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Letermovir (MK-8228) Versus Placebo in the Prevention of Clinically-Significant Cytomegalovirus (CMV) Infection in Adult, CMV-Seropositive Allogeneic Hematopoietic Stem Cell Transplant Recipients (MK-8228-001)

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ClinicalTrials.gov Identifier: NCT02137772
Recruitment Status : Completed
First Posted : May 14, 2014
Results First Posted : November 17, 2017
Last Update Posted : October 25, 2018
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Prevention
Condition Prevention of CMV Infection or Disease
Interventions Drug: Letermovir
Drug: Placebo
Enrollment 570
Recruitment Details A total of 738 participants were screened, 570 were randomized 2:1 letermovir:placebo, and 565 received at least one dose of study medication.
Pre-assignment Details Screening could occur up to 15 days before Hematopoietic Stem Cell Transplant (HSCT) and no more than Day 28 post-transplant. From the time of screening to randomization, participants were tested weekly for Cytomegalovirus (CMV) viremia; a positive test resulted in exclusion from the study.
Arm/Group Title Letermovir Placebo
Hide Arm/Group Description 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. 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.
Period Title: Overall Study
Started 376 [1] 194 [1]
Treated Participants 373 192
Completed 244 119
Not Completed 132 75
Reason Not Completed
Adverse Event             6             3
Death             71             44
Lost to Follow-up             8             4
Physician Decision             15             5
Withdrawal by Subject             28             17
Non-compliance with study drug             1             0
Not treated             3             2
[1]
Randomized participants
Arm/Group Title Letermovir Placebo Total
Hide Arm/Group Description 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. 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. Total of all reporting groups
Overall Number of Baseline Participants 376 194 570
Hide Baseline Analysis Population Description
Randomized participants
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 376 participants 194 participants 570 participants
50.8  (13.4) 50.8  (14.8) 50.8  (13.9)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 376 participants 194 participants 570 participants
Female
162
  43.1%
77
  39.7%
239
  41.9%
Male
214
  56.9%
117
  60.3%
331
  58.1%
Risk Stratum for CMV Reactivation   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 376 participants 194 participants 570 participants
High risk 122 54 176
Low risk 254 140 394
[1]
Measure Description: High risk: Participants meeting one or more of the following criteria at randomization: 1) Human leukocyte antigen (HLA)-related (sibling) donor with at least one mismatch at an HLA-A, -B or -DR gene loci 2) Haploidentical donor, 3) Unrelated donor with at least one mismatch at HLA- HLA-A, -B, -C or -DRB1 gene loci 4) Use of umbilical cord blood as stem cell source, 5) Use of ex vivo T-cell-depleted grafts, 6) Grade 2 or greater graft-versus-host disease requiring the use of systemic corticosteroids. Low risk: All other participants
1.Primary Outcome
Title Percentage of Participants With Clinically-significant CMV Infection up to Week 24 Post-transplant
Hide Description 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.
Time Frame Up to Week 24 post-transplant
Hide Outcome Measure Data
Hide Analysis Population Description
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).
Arm/Group Title Letermovir Placebo
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 325 170
Measure Type: Number
Unit of Measure: Percentage of participants
37.5 60.6
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Letermovir, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments A 1-sided p-value ≤0.0249 for the risk difference was used for declaring statistical significance
Method Mantel Haenszel
Comments The Mantel Haenszel analysis was adjusted for sample size for each stratum (high or low risk for CMV reactivation)
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value -23.5
Confidence Interval (2-Sided) 95%
-32.5 to -14.6
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Time to Onset of Clinically-significant CMV Infection (Kaplan-Meier Estimate of Percentage of Participants With a Qualifying Event at Week 24 Post-transplant)
Hide Description 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.
Time Frame Up to Week 24 post-transplant
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Letermovir Placebo
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 325 170
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
18.9
(14.4 to 23.5)
44.3
(36.4 to 52.1)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Letermovir, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Nominal 2-sided p-value
Method Log Rank
Comments The log rank test was adjusted for sample size for each stratum (high or low risk for CMV reactivation)
3.Secondary Outcome
Title Percentage of Participants With Clinically-significant CMV Infection up to Week 14 Post-transplant
Hide Description 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.
Time Frame Up to Week 14 post-transplant
Hide Outcome Measure Data
Hide Analysis Population Description
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).
Arm/Group Title Letermovir Placebo
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 325 170
Measure Type: Number
Unit of Measure: Percentage of participants
19.1 50.0
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Letermovir, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Nominal 1-sided p-value
Method Mantel Haenszel
Comments The Mantel Haenszel analysis was adjusted for sample size for each stratum (high or low risk for CMV reactivation)
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value -31.3
Confidence Interval (2-Sided) 95%
-39.9 to -22.6
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Percentage of Participants With CMV End-organ Disease up to Week 24 Post-transplant
Hide Description 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.
Time Frame Up to Week 24 post-transplant
Hide Outcome Measure Data
Hide Analysis Population Description
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).
Arm/Group Title Letermovir Placebo
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 254 123
Measure Type: Number
Unit of Measure: Percentage of participants
2.0 2.4
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Letermovir, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4056
Comments Nominal 1-sided p-value
Method Mantel Haenszel
Comments The Mantel Haenszel analysis was adjusted for sample size for each stratum (high or low risk for CMV reactivation)
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value -0.4
Confidence Interval (2-Sided) 95%
-4.0 to 3.2
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Percentage of Participants With CMV End-organ Disease up to Week 14 Post-transplant
Hide Description 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.
Time Frame Up to Week 14 post-transplant
Hide Outcome Measure Data
Hide Analysis Population Description
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).
Arm/Group Title Letermovir Placebo
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 285 145
Measure Type: Number
Unit of Measure: Percentage of participants
0.4 1.4
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Letermovir, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2258
Comments Nominal 1-sided p-value
Method Mantel Haenszel
Comments The Mantel Haenszel analysis was adjusted for sample size for each stratum (high or low risk for CMV reactivation)
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value -1.0
Confidence Interval (2-Sided) 95%
-3.5 to 1.5
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Percentage of Participants With Pre-emptive Therapy for CMV Viremia up to Week 14 Post-transplant
Hide Description 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.
Time Frame Up to Week 14 post-transplant
Hide Outcome Measure Data
Hide Analysis Population Description
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).
Arm/Group Title Letermovir Placebo
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 325 170
Measure Type: Number
Unit of Measure: Percentage of participants
18.8 49.4
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Letermovir, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Nominal 1-sided p-value
Method Mantel Haenszel
Comments The Mantel Haenszel analysis was adjusted for sample size for each stratum (high or low risk for CMV reactivation)
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value -31.0
Confidence Interval (2-Sided) 95%
-39.6 to -22.4
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Percentage of Participants With Pre-emptive Therapy for CMV Viremia up to Week 24 Post-transplant
Hide Description 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.
Time Frame Up to Week 24 post-transplant
Hide Outcome Measure Data
Hide Analysis Population Description
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).
Arm/Group Title Letermovir Placebo
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 325 170
Measure Type: Number
Unit of Measure: Percentage of participants
36.6 59.4
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Letermovir, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Nominal 1-sided p-value
Method Mantel Haenszel
Comments The Mantel Haenszel analysis was adjusted for sample size for each stratum (high or low risk for CMV reactivation)
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value -23.3
Confidence Interval (2-Sided) 95%
-32.3 to -14.3
Estimation Comments [Not Specified]
8.Secondary Outcome
Title 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)
Hide Description 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.
Time Frame Up to Week 24 post-transplant
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Letermovir Placebo
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 325 170
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
17.2
(12.8 to 21.6)
42.4
(34.7 to 50.2)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Letermovir, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Nominal 2-sided p-value
Method Log Rank
Comments The log rank test analysis was adjusted for sample size for each stratum (high or low risk for CMV reactivation)
9.Other Pre-specified Outcome
Title Percentage of Participants With One or More Adverse Events up to Week 48 Post-transplant
Hide Description 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.
Time Frame Up to Week 48 post-transplant
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least one dose of study medication
Arm/Group Title Letermovir Placebo
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 373 192
Measure Type: Number
Unit of Measure: Percentage of participants
98.4 100.0
10.Other Pre-specified Outcome
Title Percentage of Participants Discontinued From Study Medication Due to an Adverse Event
Hide Description 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.
Time Frame Up to Week 14 post-transplant
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least one dose of study medication
Arm/Group Title Letermovir Placebo
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 373 192
Measure Type: Number
Unit of Measure: Percentage of participants
19.6 51.6
Time Frame Up to Week 48 post-transplant
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Letermovir Placebo
Hide Arm/Group Description 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. 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.
All-Cause Mortality
Letermovir Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Letermovir Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   202/373 (54.16%)      115/192 (59.90%)    
Blood and lymphatic system disorders     
Agranulocytosis  1  0/373 (0.00%)  0 1/192 (0.52%)  1
Anaemia  1  2/373 (0.54%)  2 0/192 (0.00%)  0
Aplastic anaemia  1  1/373 (0.27%)  1 0/192 (0.00%)  0
Autoimmune haemolytic anaemia  1  1/373 (0.27%)  1 0/192 (0.00%)  0
Disseminated intravascular coagulation  1  1/373 (0.27%)  1 0/192 (0.00%)  0
Febrile neutropenia  1  7/373 (1.88%)  10 3/192 (1.56%)  3
Immune thrombocytopenic purpura  1  0/373 (0.00%)  0 1/192 (0.52%)  1
Leukopenia  1  1/373 (0.27%)  1 0/192 (0.00%)  0
Neutropenia  1  1/373 (0.27%)  1 0/192 (0.00%)  0
Pancytopenia  1  3/373 (0.80%)  3 0/192 (0.00%)  0
Thrombocytopenia  1  4/373 (1.07%)  4 1/192 (0.52%)  1
Cardiac disorders     
Arrhythmia  1  1/373 (0.27%)  1 0/192 (0.00%)  0
Atrial fibrillation  1  1/373 (0.27%)  1 0/192 (0.00%)  0
Atrial flutter  1  1/373 (0.27%)  1 0/192 (0.00%)  0
Cardiac arrest  1  0/373 (0.00%)  0 1/192 (0.52%)  1
Cardiac failure  1  1/373 (0.27%)  1 0/192 (0.00%)  0
Cardiogenic shock  1  0/373 (0.00%)  0 1/192 (0.52%)  1
Pericarditis  1  1/373 (0.27%)  2 0/192 (0.00%)  0
Sinus node dysfunction  1  1/373 (0.27%)  1 0/192 (0.00%)  0
Endocrine disorders     
Inappropriate antidiuretic hormone secretion  1  1/373 (0.27%)  1 0/192 (0.00%)  0
Gastrointestinal disorders     
Colitis  1  1/373 (0.27%)  1 0/192 (0.00%)  0
Constipation  1  1/373 (0.27%)  1 0/192 (0.00%)  0
Diarrhoea  1  3/373 (0.80%)  3 5/192 (2.60%)  5
Dyspepsia  1  0/373 (0.00%)  0 1/192 (0.52%)  1
Food poisoning  1  1/373 (0.27%)  1 0/192 (0.00%)  0
Gastrointestinal haemorrhage  1  3/373 (0.80%)  3 0/192 (0.00%)  0
Intestinal ischaemia  1  0/373 (0.00%)  0 1/192 (0.52%)  1
Lower gastrointestinal haemorrhage  1  1/373 (0.27%)  1 0/192 (0.00%)  0
Nausea  1  2/373 (0.54%)  2 1/192 (0.52%)  1
Pancreatitis  1  1/373 (0.27%)  1 0/192 (0.00%)  0
Stomatitis haemorrhagic  1  1/373 (0.27%)  1 0/192 (0.00%)  0
Upper gastrointestinal haemorrhage  1  1/373 (0.27%)  1 0/192 (0.00%)  0
Vomiting  1  3/373 (0.80%)  3 1/192 (0.52%)  1
General disorders     
Chest pain  1  1/373 (0.27%)  2 1/192 (0.52%)  1
Gait disturbance  1  1/373 (0.27%)  1 0/192 (0.00%)  0
Generalised oedema  1  1/373 (0.27%)  1 0/192 (0.00%)  0
Malaise  1  1/373 (0.27%)  1 1/192 (0.52%)  1
Mucosal inflammation  1  2/373 (0.54%)  2 0/192 (0.00%)  0
Multiple organ dysfunction syndrome  1  2/373 (0.54%)  2 4/192 (2.08%)  4
Pyrexia  1  10/373 (2.68%)  12 4/192 (2.08%)  4
Hepatobiliary disorders     
Acute hepatic failure  1  1/373 (0.27%)  1 0/192 (0.00%)  0
Hepatic cirrhosis  1  1/373 (0.27%)  1 0/192 (0.00%)  0
Hepatic function abnormal  1  2/373 (0.54%)  2 2/192 (1.04%)  2
Hyperbilirubinaemia  1  1/373 (0.27%)  1 0/192 (0.00%)  0
Venoocclusive liver disease  1  2/373 (0.54%)  2 3/192 (1.56%)  3
Immune system disorders     
Anaphylactic reaction  1  0/373 (0.00%)  0 1/192 (0.52%)  1
Drug hypersensitivity  1  1/373 (0.27%)  1 1/192 (0.52%)  1
Graft versus host disease  1  45/373 (12.06%)  49 29/192 (15.10%)  31
Transplant rejection  1  0/373 (0.00%)  0 1/192 (0.52%)  1
Infections and infestations     
Acute sinusitis  1  1/373 (0.27%)  1 1/192 (0.52%)  1
Adenoviral haemorrhagic cystitis  1  0/373 (0.00%)  0 1/192 (0.52%)  1
Aspergillus infection  1  1/373 (0.27%)  1 2/192 (1.04%)  2
Atypical pneumonia  1  1/373 (0.27%)  1 0/192 (0.00%)  0
Bacteraemia  1  2/373 (0.54%)  2 1/192 (0.52%)  1
BK virus infection  1  1/373 (0.27%)  1 0/192 (0.00%)  0
Bacterial sepsis  1  0/373 (0.00%)  0 1/192 (0.52%)  1
Bronchiolitis  1  1/373 (0.27%)  1 0/192 (0.00%)  0
Bronchitis  1  1/373 (0.27%)  1 0/192 (0.00%)  0
Bronchopulmonary aspergillosis  1  4/373 (1.07%)  4 1/192 (0.52%)  1
Cellulitis  1  3/373 (0.80%)  3 0/192 (0.00%)  0
Cellulitis orbital  1  1/373 (0.27%)  2 0/192 (0.00%)  0
Cerebral toxoplasmosis  1  0/373 (0.00%)  0 1/192 (0.52%)  1
Clostridium bacteraemia  1  1/373 (0.27%)  1 0/192 (0.00%)  0
Clostridium difficile colitis  1  3/373 (0.80%)  3 1/192 (0.52%)  1
Clostridium difficile infection  1  0/373 (0.00%)  0 2/192 (1.04%)  2
Cystitis viral  1  1/373 (0.27%)  1 2/192 (1.04%)  2
Cytomegalovirus infection  1  14/373 (3.75%)  15 15/192 (7.81%)  15
Cytomegalovirus viraemia  1  1/373 (0.27%)  1 0/192 (0.00%)  0
Diverticulitis  1  1/373 (0.27%)  1 0/192 (0.00%)  0
Enterococcal bacteraemia  1  1/373 (0.27%)  1 1/192 (0.52%)  1
Epstein-Barr viraemia  1  1/373 (0.27%)  1 1/192 (0.52%)  1
Epstein-Barr virus infection  1  3/373 (0.80%)  3 0/192 (0.00%)  0
Escherichia bacteraemia  1  1/373 (0.27%)  1 1/192 (0.52%)  1
Escherichia sepsis  1  0/373 (0.00%)  0 1/192 (0.52%)  1
Escherichia urinary tract infection  1  1/373 (0.27%)  1 0/192 (0.00%)  0
Fusarium infection  1  1/373 (0.27%)  1 0/192 (0.00%)  0
Gastroenteritis  1  2/373 (0.54%)  2 1/192 (0.52%)  1
Gastroenteritis adenovirus  1  0/373 (0.00%)  0 1/192 (0.52%)  1
Gastroenteritis norovirus  1  1/373 (0.27%)  1 0/192 (0.00%)  0
Gastroenteritis rotavirus  1  1/373 (0.27%)  1 0/192 (0.00%)  0
Gastroenteritis viral  1  2/373 (0.54%)  2 0/192 (0.00%)  0
Gastrointestinal candidiasis  1  1/373 (0.27%)  1 0/192 (0.00%)  0
Herpes zoster  1  2/373 (0.54%)  2 0/192 (0.00%)  0
Implant site cellulitis  1  1/373 (0.27%)  1 0/192 (0.00%)  0
Infection  1  1/373 (0.27%)  1 0/192 (0.00%)  0
Klebsiella infection  1  1/373 (0.27%)  1 0/192 (0.00%)  0
Klebsiella sepsis  1  1/373 (0.27%)  1 0/192 (0.00%)  0
Meningitis aseptic  1  1/373 (0.27%)  1 0/192 (0.00%)  0
Meningitis bacterial  1  1/373 (0.27%)  1 0/192 (0.00%)  0
Meningoencephalitis herpetic  1  1/373 (0.27%)  1 1/192 (0.52%)  1
Meningoencephalitis viral  1  0/373 (0.00%)  0 1/192 (0.52%)  1
Mucormycosis  1  1/373 (0.27%)  2 1/192 (0.52%)  1
Nasopharyngitis  1  1/373 (0.27%)  1 0/192 (0.00%)  0
Neutropenic sepsis  1  1/373 (0.27%)  1 0/192 (0.00%)  0
Oesophageal candidiasis  1  1/373 (0.27%)  1 0/192 (0.00%)  0
Otitis media acute  1  1/373 (0.27%)  1 0/192 (0.00%)  0
Parainfluenzae virus infection  1  1/373 (0.27%)  1 0/192 (0.00%)  0
Periorbital cellulitis  1  1/373 (0.27%)  1 0/192 (0.00%)  0
Pharyngitis  1  1/373 (0.27%)  1 0/192 (0.00%)  0
Pilonidal cyst  1  1/373 (0.27%)  1 0/192 (0.00%)  0
Pneumocystis jirovecii pneumonia  1  0/373 (0.00%)  0 1/192 (0.52%)  1
Pneumonia  1  15/373 (4.02%)  15 6/192 (3.13%)  6
Pneumonia adenoviral  1  1/373 (0.27%)  1 0/192 (0.00%)  0
Pneumonia bacterial  1  3/373 (0.80%)  3 1/192 (0.52%)  1
Pneumonia parainfluenzae viral  1  1/373 (0.27%)  1 0/192 (0.00%)  0
Pneumonia respiratory syncytial viral  1  1/373 (0.27%)  1 0/192 (0.00%)  0
Pneumonia staphylococcal  1  0/373 (0.00%)  0 1/192 (0.52%)  1
Pneumonia viral  1  1/373 (0.27%)  1 0/192 (0.00%)  0
Pseudomonas bronchitis  1  1/373 (0.27%)  1 0/192 (0.00%)  0
Pulmonary tuberculosis  1  0/373 (0.00%)  0 1/192 (0.52%)  1
Respiratory tract infection  1  1/373 (0.27%)  1 0/192 (0.00%)  0
Respiratory tract infection viral  1  1/373 (0.27%)  1 1/192 (0.52%)  1
Retinitis viral  1  1/373 (0.27%)  1 0/192 (0.00%)  0
Rhinovirus infection  1  2/373 (0.54%)  2 0/192 (0.00%)  0
Sepsis  1  8/373 (2.14%)  8 4/192 (2.08%)  4
Septic shock  1  5/373 (1.34%)  5 7/192 (3.65%)  7
Sinusitis  1  4/373 (1.07%)  4 1/192 (0.52%)  1
Staphylococcal bacteraemia  1  4/373 (1.07%)  4 2/192 (1.04%)  2
Staphylococcal infection  1  1/373 (0.27%)  1 0/192 (0.00%)  0
Streptococcal bacteraemia  1  1/373 (0.27%)  1 0/192 (0.00%)  0
Systemic candida  1  1/373 (0.27%)  1 0/192 (0.00%)  0
Tonsillitis  1  1/373 (0.27%)  1 0/192 (0.00%)  0
Tooth infection  1  1/373 (0.27%)  1 0/192 (0.00%)  0
Upper respiratory tract infection  1  0/373 (0.00%)  0 1/192 (0.52%)  1
Upper respiratory tract infection bacterial  1  1/373 (0.27%)  1 0/192 (0.00%)  0
Urinary tract infection  1  4/373 (1.07%)  4 0/192 (0.00%)  0
Viraemia  1  3/373 (0.80%)  3 3/192 (1.56%)  3
Viral haemorrhagic cystitis  1  3/373 (0.80%)  3 0/192 (0.00%)  0
Viral infection  1  1/373 (0.27%)  1 0/192 (0.00%)  0
Viral pharyngitis  1  0/373 (0.00%)  0 1/192 (0.52%)  1
Viral upper respiratory tract infection  1  0/373 (0.00%)  0 1/192 (0.52%)  1
Injury, poisoning and procedural complications     
Allergic transfusion reaction  1  0/373 (0.00%)  0 1/192 (0.52%)  1
Comminuted fracture  1  0/373 (0.00%)  0 1/192 (0.52%)  1
Delayed engraftment  1  1/373 (0.27%)  1 0/192 (0.00%)  0
Femur fracture  1  1/373 (0.27%)  1 1/192 (0.52%)  1
Fractured sacrum  1  0/373 (0.00%)  0 1/192 (0.52%)  1
Laceration  1  1/373 (0.27%)  1 0/192 (0.00%)  0
Subarachnoid haemorrhage  1  1/373 (0.27%)  1 1/192 (0.52%)  1
Subdural haematoma  1  0/373 (0.00%)  0 3/192 (1.56%)  3
Subdural haemorrhage  1  1/373 (0.27%)  1 0/192 (0.00%)  0
Transfusion-related acute lung injury  1  1/373 (0.27%)  1 0/192 (0.00%)  0
Transplant failure  1  3/373 (0.80%)  3 3/192 (1.56%)  3
Investigations     
Blood creatinine increased  1  1/373 (0.27%)  1 1/192 (0.52%)  1
Platelet count decreased  1  1/373 (0.27%)  1 0/192 (0.00%)  0
Metabolism and nutrition disorders     
Decreased appetite  1  1/373 (0.27%)  1 2/192 (1.04%)  2
Dehydration  1  0/373 (0.00%)  0 1/192 (0.52%)  1
Diabetes mellitus  1  1/373 (0.27%)  1 0/192 (0.00%)  0
Failure to thrive  1  1/373 (0.27%)  1 0/192 (0.00%)  0
Gout  1  1/373 (0.27%)  1 0/192 (0.00%)  0
Hypernatraemia  1  1/373 (0.27%)  1 0/192 (0.00%)  0
Hypoglycaemia  1  1/373 (0.27%)  1 0/192 (0.00%)  0
Hypokalaemia  1  1/373 (0.27%)  1 0/192 (0.00%)  0
Hyponatraemia  1  0/373 (0.00%)  0 2/192 (1.04%)  2
Lactose intolerance  1  1/373 (0.27%)  1 0/192 (0.00%)  0
Metabolic acidosis  1  0/373 (0.00%)  0 1/192 (0.52%)  1
Tetany  1  1/373 (0.27%)  1 0/192 (0.00%)  0
Musculoskeletal and connective tissue disorders     
Arthralgia  1  1/373 (0.27%)  1 0/192 (0.00%)  0
Fibromyalgia  1  1/373 (0.27%)  2 0/192 (0.00%)  0
Fracture pain  1  0/373 (0.00%)  0 1/192 (0.52%)  1
Muscular weakness  1  1/373 (0.27%)  1 0/192 (0.00%)  0
Musculoskeletal chest pain  1  0/373 (0.00%)  0 1/192 (0.52%)  1
Myopathy  1  0/373 (0.00%)  0 1/192 (0.52%)  1
Osteonecrosis  1  0/373 (0.00%)  0 1/192 (0.52%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Acute lymphocytic leukaemia  1  2/373 (0.54%)  2 0/192 (0.00%)  0
Acute lymphocytic leukaemia recurrent  1  6/373 (1.61%)  6 1/192 (0.52%)  1
Acute myeloid leukaemia  1  7/373 (1.88%)  7 4/192 (2.08%)  4
Acute myeloid leukaemia recurrent  1  23/373 (6.17%)  23 17/192 (8.85%)  17
B-cell lymphoma recurrent  1  1/373 (0.27%)  1 0/192 (0.00%)  0
Basal cell carcinoma  1  1/373 (0.27%)  1 0/192 (0.00%)  0
Bowen's disease  1  0/373 (0.00%)  0 1/192 (0.52%)  1
Chronic myeloid leukaemia  1  1/373 (0.27%)  1 0/192 (0.00%)  0
Chronic myeloid leukaemia recurrent  1  1/373 (0.27%)  1 0/192 (0.00%)  0
Diffuse large B-cell lymphoma recurrent  1  1/373 (0.27%)  1 1/192 (0.52%)  1
Mantle cell lymphoma  1  2/373 (0.54%)  2 0/192 (0.00%)  0
Mantle cell lymphoma recurrent  1  0/373 (0.00%)  0 1/192 (0.52%)  1
Mycosis fungoides  1  1/373 (0.27%)  1 0/192 (0.00%)  0
Mycosis fungoides recurrent  1  1/373 (0.27%)  1 0/192 (0.00%)  0
Myelodysplastic syndrome  1  2/373 (0.54%)  2 3/192 (1.56%)  3
Natural killer-cell leukaemia  1  1/373 (0.27%)  1 0/192 (0.00%)  0
Non-Hodgkin's lymphoma recurrent  1  0/373 (0.00%)  0 2/192 (1.04%)  2
Plasma cell myeloma  1  1/373 (0.27%)  1 0/192 (0.00%)  0
Plasma cell myeloma recurrent  1  2/373 (0.54%)  2 0/192 (0.00%)  0
Post transplant lymphoproliferative disorder  1  0/373 (0.00%)  0 1/192 (0.52%)  1
Primary myelofibrosis  1  1/373 (0.27%)  1 0/192 (0.00%)  0
Squamous cell carcinoma  1  3/373 (0.80%)  3 0/192 (0.00%)  0
Nervous system disorders     
Cerebral haemorrhage  1  1/373 (0.27%)  1 1/192 (0.52%)  1
Encephalopathy  1  1/373 (0.27%)  1 0/192 (0.00%)  0
Haemorrhage intracranial  1  0/373 (0.00%)  0 1/192 (0.52%)  1
Headache  1  3/373 (0.80%)  3 0/192 (0.00%)  0
Hepatic encephalopathy  1  1/373 (0.27%)  1 0/192 (0.00%)  0
Migraine  1  1/373 (0.27%)  1 0/192 (0.00%)  0
Neurotoxicity  1  2/373 (0.54%)  2 0/192 (0.00%)  0
Posterior reversible encephalopathy syndrome  1  1/373 (0.27%)  1 0/192 (0.00%)  0
Sciatica  1  2/373 (0.54%)  2 0/192 (0.00%)  0
Syncope  1  2/373 (0.54%)  2 0/192 (0.00%)  0
Psychiatric disorders     
Delirium  1  0/373 (0.00%)  0 1/192 (0.52%)  1
Mental status changes  1  0/373 (0.00%)  0 2/192 (1.04%)  2
Substance-induced psychotic disorder  1  1/373 (0.27%)  1 0/192 (0.00%)  0
Renal and urinary disorders     
Acute kidney injury  1  7/373 (1.88%)  7 9/192 (4.69%)  11
Chronic kidney disease  1  0/373 (0.00%)  0 1/192 (0.52%)  1
Cystitis haemorrhagic  1  3/373 (0.80%)  3 2/192 (1.04%)  2
Haematuria  1  0/373 (0.00%)  0 1/192 (0.52%)  1
Nephrolithiasis  1  1/373 (0.27%)  1 1/192 (0.52%)  1
Renal failure  1  1/373 (0.27%)  1 1/192 (0.52%)  1
Renal impairment  1  1/373 (0.27%)  1 0/192 (0.00%)  0
Reproductive system and breast disorders     
Uterine haemorrhage  1  0/373 (0.00%)  0 1/192 (0.52%)  1
Respiratory, thoracic and mediastinal disorders     
Acute respiratory distress syndrome  1  2/373 (0.54%)  2 0/192 (0.00%)  0
Acute respiratory failure  1  1/373 (0.27%)  1 0/192 (0.00%)  0
Asthma  1  1/373 (0.27%)  1 0/192 (0.00%)  0
Chronic obstructive pulmonary disease  1  0/373 (0.00%)  0 1/192 (0.52%)  1
Diffuse alveolar damage  1  0/373 (0.00%)  0 1/192 (0.52%)  1
Hypoxia  1  0/373 (0.00%)  0 2/192 (1.04%)  2
Lung disorder  1  0/373 (0.00%)  0 1/192 (0.52%)  1
Pleural effusion  1  2/373 (0.54%)  3 1/192 (0.52%)  1
Pleurisy  1  1/373 (0.27%)  1 0/192 (0.00%)  0
Pneumonia aspiration  1  1/373 (0.27%)  1 0/192 (0.00%)  0
Pneumonitis  1  0/373 (0.00%)  0 1/192 (0.52%)  1
Pneumothorax  1  2/373 (0.54%)  2 0/192 (0.00%)  0
Pulmonary oedema  1  0/373 (0.00%)  0 2/192 (1.04%)  2
Respiratory failure  1  7/373 (1.88%)  7 0/192 (0.00%)  0
Tonsillar disorder  1  1/373 (0.27%)  1 0/192 (0.00%)  0
Skin and subcutaneous tissue disorders     
Rash generalised  1  0/373 (0.00%)  0 1/192 (0.52%)  1
Stevens-Johnson syndrome  1  1/373 (0.27%)  1 0/192 (0.00%)  0
Vascular disorders     
Hypertension  1  0/373 (0.00%)  0 1/192 (0.52%)  1
Hypertensive crisis  1  1/373 (0.27%)  1 0/192 (0.00%)  0
Hypotension  1  2/373 (0.54%)  2 0/192 (0.00%)  0
Hypovolaemic shock  1  1/373 (0.27%)  1 0/192 (0.00%)  0
Orthostatic hypotension  1  1/373 (0.27%)  1 0/192 (0.00%)  0
Thrombosis  1  1/373 (0.27%)  1 0/192 (0.00%)  0
Venoocclusive disease  1  3/373 (0.80%)  3 0/192 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA version 19.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Letermovir Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   360/373 (96.51%)      186/192 (96.88%)    
Blood and lymphatic system disorders     
Anaemia  1  24/373 (6.43%)  39 12/192 (6.25%)  13
Febrile neutropenia  1  28/373 (7.51%)  28 19/192 (9.90%)  20
Neutropenia  1  18/373 (4.83%)  20 11/192 (5.73%)  12
Thrombocytopenia  1  27/373 (7.24%)  32 13/192 (6.77%)  13
Eye disorders     
Dry eye  1  24/373 (6.43%)  24 12/192 (6.25%)  12
Gastrointestinal disorders     
Abdominal pain  1  49/373 (13.14%)  53 19/192 (9.90%)  21
Abdominal pain upper  1  23/373 (6.17%)  30 17/192 (8.85%)  20
Constipation  1  30/373 (8.04%)  30 22/192 (11.46%)  24
Diarrhoea  1  108/373 (28.95%)  139 51/192 (26.56%)  64
Dry mouth  1  21/373 (5.63%)  22 11/192 (5.73%)  11
Dyspepsia  1  21/373 (5.63%)  22 6/192 (3.13%)  8
Gastrooesophageal reflux disease  1  6/373 (1.61%)  6 11/192 (5.73%)  11
Nausea  1  106/373 (28.42%)  141 53/192 (27.60%)  64
Stomatitis  1  24/373 (6.43%)  25 14/192 (7.29%)  14
Vomiting  1  79/373 (21.18%)  93 35/192 (18.23%)  40
General disorders     
Asthenia  1  29/373 (7.77%)  36 9/192 (4.69%)  13
Chest pain  1  20/373 (5.36%)  21 5/192 (2.60%)  5
Fatigue  1  55/373 (14.75%)  63 26/192 (13.54%)  30
Mucosal inflammation  1  45/373 (12.06%)  47 24/192 (12.50%)  24
Oedema peripheral  1  60/373 (16.09%)  74 23/192 (11.98%)  27
Pyrexia  1  85/373 (22.79%)  112 50/192 (26.04%)  60
Immune system disorders     
Graft versus host disease  1  147/373 (39.41%)  173 74/192 (38.54%)  91
Infections and infestations     
Bacteraemia  1  21/373 (5.63%)  24 4/192 (2.08%)  5
Cytomegalovirus infection  1  55/373 (14.75%)  65 77/192 (40.10%)  93
Nasopharyngitis  1  19/373 (5.09%)  22 8/192 (4.17%)  8
Viraemia  1  12/373 (3.22%)  12 12/192 (6.25%)  12
Investigations     
Alanine aminotransferase increased  1  26/373 (6.97%)  31 17/192 (8.85%)  20
Aspartate aminotransferase increased  1  21/373 (5.63%)  24 13/192 (6.77%)  16
Blood creatinine increased  1  39/373 (10.46%)  43 14/192 (7.29%)  17
Metabolism and nutrition disorders     
Decreased appetite  1  43/373 (11.53%)  48 26/192 (13.54%)  26
Hyperglycaemia  1  31/373 (8.31%)  31 13/192 (6.77%)  14
Hyperkalaemia  1  28/373 (7.51%)  29 5/192 (2.60%)  5
Hypokalaemia  1  23/373 (6.17%)  25 12/192 (6.25%)  13
Hypomagnesaemia  1  24/373 (6.43%)  24 15/192 (7.81%)  16
Hyponatraemia  1  23/373 (6.17%)  24 10/192 (5.21%)  10
Musculoskeletal and connective tissue disorders     
Arthralgia  1  30/373 (8.04%)  31 15/192 (7.81%)  18
Back pain  1  24/373 (6.43%)  26 20/192 (10.42%)  22
Muscle spasms  1  12/373 (3.22%)  13 10/192 (5.21%)  12
Myalgia  1  21/373 (5.63%)  21 4/192 (2.08%)  4
Pain in extremity  1  20/373 (5.36%)  24 16/192 (8.33%)  17
Nervous system disorders     
Dizziness  1  29/373 (7.77%)  30 16/192 (8.33%)  16
Dysgeusia  1  19/373 (5.09%)  19 10/192 (5.21%)  10
Headache  1  58/373 (15.55%)  68 24/192 (12.50%)  26
Tremor  1  29/373 (7.77%)  30 13/192 (6.77%)  14
Psychiatric disorders     
Anxiety  1  23/373 (6.17%)  23 5/192 (2.60%)  5
Insomnia  1  35/373 (9.38%)  37 12/192 (6.25%)  12
Renal and urinary disorders     
Acute kidney injury  1  35/373 (9.38%)  37 22/192 (11.46%)  25
Dysuria  1  17/373 (4.56%)  17 11/192 (5.73%)  11
Respiratory, thoracic and mediastinal disorders     
Cough  1  62/373 (16.62%)  70 27/192 (14.06%)  28
Dyspnoea  1  36/373 (9.65%)  38 9/192 (4.69%)  10
Epistaxis  1  25/373 (6.70%)  29 13/192 (6.77%)  13
Oropharyngeal pain  1  32/373 (8.58%)  34 19/192 (9.90%)  20
Rhinorrhoea  1  15/373 (4.02%)  18 10/192 (5.21%)  11
Skin and subcutaneous tissue disorders     
Dry skin  1  31/373 (8.31%)  32 16/192 (8.33%)  19
Erythema  1  34/373 (9.12%)  37 12/192 (6.25%)  13
Pruritus  1  31/373 (8.31%)  35 12/192 (6.25%)  14
Rash  1  90/373 (24.13%)  109 51/192 (26.56%)  62
Vascular disorders     
Hypertension  1  34/373 (9.12%)  38 23/192 (11.98%)  24
Hypotension  1  16/373 (4.29%)  16 11/192 (5.73%)  13
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA version 19.1
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The sponsor must have the opportunity to review all proposed abstracts, manuscripts or presentations regarding this trial 45 days prior to submission for publication/presentation.
Results Point of Contact
Name/Title: Senior Vice President, Global Clinical Development
Organization: Merck Sharp & Dohme Corp.
Phone: 1-800-672-6372
Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT02137772     History of Changes
Other Study ID Numbers: 8228-001
2013-003831-31 ( EudraCT Number )
152923 ( Registry Identifier: JAPIC-CTI )
First Submitted: May 12, 2014
First Posted: May 14, 2014
Results First Submitted: October 16, 2017
Results First Posted: November 17, 2017
Last Update Posted: October 25, 2018