A Proof of Concept Study of the Effectiveness of Carisbamate in the Treatment of Essential Tremor
A Proof of Concept Study of the Effectiveness of Carisbamate in the Treatment of Essential Tremor
The purpose of this study is to evaluate the effectiveness, safety and tolerability of
 carisbamate treatment for the signs, symptoms, and impairment associated with Essential
 Tremor (ET) compared to placebo treatment. The secondary objective is to evaluate the effect
 of carisbamate treatment on indicators of affect and mood in patients who have ET compared to
 placebo treatment.
The hypothesis of the study is that carisbamate will be effective in the treatment of
 Essential Tremor compared to placebo as measured by the Fahn-Tolosa-Marin Tremor Rating Scale
 (TRS). This randomized (study medication assigned by chance) study has 3 Phases:
 Screening/Washout, Double Blind Treatment (the physician and patient do not know the name of
 the study medication), and Exit. The Double Blind Treatment Phase has 2 Treatment Periods.
 Since this is a cross-over study, all subjects who complete the full Double Blind Treatment
 Phase will have the opportunity to take carisbamate. Carisbamate is administered as 100 mg
 oral tablets. During Treatment Period 1, patients will take 2 tablets of their assigned study
 medication (either carisbamate or placebo) two times a day for 21 days. Patients will return
 for clinical evaluations approximately 1 week after starting the study medication and at the
 end of Treatment Period 1. Patients will then reduce their dose of study medication to 1
 tablet twice a day for 3 days prior to stopping all study medication for at least 11 days.
 Before entering Treatment Period 2, patients will return for a clinical evaluation. During
 Treatment Period 2, patients will take 2 tablets of their assigned study medication two times
 a day for 21 days. Patients will return for clinical evaluations approximately 1 week after
 starting the second study medication and at the end of Treatment Period 2. Patients will then
 reduce their study medication to 1 tablet twice a day for 3 days before stopping all study
 medication. Patients will return for a clinical evaluation approximately 1 week after
 stopping all study medication and will be contacted by telephone approximately 30 days after
 the last dose of study medication. Safety will be assessed during each study visit by
 monitoring adverse events, clinical laboratory testing, physical and neurological
 examinations and electrocardiograms. Patients will take 2 carisbamate 100mg tablets 2 times a
 day (400 mg/day) for 21 days during one Treatment Period and 2 matching placebo tablets 2
 times a day for 21 days during the other Treatment Period. Patients will reduce the dose of
 study medication for 3 days at the end of each Treatment Period. There will be times during
 the study when no study medication is taken.
Inclusion Criteria:

 -  Patients in good general health

 -  Definite ET based on the TRIG diagnostic criteria

 -  Patients must have tremor affecting both upper extremities and at least 1 upper
 extremity must have a postural or action/intention tremor that is rated from 2
 (moderate) to 4 (severe) as defined in Part A (Tremor location/severity rating) of the
 TRS at the Visit 2 evaluation

 -  Patients must have a negative urine drug screen at screening with exceptions for
 legally prescribed benzodiazepines or opioid analgesics. Patients must have a negative
 blood alcohol test at screening and be willing to abstain from alcohol for at least 24
 hours prior to each study visit.

 Exclusion Criteria:

 -  Abnormal neurologic signs or progressive neurological disorders, such as Parkinson's
 Disease, brain tumor, demyelinating disease, CNS trauma, active CNS infection, stroke,
 or any CNS disease, other than ET, that could interfere with the evaluation of tremor

 -  Patients with dystonia or dystonic tremors, enhanced physiologic tremor, task specific
 tremor (e.g., writing tremor), or historical or clinical evidence of psychogenic or
 fictitious movement disorders

 -  Patients currently taking or recently exposed to prohibited medications unless, in the
 opinion of the study investigator, the patient is able to follow the washout procedure
 and restrictions described in the protocol prior to randomization

 -  Patients taking more than one tremor-reducing agent who are unable to discontinue all
 or all but one of these medications

 -  Patients who have achieved no discernable tremor reduction after treatment with at
 least 2 of 3 following tremor-reducing medications specifically prescribed for the
 treatment of ET: propranolol, primidone, or topiramate

 -  Prior exposure to carisbamate (RWJ-333369)

 -  Surgical procedures for treatment of ET such as deep brain stimulation or thalamic
 ablation

 -  Current or past (within 1 year) major psychotic disorder, such as schizophrenia or
 other psychotic conditions, major depressive disorder with psychotic features or other
 psychiatric disorders

 -  Exacerbation of major depression within the past 6 months

 -  History of suicide attempts or suicidal ideation in the past year

 -  History of drug or alcohol abuse within the past year

 -  Patients who are not able to abstain from alcohol consumption for 24 hours prior to
 each evaluation

 -  Patients with abnormal screening laboratory values or ECG (electrical heart tracing)

 -  Patients with a history, diagnosis or clinical signs for a significant major medical
 disorder that might disqualify.