Changes in Triglyceride and Other Lipids (Levels of Fats Found in Blood) When Taking Darunavir Compared to Atazanavir in HIV-infected Patients That Have Never Received Treatment

This study has been completed.
Sponsor:
Collaborator:
Tibotec Therapeutics, a Division of Ortho Biotech Products, L.P., USA
Information provided by:
Tibotec, Inc
ClinicalTrials.gov Identifier:
NCT00757783
First received: September 19, 2008
Last updated: February 3, 2014
Last verified: September 2012
  Purpose

The purpose of this research study is to compare changes in triglyceride and other lipids (levels of fats found in the blood) from Baseline (Day 1) to Week 12 for darunavir/ritonavir 800/100 mg once daily versus atazanavir/ritonavir 300/100 mg once daily in combination with a fixed-dose background regimen consisting of emtricitabine [FTC]/tenofovir [TDF] 200/300 mg once daily). This study will also evaluate the safety (adverse events), effectiveness, and tolerability of darunavir/ritonavir and atazanivir/ritonavir over 48 weeks.


Condition Intervention Phase
HIV
Drug: ritonavir
Drug: darunavir
Drug: emtricitabine [FTC]/tenofovir [TDF]
Drug: atazanavir
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Multicenter, Open-label, Randomized Study to Assess the Metabolics, Efficacy, and Safety of Once-daily Darunavir Versus Atazanavir in HIV-infected Treatment-naive Adult Patients

Resource links provided by NLM:


Further study details as provided by Tibotec, Inc:

Primary Outcome Measures:
  • Change From Baseline in Fasting Triglyceride (TG) Levels in the Lipid Evaluable (LE) Set at Week 12. [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
    Observed Values


Secondary Outcome Measures:
  • Change From Baseline in Total Cholesterol (TC) Levels in the LE Set at Week 12. [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
    Observed Values

  • Change From Baseline in Low Density Lipoprotein (LDL) Direct in the LE Set at Week 12. [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
    Observed Values

  • Change From Baseline in High Density Lipoprotein (HDL) in the LE Set at Week 12. [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
    Observed Values

  • Change From Baseline in Apolipoprotein A1 in the LE Set at Week 12. [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
    Observed Values

  • Change From Baseline in Apolipoprotein B in the LE Set at Week 12. [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
    Observed Values

  • Change From Baseline in TC/HDL Ratio in the LE Set at Week 12. [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
    Observed Values

  • Change From Baseline in Glucose at Week 12. [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
    Observed Values

  • Change From Baseline in Insulin at Week 12. [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
    Observed Values

  • Change From Baseline in Homeostasis Model Assessment-Insulin Resistance (HOMA-IR) at Week 12. [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
    Observed Values

  • Antiviral Activity, Human Immunodeficiency Virus Type 1 (HIV-1) RNA. [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
    Observed Values

  • Antiviral Activity, HIV-1 RNA, Missing Values as Treatment Failure (M=F) [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
    Missing Values as Treatment Failure (Missing = Failure)

  • Change From Baseline in HIV-1 RNA Viral Load at Week 12. [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
    Log Base 10 Transformed HIV-1 RNA. Observed Values.

  • Change From Baseline in CD4 Cell Count at Week 12. [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
    Observed Values

  • Change From Baseline in CD4 Cell Count at Week 12, Last Observation Carried Forward (LOCF). [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
    LOCF


Enrollment: 86
Study Start Date: September 2008
Study Completion Date: July 2012
Primary Completion Date: August 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: darunavir
darunavir 800 mg tablet once daily for 48 weeks,emtricitabine [FTC]/tenofovir [TDF] 200/300 mg tablet once daily for 48 weeks,ritonavir 100 mg capsule or tablet once daily for 48 weeks
Drug: ritonavir
100 mg capsule or tablet once daily for 48 weeks
Drug: darunavir
800 mg tablet once daily for 48 weeks
Drug: emtricitabine [FTC]/tenofovir [TDF]
200/300 mg tablet once daily for 48 weeks
Experimental: atazanavir
atazanavir 300 mg capsule once daily for 48 weeks,emtricitabine [FTC]/tenofovir [TDF] 200/300 mg once daily for 48 weeks,ritonavir 100 mg capsule or tablet once daily for 48 weeks
Drug: ritonavir
100 mg capsule or tablet once daily for 48 weeks
Drug: emtricitabine [FTC]/tenofovir [TDF]
200/300 mg once daily for 48 weeks
Drug: atazanavir
300 mg capsule once daily for 48 weeks

Detailed Description:

The purpose of this study is to expand our understanding of the metabolic effects of darunavir/ritonavir (DRV/r) in HIV-infected patients. This is a phase 4, multicenter, open-label, randomized (study drug assigned by chance), comparative study designed to compare changes in lipid, glucose, and insulin parameters in HIV-infected, anti-retroviral (ARV) naive patients treated with DRV/r 800/100 mg once daily (QD) versus atazanavir/ritonavir (ATV/r) 300/100 mg QD in combination with a common background of emtricitabine (FTC)/ tenofovir (TDF) 200/300 mg QD. In addition, changes in inflammatory markers will be measured. A substudy of the parent study TMC114HIV4023 will evaluate insulin sensitivity and endothelial function in a subset of patients. The study will be conducted at approximately 16 study sites in the United States. Approximately 60 HIV-1 infected, treatment-naive adult patients will be enrolled in the study. Screening will take place during a 4-week period. At the baseline visit, eligible patients will be randomized in a 1:1 ratio to receive DRV/r 800/100 mg QD or ATV/r 300/100 mg QD administered in combination with a fixed-dose background regimen consisting of emtricitabine (FTC)/tenofovir (TDF) 200/300 mg once daily. The treatment period is 48 weeks. Study assessments will be performed at clinic visits at the end of weeks 4, 8, 12, 24, 36, and 48. The primary endpoint will be assessed at week 12. All patients will return for follow up visits 1 week and 4 weeks after the completion of study treatment. During the treatment period, the patient will be seen at regular visits during which the investigator will assess the patient's medical condition, any Adverse Events and study drug compliance. Laboratory evaluations for efficacy and safety will be done at regular visits as well as blood pressure monitoring. Up to twenty patients (evenly randomized to receive DRV/r or ATV/r) who meet additional entry criteria will be enrolled in the substudy. The study hypothesis is the change in triglycerides and other lipids from baseline to week 12 will be similar in the DRV/r arm versus the ATV/r arm. The substudy hypothesis is that DRV/r will not adversely affect insulin sensitivity or endothelial function during 12 weeks of therapy, and the change from baseline in insulin sensitivity and endothelial function will be similar in the DRV/r arm versus the ATV/r arm. During the treatment period, the patient will be seen at regular visits during which the investigator will assess the patient's medical condition, any Adverse Events and study drug compliance. Laboratory evaluations for efficacy and safety will be done at regular visits as well as blood pressure monitoring. Patients will be randomized in a 1:1 ratio to receive darunavir/ritonavir 800/100 mg once daily (QD) plus emtricitabine (FTC)/tenofovir (TDF) 200/300 mg QD or atazanavir/ritonavir 300/100 mg QD plus emtricitabine (FTC)/tenofovir (TDF) for 48 weeks.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • HIV-1 RNA of 1000 copies/mL or more
  • No previous treatment with antiretroviral drugs for more than 10 days
  • Demonstrated sensitivity [Fold Change (FC) = lower Clinical Cut Off (CCO)] to tenofovir, darunavir and atazanavir
  • Demonstrated sensitivity to emtricitabine defined as absence of M184V/I mutation
  • Any CD4 (Cluster of Differentiation 4) cell count

Exclusion Criteria:

  • Body mass index >30 kg/m2
  • Laboratory parameters as follows: fasting glucose >110 mg/dL, Low-Density Lipoprotein (LDL) cholesterol >130 mg/dL, triglycerides >200 mg/dL
  • Presence of any currently active AIDS-defining illness
  • Treatment for primary HIV infection or postexposure prophylaxis for HIV
  • Patients with acute or chronic hepatitis A, B or C infection
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00757783

Sponsors and Collaborators
Tibotec, Inc
Tibotec Therapeutics, a Division of Ortho Biotech Products, L.P., USA
Investigators
Study Director: Tibotec, Inc. Clinical Trial Tibotec, Inc
  More Information

No publications provided by Tibotec, Inc

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Vice President, Clinical Affairs, Tibotec Therapeutics, a Division of Ortho Biotech Products, L.P., USA
ClinicalTrials.gov Identifier: NCT00757783     History of Changes
Other Study ID Numbers: CR015439, TMC114HIV4023
Study First Received: September 19, 2008
Results First Received: August 12, 2010
Last Updated: February 3, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Tibotec, Inc:
HIV
AIDS
Immunodeficiency Virus, Human
PREZISTA
darunavir
TMC114
Protease Inhibitor
Truvada
Atazanavir
REYATAZ
HIV Infections
Treatment Naïve

Additional relevant MeSH terms:
Emtricitabine
Tenofovir
Tenofovir disoproxil
Ritonavir
Atazanavir
Darunavir
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Retroviral Agents
Anti-HIV Agents
HIV Protease Inhibitors
Protease Inhibitors

ClinicalTrials.gov processed this record on September 30, 2014