Clinical trial NCT01236378: Study To Evaluate Pharmacokinetics Of Sirolimus In Stable Renal Transplant Recipients
Official title: An Open-Label, Non-Randomized Study To Evaluate The Steady-State Pharmacokinetics Of Sirolimus Tablets In Chinese Patients With Stable Renal Allografts
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Transplant Rejection
Renal Transplantation
Keywords: Organ Transplants
Anti-Rejection Therapy
Pharmacokinetics
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2010-11-07
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Sirolimus, 1 mg, white, triangular tablets (Rapamune®) was approved on 03 April 2007 in China for prophylaxis of organ rejection in renal transplantation. A pharmacokinetic (PK) study to be conducted in renal allograft recipients was requested by State Food and Drug Administration (SFDA) to provide further guidance for clinical use.

To minimize risk to patients, this study is designed to collect blood PK samples from renal allograft recipients who are currently under sirolimus (1 mg tablets) treatment with or without concomitant medication(s). PK samples will be collected from these patients to characterize the steady state PK of sirolimus during sirolimus maintenance therapy. This study will not involve any changes to the established treatment regimen for the patients who enroll in the study


Eligibility criteria: Inclusion Criteria:

* Male or female, above 18 years of age and Body Mass Index (BMI) of 18.0 to 25.0 kg/m2, inclusive;
* Subjects must have received a primary or secondary renal allograft for at least 2 months prior to Screening;
* Subjects must be currently taking Rapamune tablets for prophylaxis of renal rejection. The dosages of any medications must be stable for at least 2 weeks prior to screening and continue with no change until completion of the last PK sample collection.

Exclusion Criteria:

* Acute rejection or vascular rejection episode in the 4 weeks prior to Screening; or patients dependent on dialysis; or inadequate renal function (in the opinion of the investigator);
* Recipients of multiple organ transplants (i.e., prior or concurrent transplantation of any organs other than renal transplant);
* Current use of strong inducers or inhibitors of CYP3A4 within 2 weeks prior to collection of the first PK sample and until collection of the final PK sample;
* Any clinically significant medical or psychiatric condition or laboratory abnormality, in the judgment of the investigator.

Primary outcomes:
measure: Maximum Observed Blood Concentration at Steady State (Cmax,ss)
timeFrame: Predose (0 hour) and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12 and 24 hours post dose
measure: Time to Reach Maximum Observed Blood Concentration at Steady State (Tmax,ss)
timeFrame: Predose (0 hour) and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12 and 24 hours post dose
measure: Observed Blood Trough Concentration at Steady State (Ctrough,ss)
timeFrame: Predose (0 hour) and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12 and 24 hours post dose
measure: Average Blood Concentration at Steady State (Cave,ss)
timeFrame: Predose (0 hour) and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12 and 24 hours post dose
measure: Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) at Steady State
timeFrame: Predose (0 hour) and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12 and 24 hours post dose
measure: Degree of Fluctuation (DF)
timeFrame: Predose (0 hour) and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12 and 24 hours post dose
measure: Apparent Oral Clearance (CL/F)
timeFrame: Predose (0 hour) and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12 and 24 hours post dose
Secondary outcomes:
measure: Number of Participants With Serum Creatinine Levels More Than (>) 1.3 Times the Upper Limit of Normal
timeFrame: From baseline up to Day 4
measure: Number of Participants With Estimated Glomerular Filtration Rate (GFR) Less Than (<) 60 mL/Min/1.73 m^2
timeFrame: From baseline up to Day 4
Other outcomes:
Locations:
city: Chongqing
country: China
facility: Pfizer Investigational Site
city: Shanghai
country: China
facility: Pfizer Investigational Site
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
citation: Wang HF, Qiu F, Wu X, Fang J, Crownover P, Korth-Bradley J, Schulman S. Steady-state pharmacokinetics of sirolimus in stable adult Chinese renal transplant patients. Clin Pharmacol Drug Dev. 2014 May;3(3):235-41. doi: 10.1002/cpdd.96. Epub 2014 Feb 10.