E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Chronic HIV infection. |
Infección VIH crónica |
|
E.1.1.1 | Medical condition in easily understood language |
Chronic HIV-1 infection. |
Infección VIH crónica |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Virus Diseases [C02] |
MedDRA Classification |
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 change in BMD by dual-energy X-ray (DXA) absorptiometry in HIV-infected adults with hip or spine T-score < -1.0 by DXA at week 48 after switching to r/ATV plus lamivudine. |
Evaluar el cambio en BMD (Densidad Mineral Ósea) a las 48 semanas de cambio de tratamiento a r/ATV+Lamivudina, mediante DXA (absorciometría RX de doble densidad), en adultos infectados por VIH con T-score < -1.0 de cadera o columna. |
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E.2.2 | Secondary objectives of the trial |
To assess the effects of switching on: - Proportion of patients free of virologic failure (confirmed VL? 50 copies/mL) at 48 weeks - Adverse effects at 48 weeks - Bone turnover markers (BTMs): urinary N-terminal telopeptide of type-1 collagen (NTX), and bone-specific alkaline phosphatase at 48 weeks. - (i) Estimated glomerular filtration rate (eGFR) and phosphorus in blood sample; (ii) proximal tubule dysfunction parameters: glucose, protein, albumin, creatinin, phosphorus, beta-2 microglobuline and NAG in urine samples. at week 48 when compared to baseline |
Evaluar los efectos del cambio de terapia sobre: - Proporción de pacientes libres de fracaso virológico (CV?50 copias /mL) a las 48 semanas. - Acontecimientos adversos a las 48 semanas. - Marcadores de recambio óseo (BTMs) a las 48 semanas: telopéptido N-terminal del colágeno (NTX) en orina, y fosfatasa alcalina específica del hueso. - En la semana 48 y en comparación con visita basal: (i) Índice de filtración glomerular estimado (eGFR) y fósforo en muestra de sangre; (ii) parámetros de disfunción tubular proximal: glucosa, proteína, creatinina, fósforo, beta-2 microglobulina y NAG (n-acetilglucosaminidasa) en muestras de orina. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Adult (18 years old or more) HIV-1-infected subjects. - Hip or spine T-scores between <-1.0 measured and >-2.5 mesured by dual-energy X-ray absorptiometry (DXA) (in the previous 24 weeks). - On stable cART based on TDF+3TC or FTC+r/PI for at least 24 weeks. - Having plasma HIV-1 RNA <50 copies/mL for at least the previous 24 weeks, including at least two samples. |
- Sujetos adultos infectados por VIH-1 ((18 años o más) - T-score de cadera o columna entre < -1.0 y >- 2.5 medido con absorciometría RX de doble energía (DXA) (en las 24 semanas previas). - En tratamiento estable antirretroviral basado en TDF+3TC ó FTC+r/PI durante al menos 24 semanas. - Con HIV-1 RNA en plasma <50 copias /mL durante al menos las 24 semanas previas, incluyendo al menos dos muestras. |
|
E.4 | Principal exclusion criteria |
- Pregnancy, breast-feeding status or plans for pregnancy in the short term. - Primary genotypic resistance mutations and/or previous virological failures to ATV or 3TC/FTC. - Chronic hepatitis B infection. - Patients with indication for therapy for the prevention of bone fractures. - 25-OH vitamin D deficiency (< 10ng/mL), - Hypogonadism (low total testosterone according to local reference range), untreated. - Hypothyroidism (low T4 and increased thyroid stimulating hormone levels according to local reference ranges) - Hyperparathyroidism (increased parathyroid hormone level with hypercalcaemia according to local reference ranges). - Having received oral corticosteroids or inhaled fluticasone (daily doses higher than 5 mg/d prednisone equivalent for 3 months or more). - Using anti-resorptive therapy (Calcium and vitamin D supplements are encouraged but not mandated) - BMI lower than 19. |
- Embarazo y lactancia, o previsión de embarazo a corto plazo. - Mutaciones de resistencia genotípica primaria y/o fracaso virológico previo a ATV o 3TC/FTC. - Infección crónica por hepatitis B. - Pacientes con indicación de terapia preventiva de fracturas óseas. - Deficiencia de vitamina D 25-OH (<10 ng/mL) .- Hipogonadismo no tratado (testosterona total referida al rango de referencia local). - Hipotiroidismo (T4 baja i niveles de TSH referida al rango de referencia local). - Hiperparatiroidismo (nivel de hormona paratiroidea elevado con hipercalcemia conforme a rangos de referencia locales). - Haya recibido costicosteroides orales o fluticasona inhalada (dosis diarias mayores 5 mg/d del equivalente de prednisona durante 3 meses o más). - Utilizar terapia antirresortiva ósea (los suplementos con calcio y vitamina D son recomendables pero no obligatorios) - IMC menor de 19 |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Change in BMD by dual-energy X-ray (DXA) absorptiometry at week 48. |
Cambios en densidad mineral ósea mediante absorciometría RX de doble energía (DXA) en la semana 48. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Change in BMD by dual-energy X-ray (DXA) absorptiometry at week 48. |
Cambios en densidad mineral ósea mediante absorciometría RX de doble energía (DXA) en la semana 48. |
|
E.5.2 | Secondary end point(s) |
- Proportion of patients free of virologic failure (confirmed VL? 50 copies/mL) at 48 weeks - Proportion of patients with adverse effects at 48 weeks - Changes in bone turnover markers (BTMs): urinary N-terminal telopeptide of type-1 collagen (NTX), and bone-specific alkaline phosphatase at 48 weeks. - Changes from baseline to week 48 in: (i) estimated glomerular filtration rate (eGFR) and phosphorus in blood sample; (ii) proximal tubule dysfunction parameters: glucose, protein, albumin, creatinin, phosphorus, beta-2 microglobuline and NAG in urine samples. |
- Proporción de pacientes libres de fracaso virológico (CV?50 copias /mL) a las 48 semanas. - Proporción de pacientes con efectos adversos a las 48 semanas -Cambios en los marcadores de recambio óseo (BTMs) a las 48 semanas: telopéptido N-terminal del colágeno tipo-1 (NTX) en orina, y fosfatasa alcalina específica del hueso. - Cambios entre la visita basal y la semana 48 en: (i) Índice de filtración glomerular estimado (eGFR) y fósforo en muestra de sangre; (ii) parámetros de disfunción tubular proximal: glucosa, proteína, creatinina, fósforo, beta-2 microglobulina y NAG (n-acetilglucosaminidasa) en muestras de orina. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
- Proportion of patients free of virologic failure (confirmed VL? 50 copies/mL) at 48 weeks - Proportion of patients with adverse effects at 48 weeks - Changes in bone turnover markers (BTMs): urinary N-terminal telopeptide of type-1 collagen (NTX), and bone-specific alkaline phosphatase at 48 weeks. - Changes from baseline to week 48 in: (i) estimated glomerular filtration rate (eGFR) and phosphorus in blood sample; (ii) proximal tubule dysfunction parameters: glucose, protein, albumin, creatinin, phosphorus, beta-2 microglobuline and NAG in urine samples. |
- Proporción de pacientes libres de fracaso virológico (CV?50 copias /mL) a las 48 semanas. - Proporción de pacientes con efectos adversos a las 48 semanas -Cambios en los marcadores de recambio óseo (BTMs) a las 48 semanas: telopéptido N-terminal del colágeno tipo-1 (NTX) en orina, y fosfatasa alcalina específica del hueso. - Cambios entre la visita basal y la semana 48 en: (i) Índice de filtración glomerular estimado (eGFR) y fósforo en muestra de sangre; (ii) parámetros de disfunción tubular proximal: glucosa, proteína, creatinina, fósforo, beta-2 microglobulina y NAG (n-acetilglucosaminidasa) en muestras de orina. |
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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) | 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 | 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
| 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 | 6 |
E.8.9.1 | In the Member State concerned days | |