Letermovir (MK-8228) Versus Placebo in the Prevention of... | NCT02137772

ID	Type	Description	Link
2013-003831-31	EudraCT Number
152923	Registry Identifier	JAPIC-CTI

Label	Type	Description	Intervention Names
Letermovir	Experimental	Letermovir oral or intravenous (IV) formulation was administered once daily for up to 14 weeks, beginning up to Day 28 days post-transplant. The dose was 240 mg once daily for participants receiving concomitant cyclosporin A and 480 mg once daily for participants not receiving cyclosporin A. Intravenous infusion was administered only to participants who are unable to swallow tablets or who have a condition that may interfere with absorption of the tablets.	Drug: Letermovir
Placebo	Placebo Comparator	Placebo oral or IV formulation was administered once daily for up to 14 weeks, beginning up to Day 28 post-transplant. The number of placebo tablets was to mimic that for letermovir administration according to the concomitant cyclosporin A status. Intravenous infusion was administered only to participants who are unable to swallow tablets or who have a condition that may interfere with absorption of the tablets.	Drug: Placebo

Name	Type	Description	Arm Group Labels	Other Names
Letermovir	Drug	Letermovir 240 mg / 480 mg tablets, or 240 mg / 480 mg intravenous solution in 250 mL to be infused over 60 minutes.	Letermovir

Measure	Description	Time Frame
Percentage of Participants With Clinically-significant CMV Infection up to Week 24 Post-transplant	Clinically-significant CMV infection was defined as either one of the following: 1) onset of CMV end-organ disease, or 2) initiation of anti-CMV pre-emptive therapy based on documented CMV viremia and the clinical condition of the participant. The percentage of participants with clinically-significant CMV infection was assessed.	Up to Week 24 post-transplant

Measure	Description	Time Frame
Time to Onset of Clinically-significant CMV Infection (Kaplan-Meier Estimate of Percentage of Participants With a Qualifying Event at Week 24 Post-transplant)	Clinically-significant CMV infection was defined as either one of the following: 1) onset of CMV end-organ disease, or 2) initiation of anti-CMV pre-emptive therapy based on documented CMV viremia and the clinical condition of the participant. Time to onset of clinically-significant CMV infection was defined from the day of transplantation to the day the participant developed clinically-significant CMV infection, and was analyzed by the Kaplan-Meier method. Participants were censored at the last assessment for participants who discontinued or did not develop clinically-significant CMV infection.

Measure	Description	Time Frame
Percentage of Participants With One or More Adverse Events up to Week 48 Post-transplant	An adverse event is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An adverse event can therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an adverse event.

Name	Affiliation	Role
Medical Director	Merck Sharp & Dohme LLC	Study Director

PubMed Identifier	Type	Citation	Retractions
34674258	Derived	Prohn M, Cho CR, Viberg A, Dykstra K, Davis C, Sabato P, Stone J, Badshah C, Murata Y, Leavitt R, Fancourt C, Macha S. Exposure-Response Analyses of Letermovir Following Oral and Intravenous Administration in Allogeneic Hematopoietic Cell Transplantation Recipients. Clin Pharmacol Ther. 2022 Feb;111(2):485-495. doi: 10.1002/cpt.2456. Epub 2021 Nov 29.
33440077

ID	Title	Description
FG000	Letermovir	Letermovir oral or intravenous (IV) formulation was administered once daily for up to 14 weeks, beginning up to Day 28 post-transplant. The dose was 240 mg once daily for participants receiving concomitant cyclosporin A and 480 mg once daily for participants not receiving cyclosporin A. Intravenous infusion was administered only to participants who are unable to swallow tablets or who have a condition that may interfere with absorption of the tablets.

ID	Title	Description
BG000	Letermovir	Letermovir oral or intravenous (IV) formulation was administered once daily for up to 14 weeks, beginning up to Day 28 post-transplant. The dose was 240 mg once daily for participants receiving concomitant cyclosporin A and 480 mg once daily for participants not receiving cyclosporin A. Intravenous infusion was administered only to participants who are unable to swallow tablets or who have a condition that may interfere with absorption of the tablets.
BG001	Placebo	Placebo oral or IV formulation was administered once daily for up to 14 weeks, beginning up to Day 28 post-transplant. The number of placebo tablets was to mimic that for letermovir administration according to the concomitant cyclosporin A status. Intravenous infusion was administered only to participants who are unable to swallow tablets or who have a condition that may interfere with absorption of the tablets.
BG002	Total	Total of all reporting groups

Units	Counts
Participants	BG000376 BG001194 BG002570

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Percentage of Participants With Clinically-significant CMV Infection up to Week 24 Post-transplant

The Full Analysis Set (FAS) was all randomized participants who received ≥1 dose of study drug and had no detectable CMV DNA on Day 1 (randomization). Participants who prematurely discontinued or had a missing outcome through the 24-week visit window were considered treatment failure (i.e. Non-completers equal failure [NC=F] approach was used).

Posted

Number

Percentage of participants

Up to Week 24 post-transplant

ID	Title	Description
OG000	Letermovir	Letermovir oral or intravenous (IV) formulation was administered once daily for up to 14 weeks, beginning up to Day 28 post-transplant. The dose was 240 mg once daily for participants receiving concomitant cyclosporin A and 480 mg once daily for participants not receiving cyclosporin A. Intravenous infusion was administered only to participants who are unable to swallow tablets or who have a condition that may interfere with absorption of the tablets.
OG001	Placebo	Placebo oral or IV formulation was administered once daily for up to 14 weeks, beginning up to Day 28 post-transplant. The number of placebo tablets was to mimic that for letermovir administration according to the concomitant cyclosporin A status. Intravenous infusion was administered only to participants who are unable to swallow tablets or who have a condition that may interfere with absorption of the tablets.

Units	Counts
Participants	OG000325 OG001170

Title

Denominators

Categories

Title	Measurements
	OG00037.5 OG00160.6

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		Mantel Haenszel	The Mantel Haenszel analysis was adjusted for sample size for each stratum (high or low risk for CMV reactivation)	<0.0001	A 1-sided p-value ≤0.0249 for the risk difference was used for declaring statistical significance	Risk Difference (RD)	-23.5			2-Sided	95	-32.5	-14.6					Superiority or Other (legacy)

Secondary

Time to Onset of Clinically-significant CMV Infection (Kaplan-Meier Estimate of Percentage of Participants With a Qualifying Event at Week 24 Post-transplant)

Clinically-significant CMV infection was defined as either one of the following: 1) onset of CMV end-organ disease, or 2) initiation of anti-CMV pre-emptive therapy based on documented CMV viremia and the clinical condition of the participant. Time to onset of clinically-significant CMV infection was defined from the day of transplantation to the day the participant developed clinically-significant CMV infection, and was analyzed by the Kaplan-Meier method. Participants were censored at the last assessment for participants who discontinued or did not develop clinically-significant CMV infection.

All randomized participants who received at least one dose of study drug and had no detectable CMV viral DNA on the day treatment was initiated.

Posted

Number

95% Confidence Interval

Percentage of participants

Up to Week 24 post-transplant

ID	Title	Description
OG000	Letermovir	Letermovir oral or intravenous (IV) formulation was administered once daily for up to 14 weeks, beginning up to Day 28 post-transplant. The dose was 240 mg once daily for participants receiving concomitant cyclosporin A and 480 mg once daily for participants not receiving cyclosporin A. Intravenous infusion was administered only to participants who are unable to swallow tablets or who have a condition that may interfere with absorption of the tablets.
OG001	Placebo

Secondary

Percentage of Participants With Clinically-significant CMV Infection up to Week 14 Post-transplant

The FAS was all randomized participants who received ≥1 dose of study drug and had no detectable CMV DNA on Day 1. Participants who prematurely discontinued or had a missing outcome through the 14-week visit window were considered treatment failure (i.e. NC=F approach was used).

Posted

Number

Percentage of participants

Up to Week 14 post-transplant

ID	Title	Description
OG000	Letermovir	Letermovir oral or intravenous (IV) formulation was administered once daily for up to 14 weeks, beginning up to Day 28 post-transplant. The dose was 240 mg once daily for participants receiving concomitant cyclosporin A and 480 mg once daily for participants not receiving cyclosporin A. Intravenous infusion was administered only to participants who are unable to swallow tablets or who have a condition that may interfere with absorption of the tablets.
OG001	Placebo	Placebo oral or IV formulation was administered once daily for up to 14 weeks, beginning up to Day 28 post-transplant. The number of placebo tablets was to mimic that for letermovir administration according to the concomitant cyclosporin A status. Intravenous infusion was administered only to participants who are unable to swallow tablets or who have a condition that may interfere with absorption of the tablets.

Secondary

Percentage of Participants With CMV End-organ Disease up to Week 24 Post-transplant

CMV end-organ disease met per-protocol diagnostic criteria for CMV-pneumonia, gastrointestinal disease, hepatitis, central nervous system disease, retinitis, nephritis, cystitis, myocarditis, pancreatitis, or other disease categories. Only Clinical Adjudication Committee-confirmed CMV end-organ disease was included in this analysis. The percentage of participants with CMV end-organ disease was assessed.

The FAS was all randomized participants who received ≥1 dose of study drug and had no detectable CMV DNA on Day 1. A participant with a missing value up to Week 24 was excluded from the analysis (i.e., Data as observed [DAO] approach was used).

Posted

Number

Percentage of participants

Up to Week 24 post-transplant

ID	Title	Description
OG000	Letermovir	Letermovir oral or intravenous (IV) formulation was administered once daily for up to 14 weeks, beginning up to Day 28 post-transplant. The dose was 240 mg once daily for participants receiving concomitant cyclosporin A and 480 mg once daily for participants not receiving cyclosporin A. Intravenous infusion was administered only to participants who are unable to swallow tablets or who have a condition that may interfere with absorption of the tablets.
OG001	Placebo	Placebo oral or IV formulation was administered once daily for up to 14 weeks, beginning up to Day 28 post-transplant. The number of placebo tablets was to mimic that for letermovir administration according to the concomitant cyclosporin A status. Intravenous infusion was administered only to participants who are unable to swallow tablets or who have a condition that may interfere with absorption of the tablets.

Secondary

Percentage of Participants With CMV End-organ Disease up to Week 14 Post-transplant

The FAS was all randomized participants who received ≥1 dose of study drug and had no detectable CMV DNA on Day 1. A participant with a missing value up to Week 14 was excluded from the analysis (i.e., Data as observed [DAO] approach was used).

Posted

Number

Percentage of participants

Up to Week 14 post-transplant

ID	Title	Description
OG000	Letermovir	Letermovir oral or intravenous (IV) formulation was administered once daily for up to 14 weeks, beginning up to Day 28 post-transplant. The dose was 240 mg once daily for participants receiving concomitant cyclosporin A and 480 mg once daily for participants not receiving cyclosporin A. Intravenous infusion was administered only to participants who are unable to swallow tablets or who have a condition that may interfere with absorption of the tablets.
OG001	Placebo	Placebo oral or IV formulation was administered once daily for up to 14 weeks, beginning up to Day 28 post-transplant. The number of placebo tablets was to mimic that for letermovir administration according to the concomitant cyclosporin A status. Intravenous infusion was administered only to participants who are unable to swallow tablets or who have a condition that may interfere with absorption of the tablets.

Secondary

Percentage of Participants With Pre-emptive Therapy for CMV Viremia up to Week 14 Post-transplant

Initiation of anti-CMV pre-emptive therapy was based on documented CMV viremia and the clinical condition of the participant. The percentage of participants with initiation of anti-CMV pre-emptive anti-CMV therapy was assessed.

Posted

Number

Percentage of participants

Up to Week 14 post-transplant

ID	Title	Description
OG000	Letermovir	Letermovir oral or intravenous (IV) formulation was administered once daily for up to 14 weeks, beginning up to Day 28 post-transplant. The dose was 240 mg once daily for participants receiving concomitant cyclosporin A and 480 mg once daily for participants not receiving cyclosporin A. Intravenous infusion was administered only to participants who are unable to swallow tablets or who have a condition that may interfere with absorption of the tablets.
OG001	Placebo	Placebo oral or IV formulation was administered once daily for up to 14 weeks, beginning up to Day 28 post-transplant. The number of placebo tablets was to mimic that for letermovir administration according to the concomitant cyclosporin A status. Intravenous infusion was administered only to participants who are unable to swallow tablets or who have a condition that may interfere with absorption of the tablets.

Secondary

Percentage of Participants With Pre-emptive Therapy for CMV Viremia up to Week 24 Post-transplant

The FAS was all randomized participants who received ≥1 dose of study drug and had no detectable CMV DNA on Day 1. Participants who prematurely discontinued or had a missing outcome through the 24-week visit window were considered treatment failure (i.e. NC=F approach was used).

Posted

Number

Percentage of participants

Up to Week 24 post-transplant

ID	Title	Description
OG000	Letermovir	Letermovir oral or intravenous (IV) formulation was administered once daily for up to 14 weeks, beginning up to Day 28 post-transplant. The dose was 240 mg once daily for participants receiving concomitant cyclosporin A and 480 mg once daily for participants not receiving cyclosporin A. Intravenous infusion was administered only to participants who are unable to swallow tablets or who have a condition that may interfere with absorption of the tablets.
OG001	Placebo	Placebo oral or IV formulation was administered once daily for up to 14 weeks, beginning up to Day 28 post-transplant. The number of placebo tablets was to mimic that for letermovir administration according to the concomitant cyclosporin A status. Intravenous infusion was administered only to participants who are unable to swallow tablets or who have a condition that may interfere with absorption of the tablets.

Secondary

Time to Initiation of Pre-emptive Therapy for CMV Viremia (Kaplan-Meier Estimate of Percentage of Participants With a Qualifying Event at Week 24 Post-transplant)

The need for anti-CMV pre-emptive therapy was based on documented CMV viremia and the clinical condition of the participant. The outcome was calculated from the day of transplantation to the start of anti-CMV pre-emptive therapy, and was analyzed by the Kaplan-Meier method. Participants were censored at the last assessment for participants who discontinued or did not initiate pre-emptive therapy.

All randomized participants who received at least one dose of study drug and had no detectable CMV viral DNA on the day treatment was initiated.

Posted

Number

95% Confidence Interval

Percentage of participants

Up to Week 24 post-transplant

ID	Title	Description
OG000	Letermovir	Letermovir oral or intravenous (IV) formulation was administered once daily for up to 14 weeks, beginning up to Day 28 post-transplant. The dose was 240 mg once daily for participants receiving concomitant cyclosporin A and 480 mg once daily for participants not receiving cyclosporin A. Intravenous infusion was administered only to participants who are unable to swallow tablets or who have a condition that may interfere with absorption of the tablets.
OG001	Placebo	Placebo oral or IV formulation was administered once daily for up to 14 weeks, beginning up to Day 28 post-transplant. The number of placebo tablets was to mimic that for letermovir administration according to the concomitant cyclosporin A status. Intravenous infusion was administered only to participants who are unable to swallow tablets or who have a condition that may interfere with absorption of the tablets.

Other Pre-specified

Percentage of Participants With One or More Adverse Events up to Week 48 Post-transplant

An adverse event is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An adverse event can therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an adverse event.

All randomized participants who received at least one dose of study medication

Posted

Number

Percentage of participants

Up to Week 48 post-transplant

ID	Title	Description
OG000	Letermovir	Letermovir oral or intravenous (IV) formulation was administered once daily for up to 14 weeks, beginning up to Day 28 post-transplant. The dose was 240 mg once daily for participants receiving concomitant cyclosporin A and 480 mg once daily for participants not receiving cyclosporin A. Intravenous infusion was administered only to participants who are unable to swallow tablets or who have a condition that may interfere with absorption of the tablets.
OG001	Placebo	Placebo oral or IV formulation was administered once daily for up to 14 weeks, beginning up to Day 28 post-transplant. The number of placebo tablets was to mimic that for letermovir administration according to the concomitant cyclosporin A status. Intravenous infusion was administered only to participants who are unable to swallow tablets or who have a condition that may interfere with absorption of the tablets.

Other Pre-specified

Percentage of Participants Discontinued From Study Medication Due to an Adverse Event

All randomized participants who received at least one dose of study medication

Posted

Number

Percentage of participants

Up to Week 14 post-transplant

ID	Title	Description
OG000	Letermovir	Letermovir oral or intravenous (IV) formulation was administered once daily for up to 14 weeks, beginning up to Day 28 post-transplant. The dose was 240 mg once daily for participants receiving concomitant cyclosporin A and 480 mg once daily for participants not receiving cyclosporin A. Intravenous infusion was administered only to participants who are unable to swallow tablets or who have a condition that may interfere with absorption of the tablets.
OG001	Placebo	Placebo oral or IV formulation was administered once daily for up to 14 weeks, beginning up to Day 28 post-transplant. The number of placebo tablets was to mimic that for letermovir administration according to the concomitant cyclosporin A status. Intravenous infusion was administered only to participants who are unable to swallow tablets or who have a condition that may interfere with absorption of the tablets.

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Agranulocytosis	Blood and lymphatic system disorders	MedDRA version 19.1	Systematic Assessment	EG0000 events0 affected373 at risk EG0011 events1 affected192 at risk
Anaemia	Blood and lymphatic system disorders	MedDRA version 19.1	Systematic Assessment	EG0002 events2 affected373 at risk EG0010 events0 affected192 at risk
Aplastic anaemia	Blood and lymphatic system disorders	MedDRA version 19.1	Systematic Assessment	EG0001 events1 affected373 at risk EG0010 events0 affected192 at risk
Autoimmune haemolytic anaemia	Blood and lymphatic system disorders	MedDRA version 19.1	Systematic Assessment	EG0001 events1 affected373 at risk EG0010 events0 affected192 at risk
Disseminated intravascular coagulation	Blood and lymphatic system disorders	MedDRA version 19.1	Systematic Assessment	EG0001 events1 affected373 at risk EG0010 events0 affected192 at risk
Febrile neutropenia	Blood and lymphatic system disorders	MedDRA version 19.1	Systematic Assessment	EG00010 events7 affected373 at risk EG0013 events3 affected192 at risk
Immune thrombocytopenic purpura	Blood and lymphatic system disorders	MedDRA version 19.1	Systematic Assessment	EG0000 events0 affected373 at risk EG0011 events1 affected192 at risk
Leukopenia	Blood and lymphatic system disorders	MedDRA version 19.1	Systematic Assessment	EG0001 events1 affected373 at risk EG0010 events0 affected192 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA version 19.1	Systematic Assessment	EG0001 events1 affected373 at risk EG0010 events0 affected192 at risk
Pancytopenia	Blood and lymphatic system disorders	MedDRA version 19.1	Systematic Assessment	EG0003 events3 affected373 at risk EG0010 events0 affected192 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA version 19.1	Systematic Assessment	EG0004 events4 affected373 at risk EG0011 events1 affected192 at risk
Arrhythmia	Cardiac disorders	MedDRA version 19.1	Systematic Assessment	EG0001 events1 affected373 at risk EG0010 events0 affected192 at risk
Atrial fibrillation	Cardiac disorders	MedDRA version 19.1	Systematic Assessment	EG0001 events1 affected373 at risk EG0010 events0 affected192 at risk
Atrial flutter	Cardiac disorders	MedDRA version 19.1	Systematic Assessment	EG0001 events1 affected373 at risk EG0010 events0 affected192 at risk
Cardiac arrest	Cardiac disorders	MedDRA version 19.1	Systematic Assessment	EG0000 events0 affected373 at risk EG0011 events1 affected192 at risk
Cardiac failure	Cardiac disorders	MedDRA version 19.1	Systematic Assessment	EG0001 events1 affected373 at risk EG0010 events0 affected192 at risk
Cardiogenic shock	Cardiac disorders	MedDRA version 19.1	Systematic Assessment	EG0000 events0 affected373 at risk EG0011 events1 affected192 at risk
Pericarditis	Cardiac disorders	MedDRA version 19.1	Systematic Assessment	EG0002 events1 affected373 at risk EG0010 events0 affected192 at risk
Sinus node dysfunction	Cardiac disorders	MedDRA version 19.1	Systematic Assessment	EG0001 events1 affected373 at risk EG0010 events0 affected192 at risk
Inappropriate antidiuretic hormone secretion	Endocrine disorders	MedDRA version 19.1	Systematic Assessment	EG0001 events1 affected373 at risk EG0010 events0 affected192 at risk
Colitis	Gastrointestinal disorders	MedDRA version 19.1	Systematic Assessment	EG0001 events1 affected373 at risk EG0010 events0 affected192 at risk
Constipation	Gastrointestinal disorders	MedDRA version 19.1	Systematic Assessment	EG0001 events1 affected373 at risk EG0010 events0 affected192 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA version 19.1	Systematic Assessment	EG0003 events3 affected373 at risk EG0015 events5 affected192 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA version 19.1	Systematic Assessment	EG0000 events0 affected373 at risk EG0011 events1 affected192 at risk
Food poisoning	Gastrointestinal disorders	MedDRA version 19.1	Systematic Assessment	EG0001 events1 affected373 at risk EG0010 events0 affected192 at risk
Gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA version 19.1	Systematic Assessment	EG0003 events3 affected373 at risk EG0010 events0 affected192 at risk
Intestinal ischaemia	Gastrointestinal disorders	MedDRA version 19.1	Systematic Assessment	EG0000 events0 affected373 at risk EG0011 events1 affected192 at risk
Lower gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA version 19.1	Systematic Assessment	EG0001 events1 affected373 at risk EG0010 events0 affected192 at risk
Nausea	Gastrointestinal disorders	MedDRA version 19.1	Systematic Assessment	EG0002 events2 affected373 at risk EG0011 events1 affected192 at risk
Pancreatitis	Gastrointestinal disorders	MedDRA version 19.1	Systematic Assessment	EG0001 events1 affected373 at risk EG0010 events0 affected192 at risk
Stomatitis haemorrhagic	Gastrointestinal disorders	MedDRA version 19.1	Systematic Assessment	EG0001 events1 affected373 at risk EG0010 events0 affected192 at risk
Upper gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA version 19.1	Systematic Assessment	EG0001 events1 affected373 at risk EG0010 events0 affected192 at risk
Vomiting	Gastrointestinal disorders	MedDRA version 19.1	Systematic Assessment	EG0003 events3 affected373 at risk EG0011 events1 affected192 at risk
Chest pain	General disorders	MedDRA version 19.1	Systematic Assessment	EG0002 events1 affected373 at risk EG0011 events1 affected192 at risk
Gait disturbance	General disorders	MedDRA version 19.1	Systematic Assessment	EG0001 events1 affected373 at risk EG0010 events0 affected192 at risk
Generalised oedema	General disorders	MedDRA version 19.1	Systematic Assessment	EG0001 events1 affected373 at risk EG0010 events0 affected192 at risk
Malaise	General disorders	MedDRA version 19.1	Systematic Assessment	EG0001 events1 affected373 at risk EG0011 events1 affected192 at risk
Mucosal inflammation	General disorders	MedDRA version 19.1	Systematic Assessment	EG0002 events2 affected373 at risk EG0010 events0 affected192 at risk
Multiple organ dysfunction syndrome	General disorders	MedDRA version 19.1	Systematic Assessment	EG0002 events2 affected373 at risk EG0014 events4 affected192 at risk
Pyrexia	General disorders	MedDRA version 19.1	Systematic Assessment	EG00012 events10 affected373 at risk EG0014 events4 affected192 at risk
Acute hepatic failure	Hepatobiliary disorders	MedDRA version 19.1	Systematic Assessment	EG0001 events1 affected373 at risk EG0010 events0 affected192 at risk
Hepatic cirrhosis	Hepatobiliary disorders	MedDRA version 19.1	Systematic Assessment	EG0001 events1 affected373 at risk EG0010 events0 affected192 at risk
Hepatic function abnormal	Hepatobiliary disorders	MedDRA version 19.1	Systematic Assessment	EG0002 events2 affected373 at risk EG0012 events2 affected192 at risk
Hyperbilirubinaemia	Hepatobiliary disorders	MedDRA version 19.1	Systematic Assessment	EG0001 events1 affected373 at risk EG0010 events0 affected192 at risk
Venoocclusive liver disease	Hepatobiliary disorders	MedDRA version 19.1	Systematic Assessment	EG0002 events2 affected373 at risk EG0013 events3 affected192 at risk
Anaphylactic reaction	Immune system disorders	MedDRA version 19.1	Systematic Assessment	EG0000 events0 affected373 at risk EG0011 events1 affected192 at risk
Drug hypersensitivity	Immune system disorders	MedDRA version 19.1	Systematic Assessment	EG0001 events1 affected373 at risk EG0011 events1 affected192 at risk
Graft versus host disease	Immune system disorders	MedDRA version 19.1	Systematic Assessment	EG00049 events45 affected373 at risk EG00131 events29 affected192 at risk
Transplant rejection	Immune system disorders	MedDRA version 19.1	Systematic Assessment	EG0000 events0 affected373 at risk EG0011 events1 affected192 at risk
Acute sinusitis	Infections and infestations	MedDRA version 19.1	Systematic Assessment	EG0001 events1 affected373 at risk EG0011 events1 affected192 at risk
Adenoviral haemorrhagic cystitis	Infections and infestations	MedDRA version 19.1	Systematic Assessment	EG0000 events0 affected373 at risk EG0011 events1 affected192 at risk
Aspergillus infection	Infections and infestations	MedDRA version 19.1	Systematic Assessment	EG0001 events1 affected373 at risk EG0012 events2 affected192 at risk
Atypical pneumonia	Infections and infestations	MedDRA version 19.1	Systematic Assessment	EG0001 events1 affected373 at risk EG0010 events0 affected192 at risk
Bacteraemia	Infections and infestations	MedDRA version 19.1	Systematic Assessment	EG0002 events2 affected373 at risk EG0011 events1 affected192 at risk
BK virus infection	Infections and infestations	MedDRA version 19.1	Systematic Assessment	EG0001 events1 affected373 at risk EG0010 events0 affected192 at risk
Bacterial sepsis	Infections and infestations	MedDRA version 19.1	Systematic Assessment	EG0000 events0 affected373 at risk EG0011 events1 affected192 at risk
Bronchiolitis	Infections and infestations	MedDRA version 19.1	Systematic Assessment	EG0001 events1 affected373 at risk EG0010 events0 affected192 at risk
Bronchitis	Infections and infestations	MedDRA version 19.1	Systematic Assessment	EG0001 events1 affected373 at risk EG0010 events0 affected192 at risk
Bronchopulmonary aspergillosis	Infections and infestations	MedDRA version 19.1	Systematic Assessment	EG0004 events4 affected373 at risk EG0011 events1 affected192 at risk
Cellulitis	Infections and infestations	MedDRA version 19.1	Systematic Assessment	EG0003 events3 affected373 at risk EG0010 events0 affected192 at risk
Cellulitis orbital	Infections and infestations	MedDRA version 19.1	Systematic Assessment	EG0002 events1 affected373 at risk EG0010 events0 affected192 at risk
Cerebral toxoplasmosis	Infections and infestations	MedDRA version 19.1	Systematic Assessment	EG0000 events0 affected373 at risk EG0011 events1 affected192 at risk
Clostridium bacteraemia	Infections and infestations	MedDRA version 19.1	Systematic Assessment	EG0001 events1 affected373 at risk EG0010 events0 affected192 at risk
Clostridium difficile colitis	Infections and infestations	MedDRA version 19.1	Systematic Assessment	EG0003 events3 affected373 at risk EG0011 events1 affected192 at risk
Clostridium difficile infection	Infections and infestations	MedDRA version 19.1	Systematic Assessment	EG0000 events0 affected373 at risk EG0012 events2 affected192 at risk
Cystitis viral	Infections and infestations	MedDRA version 19.1	Systematic Assessment	EG0001 events1 affected373 at risk EG0012 events2 affected192 at risk
Cytomegalovirus infection	Infections and infestations	MedDRA version 19.1	Systematic Assessment	EG00015 events14 affected373 at risk EG00115 events15 affected192 at risk
Cytomegalovirus viraemia	Infections and infestations	MedDRA version 19.1	Systematic Assessment	EG0001 events1 affected373 at risk EG0010 events0 affected192 at risk
Diverticulitis	Infections and infestations	MedDRA version 19.1	Systematic Assessment	EG0001 events1 affected373 at risk EG0010 events0 affected192 at risk
Enterococcal bacteraemia	Infections and infestations	MedDRA version 19.1	Systematic Assessment	EG0001 events1 affected373 at risk EG0011 events1 affected192 at risk
Epstein-Barr viraemia	Infections and infestations	MedDRA version 19.1	Systematic Assessment	EG0001 events1 affected373 at risk EG0011 events1 affected192 at risk
Epstein-Barr virus infection	Infections and infestations	MedDRA version 19.1	Systematic Assessment	EG0003 events3 affected373 at risk EG0010 events0 affected192 at risk
Escherichia bacteraemia	Infections and infestations	MedDRA version 19.1	Systematic Assessment	EG0001 events1 affected373 at risk EG0011 events1 affected192 at risk
Escherichia sepsis	Infections and infestations	MedDRA version 19.1	Systematic Assessment	EG0000 events0 affected373 at risk EG0011 events1 affected192 at risk
Escherichia urinary tract infection	Infections and infestations	MedDRA version 19.1	Systematic Assessment	EG0001 events1 affected373 at risk EG0010 events0 affected192 at risk
Fusarium infection	Infections and infestations	MedDRA version 19.1	Systematic Assessment	EG0001 events1 affected373 at risk EG0010 events0 affected192 at risk
Gastroenteritis	Infections and infestations	MedDRA version 19.1	Systematic Assessment	EG0002 events2 affected373 at risk EG0011 events1 affected192 at risk
Gastroenteritis adenovirus	Infections and infestations	MedDRA version 19.1	Systematic Assessment	EG0000 events0 affected373 at risk EG0011 events1 affected192 at risk
Gastroenteritis norovirus	Infections and infestations	MedDRA version 19.1	Systematic Assessment	EG0001 events1 affected373 at risk EG0010 events0 affected192 at risk
Gastroenteritis rotavirus	Infections and infestations	MedDRA version 19.1	Systematic Assessment	EG0001 events1 affected373 at risk EG0010 events0 affected192 at risk
Gastroenteritis viral	Infections and infestations	MedDRA version 19.1	Systematic Assessment	EG0002 events2 affected373 at risk EG0010 events0 affected192 at risk
Gastrointestinal candidiasis	Infections and infestations	MedDRA version 19.1	Systematic Assessment	EG0001 events1 affected373 at risk EG0010 events0 affected192 at risk
Herpes zoster	Infections and infestations	MedDRA version 19.1	Systematic Assessment	EG0002 events2 affected373 at risk EG0010 events0 affected192 at risk
Implant site cellulitis	Infections and infestations	MedDRA version 19.1	Systematic Assessment	EG0001 events1 affected373 at risk EG0010 events0 affected192 at risk
Infection	Infections and infestations	MedDRA version 19.1	Systematic Assessment	EG0001 events1 affected373 at risk EG0010 events0 affected192 at risk
Klebsiella infection	Infections and infestations	MedDRA version 19.1	Systematic Assessment	EG0001 events1 affected373 at risk EG0010 events0 affected192 at risk
Klebsiella sepsis	Infections and infestations	MedDRA version 19.1	Systematic Assessment	EG0001 events1 affected373 at risk EG0010 events0 affected192 at risk
Meningitis aseptic	Infections and infestations	MedDRA version 19.1	Systematic Assessment	EG0001 events1 affected373 at risk EG0010 events0 affected192 at risk
Meningitis bacterial	Infections and infestations	MedDRA version 19.1	Systematic Assessment	EG0001 events1 affected373 at risk EG0010 events0 affected192 at risk
Meningoencephalitis herpetic	Infections and infestations	MedDRA version 19.1	Systematic Assessment	EG0001 events1 affected373 at risk EG0011 events1 affected192 at risk
Meningoencephalitis viral	Infections and infestations	MedDRA version 19.1	Systematic Assessment	EG0000 events0 affected373 at risk EG0011 events1 affected192 at risk
Mucormycosis	Infections and infestations	MedDRA version 19.1	Systematic Assessment	EG0002 events1 affected373 at risk EG0011 events1 affected192 at risk
Nasopharyngitis	Infections and infestations	MedDRA version 19.1	Systematic Assessment	EG0001 events1 affected373 at risk EG0010 events0 affected192 at risk
Neutropenic sepsis	Infections and infestations	MedDRA version 19.1	Systematic Assessment	EG0001 events1 affected373 at risk EG0010 events0 affected192 at risk
Oesophageal candidiasis	Infections and infestations	MedDRA version 19.1	Systematic Assessment	EG0001 events1 affected373 at risk EG0010 events0 affected192 at risk
Otitis media acute	Infections and infestations	MedDRA version 19.1	Systematic Assessment	EG0001 events1 affected373 at risk EG0010 events0 affected192 at risk
Parainfluenzae virus infection	Infections and infestations	MedDRA version 19.1	Systematic Assessment	EG0001 events1 affected373 at risk EG0010 events0 affected192 at risk
Periorbital cellulitis	Infections and infestations	MedDRA version 19.1	Systematic Assessment	EG0001 events1 affected373 at risk EG0010 events0 affected192 at risk
Pharyngitis	Infections and infestations	MedDRA version 19.1	Systematic Assessment	EG0001 events1 affected373 at risk EG0010 events0 affected192 at risk
Pilonidal cyst	Infections and infestations	MedDRA version 19.1	Systematic Assessment	EG0001 events1 affected373 at risk EG0010 events0 affected192 at risk
Pneumocystis jirovecii pneumonia	Infections and infestations	MedDRA version 19.1	Systematic Assessment	EG0000 events0 affected373 at risk EG0011 events1 affected192 at risk
Pneumonia	Infections and infestations	MedDRA version 19.1	Systematic Assessment	EG00015 events15 affected373 at risk EG0016 events6 affected192 at risk
Pneumonia adenoviral	Infections and infestations	MedDRA version 19.1	Systematic Assessment	EG0001 events1 affected373 at risk EG0010 events0 affected192 at risk
Pneumonia bacterial	Infections and infestations	MedDRA version 19.1	Systematic Assessment	EG0003 events3 affected373 at risk EG0011 events1 affected192 at risk
Pneumonia parainfluenzae viral	Infections and infestations	MedDRA version 19.1	Systematic Assessment	EG0001 events1 affected373 at risk EG0010 events0 affected192 at risk
Pneumonia respiratory syncytial viral	Infections and infestations	MedDRA version 19.1	Systematic Assessment	EG0001 events1 affected373 at risk EG0010 events0 affected192 at risk
Pneumonia staphylococcal	Infections and infestations	MedDRA version 19.1	Systematic Assessment	EG0000 events0 affected373 at risk EG0011 events1 affected192 at risk
Pneumonia viral	Infections and infestations	MedDRA version 19.1	Systematic Assessment	EG0001 events1 affected373 at risk EG0010 events0 affected192 at risk
Pseudomonas bronchitis	Infections and infestations	MedDRA version 19.1	Systematic Assessment	EG0001 events1 affected373 at risk EG0010 events0 affected192 at risk
Pulmonary tuberculosis	Infections and infestations	MedDRA version 19.1	Systematic Assessment	EG0000 events0 affected373 at risk EG0011 events1 affected192 at risk
Respiratory tract infection	Infections and infestations	MedDRA version 19.1	Systematic Assessment	EG0001 events1 affected373 at risk EG0010 events0 affected192 at risk
Respiratory tract infection viral	Infections and infestations	MedDRA version 19.1	Systematic Assessment	EG0001 events1 affected373 at risk EG0011 events1 affected192 at risk
Retinitis viral	Infections and infestations	MedDRA version 19.1	Systematic Assessment	EG0001 events1 affected373 at risk EG0010 events0 affected192 at risk
Rhinovirus infection	Infections and infestations	MedDRA version 19.1	Systematic Assessment	EG0002 events2 affected373 at risk EG0010 events0 affected192 at risk
Sepsis	Infections and infestations	MedDRA version 19.1	Systematic Assessment	EG0008 events8 affected373 at risk EG0014 events4 affected192 at risk
Septic shock	Infections and infestations	MedDRA version 19.1	Systematic Assessment	EG0005 events5 affected373 at risk EG0017 events7 affected192 at risk
Sinusitis	Infections and infestations	MedDRA version 19.1	Systematic Assessment	EG0004 events4 affected373 at risk EG0011 events1 affected192 at risk
Staphylococcal bacteraemia	Infections and infestations	MedDRA version 19.1	Systematic Assessment	EG0004 events4 affected373 at risk EG0012 events2 affected192 at risk
Staphylococcal infection	Infections and infestations	MedDRA version 19.1	Systematic Assessment	EG0001 events1 affected373 at risk EG0010 events0 affected192 at risk
Streptococcal bacteraemia	Infections and infestations	MedDRA version 19.1	Systematic Assessment	EG0001 events1 affected373 at risk EG0010 events0 affected192 at risk
Systemic candida	Infections and infestations	MedDRA version 19.1	Systematic Assessment	EG0001 events1 affected373 at risk EG0010 events0 affected192 at risk
Tonsillitis	Infections and infestations	MedDRA version 19.1	Systematic Assessment	EG0001 events1 affected373 at risk EG0010 events0 affected192 at risk
Tooth infection	Infections and infestations	MedDRA version 19.1	Systematic Assessment	EG0001 events1 affected373 at risk EG0010 events0 affected192 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA version 19.1	Systematic Assessment	EG0000 events0 affected373 at risk EG0011 events1 affected192 at risk
Upper respiratory tract infection bacterial	Infections and infestations	MedDRA version 19.1	Systematic Assessment	EG0001 events1 affected373 at risk EG0010 events0 affected192 at risk
Urinary tract infection	Infections and infestations	MedDRA version 19.1	Systematic Assessment	EG0004 events4 affected373 at risk EG0010 events0 affected192 at risk
Viraemia	Infections and infestations	MedDRA version 19.1	Systematic Assessment	EG0003 events3 affected373 at risk EG0013 events3 affected192 at risk
Viral haemorrhagic cystitis	Infections and infestations	MedDRA version 19.1	Systematic Assessment	EG0003 events3 affected373 at risk EG0010 events0 affected192 at risk
Viral infection	Infections and infestations	MedDRA version 19.1	Systematic Assessment	EG0001 events1 affected373 at risk EG0010 events0 affected192 at risk
Viral pharyngitis	Infections and infestations	MedDRA version 19.1	Systematic Assessment	EG0000 events0 affected373 at risk EG0011 events1 affected192 at risk
Viral upper respiratory tract infection	Infections and infestations	MedDRA version 19.1	Systematic Assessment	EG0000 events0 affected373 at risk EG0011 events1 affected192 at risk
Allergic transfusion reaction	Injury, poisoning and procedural complications	MedDRA version 19.1	Systematic Assessment	EG0000 events0 affected373 at risk EG0011 events1 affected192 at risk
Comminuted fracture	Injury, poisoning and procedural complications	MedDRA version 19.1	Systematic Assessment	EG0000 events0 affected373 at risk EG0011 events1 affected192 at risk
Delayed engraftment	Injury, poisoning and procedural complications	MedDRA version 19.1	Systematic Assessment	EG0001 events1 affected373 at risk EG0010 events0 affected192 at risk
Femur fracture	Injury, poisoning and procedural complications	MedDRA version 19.1	Systematic Assessment	EG0001 events1 affected373 at risk EG0011 events1 affected192 at risk
Fractured sacrum	Injury, poisoning and procedural complications	MedDRA version 19.1	Systematic Assessment	EG0000 events0 affected373 at risk EG0011 events1 affected192 at risk
Laceration	Injury, poisoning and procedural complications	MedDRA version 19.1	Systematic Assessment	EG0001 events1 affected373 at risk EG0010 events0 affected192 at risk
Subarachnoid haemorrhage	Injury, poisoning and procedural complications	MedDRA version 19.1	Systematic Assessment	EG0001 events1 affected373 at risk EG0011 events1 affected192 at risk
Subdural haematoma	Injury, poisoning and procedural complications	MedDRA version 19.1	Systematic Assessment	EG0000 events0 affected373 at risk EG0013 events3 affected192 at risk
Subdural haemorrhage	Injury, poisoning and procedural complications	MedDRA version 19.1	Systematic Assessment	EG0001 events1 affected373 at risk EG0010 events0 affected192 at risk
Transfusion-related acute lung injury	Injury, poisoning and procedural complications	MedDRA version 19.1	Systematic Assessment	EG0001 events1 affected373 at risk EG0010 events0 affected192 at risk
Transplant failure	Injury, poisoning and procedural complications	MedDRA version 19.1	Systematic Assessment	EG0003 events3 affected373 at risk EG0013 events3 affected192 at risk
Blood creatinine increased	Investigations	MedDRA version 19.1	Systematic Assessment	EG0001 events1 affected373 at risk EG0011 events1 affected192 at risk
Platelet count decreased	Investigations	MedDRA version 19.1	Systematic Assessment	EG0001 events1 affected373 at risk EG0010 events0 affected192 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA version 19.1	Systematic Assessment	EG0001 events1 affected373 at risk EG0012 events2 affected192 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA version 19.1	Systematic Assessment	EG0000 events0 affected373 at risk EG0011 events1 affected192 at risk
Diabetes mellitus	Metabolism and nutrition disorders	MedDRA version 19.1	Systematic Assessment	EG0001 events1 affected373 at risk EG0010 events0 affected192 at risk
Failure to thrive	Metabolism and nutrition disorders	MedDRA version 19.1	Systematic Assessment	EG0001 events1 affected373 at risk EG0010 events0 affected192 at risk
Gout	Metabolism and nutrition disorders	MedDRA version 19.1	Systematic Assessment	EG0001 events1 affected373 at risk EG0010 events0 affected192 at risk
Hypernatraemia	Metabolism and nutrition disorders	MedDRA version 19.1	Systematic Assessment	EG0001 events1 affected373 at risk EG0010 events0 affected192 at risk
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA version 19.1	Systematic Assessment	EG0001 events1 affected373 at risk EG0010 events0 affected192 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA version 19.1	Systematic Assessment	EG0001 events1 affected373 at risk EG0010 events0 affected192 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA version 19.1	Systematic Assessment	EG0000 events0 affected373 at risk EG0012 events2 affected192 at risk
Lactose intolerance	Metabolism and nutrition disorders	MedDRA version 19.1	Systematic Assessment	EG0001 events1 affected373 at risk EG0010 events0 affected192 at risk
Metabolic acidosis	Metabolism and nutrition disorders	MedDRA version 19.1	Systematic Assessment	EG0000 events0 affected373 at risk EG0011 events1 affected192 at risk
Tetany	Metabolism and nutrition disorders	MedDRA version 19.1	Systematic Assessment	EG0001 events1 affected373 at risk EG0010 events0 affected192 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA version 19.1	Systematic Assessment	EG0001 events1 affected373 at risk EG0010 events0 affected192 at risk
Fibromyalgia	Musculoskeletal and connective tissue disorders	MedDRA version 19.1	Systematic Assessment	EG0002 events1 affected373 at risk EG0010 events0 affected192 at risk
Fracture pain	Musculoskeletal and connective tissue disorders	MedDRA version 19.1	Systematic Assessment	EG0000 events0 affected373 at risk EG0011 events1 affected192 at risk
Muscular weakness	Musculoskeletal and connective tissue disorders	MedDRA version 19.1	Systematic Assessment	EG0001 events1 affected373 at risk EG0010 events0 affected192 at risk
Musculoskeletal chest pain	Musculoskeletal and connective tissue disorders	MedDRA version 19.1	Systematic Assessment	EG0000 events0 affected373 at risk EG0011 events1 affected192 at risk
Myopathy	Musculoskeletal and connective tissue disorders	MedDRA version 19.1	Systematic Assessment	EG0000 events0 affected373 at risk EG0011 events1 affected192 at risk
Osteonecrosis	Musculoskeletal and connective tissue disorders	MedDRA version 19.1	Systematic Assessment	EG0000 events0 affected373 at risk EG0011 events1 affected192 at risk
Acute lymphocytic leukaemia	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA version 19.1	Systematic Assessment	EG0002 events2 affected373 at risk EG0010 events0 affected192 at risk
Acute lymphocytic leukaemia recurrent	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA version 19.1	Systematic Assessment	EG0006 events6 affected373 at risk EG0011 events1 affected192 at risk
Acute myeloid leukaemia	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA version 19.1	Systematic Assessment	EG0007 events7 affected373 at risk EG0014 events4 affected192 at risk
Acute myeloid leukaemia recurrent	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA version 19.1	Systematic Assessment	EG00023 events23 affected373 at risk EG00117 events17 affected192 at risk
B-cell lymphoma recurrent	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA version 19.1	Systematic Assessment	EG0001 events1 affected373 at risk EG0010 events0 affected192 at risk
Basal cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA version 19.1	Systematic Assessment	EG0001 events1 affected373 at risk EG0010 events0 affected192 at risk
Bowen's disease	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA version 19.1	Systematic Assessment	EG0000 events0 affected373 at risk EG0011 events1 affected192 at risk
Chronic myeloid leukaemia	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA version 19.1	Systematic Assessment	EG0001 events1 affected373 at risk EG0010 events0 affected192 at risk
Chronic myeloid leukaemia recurrent	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA version 19.1	Systematic Assessment	EG0001 events1 affected373 at risk EG0010 events0 affected192 at risk
Diffuse large B-cell lymphoma recurrent	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA version 19.1	Systematic Assessment	EG0001 events1 affected373 at risk EG0011 events1 affected192 at risk
Mantle cell lymphoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA version 19.1	Systematic Assessment	EG0002 events2 affected373 at risk EG0010 events0 affected192 at risk
Mantle cell lymphoma recurrent	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA version 19.1	Systematic Assessment	EG0000 events0 affected373 at risk EG0011 events1 affected192 at risk
Mycosis fungoides	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA version 19.1	Systematic Assessment	EG0001 events1 affected373 at risk EG0010 events0 affected192 at risk
Mycosis fungoides recurrent	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA version 19.1	Systematic Assessment	EG0001 events1 affected373 at risk EG0010 events0 affected192 at risk
Myelodysplastic syndrome	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA version 19.1	Systematic Assessment	EG0002 events2 affected373 at risk EG0013 events3 affected192 at risk
Natural killer-cell leukaemia	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA version 19.1	Systematic Assessment	EG0001 events1 affected373 at risk EG0010 events0 affected192 at risk
Non-Hodgkin's lymphoma recurrent	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA version 19.1	Systematic Assessment	EG0000 events0 affected373 at risk EG0012 events2 affected192 at risk
Plasma cell myeloma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA version 19.1	Systematic Assessment	EG0001 events1 affected373 at risk EG0010 events0 affected192 at risk
Plasma cell myeloma recurrent	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA version 19.1	Systematic Assessment	EG0002 events2 affected373 at risk EG0010 events0 affected192 at risk
Post transplant lymphoproliferative disorder	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA version 19.1	Systematic Assessment	EG0000 events0 affected373 at risk EG0011 events1 affected192 at risk
Primary myelofibrosis	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA version 19.1	Systematic Assessment	EG0001 events1 affected373 at risk EG0010 events0 affected192 at risk
Squamous cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA version 19.1	Systematic Assessment	EG0003 events3 affected373 at risk EG0010 events0 affected192 at risk
Cerebral haemorrhage	Nervous system disorders	MedDRA version 19.1	Systematic Assessment	EG0001 events1 affected373 at risk EG0011 events1 affected192 at risk
Encephalopathy	Nervous system disorders	MedDRA version 19.1	Systematic Assessment	EG0001 events1 affected373 at risk EG0010 events0 affected192 at risk
Haemorrhage intracranial	Nervous system disorders	MedDRA version 19.1	Systematic Assessment	EG0000 events0 affected373 at risk EG0011 events1 affected192 at risk
Headache	Nervous system disorders	MedDRA version 19.1	Systematic Assessment	EG0003 events3 affected373 at risk EG0010 events0 affected192 at risk
Hepatic encephalopathy	Nervous system disorders	MedDRA version 19.1	Systematic Assessment	EG0001 events1 affected373 at risk EG0010 events0 affected192 at risk
Migraine	Nervous system disorders	MedDRA version 19.1	Systematic Assessment	EG0001 events1 affected373 at risk EG0010 events0 affected192 at risk
Neurotoxicity	Nervous system disorders	MedDRA version 19.1	Systematic Assessment	EG0002 events2 affected373 at risk EG0010 events0 affected192 at risk
Posterior reversible encephalopathy syndrome	Nervous system disorders	MedDRA version 19.1	Systematic Assessment	EG0001 events1 affected373 at risk EG0010 events0 affected192 at risk
Sciatica	Nervous system disorders	MedDRA version 19.1	Systematic Assessment	EG0002 events2 affected373 at risk EG0010 events0 affected192 at risk
Syncope	Nervous system disorders	MedDRA version 19.1	Systematic Assessment	EG0002 events2 affected373 at risk EG0010 events0 affected192 at risk
Delirium	Psychiatric disorders	MedDRA version 19.1	Systematic Assessment	EG0000 events0 affected373 at risk EG0011 events1 affected192 at risk
Mental status changes	Psychiatric disorders	MedDRA version 19.1	Systematic Assessment	EG0000 events0 affected373 at risk EG0012 events2 affected192 at risk
Substance-induced psychotic disorder	Psychiatric disorders	MedDRA version 19.1	Systematic Assessment	EG0001 events1 affected373 at risk EG0010 events0 affected192 at risk
Acute kidney injury	Renal and urinary disorders	MedDRA version 19.1	Systematic Assessment	EG0007 events7 affected373 at risk EG00111 events9 affected192 at risk
Chronic kidney disease	Renal and urinary disorders	MedDRA version 19.1	Systematic Assessment	EG0000 events0 affected373 at risk EG0011 events1 affected192 at risk
Cystitis haemorrhagic	Renal and urinary disorders	MedDRA version 19.1	Systematic Assessment	EG0003 events3 affected373 at risk EG0012 events2 affected192 at risk
Haematuria	Renal and urinary disorders	MedDRA version 19.1	Systematic Assessment	EG0000 events0 affected373 at risk EG0011 events1 affected192 at risk
Nephrolithiasis	Renal and urinary disorders	MedDRA version 19.1	Systematic Assessment	EG0001 events1 affected373 at risk EG0011 events1 affected192 at risk
Renal failure	Renal and urinary disorders	MedDRA version 19.1	Systematic Assessment	EG0001 events1 affected373 at risk EG0011 events1 affected192 at risk
Renal impairment	Renal and urinary disorders	MedDRA version 19.1	Systematic Assessment	EG0001 events1 affected373 at risk EG0010 events0 affected192 at risk
Uterine haemorrhage	Reproductive system and breast disorders	MedDRA version 19.1	Systematic Assessment	EG0000 events0 affected373 at risk EG0011 events1 affected192 at risk
Acute respiratory distress syndrome	Respiratory, thoracic and mediastinal disorders	MedDRA version 19.1	Systematic Assessment	EG0002 events2 affected373 at risk EG0010 events0 affected192 at risk
Acute respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA version 19.1	Systematic Assessment	EG0001 events1 affected373 at risk EG0010 events0 affected192 at risk
Asthma	Respiratory, thoracic and mediastinal disorders	MedDRA version 19.1	Systematic Assessment	EG0001 events1 affected373 at risk EG0010 events0 affected192 at risk
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	MedDRA version 19.1	Systematic Assessment	EG0000 events0 affected373 at risk EG0011 events1 affected192 at risk
Diffuse alveolar damage	Respiratory, thoracic and mediastinal disorders	MedDRA version 19.1	Systematic Assessment	EG0000 events0 affected373 at risk EG0011 events1 affected192 at risk
Hypoxia	Respiratory, thoracic and mediastinal disorders	MedDRA version 19.1	Systematic Assessment	EG0000 events0 affected373 at risk EG0012 events2 affected192 at risk
Lung disorder	Respiratory, thoracic and mediastinal disorders	MedDRA version 19.1	Systematic Assessment	EG0000 events0 affected373 at risk EG0011 events1 affected192 at risk
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA version 19.1	Systematic Assessment	EG0003 events2 affected373 at risk EG0011 events1 affected192 at risk
Pleurisy	Respiratory, thoracic and mediastinal disorders	MedDRA version 19.1	Systematic Assessment	EG0001 events1 affected373 at risk EG0010 events0 affected192 at risk
Pneumonia aspiration	Respiratory, thoracic and mediastinal disorders	MedDRA version 19.1	Systematic Assessment	EG0001 events1 affected373 at risk EG0010 events0 affected192 at risk
Pneumonitis	Respiratory, thoracic and mediastinal disorders	MedDRA version 19.1	Systematic Assessment	EG0000 events0 affected373 at risk EG0011 events1 affected192 at risk
Pneumothorax	Respiratory, thoracic and mediastinal disorders	MedDRA version 19.1	Systematic Assessment	EG0002 events2 affected373 at risk EG0010 events0 affected192 at risk
Pulmonary oedema	Respiratory, thoracic and mediastinal disorders	MedDRA version 19.1	Systematic Assessment	EG0000 events0 affected373 at risk EG0012 events2 affected192 at risk
Respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA version 19.1	Systematic Assessment	EG0007 events7 affected373 at risk EG0010 events0 affected192 at risk
Tonsillar disorder	Respiratory, thoracic and mediastinal disorders	MedDRA version 19.1	Systematic Assessment	EG0001 events1 affected373 at risk EG0010 events0 affected192 at risk
Rash generalised	Skin and subcutaneous tissue disorders	MedDRA version 19.1	Systematic Assessment	EG0000 events0 affected373 at risk EG0011 events1 affected192 at risk
Stevens-Johnson syndrome	Skin and subcutaneous tissue disorders	MedDRA version 19.1	Systematic Assessment	EG0001 events1 affected373 at risk EG0010 events0 affected192 at risk
Hypertension	Vascular disorders	MedDRA version 19.1	Systematic Assessment	EG0000 events0 affected373 at risk EG0011 events1 affected192 at risk
Hypertensive crisis	Vascular disorders	MedDRA version 19.1	Systematic Assessment	EG0001 events1 affected373 at risk EG0010 events0 affected192 at risk
Hypotension	Vascular disorders	MedDRA version 19.1	Systematic Assessment	EG0002 events2 affected373 at risk EG0010 events0 affected192 at risk
Hypovolaemic shock	Vascular disorders	MedDRA version 19.1	Systematic Assessment	EG0001 events1 affected373 at risk EG0010 events0 affected192 at risk
Orthostatic hypotension	Vascular disorders	MedDRA version 19.1	Systematic Assessment	EG0001 events1 affected373 at risk EG0010 events0 affected192 at risk
Thrombosis	Vascular disorders	MedDRA version 19.1	Systematic Assessment	EG0001 events1 affected373 at risk EG0010 events0 affected192 at risk
Venoocclusive disease	Vascular disorders	MedDRA version 19.1	Systematic Assessment	EG0003 events3 affected373 at risk EG0010 events0 affected192 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA version 19.1	Systematic Assessment	EG00039 events24 affected373 at risk EG00113 events12 affected192 at risk
Febrile neutropenia	Blood and lymphatic system disorders	MedDRA version 19.1	Systematic Assessment	EG00028 events28 affected373 at risk EG00120 events19 affected192 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA version 19.1	Systematic Assessment	EG00020 events18 affected373 at risk EG00112 events11 affected192 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA version 19.1	Systematic Assessment	EG00032 events27 affected373 at risk EG00113 events13 affected192 at risk
Dry eye	Eye disorders	MedDRA version 19.1	Systematic Assessment	EG00024 events24 affected373 at risk EG00112 events12 affected192 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA version 19.1	Systematic Assessment	EG00053 events49 affected373 at risk EG00121 events19 affected192 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA version 19.1	Systematic Assessment	EG00030 events23 affected373 at risk EG00120 events17 affected192 at risk
Constipation	Gastrointestinal disorders	MedDRA version 19.1	Systematic Assessment	EG00030 events30 affected373 at risk EG00124 events22 affected192 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA version 19.1	Systematic Assessment	EG000139 events108 affected373 at risk EG00164 events51 affected192 at risk
Dry mouth	Gastrointestinal disorders	MedDRA version 19.1	Systematic Assessment	EG00022 events21 affected373 at risk EG00111 events11 affected192 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA version 19.1	Systematic Assessment	EG00022 events21 affected373 at risk EG0018 events6 affected192 at risk
Gastrooesophageal reflux disease	Gastrointestinal disorders	MedDRA version 19.1	Systematic Assessment	EG0006 events6 affected373 at risk EG00111 events11 affected192 at risk
Nausea	Gastrointestinal disorders	MedDRA version 19.1	Systematic Assessment	EG000141 events106 affected373 at risk EG00164 events53 affected192 at risk
Stomatitis	Gastrointestinal disorders	MedDRA version 19.1	Systematic Assessment	EG00025 events24 affected373 at risk EG00114 events14 affected192 at risk
Vomiting	Gastrointestinal disorders	MedDRA version 19.1	Systematic Assessment	EG00093 events79 affected373 at risk EG00140 events35 affected192 at risk
Asthenia	General disorders	MedDRA version 19.1	Systematic Assessment	EG00036 events29 affected373 at risk EG00113 events9 affected192 at risk
Chest pain	General disorders	MedDRA version 19.1	Systematic Assessment	EG00021 events20 affected373 at risk EG0015 events5 affected192 at risk
Fatigue	General disorders	MedDRA version 19.1	Systematic Assessment	EG00063 events55 affected373 at risk EG00130 events26 affected192 at risk
Mucosal inflammation	General disorders	MedDRA version 19.1	Systematic Assessment	EG00047 events45 affected373 at risk EG00124 events24 affected192 at risk
Oedema peripheral	General disorders	MedDRA version 19.1	Systematic Assessment	EG00074 events60 affected373 at risk EG00127 events23 affected192 at risk
Pyrexia	General disorders	MedDRA version 19.1	Systematic Assessment	EG000112 events85 affected373 at risk EG00160 events50 affected192 at risk
Graft versus host disease	Immune system disorders	MedDRA version 19.1	Systematic Assessment	EG000173 events147 affected373 at risk EG00191 events74 affected192 at risk
Bacteraemia	Infections and infestations	MedDRA version 19.1	Systematic Assessment	EG00024 events21 affected373 at risk EG0015 events4 affected192 at risk
Cytomegalovirus infection	Infections and infestations	MedDRA version 19.1	Systematic Assessment	EG00065 events55 affected373 at risk EG00193 events77 affected192 at risk
Nasopharyngitis	Infections and infestations	MedDRA version 19.1	Systematic Assessment	EG00022 events19 affected373 at risk EG0018 events8 affected192 at risk
Viraemia	Infections and infestations	MedDRA version 19.1	Systematic Assessment	EG00012 events12 affected373 at risk EG00112 events12 affected192 at risk
Alanine aminotransferase increased	Investigations	MedDRA version 19.1	Systematic Assessment	EG00031 events26 affected373 at risk EG00120 events17 affected192 at risk
Aspartate aminotransferase increased	Investigations	MedDRA version 19.1	Systematic Assessment	EG00024 events21 affected373 at risk EG00116 events13 affected192 at risk
Blood creatinine increased	Investigations	MedDRA version 19.1	Systematic Assessment	EG00043 events39 affected373 at risk EG00117 events14 affected192 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA version 19.1	Systematic Assessment	EG00048 events43 affected373 at risk EG00126 events26 affected192 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA version 19.1	Systematic Assessment	EG00031 events31 affected373 at risk EG00114 events13 affected192 at risk
Hyperkalaemia	Metabolism and nutrition disorders	MedDRA version 19.1	Systematic Assessment	EG00029 events28 affected373 at risk EG0015 events5 affected192 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA version 19.1	Systematic Assessment	EG00025 events23 affected373 at risk EG00113 events12 affected192 at risk
Hypomagnesaemia	Metabolism and nutrition disorders	MedDRA version 19.1	Systematic Assessment	EG00024 events24 affected373 at risk EG00116 events15 affected192 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA version 19.1	Systematic Assessment	EG00024 events23 affected373 at risk EG00110 events10 affected192 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA version 19.1	Systematic Assessment	EG00031 events30 affected373 at risk EG00118 events15 affected192 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA version 19.1	Systematic Assessment	EG00026 events24 affected373 at risk EG00122 events20 affected192 at risk
Muscle spasms	Musculoskeletal and connective tissue disorders	MedDRA version 19.1	Systematic Assessment	EG00013 events12 affected373 at risk EG00112 events10 affected192 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA version 19.1	Systematic Assessment	EG00021 events21 affected373 at risk EG0014 events4 affected192 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA version 19.1	Systematic Assessment	EG00024 events20 affected373 at risk EG00117 events16 affected192 at risk
Dizziness	Nervous system disorders	MedDRA version 19.1	Systematic Assessment	EG00030 events29 affected373 at risk EG00116 events16 affected192 at risk
Dysgeusia	Nervous system disorders	MedDRA version 19.1	Systematic Assessment	EG00019 events19 affected373 at risk EG00110 events10 affected192 at risk
Headache	Nervous system disorders	MedDRA version 19.1	Systematic Assessment	EG00068 events58 affected373 at risk EG00126 events24 affected192 at risk
Tremor	Nervous system disorders	MedDRA version 19.1	Systematic Assessment	EG00030 events29 affected373 at risk EG00114 events13 affected192 at risk
Anxiety	Psychiatric disorders	MedDRA version 19.1	Systematic Assessment	EG00023 events23 affected373 at risk EG0015 events5 affected192 at risk
Insomnia	Psychiatric disorders	MedDRA version 19.1	Systematic Assessment	EG00037 events35 affected373 at risk EG00112 events12 affected192 at risk
Acute kidney injury	Renal and urinary disorders	MedDRA version 19.1	Systematic Assessment	EG00037 events35 affected373 at risk EG00125 events22 affected192 at risk
Dysuria	Renal and urinary disorders	MedDRA version 19.1	Systematic Assessment	EG00017 events17 affected373 at risk EG00111 events11 affected192 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA version 19.1	Systematic Assessment	EG00070 events62 affected373 at risk EG00128 events27 affected192 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA version 19.1	Systematic Assessment	EG00038 events36 affected373 at risk EG00110 events9 affected192 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA version 19.1	Systematic Assessment	EG00029 events25 affected373 at risk EG00113 events13 affected192 at risk
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA version 19.1	Systematic Assessment	EG00034 events32 affected373 at risk EG00120 events19 affected192 at risk
Rhinorrhoea	Respiratory, thoracic and mediastinal disorders	MedDRA version 19.1	Systematic Assessment	EG00018 events15 affected373 at risk EG00111 events10 affected192 at risk
Dry skin	Skin and subcutaneous tissue disorders	MedDRA version 19.1	Systematic Assessment	EG00032 events31 affected373 at risk EG00119 events16 affected192 at risk
Erythema	Skin and subcutaneous tissue disorders	MedDRA version 19.1	Systematic Assessment	EG00037 events34 affected373 at risk EG00113 events12 affected192 at risk
Pruritus	Skin and subcutaneous tissue disorders	MedDRA version 19.1	Systematic Assessment	EG00035 events31 affected373 at risk EG00114 events12 affected192 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA version 19.1	Systematic Assessment	EG000109 events90 affected373 at risk EG00162 events51 affected192 at risk
Hypertension	Vascular disorders	MedDRA version 19.1	Systematic Assessment	EG00038 events34 affected373 at risk EG00124 events23 affected192 at risk
Hypotension	Vascular disorders	MedDRA version 19.1	Systematic Assessment	EG00016 events16 affected373 at risk EG00113 events11 affected192 at risk

ID	Term
D010335	Pathologic Processes
D013568	Pathological Conditions, Signs and Symptoms

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Letermovir	Letermovir oral or intravenous (IV) formulation was administered once daily for up to 14 weeks, beginning up to Day 28 post-transplant. The dose was 240 mg once daily for participants receiving concomitant cyclosporin A and 480 mg once daily for participants not receiving cyclosporin A. Intravenous infusion was administered only to participants who are unable to swallow tablets or who have a condition that may interfere with absorption of the tablets.			202	373	360	373
EG001	Placebo	Placebo oral or IV formulation was administered once daily for up to 14 weeks, beginning up to Day 28 post-transplant. The number of placebo tablets was to mimic that for letermovir administration according to the concomitant cyclosporin A status. Intravenous infusion was administered only to participants who are unable to swallow tablets or who have a condition that may interfere with absorption of the tablets.			115	192	186	192