Clinical Trials Register

Summary
EudraCT Number:	2014-002594-11
Sponsor's Protocol Code Number:	GWEP1330
National Competent Authority:	Czechia - SUKL
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2014-12-02
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

Czechia - SUKL

A.2

EudraCT number

2014-002594-11

A.3

Full title of the trial

A double blind, randomized, placebo-controlled, two-part study to investigate the pharmacokinetics, followed by efficacy and safety of GWP42006 as add-on therapy in patients with inadequately controlled focal seizures.

A.3.1

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

A study of GWP42006 in people with focal seizures

A.4.1

Sponsor's protocol code number

GWEP1330

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT02369471

A.5.4

Other Identifiers

Name:

US NCT number

Number:

NCT02365610

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	GW Research Ltd.
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	GW Research Ltd
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	GW Research Ltd
B.5.2	Functional name of contact point	GW Research Ltd. Switchboard
B.5.3	Address:
B.5.3.1	Street Address	Sovereign House, Vision Park, Chivers Way
B.5.3.2	Town/ city	Histon, Cambridge
B.5.3.3	Post code	CB24 9BZ
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	+441223266800
B.5.5	Fax number	+441223235667
B.5.6	E-mail	info@gwpharm.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	GWP42006 Oral Solution
D.3.2	Product code	GWP42006
D.3.4	Pharmaceutical form	Oral solution
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	n/a
D.3.9.2	Current sponsor code	GWP42006
D.3.9.3	Other descriptive name	GWP42006
D.3.9.4	EV Substance Code	SUB123082
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	50
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	Yes
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.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	Oral solution
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

Epilepsy

E.1.1.1

Medical condition in easily understood language

Focal Seizures

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	10016843
E.1.2	Term	Focal seizures
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

Part A:
To determine the pharmacokinetics (PK) of GWP42006 and human metabolites, 7-hydroxy- cannabidivarin (7-OH-CBDV) and 6-hydroxy- cannabidivarin (6-OH-CBDV), in the presence of other antiepileptic drugs (AEDs).
Part B:
To evaluate the efficacy of GWP42006, compared with placebo, as add-on therapy to treat inadequately controlled focal seizures.

E.2.2

Secondary objectives of the trial

Part A:
• To evaluate the safety and tolerability of GWP42006 compared with placebo, in the presence of other AEDs.
• To evaluate effects of GWP42006 on plasma concentrations of concomitant AEDs.
Part B:
• To evaluate the effect of GWP42006 compared with placebo on other efficacy measures.
• To evaluate the safety and tolerability of GWP42006 compared with placebo.
• To evaluate the effect of GWP42006 on health utilization compared with placebo.
• To evaluate the effects of GWP42006 on cognitive function.
• To determine plasma concentrations of GWP42006 and main metabolites following multiple doses of GWP42006.
• To evaluate effects of GWP42006 on plasma concentrations of concomitant AEDs.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

• Patient must be willing and able to give informed consent for participation in the study.
• Male or female aged between 18 and 65 years, inclusive.
• Well-documented history of focal epilepsy, with focal seizures as the primary seizure type, compatible electroencephalogram and clinical history.
• Documented CT/MRI that shows no progressive neurologic abnormality.
• Has focal seizures despite prior treatment with at least two AEDs (whether as monotherapies or in combination).
• Patient is willing to keep any factors expected to affect seizures stable (such as the level of alcohol consumption and smoking).
• Patient is able (in the investigators opinion) and willing to comply with all study requirements (including accurate diary completion).
• Patient is willing to allow his or her primary care practitioner and consultant to be notified of participation in the study.

Part A only
• Currently treated with one to three AEDs as follows:
Group 1 - including Carbamazepine, Phenobarbital, Primidone or Phenytoin and excluding Valproic Acid (VPA).
Group 2 - including VPA and excluding Carbamazepine, Phenobarbital, Primidone and Phenytoin.
Group 3 - excluding VPA, Carbamazepine, Phenobarbital, Primidone and Phenytoin.
• All medications or interventions for epilepsy (including ketogenic diet and any neurostimulation devices for epilepsy) must have been stable for two weeks prior to screening and the patient is willing to maintain a stable regimen throughout the study.

Part B only
• Currently treated with one to three AEDs.
• All medications or interventions for epilepsy (including ketogenic diet) must have been stable for one month prior to screening and the patient is willing to maintain a stable regimen throughout the study.
• At the end of the baseline period patients must also meet the following criteria:
- Complied with diary completion, having no more than three missed diary entries during baseline.

E.4

Principal exclusion criteria

• Time of onset of epilepsy treatment is less than two years prior to enrolment.
• Episode(s) of status epilepticus during one year prior to screening.
• History of pseudo-seizures.
• Patient has clinically significant unstable medical conditions other than epilepsy.
• Patient has an illness in the four weeks prior to screening or randomization, other than epilepsy, which in the opinion of the investigator would affect seizure frequency.
• Patient has, in the investigator’s opinion, clinically significantly abnormal laboratory values.
• In the opinion of the investigator the patient has clinically significant abnormalities in the 12-lead electrocardiogram (ECG) measured at screening or randomization or any concurrent cardiovascular conditions, which will interfere with the ability to read their ECGs.
• Active suicidal plan/intent in the past six months, or a history of suicide attempt in the last two years, or more than one lifetime suicide attempt.
• Patient has a history or presence of alcohol or substance abuse within the two years prior to screening or daily consumption of five or more alcohol-containing beverages.
• Patient is currently using or has in the past used recreational or medicinal cannabis, or cannabinoid based medications within the three months prior to screening and is unwilling to abstain for the duration for the study.
• Patient has taken St John’s Wort in the two weeks prior to screening and/or is unwilling to abstain throughout the study.
• Any known or suspected hypersensitivity to cannabinoids, sesame oil or any of the excipients of the IMP(s).
• Female patients of child bearing potential and male patients whose partner is of child bearing potential, unless willing to ensure that they and/or their partner use a highly effective method of contraception.
• Female patient who is pregnant, lactating or planning pregnancy during the course of the study and for three months thereafter.
• Patients who have received an IMP within the 12 weeks prior to the screening visit.
• Any other significant disease or disorder which, in the opinion of the investigator, may either put the patient at risk because of participation in the study, may influence the result of the study, or the patient’s ability to participate in the study.
• Following a physical examination, the patient has any abnormalities that, in the opinion of the investigator would prevent the patient from safe participation in the study.
• Unwilling to abstain from donation of blood during the study.
• Travel outside the country of residence planned during the study.
• Patients previously randomized into this study.
• Patient has consumed grapefruit or grapefruit juice three days prior to randomization and/or unwilling to abstain in the three days prior to PK sampling visits.

Part A only
•Patient has significantly impaired hepatic function at Visit 1 (ALT >5 x ULN or TBL >2 x ULN) OR the ALT or AST >3 x ULN and TBL >2 x ULN (or INR >1.5).

Part B only
•Patient has significantly impaired hepatic function at Visit 1 defined as any of the following:
- ALT or AST >5 × ULN.
- ALT or AST >3 × ULN and TBL >2 × ULN.
-ALT or AST >3 × ULN with the presence of fatigue, nausea, vomiting, right upper quadrant pain or tenderness, fever, rash, and/or eosinophilia (>5%).
• Vagus Nerve Stimulation, Deep Brain Stimulation, Responsive Neurostimulator System or other epilepsy neurostimulation device have been implanted or activated less than one year prior to screening, and/or stimulation parameters have been stable for less than one month, and/or battery life of unit not anticipated to extend for duration of trial.

E.5 End points

E.5.1

Primary end point(s)

Part A - Primary endpoint is the plasma concentrations of GWP42006, 7-OH-CBDV and 6-OH-CBDV with the aim of defining Cmax, Cmin, tmax, AUC0-t, AUC0-inf, and t1/2.

Part B - Primary endpoint is the mean percentage change from baseline to the end of treatment in focal seizure frequency in patients taking GWP42006 compared to placebo.

E.5.1.1

Timepoint(s) of evaluation of this end point

Part A:
•Visit A2 - pre-IMP-dose and 30min, 1h, 2h, 4h and 8h after IMP dose.
•Visit A4 - pre-IMP-dose and 30min, 1h, 2h, 4h and 8h after IMP dose.
•Visit A5 - 24 +/- 6h after last IMP dose.
•Visit A6 - 72 +/- 24h after last IMP dose.
Part B:
•Baseline (Visit B1 to B2) and last 28 days of the evaluable period

E.5.2

Secondary end point(s)

The secondary endpoints for Part A are:
• Safety and tolerability (adverse events [AEs], clinical laboratory testing, vital signs)
• Plasma concentrations of concomitant AEDs.

For Part B, efficacy safety and other endpoints are as follows:
Efficacy endpoints:

• Number of patients considered treatment responders defined as those with a ≥25%, ≥50%, ≥75% and 100% reduction in focal seizure frequency.
• Proportion of patients with a 0-24%, ≥25-50%, ≥50%-74% and ≥75%-100% reduction in focal seizure frequency.
• Change in seizure subtypes frequency.
• Change in composite seizure score.
• Change in number of focal seizure free days.
• Change in use of rescue medication.
• Subject Global Impression of Change (SGIC).
• Physician Global Impression of Change (PGIC).

Safety and tolerability endpoints:
• AEs.
• Clinical laboratory testing.
• Vital signs.
• Columbia Suicide Severity Rating Scale (C-SSRS).
• Cannabis Withdrawal Scale (CWS) score.
• Abuse liability.

Other endpoints:
• Change in number of inpatient hospitalizations or out of visit contact with medical staff due to epilepsy.
• Cognitive assessment scores.
• Plasma concentrations of GWP42006 and main metabolites.
• Plasma concentrations of concomitant AEDs.

E.5.2.1

Timepoint(s) of evaluation of this end point

Part A:
•Safety and tolerability - Visit A1 to visit A7
•AEDs - Visits A2 (baseline) and A4
Part B:
•Safety and tolerability - Visit B1 to visit B9
•Efficacy - Baseline (Visit B1 to B2) and last 28 days of the evaluable period; Visit B7 for PGIC and SGIC.
•Other endpoints - Visits B2 (baseline) and B7; Visit B5 and B7 for plasma concentrations of GWP42006 and metabolites.

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

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.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

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

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

LVLS

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:

166

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

170

F.4.2.2

In the whole clinical trial

170

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)

Normal standard of care will resume as clinical evidence of the efficacy of GWP42006 in this population has yet to be determined.

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

2015-02-27

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2015-03-05

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2017-09-01

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