Clinical Trials Register

Summary
EudraCT Number:	2012-002359-40
Sponsor's Protocol Code Number:	C1202
National Competent Authority:	Germany - BfArM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2012-06-15
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

Germany - BfArM

A.2

EudraCT number

2012-002359-40

A.3

Full title of the trial

NEUPRO OL, Efficacy profile of Neurexan® in an experimental acute stress setting – an explorative open-label study in healthy probands

A.3.1

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

Study to investiagte the effect of Neurexan vs natural course in healthy volunteers under an experimental acute stress setting

A.4.1

Sponsor's protocol code number

C1202

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	Biologische Heilmittel Heel GmbH
B.1.3.4	Country	Germany
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	Biologische Heilmittel Heel GmbH
B.4.2	Country	Germany
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Theorem Clinical Research GmbH & Co. KG
B.5.2	Functional name of contact point	Project Management
B.5.3	Address:
B.5.3.1	Street Address	Hermann-Heinrich-Gossen-Str. 3
B.5.3.2	Town/ city	Köln
B.5.3.3	Post code	50858
B.5.3.4	Country	Germany
B.5.4	Telephone number	+4922341852 0
B.5.5	Fax number	+4922341852 65
B.5.6	E-mail	Geraldine.Bosse@TheoremClinical.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	Neurexan
D.2.1.1.2	Name of the Marketing Authorisation holder	Biologische Heilmittel Heel GmbH
D.2.1.2	Country which granted the Marketing Authorisation	Germany
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	Neurexan
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	COFFEA ARABICA
D.3.9.1	CAS number	8000050-74-0
D.3.9.3	Other descriptive name	COFFEA ARABICA
D.3.9.4	EV Substance Code	SUB13432MIG
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	0.6
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Zinc isovalerianate
D.3.9.3	Other descriptive name	Zincum isovalerianicum
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	0.6
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	PASSIFLORA INCARNATA
D.3.9.1	CAS number	8001000-82-6
D.3.9.3	Other descriptive name	PASSIFLORA INCARNATA
D.3.9.4	EV Substance Code	SUB14781MIG
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	0.6
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	AVENA SATIVA
D.3.9.1	CAS number	8001001-41-0
D.3.9.3	Other descriptive name	AVENA SATIVA
D.3.9.4	EV Substance Code	SUB12969MIG
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	0.6
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	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	Yes
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

Neurexan to be effective in fostering mental balance by reducing tension and nervousness during acute stress setting in healthy probands

E.1.1.1

Medical condition in easily understood language

To reduce stress symptoms in healthy volunteers

E.1.1.2

Therapeutic area

Psychiatry and Psychology [F] - Behaviours [F01]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	15.1
E.1.2	Level	LLT
E.1.2	Classification code	10042219
E.1.2	Term	Stress test
E.1.2	System Organ Class	100000004848

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 primary objective is the efficacy of Neurexan® on tension and nervousness perception using visual analogue scales (VAS) when study participants undergo an emotional stressful condition as compared to natural course. The test method for this study is the TSST protocol.

E.2.2

Secondary objectives of the trial

Secondary objectives of the study are stress-sensitive psychological and physiological measures in response to acute stress:
• stress-related biomarkers such as plasma and saliva cortisol, α-amylase, Adrenocorticotropic Hormone (ACTH), catecholamines, NK cells
• parameters of Autonomous Nervous System (ANS) such as blood pressure (BP), heart rate and heart rate variability (HRV)
• state anxiety and stress perception measured by
State-Trait Anxiety Inventory (STAI)
• physiological questionnaire (modified somatic SCL90)

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

For inclusion in the study, volunteers must fulfil all of the following criteria:
1. Provide written informed consent
2. Healthy male or female
3. age between 31 to 59 years
4. fluent in German language
5. Ability to understand the explanations and instructions given by the study physician

E.4

Principal exclusion criteria

Any of the following is regarded as a criterion for exclusion from the study:
1. allergies to ingredients of Neurexan® (Passiflora incarnata, Avena sativa, Coffea arabica, Zincum isovalerianicum, lactose monohydrate, magnesium stearate)
2. lactose intolerance
3. use of any psychological stress-management intervention within the last 4 weeks
4. sick leave for any reason
5. participation in any other clinical study 3 months prior to Screening Visit
6. current or recent (3 months prior to Screening Visit) history of substance abuse or drug dependence including nicotine and alcohol (as verified in the respective IDCL list)
7. smokers
8. alcohol intake within last 24 hours (before Baseline Visit V3)
9. shift workers or work regularly during night time
10. use of any psychotropic medication or suffering from severe psychiatric illness needing acute intervention
11. BMI > 30 kg/m2
12. currently pregnant (verified by urine pregnancy test) or lactating
13. participation in a previous TSST study
14. high chronic stress as verified with the TICS-SSCS (a score of ≥ 23 on the screening scale for chronic stress meets the criterion of being chronically stressed)
15. major mental disorder as verified with the IDCL (depressive episode, panic disorder, social phobia, obsessive-compulsory disorder; alcohol dependency; schizophrenia and mania.)
16. employee of the Sponsor, one of the investigators or the CRO
17. use of any concomitant medication except contraceptives
18. any somatic disease or other condition the Investigator or their duly assigned representatives believes may affect the ability of the individual to complete the study or the interpretation of the study results
19. Individuals whose ability to speak for themselves lacks or can be doubted

E.5 End points

E.5.1

Primary end point(s)

• Area under the curve (AUC) of VAS tension values from T1 until T15.
• Area under the curve (AUC) of VAS nervousness values from T1 until T15.
For each of the two AUCs an Analysis of Covariance (ANCOVA) model including gender and site as qualitative factors and the respective VAS value (i.e. tension or nervousness) at time point T1 (-210 min) as a covariate will be analysed to test for treatment differences

E.5.1.1

Timepoint(s) of evaluation of this end point

-210 min -180 min -150 min -120 min -90 min -60 min -30 min -15 min +15 min +25 min +40 min +55 min +70 min +100 min

E.5.2

Secondary end point(s)

• Changes in tension and nervousness VAS at all time points after time point T1 (-210 min)
• Changes in plasma and saliva cortisol and α-amylase, ACTH, catecholamines norepinephrine (NE) and epinephrine (E)
• Changes in NK cells (subgroup)
• Changes in BP, heart rate and HRV
• State anxiety and stress perception measured by STAI-X1
• Incidence of AEs
All parameters will be descriptively summarised by treatment and assessment time. The AEs and vital signs will be summarised by treatment group.

E.5.2.1

Timepoint(s) of evaluation of this end point

-60 min to +100 min, AEs from -180 min to +100 min

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)

Yes

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

Yes

E.7.1.3.1

Other trial type description

IMP administered to healthy volunteers to evaluate the efficacy

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

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

Yes

E.8.2.3.1

Comparator description

lack of treatment

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

Final visit of last subject

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

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

Yes

F.3.2

Patients

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception For clinical trials recorded in the database before the 10th March 2011 this question read: "Women of childbearing potential" and did not include the words "not using contraception". An answer of yes could have included women of child bearing potential whether or not they would be using contraception. The answer should therefore be understood in that context. This trial was recorded in the database on 2012-06-15.

Yes

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.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 discontinue do not receive special treatment

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

2012-07-13

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2012-07-18

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2013-04-04

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