A Prospective, Multi-center, Open-label, Randomized, Two Period, Two Sequence, Crossover Study to Compare the Steady State Pharmacokinetics of Generic Tacrolimus (Sandoz) to Prograf in Stable Renal Transplant Patients
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- Novartis
- 入组人数
- 71
- 试验地点
- 2
- 主要终点
- Dose-Normalized Area Under the Concentration-time Curve From Time 0 to 12 Hours (AUC0-12h) at Steady State
研究概览
简要总结
The study is designed to compare the pharmacokinetics of generic tacrolimus (Sandoz) to branded tacrolimus (Prograf) in stable renal transplant patients.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Able to participate and willing to give written informed consent and to comply with the study visits and restrictions.
- •Patient who has received a primary or secondary kidney transplant
- •Patient who is at least 6 months post transplant and on a stable dose of tacrolimus as defined by physician, one tacrolimus trough level within the physician defined target range within past 6 months and one additional trough level during the screening period within 30% of the physician defined target range.
- •Body mass index (BMI) greater than or equal to 19 but less than or equal to 35
- •Patients who are taking tacrolimus (generic, Sandoz) or Prograf
排除标准
- •Evidence of any acute rejection
- •Patients who require dialysis within 6 months prior to study entry
- •Recipients of antibodies blood group (ABO) incompatible allograft or positive crossmatch
- •Recipients of multiple organ transplants
- •Patients who have tested positive for hepatitis B surface antigen (HBsAG) or human immunodeficiency virus (HIV), or who are recipients of organ from donors who are known to be HBsAG or HIV positive. Virology screening at the time of transplant was acceptable unless more recent tests were available.
- •History of malignancy, treated or untreated, within the past 2 years with the exception of carcinoma in situ or excised basal cell carcinoma
- •Glomerular filtration rate ≤35 ml/min measured by modification of diet in renal disease (MDRD4)
- •No anticipated change in the immunosuppressive regimen during patient participation other than that required by the protocol
- •Initiation of any medications that could interfere with tacrolimus blood levels, including over the counter medications, herbal supplements, grapefruit or grapefruit juice.
- •Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive human chorionic gonadotropin (hCG) laboratory test (> 5 mIU/mL)
- •Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, UNLESS they are
- •women whose career, lifestyle, or sexual orientation precludes intercourse with a male partner
- •women whose partners have been sterilized by vasectomy or other means
- •using a highly effective method of birth control (i.e. one that results in a less than 1% per year failure rate when used consistently and correctly, such as implants, injectables, combined oral contraceptives, and some intrauterine devices (IUDs); periodic abstinence (e.g. calendar, ovulation, symptothermal, post-ovulation methods) is not acceptable.
- •Patients who are taking a generic tacrolimus product other than tacrolimus (generic, Sandoz).
研究组 & 干预措施
Sequence 1 - Branded Tacrolimus / Generic Tacrolimus
In Period 1 (Days 1-14) participants received branded tacrolimus (Prograf) orally twice a day and in Period 2 (Days 15 - 28) participants received generic tacrolimus (Sandoz) orally twice a day. Participants received the same stable dosage of tacrolimus they had been taking prior to enrollment (on a milligram for milligram basis).
干预措施: Generic Tacrolimus (Drug)
Sequence 1 - Branded Tacrolimus / Generic Tacrolimus
In Period 1 (Days 1-14) participants received branded tacrolimus (Prograf) orally twice a day and in Period 2 (Days 15 - 28) participants received generic tacrolimus (Sandoz) orally twice a day. Participants received the same stable dosage of tacrolimus they had been taking prior to enrollment (on a milligram for milligram basis).
干预措施: Branded Tacrolimus (Drug)
Sequence 2 - Generic Tacrolimus / Branded Tacrolimus
In Period 1 (Days 1 - 14) participants received generic tacrolimus (Sandoz) orally twice a day and in Period 2 (Days 15 - 28) participants received branded tacrolimus (Prograf) orally twice a day. Participants received the same stable dosage of tacrolimus they had been taking prior to enrollment (on a milligram for milligram basis).
干预措施: Generic Tacrolimus (Drug)
Sequence 2 - Generic Tacrolimus / Branded Tacrolimus
In Period 1 (Days 1 - 14) participants received generic tacrolimus (Sandoz) orally twice a day and in Period 2 (Days 15 - 28) participants received branded tacrolimus (Prograf) orally twice a day. Participants received the same stable dosage of tacrolimus they had been taking prior to enrollment (on a milligram for milligram basis).
干预措施: Branded Tacrolimus (Drug)
结局指标
主要结局
Dose-Normalized Area Under the Concentration-time Curve From Time 0 to 12 Hours (AUC0-12h) at Steady State
时间窗: Days 14 and 28: Predose and at 0.5, 1, 1.5, 1.75, 2, 3, 4, 8 and 12 hours after dosing.
Dose-normalized area under the concentration-time curve from time 0 to 12 hours (AUC0-12h) at steady state after 14 days of treatment with each study drug. Geometric mean and 95% confidence intervals were determined from an analysis of variance (ANOVA) model for the dose-normalized log transformed values with treatment, period and sequence as fixed factors and patients nested within sequences as a random factor.
Dose-normalized Maximum Plasma Drug Concentration (Cmax) at Steady State
时间窗: Days 14 and 28: Predose and at 0.5, 1, 1.5, 1.75, 2, 3, 4, 8 and 12 hours after dosing.
Maximum (peak) plasma drug concentration after drug administration at steady state (after 14 days of treatment with each study drug). Geometric mean and 95% confidence intervals were determined from an analysis of variance (ANOVA) model for the dose-normalized log transformed values with treatment, period and sequence as fixed factors and patients nested within sequences as a random factor.
次要结局
- Intra-patient Variability of Tacrolimus Pharmacokinetic Parameters(Days 7 and 14, and Days 21 and 28.)
- Trough Plasma Drug Concentration (C0) at Steady State(Days 14 and 28: predose)
- Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE)(28 Days)
- Number of Participants With Reported Biopsy Proven Acute Rejection Episodes(28 Days)