Clinical Trials Register

Summary
EudraCT Number:	2006-000848-65
Sponsor's Protocol Code Number:	20050244
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:	2006-06-27
Trial results	View 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

2006-000848-65

A.3

Full title of the trial

Estudio multicéntrico, aleatorizado y doble ciego de denosumab en comparación con ácido zoledrónico (Zometa®) en el tratamiento de metástasis óseas, en sujetos con cáncer avanzado o mieloma múltiple (excluyendo cáncer de mama y de próstata)

A.4.1

Sponsor's protocol code number

20050244

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	Amgen Inc
B.1.3.4	Country	United States
B.3.1 and B.3.2	Status of the sponsor	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	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	Denosumab
D.3.2	Product code	AMG 162
D.3.4	Pharmaceutical form	Solution for injection
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.1	CAS number	615258-40-7
D.3.9.2	Current sponsor code	AMG 162
D.3.9.3	Other descriptive name	Abx 1-6 CHO OPG Ligand mAb IgG2; Human Monoclonal Antibody to RANKL
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	70
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	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	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	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	Acido zoledrónico
D.3.4	Pharmaceutical form	Concentrate for solution for infusion
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Zoledronic acid
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	0.8
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	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Solution for injection
D.8.4	Route of administration of the placebo	Subcutaneous use
D.8 Placebo: 2
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Concentrate for solution for infusion
D.8.4	Route of administration of the placebo	Intravenous use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Tratamiento de las metástasis óseas en cáncer metastásico o mieloma múltiple (excluyendo cáncer de mana y próstata)

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

Determinar si denosumab no es inferior al ácido zoledrónico respecto a la aparición durante el estudio del primer evento relacionado con el esqueleto (ERE) en sujetos con cáncer avanzado y metástasis óseas (o lesiones osteolíticas debidas al mieloma múltiple)

E.2.2

Secondary objectives of the trial

- Determinar si denosumab es superior al ácido zoledrónico con respecto a la aparición del primer ERE
- Determinar si denosumab es superior al ácido zoledrónico con respecto al primero y posteriores ERE durante el estudio (análisis de múltiples eventos)
- Valorar la seguridad y la tolerabilidad de denosumab en comparación con el ácido zoledrónico

E.2.3

Trial contains a sub-study

Information not present in EudraCT

E.3

Principal inclusion criteria

- adultos con cáncer avanzado, confirmado histológicamente o citológicamente, incluidos tumores sólidos, mieloma múltiple y linfoma
- evidencia radiográfica previa o actual (radiografía, tomografía computarizada [TC] o resonancia magnética [RM]) de al menos una metástasis ósea (o lesión osteolítica debida al mieloma múltiple)
- estado funcional del Eastern Cooperative Oncology Group (ECOG) de 0, 1 ó 2
- función orgánica adecuada, que se define por los criterios siguientes:
aspartato aminotransferasa (AST) en suero  5 x límite superior normal (LSN)
alanina aminotransferasa (ALT) en suero  5 x LSN
bilirrubina total en suero  2 x LSN
aclaramiento de creatinina (Cockcroft-Gault)  30 ml/min
calcio sérico ajustado por la albúmina >2,0 mmol/l (8,0 mg/dl) y ≤ 2,9 mmol/l (11,5 mg/dl)
- Antes de realizar cualquiera de los procedimientos específicos del estudio, deberá obtenerse por escrito el consentimiento informado.

E.4

Principal exclusion criteria

- diagnóstico de cáncer de mama o de próstata
- administración actual o previa de bisfosfonatos IV
- administración actual o previa de bisfosfonatos orales para el tratamiento de metástasis óseas o lesiones osteolíticas
- previsión de radioterapia o cirugía ósea
- administración previa de denosumab
- metástasis cerebrales conocidas
- esperanza de vida inferior a 6 meses
- antecedentes o indicios actuales de osteonecrosis/osteomielitis de la mandíbula
- enfermedad dental o mandibular activa que precise cirugía oral
- cirugía dental/bucal no cicatrizada
- procedimientos dentales invasivos previstos durante el estudio
- evidencia de alguna de estas enfermedades según el propio paciente o la revisión de su historial:
- cualquier tumor maligno (distinto del carcinoma basocelular o cáncer cervicouterino in situ) con enfermedad activa en los 3 años anteriores a la aleatorización
- infección conocida por el virus de la inmunodeficiencia humana
- infección activa por el virus de la hepatitis B o C
- cualquier trastorno orgánico o psiquiátrico que, en opinión del investigador, pudiera impedir al sujeto completar el estudio o interferir en la interpretación de los resultados
- treinta días o menos desde que se recibió un producto o dispositivo en investigación (es decir, cuya comercialización no está autorizada; se permite el uso de talidomida) en otro ensayo clínico
- mujeres embarazadas o lactantes
- sujeto con capacidad reproductiva que no acceda a utilizar un anticonceptivo eficaz (definido por el investigador principal o su representante)
- hipersensibilidad conocida a cualquiera de los productos que se administrarán durante el estudio (p. ej., ácido zoledrónico, productos derivados de mamíferos, calcio o vitamina D)

E.5 End points

E.5.1

Primary end point(s)

Tiempo hasta el primer ERE durante el estudio (no inferioridad)

Un ERE se define como una fractura patológica (vertebral o no vertebral), radioterapia ósea (incluido el uso de radioisótopos), cirugía ósea o compresión medular

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

Yes

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

Information not present in EudraCT

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

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

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

Yes

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

Information not present in EudraCT

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

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 tendrá lugar 4 semanas después de la fecha en la que se prevé que el sujeto 745 experimentará su primer ERE durante el estudio.
Después de la visita final del estudio se recopilará información sobre la supervivencia durante el periodo de seguimiento mediante visita clínica o contacto telefónico cada 12 semanas (± 14 días) durante 2 años después de la visita final del estudio.

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

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

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)

Yes

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 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 2006-06-27.

Yes

F.3.3.2

Women of child-bearing potential using contraception

Information not present in EudraCT

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.3.3.6.1

Details of subjects incapable of giving consent

Los sujetos con capacidad reproductiva que no accedan a utilizar un anticonceptivo eficaz (definido por el investigador principal o su representante) serán excluidos del estudio.

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

100

F.4.2

For a multinational trial

F.4.2.1

In the EEA

668

F.4.2.2

In the whole clinical trial

1690

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)

Después de la visita final del estudio se recopilará información sobre la supervivencia durante el periodo de seguimiento mediante visita clínica o contacto telefónico cada 12 semanas (± 14 días) durante 2 años después de la visita final del estudio. Además, 24 semanas (unos 6 meses) después de la visita final del estudio se obtendrá una muestra de suero para evaluar la presencia de anticuerpos anti-denosumab.

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

2006-09-15

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2006-08-31

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2011-08-24

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