Clinical Trials Register

Summary
EudraCT Number:	2013-000161-36
Sponsor's Protocol Code Number:	P05267(MK-5592-055)
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:	2013-06-10
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

2013-000161-36

A.3

Full title of the trial

Phase 2 Proof-of-Activity Study of Oral Posaconazole in the Treatment of Asymptomatic Chronic Chagas Disease (Phase 2, Protocol No. P05267)

Estudio de fase 2 demostrativo preliminar de la actividad de posaconazol oral en el tratamiento de la enfermedad de Chagas crónica asintomática (fase 2, protocolo Nº P05267)

A.3.1

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

Phase 2 Study of Posaconazole in Chagas Disease

Estudio Fase 2 de Posaconazol en la Enfermedad de Chagas

A.3.2

Name or abbreviated title of the trial where available

Phase 2 Study of Posaconazole in Chagas Disease

Estudio Fase 2 de Posaconazol en la Enfermedad de Chagas

A.4.1

Sponsor's protocol code number

P05267(MK-5592-055)

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	2015 Galloping Hill Road
B.5.3.2	Town/ city	Kenilworth, NJ
B.5.3.3	Post code	07033
B.5.3.4	Country	United States
B.5.4	Telephone number	908740-2364
B.5.5	Fax number	908740-4060
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	Yes
D.2.1.1.1	Trade name	Noxafil
D.2.1.1.2	Name of the Marketing Authorisation holder	Merck Sharp & Dohme Ltd.
D.2.1.2	Country which granted the Marketing Authorisation	United Kingdom
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	Noxafil
D.3.2	Product code	Noxafil
D.3.4	Pharmaceutical form	Oral suspension
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	posaconazole
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	40
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	LAFEPE BENZNIDAZOLE
D.2.1.1.2	Name of the Marketing Authorisation holder	LAFEPE
D.2.1.2	Country which granted the Marketing Authorisation	Brazil
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	LAFEPE BENZNIDAZOLE
D.3.2	Product code	LAFEPE BENZNIDAZOLE
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	BENZNIDAZOLE
D.3.9.1	CAS number	22994-85-0
D.3.9.4	EV Substance Code	SUB05753MIG
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	Oral solution
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

Chronic Chagas Disease

Enfermedad de Chagas crónica

E.1.1.1

Medical condition in easily understood language

Chagas Disease

Enfermedad de Chagas

E.1.1.2

Therapeutic area

Diseases [C] - Parasitic Diseases [C03]

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	10066500
E.1.2	Term	Chagas disease recurrent
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

Primary objective is to evaluate efficacy of Posaconazole versus placebo in reducing parasitemia measured by qualitative PCR at end of 120 days of follow-up post treatment..

Evaluar la eficacia de posaconazol (POS) en comparación con placebo para la reducción de la parasitemia, determinada mediante reacción en cadena de la polimerasa (PCR) cualitativa, al término de 120 días de seguimiento posterior al tratamiento.

E.2.2

Secondary objectives of the trial

Secondary objectives include evaluation of safety and tolerability of posaconazole versus placebo, evaluation of relative efficacy and safety of posaconazole versus benznidazole, and evaluation of relative efficacy and safety of benznidazole versus placebo

Los objetivos secundarios incluyen: Evaluar la seguridad y la tolerabilidad de POS en comparación con placebo, evaluar la eficacia y la seguridad relativas de POS en comparación con benznidazol (BNZ) y evaluar la eficacia y la seguridad relativas de BNZ en comparación con placebo.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Each subject must be 18 to < or = to 50 years of age, of either sex and of any race, weighting > or = to 60 kg, and willing to adhere to visit schedule and study procedures.
2. Each subject must have a positive serology result for T. cruzi on any 2 of 3 of the following tests: IFA, IHA, or ELISA (testing results within the past 10 years).
3. Each subject must have a positive qualitative PCR for T. cruzi.
4. Each subject must have a normal 12-lead ECG, or it must be clinically insignificant.
5. Each subject must have a normal 2-D echocardiogram, or it must be clinically insignificant.
6. Each subject must have no evidence of ventricular tachycardia on a 24-hr Holter monitoring.

1.Los sujetos deben tener entre 18 y 50 años de edad, ser de cualquier sexo y de cualquier raza, pesar igual o más de 60 kg y estar dispuestos a cumplir con el calendario de visitas y los procedimientos del estudio.
2.Los sujetos deben presentar un resultado serológico positivo para T. cruzi en dos de tres de los siguientes análisis: inmunofluorescencia indirecta, hemoaglutinación indirecta o enzimoinmunoanálisis de adsorción (ELISA) (resultados de análisis obtenidos en los últimos 10 años provenientes de la historia clínica, del médico remitente o del centro de selección.)
3.Los sujetos deben presentar una PCR cualitativa positiva para T. cruzi.
4.Los sujetos deben tener un electrocardiograma (ECG) de 12 derivaciones normal o, si no es normal, las alteraciones halladas no deben tener importancia clínica.
5.Los sujetos deben tener un ecocardiograma bidimensional normal o, si no es normal, las alteraciones halladas no deben tener importancia clínica.
6.Los sujetos no deben presentar signos de taquicardia ventricular en el registro Holter de 24 horas.

E.4

Principal exclusion criteria

1. Subject must not weigh less than 60 kg.
2. Female subjects must not be breastfeeding, pregnant, or planning pregnancy.
3. Subjects must not be immunodeficient or immunosuppressed.
4. Subjects must not have a history of megacolon with obstipation or megaesophagus with severe swallowing impairment.
5. Subjects must not have previously received benznidazole or nifurtimox.
6. Subjects must not be a family member of a participating subject, or reside in the same household as a participating subject.
7. Subjects must not have AST or ALT levels greater than 2.5 times ULN at screening.
8. Subjects must not have serum creatinine >2.5 mg/dL or 200 micromoles at screening.
9. Subjects must not have a history of severe alcohol abuse within 2 years from screening.
10. Subjects must not be taking any prohibited medications.

1.Sujetos que pesen < 60 kg.
2.Mujeres en edad fértil que se encuentren amamantando, que estén embarazadas o que tengan la intención de quedarse embarazadas
3.Sujetos con inmunodeficiencia o en tratamiento con inmunodepresores.
4.Sujetos con antecedentes de megacolon con estreñimiento o megaesófago con deterioro intenso de la deglución.
5.Sujetos que hayan sido previamente tratados con BNZ o nifurtimox.
6.Sujetos que sean familiares de un sujeto que ya esté participando en este estudio o que vivan en el mismo hogar que un sujeto que ya esté participando en este estudio.
7.Sujetos con valores de aspartato-aminotransferasa (AST) o alanina-aminotransferasa (ALT) superiores a 2,5 veces el límite superior de la normalidad en la selección.
8.Sujetos con creatinina sérica > 2,5 mg/dl o 200 micromoles en la selección
9.Sujetos con antecedentes de alcoholismo intenso en los dos años anteriores a la selección.
10.Sujetos que tomen cualquiera de los medicamentos prohibidos durante el estudio.

E.5 End points

E.5.1

Primary end point(s)

The primary efficacy endpoint is the proportion of subjects who show a successful response for the posaconazole versus placebo comparison. A successful response is defined as both a negative qualitative PCR on Day 180, and a negative qualitative PCR on at least the two preceding samples.

El criterio principal de valoración de la eficacia para este estudio es la proporción de sujetos que presenten una respuesta satisfactoria en la comparación de POS con placebo. Se define como respuesta satisfactoria la conjunción de una PCR cualitativa negativa el día 180 o por lo menos las dos muestras precedentes

E.5.1.1

Timepoint(s) of evaluation of this end point

Day 180 (or Day 150 if Day 180 is missing) and Day 120 and 150 (or Day 90 and 120 if Day 180 is missing).

Día 180 (o día 150 si el día 180 falta) y día 120 y 150 ( o día 90 y 120 si el día 180 falta)

E.5.2

Secondary end point(s)

The secondary efficacy endpoints are the proportion of subjects who show a successful response for the other possible pairwise comparisons with the trial (i.e., posaconazole versus benznidazole, benznidazole versus placebo, posaconazole + benznidazole versus posaconazole, versus benznidazole, versus placebo) and the proportion of subjects with negative qualitative PCR at each individual evaluation during the study.

Los criterios secundarios de valoración de la eficacia son la proporción de sujetos que presenten una respuesta satisfactoria (como se la definió precedentemente) para las otras comparaciones por pares posibles en este estudio (es decir, POS en comparación con BNZ; BNZ en comparación con placebo y POS + BNZ en comparación con POS, en comparación con BNZ y en comparación con placebo) y la proporción de sujetos con PCR cualitativa negativa en cada una de las evaluaciones individuales realizadas durante el estudio

E.5.2.1

Timepoint(s) of evaluation of this end point

Day 30, 60, 90, 120, 150, 180, and 360

Días 30, 60, 90, 120, 150, 180 y 360

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

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)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

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

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

Yes

E.8.1.7.1

Other trial design description

Simple ciego para Posaconazol, abierto para Benznidazol.

Single blind for Posaconazole, Open for Benznidazole

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

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

Chile

Colombia

Guatemala

Mexico

Peru

Spain

Venezuela, Bolivarian Republic of

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

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:

160

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

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

F.4.2.2

In the whole clinical trial

160

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

2013-07-17

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2013-04-05

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2015-01-12

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