PRX-00023 Therapy in Localization-Related Epilepsy

• Status: Terminated
• Trial end date: 2017-10-05
• Target enrollment: 0
• Participant gender: All

Summary

Background:

• The brain chemical serotonin helps nerve cells communicate. Previous research suggests that serotonin activity may be lower in brain areas where seizures start, and that increasing activity at the serotonin receptor site on nerve cells may help prevent seizures. Researchers are interested in determining whether the experimental medication PRX-00023, which increases the activity of serotonin receptors, can reduce seizure frequency in people whose seizures are not well-controlled on antiseizure medication. PRX-00023 has not previously been studied in people with epilepsy and has not previously been given to people taking antiseizure medication at the same time.

Objectives:

• To evaluate the effectiveness of PRX-00023 in reducing the frequency of epileptic seizures that start from only one part of the brain.

Eligibility:

• Individuals between 18 and 65 years of age who have frequent epileptic seizures even after trying at least two different standard anti-seizure medications (either at the same time or one after the other).

Design:

• The study requires 9 outpatient visits to the NIH Clinical Center over a 34-week period. Individuals who choose to participate in additional studies may be an inpatient during some of these visits.

• Participants will be screened with a medical history and physical examination, blood and urine samples, ECG, EEG, neuropsychological studies, imaging studies, including PET and MRI scans

• Participants will have a 6-week observation and evaluation period before starting the study medication. Participants who have at least four seizures during this period will be eligible for the treatment portion of the study.

• All participants will receive either PRX-00023 or a placebo pill twice daily for 12 weeks, and will have regular clinic visits with blood samples and imaging studies.

• After the 12-week period, participants will have a 2- to 3-week washout period without any study medication.

• Participants will then have another study medication period, and will receive the opposite pill (PRX-00023 or placebo) from the one taken in the first treatment phase. Participants will continue to have regular clinic visits with blood samples, ECG, EEG and neuropsychologicalstudies.

• One month after the end of the second study medication phase, participants will have a followup evaluation with a physical examination, blood tests, ECG, EEG, mood and neuropsychological tests.

Outcome measures:

The primary outcome measure for drug efficacy will be:

Mean difference in seizure frequency comparing the active and placebo periods.

Secondary outcome measures for efficacy will be:

Proportion of patients with greater than or equal to 50% lower seizure rate on PRX-00023 than placebo

Hamilton Depression and Anxiety Rating scales

Performance on mood and neuropsychological testing scales

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Institute of Neurological Disorders and Stroke (NINDS)
• Treatments: Naluzotan; Serotonin; Serotonin 5-HT1 Receptor Agonists

Criteria

• INCLUSION CRITERIA:

1. Enrolled in protocol 01-N-0139

2. Age 18 to 65

3. Localization-related epilepsy diagnosed by standard clinical criteria that has not responded to treatment with up to two standard antiepileptic drugs either sequentially or in combination.

4. Patients must be able to provide informed consent.

5. Patients must be able to remain on their baseline AED drugs and doses for the duration of the study

6. Patients must be able to use seizure calendars to record seizures throughout the trial.

7. Experiences 4 seizures within a 6-week period

EXCLUSION CRITERIA:

1. Pregnancy or lactation

2. Women of child-bearing potential and men who are unable or unwilling to take adequate contraceptive precautions, including one of the following:

• hormonal contraception (birth control pills, injected hormones or vaginal ring);

• intrauterine device;

• barrier methods (condom or diaphragm) combined with spermicide;

• surgical sterilization (hysterectomy, tubal ligation, or vasectomy in a partner

3. Current treatment for another significant medical disorder, such as diabetes, or heart disease, or an untreated disorder, that is discovered during the screening examination and might interfere with the study and is determined by the PI to warrant exclusion of the participant.

4. An abnormality on clinical laboratory tests, physical examination, EEG or ECG that might increase the risk associated with trial participation or investigational product administration, such as hepatic enzyme elevation greater than twice normal, or hematocrit lower than 30.

5. A level 4 or 5 on the Columbia Suicide Severity Rating Scale rating for symptoms during the last month

6. Concomitant treatment with more than 2 AEDs

7. Evidence for a potentially progressive neurologic disorder, such as an astrocytoma

8. Use of sublingual lorazepam for seizure clusters more than once per wee

9. Use of any of the following prohibited medications/classes with less than required interval period:

• Any other Investigational drugs; required interval period (weeks prior to baseline) is 4

• benzodiazepines; required interval period (weeks prior to baseline) is 4

• MAO Inhibitors anti depressant; required interval period (weeks prior to baseline) is 4

• Buspirone; required interval period (weeks prior to baseline) is 2

• other psychotropic medicines; required interval period (weeks prior to baseline) is 2

• potent CYP3A4 inducers/inhibitors; required interval period (weeks prior to baseline) is 2 for:

• Itraconazole

• ketoconazole

• HIV antivirals

• clarithromycin

• phenytoin

• Prornolol is 2