EpilepsyPhase 4NCT02726919
Clobazam Adjunctive Treatment of Adults With Refractory Focal Epilepsy
A Phase 4 study testing Clobazam in people with Epilepsy, run by Pavel Klein at 1 site in United States.
Trial summary
The goal of the present study is to obtain pilot data on efficacy and safety of clobazam add-on treatment on adults with drug-resistant focal epilepsy. This will be an open label study comparing seizure frequency during 12 weeks of baseline observation period with seizure frequency during 16 weeks of clobazam… Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Epilepsy
- What is being tested?
- Clobazam
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2015to Jun 2018
- Phase
- Phase 4
- 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 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age 18-65
- Stable focal epilepsy, with partial complex seizures including partial complex seizures with or without secondary generalization, partial simple seizures with a clear motor component with or without secondary generalization, and partial simple seizures with secondary generalization.
- Stable AED doses for at least 30 days
- Epilepsy duration for > 2 years
- Past/current treatment with > 4 AEDs. Vagal nerve stimulator treatment will be allowed and will not count as an AED. VNS setting must be stable for 3 months prior to enrollment.
- Seizure frequency of ≥1/month
Who cannot join
- Primary generalized epilepsy
- Simple partial seizures without motor components or secondary generalization
- Non-epileptic seizures
- Progressive neurological disease including neoplasm, CNS degenerative disorders including Alzheimer's disease, other forms of dementia
- Any systemic illness or unstable medical condition that might pose additional risk, including renal or liver disease, clinically uncontrolled cardiac disease, other unstable metabolic or endocrine disturbances, and active systemic cancer
- Change in the dose of any Antiepileptic Drug within 30 days prior to enrollment
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- Psychosis within six months of enrollment.
- Active drug or alcohol dependence or any other factors that, in the opinion of the site investigators would interfere with adherence to study requirements;
- Pregnancy
- Use of any CNS-active investigational drugs within 3 months of enrollment.
- Inability or unwillingness of subject or legal guardian/representative to give written informed consent.
Trial locations and contacts
1 site in 1 country.
United States1 site, 1 recruiting
- Recruiting
MidAtlantic Epilepsy and Sleep Center
Bethesda, Maryland, 20817
Ivana Tyrlikova, 301-530-9744, tyrlikovai@epilepsydc.com
Pavel Klein, MD, 301-704-4925, kleinp@epilepsydc.com
About this study
Official title: Prospective Open Label Evaluation of Clobazam Adjunctive Treatment of Adults With Refractory Focal Epilepsy: A Pilot Study
The goal of the present study is to obtain pilot data on efficacy and safety of clobazam add-on treatment on adults with drug-resistant focal epilepsy.
This will be an open label study comparing seizure frequency during 12 weeks of baseline observation period with seizure frequency during 16 weeks of clobazam adjunctive treatment. 10 adults aged 18-65 with focal seizures that have failed to respond to ≥ 4 antiepileptic drugs (AEDs) +/- respective surgery will be enrolled. Following a baseline of 12 weeks patients will be started on clobazam, administered orally in b.i.d. schedule. In patients in whom seizure diaries have been kept prospectively prior to study screening visit, retrospective baseline will be accepted. Patients will be titrated up to either seizure freedom, to side effects or to 40 mg/day, whichever comes first. Titration rate will be not be forced. It is anticipated that the majority of subjects will have a 4 week-long titration period. After maximum dose is achieved, maintenance treatment will last for 12 weeks.
Read the detailed description
Approximately 35 % of patients with epilepsy do not respond to treatment with medications. There is a need for new treatment of refractory focal epilepsy. Clobazam was approved in 2011 in the US for treatment of refractory seizures in patients with Lennox Gastaut syndrome (LGS). Patients with LGS have different seizure types. While pivotal studies evaluated primary generalized seizures, LGS patients also have focal seizures. The goal of the present study is to obtain pilot data on efficacy and safety of clobazam add-on treatment on adults with drug-resistant focal epilepsy.
This will be an open label study comparing seizure frequency during 12 weeks of baseline observation period with seizure frequency during 16 weeks of clobazam adjunctive treatment. 10 adults aged 18-65 with focal seizures that have failed to respond to ≥ 4 antiepileptic drugs (AEDs) +/- respective surgery will be enrolled. Following a baseline of 12 weeks, patients will be started on clobazam, administered orally in b.i.d. schedule. In patients in whom seizure diaries have been kept prospectively prior to study screening visit, retrospective baseline will be accepted. Patients will be titrated up to either seizure freedom, to side effects or to 40 mg/day, whichever comes first. Titration rate will be not be forced. It is anticipated that the majority of subjects will have a 4 week-long titration period. After maximum dose is achieved, maintenance treatment will last for 12 weeks.
Primary efficacy outcome measure will be seizure freedom for 3 months of maintenance treatment with the highest tolerated clobazam dose. Secondary outcome measures will include >75% seizure frequency reduction and median seizure frequency reduction for the whole treatment duration and for the maintenance treatment period, comparing seizure frequency per 28 day periods during treatment vs. baseline. Primary safety outcome measures will include treatment emergent adverse events, and treatment discontinuation due to treatment emergent adverse events.
The number of subjects will be small, n=10. It is therefore likely that results obtained in the present study will not be statistically significant. The goal of the present study is to ascertain whether clobazam add-on treatment in adults with refractory focal epilepsy gives a signal of efficacy greater than that demonstrated with other second and third generation anticonvulsants such as levetiracetam, pregabalin, lacosamide and perampanel; specifically whether clobazam adjunctive treatment shows a trend towards 75% response and seizure freedom rate that surpasses those seen in phase 3 levetiracetam, pregabalin, lacosamide and perampanel studies. The results, if positive, will be used to design a larger controlled study would follow.
- Conditions
- Epilepsy
- Being tested
- Clobazam
- Keywords
- focal epilepsy, clobazam
- Medical subject headings
- Epilepsy, Epilepsies, Partial
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ClobazamDrug
Also called Onfi
Following a baseline of 12 weeks patients will be started on clobazam, administered orally in b.i.d. schedule. In patients in whom seizure diaries have been kept prospectively prior to study screening visit, retrospective baseline will be accepted. Patients will be titrated up to either seizure freedom, to side effects or to 40 mg/day, whichever comes first
| Study group | Role | What they receive |
|---|---|---|
| Clobazam treatment | Other | This will be an open label study comparing seizure frequency during 12 weeks of baseline observation period with seizure frequency during 16 weeks of clobazam adjunctive treatment Receives: Drug: Clobazam |
What is being measured
The primary outcome is the main question the study is designed to answer.
seizure freedom
seizure freedom for 3 months of maintenance treatment with the highest tolerated clobazam dose
Measured: 12 weeks
Secondary outcomes (4)
>75% seizure frequency reduction and median seizure frequency reduction for the whole treatment duration
Secondary outcome measures will include >75% seizure frequency reduction and median seizure frequency reduction for the whole treatment duration and for the maintenance treatment period, comparing seizure frequency per 28 day periods during treatment vs. baseline.
Measured: 16 weeks
median seizure frequency reduction for the whole treatment duration
median seizure frequency reduction for the whole treatment duration
Measured: 16 weeks
comparing seizure frequency per 28 day periods during treatment vs. baseline
comparing seizure frequency per 28 day periods during treatment vs. baseline
Measured: 16 weeks
quality of life questionnaire (QOLIE-31-P) scores
Measured: 16 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Apr 2016 (estimated)
- Study startFeb 2015
- Primary completionJun 2018 (estimated)
- Study completionJun 2018 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for EpilepsyStudies 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 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Pavel Klein
- Sponsor type
- University, hospital or other
- Collaborators
- H. Lundbeck A/S
- Responsible party
- Sponsor-investigator, Pavel Klein, Mid-Atlantic Epilepsy and Sleep Center, LLC
- Investigators
- Pavel Klein, M.D., Principal investigator, Mid-Atlantic Epilepsy and Sleep Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02726919
- Sponsor's protocol ID
- maes 007
- Status last verified
- Mar 2016
- First submitted
- 13 Mar 2015
- Last updated
- 23 Mar 2017
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 23 Mar 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prospective Open Label Evaluation of Clobazam Adjunctive Treatment of Adults With Refractory Focal Epilepsy: A Pilot Study
- ClinicalTrials.gov ID
- NCT02726919
- Acronym / sponsor ID
- maes 007
- Conditions
- Epilepsy
- Keywords
- focal epilepsy, clobazam
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- Pavel KleinUniversity, hospital or other
- Collaborators
- H. Lundbeck A/S
- Study start
- Feb 2015
- Primary completion
- Jun 2018 (estimated)
- Study completion
- Jun 2018 (estimated)
- First posted
- 4 Apr 2016 (estimated)
- 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.
The goal of the present study is to obtain pilot data on efficacy and safety of clobazam add-on treatment on adults with drug-resistant focal epilepsy.
This will be an open label study comparing seizure frequency during 12 weeks of baseline observation period with seizure frequency during 16 weeks of clobazam adjunctive treatment. 10 adults aged 18-65 with focal seizures that have failed to respond to ≥ 4 antiepileptic drugs (AEDs) +/- respective surgery will be enrolled. Following a baseline of 12 weeks patients will be started on clobazam, administered orally in b.i.d. schedule. In patients in whom seizure diaries have been kept prospectively prior to study screening visit, retrospective baseline will be accepted. Patients will be titrated up to either seizure freedom, to side effects or to 40 mg/day, whichever comes first. Titration rate will be not be forced. It is anticipated that the majority of subjects will have a 4 week-long titration period. After maximum dose is achieved, maintenance treatment will last for 12 weeks.
Detailed description
Approximately 35 % of patients with epilepsy do not respond to treatment with medications. There is a need for new treatment of refractory focal epilepsy. Clobazam was approved in 2011 in the US for treatment of refractory seizures in patients with Lennox Gastaut syndrome (LGS). Patients with LGS have different seizure types. While pivotal studies evaluated primary generalized seizures, LGS patients also have focal seizures. The goal of the present study is to obtain pilot data on efficacy and safety of clobazam add-on treatment on adults with drug-resistant focal epilepsy.
This will be an open label study comparing seizure frequency during 12 weeks of baseline observation period with seizure frequency during 16 weeks of clobazam adjunctive treatment. 10 adults aged 18-65 with focal seizures that have failed to respond to ≥ 4 antiepileptic drugs (AEDs) +/- respective surgery will be enrolled. Following a baseline of 12 weeks, patients will be started on clobazam, administered orally in b.i.d. schedule. In patients in whom seizure diaries have been kept prospectively prior to study screening visit, retrospective baseline will be accepted. Patients will be titrated up to either seizure freedom, to side effects or to 40 mg/day, whichever comes first. Titration rate will be not be forced. It is anticipated that the majority of subjects will have a 4 week-long titration period. After maximum dose is achieved, maintenance treatment will last for 12 weeks.
Primary efficacy outcome measure will be seizure freedom for 3 months of maintenance treatment with the highest tolerated clobazam dose. Secondary outcome measures will include >75% seizure frequency reduction and median seizure frequency reduction for the whole treatment duration and for the maintenance treatment period, comparing seizure frequency per 28 day periods during treatment vs. baseline. Primary safety outcome measures will include treatment emergent adverse events, and treatment discontinuation due to treatment emergent adverse events.
The number of subjects will be small, n=10. It is therefore likely that results obtained in the present study will not be statistically significant. The goal of the present study is to ascertain whether clobazam add-on treatment in adults with refractory focal epilepsy gives a signal of efficacy greater than that demonstrated with other second and third generation anticonvulsants such as levetiracetam, pregabalin, lacosamide and perampanel; specifically whether clobazam adjunctive treatment shows a trend towards 75% response and seizure freedom rate that surpasses those seen in phase 3 levetiracetam, pregabalin, lacosamide and perampanel studies. The results, if positive, will be used to design a larger controlled study would follow.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Clobazam treatment | Other | Drug: ClobazamThis will be an open label study comparing seizure frequency during 12 weeks of baseline observation period with seizure frequency during 16 weeks of clobazam adjunctive treatment |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Age 18-65
- Stable focal epilepsy, with partial complex seizures including partial complex seizures with or without secondary generalization, partial simple seizures with a clear motor component with or without secondary generalization, and partial simple seizures with secondary generalization.
- Stable AED doses for at least 30 days
- Epilepsy duration for > 2 years
- Past/current treatment with > 4 AEDs. Vagal nerve stimulator treatment will be allowed and will not count as an AED. VNS setting must be stable for 3 months prior to enrollment.
Key exclusion criteria (11 listed)
- Primary generalized epilepsy
- Simple partial seizures without motor components or secondary generalization
- Non-epileptic seizures
- Progressive neurological disease including neoplasm, CNS degenerative disorders including Alzheimer's disease, other forms of dementia
- Any systemic illness or unstable medical condition that might pose additional risk, including renal or liver disease, clinically uncontrolled cardiac disease, other unstable metabolic or endocrine disturbances, and active systemic cancer
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 |
|---|---|---|
| ClobazamAlso: OnfiFollowing a baseline of 12 weeks patients will be started on clobazam, administered orally in b.i.d. schedule. In patients in whom seizure diaries have been kept prospectively prior to study screening visit, retrospective baseline will be accepted. Patients will be titrated up to either seizure freedom, to side effects or to 40 mg/day, whichever comes first | Drug | Clobazam treatment |
Primary outcome
seizure freedom
Time frame: 12 weeks
seizure freedom for 3 months of maintenance treatment with the highest tolerated clobazam dose
4 secondary outcomes
>75% seizure frequency reduction and median seizure frequency reduction for the whole treatment duration
Time frame: 16 weeks
median seizure frequency reduction for the whole treatment duration
Time frame: 16 weeks
comparing seizure frequency per 28 day periods during treatment vs. baseline
Time frame: 16 weeks
quality of life questionnaire (QOLIE-31-P) scores
Time frame: 16 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Mar 2017.
- Individual participant dataSharing planned: Undecided
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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.
Pavel Klein, M.D. principal investigator
Mid-Atlantic Epilepsy and Sleep Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Clobazam in people with Epilepsy, run by Pavel Klein at 1 site 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 6 inclusion and 11 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: status not confirmed, as of the sponsor's last update on 23 Mar 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Pavel Klein, M.D. (3015309744, kleinp@epilepsydc.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
seizure freedom (time frame: 12 weeks). 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 23 Mar 2017.