Kidney TransplantationNCT03631316
Pharmacokinetic Parameters of Innovative Valganciclovir Versus Generic Valganciclovir
A study testing Generic Valganciclovir and Innovative Valganciclovir in people with Kidney Transplantation and Cytomegalovirus Infections, run by Luis Eduardo Morales Buenrostro at 1 site in Mexico.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Kidney Transplantation, Cytomegalovirus Infections, Pharmacokinetics
- What is being tested?
- Generic Valganciclovir and Innovative Valganciclovir
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 8 participants
- Where
- 1 siteMexico
- Study dates
- 1 Mar 2018to 1 Nov 2018
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
Mexico1 site
Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
Mexico City, 14080
About this study
Official title: 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.
Read the 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.
- Conditions
- Kidney Transplantation, Cytomegalovirus Infections, Pharmacokinetics, Therapeutic Equivalency
- Being tested
- Generic Valganciclovir, Innovative Valganciclovir
- Keywords
- valganciclovir, kidney transplantation, pharmacokinetics
- Medical subject headings
- Cytomegalovirus Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Generic ValganciclovirDrug
Also called Valganciclovir Pisa
900 mg daily during 4 days
Innovative ValganciclovirDrug
Also called Valcyte
900 mg daily during 4 days
| Study group | Role | What they receive |
|---|---|---|
| Generic valganciclovir | Experimental | Participants will receive generic formulation (Pisa) of valganciclovir, 450 mg tablets, total dosage 900 mg daily for 4 days. Receives: Drug: Generic Valganciclovir |
| Innovative valganciclovir | Active comparator | The same participant will receive innovative drug valcyte (roche), 450 mg tablets, total dosage 900 mg daily during 4 days. Receives: Drug: Innovative Valganciclovir |
What is being measured
The primary outcome is the main question the study is designed to answer.
Area Under the Curve, AUC (ng/h/mL)
AUC (ngh/mL) in both drugs (innovative and generic)
Measured: At day 4 of treatment
Secondary outcomes (4)
Maximum serum concentration, Cmax (ng/mL)
Cmax (ng/mL) in both drugs (innovative and generic)
Measured: At day 4 of treatment
Initial concentration, C0 (ng/mL)
C0 (ng/mL) in both drugs (innovative and generic)
Measured: At day 4 of treatment
Total clearance of the drug, CL/F (L/h)
CL/F (L/h), in both drugs (innovative and generic)
Measured: At day 4 of treatment
Distribution volume, Vd/F (L/h)
Vd/F (L/h), in both drugs (innovative and generic)
Measured: At day 4 of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Aug 2018
- Study start1 Mar 2018
- Primary completion30 Oct 2018
- Study completion1 Nov 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Kidney TransplantationStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- Pharmacovigilance study, prospective, observational, analytical, single center, cross over design, with random assignment to the sequence of both formulations in the same patient. Our aim will be compare the pharmacokinetic parameters of the innovative versus generic formulation of valGCV in renal transplant recipients under valGCV prophylaxis in the early posttransplant stage.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 8 participants (actual)
Sponsor and investigators
- Lead sponsor
- Luis Eduardo Morales Buenrostro
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Luis Eduardo Morales Buenrostro, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
- Investigators
- Luis E Morales-Buenrostro, PhD, Principal investigator, INCMNSZ
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03631316
- Sponsor's protocol ID
- 2260
- Status last verified
- Nov 2018
- First submitted
- 9 Aug 2018
- Last updated
- 21 Nov 2018
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 Nov 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Comparison on Pharmacokinetic Parameters of Innovative Valganciclovir Versus Generic Valganciclovir in Kidney Transplant Recipients
- ClinicalTrials.gov ID
- NCT03631316
- Acronym / sponsor ID
- 2260
- Conditions
- Kidney Transplantation, Cytomegalovirus Infections, Pharmacokinetics, Therapeutic Equivalency
- Keywords
- valganciclovir, kidney transplantation, pharmacokinetics
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 8 participants (actual)
- Lead sponsor
- Luis Eduardo Morales BuenrostroUniversity, hospital or other
- Study start
- 1 Mar 2018 (actual)
- Primary completion
- 30 Oct 2018 (actual)
- Study completion
- 1 Nov 2018 (actual)
- First posted
- 15 Aug 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Pharmacovigilance study, prospective, observational, analytical, single center, cross over design, with random assignment to the sequence of both formulations in the same patient. Our aim will be compare the pharmacokinetic parameters of the innovative versus generic formulation of valGCV in renal transplant recipients under valGCV prophylaxis in the early posttransplant stage.
| Arm | Type | Receives |
|---|---|---|
| Generic valganciclovir | Experimental | Drug: Generic ValganciclovirParticipants will receive generic formulation (Pisa) of valganciclovir, 450 mg tablets, total dosage 900 mg daily for 4 days. |
| Innovative valganciclovir | Active comparator | Drug: Innovative ValganciclovirThe same participant will receive innovative drug valcyte (roche), 450 mg tablets, total dosage 900 mg daily during 4 days. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Generic ValganciclovirAlso: Valganciclovir Pisa900 mg daily during 4 days | Drug | Generic valganciclovir |
| Innovative ValganciclovirAlso: Valcyte900 mg daily during 4 days | Drug | Innovative valganciclovir |
Primary outcome
Area Under the Curve, AUC (ng/h/mL)
Time frame: At day 4 of treatment
AUC (ngh/mL) in both drugs (innovative and generic)
4 secondary outcomes
Maximum serum concentration, Cmax (ng/mL)
Time frame: At day 4 of treatment
Initial concentration, C0 (ng/mL)
Time frame: At day 4 of treatment
Total clearance of the drug, CL/F (L/h)
Time frame: At day 4 of treatment
Distribution volume, Vd/F (L/h)
Time frame: At day 4 of treatment
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Nov 2018.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Luis E Morales-Buenrostro, PhD principal investigator
INCMNSZ
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Generic Valganciclovir and Innovative Valganciclovir in people with Kidney Transplantation and Cytomegalovirus Infections, run by Luis Eduardo Morales Buenrostro at 1 site in Mexico.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 Nov 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Mexico. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Area Under the Curve, AUC (ng/h/mL) (time frame: At day 4 of treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Nov 2018.