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Trial record 1 of 1 for:    NCT01236378
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Study To Evaluate Pharmacokinetics Of Sirolimus In Stable Renal Transplant Recipients

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ClinicalTrials.gov Identifier: NCT01236378
Recruitment Status : Completed
First Posted : November 8, 2010
Results First Posted : February 29, 2012
Last Update Posted : March 1, 2012
Sponsor:
Information provided by (Responsible Party):
Pfizer

Tracking Information
First Submitted Date  ICMJE November 5, 2010
First Posted Date  ICMJE November 8, 2010
Results First Submitted Date  ICMJE January 30, 2012
Results First Posted Date  ICMJE February 29, 2012
Last Update Posted Date March 1, 2012
Study Start Date  ICMJE December 2010
Actual Primary Completion Date April 2011   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 29, 2012)
  • Maximum Observed Blood Concentration at Steady State (Cmax,ss) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: Predose (0 hour) and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12 and 24 hours post dose ]
  • Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) at Steady State [ Time Frame: 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) [ Time Frame: 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.
  • Apparent Oral Clearance (CL/F) [ Time Frame: 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.
Original Primary Outcome Measures  ICMJE
 (submitted: November 5, 2010)
  • Maximum blood concentration at steady state (Cmax,ss) of sirolimus [ Time Frame: 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12 and 24 hours post dose ]
  • Time to achieve maximum blood concentration at steady state(Cmax,ss) of sirolimus (Tmax,ss) [ Time Frame: 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12 and 24 hours post dose ]
  • Trough blood concentration at steady state (Ctrough,ss) of sirolimus, and Average blood concentration at steady state(Cave,ss)of sirolimus [ Time Frame: 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12 and 24 hours post dose ]
  • Area under the blood concentration versus time curve within a dosing interval of τ (=24 hr) at steady state (AUCτ) of sirolimus [ Time Frame: 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12 and 24 hours post dose ]
  • Degree of fluctuation (DF) and Apparent clearance(CL/F )of sirolimus [ Time Frame: 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12 and 24 hours post dose ]
Change History Complete list of historical versions of study NCT01236378 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: January 30, 2012)
  • Number of Participants With Serum Creatinine Levels More Than (>) 1.3 Times the Upper Limit of Normal [ Time Frame: 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.
  • Number of Participants With Estimated Glomerular Filtration Rate (GFR) Less Than (<) 60 mL/Min/1.73 m^2 [ Time Frame: 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: November 5, 2010)
  • Serum creatinine level [ Time Frame: from signing the consent form to 28 days after end of study treatment ]
  • Calculated glomerular filtration rate (GFR) [ Time Frame: from signing the consent form to end of study treatment ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study To Evaluate Pharmacokinetics Of Sirolimus In Stable Renal Transplant Recipients
Official Title  ICMJE An Open-Label, Non-Randomized Study To Evaluate The Steady-State Pharmacokinetics Of Sirolimus Tablets In Chinese Patients With Stable Renal Allografts
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

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Transplant Rejection
  • Renal Transplantation
Intervention  ICMJE Drug: Sirolimus
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.
Other Name: Rapamune
Study Arms  ICMJE Experimental: sirolimus
Subjects must be taking sirolimus (1 mg tablet formulation) with or without concomitant medications, unless specifically excluded below, for prophylaxis of renal rejection.
Intervention: Drug: Sirolimus
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: April 29, 2011)
24
Original Estimated Enrollment  ICMJE
 (submitted: November 5, 2010)
12
Actual Study Completion Date  ICMJE April 2011
Actual Primary Completion Date April 2011   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE China
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01236378
Other Study ID Numbers  ICMJE B1741018
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Pfizer
Study Sponsor  ICMJE Pfizer
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Pfizer CT.gov Call Center Pfizer
PRS Account Pfizer
Verification Date April 2011

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP