Trial Outcomes & Findings for Efficacy and Safety Study of Maribavir Treatment Compared to Investigator-assigned Treatment in Transplant Recipients With Cytomegalovirus (CMV) Infections That Are Refractory or Resistant to Treatment With Ganciclovir, Valganciclovir, Foscarnet, or Cidofovir (NCT NCT02931539)

Last Updated: 2021-11-03

Results Overview

Confirmed CMV viremia clearance was defined as plasma CMV DNA concentration less than (\<) lower limit of quantification (LLOQ) that is, \<137 International Units per milliliter (IU/mL) when assessed by COBAS® AmpliPrep/COBAS® TaqMan® CMV Test in 2 consecutive postbaseline samples, separated by at least 5 days. Percentage of participants with confirmed CMV viremia clearance at end of study Week 8 regardless of whether either study-assigned treatment was discontinued before the end of the stipulated 8 weeks of therapy, and could not have received alternative anti-CMV treatment were reported.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

352 participants

Primary outcome timeframe

Week 8

Results posted on

2021-11-03

Participant Flow

This study was conducted at 94 sites in North America, Europe, and Asia Pacific between 22 December 2016 (first participant first visit) and 17 August 2020 (last participant last visit).

Participants with cytomegalovirus (CMV) infections were enrolled and randomized into two treatment groups: IAT (control), and Maribavir 400 mg. Participants randomized to IAT treatment arm, if met the stringent criteria for lack of improvement/worsening of CMV infection, considered eligible for entry into Maribavir rescue arm at Week 3 based on medical monitor review. As planned, combined data has been reported for IAT control group.

Participant milestones

Participant milestones
Measure	Investigator-assigned Anti-CMV Treatment (IAT) Participants received 1 or 2 of the 4 anti-CMV agents from the following: ganciclovir, valganciclovir, foscarnet, or cidofovir based on the investigator's discretion for the 8 week treatment period.	Maribavir 400 mg Participants received maribavir 400 milligram (mg) (2\*200 mg tablets), orally, twice daily for the 8 week treatment period.	Maribavir Rescue Arm Participants with clear evidence of virologic failure (not just intolerance) after a minimum of 3 weeks of therapy with IAT entered maribavir rescue arm and received maribavir 400 mg (2\*200 mg tablets), orally, twice daily for the 8 week treatment period.
Period 1: Treatment Phase STARTED	117	235	0
Period 1: Treatment Phase Treated Participants	116	234	0
Period 1: Treatment Phase IAT (Ganciclovir/ Valganciclovir)	56	0	0
Period 1: Treatment Phase IAT (Foscarnet)	47	0	0
Period 1: Treatment Phase IAT (Cidofovir)	6	0	0
Period 1: Treatment Phase IAT (Foscarnet + Valganciclovir/Ganciclovir)	7	0	0
Period 1: Treatment Phase COMPLETED	58	199	0
Period 1: Treatment Phase NOT COMPLETED	59	36	0
Period 2: Maribavir Rescue Therapy STARTED	0	0	22
Period 2: Maribavir Rescue Therapy COMPLETED	0	0	20
Period 2: Maribavir Rescue Therapy NOT COMPLETED	0	0	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Investigator-assigned Anti-CMV Treatment (IAT) Participants received 1 or 2 of the 4 anti-CMV agents from the following: ganciclovir, valganciclovir, foscarnet, or cidofovir based on the investigator's discretion for the 8 week treatment period.	Maribavir 400 mg Participants received maribavir 400 milligram (mg) (2\*200 mg tablets), orally, twice daily for the 8 week treatment period.	Maribavir Rescue Arm Participants with clear evidence of virologic failure (not just intolerance) after a minimum of 3 weeks of therapy with IAT entered maribavir rescue arm and received maribavir 400 mg (2\*200 mg tablets), orally, twice daily for the 8 week treatment period.
Period 1: Treatment Phase Investigator discretion	1	1	0
Period 1: Treatment Phase Adverse Event	5	1	0
Period 1: Treatment Phase Lost to Follow-up	1	2	0
Period 1: Treatment Phase Death	8	24	0
Period 1: Treatment Phase Withdrawal by Subject	16	8	0
Period 1: Treatment Phase Protocol Violation	6	0	0
Period 1: Treatment Phase Participants transitioned into maribavir rescue arm	22	0	0
Period 2: Maribavir Rescue Therapy Sponsor decision	0	0	2

Baseline Characteristics

Efficacy and Safety Study of Maribavir Treatment Compared to Investigator-assigned Treatment in Transplant Recipients With Cytomegalovirus (CMV) Infections That Are Refractory or Resistant to Treatment With Ganciclovir, Valganciclovir, Foscarnet, or Cidofovir

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Investigator-assigned Anti-CMV Treatment (IAT) n=117 Participants Participants received 1 or 2 of the 4 anti-CMV agents from the following: ganciclovir, valganciclovir, foscarnet, or cidofovir based on the investigator's discretion for the 8 week treatment period.	Maribavir 400 mg n=235 Participants Participants received maribavir 400 mg (2\*200 mg tablets), orally, twice daily for the 8 week treatment period.	Total n=352 Participants Total of all reporting groups
Ethnicity (NIH/OMB) Hispanic or Latino	7 Participants n=5 Participants	14 Participants n=7 Participants	21 Participants n=5 Participants
Age, Continuous	51.5 years STANDARD_DEVIATION 12.80 • n=5 Participants	53.8 years STANDARD_DEVIATION 13.39 • n=7 Participants	53.0 years STANDARD_DEVIATION 13.22 • n=5 Participants
Sex: Female, Male Female	52 Participants n=5 Participants	87 Participants n=7 Participants	139 Participants n=5 Participants
Sex: Female, Male Male	65 Participants n=5 Participants	148 Participants n=7 Participants	213 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	95 Participants n=5 Participants	198 Participants n=7 Participants	293 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	15 Participants n=5 Participants	23 Participants n=7 Participants	38 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	7 Participants n=5 Participants	9 Participants n=7 Participants	16 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	18 Participants n=5 Participants	29 Participants n=7 Participants	47 Participants n=5 Participants
Race (NIH/OMB) White	87 Participants n=5 Participants	179 Participants n=7 Participants	266 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	5 Participants n=5 Participants	18 Participants n=7 Participants	23 Participants n=5 Participants

PRIMARY outcome

Timeframe: Week 8

Population: The randomized set consisted of all participants who had signed informed consent and had begun some study procedures and were randomized to the study.

Outcome measures

Outcome measures
Measure	Investigator-assigned Anti-CMV Treatment (IAT) n=117 Participants Participants received 1 or 2 of the 4 anti-CMV agents from the following: ganciclovir, valganciclovir, foscarnet, or cidofovir based on the investigator's discretion for the 8 week treatment period.	Maribavir 400 mg n=235 Participants Participants received maribavir 400 mg (2\*200 mg tablets), orally, twice daily for the 8 week treatment period.	Maribavir 400 mg Participants received maribavir 400 mg (2\*200 mg tablets), orally, twice daily for the 8 week treatment period.
Percentage of Participants Who Achieved Confirmed Clearance of Plasma Cytomegalovirus (CMV) Deoxyribonucleic Acid (DNA) (CMV Viremia Clearance) at End of Week 8	23.9 percentage of participants	55.7 percentage of participants	—

SECONDARY outcome

Timeframe: Up to Week 16

Population: The randomized set consisted of all participants who had signed informed consent and had begun some study procedures and were randomized to the study.

Confirmed CMV viremia clearance was defined as plasma CMV DNA concentration \<LLOQ that is, \<137 IU/mL when assessed by COBAS® AmpliPrep/COBAS® TaqMan® CMV test in 2 consecutive postbaseline samples, separated by at least 5 days. CMV infection symptom control was defined as resolution or improvement of tissue invasive CMV disease or CMV syndrome for participants symptomatic at baseline, or maintaining no symptoms of tissue invasive CMV disease or CMV syndrome for participants asymptomatic at baseline. Percentage of participants who achieved CMV viremia clearance and CMV infection symptom control at end of Week 8 through Week 16 were reported.

Outcome measures

Outcome measures
Measure	Investigator-assigned Anti-CMV Treatment (IAT) n=117 Participants Participants received 1 or 2 of the 4 anti-CMV agents from the following: ganciclovir, valganciclovir, foscarnet, or cidofovir based on the investigator's discretion for the 8 week treatment period.	Maribavir 400 mg n=235 Participants Participants received maribavir 400 mg (2\*200 mg tablets), orally, twice daily for the 8 week treatment period.	Maribavir 400 mg Participants received maribavir 400 mg (2\*200 mg tablets), orally, twice daily for the 8 week treatment period.
Percentage of Participants Who Achieved Confirmed CMV Viremia Clearance and CMV Infection Symptom Control at End of Week 8, Followed by Maintenance of Treatment Effect at Week 16	10.3 percentage of participants	18.7 percentage of participants	—

SECONDARY outcome

Timeframe: At Week 8 through Weeks 12, 16 and 20

Population: The randomized set consisted of all participants who had signed informed consent and had begun some study procedures and were randomized to the study.

Confirmed CMV viremia clearance was defined as plasma CMV DNA concentration \<LLOQ that is, \<137IU/mL when assessed by COBAS® AmpliPrep/COBAS® TaqMan® CMV test in 2 consecutive postbaseline samples, separated by at least 5 days. Percentage of participants who achieved confirmed CMV viremia clearance after receiving 8 weeks study-assigned treatment at end of Week 8, and maintained this effect through 12, 16 and 20 were reported.

Outcome measures

Outcome measures
Measure	Investigator-assigned Anti-CMV Treatment (IAT) n=117 Participants Participants received 1 or 2 of the 4 anti-CMV agents from the following: ganciclovir, valganciclovir, foscarnet, or cidofovir based on the investigator's discretion for the 8 week treatment period.	Maribavir 400 mg n=235 Participants Participants received maribavir 400 mg (2\*200 mg tablets), orally, twice daily for the 8 week treatment period.	Maribavir 400 mg Participants received maribavir 400 mg (2\*200 mg tablets), orally, twice daily for the 8 week treatment period.
Percentage of Participants Who Achieved Confirmed CMV Viremia Clearance After Receiving 8 Weeks of Study-assigned Treatment At Week 8	18.8 percentage of participants	54.9 percentage of participants	—
Percentage of Participants Who Achieved Confirmed CMV Viremia Clearance After Receiving 8 Weeks of Study-assigned Treatment At Week 12	5.1 percentage of participants	22.6 percentage of participants	—
Percentage of Participants Who Achieved Confirmed CMV Viremia Clearance After Receiving 8 Weeks of Study-assigned Treatment At Week 16	5.1 percentage of participants	18.7 percentage of participants	—
Percentage of Participants Who Achieved Confirmed CMV Viremia Clearance After Receiving 8 Weeks of Study-assigned Treatment At Week 20	4.3 percentage of participants	18.3 percentage of participants	—

SECONDARY outcome

Timeframe: At Week 8 through Weeks 12, 16 and 20

Population: The randomized set consisted of all participants who had signed informed consent and had begun some study procedures and were randomized to the study.

Confirmed CMV viremia clearance was defined as plasma CMV DNA concentration \<LLOQ that is, \<137IU/mL when assessed by COBAS® AmpliPrep/COBAS® TaqMan® CMV test in 2 consecutive postbaseline samples, separated by at least 5 days. CMV infection symptom control was defined as resolution or improvement of tissue invasive CMV disease or CMV syndrome for participants symptomatic at baseline, or maintaining no symptoms of tissue invasive CMV disease or CMV syndrome for participants asymptomatic at baseline. Percentage of participants who achieved confirmed CMV viremia clearance and CMV infection control after receiving 8 weeks study-assigned treatment at end of Week 8, and maintained this effect through 12, 16 and 20 were reported.

Outcome measures

Outcome measures
Measure	Investigator-assigned Anti-CMV Treatment (IAT) n=117 Participants Participants received 1 or 2 of the 4 anti-CMV agents from the following: ganciclovir, valganciclovir, foscarnet, or cidofovir based on the investigator's discretion for the 8 week treatment period.	Maribavir 400 mg n=235 Participants Participants received maribavir 400 mg (2\*200 mg tablets), orally, twice daily for the 8 week treatment period.	Maribavir 400 mg Participants received maribavir 400 mg (2\*200 mg tablets), orally, twice daily for the 8 week treatment period.
Percentage of Participants Who Achieved Confirmed CMV Viremia Clearance and CMV Infection Symptom Control After Receiving 8 Weeks of Study-assigned Treatment Through Weeks 12, 16 and 20 At Week 8	18.8 percentage of participants	54.9 percentage of participants	—
Percentage of Participants Who Achieved Confirmed CMV Viremia Clearance and CMV Infection Symptom Control After Receiving 8 Weeks of Study-assigned Treatment Through Weeks 12, 16 and 20 At Week 12	5.1 percentage of participants	22.6 percentage of participants	—
Percentage of Participants Who Achieved Confirmed CMV Viremia Clearance and CMV Infection Symptom Control After Receiving 8 Weeks of Study-assigned Treatment Through Weeks 12, 16 and 20 At Week 16	5.1 percentage of participants	18.7 percentage of participants	—
Percentage of Participants Who Achieved Confirmed CMV Viremia Clearance and CMV Infection Symptom Control After Receiving 8 Weeks of Study-assigned Treatment Through Weeks 12, 16 and 20 At Week 20	4.3 percentage of participants	18.3 percentage of participants	—

SECONDARY outcome

Timeframe: At Week 8 through Weeks 12 and 20

Population: The randomized set consisted of all participants who had signed informed consent and had begun some study procedures and were randomized to the study.

Confirmed CMV viremia clearance was defined as plasma CMV DNA concentration \<LLOQ that is, \<137IU/mL when assessed by COBAS® AmpliPrep/COBAS® TaqMan® CMV test in 2 consecutive postbaseline samples, separated by at least 5 days. CMV infection symptom control was defined as resolution or improvement of tissue invasive CMV disease or CMV syndrome for participants symptomatic at baseline or maintaining no symptoms of tissue invasive CMV disease or CMV syndrome for participants asymptomatic at baseline. Percentage of participants who maintained CMV viremia clearance and CMV infection symptom control at the end of study Week 8 through Weeks 12 and 20 regardless of whether either study-assigned treatment was discontinued before 8 weeks of therapy were reported.

Outcome measures

Outcome measures
Measure	Investigator-assigned Anti-CMV Treatment (IAT) n=117 Participants Participants received 1 or 2 of the 4 anti-CMV agents from the following: ganciclovir, valganciclovir, foscarnet, or cidofovir based on the investigator's discretion for the 8 week treatment period.	Maribavir 400 mg n=235 Participants Participants received maribavir 400 mg (2\*200 mg tablets), orally, twice daily for the 8 week treatment period.	Maribavir 400 mg Participants received maribavir 400 mg (2\*200 mg tablets), orally, twice daily for the 8 week treatment period.
Percentage of Participants Who Maintained CMV Viremia Clearance and CMV Infection Symptom Control at the End of Study Week 8 Through Weeks 12 and 20 Regardless of Whether Either Study-assigned Treatment Was Discontinued Before 8 Weeks of Therapy At Week 8	23.9 percentage of participants	55.7 percentage of participants	—
Percentage of Participants Who Maintained CMV Viremia Clearance and CMV Infection Symptom Control at the End of Study Week 8 Through Weeks 12 and 20 Regardless of Whether Either Study-assigned Treatment Was Discontinued Before 8 Weeks of Therapy At Week 12	10.3 percentage of participants	22.6 percentage of participants	—
Percentage of Participants Who Maintained CMV Viremia Clearance and CMV Infection Symptom Control at the End of Study Week 8 Through Weeks 12 and 20 Regardless of Whether Either Study-assigned Treatment Was Discontinued Before 8 Weeks of Therapy At Week 20	9.4 percentage of participants	18.3 percentage of participants	—

SECONDARY outcome

Timeframe: At Week 8

Population: The randomized set consisted of all participants who had signed informed consent and had begun some study procedures and were randomized to the study.

Recurrence of CMV viremia was defined as plasma CMV DNA concentration greater than or equal to (\>=) LLOQ when assessed by COBAS® AmpliPrep/COBAS® TaqMan® CMV test in 2 consecutive plasma samples at least 5 days apart, after achieving confirmed viremia clearance, regardless of whether either study-assigned treatment was discontinued before the end of the stipulated 8 weeks of therapy. Percentage of participants with recurrence of CMV viremia during the first 8 weeks of study regardless of whether study-assigned treatment was discontinued before 8 weeks of therapy were reported.

Outcome measures

Outcome measures
Measure	Investigator-assigned Anti-CMV Treatment (IAT) n=117 Participants Participants received 1 or 2 of the 4 anti-CMV agents from the following: ganciclovir, valganciclovir, foscarnet, or cidofovir based on the investigator's discretion for the 8 week treatment period.	Maribavir 400 mg n=235 Participants Participants received maribavir 400 mg (2\*200 mg tablets), orally, twice daily for the 8 week treatment period.	Maribavir 400 mg Participants received maribavir 400 mg (2\*200 mg tablets), orally, twice daily for the 8 week treatment period.
Percentage of Participants With Recurrence of CMV Viremia During the First 8 Weeks of Study Regardless of Whether Study-assigned Treatment Was Discontinued Before 8 Weeks of Therapy	12.3 percentage of participants	17.9 percentage of participants	—

SECONDARY outcome

Timeframe: End of Week 8 up to Week 20 (12 weeks follow-up period)

Population: The randomized set consisted of all participants who had signed informed consent and had begun some study procedures and were randomized to the study.

Recurrence of CMV viremia was defined as plasma CMV DNA concentration \>=LLOQ when assessed by COBAS® AmpliPrep/COBAS® TaqMan® CMV test in 2 consecutive plasma samples at least 5 days apart, after achieving confirmed viremia clearance, regardless of whether either study-assigned treatment was discontinued before the end of the stipulated 8 weeks of therapy. Percentage of participants with recurrence of CMV viremia during the 12 weeks follow-up period regardless of whether study-assigned treatment was discontinued before 8 weeks of therapy were reported.

Outcome measures

Outcome measures
Measure	Investigator-assigned Anti-CMV Treatment (IAT) n=117 Participants Participants received 1 or 2 of the 4 anti-CMV agents from the following: ganciclovir, valganciclovir, foscarnet, or cidofovir based on the investigator's discretion for the 8 week treatment period.	Maribavir 400 mg n=235 Participants Participants received maribavir 400 mg (2\*200 mg tablets), orally, twice daily for the 8 week treatment period.	Maribavir 400 mg Participants received maribavir 400 mg (2\*200 mg tablets), orally, twice daily for the 8 week treatment period.
Percentage of Participants With Recurrence of CMV Viremia During the 12 Weeks Follow-up Period Regardless of Whether Study-assigned Treatment Was Discontinued Before 8 Weeks of Therapy	21.5 percentage of participants	38.6 percentage of participants	—

SECONDARY outcome

Timeframe: Baseline up to Week 20

Population: The randomized set consisted of all participants who had signed informed consent and had begun some study procedures and were randomized to the study.

Recurrence of CMV viremia was defined as plasma CMV DNA concentration \>=LLOQ when assessed by COBAS® AmpliPrep/COBAS® TaqMan® CMV test in 2 consecutive plasma samples at least 5 days apart, after achieving confirmed viremia clearance, regardless of whether either study-assigned treatment was discontinued before the end of the stipulated 8 weeks of therapy. Percentage of participants with recurrence of CMV viremia during at any time on study regardless of whether study-assigned treatment was discontinued before 8 weeks of therapy were reported.

Outcome measures

Outcome measures
Measure	Investigator-assigned Anti-CMV Treatment (IAT) n=117 Participants Participants received 1 or 2 of the 4 anti-CMV agents from the following: ganciclovir, valganciclovir, foscarnet, or cidofovir based on the investigator's discretion for the 8 week treatment period.	Maribavir 400 mg n=235 Participants Participants received maribavir 400 mg (2\*200 mg tablets), orally, twice daily for the 8 week treatment period.	Maribavir 400 mg Participants received maribavir 400 mg (2\*200 mg tablets), orally, twice daily for the 8 week treatment period.
Percentage of Participants With Recurrence of CMV Viremia at Any Time on Study Regardless of Whether Study-assigned Treatment Was Discontinued Before 8 Weeks of Therapy	33.8 percentage of participants	56.5 percentage of participants	—

SECONDARY outcome

Timeframe: Baseline up to Week 8

Population: The randomized set consisted of all participants who had signed informed consent and had begun some study procedures and were randomized to the study. Here "overall number of participants analyzed" were participants who were evaluable for this outcome measure.

Outcome measures

Outcome measures
Measure	Investigator-assigned Anti-CMV Treatment (IAT) n=37 Participants Participants received 1 or 2 of the 4 anti-CMV agents from the following: ganciclovir, valganciclovir, foscarnet, or cidofovir based on the investigator's discretion for the 8 week treatment period.	Maribavir 400 mg n=183 Participants Participants received maribavir 400 mg (2\*200 mg tablets), orally, twice daily for the 8 week treatment period.	Maribavir 400 mg Participants received maribavir 400 mg (2\*200 mg tablets), orally, twice daily for the 8 week treatment period.
Percentage of Participants Who Completed 8 Weeks of Study-assigned Treatment With Recurrence of CMV Viremia During the First 8 Weeks of the Treatment	9.7 percentage of participants	15.2 percentage of participants	—

SECONDARY outcome

Timeframe: End of Week 8 up to Week 20 (12 weeks follow-up period)

Outcome measures

Outcome measures
Measure	Investigator-assigned Anti-CMV Treatment (IAT) n=37 Participants Participants received 1 or 2 of the 4 anti-CMV agents from the following: ganciclovir, valganciclovir, foscarnet, or cidofovir based on the investigator's discretion for the 8 week treatment period.	Maribavir 400 mg n=183 Participants Participants received maribavir 400 mg (2\*200 mg tablets), orally, twice daily for the 8 week treatment period.	Maribavir 400 mg Participants received maribavir 400 mg (2\*200 mg tablets), orally, twice daily for the 8 week treatment period.
Percentage of Participants Who Completed 8 Weeks of Study-assigned Treatment With Recurrence of CMV Viremia During the 12 Weeks of Follow-up Period	35.5 percentage of participants	40.9 percentage of participants	—

SECONDARY outcome

Timeframe: Baseline up to Week 20

Recurrence of CMV viremia was defined as plasma CMV DNA concentration \>=LLOQ when assessed by COBAS® AmpliPrep/COBAS® TaqMan® CMV test in 2 consecutive plasma samples at least 5 days apart, after achieving confirmed viremia clearance. Percentage of participants with Recurrence of CMV viremia was defined as plasma CMV DNA concentration \>=LLOQ when assessed by COBAS® AmpliPrep/COBAS® TaqMan® CMV test in 2 consecutive plasma samples at least 5 days apart, after achieving confirmed viremia clearance. Percentage of participants who completed 8 weeks of study-assigned treatment with recurrence of CMV viremia during the 20 weeks of study were reported.

Outcome measures

Outcome measures
Measure	Investigator-assigned Anti-CMV Treatment (IAT) n=37 Participants Participants received 1 or 2 of the 4 anti-CMV agents from the following: ganciclovir, valganciclovir, foscarnet, or cidofovir based on the investigator's discretion for the 8 week treatment period.	Maribavir 400 mg n=183 Participants Participants received maribavir 400 mg (2\*200 mg tablets), orally, twice daily for the 8 week treatment period.	Maribavir 400 mg Participants received maribavir 400 mg (2\*200 mg tablets), orally, twice daily for the 8 week treatment period.
Percentage of Participants Who Completed 8 Weeks of Study-assigned Treatment With Recurrence of CMV Viremia During the 20 Weeks of Study	45.2 percentage of participants	56.1 percentage of participants	—

SECONDARY outcome

Timeframe: Baseline up to termination of study treatment (up to Week 8)

Population: The randomized set consisted of all participants who had signed informed consent and had begun some study procedures and were randomized to the study.

Outcome measures

Outcome measures
Measure	Investigator-assigned Anti-CMV Treatment (IAT) n=117 Participants Participants received 1 or 2 of the 4 anti-CMV agents from the following: ganciclovir, valganciclovir, foscarnet, or cidofovir based on the investigator's discretion for the 8 week treatment period.	Maribavir 400 mg n=235 Participants Participants received maribavir 400 mg (2\*200 mg tablets), orally, twice daily for the 8 week treatment period.	Maribavir 400 mg Participants received maribavir 400 mg (2\*200 mg tablets), orally, twice daily for the 8 week treatment period.
Percentage of Participants With Recurrence of CMV Viremia While on Study-assigned Treatment	4.6 percentage of participants	15.8 percentage of participants	—

SECONDARY outcome

Timeframe: Termination of study treatment (Week 8) up to the End of the Study (Week 20)

Population: The randomized set consisted of all participants who had signed informed consent and had begun some study procedures and were randomized to the study.

Outcome measures

Outcome measures
Measure	Investigator-assigned Anti-CMV Treatment (IAT) n=117 Participants Participants received 1 or 2 of the 4 anti-CMV agents from the following: ganciclovir, valganciclovir, foscarnet, or cidofovir based on the investigator's discretion for the 8 week treatment period.	Maribavir 400 mg n=235 Participants Participants received maribavir 400 mg (2\*200 mg tablets), orally, twice daily for the 8 week treatment period.	Maribavir 400 mg Participants received maribavir 400 mg (2\*200 mg tablets), orally, twice daily for the 8 week treatment period.
Percentage of Participants With Recurrence of CMV Viremia While Off Study-assigned Treatment During Follow-up Period	29.2 percentage of participants	40.8 percentage of participants	—

SECONDARY outcome

Timeframe: At Baseline

Population: The combination of maribavir resistance set (MRS) and non-MRS set (MRS+non-MRS) included all participants in modified randomized set who had been randomized in the study and who had taken any dose of study-assigned treatment with evaluable CMV genotypic data at baseline with or without pre-existing known maribavir RASs in pUL97 and/or pUL27. Here "overall number of participants analyzed" were participants who were evaluable for this outcome measure.

Resistance-associated amino acid substitutions (RASs) to maribavir are known to generally map to the pUL97 and pUL27 genes. Genotyping was performed to identify RASs mapping to the pUL97 and pUL27 genes. Number of participants who had maribavir CMV resistance at baseline were reported.

Outcome measures

Outcome measures
Measure	Investigator-assigned Anti-CMV Treatment (IAT) n=100 Participants Participants received 1 or 2 of the 4 anti-CMV agents from the following: ganciclovir, valganciclovir, foscarnet, or cidofovir based on the investigator's discretion for the 8 week treatment period.	Maribavir 400 mg n=17 Participants Participants received maribavir 400 mg (2\*200 mg tablets), orally, twice daily for the 8 week treatment period.	Maribavir 400 mg n=214 Participants Participants received maribavir 400 mg (2\*200 mg tablets), orally, twice daily for the 8 week treatment period.
Number of Participants Who Had Maribavir CMV Resistance at Baseline RASs associated with pUL97 only	3 Participants	1 Participants	0 Participants
Number of Participants Who Had Maribavir CMV Resistance at Baseline RASs associated with pUL27 only	0 Participants	0 Participants	1 Participants
Number of Participants Who Had Maribavir CMV Resistance at Baseline RASs associated with pUL97 and pUL27	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: After first dose of study drug up to Week 20

Resistance-associated amino acid substitutions (RASs) to maribavir are known to generally map to the pUL97 and pUL27 genes. Genotyping was performed to identify RASs mapping to the pUL97 and pUL27 genes. Number of participants who had post-baseline resistance to maribavir were reported.

Outcome measures

Outcome measures
Measure	Investigator-assigned Anti-CMV Treatment (IAT) n=100 Participants Participants received 1 or 2 of the 4 anti-CMV agents from the following: ganciclovir, valganciclovir, foscarnet, or cidofovir based on the investigator's discretion for the 8 week treatment period.	Maribavir 400 mg n=17 Participants Participants received maribavir 400 mg (2\*200 mg tablets), orally, twice daily for the 8 week treatment period.	Maribavir 400 mg n=214 Participants Participants received maribavir 400 mg (2\*200 mg tablets), orally, twice daily for the 8 week treatment period.
Number of Participants Who Had Post-baseline Resistance to Maribavir RASs associated with pUL97 only	0 Participants	4 Participants	45 Participants
Number of Participants Who Had Post-baseline Resistance to Maribavir RASs associated with pUL27 only	0 Participants	0 Participants	0 Participants
Number of Participants Who Had Post-baseline Resistance to Maribavir RASs associated with pUL97 and pUL27	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: From enrollment up to end of study (approximately 44 months)

Population: The randomized set consisted of all participants who had signed informed consent and had begun some study procedures and were randomized to the study.

All-cause mortality was analyzed by the end of study regardless of the use of rescue treatment or alternative anti-CMV treatment. Number of participants who died during the entire study period were reported.

Outcome measures

Outcome measures
Measure	Investigator-assigned Anti-CMV Treatment (IAT) n=117 Participants Participants received 1 or 2 of the 4 anti-CMV agents from the following: ganciclovir, valganciclovir, foscarnet, or cidofovir based on the investigator's discretion for the 8 week treatment period.	Maribavir 400 mg n=235 Participants Participants received maribavir 400 mg (2\*200 mg tablets), orally, twice daily for the 8 week treatment period.	Maribavir 400 mg Participants received maribavir 400 mg (2\*200 mg tablets), orally, twice daily for the 8 week treatment period.
Number of Participants With All-cause Mortality by the End of the Study	13 Participants	27 Participants	—

SECONDARY outcome

Timeframe: From enrollment to last serious adverse event (SAE) follow-up (approximately Week 28)

Population: The randomized set consisted of all participants who had signed informed consent and had begun some study procedures and were randomized to the study.

The time to all-cause mortality by the end of the study participation in days was calculated. Participants who were alive at the last study follow-up (regardless of use of rescue or alternative anti-CMV treatment), withdrew from study or were lost to follow-up were censored at the date of last contact.

Outcome measures

Outcome measures
Measure	Investigator-assigned Anti-CMV Treatment (IAT) n=117 Participants Participants received 1 or 2 of the 4 anti-CMV agents from the following: ganciclovir, valganciclovir, foscarnet, or cidofovir based on the investigator's discretion for the 8 week treatment period.	Maribavir 400 mg n=235 Participants Participants received maribavir 400 mg (2\*200 mg tablets), orally, twice daily for the 8 week treatment period.	Maribavir 400 mg Participants received maribavir 400 mg (2\*200 mg tablets), orally, twice daily for the 8 week treatment period.
Time to All Cause Mortality	73.0 days Interval 13.0 to 186.0	55.0 days Interval 3.0 to 182.0	—

SECONDARY outcome

Timeframe: From start of maribavir rescue treatment through 8 weeks

Population: The rescue set consisted of all participants who entered the rescue arm and received any dose of maribavir as rescue therapy. As planned, this OM was assessed only in maribavir rescue arm.

Confirmed CMV viremia clearance was defined as plasma CMV DNA concentration \<LLOQ that is, \<137 IU/mL when assessed by COBAS® AmpliPrep/COBAS® TaqMan® CMV Test in 2 consecutive postbaseline samples, separated by at least 5 days, regardless of whether the rescue treatment was discontinued before the end of the stipulated 8 weeks of therapy. Percentage of participants who achieved confirmed CMV viremia clearance at end of Week 8 after starting maribavir rescue treatment were reported.

Outcome measures

Outcome measures
Measure	Investigator-assigned Anti-CMV Treatment (IAT) n=22 Participants Participants received 1 or 2 of the 4 anti-CMV agents from the following: ganciclovir, valganciclovir, foscarnet, or cidofovir based on the investigator's discretion for the 8 week treatment period.	Maribavir 400 mg Participants received maribavir 400 mg (2\*200 mg tablets), orally, twice daily for the 8 week treatment period.	Maribavir 400 mg Participants received maribavir 400 mg (2\*200 mg tablets), orally, twice daily for the 8 week treatment period.
Percentage of Participants Who Achieved Confirmed Clearance of Plasma CMV DNA (CMV Viremia Clearance) at End of Week 8 After Starting Maribavir Rescue Treatment	50.0 percentage of participants Interval 28.22 to 71.78	—	—

SECONDARY outcome

Timeframe: Up to Week 16

Confirmed CMV viremia clearance was defined as plasma CMV DNA concentration \<LLOQ that is, \<137 IU/mL when assessed by COBAS® AmpliPrep/COBAS® TaqMan® CMV test in 2 consecutive postbaseline samples, separated by at least 5 days. CMV infection symptom control was defined as resolution or improvement of tissue invasive CMV disease or CMV syndrome for participants symptomatic at baseline, or maintaining no symptoms of tissue invasive CMV disease or CMV syndrome for participants asymptomatic at baseline. Percentage of participants receiving maribavir rescue treatment who achieved confirmed CMV viremia clearance and CMV infection symptom control at Week 8 with maintenance of effect through Week 16 were reported.

Outcome measures

Outcome measures
Measure	Investigator-assigned Anti-CMV Treatment (IAT) n=22 Participants Participants received 1 or 2 of the 4 anti-CMV agents from the following: ganciclovir, valganciclovir, foscarnet, or cidofovir based on the investigator's discretion for the 8 week treatment period.	Maribavir 400 mg Participants received maribavir 400 mg (2\*200 mg tablets), orally, twice daily for the 8 week treatment period.	Maribavir 400 mg Participants received maribavir 400 mg (2\*200 mg tablets), orally, twice daily for the 8 week treatment period.
Percentage of Participants Receiving Maribavir Rescue Treatment Who Achieved Confirmed CMV Viremia Clearance and CMV Infection Symptom Control at Week 8 With Maintenance of Effect Through Week 16	27.3 percentage of participants Interval 10.73 to 50.22	—	—

SECONDARY outcome

Timeframe: Baseline up to 7 days or 21 days (if cidofovir used) after the last dose of study treatment (up to Week 8)

Population: The safety set consisted of all participants who had taken any dose of study treatment.

An adverse event (AE) is any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. Serious AE was any untoward medical occurrence (whether considered to be related to study-assigned treatment or not) that at any dose resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, resulted in a congenital abnormality/birth defect, or was an important medical event. TEAEs was defined as any adverse events (classified by preferred term) that had a start date on or after the first dose of study treatment or that had a start date before the date of first dose of study treatment, but increased in severity after the first dose of study treatment.

Outcome measures

Outcome measures
Measure	Investigator-assigned Anti-CMV Treatment (IAT) n=116 Participants Participants received 1 or 2 of the 4 anti-CMV agents from the following: ganciclovir, valganciclovir, foscarnet, or cidofovir based on the investigator's discretion for the 8 week treatment period.	Maribavir 400 mg n=22 Participants Participants received maribavir 400 mg (2\*200 mg tablets), orally, twice daily for the 8 week treatment period.	Maribavir 400 mg n=234 Participants Participants received maribavir 400 mg (2\*200 mg tablets), orally, twice daily for the 8 week treatment period.
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs During the On-treatment Observation Period TEAEs	106 Participants	22 Participants	228 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs During the On-treatment Observation Period Serious TEAEs	43 Participants	11 Participants	90 Participants

SECONDARY outcome

Timeframe: Predose at Week 1, 4 and 8

Population: The pharmacokinetic set consisted of all participants who had taken any dose of study treatment and who had plasma samples drawn and tested for maribavir concentrations. Here "overall number of participants analyzed" were participants who were evaluable for this outcome measure and "number analyzed" were participants who were evaluable for the outcome measure at given time points.

Cmin of maribavir was reported.

Outcome measures

Outcome measures
Measure	Investigator-assigned Anti-CMV Treatment (IAT) n=208 Participants Participants received 1 or 2 of the 4 anti-CMV agents from the following: ganciclovir, valganciclovir, foscarnet, or cidofovir based on the investigator's discretion for the 8 week treatment period.	Maribavir 400 mg n=20 Participants Participants received maribavir 400 mg (2\*200 mg tablets), orally, twice daily for the 8 week treatment period.	Maribavir 400 mg Participants received maribavir 400 mg (2\*200 mg tablets), orally, twice daily for the 8 week treatment period.
Predose Concentration (Cmin) of Maribavir Cmin at Week 1	8.77 micrograms per milliliter (mcg/mL) Standard Deviation 7.88	8.57 micrograms per milliliter (mcg/mL) Standard Deviation 6.28	—
Predose Concentration (Cmin) of Maribavir Cmin at Week 4	7.59 micrograms per milliliter (mcg/mL) Standard Deviation 7.05	5.75 micrograms per milliliter (mcg/mL) Standard Deviation 3.99	—
Predose Concentration (Cmin) of Maribavir Cmin at Week 8	7.19 micrograms per milliliter (mcg/mL) Standard Deviation 6.41	5.65 micrograms per milliliter (mcg/mL) Standard Deviation 4.47	—

Adverse Events

IAT: Ganciclovir/ Valganciclovir

Serious events: 33 serious events

Other events: 54 other events

Deaths: 6 deaths

IAT: Foscarnet

Serious events: 26 serious events

Other events: 43 other events

Deaths: 7 deaths

IAT: Cidofovir

Serious events: 3 serious events

Other events: 5 other events

Deaths: 0 deaths

IAT: Foscarnet + Ganciclovir/ Valganciclovir

Serious events: 1 serious events

Other events: 7 other events

Deaths: 0 deaths

Maribavir 400 mg

Serious events: 131 serious events

Other events: 229 other events

Deaths: 27 deaths

Maribavir Rescue Arm

Serious events: 14 serious events

Other events: 22 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	IAT: Ganciclovir/ Valganciclovir n=56 participants at risk Participants received ganciclovir intravenously or valganciclovir orally based on the the investigator's discretion for the 8 week treatment period.	IAT: Foscarnet n=47 participants at risk Participants received foscarnet intravenously based on investigator's discretion for the 8 week treatment period.	IAT: Cidofovir n=6 participants at risk Participants received cidofovir intravenously based on the investigator's discretion for the 8 week treatment period.	IAT: Foscarnet + Ganciclovir/ Valganciclovir n=7 participants at risk Participants received foscarnet intravenously in combination with ganciclovir intravenously or valganciclovir orally based on investigator's discretion for the 8 week treatment period.	Maribavir 400 mg n=234 participants at risk Participants received maribavir 400 mg (2\*200 mg tablets), orally, twice daily for the 8 week treatment period.	Maribavir Rescue Arm n=22 participants at risk Participants with clear evidence of virologic failure (not just intolerance) after a minimum of 3 weeks of therapy with IAT entered maribavir rescue arm and received maribavir 400 mg (2\*200 mg tablets), orally, twice daily for the 8 week treatment period.
Gastrointestinal disorders Gastrointestinal angiodysplasia	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.43% 1/234 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Gastrointestinal disorders Ileal perforation	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.43% 1/234 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
General disorders Oedema peripheral	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.43% 1/234 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Hepatobiliary disorders Biliary colic	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.43% 1/234 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Hepatobiliary disorders Cholecystitis acute	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.43% 1/234 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Immune system disorders Graft versus host disease	1.8% 1/56 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.43% 1/234 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Immune system disorders Renal transplant failure	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.43% 1/234 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Infections and infestations Adenovirus infection	1.8% 1/56 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.00% 0/234 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Infections and infestations Atypical pneumonia	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.43% 1/234 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Blood and lymphatic system disorders Immune thrombocytopenia	1.8% 1/56 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.00% 0/234 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Cardiac disorders Atrial fibrillation	1.8% 1/56 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.00% 0/234 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Cardiac disorders Cardiac failure	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.43% 1/234 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Cardiac disorders Myocardial infarction	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.85% 2/234 • Number of events 2 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Eye disorders Glaucoma	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	2.1% 1/47 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.00% 0/234 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Eye disorders Iridocyclitis	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.43% 1/234 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Gastrointestinal disorders Food poisoning	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.43% 1/234 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Blood and lymphatic system disorders Anaemia	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	1.7% 4/234 • Number of events 4 • Baseline up to end of study (approximately 44 months)	9.1% 2/22 • Number of events 2 • Baseline up to end of study (approximately 44 months)
Blood and lymphatic system disorders Febrile neutropenia	7.1% 4/56 • Number of events 4 • Baseline up to end of study (approximately 44 months)	2.1% 1/47 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	1.3% 3/234 • Number of events 3 • Baseline up to end of study (approximately 44 months)	9.1% 2/22 • Number of events 2 • Baseline up to end of study (approximately 44 months)
Blood and lymphatic system disorders Leukocytosis	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.43% 1/234 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Blood and lymphatic system disorders Neutropenia	5.4% 3/56 • Number of events 3 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.43% 1/234 • Number of events 1 • Baseline up to end of study (approximately 44 months)	4.5% 1/22 • Number of events 1 • Baseline up to end of study (approximately 44 months)
Blood and lymphatic system disorders Pancytopenia	1.8% 1/56 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.43% 1/234 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Blood and lymphatic system disorders Sickle cell anaemia with crisis	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.43% 1/234 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Blood and lymphatic system disorders Thrombocytopenia	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.85% 2/234 • Number of events 2 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Blood and lymphatic system disorders Thrombotic microangiopathy	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.43% 1/234 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Cardiac disorders Acute myocardial infarction	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.43% 1/234 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Cardiac disorders Cardiac arrest	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.43% 1/234 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Cardiac disorders Cardiac failure congestive	1.8% 1/56 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.00% 0/234 • Baseline up to end of study (approximately 44 months)	4.5% 1/22 • Number of events 1 • Baseline up to end of study (approximately 44 months)
Cardiac disorders Pericarditis	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.43% 1/234 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Cardiac disorders Tachycardia	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.43% 1/234 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Gastrointestinal disorders Abdominal pain	1.8% 1/56 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	1.3% 3/234 • Number of events 5 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Gastrointestinal disorders Colitis	1.8% 1/56 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.00% 0/234 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Gastrointestinal disorders Diarrhoea	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	3.4% 8/234 • Number of events 8 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Gastrointestinal disorders Gastrointestinal haemorrhage	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	2.1% 1/47 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	1.3% 3/234 • Number of events 3 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Gastrointestinal disorders Haematochezia	1.8% 1/56 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.00% 0/234 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Gastrointestinal disorders Nausea	1.8% 1/56 • Number of events 1 • Baseline up to end of study (approximately 44 months)	4.3% 2/47 • Number of events 2 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	1.3% 3/234 • Number of events 3 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Gastrointestinal disorders Pancreatitis	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.43% 1/234 • Number of events 2 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Gastrointestinal disorders Vomiting	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	2.1% 1/47 • Number of events 1 • Baseline up to end of study (approximately 44 months)	16.7% 1/6 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.85% 2/234 • Number of events 2 • Baseline up to end of study (approximately 44 months)	4.5% 1/22 • Number of events 1 • Baseline up to end of study (approximately 44 months)
General disorders Adverse drug reaction	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.43% 1/234 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
General disorders Asthenia	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.43% 1/234 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
General disorders Disease progression	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	2.1% 1/47 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.00% 0/234 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
General disorders Drug interaction	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.43% 1/234 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
General disorders Fatigue	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.85% 2/234 • Number of events 2 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
General disorders General physical health deterioration	1.8% 1/56 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.85% 2/234 • Number of events 2 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
General disorders Malaise	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	1.3% 3/234 • Number of events 3 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
General disorders Multiple organ dysfunction syndrome	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	1.3% 3/234 • Number of events 3 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
General disorders Pyrexia	1.8% 1/56 • Number of events 1 • Baseline up to end of study (approximately 44 months)	4.3% 2/47 • Number of events 2 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	2.6% 6/234 • Number of events 6 • Baseline up to end of study (approximately 44 months)	4.5% 1/22 • Number of events 1 • Baseline up to end of study (approximately 44 months)
General disorders Treatment failure	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.43% 1/234 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Hepatobiliary disorders Cholecystitis	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	2.1% 1/47 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.43% 1/234 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Hepatobiliary disorders Drug-induced liver injury	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.43% 1/234 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Hepatobiliary disorders Hepatic failure	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.43% 1/234 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Immune system disorders Acute graft versus host disease	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.85% 2/234 • Number of events 2 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Immune system disorders Graft versus host disease in gastrointestinal tract	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	1.3% 3/234 • Number of events 5 • Baseline up to end of study (approximately 44 months)	4.5% 1/22 • Number of events 1 • Baseline up to end of study (approximately 44 months)
Immune system disorders Graft versus host disease in liver	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.43% 1/234 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Immune system disorders Transplant rejection	3.6% 2/56 • Number of events 2 • Baseline up to end of study (approximately 44 months)	2.1% 1/47 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	14.3% 1/7 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.85% 2/234 • Number of events 2 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Infections and infestations Arthritis bacterial	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.43% 1/234 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Infections and infestations Aspergillus infection	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.43% 1/234 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Infections and infestations BK virus infection	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	2.1% 1/47 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.00% 0/234 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Infections and infestations Bacteraemia	1.8% 1/56 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	1.3% 3/234 • Number of events 3 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Infections and infestations Bacterial pyelonephritis	1.8% 1/56 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.00% 0/234 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Infections and infestations Bronchopulmonary aspergillosis	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.43% 1/234 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Infections and infestations Cytomegalovirus chorioretinitis	1.8% 1/56 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	2.1% 5/234 • Number of events 5 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Infections and infestations Cytomegalovirus colitis	1.8% 1/56 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.43% 1/234 • Number of events 1 • Baseline up to end of study (approximately 44 months)	4.5% 1/22 • Number of events 1 • Baseline up to end of study (approximately 44 months)
Infections and infestations Cytomegalovirus infection	5.4% 3/56 • Number of events 3 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	16.7% 1/6 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	3.8% 9/234 • Number of events 9 • Baseline up to end of study (approximately 44 months)	4.5% 1/22 • Number of events 1 • Baseline up to end of study (approximately 44 months)
Infections and infestations Cytomegalovirus infection reactivation	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	3.0% 7/234 • Number of events 8 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Infections and infestations Cytomegalovirus mucocutaneous ulcer	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.43% 1/234 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Infections and infestations Cytomegalovirus syndrome	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	1.3% 3/234 • Number of events 3 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Infections and infestations Cytomegalovirus viraemia	5.4% 3/56 • Number of events 3 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	5.1% 12/234 • Number of events 13 • Baseline up to end of study (approximately 44 months)	4.5% 1/22 • Number of events 1 • Baseline up to end of study (approximately 44 months)
Infections and infestations Device related infection	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.43% 1/234 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Infections and infestations Device related sepsis	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.43% 1/234 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Infections and infestations Encephalitis cytomegalovirus	1.8% 1/56 • Number of events 1 • Baseline up to end of study (approximately 44 months)	2.1% 1/47 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	2.1% 5/234 • Number of events 6 • Baseline up to end of study (approximately 44 months)	4.5% 1/22 • Number of events 1 • Baseline up to end of study (approximately 44 months)
Infections and infestations Encephalitis viral	1.8% 1/56 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.00% 0/234 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Infections and infestations Enterococcal bacteraemia	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.43% 1/234 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Infections and infestations Erysipelas	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.43% 1/234 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Infections and infestations Escherichia bacteraemia	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.85% 2/234 • Number of events 2 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Infections and infestations Escherichia sepsis	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.85% 2/234 • Number of events 2 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Infections and infestations Gastroenteritis	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.43% 1/234 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Infections and infestations Gastroenteritis rotavirus	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.43% 1/234 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Infections and infestations H1N1 influenza	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.43% 1/234 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Infections and infestations Herpes simplex	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	2.1% 1/47 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.00% 0/234 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Infections and infestations Herpes zoster	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.85% 2/234 • Number of events 2 • Baseline up to end of study (approximately 44 months)	4.5% 1/22 • Number of events 1 • Baseline up to end of study (approximately 44 months)
Infections and infestations Herpes zoster meningoencephalitis	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.43% 1/234 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Infections and infestations Infection	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.43% 1/234 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Infections and infestations Influenza	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.85% 2/234 • Number of events 2 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Infections and infestations Osteomyelitis	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.43% 1/234 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Infections and infestations Periorbital cellulitis	1.8% 1/56 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.00% 0/234 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Infections and infestations Pneumonia	1.8% 1/56 • Number of events 1 • Baseline up to end of study (approximately 44 months)	2.1% 1/47 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	1.7% 4/234 • Number of events 4 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Infections and infestations Pneumonia cryptococcal	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.43% 1/234 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Infections and infestations Pneumonia cytomegaloviral	3.6% 2/56 • Number of events 2 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.85% 2/234 • Number of events 2 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Infections and infestations Pneumonia haemophilus	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.43% 1/234 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Infections and infestations Pseudomonal sepsis	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.43% 1/234 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Infections and infestations Pulmonary tuberculosis	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.43% 1/234 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Infections and infestations Respiratory syncytial virus infection	1.8% 1/56 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.00% 0/234 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Infections and infestations Respiratory tract infection	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.43% 1/234 • Number of events 2 • Baseline up to end of study (approximately 44 months)	4.5% 1/22 • Number of events 1 • Baseline up to end of study (approximately 44 months)
Infections and infestations Septic shock	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.85% 2/234 • Number of events 2 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Infections and infestations Sinusitis	1.8% 1/56 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.00% 0/234 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Infections and infestations Staphylococcal bacteraemia	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.85% 2/234 • Number of events 2 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Infections and infestations Streptococcal bacteraemia	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	2.1% 1/47 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.00% 0/234 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Infections and infestations Varicella zoster virus infection	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.85% 2/234 • Number of events 2 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Infections and infestations Viral upper respiratory tract infection	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.43% 1/234 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Injury, poisoning and procedural complications Incorrect dose administered	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	2.1% 1/47 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.00% 0/234 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Injury, poisoning and procedural complications Procedural pneumothorax	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.43% 1/234 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Injury, poisoning and procedural complications Spinal fracture	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	2.1% 1/47 • Number of events 1 • Baseline up to end of study (approximately 44 months)	16.7% 1/6 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.00% 0/234 • Baseline up to end of study (approximately 44 months)	4.5% 1/22 • Number of events 2 • Baseline up to end of study (approximately 44 months)
Injury, poisoning and procedural complications Transplant dysfunction	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.43% 1/234 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Investigations General physical condition abnormal	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	2.1% 1/47 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.00% 0/234 • Baseline up to end of study (approximately 44 months)	4.5% 1/22 • Number of events 1 • Baseline up to end of study (approximately 44 months)
Investigations Haemoglobin decreased	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.43% 1/234 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Investigations Hepatic enzyme increased	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.43% 1/234 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Investigations Immunosuppressant drug level increased	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.43% 1/234 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Investigations Viral load increased	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.43% 1/234 • Number of events 1 • Baseline up to end of study (approximately 44 months)	4.5% 1/22 • Number of events 1 • Baseline up to end of study (approximately 44 months)
Investigations Weight decreased	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.85% 2/234 • Number of events 3 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Metabolism and nutrition disorders Dehydration	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.85% 2/234 • Number of events 2 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Metabolism and nutrition disorders Failure to thrive	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.85% 2/234 • Number of events 2 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Metabolism and nutrition disorders Hypokalaemia	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	2.1% 1/47 • Number of events 1 • Baseline up to end of study (approximately 44 months)	16.7% 1/6 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.00% 0/234 • Baseline up to end of study (approximately 44 months)	4.5% 1/22 • Number of events 1 • Baseline up to end of study (approximately 44 months)
Metabolism and nutrition disorders Hyponatraemia	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.85% 2/234 • Number of events 2 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.43% 1/234 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Acute lymphocytic leukaemia recurrent	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.43% 1/234 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Acute myeloid leukaemia recurrent	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	2.1% 1/47 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.43% 1/234 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Leukaemia recurrent	1.8% 1/56 • Number of events 1 • Baseline up to end of study (approximately 44 months)	2.1% 1/47 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.85% 2/234 • Number of events 2 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Renal cell carcinoma	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.43% 1/234 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Nervous system disorders Paraesthesia	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	2.1% 1/47 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.00% 0/234 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Psychiatric disorders Mental status changes	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	1.3% 3/234 • Number of events 3 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Psychiatric disorders Substance-induced psychotic disorder	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	2.1% 1/47 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.00% 0/234 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Renal and urinary disorders Acute kidney injury	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	12.8% 6/47 • Number of events 6 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	5.6% 13/234 • Number of events 14 • Baseline up to end of study (approximately 44 months)	9.1% 2/22 • Number of events 2 • Baseline up to end of study (approximately 44 months)
Renal and urinary disorders Haematuria	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.43% 1/234 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Renal and urinary disorders Nephrolithiasis	1.8% 1/56 • Number of events 1 • Baseline up to end of study (approximately 44 months)	2.1% 1/47 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.00% 0/234 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Renal and urinary disorders Renal impairment	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	2.1% 1/47 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.43% 1/234 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Respiratory, thoracic and mediastinal disorders Acute respiratory distress syndrome	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	4.3% 2/47 • Number of events 2 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.00% 0/234 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	3.6% 2/56 • Number of events 2 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.00% 0/234 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Respiratory, thoracic and mediastinal disorders Dyspnoea	3.6% 2/56 • Number of events 2 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	1.3% 3/234 • Number of events 3 • Baseline up to end of study (approximately 44 months)	4.5% 1/22 • Number of events 1 • Baseline up to end of study (approximately 44 months)
Respiratory, thoracic and mediastinal disorders Hypoxia	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	2.1% 1/47 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.85% 2/234 • Number of events 2 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Respiratory, thoracic and mediastinal disorders Pleural effusion	1.8% 1/56 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.43% 1/234 • Number of events 2 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Respiratory, thoracic and mediastinal disorders Pneumomediastinum	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.43% 1/234 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.85% 2/234 • Number of events 2 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.43% 1/234 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Respiratory, thoracic and mediastinal disorders Pulmonary mass	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.43% 1/234 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Respiratory, thoracic and mediastinal disorders Respiratory distress	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.43% 1/234 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	2.1% 1/47 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	1.7% 4/234 • Number of events 4 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Vascular disorders Deep vein thrombosis	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	1.3% 3/234 • Number of events 3 • Baseline up to end of study (approximately 44 months)	4.5% 1/22 • Number of events 1 • Baseline up to end of study (approximately 44 months)
Vascular disorders Hypertension	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	2.1% 1/47 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.00% 0/234 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Vascular disorders Orthostatic hypotension	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.43% 1/234 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Blood and lymphatic system disorders Febrile bone marrow aplasia	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.43% 1/234 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Blood and lymphatic system disorders Haemolytic anaemia	1.8% 1/56 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.00% 0/234 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Infections and infestations Bacterial infection	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.43% 1/234 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Infections and infestations Campylobacter gastroenteritis	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.85% 2/234 • Number of events 2 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Infections and infestations Cellulitis	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.43% 1/234 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Infections and infestations Cerebral toxoplasmosis	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	2.1% 1/47 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.00% 0/234 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Infections and infestations Clostridium colitis	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.43% 1/234 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Infections and infestations Clostridium difficile colitis	1.8% 1/56 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.00% 0/234 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Infections and infestations Coronavirus infection	1.8% 1/56 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.00% 0/234 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Infections and infestations Cytomegalovirus enterocolitis	1.8% 1/56 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.00% 0/234 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Infections and infestations Cytomegalovirus gastroenteritis	1.8% 1/56 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.85% 2/234 • Number of events 2 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Infections and infestations Cytomegalovirus gastrointestinal infection	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.43% 1/234 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Infections and infestations Febrile infection	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.43% 1/234 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Infections and infestations Fungal skin infection	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.43% 1/234 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Infections and infestations Neutropenic sepsis	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	2.1% 1/47 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.43% 1/234 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Infections and infestations Pneumocystis jirovecii pneumonia	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	1.3% 3/234 • Number of events 3 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Infections and infestations Pneumonia fungal	1.8% 1/56 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.00% 0/234 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Infections and infestations Pneumonia respiratory syncytial viral	1.8% 1/56 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.43% 1/234 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Infections and infestations Respiratory tract infection viral	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.43% 1/234 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Infections and infestations Salmonellosis	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.43% 1/234 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Infections and infestations Sepsis	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.43% 1/234 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Infections and infestations Septic arthritis staphylococcal	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.43% 1/234 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Infections and infestations Sinusitis fungal	1.8% 1/56 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.00% 0/234 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Infections and infestations Staphylococcal osteomyelitis	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.43% 1/234 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Infections and infestations Stenotrophomonas infection	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.43% 1/234 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Infections and infestations Tuberculosis	1.8% 1/56 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.00% 0/234 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Infections and infestations Upper respiratory tract infection	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	2.1% 1/47 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.00% 0/234 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Infections and infestations Urinary tract infection	1.8% 1/56 • Number of events 1 • Baseline up to end of study (approximately 44 months)	2.1% 1/47 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.00% 0/234 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Infections and infestations Urosepsis	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.43% 1/234 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Injury, poisoning and procedural complications Skin laceration	1.8% 1/56 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.00% 0/234 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Injury, poisoning and procedural complications Transplant failure	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.43% 1/234 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Injury, poisoning and procedural complications Wound dehiscence	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.43% 1/234 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Metabolism and nutrition disorders Acidosis hyperchloraemic	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.43% 1/234 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Metabolism and nutrition disorders Diabetes mellitus inadequate control	1.8% 1/56 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.00% 0/234 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Metabolism and nutrition disorders Hypernatraemia	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.43% 1/234 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Musculoskeletal and connective tissue disorders Arthritis	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.43% 1/234 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Musculoskeletal and connective tissue disorders Intervertebral disc compression	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.43% 1/234 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Musculoskeletal and connective tissue disorders Rhabdomyolysis	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.43% 1/234 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Diffuse large B-cell lymphoma recurrent	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.43% 1/234 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Post transplant lymphoproliferative disorder	1.8% 1/56 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.00% 0/234 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Nervous system disorders Guillain-Barre syndrome	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	2.1% 1/47 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.00% 0/234 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Nervous system disorders Ischaemic stroke	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.43% 1/234 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Nervous system disorders Syncope	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	1.3% 3/234 • Number of events 3 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Product Issues Device breakage	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.43% 1/234 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Psychiatric disorders Depression	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.43% 1/234 • Number of events 1 • Baseline up to end of study (approximately 44 months)	4.5% 1/22 • Number of events 1 • Baseline up to end of study (approximately 44 months)
Renal and urinary disorders Nephrotic syndrome	1.8% 1/56 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.00% 0/234 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Renal and urinary disorders Renal artery stenosis	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.43% 1/234 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Renal and urinary disorders Urinary retention	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.43% 1/234 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Respiratory, thoracic and mediastinal disorders Pneumonia aspiration	1.8% 1/56 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.43% 1/234 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Respiratory, thoracic and mediastinal disorders Pulmonary oedema	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.43% 1/234 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Skin and subcutaneous tissue disorders Diabetic foot	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.43% 1/234 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Vascular disorders Hypotension	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.43% 1/234 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Vascular disorders Venous thrombosis	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.43% 1/234 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Infections and infestations Vascular device infection	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.00% 0/234 • Baseline up to end of study (approximately 44 months)	4.5% 1/22 • Number of events 1 • Baseline up to end of study (approximately 44 months)
Infections and infestations Pyelonephritis	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.00% 0/234 • Baseline up to end of study (approximately 44 months)	4.5% 1/22 • Number of events 2 • Baseline up to end of study (approximately 44 months)
Nervous system disorders Epilepsy	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.00% 0/234 • Baseline up to end of study (approximately 44 months)	4.5% 1/22 • Number of events 1 • Baseline up to end of study (approximately 44 months)
Nervous system disorders Transient ischaemic attack	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.00% 0/234 • Baseline up to end of study (approximately 44 months)	4.5% 1/22 • Number of events 1 • Baseline up to end of study (approximately 44 months)
Renal and urinary disorders Vesicoureteric reflux	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.00% 0/234 • Baseline up to end of study (approximately 44 months)	4.5% 1/22 • Number of events 1 • Baseline up to end of study (approximately 44 months)
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.00% 0/234 • Baseline up to end of study (approximately 44 months)	4.5% 1/22 • Number of events 1 • Baseline up to end of study (approximately 44 months)

Other adverse events

Other adverse events
Measure	IAT: Ganciclovir/ Valganciclovir n=56 participants at risk Participants received ganciclovir intravenously or valganciclovir orally based on the the investigator's discretion for the 8 week treatment period.	IAT: Foscarnet n=47 participants at risk Participants received foscarnet intravenously based on investigator's discretion for the 8 week treatment period.	IAT: Cidofovir n=6 participants at risk Participants received cidofovir intravenously based on the investigator's discretion for the 8 week treatment period.	IAT: Foscarnet + Ganciclovir/ Valganciclovir n=7 participants at risk Participants received foscarnet intravenously in combination with ganciclovir intravenously or valganciclovir orally based on investigator's discretion for the 8 week treatment period.	Maribavir 400 mg n=234 participants at risk Participants received maribavir 400 mg (2\*200 mg tablets), orally, twice daily for the 8 week treatment period.	Maribavir Rescue Arm n=22 participants at risk Participants with clear evidence of virologic failure (not just intolerance) after a minimum of 3 weeks of therapy with IAT entered maribavir rescue arm and received maribavir 400 mg (2\*200 mg tablets), orally, twice daily for the 8 week treatment period.
Respiratory, thoracic and mediastinal disorders Tonsillar hypertrophy	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	16.7% 1/6 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.00% 0/234 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Infections and infestations Rhinovirus infection	3.6% 2/56 • Number of events 2 • Baseline up to end of study (approximately 44 months)	2.1% 1/47 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	3.0% 7/234 • Number of events 9 • Baseline up to end of study (approximately 44 months)	13.6% 3/22 • Number of events 3 • Baseline up to end of study (approximately 44 months)
Hepatobiliary disorders Cholelithiasis	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	14.3% 1/7 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/234 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Musculoskeletal and connective tissue disorders Osteopenia	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	14.3% 1/7 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/234 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Nervous system disorders Peripheral sensory neuropathy	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	14.3% 1/7 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.85% 2/234 • Number of events 2 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Nervous system disorders Tremor	7.1% 4/56 • Number of events 4 • Baseline up to end of study (approximately 44 months)	2.1% 1/47 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	14.3% 1/7 • Number of events 1 • Baseline up to end of study (approximately 44 months)	3.0% 7/234 • Number of events 7 • Baseline up to end of study (approximately 44 months)	4.5% 1/22 • Number of events 1 • Baseline up to end of study (approximately 44 months)
Respiratory, thoracic and mediastinal disorders Nasal congestion	3.6% 2/56 • Number of events 2 • Baseline up to end of study (approximately 44 months)	2.1% 1/47 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	14.3% 1/7 • Number of events 1 • Baseline up to end of study (approximately 44 months)	3.0% 7/234 • Number of events 8 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Hepatobiliary disorders Cholestasis	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	14.3% 1/7 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/234 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Immune system disorders Graft versus host disease	1.8% 1/56 • Number of events 3 • Baseline up to end of study (approximately 44 months)	6.4% 3/47 • Number of events 3 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.85% 2/234 • Number of events 2 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Immune system disorders Graft versus host disease in gastrointestinal tract	5.4% 3/56 • Number of events 3 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	2.6% 6/234 • Number of events 6 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Immune system disorders Transplant rejection	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	6.4% 3/47 • Number of events 3 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	3.4% 8/234 • Number of events 9 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Infections and infestations Cytomegalovirus infection	5.4% 3/56 • Number of events 3 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	5.6% 13/234 • Number of events 15 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Infections and infestations Nasopharyngitis	3.6% 2/56 • Number of events 2 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	5.1% 12/234 • Number of events 16 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Infections and infestations Oral candidiasis	5.4% 3/56 • Number of events 3 • Baseline up to end of study (approximately 44 months)	2.1% 1/47 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	3.0% 7/234 • Number of events 8 • Baseline up to end of study (approximately 44 months)	4.5% 1/22 • Number of events 1 • Baseline up to end of study (approximately 44 months)
Infections and infestations Oral herpes	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	16.7% 1/6 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	3.8% 9/234 • Number of events 10 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Infections and infestations Pneumonia	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	4.3% 2/47 • Number of events 2 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	5.1% 12/234 • Number of events 12 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Infections and infestations Systemic bacterial infection	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	16.7% 1/6 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.00% 0/234 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Infections and infestations Varicella zoster virus infection	1.8% 1/56 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	14.3% 1/7 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.85% 2/234 • Number of events 6 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Injury, poisoning and procedural complications Fall	5.4% 3/56 • Number of events 4 • Baseline up to end of study (approximately 44 months)	2.1% 1/47 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	3.8% 9/234 • Number of events 9 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Investigations Alanine aminotransferase increased	5.4% 3/56 • Number of events 3 • Baseline up to end of study (approximately 44 months)	2.1% 1/47 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	3.0% 7/234 • Number of events 7 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Investigations Aspartate aminotransferase increased	5.4% 3/56 • Number of events 3 • Baseline up to end of study (approximately 44 months)	2.1% 1/47 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	1.7% 4/234 • Number of events 4 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Investigations Blood urea increased	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	2.1% 1/47 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	14.3% 1/7 • Number of events 1 • Baseline up to end of study (approximately 44 months)	1.7% 4/234 • Number of events 4 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Investigations Transaminases increased	3.6% 2/56 • Number of events 2 • Baseline up to end of study (approximately 44 months)	6.4% 3/47 • Number of events 3 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	2.1% 5/234 • Number of events 5 • Baseline up to end of study (approximately 44 months)	4.5% 1/22 • Number of events 1 • Baseline up to end of study (approximately 44 months)
Investigations Weight decreased	3.6% 2/56 • Number of events 2 • Baseline up to end of study (approximately 44 months)	2.1% 1/47 • Number of events 1 • Baseline up to end of study (approximately 44 months)	16.7% 1/6 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	3.4% 8/234 • Number of events 12 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Metabolism and nutrition disorders Fluid overload	1.8% 1/56 • Number of events 1 • Baseline up to end of study (approximately 44 months)	2.1% 1/47 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	14.3% 1/7 • Number of events 1 • Baseline up to end of study (approximately 44 months)	1.7% 4/234 • Number of events 4 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Metabolism and nutrition disorders Hyperglycaemia	1.8% 1/56 • Number of events 1 • Baseline up to end of study (approximately 44 months)	2.1% 1/47 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	14.3% 1/7 • Number of events 1 • Baseline up to end of study (approximately 44 months)	3.0% 7/234 • Number of events 7 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Metabolism and nutrition disorders Hyperkalaemia	5.4% 3/56 • Number of events 3 • Baseline up to end of study (approximately 44 months)	4.3% 2/47 • Number of events 3 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	4.3% 10/234 • Number of events 11 • Baseline up to end of study (approximately 44 months)	4.5% 1/22 • Number of events 2 • Baseline up to end of study (approximately 44 months)
Musculoskeletal and connective tissue disorders Back pain	3.6% 2/56 • Number of events 2 • Baseline up to end of study (approximately 44 months)	4.3% 2/47 • Number of events 2 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	7.3% 17/234 • Number of events 22 • Baseline up to end of study (approximately 44 months)	4.5% 1/22 • Number of events 1 • Baseline up to end of study (approximately 44 months)
Blood and lymphatic system disorders Anaemia	12.5% 7/56 • Number of events 8 • Baseline up to end of study (approximately 44 months)	21.3% 10/47 • Number of events 12 • Baseline up to end of study (approximately 44 months)	16.7% 1/6 • Number of events 2 • Baseline up to end of study (approximately 44 months)	14.3% 1/7 • Number of events 1 • Baseline up to end of study (approximately 44 months)	13.2% 31/234 • Number of events 36 • Baseline up to end of study (approximately 44 months)	13.6% 3/22 • Number of events 3 • Baseline up to end of study (approximately 44 months)
Blood and lymphatic system disorders Leukopenia	12.5% 7/56 • Number of events 8 • Baseline up to end of study (approximately 44 months)	4.3% 2/47 • Number of events 2 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	14.3% 1/7 • Number of events 1 • Baseline up to end of study (approximately 44 months)	5.1% 12/234 • Number of events 15 • Baseline up to end of study (approximately 44 months)	18.2% 4/22 • Number of events 4 • Baseline up to end of study (approximately 44 months)
Blood and lymphatic system disorders Neutropenia	33.9% 19/56 • Number of events 41 • Baseline up to end of study (approximately 44 months)	17.0% 8/47 • Number of events 17 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	14.3% 1/7 • Number of events 2 • Baseline up to end of study (approximately 44 months)	16.2% 38/234 • Number of events 92 • Baseline up to end of study (approximately 44 months)	31.8% 7/22 • Number of events 13 • Baseline up to end of study (approximately 44 months)
Blood and lymphatic system disorders Thrombocytopenia	12.5% 7/56 • Number of events 8 • Baseline up to end of study (approximately 44 months)	4.3% 2/47 • Number of events 2 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	7.7% 18/234 • Number of events 19 • Baseline up to end of study (approximately 44 months)	4.5% 1/22 • Number of events 1 • Baseline up to end of study (approximately 44 months)
Gastrointestinal disorders Abdominal pain	7.1% 4/56 • Number of events 4 • Baseline up to end of study (approximately 44 months)	2.1% 1/47 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	28.6% 2/7 • Number of events 2 • Baseline up to end of study (approximately 44 months)	9.4% 22/234 • Number of events 26 • Baseline up to end of study (approximately 44 months)	4.5% 1/22 • Number of events 1 • Baseline up to end of study (approximately 44 months)
Gastrointestinal disorders Abdominal pain upper	10.7% 6/56 • Number of events 8 • Baseline up to end of study (approximately 44 months)	2.1% 1/47 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	14.3% 1/7 • Number of events 1 • Baseline up to end of study (approximately 44 months)	3.8% 9/234 • Number of events 9 • Baseline up to end of study (approximately 44 months)	4.5% 1/22 • Number of events 1 • Baseline up to end of study (approximately 44 months)
Gastrointestinal disorders Constipation	12.5% 7/56 • Number of events 7 • Baseline up to end of study (approximately 44 months)	4.3% 2/47 • Number of events 3 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	14.3% 1/7 • Number of events 2 • Baseline up to end of study (approximately 44 months)	6.0% 14/234 • Number of events 14 • Baseline up to end of study (approximately 44 months)	13.6% 3/22 • Number of events 4 • Baseline up to end of study (approximately 44 months)
Gastrointestinal disorders Diarrhoea	28.6% 16/56 • Number of events 18 • Baseline up to end of study (approximately 44 months)	21.3% 10/47 • Number of events 15 • Baseline up to end of study (approximately 44 months)	16.7% 1/6 • Number of events 2 • Baseline up to end of study (approximately 44 months)	14.3% 1/7 • Number of events 4 • Baseline up to end of study (approximately 44 months)	28.6% 67/234 • Number of events 92 • Baseline up to end of study (approximately 44 months)	45.5% 10/22 • Number of events 13 • Baseline up to end of study (approximately 44 months)
Gastrointestinal disorders Nausea	21.4% 12/56 • Number of events 17 • Baseline up to end of study (approximately 44 months)	34.0% 16/47 • Number of events 19 • Baseline up to end of study (approximately 44 months)	33.3% 2/6 • Number of events 2 • Baseline up to end of study (approximately 44 months)	28.6% 2/7 • Number of events 4 • Baseline up to end of study (approximately 44 months)	28.6% 67/234 • Number of events 88 • Baseline up to end of study (approximately 44 months)	22.7% 5/22 • Number of events 6 • Baseline up to end of study (approximately 44 months)
Gastrointestinal disorders Vomiting	23.2% 13/56 • Number of events 16 • Baseline up to end of study (approximately 44 months)	19.1% 9/47 • Number of events 10 • Baseline up to end of study (approximately 44 months)	16.7% 1/6 • Number of events 1 • Baseline up to end of study (approximately 44 months)	28.6% 2/7 • Number of events 2 • Baseline up to end of study (approximately 44 months)	19.7% 46/234 • Number of events 69 • Baseline up to end of study (approximately 44 months)	9.1% 2/22 • Number of events 3 • Baseline up to end of study (approximately 44 months)
General disorders Fatigue	17.9% 10/56 • Number of events 10 • Baseline up to end of study (approximately 44 months)	10.6% 5/47 • Number of events 5 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	14.3% 1/7 • Number of events 1 • Baseline up to end of study (approximately 44 months)	15.4% 36/234 • Number of events 38 • Baseline up to end of study (approximately 44 months)	13.6% 3/22 • Number of events 3 • Baseline up to end of study (approximately 44 months)
General disorders Oedema peripheral	8.9% 5/56 • Number of events 7 • Baseline up to end of study (approximately 44 months)	14.9% 7/47 • Number of events 10 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	28.6% 2/7 • Number of events 2 • Baseline up to end of study (approximately 44 months)	11.1% 26/234 • Number of events 27 • Baseline up to end of study (approximately 44 months)	13.6% 3/22 • Number of events 3 • Baseline up to end of study (approximately 44 months)
General disorders Pyrexia	21.4% 12/56 • Number of events 15 • Baseline up to end of study (approximately 44 months)	21.3% 10/47 • Number of events 11 • Baseline up to end of study (approximately 44 months)	33.3% 2/6 • Number of events 2 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	13.7% 32/234 • Number of events 48 • Baseline up to end of study (approximately 44 months)	22.7% 5/22 • Number of events 6 • Baseline up to end of study (approximately 44 months)
Infections and infestations Cytomegalovirus viraemia	8.9% 5/56 • Number of events 5 • Baseline up to end of study (approximately 44 months)	6.4% 3/47 • Number of events 3 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	28.6% 2/7 • Number of events 2 • Baseline up to end of study (approximately 44 months)	13.7% 32/234 • Number of events 33 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Investigations Blood creatinine increased	7.1% 4/56 • Number of events 4 • Baseline up to end of study (approximately 44 months)	8.5% 4/47 • Number of events 5 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	14.3% 1/7 • Number of events 1 • Baseline up to end of study (approximately 44 months)	7.7% 18/234 • Number of events 19 • Baseline up to end of study (approximately 44 months)	4.5% 1/22 • Number of events 1 • Baseline up to end of study (approximately 44 months)
Investigations Immunosuppressant drug level increased	3.6% 2/56 • Number of events 2 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	9.0% 21/234 • Number of events 23 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Metabolism and nutrition disorders Decreased appetite	12.5% 7/56 • Number of events 7 • Baseline up to end of study (approximately 44 months)	8.5% 4/47 • Number of events 4 • Baseline up to end of study (approximately 44 months)	16.7% 1/6 • Number of events 1 • Baseline up to end of study (approximately 44 months)	14.3% 1/7 • Number of events 1 • Baseline up to end of study (approximately 44 months)	9.8% 23/234 • Number of events 25 • Baseline up to end of study (approximately 44 months)	13.6% 3/22 • Number of events 3 • Baseline up to end of study (approximately 44 months)
Metabolism and nutrition disorders Hypokalaemia	5.4% 3/56 • Number of events 4 • Baseline up to end of study (approximately 44 months)	17.0% 8/47 • Number of events 12 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	14.3% 1/7 • Number of events 1 • Baseline up to end of study (approximately 44 months)	5.6% 13/234 • Number of events 16 • Baseline up to end of study (approximately 44 months)	9.1% 2/22 • Number of events 2 • Baseline up to end of study (approximately 44 months)
Metabolism and nutrition disorders Hypomagnesaemia	8.9% 5/56 • Number of events 7 • Baseline up to end of study (approximately 44 months)	19.1% 9/47 • Number of events 10 • Baseline up to end of study (approximately 44 months)	16.7% 1/6 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	6.0% 14/234 • Number of events 17 • Baseline up to end of study (approximately 44 months)	18.2% 4/22 • Number of events 4 • Baseline up to end of study (approximately 44 months)
Musculoskeletal and connective tissue disorders Arthralgia	5.4% 3/56 • Number of events 3 • Baseline up to end of study (approximately 44 months)	6.4% 3/47 • Number of events 3 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	6.8% 16/234 • Number of events 17 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Musculoskeletal and connective tissue disorders Pain in extremity	10.7% 6/56 • Number of events 6 • Baseline up to end of study (approximately 44 months)	2.1% 1/47 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	3.4% 8/234 • Number of events 8 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Nervous system disorders Dizziness	12.5% 7/56 • Number of events 7 • Baseline up to end of study (approximately 44 months)	4.3% 2/47 • Number of events 2 • Baseline up to end of study (approximately 44 months)	16.7% 1/6 • Number of events 1 • Baseline up to end of study (approximately 44 months)	28.6% 2/7 • Number of events 3 • Baseline up to end of study (approximately 44 months)	8.5% 20/234 • Number of events 23 • Baseline up to end of study (approximately 44 months)	4.5% 1/22 • Number of events 1 • Baseline up to end of study (approximately 44 months)
Nervous system disorders Dysgeusia	7.1% 4/56 • Number of events 4 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	16.7% 1/6 • Number of events 1 • Baseline up to end of study (approximately 44 months)	14.3% 1/7 • Number of events 1 • Baseline up to end of study (approximately 44 months)	37.6% 88/234 • Number of events 95 • Baseline up to end of study (approximately 44 months)	4.5% 1/22 • Number of events 1 • Baseline up to end of study (approximately 44 months)
Nervous system disorders Headache	16.1% 9/56 • Number of events 11 • Baseline up to end of study (approximately 44 months)	19.1% 9/47 • Number of events 10 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	42.9% 3/7 • Number of events 3 • Baseline up to end of study (approximately 44 months)	12.8% 30/234 • Number of events 34 • Baseline up to end of study (approximately 44 months)	9.1% 2/22 • Number of events 3 • Baseline up to end of study (approximately 44 months)
Nervous system disorders Taste disorder	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	2.1% 1/47 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	9.0% 21/234 • Number of events 21 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Renal and urinary disorders Acute kidney injury	5.4% 3/56 • Number of events 3 • Baseline up to end of study (approximately 44 months)	14.9% 7/47 • Number of events 9 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	11.1% 26/234 • Number of events 33 • Baseline up to end of study (approximately 44 months)	4.5% 1/22 • Number of events 1 • Baseline up to end of study (approximately 44 months)
Respiratory, thoracic and mediastinal disorders Cough	12.5% 7/56 • Number of events 7 • Baseline up to end of study (approximately 44 months)	8.5% 4/47 • Number of events 4 • Baseline up to end of study (approximately 44 months)	16.7% 1/6 • Number of events 1 • Baseline up to end of study (approximately 44 months)	14.3% 1/7 • Number of events 1 • Baseline up to end of study (approximately 44 months)	9.4% 22/234 • Number of events 28 • Baseline up to end of study (approximately 44 months)	22.7% 5/22 • Number of events 5 • Baseline up to end of study (approximately 44 months)
Respiratory, thoracic and mediastinal disorders Dyspnoea	7.1% 4/56 • Number of events 5 • Baseline up to end of study (approximately 44 months)	8.5% 4/47 • Number of events 4 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	9.8% 23/234 • Number of events 24 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Vascular disorders Hypertension	3.6% 2/56 • Number of events 2 • Baseline up to end of study (approximately 44 months)	12.8% 6/47 • Number of events 7 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	14.3% 1/7 • Number of events 1 • Baseline up to end of study (approximately 44 months)	6.4% 15/234 • Number of events 15 • Baseline up to end of study (approximately 44 months)	4.5% 1/22 • Number of events 2 • Baseline up to end of study (approximately 44 months)
Blood and lymphatic system disorders Lymphadenopathy	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	16.7% 1/6 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.00% 0/234 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Endocrine disorders Adrenal insufficiency	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	14.3% 1/7 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.43% 1/234 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Eye disorders Cataract	3.6% 2/56 • Number of events 2 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	14.3% 1/7 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.85% 2/234 • Number of events 2 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Eye disorders Chorioretinopathy	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	14.3% 1/7 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/234 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Eye disorders Dry eye	1.8% 1/56 • Number of events 1 • Baseline up to end of study (approximately 44 months)	2.1% 1/47 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	14.3% 1/7 • Number of events 1 • Baseline up to end of study (approximately 44 months)	3.0% 7/234 • Number of events 8 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Eye disorders Pterygium	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	14.3% 1/7 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/234 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Eye disorders Vision blurred	1.8% 1/56 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	42.9% 3/7 • Number of events 4 • Baseline up to end of study (approximately 44 months)	1.7% 4/234 • Number of events 4 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Gastrointestinal disorders Abdominal pain lower	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	4.3% 2/47 • Number of events 2 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	14.3% 1/7 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.43% 1/234 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Gastrointestinal disorders Dry mouth	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	2.1% 1/47 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	14.3% 1/7 • Number of events 1 • Baseline up to end of study (approximately 44 months)	4.3% 10/234 • Number of events 11 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Gastrointestinal disorders Odynophagia	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	16.7% 1/6 • Number of events 1 • Baseline up to end of study (approximately 44 months)	14.3% 1/7 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.43% 1/234 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
General disorders Chills	1.8% 1/56 • Number of events 1 • Baseline up to end of study (approximately 44 months)	2.1% 1/47 • Number of events 1 • Baseline up to end of study (approximately 44 months)	16.7% 1/6 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.85% 2/234 • Number of events 2 • Baseline up to end of study (approximately 44 months)	4.5% 1/22 • Number of events 1 • Baseline up to end of study (approximately 44 months)
General disorders Gait disturbance	1.8% 1/56 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	14.3% 1/7 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/234 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
General disorders Temperature intolerance	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	14.3% 1/7 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/234 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Infections and infestations BK virus infection	1.8% 1/56 • Number of events 1 • Baseline up to end of study (approximately 44 months)	4.3% 2/47 • Number of events 2 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	14.3% 1/7 • Number of events 1 • Baseline up to end of study (approximately 44 months)	3.0% 7/234 • Number of events 8 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Infections and infestations Conjunctivitis	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	14.3% 1/7 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.85% 2/234 • Number of events 2 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Infections and infestations Cytomegalovirus infection reactivation	7.1% 4/56 • Number of events 5 • Baseline up to end of study (approximately 44 months)	4.3% 2/47 • Number of events 2 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	10.7% 25/234 • Number of events 30 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Infections and infestations Influenza	1.8% 1/56 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	16.7% 1/6 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.43% 1/234 • Number of events 1 • Baseline up to end of study (approximately 44 months)	4.5% 1/22 • Number of events 1 • Baseline up to end of study (approximately 44 months)
Infections and infestations Upper respiratory tract infection	7.1% 4/56 • Number of events 4 • Baseline up to end of study (approximately 44 months)	2.1% 1/47 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	14.3% 1/7 • Number of events 1 • Baseline up to end of study (approximately 44 months)	5.6% 13/234 • Number of events 16 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Infections and infestations Urinary tract infection	7.1% 4/56 • Number of events 4 • Baseline up to end of study (approximately 44 months)	8.5% 4/47 • Number of events 4 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	5.1% 12/234 • Number of events 13 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Investigations Blood calcium decreased	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	14.3% 1/7 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/234 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Investigations Blood magnesium decreased	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	2.1% 1/47 • Number of events 1 • Baseline up to end of study (approximately 44 months)	16.7% 1/6 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.43% 1/234 • Number of events 1 • Baseline up to end of study (approximately 44 months)	4.5% 1/22 • Number of events 1 • Baseline up to end of study (approximately 44 months)
Investigations Blood phosphorus decreased	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	2.1% 1/47 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	14.3% 1/7 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/234 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Investigations Clostridium test positive	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	2.1% 1/47 • Number of events 1 • Baseline up to end of study (approximately 44 months)	16.7% 1/6 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.00% 0/234 • Baseline up to end of study (approximately 44 months)	4.5% 1/22 • Number of events 1 • Baseline up to end of study (approximately 44 months)
Investigations Liver function test increased	1.8% 1/56 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	16.7% 1/6 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.43% 1/234 • Number of events 1 • Baseline up to end of study (approximately 44 months)	4.5% 1/22 • Number of events 1 • Baseline up to end of study (approximately 44 months)
Investigations Platelet count decreased	7.1% 4/56 • Number of events 5 • Baseline up to end of study (approximately 44 months)	2.1% 1/47 • Number of events 4 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	2.1% 5/234 • Number of events 6 • Baseline up to end of study (approximately 44 months)	4.5% 1/22 • Number of events 1 • Baseline up to end of study (approximately 44 months)
Investigations White blood cell count decreased	3.6% 2/56 • Number of events 2 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	16.7% 1/6 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.85% 2/234 • Number of events 2 • Baseline up to end of study (approximately 44 months)	9.1% 2/22 • Number of events 2 • Baseline up to end of study (approximately 44 months)
Metabolism and nutrition disorders Hypocalcaemia	3.6% 2/56 • Number of events 2 • Baseline up to end of study (approximately 44 months)	10.6% 5/47 • Number of events 5 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.00% 0/234 • Baseline up to end of study (approximately 44 months)	9.1% 2/22 • Number of events 2 • Baseline up to end of study (approximately 44 months)
Metabolism and nutrition disorders Hypophosphataemia	5.4% 3/56 • Number of events 3 • Baseline up to end of study (approximately 44 months)	12.8% 6/47 • Number of events 10 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	1.7% 4/234 • Number of events 4 • Baseline up to end of study (approximately 44 months)	9.1% 2/22 • Number of events 2 • Baseline up to end of study (approximately 44 months)
Musculoskeletal and connective tissue disorders Muscle spasms	1.8% 1/56 • Number of events 1 • Baseline up to end of study (approximately 44 months)	6.4% 3/47 • Number of events 3 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	14.3% 1/7 • Number of events 1 • Baseline up to end of study (approximately 44 months)	3.0% 7/234 • Number of events 7 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Musculoskeletal and connective tissue disorders Myalgia	1.8% 1/56 • Number of events 1 • Baseline up to end of study (approximately 44 months)	4.3% 2/47 • Number of events 2 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	14.3% 1/7 • Number of events 1 • Baseline up to end of study (approximately 44 months)	1.3% 3/234 • Number of events 3 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Nervous system disorders Aura	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	14.3% 1/7 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/234 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Nervous system disorders Paraesthesia	1.8% 1/56 • Number of events 1 • Baseline up to end of study (approximately 44 months)	10.6% 5/47 • Number of events 6 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	14.3% 1/7 • Number of events 1 • Baseline up to end of study (approximately 44 months)	2.6% 6/234 • Number of events 6 • Baseline up to end of study (approximately 44 months)	4.5% 1/22 • Number of events 1 • Baseline up to end of study (approximately 44 months)
Nervous system disorders Peroneal nerve palsy	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	16.7% 1/6 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.00% 0/234 • Baseline up to end of study (approximately 44 months)	4.5% 1/22 • Number of events 1 • Baseline up to end of study (approximately 44 months)
Psychiatric disorders Anxiety	3.6% 2/56 • Number of events 2 • Baseline up to end of study (approximately 44 months)	2.1% 1/47 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	14.3% 1/7 • Number of events 1 • Baseline up to end of study (approximately 44 months)	3.0% 7/234 • Number of events 7 • Baseline up to end of study (approximately 44 months)	4.5% 1/22 • Number of events 1 • Baseline up to end of study (approximately 44 months)
Psychiatric disorders Insomnia	3.6% 2/56 • Number of events 2 • Baseline up to end of study (approximately 44 months)	6.4% 3/47 • Number of events 3 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	1.7% 4/234 • Number of events 4 • Baseline up to end of study (approximately 44 months)	4.5% 1/22 • Number of events 1 • Baseline up to end of study (approximately 44 months)
Renal and urinary disorders Dysuria	3.6% 2/56 • Number of events 2 • Baseline up to end of study (approximately 44 months)	8.5% 4/47 • Number of events 4 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	2.6% 6/234 • Number of events 7 • Baseline up to end of study (approximately 44 months)	4.5% 1/22 • Number of events 1 • Baseline up to end of study (approximately 44 months)
Renal and urinary disorders Micturition urgency	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	6.4% 3/47 • Number of events 3 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.43% 1/234 • Number of events 2 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Renal and urinary disorders Pollakiuria	1.8% 1/56 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	14.3% 1/7 • Number of events 2 • Baseline up to end of study (approximately 44 months)	1.3% 3/234 • Number of events 4 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Renal and urinary disorders Proteinuria	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	2.1% 1/47 • Number of events 1 • Baseline up to end of study (approximately 44 months)	16.7% 1/6 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.85% 2/234 • Number of events 2 • Baseline up to end of study (approximately 44 months)	9.1% 2/22 • Number of events 2 • Baseline up to end of study (approximately 44 months)
Renal and urinary disorders Renal failure	1.8% 1/56 • Number of events 1 • Baseline up to end of study (approximately 44 months)	2.1% 1/47 • Number of events 1 • Baseline up to end of study (approximately 44 months)	16.7% 1/6 • Number of events 1 • Baseline up to end of study (approximately 44 months)	28.6% 2/7 • Number of events 2 • Baseline up to end of study (approximately 44 months)	1.3% 3/234 • Number of events 3 • Baseline up to end of study (approximately 44 months)	9.1% 2/22 • Number of events 2 • Baseline up to end of study (approximately 44 months)
Renal and urinary disorders Renal impairment	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	6.4% 3/47 • Number of events 4 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.43% 1/234 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Respiratory, thoracic and mediastinal disorders Epistaxis	8.9% 5/56 • Number of events 5 • Baseline up to end of study (approximately 44 months)	6.4% 3/47 • Number of events 3 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	1.7% 4/234 • Number of events 6 • Baseline up to end of study (approximately 44 months)	4.5% 1/22 • Number of events 1 • Baseline up to end of study (approximately 44 months)
Skin and subcutaneous tissue disorders Nail disorder	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	16.7% 1/6 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.00% 0/234 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Skin and subcutaneous tissue disorders Rash erythematous	1.8% 1/56 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	16.7% 1/6 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	1.3% 3/234 • Number of events 4 • Baseline up to end of study (approximately 44 months)	4.5% 1/22 • Number of events 1 • Baseline up to end of study (approximately 44 months)
Vascular disorders Hypotension	7.1% 4/56 • Number of events 4 • Baseline up to end of study (approximately 44 months)	4.3% 2/47 • Number of events 2 • Baseline up to end of study (approximately 44 months)	16.7% 1/6 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	4.7% 11/234 • Number of events 13 • Baseline up to end of study (approximately 44 months)	4.5% 1/22 • Number of events 1 • Baseline up to end of study (approximately 44 months)
Cardiac disorders Atrial flutter	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	14.3% 1/7 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/234 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Ear and labyrinth disorders Ear congestion	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	14.3% 1/7 • Number of events 2 • Baseline up to end of study (approximately 44 months)	0.00% 0/234 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Endocrine disorders Thyroiditis	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	16.7% 1/6 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.00% 0/234 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Eye disorders Periorbital oedema	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	2.1% 1/47 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	28.6% 2/7 • Number of events 2 • Baseline up to end of study (approximately 44 months)	0.00% 0/234 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Gastrointestinal disorders Abdominal distension	1.8% 1/56 • Number of events 1 • Baseline up to end of study (approximately 44 months)	2.1% 1/47 • Number of events 2 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	14.3% 1/7 • Number of events 1 • Baseline up to end of study (approximately 44 months)	3.0% 7/234 • Number of events 9 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
Gastrointestinal disorders Appendix disorder	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	16.7% 1/6 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	0.00% 0/234 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
General disorders Asthenia	5.4% 3/56 • Number of events 3 • Baseline up to end of study (approximately 44 months)	6.4% 3/47 • Number of events 3 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	0.00% 0/7 • Baseline up to end of study (approximately 44 months)	7.3% 17/234 • Number of events 20 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)
General disorders Device related thrombosis	0.00% 0/56 • Baseline up to end of study (approximately 44 months)	0.00% 0/47 • Baseline up to end of study (approximately 44 months)	0.00% 0/6 • Baseline up to end of study (approximately 44 months)	14.3% 1/7 • Number of events 1 • Baseline up to end of study (approximately 44 months)	0.00% 0/234 • Baseline up to end of study (approximately 44 months)	0.00% 0/22 • Baseline up to end of study (approximately 44 months)

Additional Information

Study Director

Shire

Phone: +1 866 842 5335

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee If a multicenter publication is not submitted within twelve (12) months after conclusion, abandonment or termination of the Study at all sites, or after Sponsor confirms there shall be no multicenter Study publication, the Institution and/or such Principal Investigator may publish the results from the Institution site individually.
Publication restrictions are in place

Restriction type: OTHER