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

NCT01258374 | Completed Results

• 1 other identifier: RALDAR-HCB
• Study Type: observational
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Integrase Inhibitors, HIV; HIV PROTEASE INHIB

Keywords

Pharmacokinetics, raltegravir, darunavir, NRTI sparing regimen

Outcome Measures

Primary Outcomes (4)

• 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.

  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.

  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.

  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

  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.

Study Arms (1)

Single arm with dual therapy

Dual therapy RAL 400 mg bid + DRV/r 800/100 mg QD

Drug: Raltegravir; Drug: Darunavir

Interventions

Raltegravir DRUG

Raltegravir, 400 mg bid

Also known as: Isentress

Single arm with dual therapy

Darunavir DRUG

Darunavir, 800 mg QD + ritonavir 100 mg QD

Also known as: Prezista, Norvir.

Single arm with dual therapy

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Hospital Clinic of Barcelona: lead

Study Sites (1)

Hospital Clinic

Barcelona, 08036, Spain

Location

Related Publications (1)

• Martinez-Rebollar M, Munoz A, Perez I, Hidalgo S, Brunet M, Laguno M, Gonzalez A, Calvo M, Lonca M, Blanco JL, Martinez E, Gatell JM, Mallolas J. Pharmacokinetic study of dual therapy with raltegravir 400 mg twice daily and Darunavir/Ritonavir 800/100 mg once daily in HIV-1-infected patients. Ther Drug Monit. 2013 Aug;35(4):552-6. doi: 10.1097/FTD.0b013e31828d50ef.

  PMID: 23851911 DERIVED

MeSH Terms

Interventions

Raltegravir Potassium; Darunavir; Ritonavir

Intervention Hierarchy (Ancestors)

Pyrrolidinones; Pyrrolidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Sulfonamides; Amides; Organic Chemicals; Carbamates; Acids, Acyclic; Carboxylic Acids; Sulfones; Sulfur Compounds; Furans; Thiazoles; Azoles

Limitations and Caveats

The main limitation of our study is that it is a single-arm PK study and, thus, the effect of the introduction or withdrawal of one drug over the other cannot be compared.

Results Point of Contact

• Title: Dr. Josep Mallolas Masferrer
• Organization: Hospital Clinic

mallolas@clinic.cat

00 44 93 227 54 00

Study Officials

• Josep Mallolas, MD, PhD

  Hospital Clinic of Barcelona

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PhD

Study Record Dates

• First Submitted: December 10, 2010
• First Posted: December 13, 2010
• Study Start: May 1, 2010
• Primary Completion: May 1, 2011
• Study Completion: December 1, 2011
• Last Updated: September 27, 2019
• Results First Posted: September 27, 2019

Record last verified: 2019-08

Data Sharing

• IPD Sharing: Will not share

Locations

ES (1)