NCT01281956

PRX-00023 Therapy in Localization-Related Epilepsy

Terminated Phase 2 Results posted Last updated 7 December 2018

What this trial tests

Phase 2 trial testing PRX-00023 in Epilepsy in 12 participants. Terminated before completion.

Timeline

7 January 2011

Primary endpoint
5 October 2017

5 October 2017

Quick facts

Lead sponsor	National Institute of Neurological Disorders and Stroke (NINDS)
Phase	Phase 2
Status	Terminated
Study type	INTERVENTIONAL
Allocation	randomized
Design	crossover
Masking	double
Primary purpose	treatment
Enrollment	12
Start date	7 January 2011
Primary completion	5 October 2017
Estimated completion	5 October 2017
Sites	1 location across United States

Drugs / interventions tested

• PRX-00023 — full drug profile →
• Placebo

Conditions studied

• Epilepsy — all drugs for Epilepsy →
• Epilepsy, Temporal Lobe — all drugs for Epilepsy, Temporal Lobe →
• Partial Epilepsy — all drugs for Partial Epilepsy →

Sponsor

National Institute of Neurological Disorders and Stroke (NINDS)

Who can join

Adults 18 to 65, any sex, with Epilepsy or Epilepsy, Temporal Lobe. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Seizure Frequency in the Active and Placebo Periods Primary · Three months

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.

Group	Value	95% CI
PRX-0023	66.6	± 93.3
Placebo	54.3	± 79.7

Number of Participants With > 50% Lower Seizure Rate on PRX-0023. Secondary · Three months

Participants used a seizure calendar to record the number of seizures that occurred during each three month treatment period, i.e., while participants were either on PRX-0023 or Placebo. Seizure rate was calculated as the total number of seizures occurring during the three month period. The number of participants with \>50% lower seizure frequency during the active compared with the placebo period was determined.

Group	Value	95% CI
All Participants Who Completed Study	0

Mean Score on the Hamilton Anxiety Rating Scale at the End of the Active and Placebo Periods. Secondary · Three months

Participants were administered the Hamilton Anxiety Rating Scale (HAM-A) at the end of each three month treatment period, i.e., while participants were either on PRX-0023 or Placebo. The HAM-A measures an individual's severity of anxiety symptoms. The scale consists of 14 parameters, each defined by a series of symptoms. Each group of symptoms is scored on a scale of 0 (not present) to 4 (severe), with a total score range of 0-56, where \</=17 indicates mild anxiety, 18-24 mild to moderate anxiety and 25-30 moderate to severe anxiety and \>30 severe anxiety.

Group	Value	95% CI
PRX-0023	5.1	± 5.0
Placebo	5.7	± 5.7

Mean Score on the Hamilton Depression Rating Scale at the End of the Active and Placebo Periods Secondary · Three months

The Hamilton Depression Rating Scale (HAM-D) was administered to participants at the end of each treatment period. The HAM-D is a multiple item questionnaire used to provide an indication of depression. The questionnaire is designed for adults and is used to rate the severity of their depression by probing mood, feelings of guilt, suicide ideation, insomnia, agitation or retardation, anxiety, weight loss, and somatic symptoms. Although the HAM-D form lists 21 items, the scoring is based on the first 17 items. Eight items are scored on a 5-point scale, ranging from 0 = not present to 4 = severe

Group	Value	95% CI
PRX-0023	5.3	± 3.9
Placebo	8.6	± 12.8

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

The HVLT-R is a word-list learning and memory test.The participant is read a list of words and asked to recall as many as possible, without regard to the order in which they were read.The list is read three times with recall requested after each presentation (immediate recall) and after a delay (delayed recall). Individual test results are compared to others of the same age (+/-5 years).Test results are presented as T-scores which are conventionally used in neuropsychology. The participant's raw scores are compared to a population expected raw score, for a particular age group. That score is c

Immediate Recall

Group	Value	95% CI
PRX-0023	34.8	± 13.8
Placebo	41.6	± 10.1

Delayed Recall

Group	Value	95% CI
PRX-0023	33.3	± 14.1
Placebo	39.2	± 10.8

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

The BVMT-R is a test of memory for visual information. Participants are shown a page with several geometric designs arranged in a 2x3 matrix and asked to study the designs. After the page is shown for a brief period the participant is asked to draw each figure.The same page is shown three times with recall requested after each presentation (immediate recall) and after a delay (delayed recall). Individual test results are compared to other people the same age (+/- 5 years).Test results are presented as T-scores which are conventionally used in neuropsychology. The participant's raw scores are c

Immediate Recall

Group	Value	95% CI
PRX-0023	37.4	± 9.7
Placebo	39.0	± 9.9

Delayed Recall

Group	Value	95% CI
PRX-0023	38.0	± 11.9
Placebo	37.4	± 15.4

Mean Score on the Columbia Suicide Severity Rating Scale at the End of the Active and Placebo Periods Secondary · Three months

The Columbia Suicide Severity Rating Scale (C-SSRS) was administered to subjects at the end of each treatment period. The C-SSRS, is a suicidal ideation and behavior rating scale which evaluates suicide risk. The assessment rates an individual's degree of suicidal ideation on a scale, ranging from 0 to 6 as follows: 0 = No suicide ideation; 1 = Wish to be dead; 2 = Non-Specific Active Suicidal Thoughts; 3 = Active Suicidal Ideation with any methods (No Plan) without intent to act; 4 = Active Suicidal Ideation with some intent to act, without specific plan; 5 = Active Suicidal Ideation with spe

Group	Value	95% CI
PRX-0023	9
Placebo	8
PRX-0023	0
Placebo	1
PRX-0023	0
Placebo	0
PRX-0023	0
Placebo	0

Results of Clinical Examination of the Nervous System at the End of the Active and Placebo Treatment Periods Secondary · Three months

A clinical examination of the nervous system was administered by a physician to subjects at the end of each three month treatment period, i.e., while the participant was on PRX-0023 or Placebo. Results of the examination ranged from 0-4 with scores defined as follows: 0 = normal examination; 1 = Observation only; patient asymptomatic; 2 = Patient reports complaint associated with finding but no dysfunction; 3 = Patient reports some impairment of daily function associated with finding; 4 = Patient unable to carry out usual activities due to dysfunction associated with finding.

Group	Value	95% CI
PRX-0023	8
Placebo	9
PRX-0023	0
Placebo	0
PRX-0023	1
Placebo	1
PRX-0023	0
Placebo	0

Results of Clinical Examination of the Respiratory System at the End of the Active and Placebo Treatment Periods Secondary · Three months

A clinical examination of the respiratory system was administered by a physician to subjects at the end of each three month treatment period, i.e., while the participant was on PRX-0023 or Placebo. Results of the examination ranged from 0-4 with scores defined as follows: 0 = normal examination; 1 = Observation only; patient asymptomatic; 2 = Patient reports complaint associated with finding but no dysfunction; 3 = Patient reports some impairment of daily function associated with finding; 4 = Patient unable to carry out usual activities due to dysfunction associated with finding.

Group	Value	95% CI
PRX-0023	8
Placebo	10
PRX-0023	1
Placebo	0
PRX-0023	0
Placebo	0
PRX-0023	0
Placebo	0

Results of Clinical Examination of the Cardiovascular System at the End of the Active and Placebo Treatment Periods Secondary · Three months

A clinical examination of the cardiovascular system was administered by a physician to subjects at the end of each three month treatment period, i.e., while the participant was on PRX-0023 or Placebo. Results of the examination ranged from 0-4 with scores defined as follows: 0 = normal examination; 1 = Observation only; patient asymptomatic; 2 = Patient reports complaint associated with finding but no dysfunction; 3 = Patient reports some impairment of daily function associated with finding; 4 = Patient unable to carry out usual activities due to dysfunction associated with finding.

Group	Value	95% CI
PRX-0023	8
Placebo	9
PRX-0023	1
Placebo	1
PRX-0023	0
Placebo	0
PRX-0023	0
Placebo	0

Results of Clinical Examination of the Musculoskeletal System at the End of the Active and Placebo Treatment Periods Secondary · Three months

A clinical examination of the musculoskeletal system was administered by a physician to subjects at the end of each three month treatment period, i.e., while the participant was on PRX-0023 or Placebo. Results of the examination ranged from 0-4 with scores defined as follows: 0 = normal examination; 1 = Observation only; patient asymptomatic; 2 = Patient reports complaint associated with finding but no dysfunction; 3 = Patient reports some impairment of daily function associated with finding; 4 = Patient unable to carry out usual activities due to dysfunction associated with finding.

Group	Value	95% CI
PRX-0023	9
Placebo	9
PRX-0023	0
Placebo	1
PRX-0023	0
Placebo	0
PRX-0023	0
Placebo	0

Number of Subjects With an Abnormal CBC Result at the End of the Active and Placebo Periods Secondary · Three months

A Complete Blood Count (CBC) was administered at the end of each three month treatment period. A complete blood count test measures several components and features of your blood, including: Red blood cells (which carry oxygen), White blood cells (which fight infection), Hemoglobin (the oxygen-carrying protein in red blood cells), Hematocrit (the proportion of red blood cells to the fluid component (plasma) in your blood), Platelets, (which help with blood clotting). Abnormal increases or decreases in cell counts as revealed in a complete blood count may indicate an underlying medical condition

anemia

Group	Value	95% CI
PRX-0023	2
Placebo	1

leucopenia

Group	Value	95% CI
PRX-0023	2
Placebo	1

leucocytosis

Group	Value	95% CI
PRX-0023	2
Placebo	3

thrombocytosis

Group	Value	95% CI
PRX-0023	0
Placebo	2

Adverse events — posted to ClinicalTrials.gov

Time frame: Adverse Events were collected following baseline history and physical examination and continued until study completion. Study duration was 42-46 weeks (+/- 4 weeks).. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

PRX-0023

Serious: 0/9 (0%)

Deaths: 0/9

Placebo

Serious: 0/10 (0%)

Deaths: 0/10

Other adverse events (20 terms — click to expand)

Reaction	System	PRX-0023	Placebo
Lethargy	Nervous system disorders	—	—
Upper Respiratory Infection	Infections and infestations	—	—
Itching	Skin and subcutaneous tissue disorders	—	—
Headache	Nervous system disorders	—	—
Constipation	Gastrointestinal disorders	—	—
Diarrhea	Gastrointestinal disorders	—	—
Small bumps on back	Skin and subcutaneous tissue disorders	—	—
Bumps at IV site	Skin and subcutaneous tissue disorders	—	—
GI Upset	Gastrointestinal disorders	—	—
Gait Imbalance	Nervous system disorders	—	—
Elevated liver function test >2x normal	Hepatobiliary disorders	—	—
Change in nails and hair	Skin and subcutaneous tissue disorders	—	—
Stomach flu	Infections and infestations	—	—
Injury following seizure	Musculoskeletal and connective tissue disorders	—	—
Bug bites	Skin and subcutaneous tissue disorders	—	—
Weight gain	Gastrointestinal disorders	—	—
Increased appetite	Gastrointestinal disorders	—	—
Achy and sweaty	Infections and infestations	—	—
Chest pressure during sleep	Respiratory, thoracic and mediastinal disorders	—	—
Eye pain	Eye disorders	—	—

Data from ClinicalTrials.gov NCT01281956 adverse events section.

Sponsor's own description

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

Publications & conference data

3 peer-reviewed publications reference this trial (live from Europe PMC):

1. Targeting Sigma Receptors for the Treatment of Neurodegenerative and Neurodevelopmental Disorders.
   Malar DS, Thitilertdecha P, Ruckvongacheep KS, Brimson S, et al · · 2023 · cited 39× · PMID 37166702 · DOI 10.1007/s40263-023-01007-6
2. Antidepressant Drugs for Seizures and Epilepsy: Where do we Stand?
   Tallarico M, Pisano M, Leo A, Russo E, et al · · 2023 · cited 15× · PMID 35761500 · DOI 10.2174/1570159x20666220627160048
3. Modest growth seen in epilepsy market.
   Gohil K, Enhoffer D. · · 2014 · cited 3× · PMID 25395821