Clinical Trials Register

Summary
EudraCT Number:	2004-001403-35
Sponsor's Protocol Code Number:	DOM2004 REDOX
National Competent Authority:	Spain - AEMPS
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2006-01-25
Trial results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Spain - AEMPS

A.2

EudraCT number

2004-001403-35

A.3

Full title of the trial

Estudio abierto, multicéntrico y aleatorizado sobre la eficacia y seguridad de la reducción de dosis de estavudina en pacientes en tratamiento antirretroviral que incluye estavudina a dosis estándar con buen control virológico e inmunológico.

A.3.2

Name or abbreviated title of the trial where available

REDOX

A.4.1

Sponsor's protocol code number

DOM2004 REDOX

A.7

Trial is part of a Paediatric Investigation Plan

Information not present in EudraCT

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Doctor Pere Domingo
B.1.3.4	Country	Spain
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support
B.4.2	Country
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation
B.5.2	Functional name of contact point

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Information not present in EudraCT
D.2.1.1.1	Trade name	Zerit
D.2.1.1.2	Name of the Marketing Authorisation holder	BRISTOL MYERS SQUIBB PHARMAEEIG
D.2.1.2	Country which granted the Marketing Authorisation	Spain
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Zerit
D.3.2	Product code	Zerit
D.3.4	Pharmaceutical form	Capsule, hard
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	ESTAVUDINA
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	20
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	Information not present in EudraCT
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Information not present in EudraCT
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	Information not present in EudraCT
D.3.11.8	Extractive medicinal product	Information not present in EudraCT
D.3.11.9	Recombinant medicinal product	Information not present in EudraCT
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	Information not present in EudraCT
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Information not present in EudraCT
D.2.1.1.1	Trade name	Zerit
D.2.1.1.2	Name of the Marketing Authorisation holder	BRISTOL MYERS SQUIBB PHARMAEEIG
D.2.1.2	Country which granted the Marketing Authorisation	Spain
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Zerit
D.3.2	Product code	Zerit
D.3.4	Pharmaceutical form	Capsule, hard
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	ESTAVUDINA
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	30
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	Information not present in EudraCT
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Information not present in EudraCT
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	Information not present in EudraCT
D.3.11.8	Extractive medicinal product	Information not present in EudraCT
D.3.11.9	Recombinant medicinal product	Information not present in EudraCT
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	Information not present in EudraCT
D.IMP: 3
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Information not present in EudraCT
D.2.1.1.1	Trade name	Zerit
D.2.1.1.2	Name of the Marketing Authorisation holder	BRISTOL MYERS SQUIBB PHARMAEEIG
D.2.1.2	Country which granted the Marketing Authorisation	Spain
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Zerit
D.3.2	Product code	Zerit
D.3.4	Pharmaceutical form	Capsule, hard
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	ESTAVUDINA
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	40
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	Information not present in EudraCT
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Information not present in EudraCT
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	Information not present in EudraCT
D.3.11.8	Extractive medicinal product	Information not present in EudraCT
D.3.11.9	Recombinant medicinal product	Information not present in EudraCT
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	Information not present in EudraCT

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

AIDS

MedDRA Classification

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Comparar la proporción de sujetos con rebote virológico por encima de 400 copias/ml hasta las 48 semanas de seguimiento, entre los sujetos que cambian a un régimen con estavudina a dosis reducida y aquellos que continúan su régimen actual (dosis estándar de estavudina).

E.2.2

Secondary objectives of the trial

Valoraciones hasta semana 48 en sujetos con régimen de dosis reducida de d4T frente a los que permanecieron con su régimen actual con dosis estándar: 1)Proporción de pacientes y tiempo hasta rebote virológico para estos con niveles de ARN VIH < 50 cp/ml basal.2)El % pacientes con una carga vírica > 1.000 copias/ml hasta semana 48.3)La frecuencia e intensidad de acontecimientos adversos clínicos y de laboratorio y las retiradas por ellos. 4)La magnitud del cambio del recuento de CD4 en la semana 48 respecto al basal.5)Las variaciones de los lípidos en ayunas respecto a los basales.6)Variacines de los parámetros metabólicos en ayunas .7)Variaciones respecto del basal en los niveles de d4T plasmáticos y de d4T-TP intracelulares 4 semanas tras la reducción de dosis. 8)Variaciones en las medidas antropométricas, cuestionario de morfología corporal y DEXA. 9)La intensidad de los síntomas y la toxicidad percibida por el paciente basalmente y hasta la semana 48.

E.2.3

Trial contains a sub-study

Information not present in EudraCT

E.3

Principal inclusion criteria

1. El sujeto es capaz de leer y entender el consentimiento informado aprobado por el correspondiente CEIC, firmándolo voluntariamente, tras habérsele explicado la naturaleza del estudio y haber podido preguntar todo aquello que estime oportuno.
2. Edad superior a los 18 años.
3. El paciente debe estar de acuerdo en continuar su tratamiento actual para el VIH (recordar que la aleatorización se hará en proporción 1:1).
4. Tratamiento antirretroviral triple que incluya estavudina sin modificaciones durante al menos los 6 meses previos a la inclusión en el estudio. Las pautas deberán consistir en 2 NRTIs + 1 NNRTI ó 2 NRTIs + 1 IP (potenciado o no).
5. Antecedentes de tratamiento con ARV: Se permiten dos fracasos virológicos previos como máximo. Se define el fracaso virológico como una carga viral confirmada (dos resultados consecutivos de dos muestras diferentes) por encima del límite de cuantificación de la prueba empleada. Para este estudio, los cambios de algún fármaco componente de la pauta antirretroviral no motivados por rebote virológico no se computarán como fracasos virológicos.
6. El paciente debe tener dos determinaciones consecutivas de niveles plasmáticos de ARN del VIH-1 por debajo del límite de cuantificación (ARN del VIH-1 < 50 copias/ml o, excepcionalmente, <200-400 copias/ml si lo aprueba el monitor médico). Las dos determinaciones plasmáticas de calificación del ARN del VIH aseguran que el paciente ha estado virológicamente controlado durante al menos 3 meses:
(a) El paciente debe tener un nivel plasmático de ARN del VIH por debajo del límite de cuantificación al menos 90 días antes de la visita de selección (primera carga viral de calificación).
(b) El paciente debe tener un nivel plasmático confirmado de ARN del VIH < 50 copias/ml dentro de los 30 días previos a la visita basal (segunda carga vírica de calificación), realizado por la Valoración de PCR Ultrasensible de Roche (versión 1.5).
(c) El paciente no debe tener ningún nivel plasmático de ARN del VIH  400 copias/ml entre las dos cargas virales de calificación.
7. El recuento de linfocitos CD4 debe ser > 100 células/l durante los últimos 6 meses (Consultar con Monitor Médico si cifras inferiores a 100 cel).
8. Las mujeres en edad fértil (MEF) deben estar usando un método adecuado de anticoncepción para evitar el embarazo durante todo el estudio, de manera que se reduzca al mínimo el riesgo de embarazo

E.4

Principal exclusion criteria

1. Las MEF que no deseen o sean incapaces de usar un método aceptable para evitar el embarazo durante todo el período del estudio.
2. Mujeres embarazadas o en la lactancia.
3. Mujeres con una prueba de embarazo positiva en la visita de selección o antes de la administración del fármaco en estudio.
4. Antecedentes de uso de terapias antirretrovirales subóptimas (mono o biterapia) de duración > 1 año.
5. Esperanza de vida < 12 meses.
6. Presencia de una infección oportunista relacionada con el VIH recién diagnosticada o cualquier trastorno médico que precise tratamiento agudo en el momento o en los 30 días previos a la selección.
7. Peso inferior a 40kg.
8. Diabetes mellitus conocida no controlada (HbA1c > 9% dentro de los 30 días previos a la visita de selección).
9. Uso de alcohol o sustancias suficiente, en opinión del investigador, para impedir un cumplimiento adecuado con el tratamiento en estudio o para aumentar el riesgo de desarrollar pancreatitis, hepatitis o neuropatía.
10. Hepatitis aguda demostrada o sospechada en los 30 días previos a la entrada en el estudio. Los sujetos con hepatitis crónica son elegibles siempre que sus transaminasas hepáticas (ALT/AST) sean < 5 x límite superior a la normalidad.
11. Pacientes que reciben simultáneamente un IP y un inhibidor de la transcriptasa inversa no nucleósido o bien una pauta con tres análogos de nucleósido.
12. Se excluirá aquellos pacientes que reciban o se prevea que vayan a precisar tratamiento durante el estudio con fármacos con potencial neurotoxicidad, así como tratamiento con inmunomoduladores, agentes mielotóxicos o citotóxicos.
13. Presencia de alguna de las siguientes anomalías de laboratorio:
a. Hb ≤ 9 g/dl
b. Recuento de neutrófilos ≤ 750/uL
c. Cifra de plaquetas ≤ 50.000/mL
d. ALT o AST > 5 veces por encima del límite superior de la normalidad
e. Creatinina > 1,5 veces por encima del límite superior de la normalidad
14. Fármacos o vacunas experimentales administrados en los 30 días anteriores al inicio del estudio.
15. Cualquier motivo que a juicio del investigador impida que el paciente participe en el estudio.
16. Los prisioneros o los sujetos que sean detenidos por la fuerza (encarcelados involuntariamente) para tratamiento de una enfermedad psiquiátrica o física (p. ej., enfermedad infecciosa) no deben ser reclutado en este estudio.

E.5 End points

E.5.1

Primary end point(s)

Proporción de sujetos con rebote virológico, definido como dos niveles de ARN del VIH consecutivos > 400 cp/ml hasta la semana 48.

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

Information not present in EudraCT

E.6.2

Prophylaxis

Information not present in EudraCT

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

Information not present in EudraCT

E.6.8

Bioequivalence

Yes

E.6.9

Dose response

Information not present in EudraCT

E.6.10

Pharmacogenetic

Information not present in EudraCT

E.6.11

Pharmacogenomic

Information not present in EudraCT

E.6.12

Pharmacoeconomic

Information not present in EudraCT

E.6.13

Others

Information not present in EudraCT

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

Information not present in EudraCT

E.7.1.1

First administration to humans

Information not present in EudraCT

E.7.1.2

Bioequivalence study

Information not present in EudraCT

E.7.1.3

Other

Information not present in EudraCT

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

Information not present in EudraCT

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

E.8.1.4

Double blind

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

Yes

E.8.2.2

Placebo

E.8.2.3

Other

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.5

The trial involves multiple Member States

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

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

Information not present in EudraCT

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

El final del estudio coincide con la última visita del último sujeto reclutado en el ensayo.

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

F. Population of Trial Subjects
F.1 Age Range
F.1.1	Trial has subjects under 18	Information not present in EudraCT
F.1.1.1	In Utero	Information not present in EudraCT
F.1.1.2	Preterm newborn infants (up to gestational age < 37 weeks)	Information not present in EudraCT
F.1.1.3	Newborns (0-27 days)	Information not present in EudraCT
F.1.1.4	Infants and toddlers (28 days-23 months)	Information not present in EudraCT
F.1.1.5	Children (2-11years)	Information not present in EudraCT
F.1.1.6	Adolescents (12-17 years)	Information not present in EudraCT
F.1.2	Adults (18-64 years)	Yes
F.1.3	Elderly (>=65 years)	Information not present in EudraCT
F.2 Gender
F.2.1	Female	Yes
F.2.2	Male	Yes
F.3 Group of trial subjects
F.3.1	Healthy volunteers	No
F.3.2	Patients	Yes
F.3.3	Specific vulnerable populations	Information not present in EudraCT
F.3.3.1	Women of childbearing potential not using contraception For clinical trials recorded in the database before the 10th March 2011 this question read: "Women of childbearing potential" and did not include the words "not using contraception". An answer of yes could have included women of child bearing potential whether or not they would be using contraception. The answer should therefore be understood in that context. This trial was recorded in the database on 2006-01-25.	Yes
F.3.3.2	Women of child-bearing potential using contraception	Information not present in EudraCT
F.3.3.3	Pregnant women	No
F.3.3.4	Nursing women	No
F.3.3.5	Emergency situation	No
F.3.3.6	Subjects incapable of giving consent personally	No
F.3.3.7	Others	No
F.4 Planned number of subjects to be included
F.4.1	In the member state	284
F.4.2	For a multinational trial
F.4.2.1	In the EEA	284
F.4.2.2	In the whole clinical trial	284

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2005-04-18

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2005-01-26

P. End of Trial
P.	End of Trial Status	Ongoing

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