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

NCT00458302 | Completed Phase 3 Results DMC

• 3 other identifiers: CR013159TMC114HIV30062006-006437-40
• Study Type: interventional
• Target: 256
• Locations: 11 countries
• Sites: 27

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.

Conditions

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

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Virological Response [Per Protocol (PP) - Time to Loss of Virologic Response (TLOVR), < 50 Copies/ml, Week 48]

  Virological response is defined as the number of patients in the PP population with a plasma viral load \< 50 HIV RNA copies/ml at Week 48. Treatment failure was defined as two consecutive HIV RNA levels ≥ 50 copies/mL, or discontinuation of randomised treatment (known as TLOVR). In addition, any switch in background nucleoside reverse transcriptase inhibitors (NRTIs) equaled failure\* (referred to as a Switch Equals Failure analysis). \*Discontinuations and rechallenge with NRTIs are taken into account until Week 48

  Week 48

Secondary Outcomes (12)

• Virological Response [Intent To Treat (ITT) - TLOVR, < 50 Copies/ml, Week 48]

  Week 48

• Virological Response [Per Protocol (PP), TLOVR - Switch Equals Failure, < 50 Copies/ml, Week 144]

  Week 144

• Virological Response [Intent To Treat (ITT), TLOVR - All Switches Included, < 50 Copies/ml, Week 144]

  Week 144

• Virological Response [Per Protocol (PP), TLOVR - Switch Equals Failure, <200 Copies/ml, Week 144]

  week 144

• Mean Change From Baseline in CD4+ Cell Count

  at week 4, 12, 24, 36, 48, 60, 72, 84, 96, 112, 128, 144

Study Arms (2)

darunavir monotherapy

EXPERIMENTAL

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

Drug: darunavir (DRV, TMC114)

darunavir + 2 NRTI

EXPERIMENTAL

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

Drug: darunavir (DRV, TMC114)

Interventions

darunavir (DRV, TMC114) DRUG

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

darunavir + 2 NRTI

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Janssen-Cilag International NV: lead

Study Sites (27)

Unknown Facility

Vienna, Austria

Location

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Antwerp, Belgium

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Brussels, Belgium

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Aarhus, Denmark

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Copenhagen, Denmark

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Hvidovre, Denmark

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Odense, Denmark

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Berlin, Germany

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Frankfurt, Germany

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Hamburg, Germany

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Hanover, Germany

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Kÿln N/A, Germany

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Budapest, Hungary

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Jerusalem, Israel

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Tel Aviv, Israel

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Tel Litwinsky, Israel

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Lisbon, Portugal

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Porto, Portugal

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Moscow, Russia

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Saint Petersburg, Russia

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Barcelona, Spain

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Donostia Guipuzcoa, Spain

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Granada, Spain

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Madrid, Spain

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Valladolid, Spain

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Sankt Gallen, Switzerland

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London, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 20010070 DERIVED

MeSH Terms

Conditions

HIV Infections; Acquired Immunodeficiency Syndrome

Interventions

Darunavir

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Slow Virus Diseases

Intervention Hierarchy (Ancestors)

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

Limitations and Caveats

This study was not blinded and not designed to demonstrate a safety benefit to stopping nucleoside analogues.

Results Point of Contact

• Title: EMEA Medical Affairs Director Virology
• Organization: Jan-Cilag Germany

+49 7624 907580

Study Officials

• Janssen-Cilag International NV Clinical Trial

  Janssen-Cilag International NV

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 6, 2007
• First Posted: April 10, 2007
• Study Start: June 1, 2007
• Primary Completion: February 1, 2009
• Study Completion: January 1, 2011
• Last Updated: December 19, 2012
• Results First Posted: February 26, 2010

Record last verified: 2012-12

Locations

AU (1); IL (3); RU (2); ES (5); BE (2); GB (1); DK (4); CH (1); DE (5); PT (2); HU (1)