E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10020161 |
E.1.2 | Term | HIV infection |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To compare the change in brachial artery flow mediated vasodilation (FMD) from baseline to week 24 and 48 in the two study arms (DRV/r monotherapy versus a triple combination therapy containing DRV/r and 2 NRTIs). |
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E.2.2 | Secondary objectives of the trial |
·To evaluate and compare the efficacy of a treatment simplification by a DRV/r monotherapy versus a triple combination therapy with DRV/r in HIV-infected patients at 48 weeks. ·To compare the change in circulating endothelial cells and of their precursors from baseline to week 48 ·To compare the change in mean LDL-cholesterol, HDL-cholesterol, triglycerides , HOMA-IR and Frammingham risk score from baseline to week 24 and 48 in the two study arms ·To compare body fat changes by means of leg fat content analyzed in DEXA and visceral fat content in abdomen TC in the two study arms from baseline to week 48 ·To compare the measure of drug toxicity on mtDNA, (quantified as the amount of mtDNA per cell in isolated CD4+ T cells) and soluble factors involved in mitochondrial/metabolic alterations (leptin, adiponectin); from baseline to week 48 in the two study arms ·To compare lumbar and femoral neck T-score from baseline to week 48 |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
·Patients with documented HIV-1 infection. ·Male or female aged > 18 years old. ·Patients who have voluntarily provided signed and dated consent forms. ·Patients have been receiving HAART for at least 24 weeks. ·Patients are currently on their first-line treatment and this is HAART. Note: HAART is defined as the combination of 2 NRTIs with at least 1 additional ARV from the NNRTI and/or PI class*. A first line regimen with 3 NRTIs is allowed. ·Plasma HIV-1 RNA < 50 cp/ml for at least 24 weeks before screening. ·Patient taking the same ARV combination for at least 8 weeks before screening. ·Preference for a more convenient regimen and/or any current or history of toxicity on actual regimen (examples of toxicities: CNS, gastrointestinal disturbances, jaundice, anaemia, nausea, neuropathy, paresthesia, hyperlipidaemia, glucose intolerance or diabetes, nephrolithiasis, lipodystrophy, hepatotoxicity, rash and skin related events, any other AE or intolerability or laboratory abnormalities caused by current HAART). ·CD4 > 100/mm3 at the start of HAART and > 200/mm3 at screening. |
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E.4 | Principal exclusion criteria |
·History of coronary heart disease, (history of myocardial infarction, coronary bypass surgery, coronary angioplasty, or angina pectoris with a positive stress test or angiographic documentation), uncontrolled hypertension (systolic blood pressure >160 or diastolic blood pressure >100 mmHg) peripheral vascular disease (claudication, angioplasty, or bypass procedure), or cerebrovascular disease (stroke or TIA with documented carotid or aortic atherosclerosis). ·Pregnant or breast-feeding ·Any condition that, in the opinion of the investigator, would compromise the well-being of the subject or the study ·History of virological failure on HAART. ·History of plasma HIV-1 RNA > 500 copies/ml after initial full virological suppression while on ARV therapy. ·Patients with clinical or laboratory evidence of significantly decreased hepatic function or decompensation, irrespective of liver enzyme levels (liver insufficiency). ·Patients diagnosed with acute viral hepatitis at screening. ·Patients co-infected with hepatitis B. Note: Patients co-infected with chronic hepatitis C will be allowed to enter the trial if their condition is clinically stable and is not expected to require treatment during the study period. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary parameter of the study is the change in brachial artery FMD from baseline to week 24. Brachial artery FMD is calculated as the percentage increase in brachial artery diameter with hyperemia induced relative to the resting brachial artery diameter. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Stesso Farmaco associato ad altri farmaci (2 nrti) |
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E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 6 |