A Study to Compare Brachial Artery Reactivity and Cardiovascular Risk of a Treatment Simplification by Darunavir/Ritonavir (DRV/r) 800/100 mg Versus a Triple Combination Therapy Containing DRV/r in HIV-1 Infected Patients
Information source: Janssen-Cilag S.p.A.
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Human Immunodeficiency Virus 1
Intervention: Darunavir(DRV) (Drug); Ritonavir (Drug); 2 nucleoside reverse transcriptase inhibitors (NRTIs) (Drug)
Phase: Phase 2
Status: Completed
Sponsored by: Janssen-Cilag S.p.A. Official(s) and/or principal investigator(s): Janssen-Cilag S.p.A. Clinical Trial, Study Director, Affiliation: Janssen-Cilag S.p.A.
Summary
The purpose of this study is to compare change of brachial artery flow mediated
vasodilatation using Darunavir/Ritonavir (DRV/r) 800/100 mg once daily as a monotherapy (use
of a single medication) versus a triple combination therapy containing 2 nucleoside reverse
transcriptase inhibitors (NRTIs) and DRV/r in Human immunodeficiency virus-1 (HIV-1)
infected participants.
Clinical Details
Official title: A Randomised, Controlled, Open-Label Trial to Compare Brachial Artery Reactivity and Cardiovascular Risk of a Treatment Simplification by Darunavir/Ritonavir (DRV/r) 800/100 mg O.D. Versus a Triple Combination Therapy Containing DRV/r in HIV-1 Infected Subjects With Undetectable Plasma HIV-1 RNA on Their Current Treatments.
Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: Change From Baseline to Week 24 in Brachial Artery Flow Mediated Vasodilatation (FMD): Median Change in FMD (%)
Secondary outcome: Change From Baseline to Week 48 in Brachial Artery FMD: Median Change in FMD (%)Number of Participants With a Human Immunodeficiency Virus- Ribonucleic Acid (HIV-RNA) Greater Than or Equal to 50 Copies/mL Change From Baseline to Week 48 in Circulating Endothelial Cells Change From Baseline to Week 48 in Precursors of Circulating Endothelial Cells Change From Baseline in Mean Low-density Lipoprotein (LDL) Cholesterol at Week 24 and Week 48: Median Change in LDL Change From Baseline in Mean High-density Lipoprotein (HDL) Cholesterol at Week 24 and Week 48: Median Change in HDL Change From Baseline in Mean Triglycerides at Week 24 and Week 48: Median Change in Triglycerides Change From Baseline in Insulin Sensitivity at Week 24 and Week 48: Median Change in Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) Change From Baseline in Mean Framingham Risk Score at Week 24 and Week 48: Medican Change in Framingham Risk Score Change From Baseline to Week 48 in Leg Fat Content: Median Change in Leg Fat (Total) Change From Baseline to Week 48 in Visceral Fat Content in Abdomen: Median Change in Visceral Abdominal Tissue (VAT) Change From Baseline to Week 48 in Femoral Neck T Score: Median Change in Femoral Neck T Score Change From Baseline to Week 48 in Femoral Neck Z Score: Median Change in Femoral Neck Z Score Change From Baseline to Week 48 in Lumbar T Score: Median Change in Lumbar T Score Change From Baseline to Week 48 in Lumbar Z Score: Median Change in Lumbar Z Score Change From Baseline in Cluster of Differentiation 4 (CD4) Count Over Week 48
Detailed description:
This is a Phase II, randomized (the study medication is assigned by chance), open-label (all
people know the identity of the intervention), controlled, single centre study. The study
consists of 3 phases including, the screening phase (4 weeks before administration of study
medication), treatment phase (48 weeks), and the follow-up phase (4 weeks). In the treatment
phase, HIV-infected participants who have not changed their first-line treatment of highly
active antiretroviral therapy (HAART) for at least 8 weeks and have documented evidence of
their HIV- ribonucleic acid (RNA) measurements being virologically suppressed (HIV-RNA less
than 50 copies/mL) for at least 24 weeks prior to the screening, will be randomly assigned
equally in two treatment arms: triple combination therapy arm (DRV/r 800/100 mg once daily
plus 2 NRTIs) or monotherapy arm (DRV/r 800/100 mg once daily). Participants in the triple
combination arm who are already on 2 NRTIs prior to randomization may remain on these or
switch them at baseline, where the participants on the monotherapy arm will discontinue
HAART at baseline and will start DRV/r 800/100 mg once daily. Safety evaluations will
include assessment of adverse events, significant vital signs, and significant laboratory
tests. The total duration of the study will be 56 weeks.
Eligibility
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
Criteria:
Inclusion Criteria: - Human immunodeficiency virus-1 (HIV-1) infected participants on
their first-line treatment with highly active antiretroviral therapy (HAART) (combination
of 2 or 3 nucleoside reverse transcriptase inhibitors [NRTIs] with at least 1 additional
antiretroviral [ARV] from the non-nucleoside reverse transcriptase inhibitor [NNRTI]
and/or protease inhibitors [PI] class) for at least 24 weeks, provided the same ARV
combination for at least 8 weeks before screening
- Participants' preference for a more convenient regimen and/or any current or history
of toxicity on actual regimen
- Plasma HIV-1 ribonucleic acid (RNA) less than 50 cp/ml for at least 24 weeks before
screening, where single viral blips of more than 50 copies/mL are allowed
- Cluster of differentiation 4 (CD4) count more than 100/mm3 at the start of HAART and
more than 200/mm3 at screening
- Healthy on the basis of physical examination, medical history, vital signs, clinical
laboratory tests, and 12-lead electrocardiogram performed at screening
- Agrees to protocol-defined use of effective contraception
- Postmenopausal, surgically sterile, or abstinent female participants
Exclusion Criteria:
- History of coronary heart disease, uncontrolled hypertension, peripheral vascular
disease and or cerebrovascular disease
- History of virological failure on highly active antiretroviral therapy, plasma HIV-1
ribonucleic acid more than 500 copies/mL after initial full virological suppression
while on ARV therapy and any PI mutations
- Participants with significantly hepatic and liver insufficiency or diagnosed with
acute viral hepatitis or have active clinically significant diseases and acquired
immune deficiency syndrome (AIDS) defining illness at screening
- Current significant tobacco use, active drug or alcohol use or dependence
- Use of lipid-lowering drugs within 4 weeks prior to study entry and use of
testosterone, anabolic steroids, oral contraceptives or hormonal replacement within
12 weeks prior to study entry or previous or current use of darunavir
- Use of systemic glucocorticoids, long-acting inhaled steroids (inhaled via mouth or
nose), or other immunomodulators within 30 days prior to study entry
Locations and Contacts
Additional Information
Starting date: June 2009
Last updated: May 22, 2013
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