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

NCT ID: NCT00757783

Last Updated: 2015-12-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 68 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-10-31
• Study Completion Date: 2012-07-31

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.

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.

Conditions

HIV

Keywords

HIV; AIDS; Immunodeficiency Virus, Human; PREZISTA; darunavir; TMC114; Protease Inhibitor; Truvada; Atazanavir; REYATAZ; HIV Infections; Treatment Naïve

Study Design

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

Study Groups

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

Group Type: EXPERIMENTAL

ritonavir

Intervention Type: DRUG

100 mg capsule or tablet once daily for 48 weeks

darunavir

Intervention Type: DRUG

800 mg tablet once daily for 48 weeks

emtricitabine [FTC]/tenofovir [TDF]

Intervention Type: DRUG

200/300 mg tablet once daily for 48 weeks

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

Group Type: EXPERIMENTAL

ritonavir

Intervention Type: DRUG

100 mg capsule or tablet once daily for 48 weeks

emtricitabine [FTC]/tenofovir [TDF]

Intervention Type: DRUG

200/300 mg once daily for 48 weeks

atazanavir

Intervention Type: DRUG

300 mg capsule once daily for 48 weeks

Interventions

ritonavir

100 mg capsule or tablet once daily for 48 weeks

Intervention Type: DRUG

ritonavir

100 mg capsule or tablet once daily for 48 weeks

Intervention Type: DRUG

darunavir

800 mg tablet once daily for 48 weeks

Intervention Type: DRUG

emtricitabine [FTC]/tenofovir [TDF]

200/300 mg tablet once daily for 48 weeks

Intervention Type: DRUG

emtricitabine [FTC]/tenofovir [TDF]

200/300 mg once daily for 48 weeks

Intervention Type: DRUG

atazanavir

300 mg capsule once daily for 48 weeks

Intervention Type: DRUG

Eligibility 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 99 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Tibotec Therapeutics, a Division of Ortho Biotech Products, L.P., USA

INDUSTRY

Sponsor Role: collaborator

Tibotec, Inc

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Tibotec, Inc. Clinical Trial

Role: STUDY_DIRECTOR

Tibotec, Inc

Locations

Los Angeles, California, United States

Glastonbury, Connecticut, United States

Washington D.C., District of Columbia, United States

Fort Lauderdale, Florida, United States

Miami, Florida, United States

Orlando, Florida, United States

Indianapolis, Indiana, United States

Boston, Massachusetts, United States

Minneapolis, Minnesota, United States

St Louis, Missouri, United States

Hillsborough, New Jersey, United States

New York, New York, United States

Cincinnati, Ohio, United States

Philadelphia, Pennsylvania, United States

Dallas, Texas, United States

Countries

United States

References

Overton ET, Tebas P, Coate B, Ryan R, Perniciaro A, Dayaram YK, De La Rosa G, Baugh BP. Effects of once-daily darunavir/ritonavir versus atazanavir/ritonavir on insulin sensitivity in HIV-infected persons over 48 weeks: results of an exploratory substudy of METABOLIK, a phase 4, randomized trial. HIV Clin Trials. 2016 Mar;17(2):72-7. doi: 10.1080/15284336.2016.1141468.

Reference Type: DERIVED

PMID: 26917112 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 21470045 (View on PubMed)

Other Identifiers

TMC114HIV4023

Identifier Type: OTHER

Identifier Source: secondary_id

CR015439

Identifier Type: -

Identifier Source: org_study_id