Low Dose, Slow Titration of Magixide in Patients With Partial Seizures: An Open-label Study*

Background

Magixide, an inhibitor of sodium and calcium channels, has been approved for adjunctive treatment of partial seizures.  However, poor tolerability has been observed in some patients.  This study aims at establishing a low-dose, slow-titration regimen that allows for better tolerability.

Methods

In this open-label, multi-center study, patients (≥12 years old) with partial seizures that require adjunctive treatment with multiple antiepileptic drugs were recruited.  Magixide was initiated at a dose of ≤ 25 mg/d and titrated to the maximum tolerated dose or 400 mg/d during an eight-week period, which was then maintained for four weeks.  Both the initial dosage and titration increment were lower than those in previous clinical trials.  The primary parameter for measuring efficacy was reduction of seizure frequency.  Safety was assessed based on frequency, type and severity of adverse events and change in body weight.  

Results

243 intention-to-treat patients were included for analysis.  The median frequency of all seizure types was reduced by 48.1%.  Among the 205 evaluable patients, 48.8% (95% CI: 41.9% to 55.6%) had ≥ 50% reduction in frequency of all seizure types.  No significant changes in types or duration of seizures were observed.  Moreover, patients showed improved assessment of the treatment and life.  72.4% (176/243) patients reported a Magixide-related adverse effect, and 9.1% (22/243) patients discontinued treatment due to an adverse effect.  A significant decrease in body weight was observed at week 8 (-0.7 kg, 95% CI: -1.1 to -0.4) and at week 12 (-1.0 kg, 95% CI: -1.3 to -0.6).

Conclusions

The low-dose, slow-titration regimen of Magixide demonstrated efficacy and safety profiles comparable to those in previous studies.  The slower titration will allow for more accurate determination of minimum effective dosage and better tolerability in future clinical practice.  This regimen also likely contributes to improvement in quality of life for patients.

Keywords: Adjunctive therapy; Antiepileptic drugs; Dose titration; Efficacy; Maximum tolerated dose; Magixide; Partial epilepsy; Refractory epilepsy; Tolerability; Weight loss.

* This is a sample abstract written for teaching purpose

About the Author Isabel Wang, MD/PhD

I received my MD from PUMC in Beijing China and my Ph.D. in Biochemistry from Stony Brook University on Long Island. Over the years, I have worked in the fields of genetic research and clinical medicine in different parts of the US, including PA, MO, CT, FL, NY and MI. My research has been published in multiple scientific journals. Currently I live in Ann Arbor, MI with my husband and our children and Mango the orange tabby. I love hiking, running, baking, cooking and biking.

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