Clinical Trials Register

Summary
EudraCT Number:	2013-000486-37
Sponsor's Protocol Code Number:	2013-000486-37
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:	2013-07-12
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

2013-000486-37

A.3

Full title of the trial

Rosuvastatin versus Protease Inhibitor Switching for Hypercholesterolaemia in HIV-infected Adults.

Rosuvastatina versus sustitución del Inhibidor de la Proteasa en pacientes adultos con infección por el VIH e hipercolesterolemia

A.3.1

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

Treatment with Rosuvastatin versus switching PI (protease inhibitor) in patients HIV with high cholesterol levels.

Tratamiento con Rosuvastatina versus cambio de IP (inhibidor de la proteasa) en pacientes VIH con niveles altos de colesterol

A.3.2

Name or abbreviated title of the trial where available

SOS

A.4.1

Sponsor's protocol code number

2013-000486-37

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	St. Vincent?s Hospital
B.4.2	Country	Australia
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Clinical Trial Unit
B.5.2	Functional name of contact point	Joan Albert Arnaiz
B.5.3	Address:
B.5.3.1	Street Address	Rosellón, 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	+349322754009838
B.5.5	Fax number	+3493932279877
B.5.6	E-mail	jaarnaiz@clinic.ub.es

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	Yes
D.2.1.1.1	Trade name	Crestor
D.2.1.1.2	Name of the Marketing Authorisation holder	ASTRAZENECA FARMACEUTICA SPAIN, S.A.
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	Gastro-resistant 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	Rosuvastatin calcium
D.3.9.1	CAS number	287714-41-4
D.3.9.3	Other descriptive name	ROSUVASTATIN
D.3.9.4	EV Substance Code	SUB20634
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

HIV AND HYPERCHOLESTEROLAEMIA

VIH E HIPERCOLESTEROLEMIA

E.1.1.1

Medical condition in easily understood language

HIV and high cholesterol levels

VIH y altos niveles de colesterol

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	16.0
E.1.2	Level	LLT
E.1.2	Classification code	10068341
E.1.2	Term	HIV-1 infection
E.1.2	System Organ Class	100000004862

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To compare the effect of rosuvastatin to protease inhibitor switching on fasting total cholesterol over 12 weeks

Comparar el efecto de rosuvastatina o la sustitución de inhibidor de proteasa en el colesterol total en ayunas durante 12 semanas

E.2.2

Secondary objectives of the trial

To compare the effects of rosuvastatin to protease inhibitor switching on:
1.Total cholesterol through week 12
2.Safety parameters (HIV viral load, clinical adverse events, serious adverse events, laboratory adverse events, modifications to antiretroviral therapy)
3.Quality of life (SF-12)
4.Fasting LDL cholesterol (estimated with Friedwald equation unless triglycerides >400mg/dL, in which case LDL-C would be measured directly), HDL cholesterol, total : HDL cholesterol ratio, LDL particles sizes, triglycerides
5.Fasting glucose and insulin
6.Framingham cardiovascular risk score
7.D:A:D 5-year estimated risk calculator

Comparar los efectos de rosuvastatina o sustitución de inhibidor de la proteasa sobre:

? Colesterol total en la semana 12
? Parámetros de seguridad (carga viral, acontecimientos adversos clínicos y de laboratorio, acontecimientos adversos graves, cambios del tratamiento antirretroviral)
? Calidad de vida (cuestionario SF-12)
? Colesterol LDL en ayunas, colesterol HDL, ratio colesterol total/colesterol HDL, tamaño partículas LDL, triglicéridos)
? Glucosa e insulina en ayunas
? Cálculo del riesgo cardiovascular según Framingham
? Cálculo del riesgo cardiovascular según D.A.A. estimado a 5 años

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1.HIV-positive status
2.Adults (?18 years of age)
3.Stable and well-tolerated combination ART including a ritonavir-boosted PI for the previous 6 months
4.HIV RNA <50 copies/mL for at least the preceding 3 months
5.Fasting total cholesterol ?5.5 mmol/L (>213 mg/dL)
6.Framingham risk score ?8% at 10 years OR diabetes mellitus OR a family history of premature coronary artery disease in a first-degree relative
7.Provision of written, informed consent

1. VIH positivos
2. Adultos (?18 años)
3. En combinación estable y bien tolerada de tratamiento antirretroviral que incluya un inhibidor de la proteasa potenciado con ritonavir dutante los últimos 6 meses
4. VIH RNA <50 copies/mL en los últimos 3 meses.
5. Colesterol total en ayunas ?5.5 mmol/L (>213 mg/dL)
6. Fragmingham score ?8% a 10 años o Diabetes mellitus o historia familiar de enfermedad coronaria prematura en familiar de primer grado
7. Otorgar consentimiento informado por escrito

E.4

Principal exclusion criteria

1.Any statin in the previous 12 weeks
2.Previous statin-induced myopathy or hepatitis
3.History of coronary artery disease, stroke or any other indication for the use of statin therapy (hyperlipidaemia: genetic, secondary or idiopathic)
4.Concurrent use of:
?oral corticosteroids use other than for replacement therapy (ie. prednisolone 5-7.5 mg, hydrocortisone 20-30 mg, cortisone acetate 25-37.5 mg daily)
?other immunosuppressive or immunomodulating drugs
5.Contra-indication to rosuvastatin therapy:
?liver transaminases >5 times the upper normal limit
?creatinine clearance <30 mL/min
?known myopathy
?current fibrate therapy
?known resistance to one or more ?backbone? ART drugs
6.No potent switch ART drug available to replace the current ritonavir-boosted PI
7.Known intolerance to rosuvastatin or the proposed switch ART drug
8.Women attempting or likely to become pregnant, or who are pregnant or breast-feeding
9.A patient with a history or current evidence of any condition, therapy, or 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
10.Unable to complete study procedures

1. Uso de estatinas en las últimas 12 semanas
2. Antecedentes de miopatía o hepatitis inducida por estatinas
3. Antecedentes de enfermedad coronaria, accidente cerebro-vascular, o otras indicaciones para el uso de estatinas (hiperlipidemia: genética, secundaria, o idiopática)
4. Uso concomitante de:
- Corticosteroides, salvo tratamiento sustitutivo (p.ej prednisolona 5-7.5 mg, hidrocortisona 20-30 mg, acetato de cortisona 25-37.5 mg /día)
- Otros inmunosupresores e inmunomoduladores
5. Contraindicación para el uso de Rosuvastatina:
- Transaminasas >5 veces el límite superior de normalidad
- Aclaramiento de creatinina < 30mL/min
- Miopatía conocida
- Uso actual de fibratos
- Resistencia a uno o más de los fármacos antirretrovirales que forman parte de la combinación actual
6. Ausencia de antirretroviral para sustituir al actual inhibidor de la proteasa potenciado
7. Intolerancia a Rosuvastatina o a antirretroviral sustitutivo
8. Embarazo o lactancia
9. Cualquier enfermedad médica preexistente conocida que pudiera interferir en la participación del paciente en el ensayo y en su finalización
10. Incapacidad para cumplir con los procedimientos del estudio

E.5 End points

E.5.1

Primary end point(s)

Percentage change from baseline in total cholesterol at 12 weeks

Pocentaje medio de cambio de los niveles de colesterol a las 12 semanas respecto la basal

E.5.1.1

Timepoint(s) of evaluation of this end point

12weeks

12 semanas

E.5.2

Secondary end point(s)

? Total cholesterol through week 12
? Safety parameters (HIV viral load, clinical adverse events, serious adverse events, laboratory adverse events, modifications to antiretroviral therapy)
? Quality of life (SF-12)
? Fasting LDL cholesterol (estimated with Friedwald equation unless triglycerides >400mg/dL, in which case LDL-C would be measured directly), HDL cholesterol, total : HDL cholesterol ratio, LDL particles sizes, triglycerides
? Fasting glucose and insulin
? Framingham cardiovascular risk score (available at:
http://hp2010.nhlbihin.net/atpiii/calculator.asp?usertype=prof)
? D:A:D 5-year estimated risk calculator (available at: http://www.cphiv.dk/TOOLS/DADRiskEquations/tabid/437/Default.aspx)

? Colesterol total en la semana 12
? Parámetros de seguridad (carga viral, acontecimientos adversos clínicos y de laboratorio, acontecimientos adversos graves, cambios del tratamiento antirretroviral)
? Calidad de vida (cuestionario SF-12)
? Colesterol LDL en ayunas, colesterol HDL, ratio colesterol total/colesterol HDL, tamaño partículas LDL, triglicéridos)
? Glucosa e insulina en ayunas
? Cálculo del riesgo cardiovascular según Framingham
? Cálculo del riesgo cardiovascular según D.A.A. estimado a 5 años

E.5.2.1

Timepoint(s) of evaluation of this end point

12 weeks

12 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

Yes

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)

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

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

Yes

E.8.4

The trial involves multiple sites in the 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

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

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

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

The last visit of the last subject undergoing the trial.

Se considerará final del ensayo el momento de la última visita del último sujeto reclutado.

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

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:

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

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

Yes

F.3.3.1

Women of childbearing potential not using contraception

Yes

F.3.3.2

Women of child-bearing potential using contraception

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

1-Treatment with protease inhibitor and rosuvastatina

OR

2-Treatment with ART other than protease inhibitor

1-Tratamiento con inhibidor de proteasa y rosuvastatina

O

2-Tratamiento con ART aparte de inhibidor de proteasa

G. Investigator Networks to be involved in the Trial
G.4 Investigator Network to be involved in the Trial: 1

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

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2013-07-16

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2013-06-17

P. End of Trial
P.	End of Trial Status	Completed

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