PRX-00023 Therapy in Localization-Related Epilepsy
- 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.
- To evaluate the effectiveness of PRX-00023 in reducing the frequency of epileptic seizures that start from only one part of the brain.
- 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).
- 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.
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
Epilepsy, Temporal Lobe
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
|Official Title:||A Phase II Clinical Trial of PRX-00023 Therapy in Localization-Related Epilepsy|
- Seizure frequency counts during the 3 month placebo and active treatment phases [ Time Frame: End of Phase I & amp; II ] [ Designated as safety issue: No ]
- Proportion of patients with greater than or equal to 50% lower seizure rate on PRX-0023 than placebo, Hamilton Depression and Anxiety Rating scales, and performance on neuropsychological testing scales. [ Time Frame: End Phase I and II ] [ Designated as safety issue: No ]
- Safety assessment for adverse events, changes in vital signs, laboratory test results and physical examination. [ Time Frame: Monthly Visits ] [ Designated as safety issue: Yes ]
- Hamilton Depression and Anxiety rating scales [ Time Frame: 34 weeks ] [ Designated as safety issue: No ]
- Performance on neuropsychological testing scales [ Time Frame: 34 weeks ] [ Designated as safety issue: No ]
- Columbia suicide severity rating scale [ Time Frame: 34 weeks ] [ Designated as safety issue: Yes ]
|Study Start Date:||January 2011|
|Estimated Study Completion Date:||August 2015|
|Estimated Primary Completion Date:||August 2015 (Final data collection date for primary outcome measure)|
PRX-00023 is a selective 5HT1A agonist being developed as an oral therapeutic treatment for epilepsy.
To initiate a pilot clinical trial assessing the safety, tolerability and efficacy of the 5HT1A receptor agonist PRX-00023 in patients with localization-related epilepsy. PRX-00023 is a 5HT1A receptor agonist that has shown promise in clinical trials of depression. Patients with localization-related epilepsy have reduced 5HT1A receptor binding on 18FCWAY positron emission tomography (PET). Increasing neurotransmitter activity at 5HT1A receptor sites might ameliorate seizures. Moreover, depression is a common co-morbidity in people with epilepsy. Altered 5HT1A receptor binding has been found in depression.
Thirty adults with localization-related epilepsy.
A randomized, double-blind, placebo-controlled cross-over, phase II clinical trial.
The trial will have a baseline phase in which each patient will undergo physical and neurological examination, standard blood tests, neuropsychological and mood evaluation, FCWAY PET (if not already performed) and MRI. During the subsequent first treatment phase, patients will be randomized to PRX-00023 (120mg BID) or matching placebo. After completion of the first treatment phase, patients will be crossed over to the alternate treatment arm.
- Seizure frequency counts during the 3-month placebo and active treatment phases
- Neuropsychological and mood indices
- Safety assessment will include adverse events, vital signs, laboratory signs and physical examination.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01281956
|Contact: Tamika Mason||(301) email@example.com|
|Contact: William H Theodore, M.D.||(301) firstname.lastname@example.org|
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike||Recruiting|
|Bethesda, Maryland, United States, 20892|
|Contact: For more information at the NIH Clinical Center contact Patient Recruitment and Public Liaison Office (PRPL) 800-411-1222 ext TTY8664111010 email@example.com|
|Principal Investigator:||William H Theodore, M.D.||National Institute of Neurological Disorders and Stroke (NINDS)|