Clinical trial NCT00757783: 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
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: HIV
Keywords: HIV
AIDS
Immunodeficiency Virus, Human
PREZISTA
darunavir
TMC114
Protease Inhibitor
Truvada
Atazanavir
REYATAZ
HIV Infections
Treatment Naïve
Lead sponsor: Tibotec, Inc
Sponsor class: INDUSTRY
Collaborators: name: Tibotec Therapeutics, a Division of Ortho Biotech Products, L.P., USA
First posted: 2008-09-23
Enrollment: 68
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Change From Baseline in Fasting Triglyceride (TG) Levels in the Lipid Evaluable (LE) Set at Week12
timeFrame: Baseline, Week 12
Secondary outcomes:
measure: Change From Baseline in Total Cholesterol (TC) Levels in the LE Set at Week 12 and 48
timeFrame: Baseline, Week 12 and 48
measure: Change From Baseline in Low Density Lipoprotein (LDL) Direct in the LE Set at Week 12 and 48.
timeFrame: Baseline, Week 12 and 48
measure: Change From Baseline in High Density Lipoprotein (HDL) in the LE Set at Week 12 and 48.
timeFrame: Baseline, Week 12 and 48
measure: Change From Baseline in Apolipoprotein A1 in the LE Set at Week 12 and 48.
timeFrame: Baseline, Week 12 and 48
measure: Change From Baseline in Apolipoprotein B in the LE Set at Week 12 and 48.
timeFrame: Baseline, Week 12 and 48
measure: Change From Baseline in TC/HDL Ratio in the LE Set at Week 12 and 48.
timeFrame: Baseline, Week 12 and 48
measure: Change From Baseline in Glucose at Week 12 and 48.
timeFrame: Baseline, Week 12 and 48
measure: Change From Baseline in Insulin at Week 12 and 48.
timeFrame: Baseline, Week 12 and 48
measure: Change From Baseline in Homeostasis Model Assessment-Insulin Resistance (HOMA-IR) at Week 12 and 48.
timeFrame: Baseline, Week 12 and 48
measure: Antiviral Activity, Human Immunodeficiency Virus Type 1 (HIV-1) RNA.
timeFrame: Week 12 and 48
measure: Number of Participants With Antiviral Activity, HIV-1 RNA, Missing Values as Treatment Failure (M=F)
timeFrame: Week 12 and 48
measure: Change From Baseline in HIV-1 RNA Viral Load at Week 12 and 48.
timeFrame: Baseline, Week 12 and 48
measure: Change From Baseline in CD4 Cell Count at Week 12 and 48, Observed Values.
timeFrame: Baseline, Week 12 and 48
measure: Change From Baseline in Cluster of Differentiation (CD) 4 Cell Count at Week 12 and 48, Last Observation Carried Forward (LOCF).
timeFrame: Baseline, Week 12 and 48
measure: Change From Baseline in Cluster of Differentiation (CD) 4 Percent at Week 12 and 48, Last Observation Carried Forward (LOCF).
timeFrame: Baseline, Week 12 and 48
Other outcomes:
Locations:
city: Los Angeles
country: United States
state: California
city: Glastonbury
country: United States
state: Connecticut
city: Washington
country: United States
state: District of Columbia
city: Fort Lauderdale
country: United States
state: Florida
city: Miami
country: United States
state: Florida
city: Orlando
country: United States
state: Florida
city: Indianapolis
country: United States
state: Indiana
city: Boston
country: United States
state: Massachusetts
city: Minneapolis
country: United States
state: Minnesota
city: Saint Louis
country: United States
state: Missouri
city: Hillsborough
country: United States
state: New Jersey
city: New York
country: United States
state: New York
city: Cincinnati
country: United States
state: Ohio
city: Philadelphia
country: United States
state: Pennsylvania
city: Dallas
country: United States
state: Texas
Study officials:
affiliation: Tibotec, Inc
name: Tibotec, Inc. Clinical Trial
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.