Primary Objective* To demonstrate the efficacy of adjunctive perampanel therapy, compared to placebo on primary generalized tonic-clonic (PGTC)seizuresSecondary Objectives* To evaluate the safety and tolerability of perampanel in subjects with…
ID
Source
Brief title
Condition
- Seizures (incl subtypes)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Efficacy: Efficacy will be assessed by seizure counts (via seizure diary) and
CGIC.
Secondary outcome
Pharmacokinetic: Plasma concentrations of perampanel will be determined in
blood samples collected at designated timepoints.
Safety: Safety will be assessed by monitoring of adverse events (AEs),
withdrawal from treatment, suicidality (C-SSRS), prior and concomitant
medication usage, clinical laboratory tests (chemistry, hematology, and
urinalysis), vital signs, and changes in physical and neurological
examinations. In addition, a withdrawal questionnaire will be administered to
assess potential withdrawal signs and symptoms that might be associated with
the discontinuation of perampanel.
Other Criteria for Evaluation: Perampanel exposure vs response (seizure
frequency) and vs AEs
Background summary
Currently only three new AEDs, levetiracetam, lamotrigine, and topiramate, are
indicated for the treatment of primary generalized tonic-clonic seizures. This
study is designed to evaluate the efficacy, safety, and pharmacokinetics (PK)
of perampanel on PGTC seizure frequency in adolescents and adults maintained on
one to two stable antiepileptic drugs.
The study follows the standard design utilized for the studies of previously
approved AEDs in this indication (levetiracetam, lamotrigine, and topiramate).
Study objective
Primary Objective
* To demonstrate the efficacy of adjunctive perampanel therapy, compared to
placebo on primary generalized tonic-clonic (PGTC)
seizures
Secondary Objectives
* To evaluate the safety and tolerability of perampanel in subjects with
inadequately controlled PGTC seizures
Exploratory Objectives
* To evaluate the pharmacokinetics (PK) of perampanel in subjects with
inadequately controlled PGTC seizures
* To explore the efficacy of adjunctive perampanel therapy compared to placebo,
on the physician-rated Clinical Global Impression of Change
scale (CGIC)
* To explore the relationship between plasma perampanel concentrations,
efficacy, and safety using population pharmacokinetic/ pharmacodynamic (PK/PD)
modeling
Study design
This will be a double-blind, randomized, placebo-controlled, multicenter,
parallel-group, adjunctive-therapy study. Males and females 12 years and older
who have a diagnosis of PGTC seizures receiving one to two AEDs, and
experiencing * 3 PGTC seizures during the Baseline Period, will be included in
this trial. Subjects will be administered up to 8 mg/day of perampanel or
perampanel-matched placebo in the Core Study. The study will consist of three
phases: Prerandomization, Randomization, and Extension. The Core Study will
consist of the Prerandomization and Randomization Phases. The Prerandomization
Phase will consist of two periods: Screening (up to 4 weeks) and Baseline (4-
or 8- weeks), during which subjects will be assessed for overall eligibility to
participate in the study, including seizure activity. The Randomization Phase
will consist of three periods: Titration (4 weeks), Maintenance (13 weeks), and
Follow-up for subjects not rolling over into the Extension Phase (4 weeks). The
Extension Phase (Part A and Part B) will be comprised of the Conversion (6
weeks), Maintenance (84 weeks), and Follow-up (4 weeks) Periods and will last
approximately 94 weeks, or until perampanel is made commercially available for
the treatment of primary generalized tonic-clonic (PGTC) seizures. (see section
8.1 Protocol V4.0 dd 12-Apr-12)
Intervention
Investigational drug: Perampanel, oral tablets, up to 8 mg/day (Core Study); up
to 12 mg/day (Extension Phase)
Comparator drug/reference therapy: Perampanel-matched placebo oral tablets
Study burden and risks
The most important side effects of Permapanel are sleepiness and dizziness.
Other common side effects are: spinning sensation (vertigo), blurred vision,
feeling sick (nausea), feeling very tired (fatigue), irritability, weight gain,
decreased appetite, back pain, difficulty with walking (ataxia), unsteady gait
(gait disturbance), balance problems (balance disorder), falling down (fall),
slow speech (dysarthria), anxiety, double vision (diplopia), increased
appetite, aggression and anger.
Procedures Core Study:
- Diary regarding seizures
- 3x Physical and neurological examinations
- 9x Vital signs
- 1x ECG
- 8x Pregnancy Test (1x blood, 9x urine, only women of childbearing potential)
- 1 x Urine drug testing
- 8x Questionnaires
- 8x Blood tests
- 3 x additional questionnaires about quality of life
(- 5 x questionnaire Healthcare resource utilization: to be interviewed by site
staff )
Procedures Extension Phase:
- Diary regarding seizures
- 5x Vital signs
- 7x Pregnancy Test (urine, only women of childbearing potential)
- 1 x Urine drug testing
- 7x Questionnaires
- 4x Blood tests
European Knowledge Centre, Mosquito Way
AL10 9SN Hatfield
GB
European Knowledge Centre, Mosquito Way
AL10 9SN Hatfield
GB
Listed location countries
Age
Inclusion criteria
* Ages 12 years and older; in India less than 65 years of age
* Clinical diagnosis of PGTC seizures in the setting of idiopathic generalized epilepsy (with or without other subtypes of primary generalized seizures) and experiencing * 3 PGTC seizures
during the 8-week period prior to randomization
* Have had a routine electroencephalogram (EEG) up to 5 years prior to or during the
Baseline Period with electroencephalographic features consistent with
primary generalized epilepsy; other concomitant anomaly should be
explained by adequate past medical history
* On a fixed dose of one to a maximum three concomitant AEDs for a minimum of 30
days prior to Baseline; only one inducer AED (i.e., carbamazepine,
oxcarbazepine, or phenytoin) out of the maximum of three AEDs will be
allowed
* A vagal nerve stimulator (VNS) will be allowed, but it must have been
implanted * 5 months prior to Baseline (stimulator parameters can not
be changed for 30 days prior to Baseline and for the duration of the
study)
* Have had a computed tomography (CT) or magnetic resonance imaging
(MRI) within the last 10 years (for adults) and 5 years (for adolescents)
that ruled out a progressive cause of epilepsy
* A ketogenic diet will be allowed as long as the subject has been on this
diet for 5 weeks prior to randomization
Exclusion criteria
* Participated in a study involving administration of an investigational
compound or device within the 30 days prior to Baseline, or within
approximately 5 half-lives of the previous investigational compound,
whichever is longer
* Pregnant and/or nursing
* Participated in previous perampanel studies
* A history of status epilepticus that required hospitalization within 12
months prior to Baseline
* Seizure clusters where individual seizures cannot be counted
* A history of psychogenic seizures
* Any suicidal ideation with intent with or without a plan at or within 6
months prior to Visit 2 (i.e., answering "Yes" to questions 4 or 5 on the
Suicidal Ideation section of the Columbia-Suicide Severity Rating Scale
(C-SSRS)
* Evidence of clinically significant disease (e.g., cardiac, respiratory,
gastrointestinal, renal disease) that in the opinion of the investigator(s)
could affect the subject's safety or study conduct
* Concomitant diagnosis of Partial Onset Seizures (POS)
* Progressive neurological disease
* Clinical diagnosis of Lennox-Gastaut syndrome
* History of drug or alcohol dependency or abuse within 2 years prior to
Screening
* Have had multiple drug allergies or a severe drug reaction to an
AED(s), including dermatological (e.g., Stevens-Johnson syndrome),
hematological, or organ toxicity reactions
* If felbamate is used as a concomitant AED, subjects must be on
felbamate for at least 2 years, with a stable dose for 60 days prior to
Baseline. They must not have a history of white blood cell (WBC) count
below * 2500/*L (2.50 1E+09/L), platelets < 100,000/*L, liver function
tests (LFTs) > 3 times the upper limit of normal (ULN), or other
indication of hepatic or bone marrow dysfunction while receiving
felbamate.
* Concomitant use of vigabatrin: Subjects who took vigabatrin in the
past must be discontinued for approximately 5 months prior to Baseline,
and must have documentation showing no evidence of a vigabatrinassociated
clinically significant abnormality in an automated visual
perimetry test
* Concomitant use of medications known to be inducers of CYP3A (with the exception of carbamazepine, oxcarbazepine, and phenytoin) within 30 days prior to Baseline. Concomitant use of barbiturates (except for seizure control indication) within 30 days prior to Baseline
* Use of intermittent rescue benzodiazepines (i.e., one to two doses over
a 24-hour period considered one-time rescue) two or more times within
the 30 days prior to Baseline
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2011-000265-12-NL |
| ClinicalTrials.gov | NCT01393743 |
| CCMO | NL37471.068.11 |