| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| HIV Infection |
| Infección por el VIH-1 |
|
| E.1.1.1 | Medical condition in easily understood language |
| HIV Infection |
| Infección por el VIH-1 |
|
| 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 | PT |
| E.1.2 | Classification code | 10020162 |
| E.1.2 | Term | HIV infection CDC Group I |
| E.1.2 | System Organ Class | 10021881 - Infections and infestations |
|
| 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 |
1.To evaluate the antiretroviral activity of MK-0518 400 mg b.i.d. compared with efavirenz 600 mg q.h.s., each in combination therapy with TRUVADA?, as measured by proportion of patients achieving HIV RNA <50 copies/mL at Week 48.
2.To evaluate the safety and tolerability of MK-0518 400 mg b.i.d. compared with efavirenz 600 mg q.h.s., each in combination therapy with TRUVADA?, as assessed by review of the accumulated safety data at Week 48. |
1.Evaluar la actividad antirretroviral de MK-0518 400 mg dos veces al día en comparación con efavirenz 600 mg al acostarse, ambos combinados con TRUVADA?, medida a partir de la proporción de pacientes que logra un valor de ARN del VIH < 50 copias/ml en la semana 48.
2.Evaluar la seguridad y la tolerabilidad de MK-0518 400 mg dos veces al día en comparación con efavirenz 600 mg al acostarse, ambos en combinación con TRUVADA?, a juzgar por la evaluación de los datos de seguridad acumulados en la semana 48. |
|
| E.2.2 | Secondary objectives of the trial |
1.Evaluate the antiretroviral activity of MK-0518 400 mg b.i.d. compared with efavirenz 600 mg q.h.s., each in combination therapy with TRUVADA?, as measured by the following parameters at Week 48:
?Proportion of patients achieving HIV RNA <400 copies/mL.
?Change from baseline in CD4 cell counts.
2.Evaluate the antiretroviral activity of MK-0518 400 mg b.i.d. compared with efavirenz 600 mg q.h.s., each in combination therapy with TRUVADA?, as measured by the following parameters at Week 96:
?Proportion of patients achieving HIV RNA <50 copies/mL.
?Proportion of patients achieving HIV RNA <400 copies/mL.
?Change from baseline in CD4 cell counts.
(Read the rest in the protocol) |
1.Evaluar la actividad antirretroviral de MK-0518 400 mg dos veces al día en comparación con efavirenz 600 mg al acostarse, ambos en combinación con TRUVADATM, medida por los siguientes parámetros en la semana 48:
?Proporción de pacientes que alcanzan un valor de ARN del VIH < 400 copias/ml.
?Variación del recuento de linfocitos CD4 respecto al valor basal.
2.Evaluar la actividad antirretroviral de MK-0518 400 mg dos veces al día en comparación con efavirenz 600 mg al acostarse, ambos en combinación con TRUVADATM, medida por los siguientes parámetros en la semana 96:
?Proporción de pacientes que alcanzan un valor de ARN del VIH < 50 copias/ml.
?Proporción de pacientes que alcanzan un valor de ARN del VIH < 400 copias/ml.
?Variación del recuento de linfocitos CD4 respecto al valor basal.
(Leer el resto en el protocolo) |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1.Patient is a male or female at least 18 years of age on the day of signing the informed consent.
2.Patient is HIV positive as determined by a positive result by enzyme-linked immunosorbent assay (ELISA) and has screening plasma HIV RNA (determined by the central laboratory) >5000 copies/mL within 60 days prior to the treatment phase of this study, and is indicated for treatment based on physician assessment. Local treatment guidelines should be considered in the decision to initiate therapy.
3.Patient is naïve to ART.
4.Patient has the following laboratory values within 35 days prior to the treatment phase of this study:
4.1Serum creatinine ?2.0 x upper limit of normal
4.2Alkaline phosphatase ?5.0 x upper limit of normal
4.3AST (SGOT) and ALT (SGPT) ?5.0 x upper limit of normal
5.Patient has a calculated creatinine clearance at time of screening >30 mL/min, based on the Cockcroft-Gault equation which is as follows (and 0.85X this value for females):
Clcr (mL/min) = (140-age) x weight (in kg)
72 x serum creatinine (mg/dL)
6.In the opinion of the investigator, the patient should be considered clinically stable with no signs or symptoms of active infection, at the time of entry into the study; i.e., clinical status and all chronic medications should be unchanged for at least 2 weeks prior to the start of treatment in this study.
7.Patient who is of reproductive potential agrees to use an acceptable method of birth control throughout the study. Acceptable method of birth control is defined as intrauterine device (IUD), diaphragm with spermicide, condoms, or abstinence.
OR
Patient who is not of reproductive potential ; is not sexually active, whose current partner(s) is/are not of reproductive potential, or whose sexual activity is exclusively homosexual is eligible without requiring the use of contraception. |
1.Pacientes de ambos sexos y mayores de 18 años el día de la firma del consentimiento informado.
2.El paciente es positivo para el VIH, según se determina por un resultado positivo en un enzimoinmunoanálisis de adsorción (ELISA), y tiene un ARN del VIH en el plasma > 5.000 copias/ml durante la selección (determinado por el laboratorio central) en los 60 días previos a la fase de tratamiento de este estudio, y está indicado el tratamiento de acuerdo con la evaluación del médico. Deben valorarse las directrices de tratamiento locales en la decisión de iniciar el tratamiento.
3.El paciente nunca ha recibido TAR.
4.El paciente presenta los valores analíticos siguientes dentro de los 35 días previos a la fase de tratamiento de este estudio:
4.1Creatinina sérica ?2,0 x límite superior de la normalidad
4.2Fosfatasa alcalina ?5,0 x límite superior de la normalidad.
4.3AST (SGOT) y ALT (SGPT) ?5,0 x límite superior de la normalidad.
5.El paciente tiene un aclaramiento de creatinina calculado en el momento de la selección > 30 ml/min, según la ecuación de Cockroft-Gault, mostrada a continuación (0,85 X este valor en las mujeres):
Clcr (ml/min) = _(140 - edad) x peso (en kg)_
72 x creatinina sérica (mg/dl)
6.En opinión del investigador, debe considerarse que el paciente está clínicamente estable, sin signos o síntomas de infección activa, en el momento de la entrada en el estudio, esto es, el estado clínico y los medicamentos crónicos no deberán haber cambiado como mínimo en las 2 semanas anteriores al comienzo del tratamiento en este estudio.
7.La paciente está en edad de procrear y accede a utilizar un método anticonceptivo aceptable durante la totalidad del estudio. Un método anticonceptivo aceptable se define como un dispositivo intrauterino (DIU), un diafragma con espermicida, preservativos o abstinencia.
O
Podrán participar sin necesidad de usar anticonceptivos los pacientes que no tengan capacidad reproductiva ; no sean sexualmente activos o tengan una pareja actual que no tenga capacidad de procrear. |
|
| E.4 | Principal exclusion criteria |
1.Patient has a history or current evidence of any condition, therapy, laboratory abnormality or other circumstance that might confound the results of the study, or interfere with the patient?s participation for the full duration of the study, such that it is not in the best interest of the patient to participate.
2.Patient is, at the time of signing informed consent, a user of recreational or illicit drugs or has had a recent history (within the last year) of drug or alcohol abuse or dependence.
3.Patient has been treated for a viral infection other than HIV, such as hepatitis B, with an agent that is active against HIV including but not limited to adefovir, tenofovir, emtricitabine or lamivudine.
Note: Patients may be enrolled if treatment occurred prior to the diagnosis of HIV.
4.Patient has documented resistance to tenofovir, emtricitabine, and/or efavirenz.
5.Patient is currently participating or has participated in a study with an investigational compound or device within 30 days of signing informed consent.
6.Patient has used another experimental HIV-integrase inhibitor.
7.Patient has used systemic immunosuppressive therapy within one month prior to treatment in this study. Short courses of corticosteroids (e.g., as for asthma exacerbation) will be allowed.
8.Patient requires hemodialysis.
9.Patient has significant hypersensitivity or other contraindication to any of the components of the study drugs.
10.Patient has a current (active) diagnosis of acute hepatitis due to any cause. Patients with chronic hepatitis, including chronic hepatitis B and/or C, may enter the study as long as they have stable liver function tests and meet all inclusion criteria. Patients who, in the opinion of the investigator, have evidence of impairment of hepatic synthetic function, such as hypoalbuminemia or prolonged PT and PTT should be excluded.
11.Patient is pregnant or breastfeeding, or expecting to conceive (within the duration of the study). Patient is expecting to donate eggs (within the duration of the study). Patient is expecting to donate sperm (within the duration of the study). |
1.El paciente tiene antecedentes o signos actuales de cualquier proceso, tratamiento, anomalía analítica u otra circunstancia que podrían confundir los resultados del estudio o interferir en su participación durante todo el estudio, de modo que no le conviene participar.
2.En el momento de firmar el consentimiento informado, el paciente consume drogas o tiene antecedentes recientes (en el último año) de alcoholismo o drogadicción.
3.Se ha tratado al paciente por una infección viral distinta del VIH, como la hepatitis B, con un fármaco que es activo frente al VIH, como, entre otros, adefovir, tenofovir, emtricitabina o lamivudina.
Nota: podrá incluirse al paciente si el tratamiento fue anterior al diagnóstico del VIH.
4.El paciente tiene resistencia documentada a tenofovir, emtricitabina y/o efavirenz.
5.El paciente participa en la actualidad en un estudio sobre un compuesto o dispositivo experimental, o lo ha hecho en los 30 días previos a la firma del consentimiento informado.
6.El paciente ha recibido otro inhibidor de la integrasa del VIH experimental.
7.El paciente ha utilizado un tratamiento inmunodepresor sistémico durante el mes anterior al tratamiento en este estudio. Se permiten los ciclos cortos de corticosteroides (p. ej., para una exacerbación del asma).
8.El paciente requiere hemodiálisis.
9.El paciente presenta hipersensibilidad significativa o cualquier otra contraindicación a cualquiera de los componentes de los fármacos del estudio.
10.El paciente tiene un diagnóstico actual (activo) de hepatitis aguda de cualquier causa. Los pacientes con hepatitis crónica, ya sea de tipo B o C, podrán entrar en el estudio siempre que tengan resultados estables en las pruebas de función hepática y que cumplan todos los criterios de inclusión. Se excluirá a los pacientes que, en opinión del investigador, presenten datos de alteración de la función sintética del hígado, como hipoalbuminemia o prolongación del TP y del TPT.
11.La paciente está embarazada o lactando o espera concebir (durante el período del estudio). La paciente tiene previsto donar óvulos (durante el período del estudio). El paciente tiene previsto donar esperma (durante el período del estudio). |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Efficacy and Safety |
| Eficacia y seguridad. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
Efficacy: Proportion of patients achieving HIV RNA <50 copies/mL at Wk48 .
Safety: safety and tolerability as assessed by review of the accumulated safety data at Week 48. |
Eficacia: proporción de pacientes que alcanzan un valor de ARN del VIH < 50 copias/ml en la semana 48.
Seguridad: seguridad y tolerabilidad a juzgar por la evaluación de los datos de seguridad acumulados en la semana 48. |
|
| E.5.2 | Secondary end point(s) |
| Efficacy, tolerabilty, safety and evaluate nervous symptoms. |
| Eficacia, seguridad y evaluar síntomas del sistema nervioso |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
Efficacy: Evaluate antriretroviral activity at week 48, 96
Tolerability and safety: as assessed by review of the accumulated safety data up to Week 96.
Nervous symptoms: as measured by proportion of patients with nervous system symptoms assessed by review of accumulated safety data up to Week 8. |
Eficacia: Evaluar la actividad antriretroviral en semana 48 y 96
Tolerabilidad y seguridad: evaluados al revisar los datos de seguridad acumulados hasta semana 96
Síntomas del sistema nervioso: evaluados al revisar los datos de seguridad acumulados hasta semana 8. |
|
| 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 | 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) | Yes |
| 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 | 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 | 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 | Yes |
| E.8.2.3 | Other | Yes |
| E.8.2.3.1 | Comparator description |
|
| 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
| 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 | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 19 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| Australia |
| Brazil |
| Canada |
| Chile |
| Colombia |
| France |
| Germany |
| India |
| Italy |
| Mexico |
| Peru |
| Spain |
| Thailand |
| United States |
|
| 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
|
| Refer to protocol. |
| Leer en el protocolo. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 3 |
| E.8.9.1 | In the Member State concerned months | 2 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 3 |
| E.8.9.2 | In all countries concerned by the trial months | 2 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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