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

NCT03780907 | Completed Phase 2

• 1 other identifier: E2007-E049-203
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Epilepsy

Keywords

Epilepsy; E2007; partial seizures; generalized seizures

Outcome Measures

Primary Outcomes (9)

• Number of participants with Treatment Emergent Adverse Events (TEAEs)

  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)

  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

  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

  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

  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

  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

  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

  Standard pharmacokinetic parameters for E2007 were derived from plasma drug concentrations in epileptic participants.

  Day 14

• Pharmacokinetic Parameter: Observed Accumulation Ratio (Rac) of E2007

  Standard pharmacokinetic parameters for E2007 were derived from plasma drug concentrations in epileptic participants.

  Day 14

Secondary Outcomes (7)

• Change from Baseline of Bond and Lader Scale

  Baseline, Day 28 and Day 42

• Change from Baseline of Peak Saccadic Velocity (PSV)

  Baseline, Day 28, Day 42

• Number of Particpants receiving other Anti-epileptic agents During Treatment

  Day 1 and Day 14

• Percent Change from Baseline of Failed Saccades

  Baseline, Day 28, Day 42

• Mean trough concentrations of E2007

  Day 7, Day 21, and Day 28

Study Arms (3)

E2007 1 mg

EXPERIMENTAL

Tablet, once daily to be taken in the morning by mouth, one hour before breakfast, with a glass of water.

Drug: E2007

E2007 2 mg

EXPERIMENTAL

Tablet, once daily to be taken in the morning by mouth, one hour before breakfast, with a glass of water.

Drug: E2007

Placebo

PLACEBO COMPARATOR

Tablet, once daily to be taken in the morning, one hour before breakfast, with a glass of water.

Drug: Placebo

Interventions

E2007 DRUG

1 mg of E2007 was administered by mouth once daily.

E2007 1 mg

Placebo DRUG

Placebo once daily of oral tablet formulation to be taken in the morning, one hour before breakfast, with a glass of water.

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Age: 18 to 65 years.
• Race: any.
• Patients receiving up to two additional anti-epileptic medications at doses that were stable for at least the four weeks immediately preceding baseline.
• Patients willing and able to co-operate with the study procedures including completion of patient diaries.
• Patients living at home with a partner or carer able to monitor compliance.
• Patients giving informed consent to participate in the study.

You may not qualify if:

• Pregnant or lactating women.
• 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.
• Fertile men not willing to use reliable contraception or with partners not willing to use reliable contraception.
• Patients with status epilepticus within the past 24 months.
• 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.
• Patients with significantly elevated liver enzymes (abnormal bilirubin level, or serum transaminase levels more than 1.5 times the upper limit of normal).
• 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.
• Patients with past or present drug or alcohol abuse.
• Patients with unstable psychiatric illness.
• Patients who had received an investigational drug within the three months before baseline.
• Patients without a reliable partner or carer.
• Patients with any condition which would make the patient, in the opinion of the investigator, unsuitable for the study.

Sponsors & Collaborators

• Eisai Co., Ltd.: lead

Study Sites (1)

3ClinicalResearch AG

Hennigsdorf, Germany

Location

Related Publications (1)

• Maguire M. Response to "Perampanel and pregnancy: Could experience be a gloomy lantern that does not even illuminate its bearer?". Epilepsy Behav. 2022 Apr;129:108654. doi: 10.1016/j.yebeh.2022.108654. Epub 2022 Mar 16. No abstract available.

  PMID: 35305920 DERIVED

MeSH Terms

Conditions

Epilepsy; Seizures

Interventions

perampanel

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 31, 2015
• First Posted: December 19, 2018
• Study Start: February 14, 2003
• Primary Completion: August 6, 2003
• Study Completion: August 6, 2003
• Last Updated: December 19, 2018

Record last verified: 2015-11

Locations

DE (1)