Study To Evaluate Pharmacokinetics Of Sirolimus In Stable Renal Transplant Recipients

NCT01236378 | Completed Phase 1 Results

• 1 other identifier: B1741018
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 2

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

Conditions

Transplant Rejection; Renal Transplantation

Keywords

Organ Transplants; Anti-Rejection Therapy; Pharmacokinetics

Outcome Measures

Primary Outcomes (7)

• 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

• 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)

  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.

  Predose (0 hour) and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12 and 24 hours post dose

• 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.

  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 (2)

• Number of Participants With Serum Creatinine Levels More Than (>) 1.3 Times the Upper Limit of Normal

  From baseline up to Day 4

• Number of Participants With Estimated Glomerular Filtration Rate (GFR) Less Than (<) 60 mL/Min/1.73 m^2

  From baseline up to Day 4

Study Arms (1)

sirolimus

EXPERIMENTAL

Subjects must be taking sirolimus (1 mg tablet formulation) with or without concomitant medications, unless specifically excluded below, for prophylaxis of renal rejection.

Drug: Sirolimus

Interventions

Sirolimus DRUG

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.

Also known as: Rapamune

sirolimus

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Pfizer: lead

Study Sites (2)

Pfizer Investigational Site

Chongqing, 400038, China

Location

Pfizer Investigational Site

Shanghai, 200127, China

Location

Related Publications (1)

• 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.

  PMID: 27128614 DERIVED

Related Links

• To obtain contact information for a study center near you, click here.

MeSH Terms

Interventions

Sirolimus

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer, Inc.

ClinicalTrials.gov_Inquiries@pfizer.com

1-800-718-1021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 5, 2010
• First Posted: November 8, 2010
• Study Start: December 1, 2010
• Primary Completion: April 1, 2011
• Study Completion: April 1, 2011
• Last Updated: March 1, 2012
• Results First Posted: February 29, 2012

Record last verified: 2011-04

Locations

CN (2)