Clinical Trials Register

Summary
EudraCT Number:	2017-003200-48
Sponsor's Protocol Code Number:	EP0091
National Competent Authority:	Bulgarian Drug Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2018-04-18
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

Bulgarian Drug Agency

A.2

EudraCT number

2017-003200-48

A.3

Full title of the trial

A Randomized, Double-Blind, Placebo-Controlled, Dose Finding Study to Evaluate the Efficacy and Safety of Padsevonil as Adjunctive Treatment of Focal-Onset Seizures in Adult Subjects with Drug- Resistant Epilepsy

A.3.1

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

Study to test the efficacy and safety of Padsevonil as adjunctive treatment of focal-onset seizures in adults with drug-resistant epilepsy

A.3.2

Name or abbreviated title of the trial where available

ARISE

A.4.1

Sponsor's protocol code number

EP0091

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	UCB Biopharma SPRL
B.1.3.4	Country	Belgium
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	UCB Biopharma SPRL
B.4.2	Country	Belgium
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	UCB Biosciences GmbH
B.5.2	Functional name of contact point	Clin Trial Reg & Results Disclosure
B.5.3	Address:
B.5.3.1	Street Address	Alfred-Nobel Strasse 10
B.5.3.2	Town/ city	Monheim
B.5.3.3	Post code	40789
B.5.3.4	Country	Germany
B.5.6	E-mail	clinicaltrials@ucb.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	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	UCB0942
D.3.4	Pharmaceutical form	Film-coated 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	Padsevonil
D.3.9.1	CAS number	1294000-61-5
D.3.9.2	Current sponsor code	UCB0942
D.3.9.3	Other descriptive name	UCB0942
D.3.9.4	EV Substance Code	SUB33843
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	25
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	UCB0942
D.3.4	Pharmaceutical form	Film-coated 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	Padsevonil
D.3.9.1	CAS number	1294000-61-5
D.3.9.2	Current sponsor code	UCB0942
D.3.9.3	Other descriptive name	UCB0942
D.3.9.4	EV Substance Code	SUB33843
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	100
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	UCB0942
D.3.4	Pharmaceutical form	Film-coated 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	Padsevonil
D.3.9.1	CAS number	1294000-61-5
D.3.9.2	Current sponsor code	UCB0942
D.3.9.3	Other descriptive name	UCB0942
D.3.9.4	EV Substance Code	SUB33843
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	200
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	Film-coated tablet
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	Film-coated tablet
D.8.4	Route of administration of the placebo	Oral use
D.8 Placebo: 3
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Film-coated tablet
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

Focal-Onset Seizures

E.1.1.1

Medical condition in easily understood language

Epilepsy

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	LLT
E.1.2	Classification code	10065337
E.1.2	Term	Focal epilepsy
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 primary objective of this study is to characterize the dose-response relationship with respect to efficacy of Padsevonil (PSL) administered concomitantly with up to 3 antiepileptic drugs (AEDs) for treatment of observable focal-onset seizures in subjects with drug-resistant epilepsy and to evaluate the efficacy of the 4 selected dose regimens of PSL compared with placebo.

E.2.2

Secondary objectives of the trial

The secondary objective is to assess the safety and tolerability of all doses of Padsevonil (PSL) in relation to placebo.

E.2.3

Trial contains a sub-study

Yes

E.2.3.1

Full title, date and version of each sub-study and their related objectives

During this study, subjects will have the option of providing additional informed consent for exploratory deoxyribonucleic acid (DNA) ribonucleic acid (RNA), and lipidomics/proteomics/additional blood biomarker analyses . Participation in this additional portion of the study is optional and does not preclude participation in the main study. The additional pharmacogenetic sample must not be collected if the subject has not consented to participate in this exploratory genetic substudy. A volume of 6 mL of whole blood samples will be collected at Baseline (Visit 2).

E.3

Principal inclusion criteria

- Diagnosis of focal epilepsy per 1989 International League Against Epilepsy (ILAE) criteria at least 3 years before study entry
- Subject has failed to achieve seizure control with 4 tolerated and appropriately chosen prior antiepileptic drugs (AED), including past and ongoing treatment, that were individually optimized for adequate dose and duration. Prior discontinued AED treatment would need to be assessed by the Investigator considering the patient medical records and patient and/or caregiver interview. 'Prior AED' is defined as all past and ongoing AED treatments with a start date before the Screening Visit (Visit 1)
- Average of >= 4 spontaneous and observable focal seizures (type IA1 (i.e. focal aware), IB (i.e. focal impaired awareness), IC (i.e. focal to bilateral tonic-clonic)) per month
- Current treatment with an individually optimized and stable dose of at least 1 and up to 3 AEDs for the 8 weeks prior to the Screening Visit with or without additional Vagus Nerve Stimulation (VNS) or other neurostimulation treatments

E.4

Principal exclusion criteria

- Subject has a history of or signs for idiopathic generalized (genetic) epilepsy
- Cluster seizures which are uncountable in the previous 8 weeks before study entry and during 4 weeks prospective baseline
- Current treatment with carbamazepine, phenytoin, primidone, phenobarbital
- Current treatment/ use of (non-AED) prescription, nonprescription, dietary (eg, grapefruit or passion fruit), or herbal products that are potent inducers or inhibitors of the CYP3A4 or 2C19 pathway for 2 weeks (or 5 half-lives, whichever is longer) prior to the Baseline Visit
- Subjects taking sensitive substrates of CYP2C19 for 2 weeks (or 5 half-lives, whichever is longer) prior to the Baseline Visit
- Subject has been taking vigabatrin less than 2 years at study entry
- Subject has been taking felbamate for less than 12 months
- Subject taking retigabine for less than 4 years
- Current treatment with benzodiazepines (i.e. GABA-A-ergic drugs like zolpidem, zaleplon, or zopiclone, excluding GABA-A-ergic AEDs) <3 times per week for emergencies.
- Subject has a current medical condition that occurred within the last 12 months which, in the opinion of the investigator, could compromise his/her safety or ability to participate in this study

E.5 End points

E.5.1

Primary end point(s)

1: 75 % responder rate over the 12 week Maintenance Period
2. Incidence of Treatment-Emergent Adverse Events (TEAEs) reported by
the subject and/or caregiver or observed by the Investigator during the
entire study
3. Incidence of Treatment-Emergent Adverse Events (TEAEs) leading to
study withdrawal
4. Incidence of Treatment-Emergent Serious Adverse Events (SAEs)
during the entire study

E.5.1.1

Timepoint(s) of evaluation of this end point

1: End of Maintenance Period (Week 16) following 3 weeks of titration and 1 week stabilization
2-4: From Baseline until Safety Follow-Up (up to Week 23)

E.5.2

Secondary end point(s)

1. Change in log-transformed observable focal onset seizure frequency from Baseline over the 12 week Maintenance Period
2. 50 % responder rate over the 12 week Maintenance Period
3. Percent change in observable focal-onset seizure frequency from Baseline over the 12 week Maintenance Period

E.5.2.1

Timepoint(s) of evaluation of this end point

1: From Baseline over the 12 week Maintenance Period
2-3: End of Maintenance Period (Week 16) following 3 weeks of titration and 1 week stabilization

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

Yes

E.6.10

Pharmacogenetic

Yes

E.6.11

Pharmacogenomic

Yes

E.6.12

Pharmacoeconomic

E.6.13

Others

Yes

E.6.13.1

Other scope of the trial description

Tolerability

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.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

110

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Australia

Belgium

Bulgaria

Canada

Czech Republic

France

Germany

Hungary

Italy

Japan

Lithuania

Mexico

Poland

Portugal

Slovakia

Spain

Turkey

United Kingdom

United States

E.8.7

Trial has a data monitoring committee

Yes

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

Last subject last visit (LSLV)

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

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:

350

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

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

Subjects could have potential cognitive impairment or could face other situations, which might make them unable to comprehend the ICF. Then one or more legally acceptable representatives will be required to sign the ICF as required by national law

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

210

F.4.2.2

In the whole clinical trial

400

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 will have the opportunity to move on to the open-label extension study, EudraCT 2017-003241-26.
AN OPEN-LABEL, MULTICENTER, EXTENSION STUDY TO EVALUATE THE SAFETY AND EFFICACY OF PADSEVONIL AS ADJUNCTIVE TREATMENT OF FOCAL-ONSET SEIZURES IN ADULT SUBJECTS WITH DRUG-RESISTANT EPILEPSY.

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

2018-06-18

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2018-05-22

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2020-02-26

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