Treatment Simplification by Darunavir/Ritonavir 800/100 mg Once a Day Versus a Triple Combination Therapy With Darunavir/Ritonavir

NCT ID: NCT00458302

Last Updated: 2012-12-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 256 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-06-30
• Study Completion Date: 2011-01-31

Brief Summary

The purpose of the study is to compare the efficacy, safety and tolerability of darunavir/ritonavir 800/100 mg once a day (O.D.) as a monotherapy versus a triple combination therapy containing 2 nucleosides and darunavir/ritonavir in 250 HIV-1 infected patients who have been on Highly Active Antiretroviral Therapy (HAART) and have plasma viral load below 50 copies/ml for at least 24 weeks.

Detailed Description

This study is randomised (patients are assigned different treatments based on chance), controlled, open-label trial to compare the efficacy, safety and tolerability of darunavir/ritonavir (DRV/r) 800/100 mg once a day (O.D.) as a monotherapy versus a triple combination therapy containing 2 nucleosides and DRV/r in 250 HIV-1 infected patients. Patients will be considered eligible if they have not changed any antiretroviral drugs for at least 8 weeks prior to screening and have documented evidence of plasma viral load (or plasma HIV-1 RNA) < 50 copies/mL for at least 24 weeks prior to being screened. The trial will consist of a screening period up to 4 weeks, a 48-week treatment period, followed by a 4-week follow-up (FU) period. The primary objective is to demonstrate non-inferiority in efficacy of DRV/r versus the triple combination therapy containing DRV/r, with respect to confirmed virologic response, defined as plasma HIV-1 RNA < 50 copies/mL at 48 weeks.Patients will be assigned a study medication based on a 1:1 ratio to either switch to a triple combination therapy containing 2 nucleosides and DRV/r 800/100 mg O.D, or initiate monotherapy with DRV/r 800/100 mg O.D. Patients in the triple combination arm who are already on 2 nucleosides prior to randomisation may remain on these or switch them at baseline. Patients randomised to the monotherapy arm will discontinue Highly Active Antiretroviral Therapy (HAART) at baseline and commence DRV/r 800/100 mg O.D. A Data and Safety Monitoring Board (DSMB) has been commissioned for this study. The role of the DSMB is to review the progress of the trial and the accumulating data to detect evidence of early safety issues for the patients while the trial is ongoing. An interim analysis will be performed after 24 weeks of treatment. The results of the Week 24 analysis will be used to determine whether long-term follow-up to 72 and 96 weeks will be done. The protease inhibitor (PI) component of the regimen cannot be changed until the end of the treatment period and the nucleoside reverse transcriptase inhibitors (NRTIs) cannot be modified until the end of the treatment period with the following exception: single antiretroviral (ARV) substitutions will be allowed for tolerability/toxicity reasons, as long as this can be linked to an adverse event (AE) or an serious adverse event (SAE). After withdrawal of the patient from the trial, changes in the ARV regimen are allowed after the assessments of the withdrawal visit have been performed.

Temporary interruption of all ARVs will be allowed in the event of suspected toxicity, as long as the temporary interruption is associated with and can be linked to an AE or a SAE. For the control arm, the nucleoside analogues could be re-optimized at baseline or on study, and all approved ARVs allowed. However, PIs other than DRV/r are not allowed during the treatment period. Patients who cannot resume study medication will have to be withdrawn. A physical examination will be done at protocol-scheduled visits and vital signs will be monitored at each study visit. In addition, at each study visit, every patient will be asked about the occurrence of or change to AEs since they were last seen by the investigator. Laboratory samples for haematology and serum chemistry will be drawn and the results determined and transmitted to the investigator. Urinalysis will be performed. Pregnancy test will be done at each visit for female participants of child-bearing potential. The primary endpoint will be the proportion with virologic response, defined as a confirmed plasma HIV-1 RNA < 50 copies/mL at Week 48.The study hypothesis is that DRV/r monotherapy will be as effective as a triple combination regimen and will be well tolerated in this early pre-treated HIV-1 patients. Two 400mg tablets of darunavir once daily orally within 30 minutes after completion of a meal for 48 weeks.

Conditions

HIV Infections; AIDS Virus; Human Immunodeficiency Virus; Acquired Immunodeficiency Syndrome Virus

Keywords

HIV; Monotherapy; Darunavir; Protease inhibitor; Early pre-treated; Undetectable; Treatment Experienced

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

darunavir monotherapy

darunavir (DRV, TMC114) 800 mg qd (2 x 400 mg tablet) monotherapy for 144 weeks

Group Type: EXPERIMENTAL

darunavir (DRV, TMC114)

Intervention Type: DRUG

800 mg qd (2 x 400 mg tablet) monotherapy for 144 weeks

darunavir + 2 NRTI

darunavir (DRV, TMC114) 800 mg qd (2 x 400 mg tablet) + 2 NRTI for 144 weeks

Group Type: EXPERIMENTAL

darunavir (DRV, TMC114)

Intervention Type: DRUG

800 mg qd (2 x 400 mg tablet) + 2 NRTI for 144 weeks

Interventions

darunavir (DRV, TMC114)

800 mg qd (2 x 400 mg tablet) + 2 NRTI for 144 weeks

Intervention Type: DRUG

darunavir (DRV, TMC114)

800 mg qd (2 x 400 mg tablet) monotherapy for 144 weeks

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Patients with documented HIV-1 infection
• Patients currently receiving HAART for at least 24 weeks
• Plasma viral load < 50 copies/mL for at least 24 weeks prior to screening (two results must be documented)
• Patients taking the same antiretroviral combination for at least 8 weeks before screening
• Patients and physician's preference to change the current HAART regimen for reasons of simplification and/or toxicity
• CD4 > 100/mm3 at the start of HAART and > 200/mm3 at screening.

Exclusion Criteria

• No history of virological failure defined as two consecutive plasma HIV-1 RNA > 500 copies/mL while on previous or current antiretroviral therapy
• No history of any primary PI mutations as defined by the IAS-USA guidelines 2006
• No patients co-infected with hepatitis B
• No pregnant or breastfeeding women
• No active clinically significant disease or life threatening disease or findings during screening of medical history or physical examination that, in the investigator's opinion, would compromise the patient's safety or outcome of the study.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Janssen-Cilag International NV

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Janssen-Cilag International NV Clinical Trial

Role: STUDY_DIRECTOR

Janssen-Cilag International NV

Locations

Vienna, , Austria

Antwerp, , Belgium

Brussels, , Belgium

Aarhus, , Denmark

Copenhagen, , Denmark

Hvidovre, , Denmark

Odense, , Denmark

Berlin, , Germany

Frankfurt, , Germany

Hamburg, , Germany

Hanover, , Germany

Kÿln N/A, , Germany

Budapest, , Hungary

Jerusalem, , Israel

Tel Aviv, , Israel

Tel Litwinsky, , Israel

Lisbon, , Portugal

Porto, , Portugal

Moscow, , Russia

Saint Petersburg, , Russia

Barcelona, , Spain

Donostia Guipuzcoa, , Spain

Granada, , Spain

Madrid, , Spain

Valladolid, , Spain

Sankt Gallen, , Switzerland

London, , United Kingdom

Countries

Poland; Austria; Belgium; Denmark; Germany; Hungary; Israel; Portugal; Russia; Spain; Switzerland; United Kingdom

References

Arribas JR, Horban A, Gerstoft J, Fatkenheuer G, Nelson M, Clumeck N, Pulido F, Hill A, van Delft Y, Stark T, Moecklinghoff C. The MONET trial: darunavir/ritonavir with or without nucleoside analogues, for patients with HIV RNA below 50 copies/ml. AIDS. 2010 Jan 16;24(2):223-30. doi: 10.1097/QAD.0b013e3283348944.

Reference Type: DERIVED

PMID: 20010070 (View on PubMed)

Other Identifiers

TMC114HIV3006

Identifier Type: OTHER

Identifier Source: secondary_id

2006-006437-40

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CR013159

Identifier Type: -

Identifier Source: org_study_id