Clinical Trials Register

Summary
EudraCT Number:	2018-002315-98
Sponsor's Protocol Code Number:	MedicalcannabisMSSCI2018
National Competent Authority:	Denmark - DHMA
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2018-07-09
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

Denmark - DHMA

A.2

EudraCT number

2018-002315-98

A.3

Full title of the trial

The effect of medical cannabis on neuropathic pain and spasticity in patients with Multiple Sclerosis and in patients with spinal cord injury. A multicenter national placebo-controlled trial

Effekten af medicinsk cannabis på neuropatiske smerter og spasticitet hos patienter med MS og patienter med rygmarvsskade. Et multicenter nationalt placebo-kontrolleret studium

A.3.1

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

The effect of cannabis products on nerve pain and muscle stiffness in patients with multiple sclerosis and in patients with spinal cord injury.

Effekten af medicin indeholdende cannabis produkter på nervesmerter og muskelstivhed hos patienter med multiple sklerose og hos patienter med rygmarvsskade.

A.3.2

Name or abbreviated title of the trial where available

The effect of medical cannabis on neuropathic pain and spasticity in patients with MS and SCI

Effekten af medicinsk cannabis på neuropatiske smerter og spasticitet hos patienter med MS og SCI

A.4.1

Sponsor's protocol code number

MedicalcannabisMSSCI2018

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	Aarhus Universitetshospital
B.1.3.4	Country	Denmark
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	Ministry of Health
B.4.2	Country	Denmark
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Aarhus Universitetshospital
B.5.2	Functional name of contact point	Neurologi
B.5.3	Address:
B.5.3.1	Street Address	Palle Juul-Jensens Boulevard 165
B.5.3.2	Town/ city	Aarhus N
B.5.3.3	Post code	8200
B.5.3.4	Country	Denmark
B.5.4	Telephone number	457845 4222
B.5.6	E-mail	krissven@rm.dk

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	Cannabidiol capsule 5 mg
D.3.2	Product code	N/A
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	Cannabidiol
D.3.9.1	CAS number	13956-29-1
D.3.9.3	Other descriptive name	CBD
D.3.9.4	EV Substance Code	SUB26600
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	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.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	Dronabinol capsule 2,5 mg
D.3.2	Product code	N/A
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	DRONABINOL
D.3.9.1	CAS number	1972-08-3
D.3.9.3	Other descriptive name	THC
D.3.9.4	EV Substance Code	SUB06407MIG
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	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.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	Cannabidiol / Dronabinol capsule 5 mg+2,5 mg
D.3.2	Product code	N/A
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	DRONABINOL
D.3.9.1	CAS number	1972-08-3
D.3.9.3	Other descriptive name	THC
D.3.9.4	EV Substance Code	SUB06407MIG
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	2.5
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	CBD
D.3.9.4	EV Substance Code	SUB26600
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	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
D.8 Placebo: 1
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

Central neuropathic pain and spasticity

Centrale smerter og spasticitet

E.1.1.1

Medical condition in easily understood language

Nerve pain and muscle stiffness related to a lesion in the central nervous system

Nervesmerter og muskelstivhed relateret til læsion i centralnervesystemet

E.1.1.2

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

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	10028335
E.1.2	Term	Muscle spasticity
E.1.2	System Organ Class	10029205 - Nervous system disorders

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	LLT
E.1.2	Classification code	10077975
E.1.2	Term	Central neuropathic pain
E.1.2	System Organ Class	10029205 - Nervous system 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

To evaluate the efficacy of the cannabinoids THC, CBD and a combination of CBD/THC on central neuropathic pain and spasticity in patients with multiple sclerosis and in patients with spinal cord injury

At undersøge effekten af medicinsk cannabis på neuropatiske smerter og spasticitet hos hhv. patienter med MS og patienter med rygmarvsskade. Vi ønsker desuden at undersøge forskelle i effekten af THC, CBD og kombinationen af CBD og THC.

E.2.2

Secondary objectives of the trial

To evaluate the efficacy of the cannabinoids THC, CBD and a combination of CBD/THC on the quality of life, cognition, stress, sleep, ataxia, and to explore the side effects.
We also want to study the Pharmacodynamic and pharmacokinetic of the study medications.

Som sekundære effektparametre ønsker vi at undersøge effekten på livskvalitet, kognitive funktioner, stress, søvn, ataxi (ved MS) og bivirkninger ved de enkelte præparater.
Vi ønsker også at undersøge farmakodynamik og farmakokinetik mhp. at opnå mere viden om blodkoncentration (terapeutisk niveau), virkningsvarighed og udskillelse ved specifik dosis.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1) Probable or definite neuropathic pain in more than three months with a mean baseline pain intensity NRS >3 and < 9 and/or spasticity severity NRS > 3.
2) Stable disease (MS and SCI)
3) Age ≥ 18 years
4) Written Informed consent
5) Reliable contraception for fertile women

1) Sikker eller sandsynlig neuropatisk smerte i mere end 3 mdr. med en gennemsnitlig smerteintensitet i baselineperiode NRS >3 og NRS ≤ 9 og/eller sværhedsgrad af spasticitet (NRS >3)
2) Stabil grundsygdom (for MS-patienterne betyder det, at der ikke har været attak indenfor den seneste måneder og at der ikke har været skift i forebyggende behandling de foregående 3 måneder)
3) Alder ≥ 18 år
4) Informeret samtykke foreligger
5) Fertile kvinder skal være i pålidelig antikonception iht LMS retningslinjer og der skal foreligge negativ graviditetstest

E.4

Principal exclusion criteria

1) Other pain conditions (e.g. diabetic neuropathy), which cannot be distinguished from central pain in MS and/or SCI
2) Current treatment with opioids
3) Severe Psychiatric disorder in patient or biological family (except well-treated depression)
4) History of suicidal
5) Pregnant or lactating women
6) Significant impairment of liver or kidney.
7) History of severe cardiovascular disease
8) History of seizures or epilepsy
9) Active Cancer disease
10) Abuse of cannabinoids, alcohol or medication.
11) There should not be use of cannabinoids 3 months before the study or during the study.

1) Konkurrerende smertesygdomme (som diabetisk neuropati), som ikke kan skelnes fra patientens smerte pga. rygmarvsskade eller MS
2) Opioid behandling (der ikke kan udtrappes)
3) Tidligere eller nuværende psykiatrisk sygdom hos patient eller nærmeste biologiske familie, fraset velbehandlet depression
4) Tidligere selvmordstruet
5) Graviditet og amning
6) Lever- og/eller nyreinsufficiens.
7) Kardio-vaskulær sygdom (fraset velbehandlet hypertension)
8) Tidligere krampeanfald, epilepsi
9) Aktiv kræftsygdom
10) Tidligere eller aktuel alkohol/medicin/stofmisbruger eller positiv urin screening
11) Aktuel rekreativt cannabis brug eller brug indenfor 3 måneder
12) Medicinsk cannabis ordineret indenfor 3 måneder

E.5 End points

E.5.1

Primary end point(s)

1) Mean pain intensity during the last week of active treatment compared with baseline (Diary, Numeric Rating Scale (NRS)).
2) Mean severity of spasticity during the last week of active treatment compared with baseline (Diary, NRS 0-10).

1) Smerteintensitet (neuropatisk smerte), gennemsnit af smertescoring i dagbog under de sidste 7 dages aktiv behandling (uge 6) sammenlignet med 7 dages baseline periode (NRS 0 -10)
2) Grad af spasticitet, gennemsnit af scoring i dagbog under de sidste 7 dages aktiv behandling sammenlignet med den7 dages baselineperiode (NRS 0 -10).

E.5.1.1

Timepoint(s) of evaluation of this end point

Mean pain intensity and mean spasticity score are evaluated during the last week of treatment (week 6) (from the patient diary).

Primære effektparametre vurderes gennem den sidste behandlingsuge (uge 6) (fra patient dagbog)

E.5.2

Secondary end point(s)

1) Patient Global Impression of Change (PGIC)
2) Quality of life (EQ-5D)
3) Farmakodynamic /kinetic: Cmax, Cmin, Cave, AUC0-24, Tmax, Tmin

1) Patient Global Impression of Change” (PGIC, 7-punkts skala fra meget forværret til meget forbedret)
2) Livskvalitet (EQ-5D)
3) Farmakodynamik /kinetik: De farmakokinetiske parametre: Cmax, Cmin, Cave, AUC0-24, Tmax, Tmin

E.5.2.1

Timepoint(s) of evaluation of this end point

PGIC and EQ-5D: At last visit (visit 4) in the last week in stable treatment (week 6)

Farmacodynamic/kinetic are evaluated in 24 hours in the stable period of treatment (week 3-6)

PGIC and EQ-5D: Ved sidste besøg (visit 4) i sidste uge på stabil behandling (uge 6)

Farmakodynamik/kintetik undersøges over 1 dgn i de 3 uger, hvor patienten er i stabil behandling (uge 3-6)

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

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

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)

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

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

End of Trial is when follow-up call to the last included subject has been completed

Studiet anses som afsluttet, når der er foretaget telefonisk follow-up af den sidste patient

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

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:

368

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

448

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

Ingen

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

2018-12-06

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2018-10-25

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2022-03-01

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