Clinical Trials Register

Summary
EudraCT Number:	2012-001132-60
Sponsor's Protocol Code Number:	RTG113284
Clinical Trial Type:	Outside EU/EEA
Date on which this record was first entered in the EudraCT database:	2012-03-09
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
H.4 THIRD COUNTRY IN WHICH THE TRIAL WAS FIRST AUTHORISED

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A. Protocol Information

A.2

EudraCT number

2012-001132-60

A.3

Full title of the trial

Open-label, multiple dose study to evaluate the
pharmacokinetics, safety and tolerability of ezogabine/retigabine
as adjunctive treatment in subjects aged from 12 years to less
than 18 years with partial onset seizures or Lennox-Gastaut
syndrome

A.3.1

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

Study in pediatric subjects with epilepsy

A.4.1

Sponsor's protocol code number

RTG113284

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT01494584

A.7

Trial is part of a Paediatric Investigation Plan

Yes

A.8

EMA Decision number of Paediatric Investigation Plan

P/156/2011

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	GlaxoSmithKline R&D Limited
B.1.3.4	Country	United Kingdom
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	GlaxoSmithKline R&D Limited
B.4.2	Country	United Kingdom
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	GlaxoSmithKline Research and Development
B.5.2	Functional name of contact point	Clinical Trials HelpDesk
B.5.3	Address:
B.5.3.1	Street Address	1-3 IronBridge Road
B.5.3.2	Town/ city	Uxbridge, Middlesex
B.5.3.3	Post code	UB11 1BU
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	+442089904466
B.5.5	Fax number	+442089901234
B.5.6	E-mail	GSKClinicalSupportHD@gsk.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	Potiga
D.2.1.1.2	Name of the Marketing Authorisation holder	GlaxoSmithKline Inc
D.2.1.2	Country which granted the Marketing Authorisation	United States
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	Retigabine/Ezogabine
D.3.2	Product code	GW582892
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	RETIGABINE
D.3.9.1	CAS number	150812-12-7
D.3.9.2	Current sponsor code	GW582892
D.3.9.3	Other descriptive name	EZOGABINE (US ONLY)
D.3.9.4	EV Substance Code	SUB10291MIG
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	50
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	RETIGABINE
D.3.9.1	CAS number	150812-12-7
D.3.9.2	Current sponsor code	GW582892
D.3.9.3	Other descriptive name	EZOGABINE (US ONLY)
D.3.9.4	EV Substance Code	SUB10291MIG
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.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	RETIGABINE
D.3.9.1	CAS number	150812-12-7
D.3.9.2	Current sponsor code	GW582892
D.3.9.3	Other descriptive name	EZOGABINE (US ONLY)
D.3.9.4	EV Substance Code	SUB10291MIG
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	300
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	Retigabine/Ezogabine
D.3.4	Pharmaceutical form	Tablet
D.3.4.1	Specific paediatric formulation	Yes
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	RETIGABINE
D.3.9.1	CAS number	150812-12-7
D.3.9.2	Current sponsor code	GW582892
D.3.9.3	Other descriptive name	EZOGABINE (US ONLY)
D.3.9.4	EV Substance Code	SUB10291MIG
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: 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	Retigabine/Ezogabine
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	RETIGABINE
D.3.9.1	CAS number	150812-12-7
D.3.9.2	Current sponsor code	GW582892
D.3.9.3	Other descriptive name	EZOGABINE (US ONLY)
D.3.9.4	EV Substance Code	SUB10291MIG
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.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

Uncontrolled partial onset seizures or Lennox Gastaut Syndrome

E.1.1.1

Medical condition in easily understood language

Epilepsy that affects one part of the brain (partial onset seizures) which may or may not be followed by a seizure affecting all of the brain. Seizures that occur with Lennox-Gastaut syndrome.

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	14.1
E.1.2	Level	PT
E.1.2	Classification code	10061334
E.1.2	Term	Partial seizures
E.1.2	System Organ Class	10029205 - Nervous system disorders

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.1
E.1.2	Level	PT
E.1.2	Classification code	10048816
E.1.2	Term	Lennox-Gastaut syndrome
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 characterize the pharmacokinetic profile of repeat doses of ezogabine/retigabine IR tablet in subjects aged 12 to less than 18 years old.

E.2.2

Secondary objectives of the trial

To assess the safety, tolerability, and efficacy of repeat doses of ezogabine/retigabine IR tablet in subjects aged 12 to less than 18 years old.
To determine the systemic exposure of the n-acetyl metabolite of ezogabine/retigabine (NAMR) after dosing ezogabine/retigabine IR tablets to steady-state.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

- Between 12 and 18 years of age.
- Diagnosis of uncontrolled partial onset seizures (with or without secondarily generalized seizures) or Lennox-Gastaut syndrome.
- Taking between one and three antiepileptic drugs.
- Able to swallow tablets.
- Females must be of : (1) Non-childbearing potential or (2) Child-bearing potential and agrees to use acceptable contraception.

E.4

Principal exclusion criteria

- Epilepsy secondary to progressive cerebral disease, tumor or any progressive neurodegenerative disease.
- History of status epilepticus in the last six months.
- Currently treated with felbamate or has been treated with vigabatrin within the past 6 months.
- Following the ketogenic diet.
- Suicidal intent or history of suicide attempt in the last 2 years.
- Elevated liver enzymes or abnormal kidney function.
- Current disturbance of micturition or known urinary obstructions.
- History of vesicoureteric reflux.
- Abnormal post-void residual bladder ultrasound.
- Urinary retention and/or required urinary catheterization in the preceding 6 months.
- Abnormal urine sample at screening/.baseline.
- Abnormal blood sample at screening.
- Clinically significant arrhythmias.
- Abnormal ECG at screening.
- BMI lower than the 10th percentile for age and gender or subject weighs less than 30kg.

E.5 End points

E.5.1

Primary end point(s)

Steady-state pharmacokinetics following oral administration of ezogabine/retigabine including clearance (Cl/F), volume of distribution (V/F), area under the curve over the dosing interval (AUC (0-tau)), maximum observed plasma concentration (Cmax)and trough plasma concentrations (Ctau)

E.5.1.1

Timepoint(s) of evaluation of this end point

5 to 8 timepoints at the end of weeks 1, 3, and 5.

E.5.2

Secondary end point(s)

Tolerability: Incidence of adverse events, clinical laboratory parameters, ECG parameters, vital signs, monitoring of bladder function and CNS symptoms as appropriate
• Monitoring of seizure frequency
• Estimate of systemic exposure to the n-acetyl metabolite of ezogabine/retigabine (NAMR) (AUC(0-tau), and Ctau)
• Ezogabine/retigabine time to maximum concentration (tmax) and half-life at steadystate (t1/2) (if data allow)

E.5.2.1

Timepoint(s) of evaluation of this end point

Safety parameters - Subjects will be followed until the end of titration, an expected average of 5 weeks.
Seizure frequency - Subjects will be followed until the end of titration, an expected average of 5 weeks.
Estimate of systemic exposure to the n-acetyl metabolite - 5 to 8 timepoints at the end of weeks 1, 3, and 5.
Phamacokinetic parameters - 5 to 8 timepoints at the end of weeks 1, 3, and 5.

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

Yes

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

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

E.8.1.1

Randomised

E.8.1.2

Open

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

E.8.3

Will this trial be conducted at a single site globally?

E.8.4

Will this trial be conducted at multiple sites globally?

Yes

E.8.6 Trial involving sites outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

Yes

E.8.6.3

Specify the countries outside of the EEA in which trial sites are planned

United States

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

LSLV

E.8.9 Initial estimate of the duration of the trial

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

Yes

F.1.1

Number of subjects for this age range:

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)

Yes

F.1.1.6.1

Number of subjects for this age range:

F.1.2

Adults (18-64 years)

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

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.4.2

For a multinational trial

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)

Continue treatment in a long-term extension study provided that they meet the inclusion/exclusion criteria of that study.
For those subjects who do not enter the extension study, investigators should treat the subject’s condition at their discretion with consideration to available licensed products for the treatment of epilepsy. Post-study treatment will not be provided by the sponsor.

G. Investigator Networks to be involved in the Trial

H.4 Third Country in which the Trial was first authorised
H.4.1	Third Country in which the trial was first authorised:	United States

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