Clinical Trials Register

Summary
EudraCT Number:	2015-004152-22
Sponsor's Protocol Code Number:	DEX-TRA-06
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:	2016-02-03
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

2015-004152-22

A.3

Full title of the trial

Analgesic efficacy of oral dexketoprofen trometamol/tramadol hydrochloride versus tramadol hydrochloride/paracetamol: a randomised, double-blind, placebo and active controlled, parallel group study in moderate to severe acute pain after removal of impacted lower third molar.

Eficacia analgésica de dexketoprofeno trometamol/hidrocloruro de tramadol frente a hidrocloruro de tramadol/paracetamol por vía oral: estudio aleatorizado, doble ciego, controlado con placebo y con comparador activo, de grupos paralelos, en el dolor agudo de moderado a intenso tras la extracción de tercer molar inferior impactado.

A.3.1

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

Comparison of dexketoprofen trometamol/tramadol hydrochloride with tramadol hydrochloride/paracetamol for relief of post-operative pain after dental surgery.

Comparación de dexketoprofeno trometamol/hidrocloruro de tramadol frente a hidrocloruro de tramadol/paracetamol para el alivio de dolor post-operatorio después de la cirugía.

A.4.1

Sponsor's protocol code number

DEX-TRA-06

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	MENARINI RICERCHE S.p.A
B.1.3.4	Country	Italy
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	MENARINI RICERCHE S.p.A
B.4.2	Country	Italy
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Menarini Ricerche S.p.A.
B.5.2	Functional name of contact point	Cl. Research Corporate Director
B.5.3	Address:
B.5.3.1	Street Address	Via Sette Santi 1
B.5.3.2	Town/ city	Florence
B.5.3.3	Post code	50131
B.5.3.4	Country	Italy
B.5.4	Telephone number	+34934633266
B.5.5	Fax number	+390555680 597
B.5.6	E-mail	ACapriati@menarini-ricerche.it

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	DEXKETOPROFEN TROMETAMOL - TRAMADOL HYDROCHLORIDE
D.3.2	Product code	DKP.TRIS/TRAM.HCl
D.3.4	Pharmaceutical form	Film-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	DEXKETOPROFEN
D.3.9.1	CAS number	156604-79-4
D.3.9.3	Other descriptive name	Dexketoprofen trometamol
D.3.9.4	EV Substance Code	SUB01630MIG
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	25
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Tramadol hydrochloride
D.3.9.1	CAS number	36282-47-0
D.3.9.3	Other descriptive name	TRAMADOL HYDROCHLORIDE
D.3.9.4	EV Substance Code	SUB04927MIG
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	75
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	Zaldiar®
D.2.1.1.2	Name of the Marketing Authorisation holder	Grünenthal GmbH
D.2.1.2	Country which granted the Marketing Authorisation	European Union
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	TRAMADOL HYDROCHLORIDE/PARACETAMOL
D.3.2	Product code	TRAM.HCl/paracetamol
D.3.4	Pharmaceutical form	Film-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	TRAMADOL HYDROCHLORIDE
D.3.9.1	CAS number	36282-47-0
D.3.9.3	Other descriptive name	TRAMADOL HYDROCHLORIDE
D.3.9.4	EV Substance Code	SUB04927MIG
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	37.5
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	PARACETAMOL
D.3.9.1	CAS number	8055-08-1
D.3.9.3	Other descriptive name	PARACETAMOL
D.3.9.4	EV Substance Code	SUB09611MIG
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	325
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	Film-coated 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	Film-coated tablet
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

Moderate to severe acute pain after removal of impacted lower third molar

Dolor de moderado a agudo tras la extracción del tercer molar inferior impactado

E.1.1.1

Medical condition in easily understood language

Moderate to severe pain after tooth removal

Dolor de moderado a severo tras la extracción de un diente.

E.1.1.2

Therapeutic area

Diseases [C] - Mouth and tooth diseases [C07]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	18.1
E.1.2	Level	LLT
E.1.2	Classification code	10066714
E.1.2	Term	Acute pain
E.1.2	System Organ Class	100000004867

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 comparability of DKP.TRIS/TRAM.HCl and TRAM.HCl/paracetamol in terms of analgesic efficacy on moderate to severe pain following impacted lower third molar extraction.

Evaluar la comparabilidad de DKP.TRIS/TRAM.HCl y TRAM.HCl/paracetamol en términos de eficacia analgésica en el dolor de moderado a intenso tras la extracción de tercer molar inferior impactado.

E.2.2

Secondary objectives of the trial

To confirm the safety and tolerability profile of DKP.TRIS/TRAM.HCl following single dose administration.

Confirmar el perfil de seguridad y tolerabilidad de DKP.TRIS/TRAM.HCl tras la administración de una sola dosis.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Properly executed written informed consent.
2. Male or female patients aged more than 18 years.
3. Scheduled for outpatient surgical extraction -under local anaesthesia (i.e. 2% lidocaine with 1:80,000 epinephrine) - of lower third molar teeth, with at least one of which fully or partially impacted in the mandible requiring bone manipulation (e.g. level B or C plus class II or III of the Pell-Gregory scale).
4. Females participating in the study must be either:
- Females of non-childbearing potential, defined as any woman
who had undergone surgical sterilization or is more than 2 years post-menopausal;
- Females of childbearing potential provided that they have a negative pregnancy test at baseline (screening and qualification period) and are routinely using an effective method of birth control resulting in a low failure rate (i.e. hormonal
contraception, intrauterine device, condoms in combination with a spermicidal cream, male partner sterilization ?vasectomy? or total sexual abstinence).
5. Mentally competent, able to understand and give written informed
consent prior to study entry.
6. Compliant to undergo all visits and procedures scheduled in the study, including recording of pain assessments on the electronic diary (e-Diary) as required by protocol. After surgery, patients will be eligible to progress with randomisation
ONLY if the following criterion is also met:
7. Pain of at least moderate intensity in the first 4 hours after the end of surgery (NRS score >= 4).

1.Consentimiento informado por escrito correctamente cumplimentado.
2.Pacientes masculinos o femeninos mayores de 18 años.
3.Tener programada una extracción quirúrgica ambulatoria, bajo anestesia local (es decir, 2 % de lidocaína con 1:80.000 de epinefrina), de tercer molar inferior, estando al menos uno de ellos impactado total o parcialmente en la mandíbula, haciendo necesaria una manipulación ósea (p. ej. nivel B o C más clase II o III de la escala de Pell-Gregory).
4.Las mujeres que participen en el estudio deben cumplir una de estas dos condiciones:
-Mujeres sin posibilidad de quedarse embarazadas, definidas como cualquier mujer que se haya sometido a una esterilización quirúrgica o que lleve más de dos años en estado postmenopáusico.
-Mujeres con posibilidad de quedarse embarazadas, siempre que tengan una prueba de embarazo negativa al inicio del estudio (período de selección y cualificación) y utilicen de forma habitual un método anticonceptivo con un índice de fallo bajo (es decir, anticoncepción hormonal, dispositivo intrauterino, preservativos en combinación con crema espermicida, esterilización del compañero varón [vasectomía] o abstinencia sexual total).
5.En plena posesión de sus facultades mentales, con capacidad para comprender y otorgar su consentimiento informado por escrito antes del reclutamiento en el estudio.
6.Con disposición para someterse a todas las visitas y los procedimientos programados en el estudio, incluido el registro de exploraciones del dolor en el diario electrónico (Diario-e) tal como exige el protocolo.
Después de la cirugía, los pacientes serán considerados aptos para pasar a la aleatorización SOLO si se cumple también el criterio siguiente:
7.Dolor de intensidad al menos moderada en las 4 horas siguientes a la finalización de la cirugía (puntuación NRS > 4).

E.4

Principal exclusion criteria

1. Patients who are judged by the Investigator not to be suitable candidates for the study treatments and the RM based on their medical history, physical examination, concomitant medication (CM) and concurrent systemic diseases.
2. Clinically significant abnormalities in the vital signs (VS) and / or safety laboratory tests, as per investigator?s judgement.
3. History of allergy or hypersensitivity to the study treatments, RM or to any other NSAIDs, opioids and acetyl salicylic acid.
4. History of peptic ulcer, gastrointestinal disorders by NSAIDs or gastrointestinal bleeding or other active bleedings.
5. History of severe asthma.
6. Moderate to severe renal dysfunction, severe hepatic dysfunction or severe cardiac dysfunction.
7. Coagulation disorders.
8. History of, or current epilepsy.
9. Patients with Crohn?s disease or ulcerative colitis.
10. Patients using and not suitable for withdrawing analgesics within 12 hours before surgery (5 days prior to the surgery day in case of COX-2 inhibitors) and for 8 hours post-dose [analgesics other than those specified in the protocol (namely study treatments and RM)].
11. Patients using and not suitable for withdrawing alcohol, sedatives (e.g. benzodiazepines) and hypnotic agents within 12 hours before surgery and for 8 hours post-dose.
12. Chronic opioid treatment (major opioids and tramadol).
13. Patients using and not suitable for withdrawing the following prohibited medications, within 48 hours or 5 half-lives (whichever the longer) prior to the start of surgery and for 24 hours post-dose:
- Anticoagulants, thrombolytic and antiplatelet agents
- Corticosteroids (with the exception of inhalers or topical agents);
- Monoamine oxidase (MAO) inhibitors (a minimum of 14 days must elapse prior to the start of surgery);
- Antiepileptics;
- Antipsychotics;
- Serotonin reuptake inhibitors and tricyclic antidepressants;
- Lithium;
- Methotrexate;
- Antibacterial sulfonamides.
14. Participation in other clinical studies in the previous 4 weeks.
15. History of drug or alcohol abuse. For the purpose of the study, alcohol abuse is defined as regularly intake of more than 4 units of alcohol per day (1 unit corresponds approximately to 125 ml wine, 200 ml beer, 25 ml spirit).
16. History of any illness or condition that, in the opinion of the Investigator might pose a risk to the patient or confound the efficacy and safety results of the study.
17. Pregnant and breastfeeding women. NOTE: a pregnancy test will be performed to all women of childbearing potential at Screening and another one on the day of surgery prior to randomisation.
After surgery, patients will not be eligible to progress with randomisation if the following criterion is also met:
18. Surgical complication that, in the opinion of the Investigator, advises against their inclusion in the study.

1.Pacientes que a criterio del investigador no son candidatos adecuados para los tratamientos del estudio y la MR basándose en su historia clínica, exploración física, medicamentos concomitantes (MC) y enfermedades sistémicas simultáneas.
2.Anomalías clínicamente significativas en las constantes vitales (CV) y/o pruebas de laboratorio de seguridad, a criterio del investigador.
3.Antecedentes de alergia o hipersensibilidad a los tratamientos del estudio, la MR o cualquier otro fármaco antiinflamatorio no esteroideo (AINE), opioide o ácido acetil salicílico.
4.Antecedentes de úlcera péptica, trastorno gastrointestinal causado por AINE o sangrado gastrointestinal u otros sangrados activos.
5.Antecedentes de episodios de asma graves.
6.Disfunción renal de moderada a grave, disfunción hepática grave o disfunción cardíaca grave.
7.Trastornos de la coagulación.
8.Epilepsia pasada o actual.
9.Pacientes con enfermedad de Crohn o colitis ulcerosa.
10.Pacientes que toman analgésicos cuya retirada no se considera adecuada durante las 12 horas anteriores a la cirugía (5 días anteriores al día de la cirugía en el caso de inhibidores de la COX 2) y durante el período de 8 horas posterior a la dosis (analgésicos distintos de los especificados en el protocolo [es decir, tratamientos del estudio y MR]).
11.Pacientes que consumen alcohol, sedantes (como benzodiacepinas) y agentes hipnóticos cuya retirada no se considera adecuada durante las 12 horas anteriores a la cirugía y el período de 8 horas posterior a la dosis.
12.Tratamiento crónico con opioides (principales opioides y tramadol).
13.Pacientes que toman las siguientes medicaciones prohibidas cuya retirada no se considera adecuada durante las 48 horas o 5 semividas (lo que dure más) anteriores al inicio de la cirugía y el período de 24 horas posterior a la dosis:
-Agentes anticoagulantes, trombolíticos y antiplaquetarios;
-Corticoesteroides (a excepción de inhaladores o agentes tópicos);
-Inhibidores de la monoamino oxidasa (MAO) (debe transcurrir un mínimo de 14 días antes del inicio de la cirugía);
-Antiepilépticos;
-Antipsicóticos;
-Inhibidores de la recaptación de serotonina y antidepresivos tricíclicos;
-Litio;
-Metotrexato;
-Sulfonamidas antibacterianas.
14.Participación en otros estudios clínicos en las 4 semanas anteriores.
15.Antecedentes de abuso de drogas o alcohol. A efectos del estudio, el abuso de alcohol se define como la ingesta habitual de más de 4 unidades de alcohol al día (1 unidad corresponde aproximadamente a 125 ml de vino, 200 ml de cerveza o 25 ml de licor).
16.Antecedentes de cualquier enfermedad o afección que, en opinión del investigador, pudiera suponer un riesgo para el paciente o confundir los resultados de eficacia y seguridad del estudio.
17.Mujeres embarazadas y en período de lactancia. NOTA: se efectuará una prueba de embarazo a todas las mujeres con capacidad para procrear en la fase de selección y otra el día de la cirugía antes de la aleatorización.
Después de la cirugía, los pacientes no serán considerados aptos para pasar a la aleatorización si se cumple también el criterio siguiente:
18.Complicación quirúrgica que, en opinión del investigador, desaconseja su inclusión en el estudio.

E.5 End points

E.5.1

Primary end point(s)

Total pain relief (TOTPAR), calculated as the weighted sum of the
PAR scores (measured according to a 5-point VRS from 0=no relief to
4=complete relief) over 6 hours post-dose (TOTPAR6)

Alivio del dolor total (TOTPAR), calculado como la suma ponderada de las puntuaciones de PAR (medidas utilizando una VRS de 5 puntos, desde 0 = ningún alivio hasta 4 = alivio completo), durante el período de 6 horas posterior a la dosis (TOTPAR6).

E.5.1.1

Timepoint(s) of evaluation of this end point

Over 6 hours post-dose

6 horas después de la dosis.

E.5.2

Secondary end point(s)

Efficay Endpoints:
- Mean PAR scores over the 8-hour post-dose period.
- TOTPAR over 4 and 8 hours post-dose (TOTPAR4, TOTPAR8).
- Percentage of maximum TOTPAR (% max TOTPAR) over 4, 6 and 8-
hours post-dose.
- Percentage of patients achieving at least 50% of maximum TOTPAR
over 4, 6 and 8 hours post-dose.
- Mean Pain Intensity (PI) scores (values obtained from the 11-point
NRS) at each pre-specified time point over the 8-hour post-dose period.
- Percentage of patients who achieved at least 30% of PI reduction
versus baseline at each pre-specified time point over the 8-hour postdose
period.
- Sum of Pain Intensity Differences (SPID), calculated as the weighted
sum of the pain intensity difference (PID) over 4, 6 and 8 hours postdose
(SPID4, SPID6, SPID8).
- Percentage of maximum SPID (% max SPID) over 4, 6 and 8 hours
post-dose.
- Time to FPPAR (time to onset of analgesia).
- Time to confirmed FPPAR (time to onset of analgesia) - i.e. time to
FPPAR if confirmed by experiencing MPAR
- Percentage of patients who achieved confirmed FPPAR within 30
minutes, 1 hour and 2 hours.
- Time to MPAR.
- Percentage of patients who achieved MPAR within 30 minutes, 1 hour
and 2 hours.
- PGE of the study medication (measured according to a five-point VRS
from 1 = poor to 5 = excellent), at 8 hours post-dose or whenever the
patient uses RM.
- Time to RM: Time elapsed between treatment administration and first
intake of RM.
- Percentage of patients who required RM within the first 4, 6 or 8
hours post-dose.

Safety endpoints:
a) Incidence, intensity (severity), seriousness and treatment-causality
of treatment-emergent AEs

b)Frequency of clinically significant changes in physical examination,
and VS, post-dose versus baseline.

Criterios de eficacia:
-Puntuaciones de PAR medias durante el período de 8 horas posterior a la dosis.
-TOTPAR durante los períodos de 4 y 8 horas posteriores a la dosis (TOTPAR4, TOTPAR8).
-Porcentaje de TOTPAR máximo (% TOTPAR máx.) durante los períodos de 4, 6 y 8 horas posteriores a la dosis.
-Porcentaje de pacientes que han logrado al menos un 50 % de TOTPAR máximo durante los períodos de 4, 6 y 8 horas posteriores a la dosis.
-Puntuaciones medias de intensidad del dolor (PI) (valores obtenidos con la NRS de 11 puntos) en cada punto temporal especificado previamente durante el período de 8 horas posterior a la dosis.
-Porcentaje de pacientes que han logrado al menos un 30 % de reducción de la PI frente al valor de referencia en cada punto temporal especificado previamente durante el período de 8 horas posterior a la dosis.
-Suma de las diferencias en la intensidad del dolor (SPID), calculada como la suma ponderada de la diferencia en la intensidad del dolor (PID durante los períodos de 4, 6 y 8 horas posteriores a la dosis (SPID4, SPID6, SPID8).
-Porcentaje de SPID máxima (% SPID máx.) durante los períodos de 4, 6 y 8 horas posteriores a la dosis.
-Tiempo transcurrido hasta el FPPAR (tiempo transcurrido hasta el inicio de la analgesia).
-Tiempo transcurrido hasta el FPPAR confirmado (tiempo transcurrido hasta el inicio de la analgesia); es decir, tiempo transcurrido hasta el FPPAR si se confirma mediante la experimentación de MPAR.
-Porcentaje de pacientes que han logrado un FPPAR confirmado en el plazo de 30 minutos, 1 hora y 2 horas.
-Tiempo transcurrido hasta el MPAR.
-Porcentaje de pacientes que han logrado un MPAR en el plazo de 30 minutos, 1 hora y 2 horas.
-PGE de la medicación del estudio (medida con una VRS de 5 puntos, desde 1 = mala hasta 5 = excelente), a las 8 horas posteriores a la dosis o siempre que el paciente toma MR.
-Tiempo transcurrido hasta la MR: tiempo que transcurre entre la administración del tratamiento y la primera toma de MR.
-Porcentaje de pacientes que han necesitado MR en las primeras 4, 6 u 8 horas posteriores a la dosis.
Criterios de seguridad:
-Incidencia, intensidad (severidad), gravedad y causalidad relacionada con el tratamiento de los AA surgidos durante el tratamiento (TEAE, notificados a partir de la toma de medicación del estudio).
-Frecuencia de cambios clínicamente significativos en la exploración física y la medición de CV posteriores a la dosis frente al valor de referencia.

E.5.2.1

Timepoint(s) of evaluation of this end point

Please refer to Secondary end point section.

Por favor, revisar la sección de criterios de valoración secundarios.

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

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)

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

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

Hungary

Italy

Poland

Spain

Turkey

United Kingdom

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

LPLV

Última visita del último paciente.

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:

630

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

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

162

F.4.2

For a multinational trial

F.4.2.1

In the EEA

625

F.4.2.2

In the whole clinical trial

640

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)

Patients who end their participation in the trial will be treated according to current standard of care.

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

2016-04-12

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2016-04-06

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2017-02-14

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Select Trial Status:	Select Trial Phase:
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Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
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