Clinical Trials Register

Summary
EudraCT Number:	2014-005656-26
Sponsor's Protocol Code Number:	51748.094.15
National Competent Authority:	Netherlands - Competent Authority
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2015-11-19
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

Netherlands - Competent Authority

A.2

EudraCT number

2014-005656-26

A.3

Full title of the trial

Amitriptyline 10% and ketamine 10% cream in neuropathic pain:
A randomised, double-blind, placebo-controlled cross-over pilot study
with a three months open follow-up

Amitriptyline 10% en ketamine 10% crème voor neuropathische pijn:
gerandomiseerde dubbelblinde placebo-gecontroleerde cross-over pilot studie met drie maanden open follow-up

A.3.1

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

Pilot-study with Amitriptyline 10% and Ketamine10% creme in neuropatic pain.

Pilot-study met Amitriptyline 10% en Ketamine 10% creme voor neuropatische pijn

A.3.2

Name or abbreviated title of the trial where available

Randomised study evaluating the treatment neuropatic pain with cream

Gerandomiseerd onderzoek naar de behandeling van neuropatische pijn met cremes

A.4.1

Sponsor's protocol code number

51748.094.15

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	Westfriesgasthuis
B.1.3.4	Country	Netherlands
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	Westfriesgasthuis
B.4.2	Country	Netherlands
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Westfriesgasthuis
B.5.2	Functional name of contact point	phycisian assistant
B.5.3	Address:
B.5.3.1	Street Address	Maelsonstraat 3
B.5.3.2	Town/ city	Hoorn
B.5.3.3	Post code	1624 NP
B.5.3.4	Country	Netherlands
B.5.4	Telephone number	0031229208562
B.5.5	Fax number	0031229257950

D. IMP Identification
D.IMP: 1
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	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	Ketamine
D.3.2	Product code	1867-66-9
D.3.4	Pharmaceutical form	Cream
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Cutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Ketamine.HCl
D.3.9.1	CAS number	1867-66-9
D.3.9.3	Other descriptive name	KETAMINE HYDROCHLORIDE
D.3.9.4	EV Substance Code	SUB02830MIG
D.3.10	Strength
D.3.10.1	Concentration unit	% percent
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	10
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	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	amitriptyline
D.3.2	Product code	549-18-8
D.3.4	Pharmaceutical form	Cream
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Cutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Amitriptyline.HCL
D.3.9.1	CAS number	549-18-8
D.3.9.3	Other descriptive name	AMITRIPTYLINE
D.3.9.4	EV Substance Code	SUB05462MIG
D.3.10	Strength
D.3.10.1	Concentration unit	% percent
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	10
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	Cream
D.8.4	Route of administration of the placebo	Cutaneous use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Patients with peripheral neuropathic pain or scar pain

Patiënten met perifere neuropatische of litteken pijn

E.1.1.1

Medical condition in easily understood language

patients with neuropathic pain syndrome

patiënten met neuropathische pijn syndroom

E.1.1.2

Therapeutic area

Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Anesthesia and Analgesia [E03]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	17.1
E.1.2	Level	PT
E.1.2	Classification code	10049002
E.1.2	Term	Scar pain
E.1.2	System Organ Class	10040785 - Skin and subcutaneous tissue disorders

E.1.2 Medical condition or disease under investigation

E.1.2	Version	17.1
E.1.2	Level	LLT
E.1.2	Classification code	10029181
E.1.2	Term	Nerve pain
E.1.2	System Organ Class	100000004852

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

The purpose of this study is to investigate the effect size in order to perform a power calculation for calculating a sample size for a powered RCT

Het doel van de studie is om de haalbaarheid in te schatten voor een gepowerde dubbelblinde studie en om op basis van de gemiddelde pijnvermindering een powercalculatie te kunnen maken, alsmede tolerantie en veiligheid te testen

E.2.2

Secondary objectives of the trial

none

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

- peripheral neuropatic pain (DOT: 130)
- ≥18 year, competent
- ≥5 en <10 on the numeric rating scale
- max. 10% total body surface
- in %, 1 sole: 1¾, , 1 feet: 3½, 2 feet: 7, both legs to quarter onderlegs 10, 1 hand: 3)

•perifere zenuwpijn (DOT: 130)
•≥18 jaar
•≥5 en <10 op de NRS
•max. 10% van de huidoppervlakte
(in %, 1 voetzool: 1¾, 1 voet: 3½, 2 voeten: 7, beide benen tot kwart onderbenen 10, 1 hand: 3)

E.4

Principal exclusion criteria

- pregnancy of planned pregnancy during studiyperiod
- open wounds at the same spot of the neuropatic pain
- current use of topic analgetic
- presence of other pains yndromes, such as the wide spread pain syndrome
- presence of serious psychological or psychiatric morbidity
- addiction to intoxicants
- insuffient control of the Dutch language
- hypersensitivity of the medication
- use of ketamine and amitriptyline

•Zwangerschap of geplande zwangerschap in de studieperiode
•Open wonden op de plaats van de neuropathische pijn
•Huidig gebruik van topicale analgetica
•Aanwezigheid van andere pijnsyndromen zoals het wijdverspreid pijnsyndroom
•Aanwezigheid van ernstige psychologische/psychiatrische morbiditeit
•Verslaving aan bedwelmende middelen
•Onvoldoende beheersing van de Nederlandse taal
•overgevoeligheid voor de medicatie
- gebruik van ketamine en amitriptyline

E.5 End points

E.5.1

Primary end point(s)

Difference between active and placebo cream pain score on Numeric Rating Scale

Verschil pijnscore op NRS tussen actieve crème en placebo

E.5.1.1

Timepoint(s) of evaluation of this end point

End of studyperiod

Aan het eind van het onderzoek

E.5.2

Secondary end point(s)

Feasibility of a randomised, doubleblind, placebo-controlled, cross-over study with the folowing questions: effectiveness on the other ratingscales (for example the NRS, BPI sleepingscale), percentage patients responding and will be included after the testing phase; comprehensibility and completeness of questionnaires, percentage drop-outs, side effects, logistics and randomization process, tolerance and safety of the creams

Haalbaarheid van een gerandomiseerde dubbelblinde placebo-gecontroleerde cross-over studie met de volgende vragen: effectiviteit op andere diverse meetschalen (bijvoorbeeld de NRS, BPI slaapschaal), percentage patiënten die responderen en die geïncludeerd worden na de testfase, begrijpelijkheid en volledigheid van vragenlijsten, percentage drop-outs, bijwerkingen, logistiek en randomisatieproces, tolerantie en veiligheid van de crèmes.

E.5.2.1

Timepoint(s) of evaluation of this end point

at the end of the study

aan het eind van het onderzoek

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)

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

Yes

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

In 15 weeks time, the patients will visit the clinic for outpatients four times. At the last visit the patient will be asked if the patient would like to participate in the follow up of 3 months. After these 3 months the patient will visit de clinic for outpatients for the fourth time. This is the last visit for the patient. For that patient the study is ended. If the patient is responding on the treatment, the treatment with either ketamine 10% or amitriptyline 10% cream will be continued.

Elke patiënt komt in 15 weken 4 keer op de polikliniek. Als ze voor de laatste keer op de polikliniek komen worden ze gevraagd om mee te doen aan de follow up van 3 maanden. Na deze 3 maanden komt de patiënt voor de vierde en laatste keer op de polikliniek. Op dat moment is de studie afgelopen. Als de behandeling bij een patiënt aanslaat kan deze wel doorbehandeld worden met de ketamine 10% of amitriptyline 10% creme.

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:

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

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)

After ending the study, the patiënt van, if he or she wants to, continue with the treatment with ketamine 10% or amitriptilyne 10% cream. If the patients agreed to, he of she can be asked for an other study.

Na het onderzoek kan de patiënt, als hij/zij wil, doorgaan met de behandeling met ketamine 10% of amitriptyline 10% cream. Mits de patiënt hiervoor toestemming geeft, kan de patient eventueel benaderd worden voor een andere studie.

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

2015-01-19

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2015-10-14

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

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