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 8/11/2005 and Investigator Brochure Version August 2005
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 5
- 试验地点
- 2
- 主要终点
- The primary objective of the study is to determine bioequivalence of ganciclovir from the
研究概览
简要总结
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 (D+R-, D+R+, 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.
详细描述
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 mg/kg) 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 ml/min 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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 68 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patient has received first or second kidney transplant.
- •Transplantation occurred at least 14 days before screening.
- •Patient at risk of CMV disease (serostatus, D+R-, D+R+ or D-R+).
- •Patient aged 18 to 68 years inclusive.
- •Patient able to tolerate oral medication from screening to follow-up.
- •Patient being treated with Valganciclovir for prophylaxis of CMV disease according to current center practice.
- •Patient on stable calcineurin inhibitor and 900 mg Valganciclovir therapy (≥ 4 days prior to Day 1).
- •Patient with stable serum creatinine (± 0.2 mg/dL) for duration of at least 4 days prior to dosing on Day
- •Patient with adequate hematological and renal function defined as:
- •Estimated creatinine clearance ≥ 60 ml/min
- •Absolute neutrophil count ≥ 2500 cells/µL
- •Platelet count ≥ 100,000 cells/µL
- •Hemoglobin ≥ 9.0g/dL
- •Patient agrees to use an effective method of contraception (or abstinence from sexual activity) throughout the study period and for 90 days after follow-up, if female of child-bearing potential, or if male with a female partner of child-bearing potential.
- •Females of childbearing potential with a negative pregnancy test at screening.
- •Patient able to participate, willing to give written, informed consent and comply with the study restrictions.
排除标准
- •Patients with any of the following will be excluded from the study:
- •Patient is simultaneously participating in another clinical trial, except as approved by the Sponsor.
- •Patient has used an investigational drug within three months of screening.
- •Patient has exhibited in the past an allergic, or other significant adverse reaction to acyclovir, Val acyclovir, ganciclovir or Valganciclovir.
- •Patient has severe, uncontrolled diarrhea.
- •Evidence of graft rejection as determined by the Investigator.
- •Patient requires the use of any prohibited concomitant medications (Section 4.4).
- •Patient has previously participated (i.e. completed Day 1) in this clinical trial.
- •Patient is pregnant or a lactating female who will not discontinue nursing prior to study entry.
- •Patient has received anti-CMV prophylaxis with a treatment other than intravenous cytogam, intravenous ganciclovir or Valganciclovir between transplant and enrollment.
- •Patient with active bacterial, viral, fungal or protozoal infection.
结局指标
主要结局
The primary objective of the study is to determine bioequivalence of ganciclovir from the
Valganciclovir tutti-frutti syrup formulation and the 450 mg tablet formulation at a dose of 900 mg administered in the fed state.
次要结局
- Valganciclovir strawberry syrup formulation with the valganciclovir tutti-frutti syrup formulation at a dose of 900mg.
- The secondary objective is to compare the systemic exposure to ganciclovir from the