Clinical Trials Register

Summary
EudraCT Number:	2015-001101-14
Sponsor's Protocol Code Number:	750253.01.030
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:	2016-01-11
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

2015-001101-14

A.3

Full title of the trial

Driving fitness under acute and subchronic application of Silexan® (WS® 1265) in comparison to placebo and Lorazepam with healthy volunteers in two successive, randomized, double-blind, crossover designed trial parts

A.3.1

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

Influence of Silexan® on driving fitness

A.4.1

Sponsor's protocol code number

750253.01.030

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	Dr. Willmar Schwabe GmbH & Co. KG
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	Dr. Willmar Schwabe GmbH & Co. KG
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	Dr. Willmar Schwabe GmbH & Co. KG
B.5.2	Functional name of contact point	Clinical Research Department
B.5.3	Address:
B.5.3.1	Street Address	Willmar-Schwabe-Str. 4
B.5.3.2	Town/ city	Karlsruhe
B.5.3.3	Post code	76227
B.5.3.4	Country	Germany
B.5.4	Telephone number	+497214005514
B.5.5	Fax number	+4972140058514
B.5.6	E-mail	stephan.klement@schwabe.de

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	Lasea®
D.2.1.1.2	Name of the Marketing Authorisation holder	Dr. Willmar Schwabe GmbH & Co. KG
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	Silexan
D.3.2	Product code	WS® 1265
D.3.4	Pharmaceutical form	Capsule, soft
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	Lavenderoil
D.3.9.2	Current sponsor code	WS 1265
D.3.9.3	Other descriptive name	Silexan
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	80
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	Yes
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	Tavor
D.2.1.1.2	Name of the Marketing Authorisation holder	Pfizer Pharma 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.3.4	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	Lorazepam
D.3.9.1	CAS number	846-49-1
D.3.9.3	Other descriptive name	LORAZEPAM
D.3.9.4	EV Substance Code	SUB08582MIG
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	1
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, soft
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	Capsule, hard
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

Investigation in healthy volunteers. The investigational medicinal product has a marketing authorisation in Germany for the treatment of restlessness related to anxious mood.

E.1.1.1

Medical condition in easily understood language

Intended Indication is anxiety disorder

E.1.1.2

Therapeutic area

Not possible to specify

MedDRA Classification

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 trial is divided in two parts. The first part of the trial is conducted in order to test the non-inferiority and equivalence respectively of driving fitness after acute application of 80 mg Silexan® (WS® 1265) in comparison to placebo. The second part of the trial is conducted in order to show superiority of 160 mg and 320 mg Silexan® (WS® 1265) with respect to driving fitness in comparison to 1.0 mg Lorazepam. In the second part of the trial, the comparison of 1.0 mg Lorazepam with placebo will also serve to ensure the internal validity of the experimental set-up.
Driving fitness will be assessed using a representative, alcohol-validated test course in a high-fidelity driving simulator.

E.2.2

Secondary objectives of the trial

Not applicable

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Healthy male and female volunteers aged 25-60 years.
2. Active drivers that have had a driver’s license for at least 3 years and have a minimal mileage per year of 3000 km.
3. Simulator training in the WIVW simulator passed with very good simulator tolerance.
4. Written informed consent in accordance with the legal requirements.
5. Readiness and ability of the volunteer to comply with the physician’s instructions and to fill in the self-assessment scales.
6. Only for female volunteers who have not entered menopause and who are not sterilized: Using a highly effective method of birth control that has a very low failure rate (i.e. less than 1% per year), such as implants, injectables, combined oral contraceptives, some intrauterinpessars, sexual abstinence or vasectomised partner).

E.4

Principal exclusion criteria

1. Participation in another clinical trial at the same time or within the past 4 weeks before enrolment.
2. Participation in the first study part described in the present outline excludes participation in the second study part.
3. Acute illness and/or infections and/or fever within the past 7 days prior to administration of IMP.
4. Increased intraocular pressure.
5. Chronic illness (specifically any psychiatric disorder according to DSM-IV (e.g. Major depressive disorder, Anxiety disorder etc.) and neurological disorders (e.g. epilepsy, myasthenia gravis)).
6. Gastrointestinal disorders with uncertain absorption of orally administered drugs (e.g. partial or total gastrectomy, enterectomy, inflammatory bowel disease, celiac disease, symptomatic lactose intolerance, other disorders associated with chronic diarrhoea).
7. < 3 months before inclusion of the participant: use of psychoactive substances (specifically benzodiazepines, hypnotic non-benzodiazepines like zopiclone or zolpidem, anxiolytics, tranquilizers, tri- and tetracyclic antidepressants, neuroleptics/antipsychotics, lithium, carbamazepine as long-term prophylactic treatment, treatment for neuro-degenerative diseases).
8. < 2 weeks before inclusion of the participant: use of centrally acting drugs like antihistaminics, anticonvulsants, any other antidepressants (including hypericum extracts), beta-blockers, centrally acting antihypertensive medication (e.g. guanethidine, guanoxan, clonidine, prazosine, reserpine and alpha-methyldopa), anti-emetics, analgetics of opiate type, muscle relaxants, anaesthetics, OTC drugs with antidepressant, anxiolytic or hypnotic potential and others.
9. < 3 months before inclusion of the participant: use of recreational drugs, e.g. CNS stimulants like amphetamines, cannabis, cocaine and others.
10. History or evidence of alcohol or drug abuse/dependence.
11. Positive result in the drug screening or in the alcohol breath test at screening visit.
12. Presence or history of clinically relevant allergy or a known or suspected hypersensitivity to lavender oil, Lorazepam and/or excipients of the IMP or benzodiazepines; mild seasonal hay fever is allowed as long as the season does not meet the study period.
13. Any clinically relevant laboratory value which the investigator decides might affect the study objectives.
14. Females who are breastfeeding.
15. Females who are pregnant (verified by a positive pregnancy test at screening visit).
16. Volunteers who are employees or direct relatives of an employee of the study centre or Dr. Willmar Schwabe GmbH & Co. KG.
17. Volunteers who are imprisoned or lawfully kept in an institution
18. Evidence or suspicion that the volunteer might not comply with the study directives and/ or that he/she is not reliable or trustworthy.

E.5 End points

E.5.1

Primary end point(s)

Standard Deviation of Lane Position (SDLP) during the vigilance section of the driving test.

E.5.1.1

Timepoint(s) of evaluation of this end point

Days 1, 8, 15, 22 (for both parts)

E.5.2

Secondary end point(s)

• Raters’ global assessment of subjects’ driving performance on the Fitness-to-Drive-Scale according to Neukum & Krüger (2003)
• Number of driving errors in total and in subcategories according to Kaussner et al. (2010) and Kenntner-Mabiala et al. (2015)
• Subjective assessment of driving performance on the Fitness-to-Drive-Scale according to Neukum & Krüger (2003)
• Eyelid Closure Index (Hargutt, 2003) in the vigilance section of the driving test
• Reaction time to sudden events
• Rating on the Stanford Sleepiness Scale (Hoddes, Dement & Zarcone, 1973)
• (Serious) adverse events

E.5.2.1

Timepoint(s) of evaluation of this end point

Days 1, 8, 15, 22 (for both parts)

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

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

Yes

E.6.13.1

Other scope of the trial description

The scope of this trial is to assess the influence of Silexan on driving fitness in healthy volunteers.

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

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

Yes

E.8.2.3.1

Comparator description

Tavor (Lorazepam)

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

The end of the trial is defined as the date of the report synopsis (date of internal summary of results) due to follow up of patients with queries and adverse events before unblinding.

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)

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

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)

Not applicable for healthy volunteers

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

2016-03-09

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2016-02-24

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2017-08-11

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