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

September 19, 2008
February 3, 2014
September 2008
August 2009   (final data collection date for primary outcome measure)
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
To assess change from baseline in triglyceride (TG) level at week 12 for darunavir versus atazanavir. The primary objective of the substudy is to assess the effect on insulin sensitivity at 12 weeks using the hyperinsulinemic clamp technique.
Complete list of historical versions of study NCT00757783 on ClinicalTrials.gov Archive Site
  • 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
Assess change from baseline in lipids, glucose, insulin, insulin resistance, adipose tissue, body habitus & inflammatory markers. Assess virologic suppression, immunologic response & safety. Assess endothelial function, insulin sensitivity for substudy.
Not Provided
Not Provided
 
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
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

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.

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.

Interventional
Phase 4
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
HIV
  • 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
  • Drug: emtricitabine [FTC]/tenofovir [TDF]
    200/300 mg once daily for 48 weeks
  • Drug: atazanavir
    300 mg capsule once daily for 48 weeks
  • 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
    Interventions:
    • Drug: ritonavir
    • Drug: darunavir
    • Drug: emtricitabine [FTC]/tenofovir [TDF]
  • 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
    Interventions:
    • Drug: ritonavir
    • Drug: emtricitabine [FTC]/tenofovir [TDF]
    • Drug: atazanavir
Gupta SK, Mi D, Liu Z, Saha C. Endothelial, inflammatory, coagulation, metabolic effects and safety of etravirine in HIV-uninfected volunteers. AIDS Patient Care STDS. 2011 Jun;25(6):327-31. doi: 10.1089/apc.2011.0011. Epub 2011 Apr 6.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
86
July 2012
August 2009   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
Not Provided
 
NCT00757783
CR015439, TMC114HIV4023
Not Provided
Vice President, Clinical Affairs, Tibotec Therapeutics, a Division of Ortho Biotech Products, L.P., USA
Tibotec, Inc
Tibotec Therapeutics, a Division of Ortho Biotech Products, L.P., USA
Study Director: Tibotec, Inc. Clinical Trial Tibotec, Inc
Tibotec, Inc
September 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP