Lennox Gastaut SyndromePhase 1NCT03731715
Carisbamate in Adult & Pediatric Subjects With Lennox-Gastaut Syndrome
A Phase 1 study testing Carisbamate in people with Lennox Gastaut Syndrome, run by SK Life Science, Inc. at 7 sites in United States.
Trial summary
This is an open-label, multi-center study of carisbamate in adult and pediatric subjects with LGS, with single- and multiple-dose PK assessments from Days 1 through 73. There will be a Screening Period of up to 28 days and a Treatment Period of 87 days. Read more about this study
- Who is it for?
- Ages 2 years and older
- Conditions the study is for
- Lennox Gastaut Syndrome
- What is being tested?
- Carisbamate
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 7 sitesUnited States
- Study dates
- 7 Feb 2019to 29 Jun 2022
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Diagnosis of LGS as evidenced by the following:
- More than 1 type of generalized seizure, including drop seizures (atonic, tonic, or myoclonic), for ≥6 months before Visit 1
- Previous electroencephalogram reporting diagnostic criteria for LGS (abnormal background activity accompanied by slow spike-and-wave pattern <2.5 Hz)
- Male or female aged ≥2 years at the time of consent
- Aged <11 years at the onset of LGS
- Written informed consent signed by the subject or legal guardian prior to entering the study in accordance with the ICH GCP guidelines. Age appropriate assent will be obtained for children and adolescents. If the written informed consent is provided by the legal guardian because the subject is unable to do so, a written or verbal assent from the subject must also be obtained.
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- Receiving 1 to 3 concomitant AEDs at a stable dose for ≥30 days before Visit 1 (vagal nerve stimulation [VNS] and ketogenic diet, stable and ongoing for ≥30 days before Visit 1, do not count as AEDs)
- In the Investigator's opinion, parents or caregivers must be able to report accurate seizure assessments during the screening and study periods and subjects must be able to ingest study drug
- Body weight ≥8 kg for subjects enrolled in Cohort IV
- Subjects with an implanted vagal nerve stimulator will be allowed if the vagal nerve stimulator was implanted at least 5 months prior to Visit 1 (Screening) and the stimulator parameters are not changed for 30 days prior to Visit 1 and for the duration of the study
- Subjects following a ketogenic diet will be allowed as long as the diet has been stable for at least 30 days prior to Visit 1 (Screening) and will remain stable for the duration of the study.
Who cannot join
- Progressive neurological disease
- Prior treatment with carisbamate
- Evidence of clinically significant disease or any medical condition that would compromise the subject's ability to safely complete the study
- Any surgical or medical condition that may interfere with the absorption, distribution, metabolism, or excretion of the investigational medicine product
- Acute disease state (e.g., nausea, vomiting, fever, or diarrhea) within 7 days before Day 1
- Scheduled for surgery during the study
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- Ketogenic diet or VNS, unless stable and ongoing for ≥30 days before Visit 1
- Treatment with an investigational drug or device ≥30 days before Visit 1
- Status epilepticus within 12 weeks of Visit 1
- Felbamate for <1 year (subjects taking felbamate for ≥1 year must have a stable dose for 60 days before Visit 1)
- Concomitant use of vigabatrin or other medications known to be inducers of CYP3A
- Use of drugs known as UGT inducers, e.g., carbamazepine, phenytoin, phenobarbital, primidone, or oxcarbazepine
- Use of cannabinoids (any form), cannabidiols, or medical or recreational marijuana
- Use of any prescription or non-prescription drugs, including over-the-counter medication, non-routine vitamins and herbal products within 2 weeks prior to study drug administration unless discussed and agreed with the Sponsor's medical representative in writing. (Medication used to treat TEAEs does not lead to a compulsory exclusion of subjects.)
- Consumption of any caffeine-containing products (e.g., coffee, tea, chocolate, or soda) or alcoholic beverages within 48 hours before Day 1 and until the end of each PK sampling period
- Consumption of grapefruit or grapefruit-containing products within 72 hours before Day 1 and until the end of each PK sampling period
- History of any serious drug-induced hypersensitivity reaction (including but not limited to Stevens Johnson syndrome, toxic epidermal necrolysis, Drug Rash with Eosinophilia and Systemic Symptoms [DRESS]) or any drug-related rash requiring hospitalization
- History of AED-associated rash that involved conjunctiva or mucosae
- History of more than one non-serious drug-related hypersensitivity reaction that required discontinuation of the medication
- Significant clinical laboratory abnormalities, including elevation of serum AST or ALT more than 1.5 times ULN for age group, or any elevation of bilirubin or creatinine about the ULN for age group at Screening
- Any clinically-significant uncontrolled medical illness, including hepatic or renal failure, ischemic disease, human immunodeficiency virus (HIV) infection, active sexually-transmitted disease (STD), active viral hepatitis, malignancy, or any disorder that in the judgement of the investigator places the subject at risk by participation in this study
- History of drug-induced liver injury
- Positive urine screen of drugs of abuse (if not due to concomitant medication, e.g. benzodiazepines as hypnotics) for adult and adolescent subjects.
- Adrenocorticotropic hormone within the 6 months before Visit 1
- History of anoxic episodes requiring resuscitation within 6 months before Visit 1, drug or alcohol dependency or abuse within approximately the last 2 years, or use of illegal recreational drugs
- Females who are breastfeeding or pregnant at Screening or Baseline or who are of reproductive age and do not agree to be abstinent or to use highly effective contraception
- Intermittent use of benzodiazepine of >4 single administrations in the month before Visit 1
- Clinically significant abnormality on the 12-lead ECG at Screening, and any child or adolescent with a QTcF less than 330 ms or greater than 450 ms
- Congenital short QT syndrome
- Hypersensitivity to the study drug or any of the excipients
- Psychotic disorder(s) or unstable recurrent affective disorder(s)
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
United States7 sites
Johns Hopkins Hospital
Baltimore, Maryland, 21210
Duke Health
Durham, North Carolina, 27710
Dartmouth-Hitchcock Medical Center
Lebanon, New Hampshire, 03756
Hospital of the University of Pennsylvania
Philadelphia, Pennsylvania, 19104
Oregon Health and Science University
Portland, Oregon, 97239
UW Valley Medical Center
Renton, Washington, 98055
The University of Utah School of Medicine - Primary Children's Hospital (Primary Children's Medical Center)
Salt Lake City, Utah, 84113
About this study
Official title: Phase I, Open-Label, Pharmacokinetic, Dose Escalation Study of Carisbamate in Adult and Pediatric Subjects With Lennox-Gastaut Syndrome
This is an open-label, multi-center study of carisbamate in adult and pediatric subjects with LGS, with single- and multiple-dose PK assessments from Days 1 through 73. There will be a Screening Period of up to 28 days and a Treatment Period of 87 days.
Read the detailed description
A total of 24 subjects are planned: 6 subjects in each of 4 cohorts: Cohort I (≥18 years), Cohort II (12 to <18 years), Cohort III (6 to <12 years), and Cohort IV (2 to <6 years).
For Cohorts I and II, PK assessments of carisbamate, S-enantiomer and its R-enantiomer plasma concentrations, will be conducted on Days 1, 2 and 3 of the single dose period at pre-dose and 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, and 48 hours after dosing and on Day 17 of the multiple-dose period at pre dose and 0.5, 1, 1.5, 2, 4, 6, 8, and 12 hours after dosing; trough samples will be collected on Days 45 and 73 of the dose-adjustment period.
For Cohort III, PK assessments of carisbamate, S-enantiomer and its R-enantiomer plasma concentrations will be conducted on Days 1, 2 and 3 of the single dose period at pre dose and 0.5, 1, 2, 4, 6, 8, 12, 24, and 48 hours after dosing and on Day 17 of the multiple-dose period at pre-dose and 2 hours after dosing; trough samples will be collected on Days 45 and 73 of the dose-adjustment period.
For Cohort IV, a sparse PK sampling approach will be used, and the time of PK sampling time will be based on the PK results from the other cohorts. A maximum of 2 to 4 time points on each day (1 and 17) will be collected.
Safety assessments include adverse event (AE) and concomitant medication reporting, clinical laboratory testing, vital sign measurements, 12 lead electrocardiograms (ECGs), physical examinations, and neurologic examinations.
- Conditions
- Lennox Gastaut Syndrome
- Being tested
- Carisbamate
- Keywords
- LGS
- Medical subject headings
- Lennox Gastaut Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CarisbamateDrug
Also called YKP509
An oral liquid formulation (20 mg/mL) of carisbamate (S-carisbamate)
| Study group | Role | What they receive |
|---|---|---|
| Cohort I | Experimental | Subjects ≥18 years of age. Carisbamate, 200 mg, will be administered on Day 1 and 2 of the single-dose period. Carisbamate will be administered at 100 mg twice daily (BID) during the multiple-dose period. Receives: Drug: Carisbamate |
| Cohort II | Experimental | Subjects 12 to <18 years of age. Carisbamate, 140 mg, will be administered on Day 1 and 2 of the single dose period. Carisbamate will be administered at 70 mg twice daily (BID) during the multiple-dose period. Receives: Drug: Carisbamate |
| Cohort III | Experimental | Subjects 6 to <12 years of age. Carisbamate, 60 mg, will be administered on Day 1 and 2 of the single dose period. Carisbamate will be administered at 30 mg twice daily (BID) during the multiple-dose period. Receives: Drug: Carisbamate |
| Cohort IV | Experimental | Subjects 2 to <6 years of age. The starting doses for the single dose and multiple-dose periods will be based on the PK and safety results of the first 3 cohorts. Receives: Drug: Carisbamate |
What is being measured
The primary outcome is the main question the study is designed to answer.
The area under the curve (AUC) of carisbamate after a single and multiple doses of carisbamate.
Safety Assessment
Measured: Days 1-3, Day 17
The maximum plasma concentration (Cmax) after a single and multiple doses of carisbamate.
Safety assessment
Measured: Days 1-3, Day 17
Secondary outcomes (1)
Safety - adverse events (AEs) reporting after a single and multiple doses of carisbamate.
Adverse event assessment for seriousness (yes, no), severity (mild, moderate, severe), affect on carisbamate dosing (increase, reduced, interrupted, withdrawn, no change), and outcome (recovered/resolved,recovered/resolved with sequelae, recovering/resolving, not recovered/not resolved, fatal or unknown).
Measured: Days 1-87
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Nov 2018
- Study start7 Feb 2019
- Primary completion23 May 2022
- Study completion29 Jun 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Lennox Gastaut SyndromeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- Open-label
- Masking
- None (open label)
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- SK Life Science, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Marc Kamin, MD, Study director, SK Life Science, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03731715
- Sponsor's protocol ID
- YKP509C001
- Status last verified
- May 2023
- First submitted
- 16 Oct 2018
- Last updated
- 30 May 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 May 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I, Open-Label, Pharmacokinetic, Dose Escalation Study of Carisbamate in Adult and Pediatric Subjects With Lennox-Gastaut Syndrome
- ClinicalTrials.gov ID
- NCT03731715
- Acronym / sponsor ID
- YKP509C001
- Conditions
- Lennox Gastaut Syndrome
- Keywords
- LGS
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- SK Life Science, Inc.Industry (pharma, biotech, devices)
- Study start
- 7 Feb 2019 (actual)
- Primary completion
- 23 May 2022 (actual)
- Study completion
- 29 Jun 2022 (actual)
- First posted
- 6 Nov 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is an open-label, multi-center study of carisbamate in adult and pediatric subjects with LGS, with single- and multiple-dose PK assessments from Days 1 through 73. There will be a Screening Period of up to 28 days and a Treatment Period of 87 days.
Detailed description
A total of 24 subjects are planned: 6 subjects in each of 4 cohorts: Cohort I (≥18 years), Cohort II (12 to <18 years), Cohort III (6 to <12 years), and Cohort IV (2 to <6 years).
For Cohorts I and II, PK assessments of carisbamate, S-enantiomer and its R-enantiomer plasma concentrations, will be conducted on Days 1, 2 and 3 of the single dose period at pre-dose and 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, and 48 hours after dosing and on Day 17 of the multiple-dose period at pre dose and 0.5, 1, 1.5, 2, 4, 6, 8, and 12 hours after dosing; trough samples will be collected on Days 45 and 73 of the dose-adjustment period.
For Cohort III, PK assessments of carisbamate, S-enantiomer and its R-enantiomer plasma concentrations will be conducted on Days 1, 2 and 3 of the single dose period at pre dose and 0.5, 1, 2, 4, 6, 8, 12, 24, and 48 hours after dosing and on Day 17 of the multiple-dose period at pre-dose and 2 hours after dosing; trough samples will be collected on Days 45 and 73 of the dose-adjustment period.
For Cohort IV, a sparse PK sampling approach will be used, and the time of PK sampling time will be based on the PK results from the other cohorts. A maximum of 2 to 4 time points on each day (1 and 17) will be collected.
Safety assessments include adverse event (AE) and concomitant medication reporting, clinical laboratory testing, vital sign measurements, 12 lead electrocardiograms (ECGs), physical examinations, and neurologic examinations.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
- Model description
- Open-label
| Arm | Type | Receives |
|---|---|---|
| Cohort I | Experimental | Drug: CarisbamateSubjects ≥18 years of age. Carisbamate, 200 mg, will be administered on Day 1 and 2 of the single-dose period. Carisbamate will be administered at 100 mg twice daily (BID) during the multiple-dose period. |
| Cohort II | Experimental | Drug: CarisbamateSubjects 12 to <18 years of age. Carisbamate, 140 mg, will be administered on Day 1 and 2 of the single dose period. Carisbamate will be administered at 70 mg twice daily (BID) during the multiple-dose period. |
| Cohort III | Experimental | Drug: CarisbamateSubjects 6 to <12 years of age. Carisbamate, 60 mg, will be administered on Day 1 and 2 of the single dose period. Carisbamate will be administered at 30 mg twice daily (BID) during the multiple-dose period. |
| Cohort IV | Experimental | Drug: CarisbamateSubjects 2 to <6 years of age. The starting doses for the single dose and multiple-dose periods will be based on the PK and safety results of the first 3 cohorts. |
Who may qualify
- Ages
- 2 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (11 listed)
- Diagnosis of LGS as evidenced by the following:
- Male or female aged ≥2 years at the time of consent
- Aged <11 years at the onset of LGS
- Written informed consent signed by the subject or legal guardian prior to entering the study in accordance with the ICH GCP guidelines. Age appropriate assent will be obtained for children and adolescents. If the written informed consent is provided by the legal guardian because the subject is unable to do so, a written or verbal assent from the subject must also be obtained.
- Receiving 1 to 3 concomitant AEDs at a stable dose for ≥30 days before Visit 1 (vagal nerve stimulation [VNS] and ketogenic diet, stable and ongoing for ≥30 days before Visit 1, do not count as AEDs)
Key exclusion criteria (31 listed)
- Progressive neurological disease
- Prior treatment with carisbamate
- Evidence of clinically significant disease or any medical condition that would compromise the subject's ability to safely complete the study
- Any surgical or medical condition that may interfere with the absorption, distribution, metabolism, or excretion of the investigational medicine product
- Acute disease state (e.g., nausea, vomiting, fever, or diarrhea) within 7 days before Day 1
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CarisbamateAlso: YKP509An oral liquid formulation (20 mg/mL) of carisbamate (S-carisbamate) | Drug | Cohort I, Cohort II, Cohort III, Cohort IV |
Primary outcome
The area under the curve (AUC) of carisbamate after a single and multiple doses of carisbamate.
Time frame: Days 1-3, Day 17
Safety Assessment
The maximum plasma concentration (Cmax) after a single and multiple doses of carisbamate.
Time frame: Days 1-3, Day 17
Safety assessment
1 secondary outcome
Safety - adverse events (AEs) reporting after a single and multiple doses of carisbamate.
Time frame: Days 1-87
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 May 2023.
- Individual participant dataSharing planned: No
Related trials for Lennox Gastaut Syndrome
RecruitingPhase 3
Investigate Efficacy and Safety of Carisbamate as Adjunctive Treatment for Seizures Associated With LGS in Children and Adults
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Not yet recruitingPhase 4
A Study to Investigate the Effect of Gradual Titration to Optimize Cannabidiol Treatment in Adults With LGS
Lennox-Gastaut Syndrome
Enrolling by invitationPhase 3
A Study to Investigate LP352 in Children and Adults With Developmental and Epileptic Encephalopathy (DEE)
Developmental and Epileptic Encephalopathy
RecruitingPhase 3
An Efficacy and Safety Study of Clemizole HCl in Patients With Lennox-Gastaut Syndrome
Lennox Gastaut Syndrome
Enrolling by invitation
Clinical Utility of Reduced EEG Home Monitoring in Fenfluramine Titration for Dravet and LGS
Dravet Syndrome (DS), Lennox Gastaut Syndrome (LGS)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Marc Kamin, MD study director
SK Life Science, Inc.
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Carisbamate in people with Lennox Gastaut Syndrome, run by SK Life Science, Inc. at 7 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 31 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 May 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The area under the curve (AUC) of carisbamate after a single and multiple doses of carisbamate. (time frame: Days 1-3, Day 17). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 May 2023.