebo + Best Supportive Care (BSC) n=26 Participants Participants received placebo as a 1-hour IV infusion every 3 weeks along with BSC until treatment failure, discontinuation of treatment, withdrawal from study, or until 48 weeks after last participant started study treatment, whichever occurred earlier. If a participant had documented treatment failure and wished to continue treatment, the participant's treatment assignment was unblinded. Upon unblinding placebo participants who received blinded treatment had an option to receive unblinded treatment with siltuximab. Participants who discontinued or completed treatment period up to Week 48 and who consented to enter follow-up period were continued to be followed up during the course of follow-up period (up to 3 months after last study drug intake) wherein participants were followed until death, lost to follow-up, withdrawal of consent, death of 50% of participants, or end of the study, whichever occurred earlier.	Siltuximab + Best Supportive Care (BSC) n=53 Participants Participants received siltuximab 11 milligram per kilogram (mg/kg) as a 1 hour intravenous (IV) infusion every 3 weeks along with BSC until treatment failure, discontinuation of treatment, withdrawal from study, or until 48 weeks after last participant started study treatment, whichever occurred earlier. Participants who discontinued treatment for any reason, completed End-of-Treatment (EOT) visit and entered Follow-up period. If a participant had documented treatment failure and wished to continue treatment, participant's treatment assignment was unblinded. Upon unblinding, if participant was assigned to siltuximab, study treatment was discontinued, and the participant completed EOT Visit and enter Follow up period (up to 3 months after last study drug intake) wherein participants were followed until death, lost to follow-up, withdrawal of consent, death of 50 percent (%) of participants, or end of the study, whichever occurred earlier.
Percentage of Participants Who Achieved Complete Response (CR) + Partial Response (PR) (Tumor Response Rate) - by Independent Radiology Review	3.8 Percentage of participants	37.7 Percentage of participants

SECONDARY outcome

Timeframe: From the date when tumour response is achieved until tumour progression, as assessed up to 48 weeks after the last participant started study treatment (approximately 3 years)

Population: All randomized participants who achieved tumor response during blinded treatment period as per independent review.

Duration of tumor response is defined as time from first documentation of tumor response to tumor progression. Tumour response is complete response (CR) + partial response (PR) as assessed according to Cheson criteria. CR: complete disappearance of all measurable and evaluable disease (eg, pleural effusion). PR: a >=50 percent decrease in sum of the product of the diameters of index lesion(s), with at least stable disease in all other evaluable disease. Statistical analysis shows difference of overall response rates (siltuximab+best supportive care [BSC] minus Placebo+BSC).

Outcome measures

Measure	Placebo + Best Supportive Care (BSC) n=1 Participants Participants received placebo as a 1-hour IV infusion every 3 weeks along with BSC until treatment failure, discontinuation of treatment, withdrawal from study, or until 48 weeks after last participant started study treatment, whichever occurred earlier. If a participant had documented treatment failure and wished to continue treatment, the participant's treatment assignment was unblinded. Upon unblinding placebo participants who received blinded treatment had an option to receive unblinded treatment with siltuximab. Participants who discontinued or completed treatment period up to Week 48 and who consented to enter follow-up period were continued to be followed up during the course of follow-up period (up to 3 months after last study drug intake) wherein participants were followed until death, lost to follow-up, withdrawal of consent, death of 50% of participants, or end of the study, whichever occurred earlier.	Siltuximab + Best Supportive Care (BSC) n=20 Participants Participants received siltuximab 11 milligram per kilogram (mg/kg) as a 1 hour intravenous (IV) infusion every 3 weeks along with BSC until treatment failure, discontinuation of treatment, withdrawal from study, or until 48 weeks after last participant started study treatment, whichever occurred earlier. Participants who discontinued treatment for any reason, completed End-of-Treatment (EOT) visit and entered Follow-up period. If a participant had documented treatment failure and wished to continue treatment, participant's treatment assignment was unblinded. Upon unblinding, if participant was assigned to siltuximab, study treatment was discontinued, and the participant completed EOT Visit and enter Follow up period (up to 3 months after last study drug intake) wherein participants were followed until death, lost to follow-up, withdrawal of consent, death of 50 percent (%) of participants, or end of the study, whichever occurred earlier.
Median Duration of Tumor Response - by Independent Radiology Review	70 Days Interval 70.0 to 70.0	356 Days Interval 55.0 to 674.0

SECONDARY outcome

Timeframe: From the date of randomization until a participant fails treatment, as assessed up to 48 weeks after the last participant started study treatment (approximately 3 years), whichever occurred earlier

Population: Intent-to-treat (ITT) population: all randomized participants.

Time to treatment failure was defined as the time from randomization until the participant fails treatment. Treatment failure was defined as any of the following: a sustained increase from baseline in disease related symptoms >=Grade 2 persisting for at least 3 weeks despite best supportive care (BSC); onset of any new disease related Grade 3 or higher symptom despite BSC; sustained (ie, at least 3 weeks) deterioration in performance status (increase from baseline in Eastern Cooperative Oncology Group Performance Status by more than 1 point) despite BSC; radiologic progression, as measured by modified Cheson criteria; Initiation of any other therapy intended to treat multicentric Castleman's disease ie, prohibited treatments. Statistical analysis shows difference in treatment failure rate (siltuximab+BSC minus Placebo+BSC).

Outcome measures

Measure	Placebo + Best Supportive Care (BSC) n=26 Participants Participants received placebo as a 1-hour IV infusion every 3 weeks along with BSC until treatment failure, discontinuation of treatment, withdrawal from study, or until 48 weeks after last participant started study treatment, whichever occurred earlier. If a participant had documented treatment failure and wished to continue treatment, the participant's treatment assignment was unblinded. Upon unblinding placebo participants who received blinded treatment had an option to receive unblinded treatment with siltuximab. Participants who discontinued or completed treatment period up to Week 48 and who consented to enter follow-up period were continued to be followed up during the course of follow-up period (up to 3 months after last study drug intake) wherein participants were followed until death, lost to follow-up, withdrawal of consent, death of 50% of participants, or end of the study, whichever occurred earlier.	Siltuximab + Best Supportive Care (BSC) n=53 Participants Participants received siltuximab 11 milligram per kilogram (mg/kg) as a 1 hour intravenous (IV) infusion every 3 weeks along with BSC until treatment failure, discontinuation of treatment, withdrawal from study, or until 48 weeks after last participant started study treatment, whichever occurred earlier. Participants who discontinued treatment for any reason, completed End-of-Treatment (EOT) visit and entered Follow-up period. If a participant had documented treatment failure and wished to continue treatment, participant's treatment assignment was unblinded. Upon unblinding, if participant was assigned to siltuximab, study treatment was discontinued, and the participant completed EOT Visit and enter Follow up period (up to 3 months after last study drug intake) wherein participants were followed until death, lost to follow-up, withdrawal of consent, death of 50 percent (%) of participants, or end of the study, whichever occurred earlier.
Time to Treatment Failure	134 Days Interval 85.0 to The upper limit was not estimable due to insufficient number of participants with event.	NA Days Interval 378.0 to Median time to treatment failure was not estimable due to insufficient number of participants with event.

SECONDARY outcome

Timeframe: Week 13

Population: Hemoglobin response-evaluable population: participants who received at least 1 siltuximab/placebo administration and have a baseline hemoglobin that is below the lower limit of normal as per local laboratory specifications (within 2 weeks before starting treatment) and at least 1 postbaseline hemoglobin evaluation.

Hemoglobin response rate is defined as percentage of participants who achieved >= 15 g/L hemoglobin at Week 13.

Outcome measures

Measure	Placebo + Best Supportive Care (BSC) n=11 Participants Participants received placebo as a 1-hour IV infusion every 3 weeks along with BSC until treatment failure, discontinuation of treatment, withdrawal from study, or until 48 weeks after last participant started study treatment, whichever occurred earlier. If a participant had documented treatment failure and wished to continue treatment, the participant's treatment assignment was unblinded. Upon unblinding placebo participants who received blinded treatment had an option to receive unblinded treatment with siltuximab. Participants who discontinued or completed treatment period up to Week 48 and who consented to enter follow-up period were continued to be followed up during the course of follow-up period (up to 3 months after last study drug intake) wherein participants were followed until death, lost to follow-up, withdrawal of consent, death of 50% of participants, or end of the study, whichever occurred earlier.	Siltuximab + Best Supportive Care (BSC) n=31 Participants Participants received siltuximab 11 milligram per kilogram (mg/kg) as a 1 hour intravenous (IV) infusion every 3 weeks along with BSC until treatment failure, discontinuation of treatment, withdrawal from study, or until 48 weeks after last participant started study treatment, whichever occurred earlier. Participants who discontinued treatment for any reason, completed End-of-Treatment (EOT) visit and entered Follow-up period. If a participant had documented treatment failure and wished to continue treatment, participant's treatment assignment was unblinded. Upon unblinding, if participant was assigned to siltuximab, study treatment was discontinued, and the participant completed EOT Visit and enter Follow up period (up to 3 months after last study drug intake) wherein participants were followed until death, lost to follow-up, withdrawal of consent, death of 50 percent (%) of participants, or end of the study, whichever occurred earlier.
Percentage of Participants Who Achieved Greater Than or Equal to (>=) 15 Gram Per Liter (g/L) Hemoglobin at Week 13 (Hemoglobin Response Rate)	0 Percentage of participants	61.3 Percentage of participants

SECONDARY outcome

Timeframe: Week 13

Population: Hemoglobin response-evaluable population: participants who received at least 1 siltuximab/placebo administration and have a baseline hemoglobin that is below the lower limit of normal as per local laboratory specifications (within 2 weeks before starting treatment) and at least 1 post-baseline hemoglobin evaluation.

Hemoglobin response rate is defined as percentage of participants who achieved >= 20 g/L hemoglobin at Week 13.

Outcome measures

Measure	Placebo + Best Supportive Care (BSC) n=11 Participants Participants received placebo as a 1-hour IV infusion every 3 weeks along with BSC until treatment failure, discontinuation of treatment, withdrawal from study, or until 48 weeks after last participant started study treatment, whichever occurred earlier. If a participant had documented treatment failure and wished to continue treatment, the participant's treatment assignment was unblinded. Upon unblinding placebo participants who received blinded treatment had an option to receive unblinded treatment with siltuximab. Participants who discontinued or completed treatment period up to Week 48 and who consented to enter follow-up period were continued to be followed up during the course of follow-up period (up to 3 months after last study drug intake) wherein participants were followed until death, lost to follow-up, withdrawal of consent, death of 50% of participants, or end of the study, whichever occurred earlier.	Siltuximab + Best Supportive Care (BSC) n=31 Participants Participants received siltuximab 11 milligram per kilogram (mg/kg) as a 1 hour intravenous (IV) infusion every 3 weeks along with BSC until treatment failure, discontinuation of treatment, withdrawal from study, or until 48 weeks after last participant started study treatment, whichever occurred earlier. Participants who discontinued treatment for any reason, completed End-of-Treatment (EOT) visit and entered Follow-up period. If a participant had documented treatment failure and wished to continue treatment, participant's treatment assignment was unblinded. Upon unblinding, if participant was assigned to siltuximab, study treatment was discontinued, and the participant completed EOT Visit and enter Follow up period (up to 3 months after last study drug intake) wherein participants were followed until death, lost to follow-up, withdrawal of consent, death of 50 percent (%) of participants, or end of the study, whichever occurred earlier.
Percentage of Participants Who Achieved >= 20 g/L Hemoglobin at Week 13 (Hemoglobin Response Rate)	0 Percentage of participants	41.9 Percentage of participants

SECONDARY outcome

Timeframe: From Day 1 of Cycle 1 until 48 weeks after the after the last participant started study treatment (approximately 3 years)

Population: All randomized participants who were dependent on corticosteroids at baseline.

Percentage of participants who discontinued corticosteroids during blinded treatment period and who were dependent on corticosteroids at baseline (Day 1 of Cycle 1).

Outcome measures

Measure	Placebo + Best Supportive Care (BSC) n=9 Participants Participants received placebo as a 1-hour IV infusion every 3 weeks along with BSC until treatment failure, discontinuation of treatment, withdrawal from study, or until 48 weeks after last participant started study treatment, whichever occurred earlier. If a participant had documented treatment failure and wished to continue treatment, the participant's treatment assignment was unblinded. Upon unblinding placebo participants who received blinded treatment had an option to receive unblinded treatment with siltuximab. Participants who discontinued or completed treatment period up to Week 48 and who consented to enter follow-up period were continued to be followed up during the course of follow-up period (up to 3 months after last study drug intake) wherein participants were followed until death, lost to follow-up, withdrawal of consent, death of 50% of participants, or end of the study, whichever occurred earlier.	Siltuximab + Best Supportive Care (BSC) n=13 Participants Participants received siltuximab 11 milligram per kilogram (mg/kg) as a 1 hour intravenous (IV) infusion every 3 weeks along with BSC until treatment failure, discontinuation of treatment, withdrawal from study, or until 48 weeks after last participant started study treatment, whichever occurred earlier. Participants who discontinued treatment for any reason, completed End-of-Treatment (EOT) visit and entered Follow-up period. If a participant had documented treatment failure and wished to continue treatment, participant's treatment assignment was unblinded. Upon unblinding, if participant was assigned to siltuximab, study treatment was discontinued, and the participant completed EOT Visit and enter Follow up period (up to 3 months after last study drug intake) wherein participants were followed until death, lost to follow-up, withdrawal of consent, death of 50 percent (%) of participants, or end of the study, whichever occurred earlier.
Percentage of Participants Who Discontinued Corticosteroids	11.1 Percentage of participants	30.8 Percentage of participants

SECONDARY outcome

Timeframe: until 6 years

Population: Safety Analysis set included all randomized participants who received at least 1 dose of study agent.

Overall survival was defined as percent chance of survival of participants who were still alive at 6 years from time of first study treatment was analyzed.

Outcome measures

Measure	Placebo + Best Supportive Care (BSC) n=26 Participants Participants received placebo as a 1-hour IV infusion every 3 weeks along with BSC until treatment failure, discontinuation of treatment, withdrawal from study, or until 48 weeks after last participant started study treatment, whichever occurred earlier. If a participant had documented treatment failure and wished to continue treatment, the participant's treatment assignment was unblinded. Upon unblinding placebo participants who received blinded treatment had an option to receive unblinded treatment with siltuximab. Participants who discontinued or completed treatment period up to Week 48 and who consented to enter follow-up period were continued to be followed up during the course of follow-up period (up to 3 months after last study drug intake) wherein participants were followed until death, lost to follow-up, withdrawal of consent, death of 50% of participants, or end of the study, whichever occurred earlier.	Siltuximab + Best Supportive Care (BSC) n=53 Participants Participants received siltuximab 11 milligram per kilogram (mg/kg) as a 1 hour intravenous (IV) infusion every 3 weeks along with BSC until treatment failure, discontinuation of treatment, withdrawal from study, or until 48 weeks after last participant started study treatment, whichever occurred earlier. Participants who discontinued treatment for any reason, completed End-of-Treatment (EOT) visit and entered Follow-up period. If a participant had documented treatment failure and wished to continue treatment, participant's treatment assignment was unblinded. Upon unblinding, if participant was assigned to siltuximab, study treatment was discontinued, and the participant completed EOT Visit and enter Follow up period (up to 3 months after last study drug intake) wherein participants were followed until death, lost to follow-up, withdrawal of consent, death of 50 percent (%) of participants, or end of the study, whichever occurred earlier.
6-year Survival Rate	79.5 Percent chance of survival Interval 57.5 to 91.0	86.3 Percent chance of survival Interval 71.9 to 93.6

SECONDARY outcome

Timeframe: From Day 1 of Cycle 1 (baseline) until 48 weeks after the last participant started study treatment (approximately 3 years)

Population: Intent-to-treat (ITT) population: all randomized participants.

A patient-reported symptom scale. Symptom presence/absence and severity are noted on an anchor-based numeric scale. Scores range from 1 (very mild) to 5 (very severe).

Outcome measures

Measure	Placebo + Best Supportive Care (BSC) n=26 Participants Participants received placebo as a 1-hour IV infusion every 3 weeks along with BSC until treatment failure, discontinuation of treatment, withdrawal from study, or until 48 weeks after last participant started study treatment, whichever occurred earlier. If a participant had documented treatment failure and wished to continue treatment, the participant's treatment assignment was unblinded. Upon unblinding placebo participants who received blinded treatment had an option to receive unblinded treatment with siltuximab. Participants who discontinued or completed treatment period up to Week 48 and who consented to enter follow-up period were continued to be followed up during the course of follow-up period (up to 3 months after last study drug intake) wherein participants were followed until death, lost to follow-up, withdrawal of consent, death of 50% of participants, or end of the study, whichever occurred earlier.	Siltuximab + Best Supportive Care (BSC) n=53 Participants Participants received siltuximab 11 milligram per kilogram (mg/kg) as a 1 hour intravenous (IV) infusion every 3 weeks along with BSC until treatment failure, discontinuation of treatment, withdrawal from study, or until 48 weeks after last participant started study treatment, whichever occurred earlier. Participants who discontinued treatment for any reason, completed End-of-Treatment (EOT) visit and entered Follow-up period. If a participant had documented treatment failure and wished to continue treatment, participant's treatment assignment was unblinded. Upon unblinding, if participant was assigned to siltuximab, study treatment was discontinued, and the participant completed EOT Visit and enter Follow up period (up to 3 months after last study drug intake) wherein participants were followed until death, lost to follow-up, withdrawal of consent, death of 50 percent (%) of participants, or end of the study, whichever occurred earlier.
Median Time Required to Achieve >=1 Point Decrease in the Multicentric Castleman's Disease Symptom Scale (MCD-SS) Score From Baseline	262 Days Interval 40.0 to The upper limit was not estimable due to insufficient number of participants with event.	85 Days Interval 22.0 to 379.0

SECONDARY outcome

Timeframe: From Day 1 of Cycle 1 (baseline) until 48 weeks after the last participant started study treatment (approximately 3 years)

Population: Intent-to-treat (ITT) population: all randomized participants.

The FACIT-F, a 13-item instrument, was designed to measure patient-reported fatigue. It is one of the suite of FACIT instruments developed for outcomes in cancer. Concepts measured in the scale include tiredness, weakness, and difficulty conducting usual functional activities or social interaction due to fatigue. Response options range from "not at all" (0) to "very much" (4), and yield a summary score. Total FACIT-F score is the sum of 13 items, ranging from 0 (not at all) to 52 (very much). Higher scores represent better outcomes.

Outcome measures

Measure	Placebo + Best Supportive Care (BSC) n=26 Participants Participants received placebo as a 1-hour IV infusion every 3 weeks along with BSC until treatment failure, discontinuation of treatment, withdrawal from study, or until 48 weeks after last participant started study treatment, whichever occurred earlier. If a participant had documented treatment failure and wished to continue treatment, the participant's treatment assignment was unblinded. Upon unblinding placebo participants who received blinded treatment had an option to receive unblinded treatment with siltuximab. Participants who discontinued or completed treatment period up to Week 48 and who consented to enter follow-up period were continued to be followed up during the course of follow-up period (up to 3 months after last study drug intake) wherein participants were followed until death, lost to follow-up, withdrawal of consent, death of 50% of participants, or end of the study, whichever occurred earlier.	Siltuximab + Best Supportive Care (BSC) n=53 Participants Participants received siltuximab 11 milligram per kilogram (mg/kg) as a 1 hour intravenous (IV) infusion every 3 weeks along with BSC until treatment failure, discontinuation of treatment, withdrawal from study, or until 48 weeks after last participant started study treatment, whichever occurred earlier. Participants who discontinued treatment for any reason, completed End-of-Treatment (EOT) visit and entered Follow-up period. If a participant had documented treatment failure and wished to continue treatment, participant's treatment assignment was unblinded. Upon unblinding, if participant was assigned to siltuximab, study treatment was discontinued, and the participant completed EOT Visit and enter Follow up period (up to 3 months after last study drug intake) wherein participants were followed until death, lost to follow-up, withdrawal of consent, death of 50 percent (%) of participants, or end of the study, whichever occurred earlier.
Median Time Required to Achieve >=3-point Increase in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Scores From Baseline	22 Days Interval 8.0 to 64.0	15 Days Interval 8.0 to 23.0

SECONDARY outcome

Timeframe: From Day 1 of Cycle 1 (baseline) until 48 weeks after the last participant started study treatment (approximately 3 years)

Population: Intent-to-treat (ITT) population: all randomized participants.

SF-36 is a questionnaire and PCS is a part of subscale assessing physical functioning, role-physical, bodily pain, and general health. The scores range from 0 (worst score) to 100 (best score), with a higher score indicating better quality of life.

Outcome measures

Measure	Placebo + Best Supportive Care (BSC) n=26 Participants Participants received placebo as a 1-hour IV infusion every 3 weeks along with BSC until treatment failure, discontinuation of treatment, withdrawal from study, or until 48 weeks after last participant started study treatment, whichever occurred earlier. If a participant had documented treatment failure and wished to continue treatment, the participant's treatment assignment was unblinded. Upon unblinding placebo participants who received blinded treatment had an option to receive unblinded treatment with siltuximab. Participants who discontinued or completed treatment period up to Week 48 and who consented to enter follow-up period were continued to be followed up during the course of follow-up period (up to 3 months after last study drug intake) wherein participants were followed until death, lost to follow-up, withdrawal of consent, death of 50% of participants, or end of the study, whichever occurred earlier.	Siltuximab + Best Supportive Care (BSC) n=53 Participants Participants received siltuximab 11 milligram per kilogram (mg/kg) as a 1 hour intravenous (IV) infusion every 3 weeks along with BSC until treatment failure, discontinuation of treatment, withdrawal from study, or until 48 weeks after last participant started study treatment, whichever occurred earlier. Participants who discontinued treatment for any reason, completed End-of-Treatment (EOT) visit and entered Follow-up period. If a participant had documented treatment failure and wished to continue treatment, participant's treatment assignment was unblinded. Upon unblinding, if participant was assigned to siltuximab, study treatment was discontinued, and the participant completed EOT Visit and enter Follow up period (up to 3 months after last study drug intake) wherein participants were followed until death, lost to follow-up, withdrawal of consent, death of 50 percent (%) of participants, or end of the study, whichever occurred earlier.
Median Time Required to Achieve >=5-point Increase in the Short-Form-36 (SF-36) Physical Component Summary (PCS) Scores From Baseline	NA Days Interval 169.0 to Median time was not estimable due to insufficient number of participants with event.	420 Days Interval 106.0 to The upper limit was not estimable due to insufficient number of participants with event.

Adverse Events

Placebo + Best Supportive Care (BSC) (Blinded)

Serious events: 7 serious events

Other events: 25 other events

Deaths: 0 deaths

Siltuximab + Best Supportive Care (BSC) (Blinded)

Serious events: 12 serious events

Other events: 53 other events

Deaths: 0 deaths

Siltuximab + Best Supportive Care (BSC) (Unblinded)

Serious events: 4 serious events

Other events: 13 other events

Deaths: 0 deaths

Placebo + BSC (Follow-up Period)

Serious events: 1 serious events

Other events: 5 other events

Deaths: 0 deaths

Siltuximab + BSC (Follow-up Period)

Serious events: 3 serious events

Other events: 14 other events

Deaths: 0 deaths

Serious adverse events

Measure	Placebo + Best Supportive Care (BSC) (Blinded) n=26 participants at risk Participants received placebo as a 1-hour intravenous infusion every 3 weeks along with BSC until treatment failure, discontinuation of treatment, withdrawal from the study, or until 48 weeks after the last participant started study treatment, whichever occurred earlier. Participants who discontinued or completed treatment period up to Week 48, and who consented to enter the follow-up period were continued to be followed up during the course of follow-up period.	Siltuximab + Best Supportive Care (BSC) (Blinded) n=53 participants at risk Participants received siltuximab 11mg/kg as a 1-hour intravenous infusion every 3 weeks along with BSC until treatment failure, discontinuation of treatment, withdrawal from the study, or until 48 weeks after the last participant started study treatment, whichever occurred earlier. Participants who discontinued treatment for any reason completed the end-of-treatment visit and entered the follow-up period.	Siltuximab + Best Supportive Care (BSC) (Unblinded) n=13 participants at risk Participants who had documented treatment failure and wished to continue treatment, their treatment assignment was unblinded. Upon unblinding placebo participants who received blinded treatment had an option to receive unblinded treatment with siltuximab during the unblinded treatment period.	Placebo + BSC (Follow-up Period) n=6 participants at risk No study treatment was administered during the follow-up period (up to 3 months after last study agent administration \[placebo as a 1 hour IV infusion every 3 weeks along with BSC\]) and participants were followed until death, lost to follow up, withdrawal of consent, death of 50 % of participants, or the end of the study, whichever occurred earlier.	Siltuximab + BSC (Follow-up Period) n=14 participants at risk No study treatment was administered during the follow-up period (up to 3 months after last study agent administration \[siltuximab 11mg/kg as a 1 hour IV infusion every 3 weeks along with \]) and participants were followed until death, lost to follow up, withdrawal of consent, death of 50 % of participants, or the end of the study, whichever occurred earlier.
Cardiac disorders Cardiac Failure Congestive	3.8% 1/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Endocrine disorders Hyperthyroidism	0.00% 0/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	1.9% 1/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Eye disorders Vitreous Haemorrhage	0.00% 0/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	1.9% 1/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Gastrointestinal disorders Dysphagia	3.8% 1/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Gastrointestinal disorders Umbilical Hernia	0.00% 0/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	1.9% 1/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
General disorders Oedema	0.00% 0/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	1.9% 1/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
General disorders Oedema Peripheral	3.8% 1/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.7% 1/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	16.7% 1/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Hepatobiliary disorders Cholecystitis Chronic	0.00% 0/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	1.9% 1/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.1% 1/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Hepatobiliary disorders Cholelithiasis	0.00% 0/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	1.9% 1/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Immune system disorders Anaphylactic Reaction	0.00% 0/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	1.9% 1/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Infections and infestations Anal Abscess	0.00% 0/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	1.9% 1/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Infections and infestations Bronchitis	0.00% 0/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	1.9% 1/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.1% 1/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Infections and infestations Lower Respiratory Tract Infection	0.00% 0/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	1.9% 1/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.1% 1/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Infections and infestations Lung Infection	3.8% 1/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.7% 1/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Infections and infestations Pneumonia	11.5% 3/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.7% 1/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Infections and infestations Sepsis	0.00% 0/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	1.9% 1/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Injury, poisoning and procedural complications Accidental Overdose	3.8% 1/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.7% 1/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Injury, poisoning and procedural complications Tibia Fracture	0.00% 0/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	1.9% 1/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Injury, poisoning and procedural complications Wound Secretion	0.00% 0/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	1.9% 1/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Investigations Mycobacterium Test	3.8% 1/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.7% 1/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Musculoskeletal and connective tissue disorders Muscle Spasms	0.00% 0/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	1.9% 1/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Poems Syndrome	3.8% 1/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.7% 1/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) T-Cell Lymphoma	3.8% 1/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Renal and urinary disorders Dysuria	0.00% 0/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	1.9% 1/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Renal and urinary disorders Renal Colic	0.00% 0/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	1.9% 1/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Renal and urinary disorders Ureteral Disorder	0.00% 0/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	1.9% 1/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Respiratory, thoracic and mediastinal disorders Dyspnoea	7.7% 2/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.7% 1/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	16.7% 1/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Respiratory, thoracic and mediastinal disorders Pleural Effusion	11.5% 3/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	1.9% 1/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	15.4% 2/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	16.7% 1/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Surgical and medical procedures Pain Management	3.8% 1/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.7% 1/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Vascular disorders Hypertensive Crisis	0.00% 0/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	1.9% 1/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.

Other adverse events

Measure	Placebo + Best Supportive Care (BSC) (Blinded) n=26 participants at risk Participants received placebo as a 1-hour intravenous infusion every 3 weeks along with BSC until treatment failure, discontinuation of treatment, withdrawal from the study, or until 48 weeks after the last participant started study treatment, whichever occurred earlier. Participants who discontinued or completed treatment period up to Week 48, and who consented to enter the follow-up period were continued to be followed up during the course of follow-up period.	Siltuximab + Best Supportive Care (BSC) (Blinded) n=53 participants at risk Participants received siltuximab 11mg/kg as a 1-hour intravenous infusion every 3 weeks along with BSC until treatment failure, discontinuation of treatment, withdrawal from the study, or until 48 weeks after the last participant started study treatment, whichever occurred earlier. Participants who discontinued treatment for any reason completed the end-of-treatment visit and entered the follow-up period.	Siltuximab + Best Supportive Care (BSC) (Unblinded) n=13 participants at risk Participants who had documented treatment failure and wished to continue treatment, their treatment assignment was unblinded. Upon unblinding placebo participants who received blinded treatment had an option to receive unblinded treatment with siltuximab during the unblinded treatment period.	Placebo + BSC (Follow-up Period) n=6 participants at risk No study treatment was administered during the follow-up period (up to 3 months after last study agent administration \[placebo as a 1 hour IV infusion every 3 weeks along with BSC\]) and participants were followed until death, lost to follow up, withdrawal of consent, death of 50 % of participants, or the end of the study, whichever occurred earlier.	Siltuximab + BSC (Follow-up Period) n=14 participants at risk No study treatment was administered during the follow-up period (up to 3 months after last study agent administration \[siltuximab 11mg/kg as a 1 hour IV infusion every 3 weeks along with \]) and participants were followed until death, lost to follow up, withdrawal of consent, death of 50 % of participants, or the end of the study, whichever occurred earlier.
Vascular disorders Flushing	7.7% 2/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	3.8% 2/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	15.4% 2/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Blood and lymphatic system disorders Anaemia	19.2% 5/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	9.4% 5/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	30.8% 4/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	33.3% 2/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	14.3% 2/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Blood and lymphatic system disorders Leukopenia	7.7% 2/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	5.7% 3/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.7% 1/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	33.3% 2/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.1% 1/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Blood and lymphatic system disorders Lymphopenia	11.5% 3/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	15.4% 2/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	16.7% 1/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Blood and lymphatic system disorders Neutropenia	11.5% 3/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	13.2% 7/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	15.4% 2/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	33.3% 2/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.1% 1/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Blood and lymphatic system disorders Thrombocytopenia	7.7% 2/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	15.1% 8/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.7% 1/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	16.7% 1/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	21.4% 3/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Ear and labyrinth disorders Vertigo	7.7% 2/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	3.8% 2/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	15.4% 2/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Eye disorders Noninfective Conjunctivitis	7.7% 2/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	1.9% 1/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.7% 1/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	16.7% 1/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Eye disorders Periorbital Oedema	7.7% 2/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	5.7% 3/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	15.4% 2/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.1% 1/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Eye disorders Vision Blurred	3.8% 1/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	5.7% 3/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.7% 1/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Gastrointestinal disorders Abdominal Distension	7.7% 2/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.5% 4/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.7% 1/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	21.4% 3/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Gastrointestinal disorders Abdominal Pain	7.7% 2/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	15.1% 8/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.7% 1/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.1% 1/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Gastrointestinal disorders Abdominal Pain Upper	7.7% 2/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	9.4% 5/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.7% 1/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	16.7% 1/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Gastrointestinal disorders Aphthous Ulcer	3.8% 1/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.5% 4/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.7% 1/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Gastrointestinal disorders Ascites	11.5% 3/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	5.7% 3/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.7% 1/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	16.7% 1/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	14.3% 2/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Gastrointestinal disorders Constipation	7.7% 2/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	11.3% 6/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.7% 1/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.1% 1/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Gastrointestinal disorders Diarrhoea	30.8% 8/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	24.5% 13/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	30.8% 4/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	33.3% 2/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	21.4% 3/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Gastrointestinal disorders Dyspepsia	15.4% 4/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	3.8% 2/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	23.1% 3/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.1% 1/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Gastrointestinal disorders Gastrooesophageal Reflux Disease	0.00% 0/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.5% 4/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.1% 1/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Gastrointestinal disorders Nausea	26.9% 7/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	9.4% 5/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	23.1% 3/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	16.7% 1/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Gastrointestinal disorders Tongue Ulceration	7.7% 2/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	1.9% 1/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.7% 1/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Gastrointestinal disorders Vomiting	19.2% 5/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	11.3% 6/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	23.1% 3/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	14.3% 2/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
General disorders Chest Pain	7.7% 2/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.7% 1/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
General disorders Face Oedema	3.8% 1/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	11.3% 6/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.7% 1/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	16.7% 1/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.1% 1/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
General disorders Fatigue	53.8% 14/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	34.0% 18/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	61.5% 8/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	33.3% 2/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	28.6% 4/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
General disorders Generalised Oedema	15.4% 4/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	13.2% 7/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	15.4% 2/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	33.3% 2/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.1% 1/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
General disorders Localised Oedema	11.5% 3/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	20.8% 11/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	15.4% 2/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	33.3% 2/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.1% 1/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
General disorders Malaise	26.9% 7/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	28.3% 15/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	46.2% 6/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	33.3% 2/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	35.7% 5/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
General disorders Oedema Peripheral	30.8% 8/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	35.8% 19/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	30.8% 4/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	50.0% 3/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	35.7% 5/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
General disorders Pain	7.7% 2/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	5.7% 3/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.7% 1/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
General disorders Pyrexia	15.4% 4/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	11.3% 6/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	15.4% 2/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	21.4% 3/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Hepatobiliary disorders Hepatic Function Abnormal	11.5% 3/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	3.8% 2/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	23.1% 3/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Infections and infestations Folliculitis	7.7% 2/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	1.9% 1/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	15.4% 2/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Infections and infestations Gastroenteritis	11.5% 3/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.5% 4/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.7% 1/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	14.3% 2/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Infections and infestations Nasopharyngitis	3.8% 1/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	17.0% 9/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.7% 1/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	16.7% 1/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	14.3% 2/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Infections and infestations Rash Pustular	7.7% 2/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.5% 4/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	15.4% 2/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Infections and infestations Upper Respiratory Tract Infection	23.1% 6/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	37.7% 20/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	30.8% 4/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	16.7% 1/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	14.3% 2/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Infections and infestations Urinary Tract Infection	0.00% 0/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.5% 4/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Injury, poisoning and procedural complications Ligament Sprain	7.7% 2/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	15.4% 2/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Investigations Blood Albumin Decreased	11.5% 3/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	1.9% 1/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	15.4% 2/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	16.7% 1/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.1% 1/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Investigations Serum Ferritin Decreased	0.00% 0/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	5.7% 3/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Investigations Weight Decreased	26.9% 7/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.5% 4/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	23.1% 3/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	50.0% 3/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	14.3% 2/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Investigations Weight Increased	0.00% 0/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	20.8% 11/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.1% 1/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Metabolism and nutrition disorders Decreased Appetite	26.9% 7/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	17.0% 9/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	30.8% 4/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	50.0% 3/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	28.6% 4/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Metabolism and nutrition disorders Enzyme Abnormality	15.4% 4/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	1.9% 1/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	30.8% 4/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	16.7% 1/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Metabolism and nutrition disorders Hypercholesterolaemia	0.00% 0/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	5.7% 3/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Metabolism and nutrition disorders Hyperglycaemia	7.7% 2/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	1.9% 1/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.7% 1/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.1% 1/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Metabolism and nutrition disorders Hyperkalaemia	0.00% 0/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	5.7% 3/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.1% 1/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Metabolism and nutrition disorders Hypertriglyceridaemia	7.7% 2/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	13.2% 7/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.7% 1/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.1% 1/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Metabolism and nutrition disorders Hyperuricaemia	3.8% 1/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	13.2% 7/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.7% 1/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	16.7% 1/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	21.4% 3/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Metabolism and nutrition disorders Hypoalbuminaemia	7.7% 2/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	3.8% 2/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.7% 1/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	33.3% 2/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.1% 1/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Metabolism and nutrition disorders Hypocalcaemia	15.4% 4/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	5.7% 3/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	15.4% 2/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	16.7% 1/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	21.4% 3/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Metabolism and nutrition disorders Hypoglycaemia	7.7% 2/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	1.9% 1/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	16.7% 1/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Metabolism and nutrition disorders Hypokalaemia	11.5% 3/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	11.3% 6/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.7% 1/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	16.7% 1/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.1% 1/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Musculoskeletal and connective tissue disorders Arthralgia	19.2% 5/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.5% 4/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	30.8% 4/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	16.7% 1/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.1% 1/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Musculoskeletal and connective tissue disorders Back Pain	23.1% 6/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.5% 4/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	30.8% 4/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	16.7% 1/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.1% 1/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Musculoskeletal and connective tissue disorders Muscle Spasms	7.7% 2/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	1.9% 1/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.7% 1/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Musculoskeletal and connective tissue disorders Muscular Weakness	0.00% 0/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	5.7% 3/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Musculoskeletal and connective tissue disorders Musculoskeletal Pain	7.7% 2/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	5.7% 3/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	15.4% 2/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Musculoskeletal and connective tissue disorders Myalgia	11.5% 3/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	3.8% 2/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	23.1% 3/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	16.7% 1/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Musculoskeletal and connective tissue disorders Pain in Extremity	7.7% 2/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	1.9% 1/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	15.4% 2/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	16.7% 1/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour Pain	15.4% 4/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.5% 4/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	15.4% 2/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.1% 1/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Nervous system disorders Dizziness	7.7% 2/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	11.3% 6/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Nervous system disorders Headache	3.8% 1/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	11.3% 6/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	14.3% 2/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Nervous system disorders Peripheral Motor Neuropathy	15.4% 4/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	11.3% 6/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	15.4% 2/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	33.3% 2/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.1% 1/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Nervous system disorders Peripheral Sensory Neuropathy	26.9% 7/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	24.5% 13/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	38.5% 5/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	50.0% 3/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	21.4% 3/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Psychiatric disorders Insomnia	7.7% 2/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	9.4% 5/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	16.7% 1/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Renal and urinary disorders Azotaemia	7.7% 2/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	3.8% 2/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.7% 1/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	16.7% 1/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.1% 1/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Renal and urinary disorders Pollakiuria	7.7% 2/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	1.9% 1/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.7% 1/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	16.7% 1/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Renal and urinary disorders Renal Impairment	7.7% 2/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.5% 4/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	15.4% 2/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	16.7% 1/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	14.3% 2/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Reproductive system and breast disorders Oedema Genital	7.7% 2/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	5.7% 3/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	16.7% 1/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	14.3% 2/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Respiratory, thoracic and mediastinal disorders Cough	30.8% 8/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	15.1% 8/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	23.1% 3/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	16.7% 1/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Respiratory, thoracic and mediastinal disorders Dyspnoea	34.6% 9/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	24.5% 13/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	30.8% 4/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	21.4% 3/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Respiratory, thoracic and mediastinal disorders Oropharyngeal Pain	7.7% 2/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.5% 4/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	15.4% 2/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Respiratory, thoracic and mediastinal disorders Pleural Effusion	19.2% 5/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	3.8% 2/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	15.4% 2/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	50.0% 3/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	14.3% 2/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Skin and subcutaneous tissue disorders Dermatitis Acneiform	7.7% 2/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.5% 4/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	15.4% 2/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Skin and subcutaneous tissue disorders Dry Skin	0.00% 0/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.5% 4/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Skin and subcutaneous tissue disorders Eczema	3.8% 1/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	9.4% 5/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.7% 1/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.1% 1/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Skin and subcutaneous tissue disorders Erythema	7.7% 2/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	3.8% 2/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	15.4% 2/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.1% 1/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Skin and subcutaneous tissue disorders Hyperhidrosis	26.9% 7/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	18.9% 10/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	38.5% 5/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	33.3% 2/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	14.3% 2/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Skin and subcutaneous tissue disorders Night Sweats	15.4% 4/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	17.0% 9/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	30.8% 4/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	16.7% 1/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	28.6% 4/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Skin and subcutaneous tissue disorders Pruritus	23.1% 6/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	41.5% 22/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	30.8% 4/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	33.3% 2/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	21.4% 3/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Skin and subcutaneous tissue disorders Rash	3.8% 1/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	13.2% 7/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Skin and subcutaneous tissue disorders Rash Maculo-Papular	19.2% 5/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	34.0% 18/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	23.1% 3/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	33.3% 2/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	14.3% 2/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Skin and subcutaneous tissue disorders Skin Hyperpigmentation	0.00% 0/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	9.4% 5/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.1% 1/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Skin and subcutaneous tissue disorders Skin Induration	7.7% 2/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	3.8% 2/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.7% 1/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	16.7% 1/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.1% 1/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Vascular disorders Hypertension	11.5% 3/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.5% 4/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	23.1% 3/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.1% 1/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Blood and lymphatic system disorders Coagulopathy	3.8% 1/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.7% 1/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Blood and lymphatic system disorders Leukocytosis	3.8% 1/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.7% 1/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	16.7% 1/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Blood and lymphatic system disorders Lymph Node Pain	3.8% 1/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	1.9% 1/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.7% 1/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Blood and lymphatic system disorders Monocytosis	3.8% 1/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.7% 1/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	16.7% 1/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Blood and lymphatic system disorders Neutrophilia	3.8% 1/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.7% 1/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	16.7% 1/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Blood and lymphatic system disorders Splenomegaly	0.00% 0/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	1.9% 1/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.1% 1/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Cardiac disorders Bradycardia	3.8% 1/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	1.9% 1/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.7% 1/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Cardiac disorders Ventricular Extrasystoles	0.00% 0/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	1.9% 1/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.1% 1/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Ear and labyrinth disorders Tinnitus	3.8% 1/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	16.7% 1/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Eye disorders Idiopathic Orbital Inflammation	3.8% 1/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.7% 1/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Eye disorders Visual Acuity Reduced	0.00% 0/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	3.8% 2/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.1% 1/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Gastrointestinal disorders Abdominal Discomfort	3.8% 1/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	1.9% 1/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.7% 1/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	16.7% 1/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Gastrointestinal disorders Abdominal Pain Lower	3.8% 1/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.7% 1/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Gastrointestinal disorders Haemorrhoidal Haemorrhage	0.00% 0/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	1.9% 1/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.1% 1/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Gastrointestinal disorders Ileus Paralytic	3.8% 1/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.7% 1/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Gastrointestinal disorders Oesophagitis	3.8% 1/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.7% 1/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Gastrointestinal disorders Tongue Coated	3.8% 1/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	1.9% 1/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.7% 1/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Gastrointestinal disorders Upper Gastrointestinal Haemorrhage	3.8% 1/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.7% 1/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
General disorders Chest Discomfort	0.00% 0/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	1.9% 1/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.1% 1/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
General disorders Chills	3.8% 1/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.7% 1/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	16.7% 1/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
General disorders Influenza Like Illness	3.8% 1/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.7% 1/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
General disorders Infusion Site Extravasation	3.8% 1/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.7% 1/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Immune system disorders Seasonal Allergy	3.8% 1/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	3.8% 2/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.7% 1/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Infections and infestations Bronchitis	3.8% 1/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	1.9% 1/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.7% 1/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.1% 1/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Infections and infestations Herpes Virus Infection	3.8% 1/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.7% 1/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Infections and infestations Herpes Zoster	3.8% 1/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	1.9% 1/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.7% 1/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Infections and infestations Lower Respiratory Tract Infection	0.00% 0/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	3.8% 2/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.1% 1/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Infections and infestations Oral Candidiasis	3.8% 1/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.7% 1/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Infections and infestations Pharyngitis	3.8% 1/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.7% 1/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Infections and infestations Pneumonia	0.00% 0/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	3.8% 2/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.1% 1/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Infections and infestations Respiratory Tract Infection	3.8% 1/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.7% 1/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Infections and infestations Skin Infection	3.8% 1/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.7% 1/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Infections and infestations Tonsillitis	0.00% 0/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	1.9% 1/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.1% 1/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Infections and infestations Viral Infection	3.8% 1/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.7% 1/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Injury, poisoning and procedural complications Arthropod Bite	3.8% 1/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.7% 1/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	16.7% 1/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Injury, poisoning and procedural complications Contusion	0.00% 0/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	1.9% 1/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.1% 1/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Injury, poisoning and procedural complications Head Injury	3.8% 1/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.7% 1/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Injury, poisoning and procedural complications Post-Traumatic Pain	3.8% 1/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.7% 1/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Injury, poisoning and procedural complications Procedural Nausea	3.8% 1/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.7% 1/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Injury, poisoning and procedural complications Road Traffic Accident	3.8% 1/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.7% 1/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	16.7% 1/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Injury, poisoning and procedural complications Skin Abrasion	3.8% 1/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.7% 1/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Injury, poisoning and procedural complications Wound	3.8% 1/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.7% 1/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Injury, poisoning and procedural complications Wound Complication	3.8% 1/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	1.9% 1/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.7% 1/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	16.7% 1/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Investigations Blood Creatine Phosphokinase Increased	0.00% 0/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	1.9% 1/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.1% 1/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Investigations Blood Folate Decreased	3.8% 1/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.7% 1/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Investigations Blood Iron Decreased	3.8% 1/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	1.9% 1/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.7% 1/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Investigations Blood Phosphorus Increased	0.00% 0/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	1.9% 1/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.1% 1/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Investigations Haemoglobin Increased	0.00% 0/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	3.8% 2/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.1% 1/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Investigations Iron Binding Capacity Total Decreased	3.8% 1/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.7% 1/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Investigations Iron Binding Capacity Unsaturated Decreased	3.8% 1/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.7% 1/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Investigations Platelet Count Increased	3.8% 1/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	16.7% 1/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Investigations Protein Total Decreased	0.00% 0/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	1.9% 1/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.1% 1/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Investigations Protein Total Increased	3.8% 1/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.7% 1/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	16.7% 1/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Investigations Protein Urine Present	3.8% 1/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	16.7% 1/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Investigations Reticulocyte Count Decreased	0.00% 0/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	1.9% 1/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.1% 1/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Investigations Reticulocyte Percentage Decreased	0.00% 0/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	1.9% 1/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.1% 1/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Investigations Vitamin B12 Decreased	3.8% 1/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.7% 1/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Metabolism and nutrition disorders Fluid Overload	3.8% 1/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	1.9% 1/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.7% 1/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.1% 1/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Metabolism and nutrition disorders Gout	3.8% 1/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.7% 1/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Metabolism and nutrition disorders Hyperphosphataemia	3.8% 1/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.7% 1/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Metabolism and nutrition disorders Hypocholesterolaemia	0.00% 0/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	1.9% 1/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.1% 1/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Metabolism and nutrition disorders Hyponatraemia	3.8% 1/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	1.9% 1/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.1% 1/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Musculoskeletal and connective tissue disorders Arthritis	3.8% 1/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.7% 1/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Musculoskeletal and connective tissue disorders Chondropathy	3.8% 1/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.7% 1/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Musculoskeletal and connective tissue disorders Joint Stiffness	0.00% 0/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	1.9% 1/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.1% 1/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Musculoskeletal and connective tissue disorders Synovitis	0.00% 0/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	1.9% 1/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.1% 1/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Nervous system disorders Somnolence	3.8% 1/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	1.9% 1/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.1% 1/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Nervous system disorders Syncope	0.00% 0/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	1.9% 1/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.1% 1/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Renal and urinary disorders Haematuria	0.00% 0/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	1.9% 1/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.1% 1/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Renal and urinary disorders Polyuria	3.8% 1/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.7% 1/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Renal and urinary disorders Proteinuria	3.8% 1/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	1.9% 1/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.7% 1/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.1% 1/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Reproductive system and breast disorders Benign Prostatic Hyperplasia	3.8% 1/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.7% 1/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	16.7% 1/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Reproductive system and breast disorders Pelvic Pain	3.8% 1/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.7% 1/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Reproductive system and breast disorders Scrotal Swelling	3.8% 1/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.7% 1/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Respiratory, thoracic and mediastinal disorders Epistaxis	3.8% 1/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	1.9% 1/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.7% 1/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	16.7% 1/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Respiratory, thoracic and mediastinal disorders Nasal Inflammation	3.8% 1/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.7% 1/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Respiratory, thoracic and mediastinal disorders Productive Cough	3.8% 1/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	3.8% 2/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	16.7% 1/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Respiratory, thoracic and mediastinal disorders Wheezing	3.8% 1/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.7% 1/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Skin and subcutaneous tissue disorders Blister	3.8% 1/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	1.9% 1/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.7% 1/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Skin and subcutaneous tissue disorders Rash Pruritic	3.8% 1/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	3.8% 2/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.7% 1/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Skin and subcutaneous tissue disorders Skin Ulcer	0.00% 0/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	1.9% 1/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.1% 1/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.
Vascular disorders Haemorrhage	3.8% 1/26 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/53 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	7.7% 1/13 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/6 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.	0.00% 0/14 • Up to 7 years Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.

Additional Information

DIRECTOR CLINICAL RESEARCH

Janssen R&D US

Email: ClinicalTrialDisclosure@its.jnj.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place

Restriction type: GT60