PRX-00023 Therapy in Localization-Related Epilepsy

NCT01281956 | Terminated Phase 2 Results

• 2 other identifiers: 11003911-N-0039
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief 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

Conditions

Epilepsy; Epilepsy, Temporal Lobe; Partial Epilepsy

Keywords

Epilepsy; Drug Trial; Serotonin; Serotonin 1A Receptor; Temporal Lobe Epilepsy; Partial Epilepsy

Outcome Measures

Primary Outcomes (1)

• Seizure Frequency in the Active and Placebo Periods

  Participants used a seizure calendar to record the number of seizures that occurred during the three month treatment period, i.e., while participants were either on PRX-0023 or Placebo. Seizure frequency was calculated as the total number of seizures occurring during each three month period. For each period a mean was calculated across subjects.

  Three months

Secondary Outcomes (13)

• Number of Participants With > 50% Lower Seizure Rate on PRX-0023.

  Three months

• Mean Score on the Hamilton Anxiety Rating Scale at the End of the Active and Placebo Periods.

  Three months

• Mean Score on the Hamilton Depression Rating Scale at the End of the Active and Placebo Periods

  Three months

• Mean Score on the Hopkins Verbal Learning Test-Revised (HVLT-R) at the End of the Active and Placebo Periods

  Three months

• The Mean Score on the Brief Visuospatial Memory Test-Revised (BVMT-R), at the End of the Active and Placebo Period.

  Three months

Study Arms (2)

Placebo Then PRX

EXPERIMENTAL

Subjects are administered Placebo x3 months followed by PRX (selective 5HT1A agonist) x3 months

Drug: PRX-00023; Drug: Placebo

PRX Then Placebo

EXPERIMENTAL

Subjects are administered PRX (selective 5HT1A agonist) x3 months followed by Placebo x3 months

Drug: PRX-00023; Drug: Placebo

Interventions

PRX-00023 DRUG

PRX-00023 (Selective 5HT1A agonist)

PRX Then Placebo; Placebo Then PRX

Placebo DRUG

Placebo

PRX Then Placebo; Placebo Then PRX

Eligibility Criteria

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

You may qualify if:

• Enrolled in protocol 01-N-0139
• Age 18 to 65
• 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.
• Patients must be able to provide informed consent.
• Patients must be able to remain on their baseline AED drugs and doses for the duration of the study
• Patients must be able to use seizure calendars to record seizures throughout the trial.
• Experiences 4 seizures within a 6-week period

You may not qualify if:

• Pregnancy or lactation
• 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
• 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.
• A level 4 or 5 on the Columbia Suicide Severity Rating Scale rating for symptoms during the last month
• Concomitant treatment with more than 2 AEDs
• Evidence for a potentially progressive neurologic disorder, such as an astrocytoma
• Use of sublingual lorazepam for seizure clusters more than once per wee
• 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

Sponsors & Collaborators

• National Institute of Neurological Disorders and Stroke (NINDS): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Clinckers R, Smolders I, Meurs A, Ebinger G, Michotte Y. Anticonvulsant action of hippocampal dopamine and serotonin is independently mediated by D and 5-HT receptors. J Neurochem. 2004 May;89(4):834-43. doi: 10.1111/j.1471-4159.2004.02355.x.

  PMID: 15140183 BACKGROUND

• Giovacchini G, Toczek MT, Bonwetsch R, Bagic A, Lang L, Fraser C, Reeves-Tyer P, Herscovitch P, Eckelman WC, Carson RE, Theodore WH. 5-HT 1A receptors are reduced in temporal lobe epilepsy after partial-volume correction. J Nucl Med. 2005 Jul;46(7):1128-35.

  PMID: 16000281 BACKGROUND

• Hasler G, Bonwetsch R, Giovacchini G, Toczek MT, Bagic A, Luckenbaugh DA, Drevets WC, Theodore WH. 5-HT1A receptor binding in temporal lobe epilepsy patients with and without major depression. Biol Psychiatry. 2007 Dec 1;62(11):1258-64. doi: 10.1016/j.biopsych.2007.02.015. Epub 2007 Jun 22.

  PMID: 17588547 BACKGROUND

MeSH Terms

Conditions

Epilepsy; Epilepsy, Temporal Lobe; Epilepsies, Partial

Interventions

naluzotan

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Epileptic Syndromes

Results Point of Contact

• Title: Dr. William Theodore
• Organization: National Institutes of Health

theodorw@ninds.nih.gov

301-496-1505

Study Officials

• William H Theodore, M.D.

  National Institute of Neurological Disorders and Stroke (NINDS)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

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

Study Record Dates

• First Submitted: January 21, 2011
• First Posted: January 24, 2011
• Study Start: January 7, 2011
• Primary Completion: October 5, 2017
• Study Completion: October 5, 2017
• Last Updated: December 7, 2018
• Results First Posted: December 7, 2018

Record last verified: 2017-10-05

Locations

US (1)