Cytomegalovirus Infections
Conditions
Brief summary
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.
Interventions
po daily (dose based on body surface area and CrCL)
Sponsors
Hoffmann-La Roche
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
3 Months to 16 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With 4 Grade Shift From Baseline of Adverse Events in Hematology and Serum Chemistry | Up to Week 26 | 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. |
| Mean Area Under the Concentration-Time Curve From 0 to 24 Hours of Valganciclovir | 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 | 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. |
| Number of Participants With Adverse Events Leading to Dose Interruption or Modification | Up to Week 26 | 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. |
| Number of Participants With Opportunistic Infections | Up to Week 26 | Opportunistic infections included oral candidiasis, candidiasis, herpes simplex, cytomegalovirus antigen positive, cytomegalovirus test positive. The number of participants with opportunistic infections are reported. |
| Number of Participants With Any Adverse Events and Any Serious Adverse Events | Up to Week 26 | 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. |
| Number of Participants With Adverse Events Leading to Discontinuation of the Study Drug | Up to Week 26 | 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. |
| Number of Participants With 3 Grade Shift From Baseline of Adverse Events in Hematology and Serum Chemistry | Up to Week 26 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment Failures | Up to Week 26 | 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. |
| Number of Participants Who Experienced Graft Loss | Up to Week 26 | Graft loss was defined as impairment of organ function to such a degree that the participant died or underwent re-transplantation. |
| Mean Maximum Plasma Concentration of Valganciclovir Over Time | 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 | 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. |
| Mean Elimination Half-Life of Valganciclovir Over Time | 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 | 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. |
| Number of Participants Who Experienced Episodes of Rejection Over Time | Up to Week 26 | Participants with biopsy proven active rejection are reported. |
| Number of Participants With Cytomegalovirus Disease Over Time | Up to Week 26 | 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. |
Countries
Australia, Canada, France, Germany, Mexico, Spain, United States
Participant flow
Recruitment details
A total of 63 participants were enrolled in this study conducted from 28 May 2004 to 13 May 2005. The study was conducted at 18 centers in 7 countries.
Pre-assignment details
Participants were screened within 48 hours prior to transplant surgery (Day 1) and received valganciclovir from Day 1.
Participants by arm
| Arm | Count |
|---|---|
| Valganciclovir Age Group <= 2 Years 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 was calculated using the algorithm (7 \* BSA \* CrCLS). | 17 |
| Valganciclovir Age Group >2 to < 12 Years 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 was calculated using the algorithm (7 \* BSA \* CrCLS). | 21 |
| Valganciclovir Age Group >= 12 Years 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 was calculated using the algorithm (7 \* BSA \* CrCLS). | 25 |
| Total | 63 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Admin | 0 | 2 | 0 |
| Overall Study | Death | 1 | 0 | 0 |
| Overall Study | Lost to Follow-up | 2 | 0 | 2 |
| Overall Study | Nephrectomy Planned | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Valganciclovir Age Group <= 2 Years | Valganciclovir Age Group >2 to < 12 Years | Valganciclovir Age Group >= 12 Years | Total |
|---|---|---|---|---|
| Age, Continuous | 0.6 years STANDARD_DEVIATION 0.86 | 6.9 years STANDARD_DEVIATION 3.15 | 14.2 years STANDARD_DEVIATION 1.54 | 8.1 years STANDARD_DEVIATION 5.94 |
| Sex: Female, Male Female | 9 Participants | 7 Participants | 13 Participants | 29 Participants |
| Sex: Female, Male Male | 8 Participants | 14 Participants | 12 Participants | 34 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 17 / 17 | 17 / 21 | 21 / 25 |
| serious Total, serious adverse events | 13 / 17 | 11 / 21 | 11 / 25 |
Outcome results
Primary
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.
Time frame: 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
Population: Pharmacokinetic (PK) population comprised of all participants from studies WP16296, WP16303 and WV16726 who had completed the specified treatment and from whom at least one plasma sample was taken. Here n represents number of participant with specific transplant i.e., kidney, liver, and heart.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Valganciclovir Age Group <= 2 Years | Mean Area Under the Concentration-Time Curve From 0 to 24 Hours of Valganciclovir | In liver recipients, n=9, 6, 2 | 69.4 mcg*hr/mL | Standard Deviation 35.4 |
| Valganciclovir Age Group <= 2 Years | Mean Area Under the Concentration-Time Curve From 0 to 24 Hours of Valganciclovir | In kidney recipients, n=2, 12, 19 | 65.2 mcg*hr/mL | Standard Deviation 16.6 |
| Valganciclovir Age Group <= 2 Years | Mean Area Under the Concentration-Time Curve From 0 to 24 Hours of Valganciclovir | In heart recipients, n=6, 2, 4 | 56.3 mcg*hr/mL | Standard Deviation 23.2 |
| Valganciclovir Age Group >2 to < 12 Years | Mean Area Under the Concentration-Time Curve From 0 to 24 Hours of Valganciclovir | In liver recipients, n=9, 6, 2 | 58.4 mcg*hr/mL | Standard Deviation 6.18 |
| Valganciclovir Age Group >2 to < 12 Years | Mean Area Under the Concentration-Time Curve From 0 to 24 Hours of Valganciclovir | In kidney recipients, n=2, 12, 19 | 55 mcg*hr/mL | Standard Deviation 11.9 |
| Valganciclovir Age Group >2 to < 12 Years | Mean Area Under the Concentration-Time Curve From 0 to 24 Hours of Valganciclovir | In heart recipients, n=6, 2, 4 | 60 mcg*hr/mL | Standard Deviation 19.3 |
| Valganciclovir Age Group >= 12 Years | Mean Area Under the Concentration-Time Curve From 0 to 24 Hours of Valganciclovir | In kidney recipients, n=2, 12, 19 | 50 mcg*hr/mL | Standard Deviation 11.6 |
| Valganciclovir Age Group >= 12 Years | Mean Area Under the Concentration-Time Curve From 0 to 24 Hours of Valganciclovir | In heart recipients, n=6, 2, 4 | 61.2 mcg*hr/mL | Standard Deviation 26 |
| Valganciclovir Age Group >= 12 Years | Mean Area Under the Concentration-Time Curve From 0 to 24 Hours of Valganciclovir | In liver recipients, n=9, 6, 2 | 35.6 mcg*hr/mL | Standard Deviation 2.76 |
Primary
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.
Time frame: Up to Week 26
Population: Safety population included all participants who received at least one dose of valganciclovir.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Valganciclovir Age Group <= 2 Years | Number of Participants With 3 Grade Shift From Baseline of Adverse Events in Hematology and Serum Chemistry | Hemoglobin low, n= 63 | 6 participants |
| Valganciclovir Age Group <= 2 Years | Number of Participants With 3 Grade Shift From Baseline of Adverse Events in Hematology and Serum Chemistry | White blood cell count low, n= 59 | 3 participants |
| Valganciclovir Age Group <= 2 Years | Number of Participants With 3 Grade Shift From Baseline of Adverse Events in Hematology and Serum Chemistry | Lymphocytes low, n= 54 | 3 participants |
| Valganciclovir Age Group <= 2 Years | Number of Participants With 3 Grade Shift From Baseline of Adverse Events in Hematology and Serum Chemistry | Neutrophils low, n= 54 | 7 participants |
| Valganciclovir Age Group <= 2 Years | Number of Participants With 3 Grade Shift From Baseline of Adverse Events in Hematology and Serum Chemistry | Potassium low, n=56 | 4 participants |
| Valganciclovir Age Group <= 2 Years | Number of Participants With 3 Grade Shift From Baseline of Adverse Events in Hematology and Serum Chemistry | Potassium high, n=57 | 4 participants |
| Valganciclovir Age Group <= 2 Years | Number of Participants With 3 Grade Shift From Baseline of Adverse Events in Hematology and Serum Chemistry | Alkaline Phosphatase high, n=40 | 1 participants |
| Valganciclovir Age Group <= 2 Years | Number of Participants With 3 Grade Shift From Baseline of Adverse Events in Hematology and Serum Chemistry | Alanine transaminase high, n=48 | 1 participants |
| Valganciclovir Age Group <= 2 Years | Number of Participants With 3 Grade Shift From Baseline of Adverse Events in Hematology and Serum Chemistry | Total Bilirubin high, n=38 | 1 participants |
| Valganciclovir Age Group <= 2 Years | Number of Participants With 3 Grade Shift From Baseline of Adverse Events in Hematology and Serum Chemistry | Sodium low, n=58 | 2 participants |
| Valganciclovir Age Group <= 2 Years | Number of Participants With 3 Grade Shift From Baseline of Adverse Events in Hematology and Serum Chemistry | Sodium high, n=57 | 0 participants |
| Valganciclovir Age Group <= 2 Years | Number of Participants With 3 Grade Shift From Baseline of Adverse Events in Hematology and Serum Chemistry | Calcium low, n=46 | 1 participants |
| Valganciclovir Age Group <= 2 Years | Number of Participants With 3 Grade Shift From Baseline of Adverse Events in Hematology and Serum Chemistry | Phosphate low, n=43 | 2 participants |
| Valganciclovir Age Group <= 2 Years | Number of Participants With 3 Grade Shift From Baseline of Adverse Events in Hematology and Serum Chemistry | Fasting Glucose low, n=39 | 1 participants |
| Valganciclovir Age Group <= 2 Years | Number of Participants With 3 Grade Shift From Baseline of Adverse Events in Hematology and Serum Chemistry | Uric Acid high, n=21 | 2 participants |
Primary
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.
Time frame: Up to Week 26
Population: Safety population included all participants who received at least one dose of valganciclovir.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Valganciclovir Age Group <= 2 Years | Number of Participants With 4 Grade Shift From Baseline of Adverse Events in Hematology and Serum Chemistry | Hemoglobin low, n= 63 | 0 participants |
| Valganciclovir Age Group <= 2 Years | Number of Participants With 4 Grade Shift From Baseline of Adverse Events in Hematology and Serum Chemistry | White blood cell count low, n= 59 | 1 participants |
| Valganciclovir Age Group <= 2 Years | Number of Participants With 4 Grade Shift From Baseline of Adverse Events in Hematology and Serum Chemistry | Lymphocytes low, n= 54 | 3 participants |
| Valganciclovir Age Group <= 2 Years | Number of Participants With 4 Grade Shift From Baseline of Adverse Events in Hematology and Serum Chemistry | Neutrophils low, n= 54 | 4 participants |
| Valganciclovir Age Group <= 2 Years | Number of Participants With 4 Grade Shift From Baseline of Adverse Events in Hematology and Serum Chemistry | Potassium low, n=56 | 0 participants |
| Valganciclovir Age Group <= 2 Years | Number of Participants With 4 Grade Shift From Baseline of Adverse Events in Hematology and Serum Chemistry | Potassium high, n=57 | 2 participants |
| Valganciclovir Age Group <= 2 Years | Number of Participants With 4 Grade Shift From Baseline of Adverse Events in Hematology and Serum Chemistry | Alkaline Phosphatase high, n=40 | 0 participants |
| Valganciclovir Age Group <= 2 Years | Number of Participants With 4 Grade Shift From Baseline of Adverse Events in Hematology and Serum Chemistry | Alanine transaminase high, n=48 | 0 participants |
| Valganciclovir Age Group <= 2 Years | Number of Participants With 4 Grade Shift From Baseline of Adverse Events in Hematology and Serum Chemistry | Total Bilirubin high, n=38 | 0 participants |
| Valganciclovir Age Group <= 2 Years | Number of Participants With 4 Grade Shift From Baseline of Adverse Events in Hematology and Serum Chemistry | Sodium low, n=58 | 0 participants |
| Valganciclovir Age Group <= 2 Years | Number of Participants With 4 Grade Shift From Baseline of Adverse Events in Hematology and Serum Chemistry | Sodium high, n=57 | 1 participants |
| Valganciclovir Age Group <= 2 Years | Number of Participants With 4 Grade Shift From Baseline of Adverse Events in Hematology and Serum Chemistry | Calcium low, n=46 | 3 participants |
| Valganciclovir Age Group <= 2 Years | Number of Participants With 4 Grade Shift From Baseline of Adverse Events in Hematology and Serum Chemistry | Phosphate low, n=43 | 0 participants |
| Valganciclovir Age Group <= 2 Years | Number of Participants With 4 Grade Shift From Baseline of Adverse Events in Hematology and Serum Chemistry | Fasting Glucose low, n=39 | 0 participants |
| Valganciclovir Age Group <= 2 Years | Number of Participants With 4 Grade Shift From Baseline of Adverse Events in Hematology and Serum Chemistry | Uric Acid high, n=21 | 2 participants |
Primary
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.
Time frame: Up to Week 26
Population: Safety population included all participants who received at least one dose of valganciclovir.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Valganciclovir Age Group <= 2 Years | Number of Participants With Adverse Events Leading to Discontinuation of the Study Drug | 1 participants |
| Valganciclovir Age Group >2 to < 12 Years | Number of Participants With Adverse Events Leading to Discontinuation of the Study Drug | 2 participants |
| Valganciclovir Age Group >= 12 Years | Number of Participants With Adverse Events Leading to Discontinuation of the Study Drug | 0 participants |
Primary
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.
Time frame: Up to Week 26
Population: Safety population included all participants who received at least one dose of valganciclovir.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Valganciclovir Age Group <= 2 Years | Number of Participants With Adverse Events Leading to Dose Interruption or Modification | 4 participants |
| Valganciclovir Age Group >2 to < 12 Years | Number of Participants With Adverse Events Leading to Dose Interruption or Modification | 2 participants |
| Valganciclovir Age Group >= 12 Years | Number of Participants With Adverse Events Leading to Dose Interruption or Modification | 3 participants |
Primary
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.
Time frame: Up to Week 26
Population: Safety population included all participants who received at least one dose of valganciclovir.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Valganciclovir Age Group <= 2 Years | Number of Participants With Any Adverse Events and Any Serious Adverse Events | Any AE | 17 participants |
| Valganciclovir Age Group <= 2 Years | Number of Participants With Any Adverse Events and Any Serious Adverse Events | Any SAE | 13 participants |
| Valganciclovir Age Group >2 to < 12 Years | Number of Participants With Any Adverse Events and Any Serious Adverse Events | Any AE | 18 participants |
| Valganciclovir Age Group >2 to < 12 Years | Number of Participants With Any Adverse Events and Any Serious Adverse Events | Any SAE | 11 participants |
| Valganciclovir Age Group >= 12 Years | Number of Participants With Any Adverse Events and Any Serious Adverse Events | Any AE | 24 participants |
| Valganciclovir Age Group >= 12 Years | Number of Participants With Any Adverse Events and Any Serious Adverse Events | Any SAE | 11 participants |
Primary
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.
Time frame: Up to Week 26
Population: Safety population included all participants who received at least one dose of valganciclovir.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Valganciclovir Age Group <= 2 Years | Number of Participants With Opportunistic Infections | Oral Candidiasis | 2 participants |
| Valganciclovir Age Group <= 2 Years | Number of Participants With Opportunistic Infections | Cytomegalovirus Antigen Positive | 1 participants |
| Valganciclovir Age Group <= 2 Years | Number of Participants With Opportunistic Infections | Herpes Simplex | 0 participants |
| Valganciclovir Age Group <= 2 Years | Number of Participants With Opportunistic Infections | Cytomegalovirus Test Positive | 1 participants |
| Valganciclovir Age Group <= 2 Years | Number of Participants With Opportunistic Infections | Candidiasis | 1 participants |
| Valganciclovir Age Group >2 to < 12 Years | Number of Participants With Opportunistic Infections | Cytomegalovirus Test Positive | 0 participants |
| Valganciclovir Age Group >2 to < 12 Years | Number of Participants With Opportunistic Infections | Oral Candidiasis | 0 participants |
| Valganciclovir Age Group >2 to < 12 Years | Number of Participants With Opportunistic Infections | Candidiasis | 0 participants |
| Valganciclovir Age Group >2 to < 12 Years | Number of Participants With Opportunistic Infections | Herpes Simplex | 1 participants |
| Valganciclovir Age Group >2 to < 12 Years | Number of Participants With Opportunistic Infections | Cytomegalovirus Antigen Positive | 0 participants |
| Valganciclovir Age Group >= 12 Years | Number of Participants With Opportunistic Infections | Candidiasis | 0 participants |
| Valganciclovir Age Group >= 12 Years | Number of Participants With Opportunistic Infections | Cytomegalovirus Test Positive | 0 participants |
| Valganciclovir Age Group >= 12 Years | Number of Participants With Opportunistic Infections | Cytomegalovirus Antigen Positive | 0 participants |
| Valganciclovir Age Group >= 12 Years | Number of Participants With Opportunistic Infections | Oral Candidiasis | 0 participants |
| Valganciclovir Age Group >= 12 Years | Number of Participants With Opportunistic Infections | Herpes Simplex | 0 participants |
Secondary
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.
Time frame: 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
Population: The PK analysis population comprised all participants from studies WP16296, WP16303 and WV16726 who completed the specified treatment and from whom at least one plasma sample was taken.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Valganciclovir Age Group <= 2 Years | Mean Elimination Half-Life of Valganciclovir Over Time | In kidney recipients, n=2, 12, 19 | 3.1 hours | Standard Deviation 0.59 |
| Valganciclovir Age Group <= 2 Years | Mean Elimination Half-Life of Valganciclovir Over Time | In liver recipients, n=9, 6, 2 | 2.72 hours | Standard Deviation 1.32 |
| Valganciclovir Age Group <= 2 Years | Mean Elimination Half-Life of Valganciclovir Over Time | In heart recipients, n=6, 2, 4 | 3.6 hours | Standard Deviation 1.73 |
| Valganciclovir Age Group >2 to < 12 Years | Mean Elimination Half-Life of Valganciclovir Over Time | In kidney recipients, n=2, 12, 19 | 4.47 hours | Standard Deviation 1.37 |
| Valganciclovir Age Group >2 to < 12 Years | Mean Elimination Half-Life of Valganciclovir Over Time | In liver recipients, n=9, 6, 2 | 3.61 hours | Standard Deviation 0.8 |
| Valganciclovir Age Group >2 to < 12 Years | Mean Elimination Half-Life of Valganciclovir Over Time | In heart recipients, n=6, 2, 4 | 2.62 hours | Standard Deviation 0.65 |
| Valganciclovir Age Group >= 12 Years | Mean Elimination Half-Life of Valganciclovir Over Time | In liver recipients, n=9, 6, 2 | 4.5 hours | Standard Deviation 0.25 |
| Valganciclovir Age Group >= 12 Years | Mean Elimination Half-Life of Valganciclovir Over Time | In heart recipients, n=6, 2, 4 | 5.05 hours | Standard Deviation 0.7 |
| Valganciclovir Age Group >= 12 Years | Mean Elimination Half-Life of Valganciclovir Over Time | In kidney recipients, n=2, 12, 19 | 5.69 hours | Standard Deviation 1.06 |
Secondary
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.
Time frame: 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
Population: The PK analysis population comprised all participants from studies WP16296, WP16303 and WV16726 who completed the specified treatment and from whom at least one plasma sample was taken. Here n represents number of participant with specific transplant i.e., kidney, liver, and heart.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Valganciclovir Age Group <= 2 Years | Mean Maximum Plasma Concentration of Valganciclovir Over Time | In kidney recipients, n=2, 12, 19 | 10 mcg/mL | Standard Deviation 0.04 |
| Valganciclovir Age Group <= 2 Years | Mean Maximum Plasma Concentration of Valganciclovir Over Time | In liver recipients, n=9, 6, 2 | 11.7 mcg/mL | Standard Deviation 3.59 |
| Valganciclovir Age Group <= 2 Years | Mean Maximum Plasma Concentration of Valganciclovir Over Time | In heart recipients, n=6, 2, 4 | 8.22 mcg/mL | Standard Deviation 2.44 |
| Valganciclovir Age Group >2 to < 12 Years | Mean Maximum Plasma Concentration of Valganciclovir Over Time | In heart recipients, n=6, 2, 4 | 12.5 mcg/mL | Standard Deviation 1.02 |
| Valganciclovir Age Group >2 to < 12 Years | Mean Maximum Plasma Concentration of Valganciclovir Over Time | In kidney recipients, n=2, 12, 19 | 8.74 mcg/mL | Standard Deviation 2.49 |
| Valganciclovir Age Group >2 to < 12 Years | Mean Maximum Plasma Concentration of Valganciclovir Over Time | In liver recipients, n=9, 6, 2 | 9.35 mcg/mL | Standard Deviation 2.33 |
| Valganciclovir Age Group >= 12 Years | Mean Maximum Plasma Concentration of Valganciclovir Over Time | In heart recipients, n=6, 2, 4 | 9.5 mcg/mL | Standard Deviation 3.34 |
| Valganciclovir Age Group >= 12 Years | Mean Maximum Plasma Concentration of Valganciclovir Over Time | In liver recipients, n=9, 6, 2 | 5.55 mcg/mL | Standard Deviation 1.34 |
| Valganciclovir Age Group >= 12 Years | Mean Maximum Plasma Concentration of Valganciclovir Over Time | In kidney recipients, n=2, 12, 19 | 7.85 mcg/mL | Standard Deviation 2.1 |
Secondary
Number of Participants Who Experienced Episodes of Rejection Over Time
Participants with biopsy proven active rejection are reported.
Time frame: Up to Week 26
Population: The ITT population comprised all participants who received at least one dose of the study drug, whether on-study or prematurely withdrawn.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Valganciclovir Age Group <= 2 Years | Number of Participants Who Experienced Episodes of Rejection Over Time | 5 participants |
| Valganciclovir Age Group >2 to < 12 Years | Number of Participants Who Experienced Episodes of Rejection Over Time | 2 participants |
| Valganciclovir Age Group >= 12 Years | Number of Participants Who Experienced Episodes of Rejection Over Time | 2 participants |
Secondary
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.
Time frame: Up to Week 26
Population: ITT population: The ITT population comprised all participants who received at least one dose of the study drug, whether on-study or prematurely withdrawn.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Valganciclovir Age Group <= 2 Years | Number of Participants Who Experienced Graft Loss | Recurrence of Underlying Disease | 0 participants |
| Valganciclovir Age Group <= 2 Years | Number of Participants Who Experienced Graft Loss | Technical Complications | 0 participants |
| Valganciclovir Age Group <= 2 Years | Number of Participants Who Experienced Graft Loss | Primary Graft Non-Function | 0 participants |
| Valganciclovir Age Group <= 2 Years | Number of Participants Who Experienced Graft Loss | Other | 0 participants |
| Valganciclovir Age Group <= 2 Years | Number of Participants Who Experienced Graft Loss | Acute Graft Rejection | 1 participants |
| Valganciclovir Age Group <= 2 Years | Number of Participants Who Experienced Graft Loss | Chronic Graft Rejection | 0 participants |
| Valganciclovir Age Group >2 to < 12 Years | Number of Participants Who Experienced Graft Loss | Other | 1 participants |
| Valganciclovir Age Group >2 to < 12 Years | Number of Participants Who Experienced Graft Loss | Primary Graft Non-Function | 0 participants |
| Valganciclovir Age Group >2 to < 12 Years | Number of Participants Who Experienced Graft Loss | Chronic Graft Rejection | 0 participants |
| Valganciclovir Age Group >2 to < 12 Years | Number of Participants Who Experienced Graft Loss | Acute Graft Rejection | 0 participants |
| Valganciclovir Age Group >2 to < 12 Years | Number of Participants Who Experienced Graft Loss | Recurrence of Underlying Disease | 0 participants |
| Valganciclovir Age Group >2 to < 12 Years | Number of Participants Who Experienced Graft Loss | Technical Complications | 0 participants |
| Valganciclovir Age Group >= 12 Years | Number of Participants Who Experienced Graft Loss | Acute Graft Rejection | 0 participants |
| Valganciclovir Age Group >= 12 Years | Number of Participants Who Experienced Graft Loss | Technical Complications | 1 participants |
| Valganciclovir Age Group >= 12 Years | Number of Participants Who Experienced Graft Loss | Primary Graft Non-Function | 0 participants |
| Valganciclovir Age Group >= 12 Years | Number of Participants Who Experienced Graft Loss | Recurrence of Underlying Disease | 0 participants |
| Valganciclovir Age Group >= 12 Years | Number of Participants Who Experienced Graft Loss | Other | 0 participants |
| Valganciclovir Age Group >= 12 Years | Number of Participants Who Experienced Graft Loss | Chronic Graft Rejection | 0 participants |
Secondary
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.
Time frame: Up to Week 26
Population: Safety population included all participants who received at least one dose of valganciclovir.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Valganciclovir Age Group <= 2 Years | Number of Participants With Cytomegalovirus Disease Over Time | 0 participants |
| Valganciclovir Age Group >2 to < 12 Years | Number of Participants With Cytomegalovirus Disease Over Time | 2 participants |
| Valganciclovir Age Group >= 12 Years | Number of Participants With Cytomegalovirus Disease Over Time | 2 participants |
Secondary
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.
Time frame: Up to Week 26
Population: The Intent to Treat (ITT) population comprised all participants who received at least one dose of the study drug, whether on-study or prematurely withdrawn.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Valganciclovir Age Group <= 2 Years | Number of Participants With Treatment Failures | 2 participants |
| Valganciclovir Age Group >2 to < 12 Years | Number of Participants With Treatment Failures | 2 participants |
| Valganciclovir Age Group >= 12 Years | Number of Participants With Treatment Failures | 0 participants |