Clinical Trials Register

Summary
EudraCT Number:	2010-024652-28
Sponsor's Protocol Code Number:	OLÉ
National Competent Authority:	Spain - AEMPS
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2011-09-15
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

2010-024652-28

A.3

Full title of the trial

Estudio para evaluar la actividad y la tolerabilidad de la biterapia con lopinavir/ritonavir y 3TC en sustitución de una triple terapia que incluya lopinavir/ritonavir y 3TC ó FTC en pacientes con infección por VIH y supresión virológica: ensayo clínico controlado, abierto, con asignación aleatoria, de 48 semanas de duración

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

Estudio para evaluar la actividad y seguridad de lopinavir/ritonavir y 3TC en pacientes infectados por el VIH-1 con carga viral indetectable y en tratamiento con lopinavir/ritonavir y 3TC ó FTC

A.4.1

Sponsor's protocol code number

OLÉ

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Fundació Clínic per a la Recerca Biomèdica
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	NA
B.4.2	Country	Spain
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	CTU Clinic
B.5.2	Functional name of contact point	Judit Pich
B.5.3	Address:
B.5.3.1	Street Address	Rosselló, 138
B.5.3.2	Town/ city	Barcelona
B.5.3.3	Post code	08036
B.5.3.4	Country	Spain
B.5.4	Telephone number	34932279838
B.5.5	Fax number	34932279877
B.5.6	E-mail	jpich@clinic.ub.es

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Comparator
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	No
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	lamivudina
D.3.2	Product code	3TC
D.3.4	Pharmaceutical form	Film-coated tablet
D.3.4.1	Specific paediatric formulation	No
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	lamivudina
D.3.9.1	CAS number	70913
D.3.9.2	Current sponsor code	3TC
D.3.9.3	Other descriptive name	lamivudine
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	300
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)	No
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	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
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	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
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	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Comparator
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	Yes
D.2.1.1.1	Trade name	KALETRA 200/50 mg comprimidos recubiertos con película
D.2.1.1.2	Name of the Marketing Authorisation holder	ABBOTT LABORATORIES LTD.
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.3.4	Pharmaceutical form	Film-coated tablet
D.3.4.1	Specific paediatric formulation	No
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	LOPINAVIR
D.3.9.3	Other descriptive name	LOPINAVIR
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	200
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	RITONAVIR
D.3.9.3	Other descriptive name	RITONAVIR
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	50
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)	No
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	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
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	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
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	No

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

Infección VIH

E.1.1.1

Medical condition in easily understood language

Infección por VIH

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

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Demostrar que la efectividad clínica de la biterapia es no-inferior a la del grupo de control, cuando se administra durante 48 semanas a pacientes con infección por VIH-1.

E.2.2

Secondary objectives of the trial

- Demostrar que la actividad antiviral de la biterapia es no-inferior a la del grupo de control, cuando se administra durante 48 semanas a pacientes con infección por VIH-1 que tienen cargas virales por debajo de los límites de detección (<50 copias/mL)..
- Demostrar que la seguridad y tolerabilidad de la biterapia es superior que la del grupo de control.

E.2.3

Trial contains a sub-study

Yes

E.2.3.1

Full title, date and version of each sub-study and their related objectives

- Subestudio de composición corporal y densidad mineral ósea, versión 1.0 de 24/01/11.
- Subestudio de metabolismo lipídico, versión 1.0 de 24/01/11.
- Subestudio neurocognitivo, versión 1.0 de 24/01/11.

E.3

Principal inclusion criteria

a. Pacientes de ambos sexos* de 18 o más años de edad.
b. Seropositivos para el VIH-1 según criterios diagnósticos estándar.
c. En supresión virológica durante los 6 meses previos a la inclusión, definido como dos determinaciones de carga viral plasmática por debajo 50 copias/mL separadas al menos 6 meses y ninguna >50 copias/mL.
d. En tratamiento continuo con TARGA compuesto de lopinavir/ritonavir, emtricitabina (FTC) ó 3TC (lamivudina) y un ITIN durante al menos 2 meses antes de ser aleatorizados en este estudio.
e. Clínicamente estables, en opinión del investigador, en el momento de la inclusión (la situación clínica y la medicación crónica no deben haberse modificado como mínimo en los 14 días previos a la aleatorización).
f. Que, adecuadamente informados, otorguen su consentimiento por escrito para participar en el estudio y someterse a las pruebas y exploraciones que ello comporta

*Las mujeres en edad fértil deben comprometerse a la abstinencia sexual o a la utilización de métodos anticonceptivos de barrera durante el estudio. Además, deben tener una prueba de embarazo en orina durante los 10 días previos a la inclusión en el estudio.

E.4

Principal exclusion criteria

a. Embarazo, lactancia o previsión de embarazo durante el periodo de estudio.
b. Fracaso previo con pautas que incluyan un inhibidor de la proteasa (IP) ó 3TC/FTC.
c. Mutaciones de resistencia a IPs ó 3TC/FTC conocidas.
d. Pacientes con infección oportunista o neoplasia activas que requieran tratamiento por vía parenteral oquimioterapia.
e. Cualquier enfermedad o antecedente patológico que, en opinión del investigador, pudiera confundir los resultados del estudio o suponer un riesgo adicional al tratamiento del paciente.
f. Pacientes con hepatitis crónica B en tratamiento con tenofovir + 3TC/FTC
g. Utilización de fármacos contraindicados formalmente en la ficha técnica de cualquiera de los medicamentos en studio.
h. Contraindicación para el uso de alguno de los fármacos en estudio

E.5 End points

E.5.1

Primary end point(s)

Proporción de pacientes libres de fracaso terapéutico a las 48 semanas, definido como dos determinaciones consecutivas de carga viral >50 copias/mL separadas al menos por 2 semanas, muerte, progresión a una nueva enfermedad definitoria de SIDA, pérdida de seguimiento o cambio o interrupción permanente de cualquiera de los tratamientos antirretrovirales por cualquier motivo

E.5.1.1

Timepoint(s) of evaluation of this end point

48 semanas

E.5.2

Secondary end point(s)

- proporción de pacientes libres de fracaso virológcio a las 48 semanas (considerando CV>50 copias/ml)
- proporción de pacientes libres de fracaso terapéutico a las 48 semanas (considerando CV>400 copias/ml)
- - proporción de pacientes libres de fracaso virológcio a las 48 semanas (considerando CV>400 copias/ml)
- tiempo hasta fracaso virológico y terapéutico
- proporción de pacietnes con blips
- cambio respecto al basal en las cifras de CD4+
- cambios respecto al basal de los niveles de TG, colesterol total, LDL y HDL
- cambios en el aclaramiento de creatinina mediante Cockroft-Gault y MDRD
-proporción de pacientes con disfunción tubular renal
- cambios en lipoatrofia y/o acúmulo grado
- cambios de adherencia
- mortalidad y progresión a SIDA y acontecimientos no definitorios de SIDA
- incidencia de acontecimientos adversos clínicos
- proporción de pacientes que cambian el tratamiento en estudio a causa de acontecimientos adversos relacionados con la medicación
- proporción de pacientes con acontecimientos adversos graves relacionados con la medicación

E.5.2.1

Timepoint(s) of evaluation of this end point

48 semanas

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

E.7.4

Therapeutic use (Phase IV)

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.8.2.4

Number of treatment arms in the trial

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.8.4.1

Number of sites anticipated in Member State concerned

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

E.8.7

Trial has a data monitoring committee

Yes

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

last visit las subject

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

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

306

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

306

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

F.3.3.1

Women of childbearing potential not using contraception