Clinical Trials Register

Summary
EudraCT Number:	2014-002720-27
Sponsor's Protocol Code Number:	2014-002720-27
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:	2014-11-19
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

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Spain - AEMPS

A.2

EudraCT number

2014-002720-27

A.3

Full title of the trial

Simplification from Tenofovir plus Lamivudine or Emtricitabine plus Ritonavir-Boosted-Protease Inhibitor to Ritonavir-Boosted-Atazanavir plus Lamivudine in Virologically-Suppressed-HIV-Infected Adults with Osteopenia: a pilot study

Estudio piloto de simplificación del tratamiento antirretroviral con Tenofovir +Lamivudina o Emtricitabina + Ritonavir/Inhibidor de la proteasa a Ritonavir/Atazanavir+Lamivudina, en adultos infectados por el VIH en supresión virológica, con osteopenia.

A.3.1

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

A.3.2

Name or abbreviated title of the trial where available

Osteosimply014

A.4.1

Sponsor's protocol code number

2014-002720-27

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	BMS (Brystol Myers Squibb)
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 (Clinical Trial Unit)
B.5.2	Functional name of contact point	Jaime Camacho
B.5.3	Address:
B.5.3.1	Street Address	Villarroel 170
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	34932275400
B.5.5	Fax number	34932279877
B.5.6	E-mail	jcamacho@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.2.1.2	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	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	LAMIVUDINE
D.3.9.1	CAS number	134678-17-4
D.3.9.4	EV Substance Code	SUB08392MIG
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	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	Norvir
D.2.1.1.2	Name of the Marketing Authorisation holder	AbbVie 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.3.1	Product name	Norvir
D.3.4	Pharmaceutical form	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	RITONAVIR
D.3.9.1	CAS number	155213-67-5
D.3.9.4	EV Substance Code	SUB10342MIG
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	100
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: 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	Yes
D.2.1.1.1	Trade name	Reyataz
D.2.1.1.2	Name of the Marketing Authorisation holder	BRISTOL-MYERS SQUIBB PHARMA EEIG
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	Reyataz
D.3.4	Pharmaceutical form	Capsule, hard
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	Atazanavir
D.3.9.3	Other descriptive name	ATAZANAVIR SULFATE
D.3.9.4	EV Substance Code	SUB20595
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.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

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

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.

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.

E.2.3

Trial contains a sub-study

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.

E.5.2.1

Timepoint(s) of evaluation of this end point

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

E.6.5

Efficacy

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

E.8.1.1

Randomised

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)

E.8.2.2

Placebo

E.8.2.3

Other

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

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.7

Trial has a data monitoring committee

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

LVLS

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

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)

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.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)

None

Ninguno

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

2014-12-04

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2014-10-31

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

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials