Pharmacokinetic Parameters of Innovative Valganciclovir Versus Generic Valganciclovir

November 20, 2018 updated by: Luis Eduardo Morales Buenrostro

Comparison on Pharmacokinetic Parameters of Innovative Valganciclovir Versus Generic Valganciclovir in Kidney Transplant Recipients

Cytomegalovirus (CMV) is the most common opportunistic viral pathogen in solid organ transplant receptors (SOTR). In Mexico, the experience using generic immunosuppressants have been demonstrated a wide variation in the pharmacokinetic parameters between generic and innovative formulation, resulting in a suboptimal absorption of the drug and reaching infratherapeutic trough levels in blood. In this study the investigators will compare the pharmacokinetic parameters of innovative and generic valganciclovir in renal transplant recipients.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Cytomegalovirus (CMV) is the most common opportunistic viral pathogen in solid organ transplant receptors (SOTR). In the absence of prophylaxis, the frequency of CMV disease in high-risk recipients (R- / D +) is 60% and 20% for intermediate-risk patients (R + / D + or -). For universal prophylaxis, the antivirals most commonly used are valganciclovir (valGCV) and IV ganciclovir. ValGCV, a prodrug of ganciclovir, has a bioavailability of 60%, which represents more than 10 times that those obtained with ganciclovir.

Pharmacokinetic studies of Valganciclovir in SOTR have been demonstrated that insufficient doses can diminish its clinical efficacy and the development of viral resistance, while excessive doses can increase its toxicity.

The risk of viremia may be associated with ineffective plasma doses, as described by Wiltshire et al., where values of the area under the curve (AUC) between 40 and 50 μg/h/ml were associated with a lower incidence of viremia, while lower AUC values are associated with an increase 8 times more for viral replication rates. As a result, pharmacokinetic studies in SOTR guide the investigators in continuing with the research of their clinical impact.

A generic drug before their release to the market needs to show that is bioequivalent with the innovative drug, assuming that it has the same therapeutic effects.

The studies for demonstrate bioequivalence are carried out in controlled conditions with healthy participants, different of SOTR characteristics as: age, gender, race, comorbidities and concomitant medication. In addition, the excipients used in generic drug are different from those of the innovative drug, so the properties of the formulation can be modified (particle size or half-life), therefore, the efficacy and drug safety.

The primary outcome will be compare the pharmacokinetic parameters of the innovative versus generic formulation of valGCV in renal transplant recipients.

Study Type

Interventional

Enrollment (Actual)

8

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Mexico
      • Mexico City, Mexico, 14080
        • Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 68 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Signed consent form for the study
  • Age between 18 and 70 years
  • Kidney transplant recipients who are stable during their follow-up
  • Kidney transplant recipients between day 31 and 90 post-transplant surgery
  • Kidney transplant recipients under prophylaxis with valganciclovir

Exclusion Criteria:

  • Participants who can not stay 12 hours at the hospital for taking the blood samples.
  • Participants with an acute rejection event
  • Participants with active cytomegalovirus disease
  • Participants with measurements of pharmacokinetic parameters with a single formulation without comparator
  • Participants that withdraw their informed consent

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Generic valganciclovir
Participants will receive generic formulation (Pisa) of valganciclovir, 450 mg tablets, total dosage 900 mg daily for 4 days.
Drug: Generic Valganciclovir
900 mg daily during 4 days
Other Names:
  • Valganciclovir Pisa
Active Comparator: Innovative valganciclovir
The same participant will receive innovative drug valcyte (roche), 450 mg tablets, total dosage 900 mg daily during 4 days.
Drug: Innovative Valganciclovir
900 mg daily during 4 days
Other Names:
  • Valcyte

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Area Under the Curve, AUC (ng/h/mL)
Time Frame: At day 4 of treatment
AUC (ngh/mL) in both drugs (innovative and generic)
At day 4 of treatment

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Maximum serum concentration, Cmax (ng/mL)
Time Frame: At day 4 of treatment
Cmax (ng/mL) in both drugs (innovative and generic)
At day 4 of treatment
Initial concentration, C0 (ng/mL)
Time Frame: At day 4 of treatment
C0 (ng/mL) in both drugs (innovative and generic)
At day 4 of treatment
Total clearance of the drug, CL/F (L/h)
Time Frame: At day 4 of treatment
CL/F (L/h), in both drugs (innovative and generic)
At day 4 of treatment
Distribution volume, Vd/F (L/h)
Time Frame: At day 4 of treatment
Vd/F (L/h), in both drugs (innovative and generic)
At day 4 of treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Luis Eduardo Morales Buenrostro

Investigators

  • Principal Investigator: Luis E Morales-Buenrostro, PhD, INCMNSZ

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 1, 2018

Primary Completion (Actual)

October 30, 2018

Study Completion (Actual)

November 1, 2018

Study Registration Dates

First Submitted

August 9, 2018

First Submitted That Met QC Criteria

August 13, 2018

First Posted (Actual)

August 15, 2018

Study Record Updates

Last Update Posted (Actual)

November 21, 2018

Last Update Submitted That Met QC Criteria

November 20, 2018

Last Verified

November 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2260

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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