A Study of Valcyte (Valganciclovir) Syrup Formulation in Pediatric Solid Organ Transplant Recipients

Study Overview
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Brief Summary
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This study will assess the safety and pharmacokinetics of Valcyte syrup in pediatric solid organ transplant recipients. The anticipated time on study treatment is 3-12 months and the target sample size is less than 100 individuals.

Official Title
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Safety and Pharmacokinetics of Valganciclovir Syrup Formulation in Pediatric Solid Organ Transplant Recipients

Conditions
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Cytomegalovirus Infections

Intervention / Treatment
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* Drug: valganciclovir [Valcyte]


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: patients between 3 months and 16 years of age; first solid organ transplant (eg, kidney, liver, heart); able to tolerate oral medication; females of childbearing potential must agree to utilize an effective method of contraception throughout the study and for 90 days following discontinuation of study drug; patients at risk of developing CMV disease (all transplant recipients other than those who are D-R- for CMV). Exclusion Criteria: patients who have previously participated in this study; patients who are participating in another clinical trial (except with the approval of the Sponsor); severe, uncontrolled diarrhea (more than 5 watery stools per day); pregnant or lactating females.

Ages Eligible for Study
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Minimum Age: 3 Months
Maximum Age: 16 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Valganciclovir Age Group <= 2 Years<br>Eligible participants aged <= 2 years received valganciclovir up to maximum of 900 milligrams (mg) once daily oral dose (solution or tablets) from the time of kidney transplantation for up to 100 days post-transplant. Dose = 7 * body surface area (BSA) * creatinine clearance (CrCLS). | Drug: valganciclovir [Valcyte]<br>* po daily (dose based on body surface area and CrCL)<br>|
| Experimental: Valganciclovir Age Group >2 to <12 Years<br>Eligible participants aged >2 to <12 years received valganciclovir up to maximum of 900 mg once daily oral dose (solution or tablets) from the time of kidney transplantation for up to 100 days post-transplant. Dose = 7 * BSA * CrCLS. | Drug: valganciclovir [Valcyte]<br>* po daily (dose based on body surface area and CrCL)<br>|
| Experimental: Valganciclovir Age Group >= 12 Years<br>Eligible participants aged >= 12 years received valganciclovir up to maximum of 900 mg once daily oral dose (solution or tablets) from the time of kidney transplantation for up to 100 days post-transplant. Dose = 7 * BSA * CrCLS. | Drug: valganciclovir [Valcyte]<br>* po daily (dose based on body surface area and CrCL)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Area Under the Concentration-Time Curve From 0 to 24 Hours of Valganciclovir | Area Under the Plasma Concentration-Time Curve (AUC) is a measure of the plasma concentration of the drug over time. The AUC 0-24 hours is area under the plasma concentration-time curve from time zero through 24 hours after dosing. A compartmental model was used to measure the plasma concentrations of valganciclovir. One participant was not analyzed for this outcome measure as the participant underwent both a kidney and liver transplant. | Pre-dose; 1-3, 3-7, 7-12 hours post dose on any day between Day 7 to Day 14; Week 6, Week 10, and Week 14 | 
| Number of Participants With Adverse Events Leading to Dose Interruption or Modification | An adverse event (AE) was defined as any untoward medical occurrence in a clinical investigation in participant administered a pharmaceutical product, which did not necessarily have to have a causal relationship with this treatment. The number of participants with AEs leading to dose interruptions or modifications are reported. | Up to Week 26 | 
| Number of Participants With Opportunistic Infections | Opportunistic infections included oral candidiasis, candidiasis, herpes simplex, cytomegalovirus antigen positive, cytomegalovirus test positive. The number of participants with opportunistic infections are reported. | Up to Week 26 | 
| Number of Participants With Any Adverse Events and Any Serious Adverse Events | An AE was defined as any untoward medical occurrence in a clinical investigation in participant administered a pharmaceutical product, which did not necessarily have to have a causal relationship with this treatment. A serious adverse event (SAE) is any experience or a significant hazard, that is fatal, life-threatening, requires in-patient hospitalization or prolongation of existing one, results in persistent or significant disability, is a congenital anomaly, is medically significant or requires intervention to prevent one or other of the outcomes listed above. | Up to Week 26 | 
| Number of Participants With Adverse Events Leading to Discontinuation of the Study Drug | An AE was defined as any untoward medical occurrence in a clinical investigation in participant administered a pharmaceutical product, which did not necessarily have to have a causal relationship with this treatment. The number of participants with AEs leading to discontinuation of the study drug is reported. | Up to Week 26 | 
| Number of Participants With 3 Grade Shift From Baseline of Adverse Events in Hematology and Serum Chemistry | The number of participants experiencing a 3 grade shift (example from Grade 0 to Grade 3) from baseline (BL) in hematology and serum chemistry laboratory parameters are reported. The data was analyzed for overall study only. | Up to Week 26 | 
| Number of Participants With 4 Grade Shift From Baseline of Adverse Events in Hematology and Serum Chemistry | The number of participants experiencing a 4 grade shift (example from Grade 0 to Grade 4) from BL in hematology and serum chemistry laboratory parameters are reported. The data was analyzed for overall study only. | Up to Week 26 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Cytomegalovirus Disease Over Time | Cytomegalovirus (CMV) disease is defined as syndrome or tissue invasive disease in which CMV virus was identified in blood, urine, biopsy or other suitable specimen, which could be in conjunction with one or more of the following events: a) CMV syndrome was defined as virus present in blood or other suitable specimen, plus fever, and any of the following: leukopenia, atypical lymphocytosis, thrombopenia or elevated hepatic transaminases (for non-liver recipients). b) The diagnosis of organ specific tissue invasive CMV disease was evidence of CMV in the tissue (CMV inclusion bodies or in situ detection of CMV antigen or DNA), plus signs/symptoms of organ dysfunction. | Up to Week 26 | 
| Number of Participants With Treatment Failures | Treatment failure was defined as either the development of CMV (viremia, antigenemia or test positive) requiring treatment up to day 100 post-transplant (i.e, while undergoing prophylaxis with valganciclovir up to day 100) or discontinuation of study medication due to lack of efficacy or to toxicity. | Up to Week 26 | 
| Number of Participants Who Experienced Graft Loss | Graft loss was defined as impairment of organ function to such a degree that the participant died or underwent re-transplantation. | Up to Week 26 | 
| Mean Maximum Plasma Concentration of Valganciclovir Over Time | Maximum Plasma Concentration (Cmax) is defined as the maximum observed plasma concentration of Valganciclovir. Participants with kidney, liver and heart transplant were analyzed. One participant was not analyzed for this outcome measure as the participant underwent both a kidney and liver transplant. | Pre-dose; 1-3, 3-7, 7-12 hours post dose on any day between Day (D) 7 to D 14; and at Week (W) 6, W 10, and W 14 | 
| Mean Elimination Half-Life of Valganciclovir Over Time | The Elimination Half-Life Period is defined as the time measured for the plasma concentration to decrease by half to its original concentration. One participant was not analyzed for this outcome measure as the participant underwent both a kidney and liver transplant. Here n represents number of participant with specific transplant i.e., kidney, liver, and heart. | Pre-dose; 1-3, 3-7, 7-12 hours post dose on any day between Day 7 to Day 14; Week 6, Week 10, and Week 14 | 
| Number of Participants Who Experienced Episodes of Rejection Over Time | Participants with biopsy proven active rejection are reported. | Up to Week 26 |