Trial Outcomes & Findings for MK-8228 (Letermovir) in the Prevention of Human Cytomegalovirus (CMV) Infection and Disease in Adult Japanese Kidney Transplant Recipients (MK-8228-042) (NCT NCT04129398)
NCT ID: NCT04129398
Last Updated: 2024-08-21
Results Overview
Percentage of participants with one or more adverse events (AEs)
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
22 participants
Primary outcome timeframe
Up to week 52 post-transplant
Results posted on
2024-08-21
Participant Flow
This study enrolled adult Japanese kidney transplant recipients who are organ donor (D) or organ recipient (R) seropositive (D+/R-, D+/R+ or D-/R+) for Cytomegalovirus (CMV) as participants.
Intravenous (IV) infusion of letermovir (LET) was intended to administer participants who cannot tolerate swallowing oral letermovir and/or does develop a condition that may interfere with the absorption of the oral LET. None of the participants received IV LET.
Participant milestones
| Measure |
Letermovir
Letermovir oral or intravenous (IV) formulation was administered once daily for up to 28 weeks, beginning up to 7 days post-transplant. The dose was 240 mg once daily for participants receiving concomitant cyclosporin A (CsA) and 480 mg once daily for participants not receiving CsA. IV infusion was administered only to participants who were unable to swallow tablets or who had a condition that may have interfered with absorption of the tablets.
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|---|---|
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Overall Study
STARTED
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22
|
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Overall Study
COMPLETED
|
20
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Overall Study
NOT COMPLETED
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2
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Reasons for withdrawal
| Measure |
Letermovir
Letermovir oral or intravenous (IV) formulation was administered once daily for up to 28 weeks, beginning up to 7 days post-transplant. The dose was 240 mg once daily for participants receiving concomitant cyclosporin A (CsA) and 480 mg once daily for participants not receiving CsA. IV infusion was administered only to participants who were unable to swallow tablets or who had a condition that may have interfered with absorption of the tablets.
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|---|---|
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Overall Study
Physician Decision
|
2
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Baseline Characteristics
MK-8228 (Letermovir) in the Prevention of Human Cytomegalovirus (CMV) Infection and Disease in Adult Japanese Kidney Transplant Recipients (MK-8228-042)
Baseline characteristics by cohort
| Measure |
Letermovir
n=22 Participants
Letermovir oral or intravenous (IV) formulation was administered once daily for up to 28 weeks, beginning up to 7 days post-transplant. The dose was 240 mg once daily for participants receiving concomitant cyclosporin A (CsA) and 480 mg once daily for participants not receiving CsA. IV infusion was administered only to participants who were unable to swallow tablets or who had a condition that may have interfered with absorption of the tablets.
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|---|---|
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Age, Continuous
|
48.5 Years
STANDARD_DEVIATION 12.3 • n=99 Participants
|
|
Sex: Female, Male
Female
|
6 Participants
n=99 Participants
|
|
Sex: Female, Male
Male
|
16 Participants
n=99 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=99 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
22 Participants
n=99 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Asian
|
22 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
White
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
PRIMARY outcome
Timeframe: Up to week 52 post-transplantPopulation: All participants who received at least one dose of study treatment.
Percentage of participants with one or more adverse events (AEs)
Outcome measures
| Measure |
Letermovir
n=22 Participants
Letermovir oral or intravenous (IV) formulation was administered once daily for up to 28 weeks, beginning up to 7 days post-transplant. The dose was 240 mg once daily for participants receiving concomitant cyclosporin A (CsA) and 480 mg once daily for participants not receiving CsA. IV infusion was administered only to participants who were unable to swallow tablets or who had a condition that may have interfered with absorption of the tablets.
|
Letermovir D+/R-
Letermovir oral or intravenous (IV) formulation was administered once daily for up to 28 weeks, beginning up to 7 days post-transplant. The dose was 240 mg once daily for participants receiving concomitant cyclosporin A (CsA) and 480 mg once daily for participants not receiving CsA. IV infusion was administered only to participants who were unable to swallow tablets or who had a condition that may have interfered with absorption of the tablets. Letermovir D+/R- represents the D+/R- subgroup.
|
Letermovir R+
Letermovir oral or intravenous (IV) formulation was administered once daily for up to 28 weeks, beginning up to 7 days post-transplant. The dose was 240 mg once daily for participants receiving concomitant cyclosporin A (CsA) and 480 mg once daily for participants not receiving CsA. IV infusion was administered only to participants who were unable to swallow tablets or who had a condition that may have interfered with absorption of the tablets. Letermovir R+ represents the R+ subgroup (D+/R+ or D-/R+)
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|---|---|---|---|
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Percentage of Participants With Adverse Events (AEs)
|
90.9 Percentage of Participants
|
—
|
—
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PRIMARY outcome
Timeframe: Up to week 28 post-transplantPopulation: All participants who received at least one dose of treatment.
Percentage of participants who discontinued from study drug due to an AE
Outcome measures
| Measure |
Letermovir
n=22 Participants
Letermovir oral or intravenous (IV) formulation was administered once daily for up to 28 weeks, beginning up to 7 days post-transplant. The dose was 240 mg once daily for participants receiving concomitant cyclosporin A (CsA) and 480 mg once daily for participants not receiving CsA. IV infusion was administered only to participants who were unable to swallow tablets or who had a condition that may have interfered with absorption of the tablets.
|
Letermovir D+/R-
Letermovir oral or intravenous (IV) formulation was administered once daily for up to 28 weeks, beginning up to 7 days post-transplant. The dose was 240 mg once daily for participants receiving concomitant cyclosporin A (CsA) and 480 mg once daily for participants not receiving CsA. IV infusion was administered only to participants who were unable to swallow tablets or who had a condition that may have interfered with absorption of the tablets. Letermovir D+/R- represents the D+/R- subgroup.
|
Letermovir R+
Letermovir oral or intravenous (IV) formulation was administered once daily for up to 28 weeks, beginning up to 7 days post-transplant. The dose was 240 mg once daily for participants receiving concomitant cyclosporin A (CsA) and 480 mg once daily for participants not receiving CsA. IV infusion was administered only to participants who were unable to swallow tablets or who had a condition that may have interfered with absorption of the tablets. Letermovir R+ represents the R+ subgroup (D+/R+ or D-/R+)
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|---|---|---|---|
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Percentage of Participants Who Discontinued From Study Drug Due to an AE
|
13.6 Percentage of participants
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—
|
—
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SECONDARY outcome
Timeframe: Up to Week 52 post-transplantPopulation: All allocated participants who received at least one dose of study treatment, who were organ donor (D) or organ recipient (R) seropositive (D+/R-, D+/R+ or D-/R+) for Cytomegalovirus (CMV) and had no detectable CMV viral DNA (measured by central laboratory) on Day 1.
CMV disease was defined as the presence of either CMV end-organ disease or CMV syndrome and was confirmed by an independent, blinded Clinical Adjudication Committee (CAC). Only CAC-confirmed ("adjudicated") cases were included in percentage of participants who met the endpoint. Investigator-assessed cases which were not confirmed by the CAC were not included. Participants who have undergone anti-CMV treatment was defined as initiation of approved anti-CMV agents based on at least one positive cell on CMV antigenemia and/or quantifiable CMV DNA PCR assay performed locally.
Outcome measures
| Measure |
Letermovir
n=21 Participants
Letermovir oral or intravenous (IV) formulation was administered once daily for up to 28 weeks, beginning up to 7 days post-transplant. The dose was 240 mg once daily for participants receiving concomitant cyclosporin A (CsA) and 480 mg once daily for participants not receiving CsA. IV infusion was administered only to participants who were unable to swallow tablets or who had a condition that may have interfered with absorption of the tablets.
|
Letermovir D+/R-
n=12 Participants
Letermovir oral or intravenous (IV) formulation was administered once daily for up to 28 weeks, beginning up to 7 days post-transplant. The dose was 240 mg once daily for participants receiving concomitant cyclosporin A (CsA) and 480 mg once daily for participants not receiving CsA. IV infusion was administered only to participants who were unable to swallow tablets or who had a condition that may have interfered with absorption of the tablets. Letermovir D+/R- represents the D+/R- subgroup.
|
Letermovir R+
n=9 Participants
Letermovir oral or intravenous (IV) formulation was administered once daily for up to 28 weeks, beginning up to 7 days post-transplant. The dose was 240 mg once daily for participants receiving concomitant cyclosporin A (CsA) and 480 mg once daily for participants not receiving CsA. IV infusion was administered only to participants who were unable to swallow tablets or who had a condition that may have interfered with absorption of the tablets. Letermovir R+ represents the R+ subgroup (D+/R+ or D-/R+)
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|---|---|---|---|
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Percentage of Participants With Adjudicated CMV Disease or Undergone Anti-CMV Treatment
With CMV Disease or Started Anti-CMV Treatment Through Week 52 Post-Transplant
|
19.0 Percentage of Participants
Interval 5.4 to 41.9
|
33.3 Percentage of Participants
Interval 9.9 to 65.1
|
0.0 Percentage of Participants
Interval 0.0 to 33.6
|
|
Percentage of Participants With Adjudicated CMV Disease or Undergone Anti-CMV Treatment
With CMV Disease or Started Anti-CMV Treatment Through Week 28 Post-Transplant
|
0.0 Percentage of Participants
Interval 0.0 to 16.1
|
0.0 Percentage of Participants
Interval 0.0 to 26.5
|
0.0 Percentage of Participants
Interval 0.0 to 33.6
|
SECONDARY outcome
Timeframe: Up to Week 52 post-transplantPopulation: All allocated participants who received at least one dose of study treatment, who were organ donor (D) or organ recipient (R) seropositive (D+/R-, D+/R+ or D-/R+) for Cytomegalovirus (CMV) and had no detectable CMV viral DNA (measured by central laboratory) on Day 1.
CMV disease was defined as the presence of either CMV end-organ disease or CMV syndrome and was confirmed by an independent, blinded Clinical Adjudication Committee (CAC). Only CAC-confirmed ("adjudicated") cases were included in percentage of participants who met the endpoint. Investigator-assessed cases which were not confirmed by the CAC were not included.
Outcome measures
| Measure |
Letermovir
n=21 Participants
Letermovir oral or intravenous (IV) formulation was administered once daily for up to 28 weeks, beginning up to 7 days post-transplant. The dose was 240 mg once daily for participants receiving concomitant cyclosporin A (CsA) and 480 mg once daily for participants not receiving CsA. IV infusion was administered only to participants who were unable to swallow tablets or who had a condition that may have interfered with absorption of the tablets.
|
Letermovir D+/R-
n=12 Participants
Letermovir oral or intravenous (IV) formulation was administered once daily for up to 28 weeks, beginning up to 7 days post-transplant. The dose was 240 mg once daily for participants receiving concomitant cyclosporin A (CsA) and 480 mg once daily for participants not receiving CsA. IV infusion was administered only to participants who were unable to swallow tablets or who had a condition that may have interfered with absorption of the tablets. Letermovir D+/R- represents the D+/R- subgroup.
|
Letermovir R+
n=9 Participants
Letermovir oral or intravenous (IV) formulation was administered once daily for up to 28 weeks, beginning up to 7 days post-transplant. The dose was 240 mg once daily for participants receiving concomitant cyclosporin A (CsA) and 480 mg once daily for participants not receiving CsA. IV infusion was administered only to participants who were unable to swallow tablets or who had a condition that may have interfered with absorption of the tablets. Letermovir R+ represents the R+ subgroup (D+/R+ or D-/R+)
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|---|---|---|---|
|
Percentage of Participants With Adjudicated CMV Disease
With CMV Disease Through Week 28 Post-Transplant
|
0.0 Percentage of Participants
Interval 0.0 to 16.1
|
0.0 Percentage of Participants
Interval 0.0 to 26.5
|
0.0 Percentage of Participants
Interval 0.0 to 33.6
|
|
Percentage of Participants With Adjudicated CMV Disease
With CMV Disease Through Week 52 Post-Transplant
|
9.5 Percentage of Participants
Interval 1.2 to 30.4
|
16.7 Percentage of Participants
Interval 2.1 to 48.4
|
0.0 Percentage of Participants
Interval 0.0 to 33.6
|
SECONDARY outcome
Timeframe: Up to Week 52 post-transplantPopulation: All allocated participants who received at least one dose of study treatment, who were organ donor (D) or organ recipient (R) seropositive (D+/R-, D+/R+ or D-/R+) for Cytomegalovirus (CMV) and had no detectable CMV viral DNA (measured by central laboratory) on Day 1.
Quantifiable CMV DNAemia (central) was defined as any case with a numeric value or \>910,000,000 (not including reporting of PCR results as "detected, not quantifiable") using the Roche COBAS® AmpliPrep/COBAS TaqMan® (CAP/CTM) assay, which was performed by the central laboratory.
Outcome measures
| Measure |
Letermovir
n=21 Participants
Letermovir oral or intravenous (IV) formulation was administered once daily for up to 28 weeks, beginning up to 7 days post-transplant. The dose was 240 mg once daily for participants receiving concomitant cyclosporin A (CsA) and 480 mg once daily for participants not receiving CsA. IV infusion was administered only to participants who were unable to swallow tablets or who had a condition that may have interfered with absorption of the tablets.
|
Letermovir D+/R-
n=12 Participants
Letermovir oral or intravenous (IV) formulation was administered once daily for up to 28 weeks, beginning up to 7 days post-transplant. The dose was 240 mg once daily for participants receiving concomitant cyclosporin A (CsA) and 480 mg once daily for participants not receiving CsA. IV infusion was administered only to participants who were unable to swallow tablets or who had a condition that may have interfered with absorption of the tablets. Letermovir D+/R- represents the D+/R- subgroup.
|
Letermovir R+
n=9 Participants
Letermovir oral or intravenous (IV) formulation was administered once daily for up to 28 weeks, beginning up to 7 days post-transplant. The dose was 240 mg once daily for participants receiving concomitant cyclosporin A (CsA) and 480 mg once daily for participants not receiving CsA. IV infusion was administered only to participants who were unable to swallow tablets or who had a condition that may have interfered with absorption of the tablets. Letermovir R+ represents the R+ subgroup (D+/R+ or D-/R+)
|
|---|---|---|---|
|
Percentage of Participants With Quantifiable CMV DNAemia
Quantifiable CMV DNAemia Through Week 52 Post-transplant
|
23.8 Percentage of participants
Interval 8.2 to 47.2
|
41.7 Percentage of participants
Interval 15.2 to 72.3
|
0.0 Percentage of participants
Interval 0.0 to 33.6
|
|
Percentage of Participants With Quantifiable CMV DNAemia
Quantifiable CMV DNAemia Through Week 28 Post-transplant
|
4.8 Percentage of participants
Interval 0.1 to 23.8
|
8.3 Percentage of participants
Interval 0.2 to 38.5
|
0.0 Percentage of participants
Interval 0.0 to 33.6
|
SECONDARY outcome
Timeframe: Any day between Days 6-10: pre-dose, 1, 2.5, 5, 8 and 24 hrs post-dosePopulation: The analysis population consisted of all participants who received at least 1 dose of study treatment and had at least one measurable pharmacokinetic (PK) sample.
AUCtau was defined as a measure of letermovir exposure that was calculated as the product of plasma drug concentration and time following an oral administration of letermovir.
Outcome measures
| Measure |
Letermovir
n=21 Participants
Letermovir oral or intravenous (IV) formulation was administered once daily for up to 28 weeks, beginning up to 7 days post-transplant. The dose was 240 mg once daily for participants receiving concomitant cyclosporin A (CsA) and 480 mg once daily for participants not receiving CsA. IV infusion was administered only to participants who were unable to swallow tablets or who had a condition that may have interfered with absorption of the tablets.
|
Letermovir D+/R-
Letermovir oral or intravenous (IV) formulation was administered once daily for up to 28 weeks, beginning up to 7 days post-transplant. The dose was 240 mg once daily for participants receiving concomitant cyclosporin A (CsA) and 480 mg once daily for participants not receiving CsA. IV infusion was administered only to participants who were unable to swallow tablets or who had a condition that may have interfered with absorption of the tablets. Letermovir D+/R- represents the D+/R- subgroup.
|
Letermovir R+
Letermovir oral or intravenous (IV) formulation was administered once daily for up to 28 weeks, beginning up to 7 days post-transplant. The dose was 240 mg once daily for participants receiving concomitant cyclosporin A (CsA) and 480 mg once daily for participants not receiving CsA. IV infusion was administered only to participants who were unable to swallow tablets or who had a condition that may have interfered with absorption of the tablets. Letermovir R+ represents the R+ subgroup (D+/R+ or D-/R+)
|
|---|---|---|---|
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Area Under the Concentration-time Curve During a Dosing Interval (AUCtau) of Plasma Letermovir-oral Treatment
|
156000 ng*hr/mL
Geometric Coefficient of Variation 47.3
|
—
|
—
|
SECONDARY outcome
Timeframe: Any day between Days 6-10: 24hrs post-dosePopulation: The analysis population consisted of all participants who received at least 1 dose of study treatment and had at least one measurable PK sample.
Ctrough was defined as the minimum concentration of letermovir that occurred immediately following an oral administration of letermovir.
Outcome measures
| Measure |
Letermovir
n=21 Participants
Letermovir oral or intravenous (IV) formulation was administered once daily for up to 28 weeks, beginning up to 7 days post-transplant. The dose was 240 mg once daily for participants receiving concomitant cyclosporin A (CsA) and 480 mg once daily for participants not receiving CsA. IV infusion was administered only to participants who were unable to swallow tablets or who had a condition that may have interfered with absorption of the tablets.
|
Letermovir D+/R-
Letermovir oral or intravenous (IV) formulation was administered once daily for up to 28 weeks, beginning up to 7 days post-transplant. The dose was 240 mg once daily for participants receiving concomitant cyclosporin A (CsA) and 480 mg once daily for participants not receiving CsA. IV infusion was administered only to participants who were unable to swallow tablets or who had a condition that may have interfered with absorption of the tablets. Letermovir D+/R- represents the D+/R- subgroup.
|
Letermovir R+
Letermovir oral or intravenous (IV) formulation was administered once daily for up to 28 weeks, beginning up to 7 days post-transplant. The dose was 240 mg once daily for participants receiving concomitant cyclosporin A (CsA) and 480 mg once daily for participants not receiving CsA. IV infusion was administered only to participants who were unable to swallow tablets or who had a condition that may have interfered with absorption of the tablets. Letermovir R+ represents the R+ subgroup (D+/R+ or D-/R+)
|
|---|---|---|---|
|
Trough Concentration (Ctrough) of Plasma Letermovir - Oral Treatment
|
1700 ng/mL
Geometric Coefficient of Variation 121.9
|
—
|
—
|
SECONDARY outcome
Timeframe: Any day between Days 6-10: pre-dose, 1, 2.5, 5, 8 and 24 hrs post-dosePopulation: The analysis population consisted of all participants who received at least 1 dose of study treatment and had at least one measurable PK sample.
Cmax was defined as the maximum concentration of letermovir observed in plasma following an oral administration of letermovir.
Outcome measures
| Measure |
Letermovir
n=21 Participants
Letermovir oral or intravenous (IV) formulation was administered once daily for up to 28 weeks, beginning up to 7 days post-transplant. The dose was 240 mg once daily for participants receiving concomitant cyclosporin A (CsA) and 480 mg once daily for participants not receiving CsA. IV infusion was administered only to participants who were unable to swallow tablets or who had a condition that may have interfered with absorption of the tablets.
|
Letermovir D+/R-
Letermovir oral or intravenous (IV) formulation was administered once daily for up to 28 weeks, beginning up to 7 days post-transplant. The dose was 240 mg once daily for participants receiving concomitant cyclosporin A (CsA) and 480 mg once daily for participants not receiving CsA. IV infusion was administered only to participants who were unable to swallow tablets or who had a condition that may have interfered with absorption of the tablets. Letermovir D+/R- represents the D+/R- subgroup.
|
Letermovir R+
Letermovir oral or intravenous (IV) formulation was administered once daily for up to 28 weeks, beginning up to 7 days post-transplant. The dose was 240 mg once daily for participants receiving concomitant cyclosporin A (CsA) and 480 mg once daily for participants not receiving CsA. IV infusion was administered only to participants who were unable to swallow tablets or who had a condition that may have interfered with absorption of the tablets. Letermovir R+ represents the R+ subgroup (D+/R+ or D-/R+)
|
|---|---|---|---|
|
Maximum Concentration (Cmax) of Plasma Letermovir - Oral Treatment
|
17900 ng/mL
Geometric Coefficient of Variation 31.1
|
—
|
—
|
SECONDARY outcome
Timeframe: Any day between Days 6-10: pre-dose, 1, 2.5, 5, 8 and 24 hrs post-dosePopulation: The analysis population consisted of all participants who received at least 1 dose of study treatment and had at least one measurable PK sample.
Tmax was defined as the time required post dosing to reach a maximum plasma concentration of letermovir following an oral administration of letermovir.
Outcome measures
| Measure |
Letermovir
n=21 Participants
Letermovir oral or intravenous (IV) formulation was administered once daily for up to 28 weeks, beginning up to 7 days post-transplant. The dose was 240 mg once daily for participants receiving concomitant cyclosporin A (CsA) and 480 mg once daily for participants not receiving CsA. IV infusion was administered only to participants who were unable to swallow tablets or who had a condition that may have interfered with absorption of the tablets.
|
Letermovir D+/R-
Letermovir oral or intravenous (IV) formulation was administered once daily for up to 28 weeks, beginning up to 7 days post-transplant. The dose was 240 mg once daily for participants receiving concomitant cyclosporin A (CsA) and 480 mg once daily for participants not receiving CsA. IV infusion was administered only to participants who were unable to swallow tablets or who had a condition that may have interfered with absorption of the tablets. Letermovir D+/R- represents the D+/R- subgroup.
|
Letermovir R+
Letermovir oral or intravenous (IV) formulation was administered once daily for up to 28 weeks, beginning up to 7 days post-transplant. The dose was 240 mg once daily for participants receiving concomitant cyclosporin A (CsA) and 480 mg once daily for participants not receiving CsA. IV infusion was administered only to participants who were unable to swallow tablets or who had a condition that may have interfered with absorption of the tablets. Letermovir R+ represents the R+ subgroup (D+/R+ or D-/R+)
|
|---|---|---|---|
|
Time to Reach Cmax (Tmax) of Plasma Letermovir - Oral Treatment
|
2.50 hr
Interval 0.92 to 23.35
|
—
|
—
|
SECONDARY outcome
Timeframe: Any day between Days 6-10: pre-dose, 1, 2.5, 5, 8 and 24 hrs post-dosePopulation: The analysis population consisted of all participants who received at least 1 dose of study treatment and had at least one measurable PK sample.
Apparent clearance at steady state (CLss/F) of plasma letermovir following an oral administration of letermovir.
Outcome measures
| Measure |
Letermovir
n=21 Participants
Letermovir oral or intravenous (IV) formulation was administered once daily for up to 28 weeks, beginning up to 7 days post-transplant. The dose was 240 mg once daily for participants receiving concomitant cyclosporin A (CsA) and 480 mg once daily for participants not receiving CsA. IV infusion was administered only to participants who were unable to swallow tablets or who had a condition that may have interfered with absorption of the tablets.
|
Letermovir D+/R-
Letermovir oral or intravenous (IV) formulation was administered once daily for up to 28 weeks, beginning up to 7 days post-transplant. The dose was 240 mg once daily for participants receiving concomitant cyclosporin A (CsA) and 480 mg once daily for participants not receiving CsA. IV infusion was administered only to participants who were unable to swallow tablets or who had a condition that may have interfered with absorption of the tablets. Letermovir D+/R- represents the D+/R- subgroup.
|
Letermovir R+
Letermovir oral or intravenous (IV) formulation was administered once daily for up to 28 weeks, beginning up to 7 days post-transplant. The dose was 240 mg once daily for participants receiving concomitant cyclosporin A (CsA) and 480 mg once daily for participants not receiving CsA. IV infusion was administered only to participants who were unable to swallow tablets or who had a condition that may have interfered with absorption of the tablets. Letermovir R+ represents the R+ subgroup (D+/R+ or D-/R+)
|
|---|---|---|---|
|
Apparent Clearance at Steady State (CLss/F) of Plasma Letermovir - Oral Treatment
|
3.08 L/hr
Geometric Coefficient of Variation 47.3
|
—
|
—
|
SECONDARY outcome
Timeframe: Any day between Days 6-10: pre-dose, 1, 2.5, 5, 8 and 24 hrs post-dosePopulation: The analysis population consisted of all participants who received at least 1 dose of study treatment and had at least one measurable PK sample. None of the participants received letermovir IV.
AUCtau was defined as a measure of letermovir exposure that was calculated as the product of plasma drug concentration and time following an IV administration of letermovir was intended to measure.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Pre-dose on Weeks 1, 2, 4, 6, 8, 10, 12, 16, 20, 24 and 28Population: The analysis population consisted of all participants who received at least 1 dose of study treatment and had at least one measurable PK sample. None of the participants received letermovir IV.
Ctrough was defined as the minimum concentration of letermovir that occurred immediately following an IV administration of letermovir was intended to measure.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Any day between Days 6-10: at end of infusion (1 hours post dose)Population: The analysis population consisted of all participants who received at least 1 dose of study treatment and had at least one measurable PK sample. None of the participants received letermovir IV.
Ceoi is defined as the amount of letermovir in plasma following an IV administration of letermovir was intended to measure.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Any day between Days 6-10: pre-dose, 1, 2.5, 5, 8 and 24 hrs post-dosePopulation: The analysis population consisted of all participants who received at least 1 dose of study treatment and had at least one measurable PK sample. None of the participants received letermovir IV.
Clearance at steady state (CLss) of plasma letermovir following an IV administration of letermovir was intended to measure.
Outcome measures
Outcome data not reported
Adverse Events
Letermovir
Serious events: 7 serious events
Other events: 13 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Letermovir
n=22 participants at risk
Letermovir oral or intravenous (IV) formulation was administered once daily for up to 28 weeks, beginning up to 7 days post-transplant. The dose was 240 mg once daily for participants receiving concomitant cyclosporin A (CsA) and 480 mg once daily for participants not receiving CsA. IV infusion was administered only to participants who were unable to swallow tablets or who had a condition that may have interfered with absorption of the tablets.
|
|---|---|
|
Gastrointestinal disorders
Constipation
|
4.5%
1/22 • Number of events 1 • Up to week 52 post-transplant
All-Cause Mortality included all randomized participants. Non-serious and SAEs were reported for all randomized participants who received at least one dose of study treatment.
|
|
Infections and infestations
Adenoviral haemorrhagic cystitis
|
4.5%
1/22 • Number of events 1 • Up to week 52 post-transplant
All-Cause Mortality included all randomized participants. Non-serious and SAEs were reported for all randomized participants who received at least one dose of study treatment.
|
|
Infections and infestations
Herpes zoster
|
4.5%
1/22 • Number of events 1 • Up to week 52 post-transplant
All-Cause Mortality included all randomized participants. Non-serious and SAEs were reported for all randomized participants who received at least one dose of study treatment.
|
|
Infections and infestations
Pneumocystis jirovecii pneumonia
|
4.5%
1/22 • Number of events 1 • Up to week 52 post-transplant
All-Cause Mortality included all randomized participants. Non-serious and SAEs were reported for all randomized participants who received at least one dose of study treatment.
|
|
Infections and infestations
Tonsillitis
|
4.5%
1/22 • Number of events 1 • Up to week 52 post-transplant
All-Cause Mortality included all randomized participants. Non-serious and SAEs were reported for all randomized participants who received at least one dose of study treatment.
|
|
Infections and infestations
Urinary tract infection
|
4.5%
1/22 • Number of events 2 • Up to week 52 post-transplant
All-Cause Mortality included all randomized participants. Non-serious and SAEs were reported for all randomized participants who received at least one dose of study treatment.
|
|
Injury, poisoning and procedural complications
Complications of transplanted kidney
|
4.5%
1/22 • Number of events 1 • Up to week 52 post-transplant
All-Cause Mortality included all randomized participants. Non-serious and SAEs were reported for all randomized participants who received at least one dose of study treatment.
|
|
Vascular disorders
Lymphocele
|
4.5%
1/22 • Number of events 1 • Up to week 52 post-transplant
All-Cause Mortality included all randomized participants. Non-serious and SAEs were reported for all randomized participants who received at least one dose of study treatment.
|
Other adverse events
| Measure |
Letermovir
n=22 participants at risk
Letermovir oral or intravenous (IV) formulation was administered once daily for up to 28 weeks, beginning up to 7 days post-transplant. The dose was 240 mg once daily for participants receiving concomitant cyclosporin A (CsA) and 480 mg once daily for participants not receiving CsA. IV infusion was administered only to participants who were unable to swallow tablets or who had a condition that may have interfered with absorption of the tablets.
|
|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
9.1%
2/22 • Number of events 2 • Up to week 52 post-transplant
All-Cause Mortality included all randomized participants. Non-serious and SAEs were reported for all randomized participants who received at least one dose of study treatment.
|
|
Blood and lymphatic system disorders
Leukopenia
|
9.1%
2/22 • Number of events 2 • Up to week 52 post-transplant
All-Cause Mortality included all randomized participants. Non-serious and SAEs were reported for all randomized participants who received at least one dose of study treatment.
|
|
Gastrointestinal disorders
Diarrhoea
|
13.6%
3/22 • Number of events 3 • Up to week 52 post-transplant
All-Cause Mortality included all randomized participants. Non-serious and SAEs were reported for all randomized participants who received at least one dose of study treatment.
|
|
Gastrointestinal disorders
Nausea
|
9.1%
2/22 • Number of events 2 • Up to week 52 post-transplant
All-Cause Mortality included all randomized participants. Non-serious and SAEs were reported for all randomized participants who received at least one dose of study treatment.
|
|
Gastrointestinal disorders
Stomatitis
|
18.2%
4/22 • Number of events 4 • Up to week 52 post-transplant
All-Cause Mortality included all randomized participants. Non-serious and SAEs were reported for all randomized participants who received at least one dose of study treatment.
|
|
Infections and infestations
Urinary tract infection
|
9.1%
2/22 • Number of events 2 • Up to week 52 post-transplant
All-Cause Mortality included all randomized participants. Non-serious and SAEs were reported for all randomized participants who received at least one dose of study treatment.
|
|
Injury, poisoning and procedural complications
Incisional hernia
|
9.1%
2/22 • Number of events 2 • Up to week 52 post-transplant
All-Cause Mortality included all randomized participants. Non-serious and SAEs were reported for all randomized participants who received at least one dose of study treatment.
|
|
Investigations
Neutrophil count decreased
|
13.6%
3/22 • Number of events 4 • Up to week 52 post-transplant
All-Cause Mortality included all randomized participants. Non-serious and SAEs were reported for all randomized participants who received at least one dose of study treatment.
|
|
Metabolism and nutrition disorders
Hyperlipidaemia
|
13.6%
3/22 • Number of events 3 • Up to week 52 post-transplant
All-Cause Mortality included all randomized participants. Non-serious and SAEs were reported for all randomized participants who received at least one dose of study treatment.
|
|
Psychiatric disorders
Insomnia
|
9.1%
2/22 • Number of events 2 • Up to week 52 post-transplant
All-Cause Mortality included all randomized participants. Non-serious and SAEs were reported for all randomized participants who received at least one dose of study treatment.
|
|
Renal and urinary disorders
Haematuria
|
9.1%
2/22 • Number of events 2 • Up to week 52 post-transplant
All-Cause Mortality included all randomized participants. Non-serious and SAEs were reported for all randomized participants who received at least one dose of study treatment.
|
Additional Information
Senior Vice President, Global Clinical Development
Merck Sharp & Dohme LLC
Phone: 1-800-672-6372
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee The Sponsor will generally support publication of multicenter studies only in their entirety and not as individual site data. In this case, a coordinating investigator will be designated by mutual agreement. If publication activity is not directed by the Sponsor, the investigator agrees to submit all manuscripts or abstracts to the Sponsor before submission. This allows the Sponsor to protect proprietary information and to provide comments.
- Publication restrictions are in place
Restriction type: OTHER