Dual Therapy With Raltegravir and Darunavir/Ritonavir in HIV Infected Patients. (RALDAR)

August 29, 2019 updated by: Josep Mallolas Masferrer, Hospital Clinic of Barcelona

Dual Therapy With Raltegravir 400 mg BID and Darunavir/Ritonavir 800/100 mg QD in HIV Infected Patients Failing to Nucleoside Reverse Transcriptase Inhibitors Based Regimens

While 3-drug regimens remain standard of care, concerns exist regarding the safety of multi-drug regimens taken for a lifetime. Problems with nucleoside analogue therapy prompted successful trials with ritonavir (RTV) boosted PI monotherapy, however long term safety and efficacy of such regimens remains unknown. Clinical trials have shown Raltegravir (RAL) to have potent activity when patients have few active background drugs; it has a superior lipid profile compared with EFV and LPV/RTV. Darunavir/r (DRV) is a potent, well tolerated PI with few GI side effects and lipid disturbances and with a high genetic barrier. The investigators hypothesized that RAL/DRV would be a well tolerated and effective regimen for those patients who are failing nucleoside reverse transcriptase inhibitors based regimens, due to poor tolerability or resistance. The investigators also would like to explore the plasma pharmacokinetics of Raltegravir combined with Darunavir in a sub-group of 12 HIV-infected patients.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Hypothesis

  • NRTI-sparing regimens are attractive options to avoid NRTI-associated toxicity and to provide a full active regimen in patients with some extent of NRTI resistance.
  • Raltegravir (RAL) and Darunavir (DRV) are potent "third drugs" and they provide a synergistic inhibition of 2 different steps in HIV replication.
  • DRV has a high genetic barrier, and could be an excellent accompanying drug for Raltegravir, providing a potent, safe and well tolerated dual therapy to patients who are failing NNRTI based treatments.

Objectives:

  • To describe the safety, tolerability and efficacy of the combination of Raltegravir and Darunavir after 24 weeks of follow up in HIV infected patients failing a NRTI based regimen.
  • To describe plasma pharmacokinetics of Raltegravir when combined with Darunavir 800mg QD in HIV-infected patients.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
15

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

  • Spain
      • Barcelona, Spain, 08036
        • Hospital Clinic

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 65 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Probability Sample

Study Population

A total of 20 HIV-infected patients failing NRTI based regimens will be included . At least 12 of these patients will undergo a complete pharmacokinetic study.

Description

Inclusion Criteria:

  • Documented HIV infection
  • Naïve to Raltegravir.
  • CD4 cell count above 200 cell/mm3.
  • No history of failure to PI containing regimens.
  • No evidence of PI mutations (IAS-mutation list) by genotype test.
  • Failing to a NRTI based regimen.
  • The treating physician decides a NRTI sparing regimen which includes DRV/r 800/100 mg QD plus Raltegravir 400 mg BID.
  • Signed informed consent form
  • In opinion of the investigator, the patient should be considered clinically stable and could follow regular visits as scheduled per protocol.

Exclusion Criteria:

  • Patients receiving drugs considered contraindicated to Raltegravir and DRV/r. Contraindicated drugs are: rifampin, fenitoin, phenobarbital in the case of raltegravir. Pravastatin, astemizole, sildenafil, are contraindicated in combination with DRV/r.
  • Pregnancy
  • Documented PI mutations

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

Cohorts and Interventions

Group / Cohort

Group / Cohort

A group or subgroup of participants in an observational study that is assessed for biomedical or health outcomes.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Single arm with dual therapy
Dual therapy RAL 400 mg bid + DRV/r 800/100 mg QD
Drug: Raltegravir
Raltegravir, 400 mg bid
Other Names:
  • Isentress
Drug: Darunavir
Darunavir, 800 mg QD + ritonavir 100 mg QD
Other Names:
  • Prezista, Norvir.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Geometric Mean of C-Trough, of Raltegravir (RAL) at a Dose of 400 mg Twice a Day Plus Darunavir/Ritonavir (DRV/RTV) at a Dose of 800/100 mg Once a Day in HIV-1-infected Patients Were Mesured After 15 Days of Therapy.
Time Frame: After at least 15 days on therapy, patients were admitted for a 24-hour PK study. The moorning dose of RAL adn DRV/r was administered in the clinic with. Blood samples were drawn immediatly before breakfast and 0.5, 1,2,3,4,6,8,12 and 24 hours afterward.
Geometric mean of C-Trough, of raltegravir (RAL) at a dose of 400 mg twice a day plus darunavir/ritonavir (DRV/RTV) at a dose of 800/100 mg once a day in HIV-1-infected patients were mesured after 15 days of therapy.The treating physician chose an NRTI-sparing regimen because of toxicity or resistance mutations to NRTIs, which included DRV/RTV 800/100 mg once daily plus RAL 400 mg twice daily. All patients were RAL and DRV naive and had no evidence of protease inhibitor mutations.
After at least 15 days on therapy, patients were admitted for a 24-hour PK study. The moorning dose of RAL adn DRV/r was administered in the clinic with. Blood samples were drawn immediatly before breakfast and 0.5, 1,2,3,4,6,8,12 and 24 hours afterward.
Geometric Mean of AUC, of Raltegravir (RAL) at a Dose of 400 mg Twice a Day Plus Darunavir/Ritonavir (DRV/RTV) at a Dose of 800/100 mg Once a Day in HIV-1-infected Patients Were Mesured After 15 Days of Therapy.
Time Frame: After at least 15 days on therapy, patients were admitted for a 24-hour PK study. The moorning dose of RAL adn DRV/r was administered in the clinic with. Blood samples were drawn immediatly before breakfast and 0.5, 1,2,3,4,6,8,12 and 24 hours afterward.
Geometric mean of AUC0 of raltegravir (RAL) at a dose of 400 mg twice a day plus darunavir/ritonavir (DRV/RTV) at a dose of 800/100 mg once a day in HIV-1-infected patients were mesured after 15 days of therapy. The treating physician chose an NRTI-Geometric mean of C-Trough, of raltegravir (RAL) at a dose of 400 mg twice a day plus darunavir/ritonavir (DRV/RTV) at a dose of 800/100 mg once a day in HIV-1-infected patients were mesured after 15 days of therapy.sparing regimen because of toxicity or resistance mutations to NRTIs, which included DRV/RTV 800/100 mg once daily plus RAL 400 mg twice daily. All patients were RAL and DRV naive and had no evidence of protease inhibitor mutations.
After at least 15 days on therapy, patients were admitted for a 24-hour PK study. The moorning dose of RAL adn DRV/r was administered in the clinic with. Blood samples were drawn immediatly before breakfast and 0.5, 1,2,3,4,6,8,12 and 24 hours afterward.
Geometric Mean of C-max, of Raltegravir (RAL) at a Dose of 400 mg Twice a Day Plus Darunavir/Ritonavir (DRV/RTV) at a Dose of 800/100 mg Once a Day in HIV-1-infected Patients Were Mesured After 15 Days of Therapy.
Time Frame: After at least 15 days on therapy, patients were admitted for a 24-hour PK study. The moorning dose of RAL adn DRV/r was administered in the clinic with. Blood samples were drawn immediatly before breakfast and 0.5, 1,2,3,4,6,8,12 and 24 hours afterward.
Geometric mean of C-max of raltegravir (RAL) at a dose of 400 mg twice a day plus darunavir/ritonavir (DRV/RTV) at a dose of 800/100 mg once a day in HIV-1-infected patients were mesured after 15 days of therapy. The treating physician chose an NRTI-Geometric mean of C-max, of raltegravir (RAL) at a dose of 400 mg twice a day plus darunavir/ritonavir (DRV/RTV) at a dose of 800/100 mg once a day in HIV-1-infected patients were mesured after 15 days of therapy.sparing regimen because of toxicity or resistance mutations to NRTIs, which included DRV/RTV 800/100 mg once daily plus RAL 400 mg twice daily. All patients were RAL and DRV naive and had no evidence of protease inhibitor mutations.
After at least 15 days on therapy, patients were admitted for a 24-hour PK study. The moorning dose of RAL adn DRV/r was administered in the clinic with. Blood samples were drawn immediatly before breakfast and 0.5, 1,2,3,4,6,8,12 and 24 hours afterward.
Geometric Mean of t1/2, of Raltegravir (RAL) at a Dose of 400 mg Twice a Day Plus Darunavir/Ritonavir (DRV/RTV) at a Dose of 800/100 mg Once a Day in HIV-1-infected Patients Were Mesured After 15 Days of Therapy
Time Frame: After at least 15 days on therapy, patients were admitted for a 24-hour PK study. The moorning dose of RAL adn DRV/r was administered in the clinic with. Blood samples were drawn immediatly before breakfast and 0.5, 1,2,3,4,6,8,12 and 24 hours afterward.
Geometric mean of t1/2 of raltegravir (RAL) at a dose of 400 mg twice a day plus darunavir/ritonavir (DRV/RTV) at a dose of 800/100 mg once a day in HIV-1-infected patients were mesured after 15 days of therapy. The treating physician chose an NRTI-Geometric mean of t1/2, of raltegravir (RAL) at a dose of 400 mg twice a day plus darunavir/ritonavir (DRV/RTV) at a dose of 800/100 mg once a day in HIV-1-infected patients were mesured after 15 days of therapy.sparing regimen because of toxicity or resistance mutations to NRTIs, which included DRV/RTV 800/100 mg once daily plus RAL 400 mg twice daily. All patients were RAL and DRV naive and had no evidence of protease inhibitor mutations.
After at least 15 days on therapy, patients were admitted for a 24-hour PK study. The moorning dose of RAL adn DRV/r was administered in the clinic with. Blood samples were drawn immediatly before breakfast and 0.5, 1,2,3,4,6,8,12 and 24 hours afterward.

Collaborators and Investigators

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

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Hospital Clinic of Barcelona

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Josep Mallolas, MD, PhD, Hospital Clinic of Barcelona

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
May 1, 2010

Primary Completion (ACTUAL)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
May 1, 2011

Study Completion (ACTUAL)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 1, 2011

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
December 10, 2010

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 10, 2010

First Posted (ESTIMATE)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
December 13, 2010

Study Record Updates

Last Update Posted (ACTUAL)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
September 27, 2019

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 29, 2019

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • RALDAR-HCB

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

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