Safety and Pharmacokinetics Study of E2007 to Treat Partial and Generalised Seizures in People With Epilepsy

December 17, 2018 updated by: Eisai Co., Ltd.

A Randomised, Double-Blind, Placebo-Controlled Study of the Tolerability, Safety and Pharmacokinetics of E2007 in Epileptic Patients With Partial and Generalised Seizures

The objectives of this study were to assess the tolerability and safety of E2007 in patients with refractory partial or generalised seizures and to assess the pharmacokinetics of E2007 in epileptic patients receiving at least one concomitant anti-epileptic drug.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
18

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Germany
      • Hennigsdorf, Germany
        • 3ClinicalResearch AG

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria

A patient who met the following inclusion criteria was eligible to participate in the study:

  1. Males or females with simple or complex partial seizures with or without secondary generalization, or primary generalized tonic-clonic seizures according to the International League against Epilepsy classification. Patient records were to document the frequency of seizure.
  2. Age: 18 to 65 years.
  3. Race: any.
  4. Patients receiving up to two additional anti-epileptic medications at doses that were stable for at least the four weeks immediately preceding baseline.
  5. Patients willing and able to co-operate with the study procedures including completion of patient diaries.
  6. Patients living at home with a partner or carer able to monitor compliance.
  7. Patients giving informed consent to participate in the study.

Exclusion Criteria

A patient who met the following exclusion criteria was not eligible to participate in the study:

  1. Pregnant or lactating women.
  2. Women of childbearing potential unless (1) surgically sterile or (2) practicing effective contraception (eg, abstinence, IUD or barrier method plus hormonal method) and having a negative serum beta-HCG result at screening and being willing to remain on the current form of contraception for the duration of the study. Postmenopausal women could be included but were to have been amenorrhoeic for at least 12 months to be considered as not being of child-bearing potential.
  3. Fertile men not willing to use reliable contraception or with partners not willing to use reliable contraception.
  4. Patients with status epilepticus within the past 24 months.
  5. Patients with unstable abnormalities of the hepatic, renal, cardiovascular, respiratory, abdominal, haematological, endocrine or metabolic systems which might complicate assessment of the tolerability of the study medication.
  6. Patients with significantly elevated liver enzymes (abnormal bilirubin level, or serum transaminase levels more than 1.5 times the upper limit of normal).
  7. Patients taking drugs other than anti-epileptic agents which induce the enzyme cytochrome P450 3A4 (since these might reduce the plasma concentration of E2007), including dexamethasone, rifabutin, rifampacin, St John's Wort.
  8. Patients with past or present drug or alcohol abuse.
  9. Patients with unstable psychiatric illness.
  10. Patients who had received an investigational drug within the three months before baseline.
  11. Patients without a reliable partner or carer.
  12. Patients with any condition which would make the patient, in the opinion of the investigator, unsuitable for the study.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: E2007 1 mg
Tablet, once daily to be taken in the morning by mouth, one hour before breakfast, with a glass of water.
Drug: E2007
1 mg of E2007 was administered by mouth once daily.
Drug: E2007
2 mg of E2007 was administered by mouth once daily.
Experimental: E2007 2 mg
Tablet, once daily to be taken in the morning by mouth, one hour before breakfast, with a glass of water.
Drug: E2007
1 mg of E2007 was administered by mouth once daily.
Drug: E2007
2 mg of E2007 was administered by mouth once daily.
Placebo Comparator: Placebo
Tablet, once daily to be taken in the morning, one hour before breakfast, with a glass of water.
Drug: Placebo
Placebo once daily of oral tablet formulation to be taken in the morning, one hour before breakfast, with a glass of water.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Number of participants with Treatment Emergent Adverse Events (TEAEs)
Time Frame: From administration of first dose of study drug up until 42 days.
The TEAEs were defined as those Adverse Events (AEs) that start on or after the first dose of the treatment until the end of the study. AEs were classified by the investigator as 'not related', 'possibly related' or 'probably related'.
From administration of first dose of study drug up until 42 days.
Clinical Global Impression of Tolerability (CGIT)
Time Frame: Day 28
The investigator's global impressions of the tolerability of the study treatment was based on a five point scale: 1 - very good, 2 - good, 3 - moderate, 4 - poor, and 5 - very poor.
Day 28
Pharmacokinetic Parameter: Area Under the Curve (AUC)(0-24hr) of E2007
Time Frame: Day 1 and Day 14
Standard pharmacokinetic parameters for E2007 were derived from plasma drug concentrations in epileptic participants. A measure of systemic drug exposure over 24 hours, which is obtained by collecting a series of blood samples and measuring the concentrations of drug in each sample.
Day 1 and Day 14
Pharmacokinetic Parameter: Cmax (Maximum Observed Plasma Concentration) of E2007
Time Frame: Day 1 and Day 14
Standard pharmacokinetic parameters for E2007 were derived from plasma drug concentrations in epileptic participants. The maximum concentration of a drug observed after its administration.
Day 1 and Day 14
Pharmacokinetic Parameter: Tmax (Time to Maximum Concentration) of E2007
Time Frame: Day 1 and Day 14
Standard pharmacokinetic parameters for E2007 were derived from plasma drug concentrations in epileptic participants. The time after dosing when a drug attains its highest measurable concentration (Cmax).
Day 1 and Day 14
Pharmacokinetic Parameter: Css,min (Minimum Steady State Plasma Concentration) of E2007
Time Frame: Day 14
Standard pharmacokinetic parameters for E2007 were derived from plasma drug concentrations in epileptic participants. Lowest plasma concentration within a steady-state dosing interval.
Day 14
Pharmacokinetic Parameter: Cav (Average Plasma Concentration) of E2007
Time Frame: Day 14
Standard pharmacokinetic parameters for E2007 were derived from plasma drug concentrations in epileptic participants.
Day 14
Pharmacokinetic Parameter: Peak-to-trough Fluctuation (PTF) of E2007
Time Frame: Day 14
Standard pharmacokinetic parameters for E2007 were derived from plasma drug concentrations in epileptic participants.
Day 14
Pharmacokinetic Parameter: Observed Accumulation Ratio (Rac) of E2007
Time Frame: Day 14
Standard pharmacokinetic parameters for E2007 were derived from plasma drug concentrations in epileptic participants.
Day 14

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Change from Baseline of Bond and Lader Scale
Time Frame: Baseline, Day 28 and Day 42
The Bond and Lader visual analogue mood scale (VAMS) had a score from 0 - 100; a higher score represented worsening of the participants condition attributed to 3 factors, (1) Anxiety (e.g., calmness), (2) Sedation (e.g., alertness, (3) Dysphoria (e.g., contentedness). The change was visit minus baseline.
Baseline, Day 28 and Day 42
Change from Baseline of Peak Saccadic Velocity (PSV)
Time Frame: Baseline, Day 28, Day 42
Saccadic velocity is the rate of eye movement in response to stimulus. The saccadic eye movement was used to allow comparison of any sedative effects seen.
Baseline, Day 28, Day 42
Number of Particpants receiving other Anti-epileptic agents During Treatment
Time Frame: Day 1 and Day 14
Day 1 and Day 14
Percent Change from Baseline of Failed Saccades
Time Frame: Baseline, Day 28, Day 42
Failed saccades is stimulus resulting in no eye movement above a defined threshold within a specified time.
Baseline, Day 28, Day 42
Mean trough concentrations of E2007
Time Frame: Day 7, Day 21, and Day 28
Day 7, Day 21, and Day 28
Number of seizures
Time Frame: Baseline (Day-1) to Day 42
Baseline (Day-1) to Day 42
The Clinical Global Impression of Change
Time Frame: Day 28
Day 28

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Eisai Co., Ltd.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
February 14, 2003

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
August 6, 2003

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
August 6, 2003

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
July 31, 2015

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 17, 2018

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
December 19, 2018

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
December 19, 2018

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 17, 2018

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
November 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • E2007-E049-203

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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