Feature article: The research pipeline and what this means for the future of those living with epilepsy
Any medication that your doctor prescribes has come down a long path starting in a laboratory with animal subjects and then moving on to clinical trials with humans until it eventually reached your pharmacy and you. Typically, a specific drug is developed to treat a certain disease or symptom but sometimes its utility can also be discovered quite by accident. Anti-seizure medications follow the same pathway as all other drugs.
How is the safety of medications ensured?
Many drugs never even make it to human testing or review by the Food and Drug Administration (FDA). Drugs that do make it to clinical human trials are rigorously evaluated by the FDA. Everything about the drug--from how clinical trials are designed, to the presence of adverse events and side effects, to the conditions under which the drug is manufactured- all fall under the oversight of the FDA.
The FDA is the oldest US federal government consumer protection agency. It can trace its origins to the passage of the 1906 Pure Food and Drugs Act, a law that was meant to prevent interstate commerce of contaminated and mislabeled food and drugs. Over the last 100+ years, the FDA has evolved into what it is now which is an agency that oversees new medications and treatments thereby ensuring safety for patients. In 2005, the Drug Safety Oversight Board (DSB), was created and mandated by law in the FDA Amendments Act of 2007. The purpose of this Board is to advise the Center for Drug Evaluation and Research (CDER) director on managing and communicating important issues involving emerging drug safety issues.
A very brief history of anti-seizure medications
Anti-seizure medications (or anti-convulsant medications) are a variety of pharmacological agents that are used to treat epileptic seizures. In the 1800's a doctor observed quite by accident that potassium bromide acted as a sedative and was later used in the treatment of epilepsy with some success (although with some very unpleasant side effects). In 1912, phenobarbital was also accidentally observed to have sedative qualities and later to have positive effects on patients who had epilepsy. To this day. phenobarbital is still one of the drugs in the epileptologists' armamentarium. In the 1930's phenytoin emerged and in the 60's and 70's valproate and carbamazepine were developed. And then in the last 50 years, there has been a virtual boom in the development of new anti-seizure medications which has broadened the options available to patients and their doctors in an incredible manner. This was partially the result of a partnership that developed between the US National Institutes of Health (NIH), National Institutes of Neurological Disorders and Stroke (NINDS)-sponsored Anticonvulsant Screening Program and the pharmaceutical industry.
Clinical trials are performed as one of the last steps before new medications can be made available to all humans. These trials are developed together with the FDA and there is considerable oversight from the beginning to the end to ensure patient safety.
There are currently several clinical trials available at NEREG and MAESC testing anti-seizure medications (read more below):
List of current clinical trials at MAESC:
Study 1:
* A medication that works on the cholesterol pathway in the brain to decrease seizures. It also has anti-inflammatory and neuroprotective effects.
* This is a double-blind, randomized, placebo-controlled clinical trial.
* Pediatric and adult patients with Lennox Gastaut Syndrome from 2-55 years of age are eligible.
* The safety, efficacy and tolerability will be studied.
* The trial duration is about 23 weeks.
Study 2:
* A medication that works in a unique way to combat seizures.
* This is a double-blind, randomized, placebo-controlled clinical trial.
* Pediatric and adult patients with Lennox Gastaut Syndrome from 4-55 years of age are eligible.
* The safety, efficacy and tolerability will be studied.
* Patients who complete the study may be eligible for an open-label extension trial.
* The trial duration is about 23 weeks.
Study 3:
* A medication that works at the serotonin pathway to decrease seizure activity.
* This is a double-blind, randomized, placebo-controlled clinical trial.
* Adult patients with developmental epileptic encephalopathies such as Lennox Gastaut Syndrome, Dravet Syndrome, CDKL-5 deficiency disorder, as well as tuberous sclerosis complex from 12-65 years of age are eligible.
* The safety, tolerability and efficacy will be studied.
* The trial duration is about 22 weeks.
Study 4:
* A medication that works at the serotonin pathway to decrease seizure activity.
* This is a double-blind, randomized, placebo-controlled clinical trial.
* Pediatric and adult patients Dravet Syndrome from 2 years of age and older are eligible.
* The safety, tolerability and efficacy will be studied.
* Patients who complete the study may be eligible for an open-label extension trial.
* The trial duration is about 15 months.
Study 5:
* A medication that has been an exceptionally effective medication for adults with epilepsy. It has led to seizure freedom in over 20% of patients. It is now being studied for use in children.
* This is an open label safety and efficacy phase 3 study with open-label extension, where patients can receive the medication after the trial ends, if desired.
* Children with focal (partial onset) seizures aged 2-17 years old are eligible.
* Safety and tolerability will be studied.
* Total duration is about 6 months, followed by open-label extension.
Study 6:
* Prolonged seizures or seizure clusters require rapid, effective treatments that can be given easily by a caregiver. This medication (which has been used since the 1970's) will be delivered through a new device where patients breathe in the medication, similar to asthma inhalers. This causes the medication to act very fast compared to other rescue medications.
* This is an open-label study in patients 12 years and older with prolonged seizures or clusters of seizures.
* Every participant will receive a single dose of the medication (no seizures required) to study how the medication is absorbed.
Study 7:
* This medication has a unique way of targeting the GABAA receptor pathway that may be affected in tuberous sclerosis complex (TSC), and prior studies showed reduction in seizures in TSC patients.
* This is a phase 3, double-blind, randomized clinical trial to study the effects of this medication on epilepsy in TSC.
* Patients with TSC, between 1 to 65 years of age, and with epilepsy refractory to > 2 antiseizure medications are eligible.
* The study duration is about 20 weeks.
* After the trial, there is an open-label extension, during which patients may receive the treatment at no cost.
Study 8:
* This medication is being evaluated for effectiveness in adults with treatment resistant focal (partial onset) epilepsy.
* This is a randomized, double-blind, placebo-controlled trial.
* Patients from 16 and 64 years old, with a diagnosis of focal (partial onset)epilepsy may be eligible.
* The study is evaluating the efficacy, safety, and tolerability of this medication 50 mg or 200 mg compared to placebo in adults with treatment resistant focal epilepsy.
* The trial duration is about 10 weeks.
For adults (over age 18 years):
Study 9:
* Several antiseizure medications are often used to control seizures in an individual and levetiracetam is a commonly used medication. This new drug added to levetiracetam increases the response to levetiracetam by 25 times. This trial will study the effects of the drug on seizures in patients treated with levetiracetam or other anti-epileptic drugs.
* This is a double-blind, randomized, placebo-controlled clinical trial.
* Adults with focal (partial onset) seizures 18 to 69 years of age are eligible.
* The safety, efficacy and tolerability will be studied.
* The trial duration is about 22 weeks.
Study 10:
* This medication works in a new way and has shown very high effectiveness in studies so far.
* This is the last, large study, a phase 3, double-blind, randomized clinical trial to study the effects of this medication on seizures in patients with focal (partial onset) epilepsy that is not completely controlled with other drugs.
* Adults with focal epilepsy 18 to 75 years of age are eligible.
* The safety, efficacy and tolerability will be studied.
* Patients who complete the study may be eligible for an open-label extension trial.
* The trial is about 6 months.
Study 11:
* Benzodiazepines (drugs such as valium) are often used for seizure control but are accompanied by many side effects including sleepiness. This novel medication works similarly but avoids many of these side effects.
* This is a double-blind, placebo-controlled trial with an open label extension to assess the safety and efficacy of this adjunctive medication in individuals with drug-resistant focal (partial onset) seizures.
* Patients with epilepsy with focal onset and motor components for at least two years, average 4 seizures per month for 3 months, between 18-75 years old are eligible.
* Safety, tolerability, and efficacy of the treatment will be studied.
* Total duration is about 6 months.
Study 12:
* This is a randomized, double-blind, placebo-controlled, adjunctive treatment trial to evaluate the efficacy and safety of this medication in patients with treatment-refractory focal (partial onset) seizures.
* Patients with focal epilepsy between 18 to 75 years old are eligible.
* Safety, tolerability, and efficacy of the tablets will be studied.
* Total duration is about 7 months.
List of current clinical trials at the Northeast Regional Epilepsy Group (NEREG):
For children:
Study 1:
An Open Label Study with Extension Phase to Evaluate the Efficacy and Safety of A novel medication as an Adjunctive Therapy in Pediatric Subjects (Age 1 month to less than 18 years) with Childhood Epilepsy.
Study 2:
An Open Label, Single-Dose, Pharmacokinetics Study of novel medication with Open Label safety period in Pediatric Subjects with Epilepsy (2 to 5 years)
Study 3:
A Randomized, Double-blind, Placebo-controlled, Multicenter Study to Evaluate the Efficacy and Safety of a novel medication as a adjunctive therapy in subjects with Primary Generalized Tonic-Clonic Seizures (12-60 years).
Study 4:
A phase 1, open label pharmacokentic dose escalation study of a novel medication (YKP3089) in Pediatric Subjects with POS (2-18 years)
Study 5:
A Randomized, Doubleblind, Placebo-Controlled Study to Investigate the Efficacy and Safety of a novel medication as Adjunctive Treatment for Seizures Associated with Lennox-Gastaut Syndrome in Children and Adults, with Optional Open-Label Extension (4-55 years)
Study 6:
Open-Label Safety and Efficacy Study of a novel medication in Pediatric Subjects with Partial-onset (Focal) Seizures (2-17 years).
Study 7:
A phase 3, double blind randomized placebo-controlled trial of adjunctive novel medication treatment in children and Adults with Tuberous Sclerosis Complex (TSC) related Epilepsy (1-65 years).
For adults:
Study 8:
A Randomized, Double-Blind, Placebo-Controlled, Parallel Group, Multicenter Trial of a novel medication as Adjunctive Therapy in Adults with Drug-Resistant Focal Onset Seizures (18 to 75 years)
Study 9:
A Randomized, Double-blind, Placebo-controlled, Multicenter Study to Evaluate the Efficacy and Safety of a novel medication Adjunctive Therapy in Subjects with Primary Generalized Tonic-Clonic Seizures (12-60 years)
Study 10:
A Randomized, Double-blind, Placebo-Controlled Study to Investigate the Efficacy and Safety of a novel medication as Adjunctive Treatment for Seizures Associated with Lennox-Gastaut Syndrome in Children and Adults, with Optional Open-Label Extension (4-55 years)
Study 11:
Equilibre/A Randomized Phase 2 Study of Adjunctive novel medication for Uncontrolled Focal Onset Seizures (16-55 years).
Study 12:
A phase 3, double blind randomized placebo-controlled trial of adjunctive novel medication for treatment in children and Adults with Tuberous Sclerosis Complex (TSC) related Epilepsy (1-65 years).
Study 13:
A Randomized, Double-Blind Placebo-controlled multicenter Phase 3 Study to Evaluate the safety tolerability and efficacy of a as adjunctive Therapy in focal onset Epilepsy 18-75 years). novel medication in a Randomized double-blind placebo controlled adjunctive treatment trial to evaluate the efficacy and safety of this medicatin in patients with treatment refractory Focal seizures (18-75 years).
A few final frequently-asked-questions about pharmaceutical trials and their answers:
In a few words, why are clinical trials conducted? Clinical trials are performed for patients to gain access to new medications that can provide better seizure coverage with less side effects. All medications are approved by the FDA before they can be available to patients. In order for new medications to be approved by the FDA and available for use, clinical trials are needed before a medication becomes publicly available. These trials are all developed together with the FDA.
How does a patient enroll? The patient's epilepsy doctor may bring this up directly during the office visit as a treatment option and refer the patient for screening with the research staff or the patient may contact our research program directly at 551-497-5000. For more information, visit: https://epilepsygroup.com/info23-70/open-clinical-studies.htm
For patients enrolling in MAESC, contact Research Coordinators: Arkady Barber and Salman Hashmi at 301-530-9744 and Fax: 301-530-0046.
What does it mean to be eligible for a study? Patients may be eligible if they have uncontrolled seizures. Before entering a study, the patient will be screened by NEREG and MAESC physicians and research coordinators.
What should a patient expect once they are enrolled? Primarily, the patient should expect to receive a new treatment in addition to his/her current treatments. In addition, they may experience free visits and free transportation to and from the office while participating in the study. Studies can last from 4 months to a couple of years.
What are some of the reasons that someone might want to participate in one of these studies? The primary reason that someone might want to be part of a study is to help improve their seizures. Secondarily, the patient may benefit from the free visits and free transportation to the site. Last but not least, patients may want to assist the epilepsy community as a whole by helping with the study and launching of novel and hopefully better treatments.
In conclusion, numerous clinical trials are currently underway in our northeast region (New York, New Jersey, and Maryland) and may lead in the not-too-distant future to improved treatment options allowing doctors and their patients more options in the battle against seizures. Furthermore, the addition of Dr. Pavel Klein to NEREG's research program represents a significant step for the future of both programs research initiatives.
