Ignite Creation Date:
2024-05-05 @ 4:35 PM
Last Modification Date:
2024-10-26 @ 9:22 AM
Study NCT ID:
NCT00275314
Status:
TERMINATED
Last Update Posted:
2015-12-17
First Post:
2006-01-09
Brief Title:
WP16302 A Bioequivalence Study Comparing Ganciclovir From the Valganciclovir Syrup Formulation and the Commercial Valganciclovir 450mg Tablet Valcyte at a Dose of 900mg in Kidney Transplant Recipients
Sponsor:
University of Pittsburgh
Organization:
University of Pittsburgh
Study Overview
Official Title:
WP16302 A Bioequivalence Study Comparing Ganciclovir From the Valganciclovir Syrup Formulation and the Commercial Valganciclovir 450mg Tablet Valcyte at a Dose of 900mg in Kidney Transplant Recipients Sponsor Protocol Dated 8112005 and Investigator Brochure Version August 2005
Status:
TERMINATED
Status Verified Date:
2015-12
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Study never started at our site Funding issue
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This is a multi-center open label randomized 3-way cross-over study 21 subjects will be randomized to receive all three treatments in one of three treatment sequences
Patients at risk of CMV disease DR- DR D-R who are being treated prophylactically with Valcyte commercially available tablets after their first or second kidney transplant and who have adequate renal and hematological function will be eligible for the study Screening may be at any time after transplantation provided that follow-up procedures can be completed during the scheduled time of prophylaxis The first dose of study drug may be between 1 and 14 days after screening provided the transplant has stabilized stable serum creatinine and steady-state kinetics of ganciclovir and calcineurin inhibitor therapy have been attained Follow-up will take place 7- 14 days after last dose of study drug administration therefore the duration of the study will be up to 5 weeks
Patients at risk of CMV disease DR- DR D-R who are being treated prophylactically with Valcyte commercially available tablets after their first or second kidney transplant and who have adequate renal and hematological function will be eligible for the study Screening may be at any time after transplantation provided that follow-up procedures can be completed during the scheduled time of prophylaxis The first dose of study drug may be between 1 and 14 days after screening provided the transplant has stabilized stable serum creatinine and steady-state kinetics of ganciclovir and calcineurin inhibitor therapy have been attained Follow-up will take place 7- 14 days after last dose of study drug administration therefore the duration of the study will be up to 5 weeks
Detailed Description:
Each patient will receive 900 mg of Valcyte daily with food for the period specified in that center typically 100 days starting as soon as possible after the transplant According to routine practice intravenous ganciclovir 5 mgkg may be substituted if the patient is unable to tolerate oral medication during which time the patient will not be enrolled into the study The dose of Valganciclovir may be reduced or interrupted at the discretion of the Investigator if he or she suspects that ganciclovir-related toxicity has occurred or if the estimated creatinine clearance of the patient drops below 60 mlmin For the actual study each patient will receive 2 days treatment on consecutive days with each Valganciclovir syrup formulation 900 mg once a day and the tablet formulation 900 mg once a day in a randomized order before continuing with Valcyte prophylaxis commercially available tablets The following three treatments will be administered in this study Randomization will occur through the IDS pharmacy and a computerized system will randomize the subjects
Treatment A Reference Valganciclovir tablets 2 x 450 mg once a day for 2 days
Treatment B Test Valganciclovir tutti-frutti flavored syrup 900 mg once a day for 2 days
Treatment C First formulation Valganciclovir strawberry flavored syrup 900 mg once a day for 2 days
All formulations will be administered orally within 15 minutes of completion of a standard breakfast 400-800 kcal Patients will be seen at that GCRC General Clinic Research Center on the 8th floor of Montefiore Hospital for all study visits except follow-up This visit will take place in the Infectious Disease Clinic 7th floor Falk Clinic
Screening
A screening examination will be performed between 1 and 14 days before the start of the study the day of first dosing with study drug Patients who fulfill all of the inclusion and none of the exclusion criteria will be accepted on to the study Patients who fail the renal or hematological function criteria may be re-screened if these parameters improve and if they are still being treated with Valcyte The following procedures will be performed to establish each patients general health and eligibility for enrollment into the study Record medical history including etiology of end-stage organ disease details of transplant date and type any previous disease including CMV and treatments immunosuppressive drugs and doses within the previous month or from transplantation whichever is the shorter Record CMV serology of donor and recipient perform physical examination record demographic information including sex age and raceethnicity Obtain vital signs height and weight Draw blood samples for laboratory screening of hematology about one teaspoon of blood and routine serum chemistry including calculation of estimated creatinine clearance Obtain a mid-stream urine sample for urinalysis and a pregnancy test females only This visit will take about 30 minutes Patient will be seen while in hospital by the research coordinators and research physicians while recovering from the kidney transplant procedure
Day 1
Patients will come to the GCRC the evening before or during the morning of Day 1 within 14 days of screening The following procedures will be carried out on all patients
Assessment that the patient is on stable calcineurin inhibitors and Valganciclovir therapy 4 days assignment of patient identification number physical examination concomitant medication since the last visit will be collected vital signs and weight blood samples for hematology and serum chemistry 5 cc mid-stream sample of urine for urinalysis and pregnancy testing females of childbearing potential only and breakfast
Study drug will be administered either two Valganciclovir tablets or 900 mg 18 mL of syrup formulation of Valganciclovir with breakfast must be within 15 minutes of completion of breakfast Adverse events and concomitant medications will be recorded Patients may be discharged after dosing This visit will take about 2-3 hours to complete
Days 2 4 and 6
Patients will return to the GCRC during the morning of these days The following procedures will be carried out on all patients
Pre-dose PK blood sample for determination of trough levels of ganciclovir 5cc
Breakfast will start within 15 minutes of the pre-dose PK blood sample The study drug either two Valganciclovir tablets or 900 mg 18 mL of syrup formulation of Valganciclovir will be administered with breakfast must be within 15 minutes of completion of breakfast
The following procedures will be carried out after dosing pharmacokinetic blood samples total blood collected each day is 11cc for determination of plasma levels of ganciclovir 05 075 10 15 20 30 40 60 80 and 12 hours post-dose time windows of 5 minutes are allowed for all samples up to 4 hours and 20 minutes for samples between 6 and 12 hours
Adverse events and concomitant medications will be documented Patients may be discharged after the 12-hour sample This day will take twelve -thirteen hours to complete
Days 3 and 5
Patients will return to the GCRC during the morning The following procedures will be carried out on all patients
Vital signs and weight 24 hour PK blood sample 30 minutes for determination of trough levels of ganciclovir before dosing with the next formulation of study drug 1cc Breakfast will start within 15 minutes of the pre-dose PK blood sample
Study drug will be administer either two Valganciclovir tablets or 900 mg 18 mL of syrup formulation of Valganciclovir with breakfast must be within 15 minutes of completion of breakfast Adverse events and concomitant medications will be recorded Patients may be discharged after dosing This visit will take about 2-3 hours to complete
Day 7
Patients will return to the GCRC during the morning The following procedures will be carried out on all patients
Blood samples for hematology and serum chemistry 5cc mid-stream sample of urine for urinalysis 24 hour PK blood sample 30 minutes for determination of trough levels of ganciclovir before dosing 5cc Breakfast will start within 15 minutes of the pre-dose PK blood sample
Two Valcyte tablets will be administered supplied by the center with breakfast must be within 15 minutes of completion of breakfast Adverse events and concomitant medications will be recorded and patients may then be discharged from the GCRC This visit will take about 2-3 hours to complete
During the Study The following safety assessments will be made throughout the study from screening to follow-up as applicable adverse events AEs including rejection and graft loss opportunistic infections CMV and others and treatments concomitant treatments including immunosuppressive therapy induction maintenance and treatment of rejection and patient survival will be documented
Follow-up Phase Patients will return between Days 13 to 20 for follow-up The follow-up procedures will include a physical examination body weight vital signs clinical laboratory safety tests hematology serum chemistry and urinalysis 5cc urine pregnancy test females of childbearing potential only and the recording of adverse events and concomitant medications Once this visit is complete the patient will have completed the study This visit should take about one hour to complete
Treatment A Reference Valganciclovir tablets 2 x 450 mg once a day for 2 days
Treatment B Test Valganciclovir tutti-frutti flavored syrup 900 mg once a day for 2 days
Treatment C First formulation Valganciclovir strawberry flavored syrup 900 mg once a day for 2 days
All formulations will be administered orally within 15 minutes of completion of a standard breakfast 400-800 kcal Patients will be seen at that GCRC General Clinic Research Center on the 8th floor of Montefiore Hospital for all study visits except follow-up This visit will take place in the Infectious Disease Clinic 7th floor Falk Clinic
Screening
A screening examination will be performed between 1 and 14 days before the start of the study the day of first dosing with study drug Patients who fulfill all of the inclusion and none of the exclusion criteria will be accepted on to the study Patients who fail the renal or hematological function criteria may be re-screened if these parameters improve and if they are still being treated with Valcyte The following procedures will be performed to establish each patients general health and eligibility for enrollment into the study Record medical history including etiology of end-stage organ disease details of transplant date and type any previous disease including CMV and treatments immunosuppressive drugs and doses within the previous month or from transplantation whichever is the shorter Record CMV serology of donor and recipient perform physical examination record demographic information including sex age and raceethnicity Obtain vital signs height and weight Draw blood samples for laboratory screening of hematology about one teaspoon of blood and routine serum chemistry including calculation of estimated creatinine clearance Obtain a mid-stream urine sample for urinalysis and a pregnancy test females only This visit will take about 30 minutes Patient will be seen while in hospital by the research coordinators and research physicians while recovering from the kidney transplant procedure
Day 1
Patients will come to the GCRC the evening before or during the morning of Day 1 within 14 days of screening The following procedures will be carried out on all patients
Assessment that the patient is on stable calcineurin inhibitors and Valganciclovir therapy 4 days assignment of patient identification number physical examination concomitant medication since the last visit will be collected vital signs and weight blood samples for hematology and serum chemistry 5 cc mid-stream sample of urine for urinalysis and pregnancy testing females of childbearing potential only and breakfast
Study drug will be administered either two Valganciclovir tablets or 900 mg 18 mL of syrup formulation of Valganciclovir with breakfast must be within 15 minutes of completion of breakfast Adverse events and concomitant medications will be recorded Patients may be discharged after dosing This visit will take about 2-3 hours to complete
Days 2 4 and 6
Patients will return to the GCRC during the morning of these days The following procedures will be carried out on all patients
Pre-dose PK blood sample for determination of trough levels of ganciclovir 5cc
Breakfast will start within 15 minutes of the pre-dose PK blood sample The study drug either two Valganciclovir tablets or 900 mg 18 mL of syrup formulation of Valganciclovir will be administered with breakfast must be within 15 minutes of completion of breakfast
The following procedures will be carried out after dosing pharmacokinetic blood samples total blood collected each day is 11cc for determination of plasma levels of ganciclovir 05 075 10 15 20 30 40 60 80 and 12 hours post-dose time windows of 5 minutes are allowed for all samples up to 4 hours and 20 minutes for samples between 6 and 12 hours
Adverse events and concomitant medications will be documented Patients may be discharged after the 12-hour sample This day will take twelve -thirteen hours to complete
Days 3 and 5
Patients will return to the GCRC during the morning The following procedures will be carried out on all patients
Vital signs and weight 24 hour PK blood sample 30 minutes for determination of trough levels of ganciclovir before dosing with the next formulation of study drug 1cc Breakfast will start within 15 minutes of the pre-dose PK blood sample
Study drug will be administer either two Valganciclovir tablets or 900 mg 18 mL of syrup formulation of Valganciclovir with breakfast must be within 15 minutes of completion of breakfast Adverse events and concomitant medications will be recorded Patients may be discharged after dosing This visit will take about 2-3 hours to complete
Day 7
Patients will return to the GCRC during the morning The following procedures will be carried out on all patients
Blood samples for hematology and serum chemistry 5cc mid-stream sample of urine for urinalysis 24 hour PK blood sample 30 minutes for determination of trough levels of ganciclovir before dosing 5cc Breakfast will start within 15 minutes of the pre-dose PK blood sample
Two Valcyte tablets will be administered supplied by the center with breakfast must be within 15 minutes of completion of breakfast Adverse events and concomitant medications will be recorded and patients may then be discharged from the GCRC This visit will take about 2-3 hours to complete
During the Study The following safety assessments will be made throughout the study from screening to follow-up as applicable adverse events AEs including rejection and graft loss opportunistic infections CMV and others and treatments concomitant treatments including immunosuppressive therapy induction maintenance and treatment of rejection and patient survival will be documented
Follow-up Phase Patients will return between Days 13 to 20 for follow-up The follow-up procedures will include a physical examination body weight vital signs clinical laboratory safety tests hematology serum chemistry and urinalysis 5cc urine pregnancy test females of childbearing potential only and the recording of adverse events and concomitant medications Once this visit is complete the patient will have completed the study This visit should take about one hour to complete
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None