E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Virus Diseases [C02] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10068341 |
E.1.2 | Term | HIV-1 infection |
E.1.2 | System Organ Class | 100000004862 |
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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 |
Primary Objective: A reduction of > 5% in the plasma concentration of direct LDL cholesterol from baseline to week 12 or > 10% reduction of total cholesterol or reduction of lipid lowering agents is expected. Reduction of lipid lowering agents is defined as reduction due to amelioration of lipid profiles and does not include reduction due to side effects or other toxicity issues.
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E.2.2 | Secondary objectives of the trial |
• To assess changes and percent changes from baseline in total cholesterol, triglycerides and HDL cholesterol over time and at endpoint • To evaluate risk reduction of cardiovascular risk during the treatment period according to Framingham risk score calculation • To evaluate percent changes from baseline to endpoint in triglycerides and an advanced lipoprotein analysis as well as determination of insulin (HOMA- IR index) • Optional: To evaluate and compare endothelial function as determined with flow mediated dilatation
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Signed informed consent • Documented HIV-1 infection in female patients, age ≥18 years • Patients receiving antiretroviral therapy consisting of at least 2 antiretroviral agents other than protease inhibitor plus a ritonavir-boosted protease inhibitor (PI) including indinavir, fosamprenavir, saquinavir, lopinavir, atazanavir, tipranavir, or darunavir for at least the previous 6 months • Plasma HIV viral load <200 copies/ml (as recommended by the Department of Health and Human Services DHHS Guidelines) on current boosted PI containing regimen for ≥ 6 months prior to study entry • Patients receiving prophylaxis or treatment for an opportunistic infection or malignancy may be included as long as following laboratory requirements were met approximately 1 month prior to screening: o hemoglobin > 8.0g/dl o neutrophil count > 750/µl o platelet count > 50000/µl o creatinine < 2.0mg/dl o both alanine and aspartate aminotransferases < 200mg/dl • Fasting LDL cholesterol >130 mg/dl Fasting triglycerides <450 mg/dl •For patients on lipid lowering agents, a stable regimen for the past 3 months will be required
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E.4 | Principal exclusion criteria |
• Breast feeding or pregnancy or wish to become pregnant during the study period. • Lack of expectation to maintain assigned medication during study period • NRTI mutations • Prior treatment with raltegravir • Prior treatment with investigational drugs in the previous 3 months • Need for medication with known interactions with raltegravir (rifampin for example) • Active drug or alcohol abuse • Unstable clinical condition • Visceral Kaposi sarcoma • Acute hepatitis in the previous 6 months • Any condition or history or any illness which, in the opinion of the investigator, might confound the results of the study or pose additional risk when switching the therapy of the patient
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E.5 End points |
E.5.1 | Primary end point(s) |
A reduction of > 5% in the plasma concentration of direct LDL cholesterol from baseline to week 12 or > 10% reduction of total cholesterol or reduction of lipid lowering agents is expected. Reduction of lipid lowering agents is defined as reduction due to amelioration of lipid profiles and does not include reduction due to side effects or other toxicity issues.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
4 +12 + 24 after treatment start |
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E.5.2 | Secondary end point(s) |
• To assess changes and percent changes from baseline in total cholesterol, triglycerides and HDL cholesterol over time and at endpoint • To evaluate risk reduction of cardiovascular risk during the treatment period according to Framingham risk score calculation • To evaluate percent changes from baseline to endpoint in triglycerides and an advanced lipoprotein analysis as well as determination of insulin (HOMA- IR index) • Optional: To evaluate and compare endothelial function as determined with flow mediated dilatation
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
4 +12 + 24 after treatment start |
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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 | No |
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 | No |
E.8.1.1 | Randomised | No |
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 | No |
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 | 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 | 3 |
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 | No |
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 | 3 |
E.8.9.1 | In the Member State concerned days | |