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 | PT |
E.1.2 | Classification code | 10020161 |
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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 evaluate variation in endothelial adhesion molecules and leukocyte activation markers in HIV-positive na�ve patients treated with abacavir compared to tenofovir in combination with fixed NNRTI composed by efavirenz |
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E.2.2 | Secondary objectives of the trial |
1. Evaluation of fasting metabolic parameters (e.g. LDL, HDL, non-HDL cholesterol, triglycerides and cholesterol ratio) at baseline, week 4, 12 and 24 2. Evaluation of endothelium function measured by flow-mediated dilation (FMD) of the radial artery and brachial artery diameter (BAD), aortic stiffness measure by aortic pulse-wave velocity (PWV) and endothelium structure measured by echodoppler evaluation of carotid intima-media thickness (IMT) from baseline at week 24 3.Evaluation of efficacy and safety by assessing adverse events, clinical laboratory tests, physical examinations and vital sing at every visit 4.Evaluation of change in the 10-year risk factor for coronary heart disease outcomes as measured by Framinghan formula |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Signed informed consent in accordance with GCP and local regulatory requirements prior to trial participation - HIV-1-infected males or females >18 years of age - Positive serology for HIV (ELISA) confirmed by Western Blot - CD4 + cell count between 250-350 cells/L - HIV-RNA < 100.000 cp/ml - BMI <30 - No previous antiretroviral treatment - Negative pregnancy test at least 14 days before the beginning of treatment, women of childbearing potential must be using a highly effective method of contraception to avoid pregnancy throughout the study - Study drugs susceptibility based on HIV-1 genotypic resistance test |
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E.4 | Principal exclusion criteria |
- Presence of HLA-B 5701 - Current smoker - Presence of diabetes - Presence of active inflammatory requiring anti-inflammatory therapy - Presence of opportunistic infections - Actual or previous cardiovascular diseases - Prior history of bone diseases - Actual or previous autoimmune disease - Previous documented altered expression of endothelial molecules and activation markers on CD4+ lymphocytes - Adequate renal function defined as a calculated creatinine clearance (CLCr) > 50 ml/min according to the MDRD formula The estimate was calculated using the Modification of Diet in Renal Diseases (MDRD) formula: eGFR (MDRD) = 186 x serum creatinine -1.154 x age -0.203 x 0.742 (if female) x 1.21 (if black) - Framinghan score > 10% (age, sex, systolic blood pressure, total cholesterol, HDL cholesterol, smoking status) www.chip.dk/tools.aspx - Presence of family history of cardiovascular disease Presence of thyroid disfunctions - Known intolerance or allergies to the investigational drugs treatments - Use of immunomodulant substances, growth factors, cytokines (e.g. interferon, cyclosporine, hydrohyurea, interleukin 2) or vaccines within 3 months - Use of lipid-lowering therapy is allowed if stable ≥ 12 weeks before and throughout study - Have systemic treatment with corticosteroid (e.g. chronic treatment with prednisone) or hormone therapy or chronic treatment with high dose non steroidal anti-inflammatory drugs (e.g. ibuprofene) within 3 months prior to study enter or are expected to receive these during the study - Ongoing therapy with nephrotoxic drugs (e.g. aminoglycosides, amphotericine B, vancomycin, cidofovir, foscarnet, cisplatin, pentamidine, tacrolimus) or in 3 months prior to baseline or are expected to receive these during the study - Patients who are receiving systemic treatment for malignant disease - Pregnant or breast-feeding patients - Any current known clinical or symptomatic laboratory parameter Grade 4. Asymptomatic laboratory parameter will be permitted at the discretion of the investigator if deemed clinically appropriate (excluding adverse events and laboratory parameters mentioned in the exclusion/inclusion criteria) - Karnofsky index < 50 - Use of medications during the course of the study which are known to alter serum lipid levels, including growth hormone, anabolic steroids, megestrol, thalidomide, pentoxyfylline, systemic ketoconzole, cyclosporine or prolonged pharmacologic doses of glucocorticoids or testosterone preparations. Subjects who require hormone replacement therapy for endocrine conditions (e.g., testosterone, estrogen, progesterone, hydrocortisone, thyroid hormone) are allowed to participate, as long as they are receiving a physiologic replacement dose. |
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E.5 End points |
E.5.1 | Primary end point(s) |
To evaluate changes from baseline in expression of endothelial adhesion molecules and activation markers on CD4+ lymphocytes (DRII, CD11A, CD62L, CD49D, CD44) and monocytes (CD36, TLR2, TLR4, CD80, CD86) after 24 weeks. |
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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 | Yes |
E.6.4 | Safety | No |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
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) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
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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Ultima visita dell`ultimo soggetto inserito nella sperimentazione |
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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 | 0 |
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 | 0 |