E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
HIV-1 infection |
Infección por el VIH-1 |
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E.1.1.1 | Medical condition in easily understood language |
HIV infection |
Infección por el VIH |
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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 | 14.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10068341 |
E.1.2 | Term | HIV-1 infection |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
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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 assess the cholesterol-lowering ability of TDF/FTC co-formulation in HIV-1-infected subjects with high cholesterol levels. |
Evaluar la capacidad para reducir el colesterol de TDF / FTC co-formulado en sujetos infectados por VIH-1 con niveles altos de colesterol. |
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E.2.2 | Secondary objectives of the trial |
- To assess the ability of TDF/FTC co-formulation to decrease trygliceride levels and increase HDL-cholesterol levels in HIV-1-infected subjects with dyslipidemia. - To evaluate changes in CD4-cell count, liver enzymes, phosphate, creatinine and glomerular filtration rate during the addition of TDF/FTC co-formulation. - To evaluate the rates of sustained RNA HIV viral load suppression <50 copies/mL during the study, particularly during the addition of TDF/FTC co-formulation. - To evaluate adverse events, including laboratory abnormalities. |
- Evaluar la capacidad de TDF / FTC co-formulado para disminuir los niveles de triglicéridos y aumentar el colesterol HDL en pacientes infectados por el VIH-1 con dislipidemia.
- Evaluar los cambios en el recuento de células CD4, las enzimas hepáticas, fosfato, creatinina y la tasa de filtrado glomerular durante la adición de TDF / FTC co-formulado.
- Evaluar las tasas del mantenimiento de la supresión viral (RNA < 50 copias/mL) durante el estudio, en particular durante la adición de TDF / FTC co-formulado.
- Evaluar los eventos adversos, incluyendo anomalías de laboratorio.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Age ≥ 18 years 2. Chronic HIV-1 infection 3. Antiretroviral treatment with either DRV/r (800/100 mg QD) or LPV/r (400/100 mg BID) monotherapy during at least 6 months prior to screening. 4. Fasting total cholesterol or LDL-cholesterol levels ? 200 and ?130 mg/dL respectively, in the previous two consecutive tests obtained at least 4 weeks apart before screening. 5. Calculated creatinine clearance ? 60 mL/min, according to the Cockcroft-Gault formula. 6. Undetectable plasma HIV-1 RNA levels (< 50 copies/mL) during at least 6 months prior to screening. 7. Adequate treatment adherence. 8. Absence of TDF or FTC resistances. 9. Written informed consent to participate into the study. |
1. Edad ≥ 18 años 2. Infección crónica por VIH-1 3. Tratamiento antirretroviral, ya sea con DRV/r (800/100 mg QD) o LPV/r (400/100 mg BID) durante al menos 6 meses previos a la visita screening. 4. Niveles de colesterol total en ayunas o colesterol-LDL ≥ 200 y ≥ 130 mg / dL, respectivamente, en las dos últimas determinaciones consecutivas obtenidas al menos 4 semanas antes del screening. 5. Clearance de creatinina ≥ 60 mL / min, de acuerdo con la fórmula de Cockcroft-Gault. 6. Niveles de VIH-1 ARN en plasma indetectables (<50 copias/ml) durante al menos 6 meses anteriores al screening. 7. Adecuada adherencia al tratamiento 8. Ausencia de resistencias a TDF o FTC. 9. Consentimiento informado por escrito para participar en el estudio.
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E.4 | Principal exclusion criteria |
1. Acute infections or uncontrolled chronic infection in the 2 months previous to the inclusion or physical examination that, in the investigator's opinion, would compromise the patient's safety or outcome of the study 2. Lactating, pregnancy or fertile women willing to be pregnant. 3. Concomitant use of any drug with potential drug-drug interaction with DRV/r, LPV/r or TDF/FTC co-formulation at study entry. 4. Concomitant use of any lipid-lowering drugs at study entry. 5. Prior documented intolerance or hypersensitivity to TDF, FTC, LPV/r or DRV/r. 6. Therapies including interferon, interleukin-2, cytotoxic chemotherapy or immunosuppressors at study entry. 7. Acute or chronic renal documented pathologies. 8. Documented resistance to any of the study drugs (either genotypic or phenotypic) 9. Life expectancy less or equal to 1 year. 10. Current alcohol or substance use judged by the investigator to potentially interfere with subject study compliance. 11. Subjects currently taking part in any other clinical trial using an investigational product, with the exception of studies where the treatment studied have stopped for more than 12 weeks. 12. Any other clinical condition or prior therapy that, in the opinion of the investigator, would make the subject unsuitable for the study or unable to comply with the dosing requirements. |
1. Infecciones agudas o infecciones crónicas no controlados en los 2 meses anteriores a la inclusión o exploración física que, en opinión del investigador, podría comprometer la seguridad del paciente o el resultado del estudio. 2. Período de lactancia, embarazo o mujeres en edad fértil dispuestas a quedarse embarazada. 3. Uso concomitante de cualquier fármaco con potencial interacción con DRV/r, LPV/r o TDF/FTC co-formulado al inicio del estudio. 4. Uso concomitante de medicamentos hipolipemiantes al inicio del estudio. 5. Intolerancia o hipersensibilidad previa documentada a TDF, FTC, LPV/r o DRV/r. 6. Terapias que incluyan interferón, interleucina-2, quimioterapia citotóxica o inmunosupresores al inicio del estudio. 7. Patología renal aguda o crónica documentada. 8. Resistencia documentada a cualquiera de los fármacos del estudio (ya sea genotípica o fenotípica). 9. Esperanza de vida menor o igual a 1 año. 10. Uso actual de alcohol o otras sustancias que en opinión del investigador pueda interferir potencialmente en el cumplimiento del sujeto en el estudio. 11. Sujetos que participan actualmente en cualquier otro ensayo clínico con un producto en investigación, con la excepción de estudios en los que el tratamiento estudiado se haya detenido desde hace más de 12 semanas. 12. Cualquier otra condición clínica o terapia previa que, en opinión del investigador, pudiera hacer que el sujeto no fuera apto para el estudio o no estuviera en condiciones de cumplir con los requisitos de la administración.
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E.5 End points |
E.5.1 | Primary end point(s) |
Changes in median fasting total and LDL cholesterol levels during TDF/FTC co-formulation addition compared to placebo. |
Cambios en las madianas del los niveles en ayunas de colesterol total y LDL durante la adición de TDF/FTC co-formulado comparado con placebo. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Every 3 months throughout the study |
Cada 3 meses a lo largo del estudio. |
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E.5.2 | Secondary end point(s) |
- Percentage of patients with dyslipidemia during TDF/FTC co-formulation addition, compared to placebo. Hypercholesterolemia will be defined according to the National Cholesterol Education Program, ATP III guidelines, i.e.: total cholesterol >= 200 mg/dL, LDL cholesterol >= 130 mg/dL and HDL cholesterol =< 40 mg/dL. - Proportion of patients with virological failure, defined as 2 consecutive RNA HIV-1 viral loads > 50 copies/mL while receiving ART. - Median changes in CD4-cell count, triglycerides, liver enzymes, phosphate, creatinine and glomerular filtration rate during the addition of TDF/FTC. - Percentage of patients with >= grade 3 toxicity. - Percentage of patients who withdraw from the study. - Percentage of patients who withdraw from the study due to toxicity. - Percentage of patients requiring lipid-lowering drugs. |
- Porcentaje de pacientes con dislipemia durante la adición de TDF/FTC co-formulado, comparado con la adición de placebo. La hipercolesterolemia se definirá según las Guías ATP III del National Cholesterol Education Program, que son: Colesterol total >= 200 mg/dL, Colesterol LDL >= 130 mg/dL y colesterol HDL => 40 mg/dL. - Proporción de pacientes con fracaso virológico, definido como 2 cargas virales de RNA VIH-< por encima de 50 copias/mL mientras se recibe tratamiento antirretroviral. - Media de los cambios en el recuento de CD4, triglicéridos, enzimas hepáticas, fosfato, creatinina y tasa de filtrado glomerular (MDRD) durante la adición de TDF/FTC co-formulado. - Porcentaje de pacientes con toxicidad >= a grado 3. - Porcentaje de pacientes que abandonan el estudio - Porcentaje de pacientes que abandonan el estudio por toxicidad - Porcentaje de pacientes que requiere agentes hipolipemiantes |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Every 3 months throughout the study |
Cada 3 meses a lo largo del estudio. |
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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) | 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 | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | Yes |
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 | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
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.8.5 | 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 | 1 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 1 |
E.8.9.2 | In all countries concerned by the trial days | 0 |