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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

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ClinicalTrials.gov Identifier: NCT00757783
Recruitment Status : Completed
First Posted : September 23, 2008
Results First Posted : September 10, 2010
Last Update Posted : December 30, 2015
Sponsor:
Collaborator:
Tibotec Therapeutics, a Division of Ortho Biotech Products, L.P., USA
Information provided by (Responsible Party):
Tibotec, Inc

Study Description
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Brief Summary:
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 or disease Intervention/treatment Phase
HIV Drug: ritonavir Drug: darunavir Drug: emtricitabine [FTC]/tenofovir [TDF] Drug: atazanavir Phase 4

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.

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 68 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (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
Study Start Date : October 2008
Actual Primary Completion Date : August 2009
Actual Study Completion Date : July 2012

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS
U.S. FDA Resources

Arms and Interventions
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Arm Intervention/treatment
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


Outcome Measures
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Primary Outcome Measures :
  1. Change From Baseline in Fasting Triglyceride (TG) Levels in the Lipid Evaluable (LE) Set at Week12 [ Time Frame: Baseline, Week 12 ]
    Observed values.


Secondary Outcome Measures :
  1. Change From Baseline in Total Cholesterol (TC) Levels in the LE Set at Week 12 and 48 [ Time Frame: Baseline, Week 12 and 48 ]
    Observed Values

  2. Change From Baseline in Low Density Lipoprotein (LDL) Direct in the LE Set at Week 12 and 48. [ Time Frame: Baseline, Week 12 and 48 ]
    Observed Values

  3. Change From Baseline in High Density Lipoprotein (HDL) in the LE Set at Week 12 and 48. [ Time Frame: Baseline, Week 12 and 48 ]
    Observed Values

  4. Change From Baseline in Apolipoprotein A1 in the LE Set at Week 12 and 48. [ Time Frame: Baseline, Week 12 and 48 ]
    Observed Values

  5. Change From Baseline in Apolipoprotein B in the LE Set at Week 12 and 48. [ Time Frame: Baseline, Week 12 and 48 ]
    Observed Values

  6. Change From Baseline in TC/HDL Ratio in the LE Set at Week 12 and 48. [ Time Frame: Baseline, Week 12 and 48 ]
    Participants TC and HDL was analyzed at Baseline and Week 12 and 48. Change from Baseline at Week 12 and 48 was calculated as ratio using observed values.

  7. Change From Baseline in Glucose at Week 12 and 48. [ Time Frame: Baseline, Week 12 and 48 ]
    Participants glucose level was analyzed at Baseline and Week 12 and 48. Change from Baseline at Week 12 and 48 was reported.

  8. Change From Baseline in Insulin at Week 12 and 48. [ Time Frame: Baseline, Week 12 and 48 ]
    Participants insulin was analyzed at Baseline and Week 12 and 48 and change from Baseline at Week 12 and 48 were reported.

  9. Change From Baseline in Homeostasis Model Assessment-Insulin Resistance (HOMA-IR) at Week 12 and 48. [ Time Frame: Baseline, Week 12 and 48 ]
    Participants homeostasis model assessment-insulin resistance (HOMA-IR) were observed and change from Baseline were reported. HOMA-IR score was calculated as: (fasting plasma glucose*fasting serum insulin)/22.5. Low HOMA IR values indicate high insulin sensitivity and high HOMA IR values indicate low insulin sensitivity (insulin resistance).

  10. Antiviral Activity, Human Immunodeficiency Virus Type 1 (HIV-1) RNA. [ Time Frame: Week 12 and 48 ]
    Number of Participants with antiviral activity, human immunodeficiency virus Type 1 (HIV-1) RNA less than (<) 50 copies per milliliters (copies/mL) or < 400 copies/mL.

  11. Number of Participants With Antiviral Activity, HIV-1 RNA, Missing Values as Treatment Failure (M=F) [ Time Frame: Week 12 and 48 ]
    Number of participants with antiviral activity, HIV-1 RNA, missing values as treatment failure (Missing = Failure) were observed.

  12. Change From Baseline in HIV-1 RNA Viral Load at Week 12 and 48. [ Time Frame: Baseline, Week 12 and 48 ]
    the HIV-1 RNA viral load was calculated using Log Base 10 transformed HIV-1 RNA observed values.

  13. Change From Baseline in CD4 Cell Count at Week 12 and 48, Observed Values. [ Time Frame: Baseline, Week 12 and 48 ]
    Participants' Cluster of Differentiation (CD) 4 Cell Count were at baseline and the change values at Week 12 and 48 were observed.

  14. Change From Baseline in Cluster of Differentiation (CD) 4 Cell Count at Week 12 and 48, Last Observation Carried Forward (LOCF). [ Time Frame: Baseline, Week 12 and 48 ]
    Participants' Cluster of Differentiation (CD) 4 Cell Count were observed at baseline and the change values at Week 12 and 48 was calculated using LOCF.

  15. Change From Baseline in Cluster of Differentiation (CD) 4 Percent at Week 12 and 48, Last Observation Carried Forward (LOCF). [ Time Frame: Baseline, Week 12 and 48 ]
    Participants' Cluster of Differentiation (CD) 4 percent were observed at baseline and the change values at Week 12 and 48 was calculated using LOCF.


Eligibility Criteria
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Ages Eligible for Study:   18 Years to 99 Years   (Adult, Senior)
Sexes Eligible for Study:   All
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
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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00757783


Locations
United States, California
Los Angeles, California, United States
United States, Connecticut
Glastonbury, Connecticut, United States
United States, District of Columbia
Washington, District of Columbia, United States
United States, Florida
Fort Lauderdale, Florida, United States
Miami, Florida, United States
Orlando, Florida, United States
United States, Indiana
Indianapolis, Indiana, United States
United States, Massachusetts
Boston, Massachusetts, United States
United States, Minnesota
Minneapolis, Minnesota, United States
United States, Missouri
Saint Louis, Missouri, United States
United States, New Jersey
Hillsborough, New Jersey, United States
United States, New York
New York, New York, United States
United States, Ohio
Cincinnati, Ohio, United States
United States, Pennsylvania
Philadelphia, Pennsylvania, United States
United States, Texas
Dallas, Texas, United States
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
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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Tibotec, Inc
ClinicalTrials.gov Identifier: NCT00757783     History of Changes
Other Study ID Numbers: CR015439
TMC114HIV4023 ( Other Identifier: Tibotec, Inc. )
First Posted: September 23, 2008    Key Record Dates
Results First Posted: September 10, 2010
Last Update Posted: December 30, 2015
Last Verified: November 2015

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:
Ritonavir
Darunavir
Atazanavir Sulfate
Tenofovir
Emtricitabine
HIV Protease Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
 Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Cytochrome P-450 CYP3A Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors