Study To Evaluate Pharmacokinetics Of Sirolimus In Stable Renal Transplant Recipients

An Open-Label, Non-Randomized Study To Evaluate The Steady-State Pharmacokinetics Of Sirolimus Tablets In Chinese Patients With Stable Renal Allografts

Status

Completed

Phases

Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01236378

Enrollment

Registered

2010-11-08

Start date

2010-12-31

Completion date

2011-04-30

Last updated

2012-03-01

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Renal Transplantation, Transplant Rejection

Keywords

Organ Transplants, Anti-Rejection Therapy, Pharmacokinetics

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

Interventions

DRUGSirolimus

Sirolimus, 1 mg, white, triangular tablets, daily dose, dosages of any of these 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.

Study design

Allocation

NON_RANDOMIZED

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

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.

Design outcomes

Primary

Measure	Time frame	Description
Apparent Oral Clearance (CL/F)	Predose (0 hour) and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12 and 24 hours post dose	Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Clearance was estimated from population pharmacokinetic (PK) modeling. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed.
Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) at Steady State	Predose (0 hour) and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12 and 24 hours post dose	—
Degree of Fluctuation (DF)	Predose (0 hour) and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12 and 24 hours post dose	DF, also known as peak to trough fluctuation (PTF) (calculated as \[Cmax minus Ctrough\] divided by Cave), is a unit-less ratio of the Cmax to Ctrough decrease expressed as a fraction of the average concentration during a dosing interval.
Maximum Observed Blood Concentration at Steady State (Cmax,ss)	Predose (0 hour) and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12 and 24 hours post dose	—
Time to Reach Maximum Observed Blood Concentration at Steady State (Tmax,ss)	Predose (0 hour) and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12 and 24 hours post dose	—
Observed Blood Trough Concentration at Steady State (Ctrough,ss)	Predose (0 hour) and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12 and 24 hours post dose	—
Average Blood Concentration at Steady State (Cave,ss)	Predose (0 hour) and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12 and 24 hours post dose	—

Secondary

Measure	Time frame	Description
Number of Participants With Estimated Glomerular Filtration Rate (GFR) Less Than (<) 60 mL/Min/1.73 m^2	From baseline up to Day 4	GFR, an index of kidney function, describes flow rate of filtered fluid through the kidney. GFR can be measured directly or estimated using established formulas. GFR was calculated using the Simplified Modification of Diet in Renal Dysfunction (MDRD) GFR equation. Normal GFR is \>90 mL/min/1.73 m\^2; children and older people usually have lower GFR. Often, kidney transplant recipients do not have normal GFRs. Lower values indicate poor kidney function. GFR \<15 mL/min/1.73 m\^2 is consistent with kidney failure. For this posting, the number of subjects with a GFR \<60 mL/min/1.73 m\^2 is listed.
Number of Participants With Serum Creatinine Levels More Than (>) 1.3 Times the Upper Limit of Normal	From baseline up to Day 4	Serum creatinine, an indicator of kidney function, formed from the metabolism of creatine, commonly found in blood, urine, and muscle tissue, is removed from blood by kidneys and excreted in urine. Increased creatinine in blood indicates decreased kidney function. Creatinine levels are age, gender and race dependent as they are related to an individual's muscle mass. Renal transplant recipients may have elevated serum creatinine. For this study an abnormal serum creatinine level is defined as 1.3 times the upper limit of normal (ULN) for the laboratory where the determination was performed.

Countries

China

Participant flow

Participants by arm

Arm	Count
Sirolimus Sirolimus, 1 mg tablet formulation; total daily dosage could have varied from participant to participant, dosage must have been stable for at least 2 weeks prior to screening and continued with no change until completion of the last PK sample collection.	24
Total	24

Baseline characteristics

Characteristic	Sirolimus
Age, Customized 18 to 44 years	16 participants
Age, Customized 45 to 64 years	8 participants
Sex: Female, Male Female	3 Participants
Sex: Female, Male Male	21 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	— / —
other Total, other adverse events	0 / 24
serious Total, serious adverse events	0 / 24

Outcome results

Primary

Apparent Oral Clearance (CL/F)

Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Clearance was estimated from population pharmacokinetic (PK) modeling. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed.