Outcome
| Type |
Measure |
Description |
Time frame |
Safety issue |
| 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. |
Day 7: Pre-dose, 1, 2.5, 8, and 24 hours post-dose |
|
| 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. |
Day 7: Pre-dose, 1, 2.5, 8, and 24 hours post-dose |
|
| 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. |
Day 7: Pre-dose, 1, 2.5, 8, and 24 hours post-dose |
|
| 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. |
Day 7: Pre-dose, 1, 2.5, 8, and 24 hours post-dose |
|
| 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. |
Day 7: Pre-dose, 1, 2.5, 8, and 24 hours post-dose |
|
| 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 |
Day 7: Pre-dose, 1, 2.5, 8, and 24 hours post-dose |
|
| 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. |
Day 7: 24 hours post-dose |
|
| 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. |
Day 7: Pre-dose, 1, 2.5, 8, and 24 hours post-dose |
|
| 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. |
Day 7: 24 hours post-dose |
|
| 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. |
Day 7: Pre-dose, 1, 2.5, 8, and 24 hours post-dose |
|
| 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. |
Day 7: Pre-dose, 1, 2.5, 8, and 24 hours post-dose |
|
| 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. |
Day 7: Pre-dose, 1, 2.5, 8, and 24 hours post-dose |
|
| 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. |
Day 7: Pre-dose, 1, 2.5, 8, and 24 hours post-dose |
|
| 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. |
Day 7: Pre-dose, 1, 2.5, 8, and 24 hours post-dose |
|
| 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. |
Day 7: Pre-dose, 1, 2.5, 8, and 24 hours post-dose |
|
| 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. |
Day 7: Pre-dose, 1, 2.5, 8, and 24 hours post-dose |
|
| 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. |
Day 7: Pre-dose, 1, 2.5, 8, and 24 hours post-dose |
|
| 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. |
Day 7: 24 hours post-dose |
|
| 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. |
Day 7: 24 hours post-dose |
|
| 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. |
Day 7: Pre-dose, 1, 2.5, 8, and 24 hours post-dose |
|
| 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. |
Day 7: Pre-dose, 1, 2.5, 8, and 24 hours post-dose |
|
| 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. |
Day 7: 24 hours post-dose |
|
| 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. |
Day 7: 24 hours post-dose |
|
| 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. |
Up to Week 48 post-transplant (up to 52 weeks) |
|
| 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. |
Up to Week 14 post-transplant (up to 18 weeks) |
|
| 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. |
Up to Week 14 post-transplant (up to 18 weeks) |
|
| 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. |
Up to Week 24 post-transplant (up to 28 weeks) |
|
| 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. |
Day 1 of administration of oral formulation up to Week 14 post-transplant (up to 18 weeks) |
|
| 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. |
Day 8 of administration of oral formulation up to Week 14 post-transplant (up to 18 weeks) |
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