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PRX-00023 Therapy in Localization-Related Epilepsy

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by National Institutes of Health Clinical Center (CC)
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute of Neurological Disorders and Stroke (NINDS) )
ClinicalTrials.gov Identifier:
NCT01281956
First received: January 21, 2011
Last updated: June 20, 2014
Last verified: June 2014
  Purpose

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

...


Condition Intervention Phase
Epilepsy
Epilepsy, Temporal Lobe
Partial Epilepsy
Drug: PRX-00023
Phase 2

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 30
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)
Intervention Details:
    Drug: PRX-00023
    N/A
Detailed Description:

Introduction:

PRX-00023 is a selective 5HT1A agonist being developed as an oral therapeutic treatment for epilepsy.

Objective:

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.

Study Population:

Thirty adults with localization-related epilepsy.

Design:

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.

Outcome measures:

  1. Seizure frequency counts during the 3-month placebo and active treatment phases
  2. Neuropsychological and mood indices
  3. Safety assessment will include adverse events, vital signs, laboratory signs and physical examination.
  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION CRITERIA:

    1. Age 18 to 65
    2. 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.
    3. Patients must be able to provide informed consent.
    4. Patients must be able to remain on their baseline AED drugs and doses for the 34 weeks of the study
    5. Patients must be able to use seizure calendars to record seizures throughout the trial.

EXCLUSION CRITERIA:

  1. Pregnancy or lactation or women of child-bearing potential 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
  2. Use of any alcohol or recreational drugs starting two weeks before entering baseline
  3. Contraindication to MRI such as presence of prohibited implants, aneurysm clips, metallic prostheses (including metal pins and rods, heart valves, and cochlear implants), permanent eyeliner, implanted delivery pump, or shrapnel fragments
  4. 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
  5. Inability to participate in the study procedures, such as MRI, PET, seizure and adverse event recording, or drug titration
  6. 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.
  7. A level 4 or 5 on the Columbia Suicide Severity Rating Scale rating for symptoms during the last three months
  8. Concomitant treatment with more than 2 AEDs
  9. Evidence for a potentially progressive neurologic disorder, such as an astrocytoma
  10. Use of sublingual lorazepam for seizure clusters more than once per wee
  11. 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
    • Fluvoxamine; required interval period (weeks prior to baseline) is 2
    • Citalopram; required interval period (weeks prior to baseline) is 2
    • Paroxetine; required interval period (weeks prior to baseline) is 2
    • Sertraline; required interval period (weeks prior to baseline) is 2
    • buproprion; required interval period (weeks prior to baseline) is 2
    • Mirtazepine; required interval period (weeks prior to baseline) is 2
    • Nefazodone; required interval period (weeks prior to baseline) is 2
    • Venlafaxine; required interval period (weeks prior to baseline) is 2
    • Duloxetine; required interval period (weeks prior to baseline) is 2
    • Trazodone; required interval period (weeks prior to baseline) is 2
    • tricyclic and heterocyclic antidepressants; 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01281956

Contacts
Contact: Patricia M Reeves-Tyer, R. EEG T. (301) 496-1923 tyerp@ninds.nih.gov
Contact: William H Theodore, M.D. (301) 496-1505 theodorw@ninds.nih.gov

Locations
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    prpl@mail.cc.nih.gov   
Sponsors and Collaborators
Investigators
Principal Investigator: William H Theodore, M.D. National Institute of Neurological Disorders and Stroke (NINDS)
  More Information

Additional Information:
Publications:
Responsible Party: National Institutes of Health Clinical Center (CC) ( National Institute of Neurological Disorders and Stroke (NINDS) )
ClinicalTrials.gov Identifier: NCT01281956     History of Changes
Other Study ID Numbers: 110039, 11-N-0039
Study First Received: January 21, 2011
Last Updated: June 20, 2014
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Epilepsy
Drug Trial
Serotonin
Serotonin 1A Receptor
Temporal Lobe Epilepsy
Partial Epilepsy

Additional relevant MeSH terms:
Epilepsies, Partial
Epilepsy
Epilepsy, Temporal Lobe
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases

ClinicalTrials.gov processed this record on November 27, 2014