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Clobazam Adjunctive Treatment of Adults With Refractory Focal Epilepsy

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ClinicalTrials.gov Identifier: NCT02726919
Recruitment Status : Unknown
Verified March 2016 by Pavel Klein, Mid-Atlantic Epilepsy and Sleep Center, LLC.
Recruitment status was:  Recruiting
First Posted : April 4, 2016
Last Update Posted : March 23, 2017
Sponsor:
Collaborator:
H. Lundbeck A/S
Information provided by (Responsible Party):
Pavel Klein, Mid-Atlantic Epilepsy and Sleep Center, LLC

Brief 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 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.


Condition or disease Intervention/treatment Phase
Epilepsy Drug: Clobazam Phase 4

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 Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Prospective Open Label Evaluation of Clobazam Adjunctive Treatment of Adults With Refractory Focal Epilepsy: A Pilot Study
Study Start Date : February 2015
Estimated Primary Completion Date : June 2018
Estimated Study Completion Date : June 2018


Arm Intervention/treatment
Clobazam treatment
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
Drug: Clobazam
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
Other Name: Onfi




Primary Outcome Measures :
  1. seizure freedom [ Time Frame: 12 weeks ]
    seizure freedom for 3 months of maintenance treatment with the highest tolerated clobazam dose


Secondary Outcome Measures :
  1. >75% seizure frequency reduction and median seizure frequency reduction for the whole treatment duration [ Time Frame: 16 weeks ]
    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.

  2. median seizure frequency reduction for the whole treatment duration [ Time Frame: 16 weeks ]
    median seizure frequency reduction for the whole treatment duration

  3. comparing seizure frequency per 28 day periods during treatment vs. baseline [ Time Frame: 16 weeks ]
    comparing seizure frequency per 28 day periods during treatment vs. baseline

  4. quality of life questionnaire (QOLIE-31-P) scores [ Time Frame: 16 weeks ]


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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age 18-65
  2. 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.
  3. Stable AED doses for at least 30 days
  4. Epilepsy duration for > 2 years
  5. 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.
  6. Seizure frequency of ≥1/month

Exclusion Criteria:

  1. Primary generalized epilepsy
  2. Simple partial seizures without motor components or secondary generalization
  3. Non-epileptic seizures
  4. Progressive neurological disease including neoplasm, CNS degenerative disorders including Alzheimer's disease, other forms of dementia
  5. 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
  6. Change in the dose of any Antiepileptic Drug within 30 days prior to enrollment
  7. Psychosis within six months of enrollment.
  8. Active drug or alcohol dependence or any other factors that, in the opinion of the site investigators would interfere with adherence to study requirements;
  9. Pregnancy
  10. Use of any CNS-active investigational drugs within 3 months of enrollment.
  11. Inability or unwillingness of subject or legal guardian/representative to give written informed consent.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02726919


Contacts
Contact: Pavel Klein, M.D. 3015309744 kleinp@epilepsydc.com
Contact: Ivana Tyrlikova, M.D. 2404089665 tyrlikovai@epilepsydc.com

Locations
United States, Maryland
MidAtlantic Epilepsy and Sleep Center Recruiting
Bethesda, Maryland, United States, 20817
Contact: Ivana Tyrlikova    301-530-9744    tyrlikovai@epilepsydc.com   
Contact: Pavel Klein, MD    301-704-4925    kleinp@epilepsydc.com   
Principal Investigator: Pavel Klein, MD         
Sponsors and Collaborators
Pavel Klein
H. Lundbeck A/S
Investigators
Principal Investigator: Pavel Klein, M.D. Mid-Atlantic Epilepsy and Sleep Center

Responsible Party: Pavel Klein, Director, Mid-Atlantic Epilepsy and Sleep Center, LLC
ClinicalTrials.gov Identifier: NCT02726919     History of Changes
Other Study ID Numbers: maes 007
First Posted: April 4, 2016    Key Record Dates
Last Update Posted: March 23, 2017
Last Verified: March 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Keywords provided by Pavel Klein, Mid-Atlantic Epilepsy and Sleep Center, LLC:
focal epilepsy
clobazam

Additional relevant MeSH terms:
Epilepsy
Epilepsies, Partial
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Clobazam
Anticonvulsants