Clinical Trials Register

Summary
EudraCT Number:	2011-003938-14
Sponsor's Protocol Code Number:	MK-5592-069(P06200)
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:	2013-02-04
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

2011-003938-14

A.3

Full title of the trial

A Phase 3 Randomized Study of the Efficacy and Safety of Posaconazole versus Voriconazole for the Treatment of Invasive Aspergillosis in Adults and Adolescents (Phase 3; Protocol No. MK-5592-069)

Estudio de fase 3 aleatorizado de la eficacia y la seguridad de posaconazol en comparación con voriconazol para el tratamiento de la aspergilosis invasiva en adultos y adolescentes (fase 3; protocolo n.º MK 5592 069)

A.3.1

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

MK-5592 Protocol 069 (POS vs VOR for the treatment of a fungal infection (Invasive Aspergillosis) in Adults and Adolescents

MK-5592 Protocolo 069 (Pos Vs Vor para el tratamiento de la de la aspergilosis invasiva) en adultos y adolescentes

A.4.1

Sponsor's protocol code number

MK-5592-069(P06200)

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	Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., 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	Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
B.5.2	Functional name of contact point	Global Clinical Trials Operations
B.5.3	Address:
B.5.3.1	Street Address	One Merck Drive PO Box 100
B.5.3.2	Town/ city	Whitehouse Station, NJ
B.5.3.3	Post code	08889-0100
B.5.3.4	Country	United States
B.5.4	Telephone number	1732740 2364
B.5.5	Fax number	1732740 4060
B.5.6	E-mail	hetty.waskin@merck.com

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	SCH56592/MK-5592
D.3.2	Product code	SCH56592/MK-5592
D.3.4	Pharmaceutical form	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	SCH56592/MK-5592
D.3.9.2	Current sponsor code	SCH56592/MK-5592
D.3.9.3	Other descriptive name	POSACONAZOLE
D.3.9.4	EV Substance Code	SUB20322
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: 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	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	SCH56592/MK-5592
D.3.2	Product code	SCH56592/MK-5592
D.3.4	Pharmaceutical form	Infusion
D.3.4.1	Specific paediatric formulation	No
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	SCH56592/MK-5592
D.3.9.2	Current sponsor code	SCH56592/MK-5592
D.3.9.3	Other descriptive name	POSACONAZOLE
D.3.9.4	EV Substance Code	SUB20322
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	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	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	SCH56592/MK-5592
D.3.2	Product code	SCH56592/MK-5592
D.3.4	Pharmaceutical form	Infusion
D.3.4.1	Specific paediatric formulation	No
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	SCH56592/MK-5592
D.3.9.2	Current sponsor code	SCH56592/MK-5592
D.3.9.3	Other descriptive name	POSACONAZOLE
D.3.9.4	EV Substance Code	SUB20322
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	200
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: 4
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	VFEND IV (Voriconazole)
D.2.1.1.2	Name of the Marketing Authorisation holder	Pfizer
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	VFEND IV (Voriconazole)
D.3.2	Product code	VFEND IV (Voriconazole)
D.3.4	Pharmaceutical form	Infusion
D.3.4.1	Specific paediatric formulation	No
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	VORICONAZOLE
D.3.9.1	CAS number	137234-62-9
D.3.9.4	EV Substance Code	SUB00087MIG
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	200
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: 5
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	VFEND Tablets (Voriconazole)
D.2.1.1.2	Name of the Marketing Authorisation holder	Pfizer
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	VFEND Tablets (Voriconazole)
D.3.2	Product code	VFEND Tablets (Voriconazole)
D.3.4	Pharmaceutical form	Capsule
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	VORICONAZOLE
D.3.9.1	CAS number	137234-62-9
D.3.9.4	EV Substance Code	SUB00087MIG
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.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	Tablet
D.8.4	Route of administration of the placebo	Oral use
D.8 Placebo: 2
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Capsule
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Invasive aspergillosis

aspergilosis invasiva

E.1.1.1

Medical condition in easily understood language

fungal infection

infección por hongo

E.1.1.2

Therapeutic area

Diseases [C] - Bacterial Infections and Mycoses [C01]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.1
E.1.2	Level	PT
E.1.2	Classification code	10003488
E.1.2	Term	Aspergillosis
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

Compare global clinical response of POS vs VOR in the first-line treatment of invasive aspergillosis at Week 6 in those subjects with proven or probable invasive aspergillosis (FAS population)

Comparar la respuesta clínica global de posaconazol (POS) con la de voriconazol (VOR) en el tratamiento de primera línea de la aspergilosis invasiva (AI) en la semana 6 en los sujetos con AI comprobada o probable (en la población GAC [grupo de análisis completo]).

E.2.2

Secondary objectives of the trial

Evaluate all-cause mortality for POS vs VOR at Week 6 in FAS population

Evaluate global clinical response for POS vs VOR at Week 12 in FAS population

Evaluate all-cause mortality for POS vs. VOR at Week 12 in FAS population

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

A Phase 3 Randomized Study of the Efficacy and Safety of Posaconazole ersus Voriconazole for the Treatment of Invasive Aspergillosis in Adults and Adolescents (Phase 3; Protocol No. MK-5592-069)
Genetic Consent Version 00 General January-7-2013

E.3

Principal inclusion criteria

1. Each subject must be willing and able to provide written informed consent for the trial. The legal representative (e.g. parent or guardian) for a subject under the age of legal consent or who otherwise is unable to provide independent consent may provide written informed consent for the subject. Each subject of the age of assent must be willing and able to provide assent in addition to consent from the legal representative to participate in the trial.
2. Each subject must be > or = to 13 years of age weighing >40 kg [88 lb] and < or = to 150 kg [330 lb] at the time of randomization. Each subject between 13 and 14 years of age must weigh > or = to 50 kg [110 lb]. Subjects may be of either sex and of any race/ethnicity.
3. Each subject must meet the criteria for proven, probable, or possible invasive aspergillosisIA as per 2008 EORTC/MSG disease definitions at the time of randomization. Proven IA will include those subjects with the demonstration of fungal elements (by cytology, microscopy, or culture) in diseased tissue (sterile sampling). Probable IA includes subjects with at least 1 host factor, clinical criteria, as well as mycological criteria including both direct and indirect (i.e., detection of serum, or BAL fluid Aspergillus galactomannan antigen by sandwich EIA) methods. If using the galactomannan test for diagnosis, a positive test results is defined as a cut-off index of > or = to 1.0 for both serum and BAL. Two positive test results will qualify the subject for meeting the criteria as probable IA. Possible IA includes subjects with at least 1 host factor and clinical criteria but without mycological criteria. See Appendix 3 for tables of diagnostic criteria.
4. Each subject with possible invasive aspergillosisIA at time of randomization must be willing or be in process of an ongoing diagnostic work up which is anticipated to result in a mycological diagnosis of proven or probable IA within 7 days post-randomization. In the event this does not result in mycological diagnosis of proven or probable IA, the patient must be willing to continue on study therapy and remain in the study.
5. Each subject must have a central catheterline (e.g., central venous catheter, peripherally-inserted central catheter, etc.) in place or planned to be in place prior to beginning IV study therapy.
6. Each subject must have acute invasive aspergillosisIA defined as duration of clinical syndrome of <30 days.
7. Each subject must be willing to adhere to dosing, study visit schedule, and mandatory procedures as outlined in the protocol.
8. The subject must have the ability to transition to oral study therapy during the course of the study or be willing to receive the entire 12-week study treatment course intravenously.

1.El sujeto deberá estar dispuesto a otorgar su consentimiento informado por escrito para el ensayo y ser capaz de hacerlo. En el caso de un sujeto con una edad que esté por debajo de la de consentimiento legal o que, por cualquier otro motivo, no pueda otorgar su consentimiento informado por escrito de forma independiente, en su lugar podrá hacerlo su representante legal (por ejemplo, progenitor o tutor). Un sujeto en edad de asentimiento deberá estar dispuesto a otorgar su asentimiento y ser capaz de hacerlo, además del consentimiento del representante legal para participar en el ensayo.
2.El sujeto deberá tener una edad mínima de 13 años y pesar > 40 y < ó = a 150 kg en el momento de aleatorización. Los sujetos de entre 13 y 14 años de edad deberán pesar > ó = a 50 kg. Los sujetos podrán ser de cualquier sexo y de cualquier raza o etnia.
3.El sujeto deberá cumplir los criterios de AI comprobada, probable o posible de acuerdo con las definiciones de enfermedad de la EORTC/MSG de 2008 en el momento de aleatorización. En la categoría de AI comprobada se incluirá a los sujetos con demostración de elementos fúngicos (mediante citología, microscopia o cultivo) en tejido enfermo (obtención estéril de las muestras). En la categoría de AI probable se incluirá a los sujetos con al menos un factor del huésped, criterios clínicos y criterios micológicos, que comprenden métodos directos e indirectos (es decir, detección en suero o líquido de LBA de antígeno galactomanano de Aspergillus mediante EIA en sándwich). Podrán utilizarse dos valores de EIA de galactomanano en suero consecutivos > ó = a 0,5 o un solo valor > ó = a 1,0 como único criterio microbiológico de AI probable. Podrá utilizarse un solo valor de EIA de galactomanano > ó = a 1,0 en una muestra de LBA para cumplir los criterios microbiológicos de AI probable. En la categoría de AI posible se incluirá a los sujetos con al menos un factor del huésped y criterios clínicos, pero sin criterios micológicos. En el apéndice 3 se recogen las tablas de criterios diagnósticos.
4.Un sujeto con una AI posible en el momento de aleatorización deberá estar dispuesto a someterse o estar sometiéndose a una evaluación diagnóstica que se prevé que dé lugar a un diagnóstico micológico de AI comprobada o probable en los 7 días posteriores a la aleatorización.
5.El sujeto deberá tener una vía central (por ejemplo, catéter venoso central, catéter central insertado por vía periférica, etc.) colocada, o estar prevista su colocación, antes de comenzar el tratamiento del estudio IV.
6.El sujeto deberá presentar una AI aguda, definida como una duración < 30 días del síndrome clínico.
7.El sujeto deberá estar dispuesto a cumplir el tratamiento, el calendario de visitas del estudio y los procedimientos obligatorios tal como se describe en el protocolo.
8.El sujeto deberá tener la posibilidad de pasar a recibir el tratamiento del estudio por vía oral durante el transcurso del estudio o estar dispuesto a recibir todo el tratamiento del estudio durante 12 semanas por vía intravenosa.

E.4

Principal exclusion criteria

1.The subject has chronic (>1 month duration) IA, relapsed/recurrent IA, or refractory IA which has not responded to prior antifungal therapy.
2.The subject has sarcoidosis, aspergilloma, or allergic bronchopulmonary aspergillosis (ABPA).
3.The subject has a known mixed invasive mold fungal infection including Zygomycetes, and/or a known invasive Aspergillus fungal infection in which either study drug may not be considered active.
4.The subject has received any systemic (oral, intravenous, or inhaled) antifungal therapy for this infection episode for 4 or more consecutive days immediately prior to randomization.
5.The subject is taking mold-active antifungal prophylaxis and the IA infection is considered to be a breakthrough. A breakthrough IA infection is one that develops after the initiation of 13 days or more of preventative systemic antifungal therapy.
6.The subject has received POS or VOR as empirical treatment for this infection for 4 days (96 hours) or more within the 15 days immediately prior to randomization.

1.El sujeto presenta una AI crónica (> 1 mes de duración), recidivante/recurrente o resistente que no ha respondido al tratamiento antimicótico previo.
2.El sujeto presenta una sarcoidosis, aspergiloma o aspergilosis broncopulmonar alérgica (ABPA).
3.El sujeto presenta una micosis invasiva mixta por mohos, incluidos zigomicetos, o una micosis invasiva por Aspergillus en la que podría considerarse que alguno de los fármacos del estudio no es activo.
4.El sujeto ha recibido algún tratamiento antimicótico sistémico (oral, intravenoso o inhalado) contra este episodio de infección durante 4 días consecutivos o más inmediatamente antes de la aleatorización.
5.El sujeto está recibiendo profilaxis antimicótica activa contra mohos y se considera que la infección es intercurrente. Una AI intercurrente es aquella que aparece tras la administración durante 13 días o más de un tratamiento antimicótico sistémico activo contra mohos con fines preventivos.
6.El sujeto ha recibido POS o VOR como tratamiento empírico contra esta infección durante 4 días (96 horas) o más en los 15 días inmediatamente anteriores a la aleatorización.

E.5 End points

E.5.1

Primary end point(s)

Global clinical response of POS vs VOR in the first-line treatment of invasive aspergillosis at Week 6 in those subjects with proven or probable invasive aspergillosis (FAS population)

E.5.1.1

Timepoint(s) of evaluation of this end point

Week 6 of therapy

Semana 6 de tratamiento.

E.5.2

Secondary end point(s)

Evaluate of all-cause mortality for POS vs VOR at Week 6 in FAS population
Evaluate of global clinical response for POS vs VOR at Week 12 in FAS population
Evaluate of all-cause mortality for POS vs. VOR at Week 12 in FAS population
Evaluate the time to global clinical response for POS vs. VOR in the FAS population.
Evaluate the time to death (all causes) for POS vs. VOR in the FAS population.
Evaluate mortality due to IA at Weeks 6 and Week 12 for POS vs. VOR in the FAS population.
Evaluate the all-cause mortality and global clinical response at Weeks 6 and 12 in subjects with a diagnosis of possible, probable, or proven IA receiving POS vs. VOR (Intention to Treat [ITT] population).
Evaluate the safety and tolerability of POS and VOR by analyzing Tier 1 Safety events and all adverse events.
Evaluate the safety of POS compared to VOR therapy in the All-Patients-as-Treated (APaT) population.
Evaluate the pharmacokinetic profile of POS and VOR, and the exposure-response (efficacy and safety endpoints) relationships of POS and VOR in a subset of subjects.

Evaluar la mortalidad global con POS en comparación con VOR en la semana 6 en la población GAC.
Evaluar la respuesta clínica global con POS en comparación con VOR en la semana 12 en la población GAC.
Evaluar la mortalidad global con POS en comparación con VOR en la semana 12 en la población GAC.
Evaluar el tiempo transcurrido hasta la respuesta clínica global con POS en comparación con VOR en la población GAC.

Evaluar el tiempo transcurrido hasta la muerte (por todas las causas) con POS en comparación con VOR en la población GAC.

Evaluar la mortalidad por AI en las semanas 6 y 12 con POS en comparación con VOR en la población GAC.
Evaluar la mortalidad global y respuesta clínica global en las semanas 6 y 12 en los sujetos con un diagnóstico de AI posible, probable o comprobada tratados con
POS en comparación con VOR en la población IT.

Evaluar la seguridad y la tolerabilidad de POS y VOR mediante un análisis de los acontecimientos de seguridad de nivel 1 y todos los acontecimientos adversos.
Evaluar la seguridad de POS en comparación con VOR en la población de todos los pacientes según el tratamiento recibido (TPsT).
Evaluar el perfil farmacocinético de POS y VOR y las relaciones exposición-respuesta (criterios de valoración de la eficacia y seguridad) de POS y VOR.

E.5.2.1

Timepoint(s) of evaluation of this end point

Week 6 and Week 12 of therapy, end of study

Semana 6 y semana 12 de tratamiento, fin de estudio.

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

Yes

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

Yes

E.6.11

Pharmacogenomic

Yes

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

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

Yes

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

Yes

E.8.5.1

Number of sites anticipated in the EEA

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

Argentina

Belgium

Brazil

Canada

Chile

China

Colombia

Estonia

France

Germany

Greece

Guatemala

India

Ireland

Israel

Italy

Korea, Republic of

Lithuania

Malaysia

Mexico

Peru

Poland

Portugal

Russian Federation

Singapore

Spain

Switzerland

Taiwan

Turkey

United Kingdom

United States

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

LVLS

LPLV

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

Yes

F.1.1

Number of subjects for this age range:

200

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)

Yes

F.1.1.6.1

Number of subjects for this age range:

200

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

200

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

200

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

F.3.3.2

Women of child-bearing potential using contraception

Yes

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

500

F.4.2.2

In the whole clinical trial

600

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)

Subjects who require additional therapy following completion of the study will receive standard of care treatment at local clinic.

Los pacientes que requieran tratamiento adicional tras completar el ensayo clinico recibirán su tratamiento habitual.

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

2013-04-09

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2013-03-13

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2019-09-10

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