Clinical Trials Register

Summary
EudraCT Number:	2018-004378-92
Sponsor's Protocol Code Number:	EdomTHC
National Competent Authority:	Spain - AEMPS
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2019-04-11
Trial results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Spain - AEMPS

A.2

EudraCT number

2018-004378-92

A.3

Full title of the trial

Effect of cannabinoids (THC / CBD) on hyperalgesia in patients with deep endometriosis

Efecto de los cannabinoides (THC/CBD) sobre la hiperalgesia en pacientes con endometriosis profunda

A.3.1

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

Study of the effect of cannabis in relieving the symptoms of endometriosis

Estudio del efecto del canabis en el alivio de los síntomas de la endometriosis

A.4.1

Sponsor's protocol code number

EdomTHC

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Fundació Clínic per la Recerca Biomèdica
B.1.3.4	Country	Spain
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Almirall
B.4.2	Country	Spain
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Fundació Clínic per la Recerca Biomèdica
B.5.2	Functional name of contact point	David Garcia
B.5.3	Address:
B.5.3.1	Street Address	c/ Villarroel 170
B.5.3.2	Town/ city	Barcelona
B.5.3.3	Post code	08036
B.5.3.4	Country	Spain
B.5.6	E-mail	dgarcia@clinic.cat

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	Sativex
D.2.1.1.2	Name of the Marketing Authorisation holder	GW Pharma Ltd
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	Sativex
D.3.4	Pharmaceutical form	Oromucosal spray
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Buccal use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	dronabinol
D.3.9.1	CAS number	1972-08-3
D.3.9.3	Other descriptive name	DELTA-9-TETRAHYDROCANNABINOL
D.3.9.4	EV Substance Code	SUB27785
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	2.7
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Cannabidiol
D.3.9.1	CAS number	13956-29-1
D.3.9.3	Other descriptive name	CANNABIDIOL
D.3.9.4	EV Substance Code	SUB26600
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	2.5
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Deep endometriosis

Endometriosis profunda

E.1.1.1

Medical condition in easily understood language

Endometriosis

E.1.1.2

Therapeutic area

Diseases [C] - Female diseases of the urinary and reproductive systems and pregancy complications [C13]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	PT
E.1.2	Classification code	10014778
E.1.2	Term	Endometriosis
E.1.2	System Organ Class	10038604 - Reproductive system and breast disorders

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Demonstrate that cannabinoid treatment decreases hyperalgesia in patients with deep endometriosis

Demostrar que el tratamiento con cannabinoides disminuye la hiperalgesia en pacientes con endometriosis profunda

E.2.2

Secondary objectives of the trial

- Decrease in pain associated with endometriosis
- Objectify anxiety and depression are reduced by sativex
- Demonstrate the increase in the quality of life induced by the cannabinoid
- Assess if sativex improves the cognitive deficit in these patients
- Asses sleep quality

- Disminución del dolor asociado a la endometriosis
- Objetivar la disminución de la ansiedad y depresión inducida por el sativex
- Demostrar el aumento de la calidad de vida inducida por el cannabinoide
- Valorar si el sativex mejora el déficit cognitivo en estas pacientes
- Valorar calidad del sueño

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Patients previously submitted to open abdominal surgery.
2. History of cancer.
3. Suspicion or diagnosis of endocrine, cardio-vascular or systemic pathology relevant.
4. Pregnancy or anticipation of pregnancy up to 3 months after the end of the study.
6. Current breastfeeding.
8. Use of hormonal treatment (combined oral contraception, gestagens in the 3 months prior to the study, GNRH analogs in the 6 months prior to the start of the study).
9. Use of other analgesics different from those allowed in the study.
10. Recreational or pharmacological use of cannabinoids.
11. Hypersensitivity to cannabinoids or any of the exceptions.
12. Known or suspected personal history, or family history of schizophrenia or other psychotic illnesses, severe personality disorder or other major psychiatric disorders.
13. Patients with liver or kidney failure, severe cardiovascular disease and a history of epilepsy or recurrent seizures.
14. Patients who use concomitant potent CYP3A4 enzyme inducers, such as rifampicin, carbamazepine, phenytoin, phenobarbital, and St. John's wort.

1. Mujeres con edad comprendida entre 18 y 40 años.
2. Diagnóstico de endometriosis profunda tras sospecha clínica y confirmación mediante prueba de imagen.
3. Dolor con puntuación de 4 o más en una escala visual numérica de 11 niveles (EVN 0-10) en los últimos 3 meses (incluye cualquier tipo de dolor asociado a endometriosis: dismenorrea, dispareunia, disquecia, disuria y/o dolor pélvico).
4. Las mujeres en edad fértil deben tener una prueba negativa de embarazo antes de la inclusión en el estudio y deben comprometerse a utilizar métodos anticonceptivos altamente eficaces (anticonceptivos hormonales, dispositivo intrauterino, sistemas intrauterino de liberación hormonal, oclusión tubária bilateral, vasectomía de la pareja, métodos de barrera y abstinencia sexual) durante toda la duración del estudio y hasta 3 meses después de la finalización del mismo.
5. Aceptación de la participación en el estudio mediante la firma del consentimiento informado.

E.4

Principal exclusion criteria

1. Women between the ages of 18 and 40.
2. Diagnosis of deep endometriosis after clinical suspicion and confirmation by imaging test.
3. Pain with a score of 4 or more on a numerical visual scale of 11 levels (EVN 0-10) in the last 3 months (includes any type of pain associated with endometriosis: dysmenorrhea, dyspareunia, dyschezia, dysuria and / or pelvic pain ).
4. Women of childbearing age should have a negative pregnancy test before inclusion in the study and should commit to using highly effective contraceptive methods (hormonal contraceptives, intrauterine device, intrauterine hormone-releasing systems, bilateral tubal occlusion, vasectomy of the couple, barrier methods and sexual abstinence) throughout the duration of the study and up to 3 months after the end of it.
5. Acceptance of participation in the study by signing the informed consent.

1. Pacientes sometidas previamente a cirugía abdominal abierta.
2. Antecedente de cáncer.
3. Sospecha o diagnóstico de patología endocrina, cardio-vascular o sistémica relevante.
4. Embarazo o previsión de embarazo hasta 3 meses tras la finalización del estudio.
6. Lactancia materna actual.
8. Uso de tratamiento hormonal (anticoncepción oral combinada, gestágenos en los 3 meses previos al estudio, análogos de la GNRH en los 6 meses previos al inicio del estudio).
9. Uso de otros analgésicos diferentes a los permitidos en el estudio.
10. Uso recreativo o farmacológico de cannabinoides.
11. Hipersensibilidad a los cannabinoides o a alguno de los excepientes.
12. Antecedentes personales conocidos o sospechachados, o antecedentes familiares de esquizofrenia u otras enfermedades psicóticas, trastorno grave de la personalidad u otros trastornos psiquiátricos importantes.
13. .Pacientes con insuficiencia hepática o renal, enfermedad cardiovascular grave y antecedentes de epilepsia o crisis recurrentes.
14. Pacientes que hagan uso concomitante de inductores enzimáticos potentes del CYP3A4, como la rifampicina, carbamazepina, fenitoína, fenobarbital y hierba de San Juan.

E.5 End points

E.5.1

Primary end point(s)

Pain threshold after mechanical stimulation in hypogastrium (anterior central L2 dermatoma).

Umbral de dolor frente a estímulo mecánico en hipogastrio (dermatoma L2 central anterior).

E.5.1.1

Timepoint(s) of evaluation of this end point

15, 30 and 45 days

15, 30 y 45 días

E.5.2

Secondary end point(s)

- Pain threshold after mechanical stimulation in dermatomes L2 anterior, posterior L2, and T1 of the dominant upper extremity.
- Sensory threshold versus after stimulus (cold heat) in anterior central L2 dermatomes, posterior central L2, and T1 of the dominant upper extremity.
- General intensity of pain associated with endometriosis measured by NVA (0-10)
- Anxiety and depression measured with the Scale of Anxiety and Hospital Depression Scale (HADS).
- Quality of Life measured through the EQ-5D-5L questionnaire.
- Central sensitization measured with the CSI questionnaire.
- Cognitive disorder measured by a list of words (immediate memory and retention) and digits (attentional capacity) of the Wechsler Memory Scale (WMS-III).
- EVA 0-10 about sleep quality

- Umbral de dolor frente a estímulo mecánico en dermatomas L2 anterior, L2 posterior, y T1 de la extremidad superior dominante.
- Umbral de sensación frente a estímulo térmico (calor frío) en dermatomas L2 central anterior, L2 central posterior, y T1 de la extremidad superior dominante.
- Intensidad general del dolor asociado a endometriosis medida mediante una EVN (0-10)
- Ansiedad y depresión medidas con el cuestionario Escala de Ansiedad y Depresión Hospitalaria (HADS).
- Calidad de Vida medida mediante el cuestionario EQ-5D-5L.
- Sensibilización central medida con el cuestionario CSI.
- Trastorno cognitivo medido mediante una lista de palabras (memoria inmediata y retención) y dígitos (capacidad atencional) de la Escala de Memoria de Wechsler (WMS-III).
- EVA 0-10 sobre calidad de sueño

E.5.2.1

Timepoint(s) of evaluation of this end point

- 15, 30 and 45 days

- 15, 30 y 45 días

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

E.6.5

Efficacy

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

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

E.8.1.1

Randomised

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

Yes

E.8.4

The trial involves multiple sites in the Member State concerned

E.8.5

The trial involves multiple Member States

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.7

Trial has a data monitoring committee

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

LVLS

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

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:

F.1.3

Elderly (>=65 years)

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

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

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

2019-05-27

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2019-05-22

P. End of Trial
P.	End of Trial Status	Ongoing

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