Trial Outcomes & Findings for Durability of Virologic Response and/or Viral Resistance Patterns in Participants With Chronic Hepatitis C Who Have Been Previously Treated With Grazoprevir (MK-5172) (MK-5172-017) (NCT NCT01667081)

NCT ID: NCT01667081

Last Updated: 2022-06-06

Results Overview

Viral relapse is defined as any participant who has confirmed HCV Ribonucleic acid (RNA) ≥ Lower limit of quantification (LLoQ) of 15 IU/mL and had achieved sustained virologic response (SVR) in the follow up in the prior treatment study. Time to relapse is defined as the time from last dose of study therapy taken in the prior treatment study until the date where HCV RNA is ≥LLoQ.

• Recruitment status: COMPLETED
• Target enrollment: 2438 participants
• Primary outcome timeframe: Up to ~60 months after enrollment in this study
• Results posted on: 2022-06-06

Participant Flow

A total of 2438 adult Hepatitis C Virus (HCV)-infected participants who were previously treated in 18 prior clinical trials, enrolled in this study.

Of the 2438 participants, three participants were excluded from all analyses. Two participants enrolled in error failed to receive at least 1 dose of Grazoprevir (GZR) in a prior study (each received a comparator regimen in a prior base study) and 1 participant had insufficient long-term follow-up data (participant withdrew consent on Day 27).

Participant milestones

Measure	Grazoprevir (GZR) 100 mg + Elbasvir (EBR) 50 mg +/- Ribavirin (RBV) Participants previously received GZR 100mg +EBR 50mg with or without RBV in a prior study.	Other GZR Regimen Participants previously received at least one dose of GZR in a prior study
Overall Study STARTED	1909	526
Overall Study COMPLETED	132	169
Overall Study NOT COMPLETED	1777	357

Reasons for withdrawal

Measure	Grazoprevir (GZR) 100 mg + Elbasvir (EBR) 50 mg +/- Ribavirin (RBV) Participants previously received GZR 100mg +EBR 50mg with or without RBV in a prior study.	Other GZR Regimen Participants previously received at least one dose of GZR in a prior study
Overall Study Death	43	3
Overall Study Lost to Follow-up	99	48
Overall Study Physician Decision	16	2
Overall Study Participants were discontinued due to amendment 3 which modified the study discontinuation criteria	1529	269
Overall Study Withdrawal by Subject	90	35

Baseline Characteristics

Durability of Virologic Response and/or Viral Resistance Patterns in Participants With Chronic Hepatitis C Who Have Been Previously Treated With Grazoprevir (MK-5172) (MK-5172-017)

Baseline characteristics by cohort

Measure	GZR 100 mg + EBR 50 mg +/- RBV n=1909 Participants Participants previously received GZR 100mg +EBR 50mg with or without RBV in a prior study.	Other GZR Regimen n=526 Participants Participants previously received at least one dose of GZR in a prior study	Total n=2435 Participants Total of all reporting groups
Age, Continuous	51.9 Years STANDARD_DEVIATION 11.0 • n=93 Participants	49.7 Years STANDARD_DEVIATION 11.4 • n=4 Participants	51.4 Years STANDARD_DEVIATION 11.1 • n=27 Participants
Sex: Female, Male Female	785 Participants n=93 Participants	238 Participants n=4 Participants	1023 Participants n=27 Participants
Sex: Female, Male Male	1124 Participants n=93 Participants	288 Participants n=4 Participants	1412 Participants n=27 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	135 Participants n=93 Participants	68 Participants n=4 Participants	203 Participants n=27 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	1730 Participants n=93 Participants	444 Participants n=4 Participants	2174 Participants n=27 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	44 Participants n=93 Participants	14 Participants n=4 Participants	58 Participants n=27 Participants
Race (NIH/OMB) American Indian or Alaska Native	5 Participants n=93 Participants	2 Participants n=4 Participants	7 Participants n=27 Participants
Race (NIH/OMB) Asian	283 Participants n=93 Participants	12 Participants n=4 Participants	295 Participants n=27 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=93 Participants	1 Participants n=4 Participants	2 Participants n=27 Participants
Race (NIH/OMB) Black or African American	253 Participants n=93 Participants	35 Participants n=4 Participants	288 Participants n=27 Participants
Race (NIH/OMB) White	1345 Participants n=93 Participants	470 Participants n=4 Participants	1815 Participants n=27 Participants
Race (NIH/OMB) More than one race	21 Participants n=93 Participants	6 Participants n=4 Participants	27 Participants n=27 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=93 Participants	0 Participants n=4 Participants	1 Participants n=27 Participants

PRIMARY outcome

Timeframe: Up to ~60 months after enrollment in this study

Population: All participants who achieved SVR during the follow-up period of the prior treatment study and did not start any new HCV therapy between the end of the prior treatment study and entry in this study

Viral relapse is defined as any participant who has confirmed HCV Ribonucleic acid (RNA) ≥ Lower limit of quantification (LLoQ) of 15 IU/mL and had achieved sustained virologic response (SVR) in the follow up in the prior treatment study. Time to relapse is defined as the time from last dose of study therapy taken in the prior treatment study until the date where HCV RNA is ≥LLoQ.

Outcome measures

Measure	GZR 100 mg + EBR 50 mg +/- RBV n=1837 Participants Participants previously received GZR 100mg +EBR 50mg with or without RBV in a prior study.	Other GZR Regimen n=495 Participants Participants previously received at least one dose of GZR in a prior study	EBR/GZR +/-RBV: Both NS3 and NS5A RASs Participants previously received EBR and GZR with or without RBV in a prior study and had both treatment-emergent NS3 and NS5A RASs	GZR + Pegylated Interferon/Ribavirin (PR): NS3 RASs Participants previously received GZR and PR for 12 weeks in a prior study and had treatment-emergent NS3 RASs
Time to Viral Relapse	NA Months Median time to viral relapse and interquartile range not reached due to the low rate of late virologic relapse.	NA Months Median time to viral relapse and interquartile range not reached due to the low rate of late virologic relapse.	—	—

PRIMARY outcome

Timeframe: Up to ~60 months after enrollment in this study

Population: Participants met the criteria of virologic failure either in the prior base study or had HCV RNA Target detected, quantifiable \[TD(q)\] at entry in current study. Participants did not receive new HCV therapy between the end of the prior base study and entry into this study. Only HCV genotype infections that had adequate reference information were included.

In adult participants with HCV RNA ≥1000 IU/mL at entry or during the study period, HCV sequence analysis was performed to evaluate the presence of RASs and the persistence of RASs over time.

Outcome measures

Measure	GZR 100 mg + EBR 50 mg +/- RBV n=31 Participants Participants previously received GZR 100mg +EBR 50mg with or without RBV in a prior study.	Other GZR Regimen n=31 Participants Participants previously received at least one dose of GZR in a prior study	EBR/GZR +/-RBV: Both NS3 and NS5A RASs n=31 Participants Participants previously received EBR and GZR with or without RBV in a prior study and had both treatment-emergent NS3 and NS5A RASs	GZR + Pegylated Interferon/Ribavirin (PR): NS3 RASs n=16 Participants Participants previously received GZR and PR for 12 weeks in a prior study and had treatment-emergent NS3 RASs
Persistence of Treatment-Emergent Nonstructural Protein (NS)3 and NS5A Resistance-associated Substitutions (RASs) in Participants With HCV Genotype (GT) 1a Infections Failure	22 Participants	25 Participants	18 Participants	11 Participants
Persistence of Treatment-Emergent Nonstructural Protein (NS)3 and NS5A Resistance-associated Substitutions (RASs) in Participants With HCV Genotype (GT) 1a Infections 24 weeks post failure	10 Participants	25 Participants	8 Participants	2 Participants
Persistence of Treatment-Emergent Nonstructural Protein (NS)3 and NS5A Resistance-associated Substitutions (RASs) in Participants With HCV Genotype (GT) 1a Infections 48 weeks post failure	6 Participants	22 Participants	4 Participants	2 Participants
Persistence of Treatment-Emergent Nonstructural Protein (NS)3 and NS5A Resistance-associated Substitutions (RASs) in Participants With HCV Genotype (GT) 1a Infections 96 weeks post failure	4 Participants	15 Participants	3 Participants	1 Participants
Persistence of Treatment-Emergent Nonstructural Protein (NS)3 and NS5A Resistance-associated Substitutions (RASs) in Participants With HCV Genotype (GT) 1a Infections ≥144 weeks post failure	2 Participants	11 Participants	1 Participants	1 Participants

PRIMARY outcome

Timeframe: Up to ~60 months after enrollment in this study

Population: Participants met the criteria of virologic failure either in the prior base study or had HCV RNA TD(q) at entry in current study. Participants did not receive new HCV therapy between the end of the prior base study and entry into this study. Only HCV genotype infections that had adequate reference information were included.

In adult participants with HCV RNA ≥1000 IU/mL at entry or during the study period, HCV sequence analysis was performed to evaluate the presence of RASs and the persistence of RASs over time.

Outcome measures

Measure	GZR 100 mg + EBR 50 mg +/- RBV n=9 Participants Participants previously received GZR 100mg +EBR 50mg with or without RBV in a prior study.	Other GZR Regimen n=9 Participants Participants previously received at least one dose of GZR in a prior study	EBR/GZR +/-RBV: Both NS3 and NS5A RASs n=9 Participants Participants previously received EBR and GZR with or without RBV in a prior study and had both treatment-emergent NS3 and NS5A RASs	GZR + Pegylated Interferon/Ribavirin (PR): NS3 RASs n=5 Participants Participants previously received GZR and PR for 12 weeks in a prior study and had treatment-emergent NS3 RASs
Persistence of Treatment-Emergent NS3 and NS5A RASs in Participants With HCV Genotype 1b Infections Failure	4 Participants	7 Participants	2 Participants	3 Participants
Persistence of Treatment-Emergent NS3 and NS5A RASs in Participants With HCV Genotype 1b Infections 24 weeks post failure	2 Participants	7 Participants	0 Participants	1 Participants
Persistence of Treatment-Emergent NS3 and NS5A RASs in Participants With HCV Genotype 1b Infections 48 weeks post failure	1 Participants	5 Participants	0 Participants	1 Participants
Persistence of Treatment-Emergent NS3 and NS5A RASs in Participants With HCV Genotype 1b Infections 96 weeks post failure	1 Participants	3 Participants	0 Participants	1 Participants
Persistence of Treatment-Emergent NS3 and NS5A RASs in Participants With HCV Genotype 1b Infections ≥144 weeks post failure	0 Participants	3 Participants	0 Participants	1 Participants

PRIMARY outcome

Timeframe: Up to ~60 months after enrollment in this study

Population: Participants met the criteria of virologic failure either in the prior base study or had HCV RNA TD(q) at entry in current study. Participants did not receive new HCV therapy between the end of the prior base study and entry into this study. Only HCV genotype infections that had adequate reference information were included.

In adult participants with HCV RNA ≥1000 IU/mL at entry or during the study period, HCV sequence analysis was performed to evaluate the presence of RASs and the persistence of RASs over time.

Outcome measures

Measure	GZR 100 mg + EBR 50 mg +/- RBV n=5 Participants Participants previously received GZR 100mg +EBR 50mg with or without RBV in a prior study.	Other GZR Regimen n=5 Participants Participants previously received at least one dose of GZR in a prior study	EBR/GZR +/-RBV: Both NS3 and NS5A RASs n=5 Participants Participants previously received EBR and GZR with or without RBV in a prior study and had both treatment-emergent NS3 and NS5A RASs	GZR + Pegylated Interferon/Ribavirin (PR): NS3 RASs Participants previously received GZR and PR for 12 weeks in a prior study and had treatment-emergent NS3 RASs
Persistence of Treatment-Emergent NS3 and NS5A RASs in Participants With Genotype 4 Infections Failure	2 Participants	4 Participants	2 Participants	—
Persistence of Treatment-Emergent NS3 and NS5A RASs in Participants With Genotype 4 Infections 24 weeks post failure	1 Participants	3 Participants	1 Participants	—
Persistence of Treatment-Emergent NS3 and NS5A RASs in Participants With Genotype 4 Infections 48 weeks post failure	1 Participants	2 Participants	1 Participants	—
Persistence of Treatment-Emergent NS3 and NS5A RASs in Participants With Genotype 4 Infections 96 weeks post failure	1 Participants	2 Participants	1 Participants	—
Persistence of Treatment-Emergent NS3 and NS5A RASs in Participants With Genotype 4 Infections ≥144 weeks post failure	1 Participants	2 Participants	1 Participants	—

PRIMARY outcome

Timeframe: Up to ~ 60 months after enrollment in this study

Population: All participants treated with GZR in a prior study. Three participants were excluded from analysis; two participants enrolled in error failed to receive at least one dose of GZR in a prior study (each received a comparator regimen in a prior base study) and one participant had insufficient long-term follow-up data (participant withdrew consent on Day 27).

An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The study investigator determined whether the adverse event was drug-related.

Outcome measures

Measure	GZR 100 mg + EBR 50 mg +/- RBV n=1909 Participants Participants previously received GZR 100mg +EBR 50mg with or without RBV in a prior study.	Other GZR Regimen n=526 Participants Participants previously received at least one dose of GZR in a prior study	EBR/GZR +/-RBV: Both NS3 and NS5A RASs Participants previously received EBR and GZR with or without RBV in a prior study and had both treatment-emergent NS3 and NS5A RASs	GZR + Pegylated Interferon/Ribavirin (PR): NS3 RASs Participants previously received GZR and PR for 12 weeks in a prior study and had treatment-emergent NS3 RASs
Number of Participants Who Experienced a Drug-Related Adverse Event (AE) During the Long-Term Follow-Up	1 Participants	1 Participants	—	—

PRIMARY outcome

Timeframe: Up to ~60 months after enrollment in this study

Population: All participants treated with GZR in a prior study. Three participants were excluded from analysis; two participants enrolled in error failed to receive at least one dose of GZR in a prior study (each received a comparator regimen in a prior base study) and one participant had insufficient long-term follow-up data (participant withdrew consent on Day 27).

A serious adverse event (SAE) is any adverse experience occurring at any dose that either results in death, is life threatening, results in a persistent or significant disability/incapacity, results in or prolongs an existing inpatient hospitalization, is a congenital anomaly/birth defect, is a cancer, is an overdose (whether accidental or intentional), or other important medical events that may not result in death, not be life threatening, or not require hospitalization may be considered a serious adverse experience when, based upon appropriate medical judgment, the event may jeopardize the participant and may require medical or surgical intervention to prevent one of the outcomes listed previously. The study investigator determined whether the adverse event was drug-related.

Outcome measures

Measure	GZR 100 mg + EBR 50 mg +/- RBV n=1909 Participants Participants previously received GZR 100mg +EBR 50mg with or without RBV in a prior study.	Other GZR Regimen n=526 Participants Participants previously received at least one dose of GZR in a prior study	EBR/GZR +/-RBV: Both NS3 and NS5A RASs Participants previously received EBR and GZR with or without RBV in a prior study and had both treatment-emergent NS3 and NS5A RASs	GZR + Pegylated Interferon/Ribavirin (PR): NS3 RASs Participants previously received GZR and PR for 12 weeks in a prior study and had treatment-emergent NS3 RASs
Number of Participants Who Experienced a Drug-Related Serious Adverse Event (SAE) During the Long-Term Follow-Up	1 Participants	1 Participants	—	—

PRIMARY outcome

Timeframe: Up to ~60 months after enrollment in this study

Population: All participants treated with GZR in a prior study. Three participants were excluded from analysis; two participants enrolled in error failed to receive at least one dose of GZR in a prior study (each received a comparator regimen in a prior base study) and one participant had insufficient long-term follow-up data (participant withdrew consent on Day 27).

An ECI includes spontaneous bacterial peritonitis, variceal bleeding, ascites, encephalopathy, hepatorenal syndrome, hepatocellular carcinoma, liver transplant, cardiovascular disease limited to angina and myocardial infarction, neurologic disorders limited to transient ischemic attack (TIA) or stroke, graft rejection in participants who have undergone liver or kidney transplant, or one of the following in participants from the MK-5172-052 (NCT02092350) base study: kidney transplant, decreased estimated glomerular filtration rate (eGFR), new onset diabetes, cryoglobulinemia, or post transplantation glomerulonephritis.

Outcome measures

Measure	GZR 100 mg + EBR 50 mg +/- RBV n=1909 Participants Participants previously received GZR 100mg +EBR 50mg with or without RBV in a prior study.	Other GZR Regimen n=526 Participants Participants previously received at least one dose of GZR in a prior study	EBR/GZR +/-RBV: Both NS3 and NS5A RASs Participants previously received EBR and GZR with or without RBV in a prior study and had both treatment-emergent NS3 and NS5A RASs	GZR + Pegylated Interferon/Ribavirin (PR): NS3 RASs Participants previously received GZR and PR for 12 weeks in a prior study and had treatment-emergent NS3 RASs
Number of Participants Who Experienced an Event of Clinical Interest (ECI) During the Long-Term Follow-Up	98 Participants	4 Participants	—	—

Adverse Events

GZR 100 mg + EBR 50 mg +/- RBV

Serious events: 100 serious events

Other events: 0 other events

Deaths: 44 deaths

Other GZR Regimen

Serious events: 4 serious events

Other events: 0 other events

Deaths: 3 deaths

Non-GZR Regimen

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Measure	GZR 100 mg + EBR 50 mg +/- RBV n=1909 participants at risk Participants previously received GZR 100mg +EBR 50mg with or without RBV in a prior study.	Other GZR Regimen n=526 participants at risk Participants previously received at least one dose of GZR in a prior study	Non-GZR Regimen Participants received a non-GZR regimen in a prior study
Nervous system disorders Transient ischaemic attack	0.16% 3/1909 • Number of events 5 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).	0.00% 0/526 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).	— 0/0 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).
Psychiatric disorders Anxiety	0.05% 1/1909 • Number of events 1 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).	0.00% 0/526 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).	— 0/0 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).
Cardiac disorders Acute coronary syndrome	0.10% 2/1909 • Number of events 2 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).	0.00% 0/526 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).	— 0/0 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).
Cardiac disorders Acute myocardial infarction	0.05% 1/1909 • Number of events 1 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).	0.00% 0/526 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).	— 0/0 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).
Cardiac disorders Angina pectoris	0.05% 1/1909 • Number of events 1 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).	0.00% 0/526 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).	— 0/0 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).
Cardiac disorders Angina unstable	0.05% 1/1909 • Number of events 1 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).	0.00% 0/526 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).	— 0/0 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).
Cardiac disorders Cardiac arrest	0.21% 4/1909 • Number of events 4 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).	0.00% 0/526 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).	— 0/0 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).
Cardiac disorders Cardiac failure	0.05% 1/1909 • Number of events 1 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).	0.00% 0/526 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).	— 0/0 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).
Cardiac disorders Coronary artery disease	0.05% 1/1909 • Number of events 1 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).	0.00% 0/526 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).	— 0/0 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).
Cardiac disorders Myocardial infarction	0.16% 3/1909 • Number of events 3 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).	0.00% 0/526 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).	— 0/0 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).
Cardiac disorders Myocardial ischaemia	0.10% 2/1909 • Number of events 2 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).	0.00% 0/526 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).	— 0/0 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).
Cardiac disorders Pulseless electrical activity	0.05% 1/1909 • Number of events 1 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).	0.00% 0/526 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).	— 0/0 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).
Gastrointestinal disorders Ascites	0.10% 2/1909 • Number of events 2 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).	0.00% 0/526 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).	— 0/0 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).
Renal and urinary disorders Chronic kidney disease	0.37% 7/1909 • Number of events 7 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).	0.00% 0/526 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).	— 0/0 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).
Gastrointestinal disorders Gastrointestinal haemorrhage	0.05% 1/1909 • Number of events 1 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).	0.00% 0/526 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).	— 0/0 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).
Gastrointestinal disorders Upper gastrointestinal haemorrhage	0.05% 1/1909 • Number of events 1 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).	0.00% 0/526 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).	— 0/0 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).
General disorders Chest pain	0.05% 1/1909 • Number of events 2 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).	0.00% 0/526 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).	— 0/0 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).
General disorders Death	0.42% 8/1909 • Number of events 8 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).	0.00% 0/526 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).	— 0/0 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).
General disorders Multiple organ dysfunction syndrome	0.05% 1/1909 • Number of events 1 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).	0.00% 0/526 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).	— 0/0 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).
General disorders Sudden death	0.05% 1/1909 • Number of events 1 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).	0.00% 0/526 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).	— 0/0 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).
Hepatobiliary disorders Chronic hepatic failure	0.05% 1/1909 • Number of events 1 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).	0.00% 0/526 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).	— 0/0 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).
Hepatobiliary disorders Hepatic cirrhosis	0.00% 0/1909 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).	0.19% 1/526 • Number of events 1 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).	— 0/0 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).
Immune system disorders Kidney transplant rejection	0.05% 1/1909 • Number of events 1 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).	0.00% 0/526 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).	— 0/0 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).
Infections and infestations Device related sepsis	0.05% 1/1909 • Number of events 1 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).	0.00% 0/526 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).	— 0/0 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).
Infections and infestations Peritonitis	0.05% 1/1909 • Number of events 1 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).	0.00% 0/526 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).	— 0/0 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).
Infections and infestations Pneumonia	0.10% 2/1909 • Number of events 2 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).	0.00% 0/526 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).	— 0/0 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).
Infections and infestations Sepsis	0.10% 2/1909 • Number of events 2 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).	0.00% 0/526 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).	— 0/0 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).
Infections and infestations Septic shock	0.10% 2/1909 • Number of events 2 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).	0.00% 0/526 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).	— 0/0 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).
Infections and infestations Wound infection	0.05% 1/1909 • Number of events 1 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).	0.00% 0/526 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).	— 0/0 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).
Renal and urinary disorders End stage renal disease	0.89% 17/1909 • Number of events 17 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).	0.00% 0/526 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).	— 0/0 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).
Renal and urinary disorders Glomerulonephritis chronic	0.10% 2/1909 • Number of events 2 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).	0.00% 0/526 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).	— 0/0 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).
Injury, poisoning and procedural complications Injury	0.05% 1/1909 • Number of events 1 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).	0.00% 0/526 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).	— 0/0 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).
Injury, poisoning and procedural complications Overdose	0.05% 1/1909 • Number of events 1 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).	0.00% 0/526 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).	— 0/0 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).
Injury, poisoning and procedural complications Transplant dysfunction	0.05% 1/1909 • Number of events 1 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).	0.00% 0/526 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).	— 0/0 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).
Investigations Glomerular filtration rate decreased	0.26% 5/1909 • Number of events 5 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).	0.00% 0/526 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).	— 0/0 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).
Metabolism and nutrition disorders Failure to thrive	0.05% 1/1909 • Number of events 1 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).	0.00% 0/526 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).	— 0/0 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Adenocarcinoma pancreas	0.05% 1/1909 • Number of events 1 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).	0.00% 0/526 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).	— 0/0 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Diffuse large B-cell lymphoma	0.05% 1/1909 • Number of events 1 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).	0.00% 0/526 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).	— 0/0 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Hepatocellular carcinoma	0.63% 12/1909 • Number of events 12 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).	0.19% 1/526 • Number of events 1 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).	— 0/0 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).
Renal and urinary disorders Renal failure	0.31% 6/1909 • Number of events 6 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).	0.00% 0/526 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).	— 0/0 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).
Renal and urinary disorders Renal impairment	0.10% 2/1909 • Number of events 2 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).	0.00% 0/526 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).	— 0/0 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung neoplasm malignant	0.10% 2/1909 • Number of events 2 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).	0.00% 0/526 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).	— 0/0 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Non-small cell lung cancer	0.05% 1/1909 • Number of events 1 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).	0.00% 0/526 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).	— 0/0 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).
Respiratory, thoracic and mediastinal disorders Asphyxia	0.05% 1/1909 • Number of events 1 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).	0.00% 0/526 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).	— 0/0 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).
Respiratory, thoracic and mediastinal disorders Pneumonia aspiration	0.05% 1/1909 • Number of events 1 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).	0.00% 0/526 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).	— 0/0 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Pancreatic carcinoma	0.05% 1/1909 • Number of events 1 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).	0.00% 0/526 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).	— 0/0 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).
Nervous system disorders Cerebrovascular accident	0.10% 2/1909 • Number of events 3 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).	0.00% 0/526 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).	— 0/0 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).
Nervous system disorders Embolic stroke	0.05% 1/1909 • Number of events 1 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).	0.00% 0/526 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).	— 0/0 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).
Nervous system disorders Encephalopathy	0.05% 1/1909 • Number of events 1 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).	0.00% 0/526 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).	— 0/0 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).
Nervous system disorders Hepatic encephalopathy	0.05% 1/1909 • Number of events 1 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).	0.00% 0/526 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).	— 0/0 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).
Nervous system disorders Ischaemic cerebral infarction	0.05% 1/1909 • Number of events 1 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).	0.00% 0/526 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).	— 0/0 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).
Nervous system disorders Ischaemic stroke	0.10% 2/1909 • Number of events 2 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).	0.00% 0/526 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).	— 0/0 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).
Nervous system disorders Optic neuritis	0.00% 0/1909 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).	0.19% 1/526 • Number of events 1 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).	— 0/0 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).
Nervous system disorders Paraesthesia	0.00% 0/1909 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).	0.19% 1/526 • Number of events 1 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).	— 0/0 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).
Respiratory, thoracic and mediastinal disorders Respiratory arrest	0.00% 0/1909 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).	0.19% 1/526 • Number of events 1 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).	— 0/0 • From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).

Other adverse events

Adverse event data not reported

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme Corp.

Phone: 1-800-672-6372

Email: ClinicalTrialsDisclosure@merck.com

Results disclosure agreements

• Principal investigator is a sponsor employee The sponsor must have the opportunity to review all proposed abstracts, manuscripts, or presentations regarding this study 45 days prior to submission for publication/presentation. Any information identified by the sponsor as confidential must be deleted prior to submission.
• Publication restrictions are in place

Restriction type: OTHER