Monotherapy in adult patients

VIMPAT ESTABLISHED EFFICACY IN MONOTHERAPY.2

VIMPAT MET THE PRE-SPECIFIED CRITERIA FOR EFFICACY IN ADULTS WITH PARTIAL-ONSET SEIZURES.2

Separation of the VIMPAT 95% confidence interval upper limit from the
historical control's 95% prediction interval lower limit established the
efficacy of VIMPAT as monotherapy2,7
VIMPAT® (lacosamide) CV Monotherapy Clinical Trials Chart

Trial demonstrated the efficacy of VIMPAT for conversion to monotherapy in adult patients with partial-onset seizures, with statistical superiority to the historical control.2

For the VIMPAT 400 mg/day (200 mg twice-daily) group, the estimate of the percentage of patients meeting at least 1 exit criterion was 30% (95% confidence interval: 25%, 36%). The upper limit of the 2-sided 95% confidence interval (36%) was below 65%, the lower limit of the historical control 95% prediction interval derived from the historical control data, meeting the pre-specified criteria for efficacy.2

The VIMPAT 300 mg/day (150 mg twice-daily) group also met the pre-specified criteria for efficacy.2

SELECT IMPORTANT SAFETY INFORMATION

Adverse Reactions

Monotherapy: In the adult clinical trial, adverse reactions were generally similar to those observed and attributed to drug in adjunctive placebo-controlled trials, with the exception of insomnia (occurred at a higher rate of ≥2%).

VIMPAT USE AS MONOTHERAPY IN ADULTS WITH PARTIAL-ONSET SEIZURES WAS EVALUATED WITH A HISTORICAL CONTROL.2

THE VIMPAT HISTORICAL CONTROL STUDY WAS DESIGNED TO EVALUATE EFFICACY WITHOUT

THE EXPOSURE OF SUBJECTS TO SUBOPTIMAL AED DOSING.2,8

VIMPAT was tested in a conversion-to-monotherapy trial using a historical control group derived from a meta-analysis of data from 8 previous AED monotherapy trials of similar design, which utilized a subtherapeutic dose of an AED as a control.2,8

VIMPAT® (lacosamide) CV Monotherapy Historical Control Chart

Trial design: Using a historical control to evaluate efficacy and safety in monotherapy2

  • A historical control, multicenter, randomized trial* was conducted to assess the efficacy and safety of conversion to monotherapy with VIMPAT in epilepsy patients with partial-onset seizures (POS) on a stable regimen of 1 or 2 AEDs. Patients taking 2 AEDs must have been taking ≤50% of the minimum FDA-recommended maintenance dose of 1 of the 2 AEDs
  • The primary efficacy variable was the percentage of patients taking VIMPAT 400 mg/day meeting 1 or more predefined exit criteria of clinically relevant worsening of seizures8 by Day 112 of the maintenance phase compared to the percentage of patients exiting in the historical control group
  • A lower exit percentage indicates superior outcome to historical control

Baseline demographics and characteristics (N=425)

  • The study population profile appeared comparable to the historical control population.2 Patients averaged 17.2 years since diagnosis of epilepsy, with a median baseline seizure frequency of 6.6 per 28 days7
  • History of, or presently having: baseline simple partial seizures, 47.3% (n=201); complex partial seizures, 85.4% (n=363); partial seizures with secondary generalization, 67.5% (n=287)
  • 73.4% taking 1 background AED; 26.6% taking 2 background AEDs. Most common primary background AEDs: carbamazepine, lamotrigine, and levetiracetam§

*Patients were randomized 3 to 1 to receive either VIMPAT 400 mg/day or 300 mg/day.

The exit criteria were 1 or more of the following: (1) doubling of average monthly seizure frequency during any 28 consecutive days, (2) doubling of highest consecutive 2-day seizure frequency, (3) occurrence of a single generalized tonic-clonic seizure, (4) clinically significant prolongation or worsening of overall seizure duration, frequency, type, or pattern considered by the investigator to require trial discontinuation, (5) status epilepticus or new onset serial/cluster seizures.

Some patients experienced more than 1 seizure type at baseline and, therefore, were represented in more than 1 group.

§Levetiracetam is a product manufactured by UCB.

Download Complimentary adult Monotherapy Pivotal Trial Publication

Study 1

Wechsler RT, Li G, French J, et al. Conversion to lacosamide monotherapy in the treatment of focal epilepsy: Results from a historical-controlled, multicenter, double-blind study. Epilepsia. 2014;55(7):1088-1098.

DOWNLOAD PUBLICATION 01

Important Safety Information

Warnings and Precautions

  • Suicidal Behavior and Ideation: Antiepileptic drugs (AEDs), including VIMPAT, increase the risk of suicidal behavior and ideation. Monitor patients taking VIMPAT for the emergence or worsening of depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior. Advise patients and caregivers to be alert for these behavioral changes and to immediately report them to the healthcare provider.

  • Dizziness and Ataxia: VIMPAT may cause dizziness and ataxia. In adult clinical trials, the onset of dizziness and ataxia was most commonly observed during titration. Advise patients not to drive, operate complex machinery, or engage in other hazardous activities until they are familiar with the effects of VIMPAT on their ability to perform such activities. Dizziness and ataxia were also observed in pediatric clinical trials.

  • Cardiac Rhythm and Conduction Abnormalities:

    PR interval prolongation

    Dose-dependent prolongations in PR interval with VIMPAT have been observed in clinical studies in adult patients and in healthy volunteers. Second-degree and complete AV block have been reported in patients with seizures. When VIMPAT is given with other drugs that prolong the PR interval, further PR prolongation is possible.

    Use VIMPAT with caution in patients with known cardiac conduction problems (e.g., marked first-degree AV block, second-degree or higher AV block and sick sinus syndrome without pacemaker), sodium channelopathies (e.g., Brugada Syndrome), or with severe cardiac disease such as myocardial ischemia or heart failure, or structural heart disease. Also, use VIMPAT with caution in patients on concomitant medications that prolong PR interval (e.g., beta-blockers and calcium channel blockers) because of a risk of AV block or bradycardia. In such patients, obtaining an ECG before beginning VIMPAT, and after VIMPAT is titrated to steady-state maintenance dose, is recommended. In addition, closely monitor these patients if they are administered VIMPAT through the intravenous route.

    Atrial fibrillation and Atrial flutter

    VIMPAT administration may predispose to atrial arrhythmias (atrial fibrillation or flutter), especially in patients with diabetic neuropathy and/or cardiovascular disease.

  • Syncope: VIMPAT may cause syncope in adult and pediatric patients.

  • Withdrawal of Antiepileptic Drugs: Gradually withdraw VIMPAT (over a minimum of 1 week) to minimize the potential of increased seizure frequency.

  • Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS): Also known as multi-organ hypersensitivity, has been reported with antiepileptic drugs. Some of these events have been fatal or life-threatening. If signs or symptoms are present, immediately evaluate the patient. Discontinue VIMPAT if an alternative etiology for the signs and symptoms cannot be established.

  • Risks in Patients with Phenylketonuria: VIMPAT oral solution contains aspartame, a source of phenylalanine which can be harmful in patients with phenylketonuria (PKU). A 200 mg dose of VIMPAT oral solution (equivalent to 20 mL) contains 0.32 mg of phenylalanine.

Adverse Reactions

  • Adjunctive therapy: In the adult placebo-controlled clinical trials, the most frequently seen adverse reaction with VIMPAT was dizziness (31% vs 8% placebo). Other common adverse reactions occurring in ≥10 percent of VIMPAT-treated patients, and greater than placebo, were headache, nausea, and diplopia.

  • Monotherapy: In the adult clinical trial, adverse reactions were generally similar to those observed and attributed to drug in adjunctive placebo-controlled trials, with the exception of insomnia (occurred at a higher rate of ≥2%).

  • Pediatric patients: Adverse reactions reported in clinical studies of pediatric patients 4 to less than 17 years of age were similar to those seen in adult patients.

  • Injection: In adult adjunctive therapy clinical trials, adverse reactions with intravenous administration generally were similar to those that occurred with the oral formulation, although intravenous administration was associated with local adverse reactions such as injection site pain or discomfort (2.5%), irritation (1%), and erythema (0.5%). When administering a loading dose, the incidence of CNS adverse reactions, such as dizziness, somnolence, and paresthesia may be higher with 15-minute administration than over a 30- to 60-minute period.

Dosing Considerations

VIMPAT injection is for intravenous and adult use only when oral administration is temporarily not feasible. The loading dose for adult patients should be administered with medical supervision considering the VIMPAT pharmacokinetics and increased incidence of CNS adverse reactions. The safety of VIMPAT injection and the use of a loading dose in pediatric patients have not been studied. Dosage adjustments are recommended for patients with mild or moderate hepatic impairment or severe renal impairment. Use in patients with severe hepatic impairment is not recommended. Perform dose titration with caution in all patients with renal and/or hepatic impairment.

VIMPAT is a Schedule V controlled substance.

Please see full Prescribing Information.

For more information on VIMPAT® contact 844-599-CARE (2273).