Cytomegalovirus (CMV) Infection
Conditions
Brief summary
The primary objective of this study is to evaluate the pharmacokinetics (PK) of letermovir (LET) in pediatric participants. Participants will be enrolled in the following 3 age groups: Age Group 1: From 12 to \<18 years of age (adolescents); Age Group 2: From 2 to \<12 years of age (children); and Age Group 3: From birth to \<2 years of age (neonates, infants and toddlers). All participants will receive open label LET for 14 weeks (\ 100 days) post-transplant, with doses based on body weight and age.
Interventions
DRUGLetermovir oral granules
Granules administered orally based on age, weight, and whether participant takes cyclosporin A as a concomitant medication.
Tablet administered orally based on age, weight, and whether participant takes cyclosporin A as a concomitant medication.
DRUGLetermovir intravenous
Letermovir administered intravenously based on age, weight, and whether participant takes cyclosporin A as a concomitant medication.
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 17 Years
Healthy volunteers
No
Inclusion criteria
* All participants 12 to \<18 years old must have documented positive CMV serostatus (CMV IgG seropositive) for the recipient (R+) within 90 days prior to enrollment. Participants from birth to \<12 years old must have documented positive CMV serostatus (CMV IgG seropositive) for the recipient (R+) within 90 days prior to enrollment and/or the donor (D+); the donor serostatus should be documented within 1 year prior to enrollment. * Is the recipient of a first allogeneic HSCT (bone marrow, peripheral blood stem cell, or cord blood transplant). * Has undetectable CMV DNA from a plasma or whole blood sample collected within 5 days prior to enrollment. * Is within 28 days post-HSCT at the time of enrollment. * Females are not pregnant, not breastfeeding,and is not a woman of childbearing potential (WOCBP); or is a WOCBP who agrees to follow the contraceptive guidance during the treatment period and for at least 28 days after the last dose of study intervention. * Participants from 2 to \<18 years of age must not be on concomitant Cyclosporin A (CsA), and must be able to take LET tablets or the oral granules (either by mouth or via G tube/NG tube), provided the participant does not have a condition that may interfere with the absorption of oral medication (e.g. vomiting, diarrhea, or a malabsorptive condition) from the day of enrollment until the intensive PK sampling is completed in these participants. * For participants 2 \<12 years old their weight should be at least 10 kg; for participants from birth to \<2 years old their weight should be at least 2.5 kg and less than or equal to 15 kg at the time of enrollment.
Exclusion criteria
* Has received a previous allogeneic HSCT (Note: receipt of a previous autologous HSCT is acceptable). * Has a history of CMV end-organ disease within 6 months prior to enrollment. * Has evidence of CMV viremia at any time from either signing of the ICF or the HSCT procedure, whichever is earlier, until the time of enrollment. * Has suspected or known hypersensitivity to active or inactive ingredients of LET formulations. * Has severe hepatic insufficiency within 5 days prior to enrollment. * Is a) on renal replacement therapy (eg, hemodialysis, peritoneal dialysis) OR b) has end-stage renal impairment. * Has both moderate hepatic insufficiency and moderate-to-severe renal insufficiency. * Has an uncontrolled infection on the day of enrollment. * Requires mechanical ventilation or is hemodynamically unstable at the time of enrollment. * Has a documented positive result for a human immunodeficiency virus antibody (HIVAb) test at any time prior to enrollment, or for hepatitis C virus antibody (HCV-Ab) with detectable HCV RNA, or hepatitis B surface antigen (HBsAg) within 90 days prior to enrollment. * Has active solid tumor malignancies with the exception of localized basal cell or squamous cell skin cancer or the condition under treatment (e.g. lymphomas). * Has a preexisting cardiac condition a) for which the patient is currently being treated or b) which required hospitalization within the last 6 months or c) that may be expected to recur during the course of the trial. * Has received within 7 days prior to screening any of the following: ganciclovir; valganciclovir; foscarnet; acyclovir; valacyclovir; famciclovir. * Has received within 30 days prior to screening of any of the following: cidofovir; CMV immunoglobulin; any investigational CMV antiviral agent/biologic therapy; Rifampin and other strong inducers (such as phenytoin, carbamazepine, St John's wort (Hypericum perforatum), rifabutin and phenobarbital) and moderate inducers such as nafcillin, thioridazine, modafinil and bosentan. * Has received LET at any time prior to enrollment in this study. * Is currently participating or has participated in a study with an unapproved investigational compound or device within 28 days, or 5X half-life of the investigational compound (excluding monoclonal antibodies), whichever is longer, of initial dosing in this study. * Has previously participated in this study or any other study involving LET. * Has previously participated or is currently participating in any study involving administration of a CMV vaccine or another CMV investigational agent, or is planning to participate in a study of a CMV vaccine or another CMV investigational agent during the course of this study. * Is pregnant or expecting to conceive, is breastfeeding, or plans to breastfeed from the time of consent through 28 days after the last dose of study intervention. * Is expecting to donate eggs starting from the time of consent through 28 days after the last dose of study intervention. * Has clinically relevant drug or alcohol abuse within 12 months of screening that may interfere with participant treatment, assessment, or compliance with the protocol, as assessed by the investigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Ctrough of Plasma Letermovir Taken During Sparse PK as IV Formulation | Day 7: 24 hours post-dose | Blood was collected on treatment Day 7 in order to determine the Ctrough of plasma letermovir for participants receiving IV formulation during sparse PK. Individual values were natural log transformed and evaluated separately with a linear mixed effects model containing a fixed effect for treatment and a random effect for participant. |
| Area Under the Concentration-time Curve From Time 0 to 24 Hours Post-dose (AUC0-24) of Plasma Letermovir Taken as Oral Formulation by Ages 2 - <18 Years | Day 7: Pre-dose, 1, 2.5, 8, and 24 hours post-dose | Blood was collected on treatment Day 7 from participants aged 2 - \<18 years in order to determine the AUC0-24 of plasma letermovir for participants receiving oral formulation. Individual values were natural log transformed and evaluated separately with a linear mixed effects model containing a fixed effect for treatment and a random effect for participant. Participants aged \< 2 years were not presented as their data analysis resulted in a different measure type and method of dispersion. |
| AUC0-24 of Plasma Letermovir Taken as Oral Formulation by Ages 2 to <12 Years | Day 7: Pre-dose, 1, 2.5, 8, and 24 hours post-dose | Blood was collected on treatment Day 7 from participants aged 2 to \<12 years in order to determine the AUC0-24 of plasma letermovir for participants receiving oral formulation. Individual values were natural log transformed and evaluated separately with a linear mixed effects model containing a fixed effect for treatment and a random effect for participant. Participants aged \<2 and \>12 years were not presented as their data analysis resulted in a different measure type and method of dispersion. |
| AUC0-24 of Plasma Letermovir Taken as Oral Formulation by Ages <2 Years | Day 7: Pre-dose, 1, 2.5, 8, and 24 hours post-dose | Blood was collected on treatment Day 7 from participants aged \<2 years in order to determine the AUC0-24 of plasma letermovir for participants receiving oral formulation. Individual values were natural log transformed and evaluated separately with a linear mixed effects model containing a fixed effect for treatment and a random effect for participant. Participants aged 2 - \<18 years were not presented as their data analysis resulted in a different measure type and method of dispersion. The measure of dispersion is not determined when N \<2. |
| Maximal Concentration (Cmax) of Plasma Letermovir Taken as Oral Formulation by Ages 2 - <18 Years | Day 7: Pre-dose, 1, 2.5, 8, and 24 hours post-dose | Blood was collected on treatment Day 7 from participants aged 2 - \<18 years in order to determine the Cmax of plasma letermovir for participants receiving oral formulation. Individual values were natural log transformed and evaluated separately with a linear mixed effects model containing a fixed effect for treatment and a random effect for participant. Participants aged \< 2 years were not presented as their data analysis resulted in a different measure type and method of dispersion. |
| Cmax of Plasma Letermovir Taken as Oral Formulation by Ages 2 to <12 Years | Day 7: Pre-dose, 1, 2.5, 8, and 24 hours post-dose | Blood was collected on treatment Day 7 from participants aged 2 to \<12 years in order to determine Cmax of plasma letermovir for participants receiving oral formulation. Individual values were natural log transformed and evaluated separately with a linear mixed effects model containing a fixed effect for treatment and a random effect for participant. Participants aged \<2 and \>12 years were not presented as their data analysis resulted in a different measure type and method of dispersion. |
| Cmax of Plasma Letermovir Taken as Oral Formulation by Ages < 2 Years | Day 7: Pre-dose, 1, 2.5, 8, and 24 hours post-dose | Blood was collected on treatment Day 7 from participants aged \<2 years in order to determine the Cmax of plasma letermovir for participants receiving oral formulation. Individual values were natural log transformed and evaluated separately with a linear mixed effects model containing a fixed effect for treatment and a random effect for participant. Participants aged 2 - \<18 years were not presented as their data analysis resulted in a different measure type and method of dispersion. The measure of dispersion is not determined when N \<2 |
| Minimum Concentration of Plasma Letermovir Observed Before Next Dose (Ctrough) Taken as Oral Formulation by Ages 2 - <18 Years | Day 7: 24 hours post-dose | Blood was collected on treatment Day 7 from participants aged 2 - \<18 years in order to determine the Ctrough of plasma letermovir for participants receiving oral formulation. Individual values were natural log transformed and evaluated separately with a linear mixed effects model containing a fixed effect for treatment and a random effect for participant. Participants aged \< 2 years were not presented as their data analysis resulted in a different measure type and method of dispersion. |
| Ctrough of Plasma Letermovir Taken as Oral Formulation by Ages 2 to <12 Years | Day 7: Pre-dose, 1, 2.5, 8, and 24 hours post-dose | Blood was collected on treatment Day 7 from participants aged 2 to \<12 years in order to determine Ctrough of plasma letermovir for participants receiving oral formulation. Individual values were natural log transformed and evaluated separately with a linear mixed effects model containing a fixed effect for treatment and a random effect for participant. Participants aged \<2 and \>12 years were not presented as their data analysis resulted in a different measure type and method of dispersion. |
| Ctrough of Plasma Letermovir Taken as Oral Formulation by Ages < 2 Years | Day 7: 24 hours post-dose | Blood was collected on treatment Day 7 from participants aged \<2 years in order to determine the Ctrough of plasma letermovir for participants receiving oral formulation. Individual values were natural log transformed and evaluated separately with a linear mixed effects model containing a fixed effect for treatment and a random effect for participant. Participants aged 2 - \<18 years were not presented as their data analysis resulted in a different measure type and method of dispersion. The measure of dispersion is not determined when N \<2. |
| Ceoi of Plasma Letermovir Taken as IV Formulation by Ages <2 Years | Day 7: Pre-dose, 1, 2.5, 8, and 24 hours post-dose | Blood was collected on treatment Day 7 from participants aged \<2 years in order to determine the Ceoi of plasma letermovir for participants receiving IV formulation. As samples were collected outside the collection window Ceoi for these samples were predicted by using a log linear model. Participants aged \> 2 years were not presented as their data analysis resulted in a different measure type and method of dispersion. A measure of dispersion is not determined when N \<2. |
| AUC0-24 of Plasma Letermovir Taken as Intravenous (IV) Formulation by Ages 12 - <18 Years | Day 7: Pre-dose, 1, 2.5, 8, and 24 hours post-dose | Blood was collected on treatment Day 7 from participants aged 12 - \<18 years in order to determine the AUC0-24 of plasma letermovir for participants receiving IV formulation. Individual values were natural log transformed and evaluated separately with a linear mixed effects model containing a fixed effect for treatment and a random effect for participant. Participants aged \< 12 years were not presented as their data analysis resulted in a different measure type and method of dispersion. |
| AUC0-24 of Plasma Letermovir Taken as IV Formulation by Ages 2 to <12 Years | Day 7: Pre-dose, 1, 2.5, 8, and 24 hours post-dose | Blood was collected on treatment Day 7 from participants aged 2 to \<12 years in order to determine the AUC0-24 of plasma letermovir for participants receiving IV formulation. Individual values were natural log transformed and evaluated separately with a linear mixed effects model containing a fixed effect for treatment and a random effect for participant. Participants aged \< 2 years and \> 12 years were not presented as their data analysis resulted in a different measure type and method of dispersion. |
| AUC0-24 of Plasma Letermovir Taken as IV Formulation by Ages <2 Years | Day 7: Pre-dose, 1, 2.5, 8, and 24 hours post-dose | Blood was collected on treatment Day 7 from participants aged \<2 years in order to determine the AUC0-24 of plasma letermovir for participants receiving IV formulation. Individual values were natural log transformed and evaluated separately with a linear mixed effects model containing a fixed effect for treatment and a random effect for participant. Participants aged \> 2 years were not presented as their data analysis resulted in a different measure type and method of dispersion. The measure of dispersion is not determined when N \<2. |
| Concentration at the End of Infusion (Ceoi) of Plasma Letermovir Taken as IV Formulation by Ages 12 - <18 Years | Day 7: Pre-dose, 1, 2.5, 8, and 24 hours post-dose | Blood was collected on treatment Day 7 from participants aged 12 - \<18 years in order to determine the Ceoi of plasma letermovir for participants receiving IV formulation. As samples were collected outside the collection window Ceoi for these samples were predicted by using a log linear model .Participants aged \< 12 years were not presented as their data analysis resulted in a different measure type and method of dispersion. |
| Ceoi of Plasma Letermovir Taken as IV Formulation by Ages 2 to <12 Years | Day 7: Pre-dose, 1, 2.5, 8, and 24 hours post-dose | Blood was collected on treatment Day 7 from participants aged 2 to \<12 years in order to determine the Ceoi of plasma letermovir for participants receiving IV formulation. As samples were collected outside the collection window Ceoi for these samples were predicted by using a log linear model. Participants aged \< 2 years and \> 12 years were not presented as their data analysis resulted in a different measure type and method of dispersion. |
| Ceoi of Plasma Letermovir Taken as IV Formulation by Ages s 2 to <12 Years | Day 7: Pre-dose, 1, 2.5, 8, and 24 hours post-dose | Blood was collected on treatment Day 7 from participants aged 2 to \<12 years in order to determine the Ceoi of plasma letermovir for participants receiving IV formulation. As samples were collected outside the collection window Ceoi for these samples were predicted by using a log linear model. Participants aged \> 2 years were not presented as their data analysis resulted in a different measure type and method of dispersion. A measure of dispersion is not determined when N \<2. |
| Ctrough of Plasma Letermovir Taken as IV Formulation by Ages 12 - <18 Years | Day 7: 24 hours post-dose | Blood was collected on treatment Day 7 from participants aged 12 - \<18 years in order to determine the Ctrough of plasma letermovir for participants receiving IV formulation. Individual values were natural log transformed and evaluated separately with a linear mixed effects model containing a fixed effect for treatment and a random effect for participant. Participants aged \< 12 years were not presented as their data analysis resulted in a different measure type and method of dispersion. |
| Ctrough of Plasma Letermovir Taken as IV Formulation by Ages 2 to <12 Years | Day 7: 24 hours post-dose | Blood was collected on treatment Day 7 from participants aged 2 to \<12 years in order to determine the Ctrough of plasma letermovir for participants receiving IV formulation. Individual values were natural log transformed and evaluated separately with a linear mixed effects model containing a fixed effect for treatment and a random effect for participant. Participants aged \< 2 years and \> 12 years were not presented as their data analysis resulted in a different measure type and method of dispersion. |
| Ctrough of Plasma Letermovir Taken as IV Formulation by Ages <2 Years | Day 7: Pre-dose, 1, 2.5, 8, and 24 hours post-dose | Blood was collected on treatment Day 7 from participants aged \<2 years in order to determine the Ctrough of plasma letermovir for participants receiving IV formulation. Individual values were natural log transformed and evaluated separately with a linear mixed effects model containing a fixed effect for treatment and a random effect for participant. Participants aged \> 2 years were not presented as their data analysis resulted in a different measure type and method of dispersion. The measure type is Geometric Mean, and a measure of dispersion is not determined when N \<2. |
| Ctrough of Plasma Letermovir Taken During Sparse PK for Oral Formulation | Day 7: 24 hours post-dose | Blood was collected on treatment Day 7 in order to determine the Ctrough of plasma letermovir during sparse PK for participants receiving oral formulation. Individual values were natural log transformed and evaluated separately with a linear mixed effects model containing a fixed effect for treatment and a random effect for participant. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With One or More Adverse Event (AE) | Up to Week 48 post-transplant (up to 52 weeks) | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The 95% confidence interval (CI) is based on the exact binomial method proposed by Clopper and Pearson. |
| Percentage of Participants Who Discontinued Study Medication Due to an AE. | Up to Week 14 post-transplant (up to 18 weeks) | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The 95% CI is based on the exact binomial method proposed by Clopper and Pearson. |
| Percentage of Participants With Clinically Significant CMV Infection Through Week 14 Post-transplant | Up to Week 14 post-transplant (up to 18 weeks) | Clinically significant cytomegalovirus (CMV) infection is defined as CMV end organ disease (proven or probable) or initiation of pre-emptive therapy (PET) based on documented CMV viremia and the clinical condition of the participant. The 95% confidence interval (CI) was based on the exact binomial method proposed by Clopper and Pearson. Missing values: were handled by the Non-Completer=Failure (NC=F) approach. where failure was defined as all participants who developed clinically significant CMV infection or prematurely discontinued from the study or had a missing outcome through week 14 post-transplant visit window. |
| Percentage of Participants With Clinically Significant CMV Infection Through Week 24 Post-transplant | Up to Week 24 post-transplant (up to 28 weeks) | Clinically significant CMV infection is defined as CMV end organ disease (proven or probable) or initiation of PET based on documented CMV viremia and the clinical condition of the participant. The 95% confidence interval (CI) was based on the exact binomial method proposed by Clopper and Pearson. Missing values: were handled by the Non-Completer=Failure (NC=F) approach. where failure was defined as all participants who developed clinically significant CMV infection or prematurely discontinued from the study or had a missing outcome through week 24 post-transplant visit window. |
| Number of Participants Receiving Oral Granules With Palatability Response, Based on Taste of Medication on the First Day of Administration of Oral Formulation | Day 1 of administration of oral formulation up to Week 14 post-transplant (up to 18 weeks) | Palatability was measured by response to a questionnaire on the taste of medication , with responses from very good, good, neither good nor bad, bad or very bad. |
| Number of Participants Receiving Oral Granules With Palatability Response, Based on Taste of Medication on the Eighth Day of Administration of Oral Formulation | Day 8 of administration of oral formulation up to Week 14 post-transplant (up to 18 weeks) | Palatability was measured by response to a questionnaire on the taste of medication , with responses from very good, good, neither good nor bad, bad or very bad. |
Countries
Australia, Colombia, France, Germany, Israel, Japan, Mexico, Poland, Spain, Turkey (Türkiye), United States
Participant flow
Recruitment details
Male and female recipients of a first allogeneic hematopoietic stem cell transplant (HSCT), between the ages of birth and \<18 years of age, who were at risk for cytomegalovirus (CMV) infection and/or disease, and who had undetectable CMV deoxyribonucleic acid (DNA) collected within 5 days before enrollment. were enrolled in this study.
Participants by arm
| Arm | Count |
|---|---|
| 12 - <18 Years LET 480 mg without CsA, or 240 mg with CsA, administered either orally as tablets or in granular form, or by IV infusion, QD through week 14 (\
100 days) post-transplant. | 28 |
| 2 - <12 Years Participants ≥30 kg BW: LET 480 mg orally without CsA, or 240 mg with CsA, in granular form, or 240 mg IV with or without CsA; 18 to \<30 kg BW: LET 240 mg orally without CsA, or 120 mg with CsA, either in granular form, or 120 mg IV with or without CsA; 10 to \<18 kg BW: LET 120 mg orally without CsA, or 60 mg with CsA, in granular form, or 60 mg IV with or without CsA, all QD through week 14 (\
100 days) post-transplant. | 27 |
| Birth - <2 Years 10 to ≤15 kg BW: LET 120 mg orally without CsA, or 60 mg with CsA, in granular form, or 60 mg IV with or without CsA; 7.5 to \<10 kg BW: LET 80 mg orally without CsA, or 40 mg with CsA, either in granular form, or 40 mg IV with or without CsA; 5.0 to \<7.5 kg BW: LET 40 mg orally without CsA, or 20 mg with CsA, in granular form, or 20 mg IV with or without CsA; 2.5 to \<5.0 kg BW: LET 20 mg orally without CsA, or 10 mg with CsA, in granular form, or 10 mg IV with or without CsA, all QD through week 14 (\
100 days) post-transplant. | 8 |
| Total | 63 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Death | 3 | 2 | 0 |
| Overall Study | Not Treated | 0 | 2 | 0 |
| Overall Study | Physician Decision | 1 | 0 | 1 |
| Overall Study | Withdrawal By Parent/Guardian | 3 | 4 | 1 |
Baseline characteristics
| Characteristic | 12 - <18 Years | 2 - <12 Years | Birth - <2 Years | Total |
|---|---|---|---|---|
| Age, Continuous | 14.1 Years STANDARD_DEVIATION 1.5 | 6.6 Years STANDARD_DEVIATION 3.2 | 0.7 Years STANDARD_DEVIATION 0.3 | 9.1 Years STANDARD_DEVIATION 5.3 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 9 Participants | 4 Participants | 1 Participants | 14 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 14 Participants | 21 Participants | 6 Participants | 41 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 5 Participants | 2 Participants | 1 Participants | 8 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 6 Participants | 3 Participants | 0 Participants | 9 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 0 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 4 Participants | 2 Participants | 1 Participants | 7 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 15 Participants | 22 Participants | 7 Participants | 44 Participants |
| Sex: Female, Male Female | 13 Participants | 5 Participants | 1 Participants | 19 Participants |
| Sex: Female, Male Male | 15 Participants | 22 Participants | 7 Participants | 44 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 4 / 28 | 2 / 29 | 0 / 8 |
| other Total, other adverse events | 27 / 28 | 27 / 27 | 8 / 8 |
| serious Total, serious adverse events | 13 / 28 | 18 / 27 | 7 / 8 |
Outcome results
Primary
Area Under the Concentration-time Curve From Time 0 to 24 Hours Post-dose (AUC0-24) of Plasma Letermovir Taken as Oral Formulation by Ages 2 - <18 Years
Blood was collected on treatment Day 7 from participants aged 2 - \<18 years in order to determine the AUC0-24 of plasma letermovir for participants receiving oral formulation. Individual values were natural log transformed and evaluated separately with a linear mixed effects model containing a fixed effect for treatment and a random effect for participant. Participants aged \< 2 years were not presented as their data analysis resulted in a different measure type and method of dispersion.
Time frame: Day 7: Pre-dose, 1, 2.5, 8, and 24 hours post-dose
Population: All participants with at least one measurable PK sample who comply with the protocol sufficiently to ensure that generated data will be likely to exhibit the effects of treatment, according to the underlying scientific model. Compliance covers such considerations as exposure to treatment, availability of measurements and absence of important protocol deviations.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 12 - <18 Years | Area Under the Concentration-time Curve From Time 0 to 24 Hours Post-dose (AUC0-24) of Plasma Letermovir Taken as Oral Formulation by Ages 2 - <18 Years | 80300 hr*ng/mL | Geometric Coefficient of Variation 74.9 |
| 2 - <12 Years | Area Under the Concentration-time Curve From Time 0 to 24 Hours Post-dose (AUC0-24) of Plasma Letermovir Taken as Oral Formulation by Ages 2 - <18 Years | 62900 hr*ng/mL | Geometric Coefficient of Variation 37.4 |
Primary
AUC0-24 of Plasma Letermovir Taken as Intravenous (IV) Formulation by Ages 12 - <18 Years
Blood was collected on treatment Day 7 from participants aged 12 - \<18 years in order to determine the AUC0-24 of plasma letermovir for participants receiving IV formulation. Individual values were natural log transformed and evaluated separately with a linear mixed effects model containing a fixed effect for treatment and a random effect for participant. Participants aged \< 12 years were not presented as their data analysis resulted in a different measure type and method of dispersion.
Time frame: Day 7: Pre-dose, 1, 2.5, 8, and 24 hours post-dose
Population: All participants with at least one measurable PK sample who comply with the protocol sufficiently to ensure that generated data will be likely to exhibit the effects of treatment, according to the underlying scientific model. Compliance covers such considerations as exposure to treatment, availability of measurements and absence of important protocol deviations.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 12 - <18 Years | AUC0-24 of Plasma Letermovir Taken as Intravenous (IV) Formulation by Ages 12 - <18 Years | 114000 hr*ng/mL | Geometric Coefficient of Variation 37.8 |
Primary
AUC0-24 of Plasma Letermovir Taken as IV Formulation by Ages 2 to <12 Years
Blood was collected on treatment Day 7 from participants aged 2 to \<12 years in order to determine the AUC0-24 of plasma letermovir for participants receiving IV formulation. Individual values were natural log transformed and evaluated separately with a linear mixed effects model containing a fixed effect for treatment and a random effect for participant. Participants aged \> 2 years were not presented as their data analysis resulted in a different measure type and method of dispersion. The measure of dispersion is not determined when N \<2.
Time frame: Day 7: Pre-dose, 1, 2.5, 8, and 24 hours post-dose
Population: All participants with at least one measurable PK sample who comply with the protocol sufficiently to ensure that generated data will be likely to exhibit the effects of treatment, according to the underlying scientific model. Compliance covers such considerations as exposure to treatment, availability of measurements and absence of important protocol deviations.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 2 - <12 Years | AUC0-24 of Plasma Letermovir Taken as IV Formulation by Ages 2 to <12 Years | 25300 hr*ng/mL |
Primary
AUC0-24 of Plasma Letermovir Taken as IV Formulation by Ages 2 to <12 Years
Blood was collected on treatment Day 7 from participants aged 2 to \<12 years in order to determine the AUC0-24 of plasma letermovir for participants receiving IV formulation. Individual values were natural log transformed and evaluated separately with a linear mixed effects model containing a fixed effect for treatment and a random effect for participant. Participants aged \< 2 years and \> 12 years were not presented as their data analysis resulted in a different measure type and method of dispersion.
Time frame: Day 7: Pre-dose, 1, 2.5, 8, and 24 hours post-dose
Population: All participants with at least one measurable PK sample who comply with the protocol sufficiently to ensure that generated data will be likely to exhibit the effects of treatment, according to the underlying scientific model. Compliance covers such considerations as exposure to treatment, availability of measurements and absence of important protocol deviations.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| 2 - <12 Years | AUC0-24 of Plasma Letermovir Taken as IV Formulation by Ages 2 to <12 Years | 36200 hr*ng/mL |
| Birth - <2 Years | AUC0-24 of Plasma Letermovir Taken as IV Formulation by Ages 2 to <12 Years | 31500 hr*ng/mL |
Primary
AUC0-24 of Plasma Letermovir Taken as IV Formulation by Ages <2 Years
Blood was collected on treatment Day 7 from participants aged \<2 years in order to determine the AUC0-24 of plasma letermovir for participants receiving IV formulation. Individual values were natural log transformed and evaluated separately with a linear mixed effects model containing a fixed effect for treatment and a random effect for participant. Participants aged \> 2 years were not presented as their data analysis resulted in a different measure type and method of dispersion. The measure of dispersion is not determined when N \<2.
Time frame: Day 7: Pre-dose, 1, 2.5, 8, and 24 hours post-dose
Population: All participants with at least one measurable PK sample who comply with the protocol sufficiently to ensure that generated data will be likely to exhibit the effects of treatment, according to the underlying scientific model. Compliance covers such considerations as exposure to treatment, availability of measurements and absence of important protocol deviations.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Birth - <2 Years | AUC0-24 of Plasma Letermovir Taken as IV Formulation by Ages <2 Years | 37300 hr*ng/mL |
Primary
AUC0-24 of Plasma Letermovir Taken as Oral Formulation by Ages 2 to <12 Years
Blood was collected on treatment Day 7 from participants aged 2 to \<12 years in order to determine the AUC0-24 of plasma letermovir for participants receiving oral formulation. Individual values were natural log transformed and evaluated separately with a linear mixed effects model containing a fixed effect for treatment and a random effect for participant. Participants aged \<2 and \>12 years were not presented as their data analysis resulted in a different measure type and method of dispersion.
Time frame: Day 7: Pre-dose, 1, 2.5, 8, and 24 hours post-dose
Population: All participants with at least one measurable PK sample who comply with the protocol sufficiently to ensure that generated data will be likely to exhibit the effects of treatment, according to the underlying scientific model. Compliance covers such considerations as exposure to treatment, availability of measurements and absence of important protocol deviations.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| 2 - <12 Years | AUC0-24 of Plasma Letermovir Taken as Oral Formulation by Ages 2 to <12 Years | 39500 hr*ng/mL |
Primary
AUC0-24 of Plasma Letermovir Taken as Oral Formulation by Ages <2 Years
Blood was collected on treatment Day 7 from participants aged \<2 years in order to determine the AUC0-24 of plasma letermovir for participants receiving oral formulation. Individual values were natural log transformed and evaluated separately with a linear mixed effects model containing a fixed effect for treatment and a random effect for participant. Participants aged 2 - \<18 years were not presented as their data analysis resulted in a different measure type and method of dispersion. The measure of dispersion is not determined when N \<2.
Time frame: Day 7: Pre-dose, 1, 2.5, 8, and 24 hours post-dose
Population: All participants with at least one measurable PK sample who comply with the protocol sufficiently to ensure that generated data will be likely to exhibit the effects of treatment, according to the underlying scientific model. Compliance covers such considerations as exposure to treatment, availability of measurements and absence of important protocol deviations.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Birth - <2 Years | AUC0-24 of Plasma Letermovir Taken as Oral Formulation by Ages <2 Years | 26200 hr*ng/mL |
Primary
Ceoi of Plasma Letermovir Taken as IV Formulation by Ages 2 to <12 Years
Blood was collected on treatment Day 7 from participants aged 2 to \<12 years in order to determine the Ceoi of plasma letermovir for participants receiving IV formulation. As samples were collected outside the collection window Ceoi for these samples were predicted by using a log linear model. Participants aged \< 2 years and \> 12 years were not presented as their data analysis resulted in a different measure type and method of dispersion.
Time frame: Day 7: Pre-dose, 1, 2.5, 8, and 24 hours post-dose
Population: All participants with at least one measurable PK sample who comply with the protocol sufficiently to ensure that generated data will be likely to exhibit the effects of treatment, according to the underlying scientific model. Compliance covers such considerations as exposure to treatment, availability of measurements and absence of important protocol deviations.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| 2 - <12 Years | Ceoi of Plasma Letermovir Taken as IV Formulation by Ages 2 to <12 Years | 16800 ng/mL |
| Birth - <2 Years | Ceoi of Plasma Letermovir Taken as IV Formulation by Ages 2 to <12 Years | 8200 ng/mL |
Primary
Ceoi of Plasma Letermovir Taken as IV Formulation by Ages <2 Years
Blood was collected on treatment Day 7 from participants aged \<2 years in order to determine the Ceoi of plasma letermovir for participants receiving IV formulation. As samples were collected outside the collection window Ceoi for these samples were predicted by using a log linear model. Participants aged \> 2 years were not presented as their data analysis resulted in a different measure type and method of dispersion. A measure of dispersion is not determined when N \<2.
Time frame: Day 7: Pre-dose, 1, 2.5, 8, and 24 hours post-dose
Population: All participants with at least one measurable PK sample who comply with the protocol sufficiently to ensure that generated data will be likely to exhibit the effects of treatment, according to the underlying scientific model. Compliance covers such considerations as exposure to treatment, availability of measurements and absence of important protocol deviations.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Birth - <2 Years | Ceoi of Plasma Letermovir Taken as IV Formulation by Ages <2 Years | 11700 ng/mL |
Primary
Ceoi of Plasma Letermovir Taken as IV Formulation by Ages s 2 to <12 Years
Blood was collected on treatment Day 7 from participants aged 2 to \<12 years in order to determine the Ceoi of plasma letermovir for participants receiving IV formulation. As samples were collected outside the collection window Ceoi for these samples were predicted by using a log linear model. Participants aged \> 2 years were not presented as their data analysis resulted in a different measure type and method of dispersion. A measure of dispersion is not determined when N \<2.
Time frame: Day 7: Pre-dose, 1, 2.5, 8, and 24 hours post-dose
Population: All participants with at least one measurable PK sample who comply with the protocol sufficiently to ensure that generated data will be likely to exhibit the effects of treatment, according to the underlying scientific model. Compliance covers such considerations as exposure to treatment, availability of measurements and absence of important protocol deviations.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 2 - <12 Years | Ceoi of Plasma Letermovir Taken as IV Formulation by Ages s 2 to <12 Years | 8630 ng/mL |
Primary
Cmax of Plasma Letermovir Taken as Oral Formulation by Ages 2 to <12 Years
Blood was collected on treatment Day 7 from participants aged 2 to \<12 years in order to determine Cmax of plasma letermovir for participants receiving oral formulation. Individual values were natural log transformed and evaluated separately with a linear mixed effects model containing a fixed effect for treatment and a random effect for participant. Participants aged \<2 and \>12 years were not presented as their data analysis resulted in a different measure type and method of dispersion.
Time frame: Day 7: Pre-dose, 1, 2.5, 8, and 24 hours post-dose
Population: All participants with at least one measurable PK sample who comply with the protocol sufficiently to ensure that generated data will be likely to exhibit the effects of treatment, according to the underlying scientific model. Compliance covers such considerations as exposure to treatment, availability of measurements and absence of important protocol deviations.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| 2 - <12 Years | Cmax of Plasma Letermovir Taken as Oral Formulation by Ages 2 to <12 Years | 5500 ng/mL |
Primary
Cmax of Plasma Letermovir Taken as Oral Formulation by Ages < 2 Years
Blood was collected on treatment Day 7 from participants aged \<2 years in order to determine the Cmax of plasma letermovir for participants receiving oral formulation. Individual values were natural log transformed and evaluated separately with a linear mixed effects model containing a fixed effect for treatment and a random effect for participant. Participants aged 2 - \<18 years were not presented as their data analysis resulted in a different measure type and method of dispersion. The measure of dispersion is not determined when N \<2
Time frame: Day 7: Pre-dose, 1, 2.5, 8, and 24 hours post-dose
Population: All participants with at least one measurable PK sample who comply with the protocol sufficiently to ensure that generated data will be likely to exhibit the effects of treatment, according to the underlying scientific model. Compliance covers such considerations as exposure to treatment, availability of measurements and absence of important protocol deviations.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Birth - <2 Years | Cmax of Plasma Letermovir Taken as Oral Formulation by Ages < 2 Years | 2950 ng/mL |
Primary
Concentration at the End of Infusion (Ceoi) of Plasma Letermovir Taken as IV Formulation by Ages 12 - <18 Years
Blood was collected on treatment Day 7 from participants aged 12 - \<18 years in order to determine the Ceoi of plasma letermovir for participants receiving IV formulation. As samples were collected outside the collection window Ceoi for these samples were predicted by using a log linear model .Participants aged \< 12 years were not presented as their data analysis resulted in a different measure type and method of dispersion.
Time frame: Day 7: Pre-dose, 1, 2.5, 8, and 24 hours post-dose
Population: All participants with at least one measurable PK sample who comply with the protocol sufficiently to ensure that generated data will be likely to exhibit the effects of treatment, according to the underlying scientific model. Compliance covers such considerations as exposure to treatment, availability of measurements and absence of important protocol deviations.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 12 - <18 Years | Concentration at the End of Infusion (Ceoi) of Plasma Letermovir Taken as IV Formulation by Ages 12 - <18 Years | 30600 ng/mL | Geometric Coefficient of Variation 16.4 |
Primary
Ctrough of Plasma Letermovir Taken as IV Formulation by Ages 12 - <18 Years
Blood was collected on treatment Day 7 from participants aged 12 - \<18 years in order to determine the Ctrough of plasma letermovir for participants receiving IV formulation. Individual values were natural log transformed and evaluated separately with a linear mixed effects model containing a fixed effect for treatment and a random effect for participant. Participants aged \< 12 years were not presented as their data analysis resulted in a different measure type and method of dispersion.
Time frame: Day 7: 24 hours post-dose
Population: All participants with at least one measurable PK sample who comply with the protocol sufficiently to ensure that generated data will be likely to exhibit the effects of treatment, according to the underlying scientific model. Compliance covers such considerations as exposure to treatment, availability of measurements and absence of important protocol deviations.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 12 - <18 Years | Ctrough of Plasma Letermovir Taken as IV Formulation by Ages 12 - <18 Years | 709 ng/mL | Geometric Coefficient of Variation 256.8 |
Primary
Ctrough of Plasma Letermovir Taken as IV Formulation by Ages 2 to <12 Years
Blood was collected on treatment Day 7 from participants aged \<2 years in order to determine the Ctrough of plasma letermovir for participants receiving IV formulation. Individual values were natural log transformed and evaluated separately with a linear mixed effects model containing a fixed effect for treatment and a random effect for participant. Participants aged \> 2 years were not presented as their data analysis resulted in a different measure type and method of dispersion. The measure of dispersion is not determined when N \<2.
Time frame: Day 7: Pre-dose, 1, 2.5, 8, and 24 hours post-dose
Population: All participants with at least one measurable PK sample who comply with the protocol sufficiently to ensure that generated data will be likely to exhibit the effects of treatment, according to the underlying scientific model. Compliance covers such considerations as exposure to treatment, availability of measurements and absence of important protocol deviations.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 2 - <12 Years | Ctrough of Plasma Letermovir Taken as IV Formulation by Ages 2 to <12 Years | 216 ng/mL |
Primary
Ctrough of Plasma Letermovir Taken as IV Formulation by Ages 2 to <12 Years
Blood was collected on treatment Day 7 from participants aged 2 to \<12 years in order to determine the Ctrough of plasma letermovir for participants receiving IV formulation. Individual values were natural log transformed and evaluated separately with a linear mixed effects model containing a fixed effect for treatment and a random effect for participant. Participants aged \< 2 years and \> 12 years were not presented as their data analysis resulted in a different measure type and method of dispersion.
Time frame: Day 7: 24 hours post-dose
Population: All participants with at least one measurable PK sample who comply with the protocol sufficiently to ensure that generated data will be likely to exhibit the effects of treatment, according to the underlying scientific model. Compliance covers such considerations as exposure to treatment, availability of measurements and absence of important protocol deviations.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| 2 - <12 Years | Ctrough of Plasma Letermovir Taken as IV Formulation by Ages 2 to <12 Years | 71.6 ng/mL |
| Birth - <2 Years | Ctrough of Plasma Letermovir Taken as IV Formulation by Ages 2 to <12 Years | 318 ng/mL |
Primary
Ctrough of Plasma Letermovir Taken as IV Formulation by Ages <2 Years
Blood was collected on treatment Day 7 from participants aged \<2 years in order to determine the Ctrough of plasma letermovir for participants receiving IV formulation. Individual values were natural log transformed and evaluated separately with a linear mixed effects model containing a fixed effect for treatment and a random effect for participant. Participants aged \> 2 years were not presented as their data analysis resulted in a different measure type and method of dispersion. The measure type is Geometric Mean, and a measure of dispersion is not determined when N \<2.
Time frame: Day 7: Pre-dose, 1, 2.5, 8, and 24 hours post-dose
Population: All participants with at least one measurable PK sample who comply with the protocol sufficiently to ensure that generated data will be likely to exhibit the effects of treatment, according to the underlying scientific model. Compliance covers such considerations as exposure to treatment, availability of measurements and absence of important protocol deviations.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Birth - <2 Years | Ctrough of Plasma Letermovir Taken as IV Formulation by Ages <2 Years | 98.3 ng/mL |
Primary
Ctrough of Plasma Letermovir Taken as Oral Formulation by Ages 2 to <12 Years
Blood was collected on treatment Day 7 from participants aged 2 to \<12 years in order to determine Ctrough of plasma letermovir for participants receiving oral formulation. Individual values were natural log transformed and evaluated separately with a linear mixed effects model containing a fixed effect for treatment and a random effect for participant. Participants aged \<2 and \>12 years were not presented as their data analysis resulted in a different measure type and method of dispersion.
Time frame: Day 7: Pre-dose, 1, 2.5, 8, and 24 hours post-dose
Population: All participants with at least one measurable PK sample who comply with the protocol sufficiently to ensure that generated data will be likely to exhibit the effects of treatment, according to the underlying scientific model. Compliance covers such considerations as exposure to treatment, availability of measurements and absence of important protocol deviations.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| 2 - <12 Years | Ctrough of Plasma Letermovir Taken as Oral Formulation by Ages 2 to <12 Years | 481 ng/mL |
Primary
Ctrough of Plasma Letermovir Taken as Oral Formulation by Ages < 2 Years
Blood was collected on treatment Day 7 from participants aged \<2 years in order to determine the Ctrough of plasma letermovir for participants receiving oral formulation. Individual values were natural log transformed and evaluated separately with a linear mixed effects model containing a fixed effect for treatment and a random effect for participant. Participants aged 2 - \<18 years were not presented as their data analysis resulted in a different measure type and method of dispersion. The measure of dispersion is not determined when N \<2.
Time frame: Day 7: 24 hours post-dose
Population: All participants with at least one measurable PK sample who comply with the protocol sufficiently to ensure that generated data will be likely to exhibit the effects of treatment, according to the underlying scientific model. Compliance covers such considerations as exposure to treatment, availability of measurements and absence of important protocol deviations.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Birth - <2 Years | Ctrough of Plasma Letermovir Taken as Oral Formulation by Ages < 2 Years | 61.7 ng/mL |
Primary
Ctrough of Plasma Letermovir Taken During Sparse PK as IV Formulation
Blood was collected on treatment Day 7 in order to determine the Ctrough of plasma letermovir for participants receiving IV formulation during sparse PK. Individual values were natural log transformed and evaluated separately with a linear mixed effects model containing a fixed effect for treatment and a random effect for participant.
Time frame: Day 7: 24 hours post-dose
Population: Per protocol, sparse PK results were not planned as either primary or secondary outcome measures. As sparse PK data were instead used in population PK model development, they were not summarized in this outcome measure.
Primary
Ctrough of Plasma Letermovir Taken During Sparse PK for Oral Formulation
Blood was collected on treatment Day 7 in order to determine the Ctrough of plasma letermovir during sparse PK for participants receiving oral formulation. Individual values were natural log transformed and evaluated separately with a linear mixed effects model containing a fixed effect for treatment and a random effect for participant.
Time frame: Day 7: 24 hours post-dose
Population: Per protocol, sparse PK results were not planned as either primary or secondary outcome measures. As sparse PK data were instead used in population PK model development, they were not summarized in this outcome measure.
Primary
Maximal Concentration (Cmax) of Plasma Letermovir Taken as Oral Formulation by Ages 2 - <18 Years
Blood was collected on treatment Day 7 from participants aged 2 - \<18 years in order to determine the Cmax of plasma letermovir for participants receiving oral formulation. Individual values were natural log transformed and evaluated separately with a linear mixed effects model containing a fixed effect for treatment and a random effect for participant. Participants aged \< 2 years were not presented as their data analysis resulted in a different measure type and method of dispersion.
Time frame: Day 7: Pre-dose, 1, 2.5, 8, and 24 hours post-dose
Population: All participants with at least one measurable PK sample who comply with the protocol sufficiently to ensure that generated data will be likely to exhibit the effects of treatment, according to the underlying scientific model. Compliance covers such considerations as exposure to treatment, availability of measurements and absence of important protocol deviations.
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 12 - <18 Years | Maximal Concentration (Cmax) of Plasma Letermovir Taken as Oral Formulation by Ages 2 - <18 Years | 7410 ng/mL | Geometric Coefficient of Variation 70.1 |
| 2 - <12 Years | Maximal Concentration (Cmax) of Plasma Letermovir Taken as Oral Formulation by Ages 2 - <18 Years | 10800 ng/mL | Geometric Coefficient of Variation 17.4 |
Primary
Minimum Concentration of Plasma Letermovir Observed Before Next Dose (Ctrough) Taken as Oral Formulation by Ages 2 - <18 Years
Blood was collected on treatment Day 7 from participants aged 2 - \<18 years in order to determine the Ctrough of plasma letermovir for participants receiving oral formulation. Individual values were natural log transformed and evaluated separately with a linear mixed effects model containing a fixed effect for treatment and a random effect for participant. Participants aged \< 2 years were not presented as their data analysis resulted in a different measure type and method of dispersion.
Time frame: Day 7: 24 hours post-dose
Population: All participants with at least one measurable PK sample who comply with the protocol sufficiently to ensure that generated data will be likely to exhibit the effects of treatment, according to the underlying scientific model. Compliance covers such considerations as exposure to treatment, availability of measurements and absence of important protocol deviations.
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 12 - <18 Years | Minimum Concentration of Plasma Letermovir Observed Before Next Dose (Ctrough) Taken as Oral Formulation by Ages 2 - <18 Years | 845 ng/mL | Geometric Coefficient of Variation 107.5 |
| 2 - <12 Years | Minimum Concentration of Plasma Letermovir Observed Before Next Dose (Ctrough) Taken as Oral Formulation by Ages 2 - <18 Years | 171 ng/mL | Geometric Coefficient of Variation 2046.8 |
Secondary
Number of Participants Receiving Oral Granules With Palatability Response, Based on Taste of Medication on the Eighth Day of Administration of Oral Formulation
Palatability was measured by response to a questionnaire on the taste of medication , with responses from very good, good, neither good nor bad, bad or very bad.
Time frame: Day 8 of administration of oral formulation up to Week 14 post-transplant (up to 18 weeks)
Population: Participants who received ≥1 dose of study intervention, and completed palatability questionnaire
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 12 - <18 Years | Number of Participants Receiving Oral Granules With Palatability Response, Based on Taste of Medication on the Eighth Day of Administration of Oral Formulation | Very bad | 0 Participants |
| 12 - <18 Years | Number of Participants Receiving Oral Granules With Palatability Response, Based on Taste of Medication on the Eighth Day of Administration of Oral Formulation | Bad | 0 Participants |
| 12 - <18 Years | Number of Participants Receiving Oral Granules With Palatability Response, Based on Taste of Medication on the Eighth Day of Administration of Oral Formulation | Good | 1 Participants |
| 12 - <18 Years | Number of Participants Receiving Oral Granules With Palatability Response, Based on Taste of Medication on the Eighth Day of Administration of Oral Formulation | Neither good nor bad | 1 Participants |
| 12 - <18 Years | Number of Participants Receiving Oral Granules With Palatability Response, Based on Taste of Medication on the Eighth Day of Administration of Oral Formulation | Very good | 0 Participants |
| 2 - <12 Years | Number of Participants Receiving Oral Granules With Palatability Response, Based on Taste of Medication on the Eighth Day of Administration of Oral Formulation | Bad | 5 Participants |
| 2 - <12 Years | Number of Participants Receiving Oral Granules With Palatability Response, Based on Taste of Medication on the Eighth Day of Administration of Oral Formulation | Good | 4 Participants |
| 2 - <12 Years | Number of Participants Receiving Oral Granules With Palatability Response, Based on Taste of Medication on the Eighth Day of Administration of Oral Formulation | Neither good nor bad | 8 Participants |
| 2 - <12 Years | Number of Participants Receiving Oral Granules With Palatability Response, Based on Taste of Medication on the Eighth Day of Administration of Oral Formulation | Very bad | 3 Participants |
| 2 - <12 Years | Number of Participants Receiving Oral Granules With Palatability Response, Based on Taste of Medication on the Eighth Day of Administration of Oral Formulation | Very good | 3 Participants |
| Birth - <2 Years | Number of Participants Receiving Oral Granules With Palatability Response, Based on Taste of Medication on the Eighth Day of Administration of Oral Formulation | Very good | 0 Participants |
| Birth - <2 Years | Number of Participants Receiving Oral Granules With Palatability Response, Based on Taste of Medication on the Eighth Day of Administration of Oral Formulation | Very bad | 0 Participants |
| Birth - <2 Years | Number of Participants Receiving Oral Granules With Palatability Response, Based on Taste of Medication on the Eighth Day of Administration of Oral Formulation | Good | 3 Participants |
| Birth - <2 Years | Number of Participants Receiving Oral Granules With Palatability Response, Based on Taste of Medication on the Eighth Day of Administration of Oral Formulation | Bad | 0 Participants |
| Birth - <2 Years | Number of Participants Receiving Oral Granules With Palatability Response, Based on Taste of Medication on the Eighth Day of Administration of Oral Formulation | Neither good nor bad | 4 Participants |
Secondary
Number of Participants Receiving Oral Granules With Palatability Response, Based on Taste of Medication on the First Day of Administration of Oral Formulation
Palatability was measured by response to a questionnaire on the taste of medication , with responses from very good, good, neither good nor bad, bad or very bad.
Time frame: Day 1 of administration of oral formulation up to Week 14 post-transplant (up to 18 weeks)
Population: Participants who received ≥1 dose of study intervention, and completed palatability questionnaire
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 12 - <18 Years | Number of Participants Receiving Oral Granules With Palatability Response, Based on Taste of Medication on the First Day of Administration of Oral Formulation | Bad | 1 Participants |
| 12 - <18 Years | Number of Participants Receiving Oral Granules With Palatability Response, Based on Taste of Medication on the First Day of Administration of Oral Formulation | Neither good nor bad | 1 Participants |
| 12 - <18 Years | Number of Participants Receiving Oral Granules With Palatability Response, Based on Taste of Medication on the First Day of Administration of Oral Formulation | Very good | 0 Participants |
| 12 - <18 Years | Number of Participants Receiving Oral Granules With Palatability Response, Based on Taste of Medication on the First Day of Administration of Oral Formulation | Good | 1 Participants |
| 12 - <18 Years | Number of Participants Receiving Oral Granules With Palatability Response, Based on Taste of Medication on the First Day of Administration of Oral Formulation | Very bad | 1 Participants |
| 2 - <12 Years | Number of Participants Receiving Oral Granules With Palatability Response, Based on Taste of Medication on the First Day of Administration of Oral Formulation | Neither good nor bad | 8 Participants |
| 2 - <12 Years | Number of Participants Receiving Oral Granules With Palatability Response, Based on Taste of Medication on the First Day of Administration of Oral Formulation | Very good | 3 Participants |
| 2 - <12 Years | Number of Participants Receiving Oral Granules With Palatability Response, Based on Taste of Medication on the First Day of Administration of Oral Formulation | Good | 5 Participants |
| 2 - <12 Years | Number of Participants Receiving Oral Granules With Palatability Response, Based on Taste of Medication on the First Day of Administration of Oral Formulation | Bad | 8 Participants |
| 2 - <12 Years | Number of Participants Receiving Oral Granules With Palatability Response, Based on Taste of Medication on the First Day of Administration of Oral Formulation | Very bad | 3 Participants |
| Birth - <2 Years | Number of Participants Receiving Oral Granules With Palatability Response, Based on Taste of Medication on the First Day of Administration of Oral Formulation | Very bad | 0 Participants |
| Birth - <2 Years | Number of Participants Receiving Oral Granules With Palatability Response, Based on Taste of Medication on the First Day of Administration of Oral Formulation | Bad | 3 Participants |
| Birth - <2 Years | Number of Participants Receiving Oral Granules With Palatability Response, Based on Taste of Medication on the First Day of Administration of Oral Formulation | Very good | 0 Participants |
| Birth - <2 Years | Number of Participants Receiving Oral Granules With Palatability Response, Based on Taste of Medication on the First Day of Administration of Oral Formulation | Neither good nor bad | 1 Participants |
| Birth - <2 Years | Number of Participants Receiving Oral Granules With Palatability Response, Based on Taste of Medication on the First Day of Administration of Oral Formulation | Good | 3 Participants |
Secondary
Percentage of Participants Who Discontinued Study Medication Due to an AE.
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The 95% CI is based on the exact binomial method proposed by Clopper and Pearson.
Time frame: Up to Week 14 post-transplant (up to 18 weeks)
Population: All participants who received ≥1 dose of study intervention.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 12 - <18 Years | Percentage of Participants Who Discontinued Study Medication Due to an AE. | 17.9 Percentage of participants |
| 2 - <12 Years | Percentage of Participants Who Discontinued Study Medication Due to an AE. | 7.4 Percentage of participants |
| Birth - <2 Years | Percentage of Participants Who Discontinued Study Medication Due to an AE. | 12.5 Percentage of participants |
Secondary
Percentage of Participants With Clinically Significant CMV Infection Through Week 14 Post-transplant
Clinically significant cytomegalovirus (CMV) infection is defined as CMV end organ disease (proven or probable) or initiation of pre-emptive therapy (PET) based on documented CMV viremia and the clinical condition of the participant. The 95% confidence interval (CI) was based on the exact binomial method proposed by Clopper and Pearson. Missing values: were handled by the Non-Completer=Failure (NC=F) approach. where failure was defined as all participants who developed clinically significant CMV infection or prematurely discontinued from the study or had a missing outcome through week 14 post-transplant visit window.
Time frame: Up to Week 14 post-transplant (up to 18 weeks)
Population: Participants who received ≥1 dose of study intervention, had no detectable CMV viral DNA on the day study intervention was initiated, had not prematurely discontinued from the study and had an outcome through week 14 post-transplant.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 12 - <18 Years | Percentage of Participants With Clinically Significant CMV Infection Through Week 14 Post-transplant | 20.0 Percentage of participants |
| 2 - <12 Years | Percentage of Participants With Clinically Significant CMV Infection Through Week 14 Post-transplant | 16.7 Percentage of participants |
| Birth - <2 Years | Percentage of Participants With Clinically Significant CMV Infection Through Week 14 Post-transplant | 28.5 Percentage of participants |
Secondary
Percentage of Participants With Clinically Significant CMV Infection Through Week 24 Post-transplant
Clinically significant CMV infection is defined as CMV end organ disease (proven or probable) or initiation of PET based on documented CMV viremia and the clinical condition of the participant. The 95% confidence interval (CI) was based on the exact binomial method proposed by Clopper and Pearson. Missing values: were handled by the Non-Completer=Failure (NC=F) approach. where failure was defined as all participants who developed clinically significant CMV infection or prematurely discontinued from the study or had a missing outcome through week 24 post-transplant visit window.
Time frame: Up to Week 24 post-transplant (up to 28 weeks)
Population: Participants who received ≥1 dose of study intervention, had no detectable CMV viral DNA on the day study intervention was initiated, had not prematurely discontinued from the study and had an outcome through week 24 post-transplant.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 12 - <18 Years | Percentage of Participants With Clinically Significant CMV Infection Through Week 24 Post-transplant | 24.0 Percentage of participants |
| 2 - <12 Years | Percentage of Participants With Clinically Significant CMV Infection Through Week 24 Post-transplant | 25.0 Percentage of participants |
| Birth - <2 Years | Percentage of Participants With Clinically Significant CMV Infection Through Week 24 Post-transplant | 28.6 Percentage of participants |
Secondary
Percentage of Participants With One or More Adverse Event (AE)
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The 95% confidence interval (CI) is based on the exact binomial method proposed by Clopper and Pearson.
Time frame: Up to Week 48 post-transplant (up to 52 weeks)
Population: All participants who received ≥1 dose of study intervention.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 12 - <18 Years | Percentage of Participants With One or More Adverse Event (AE) | 100.0 Percentage of participants |
| 2 - <12 Years | Percentage of Participants With One or More Adverse Event (AE) | 100.0 Percentage of participants |
| Birth - <2 Years | Percentage of Participants With One or More Adverse Event (AE) | 100.0 Percentage of participants |