Results of an early clinical trial found that a partial-onset seizure treatment, ADS-4101 (modified-release lacosamide) tablets, are safe and well-tolerated when compared to Vimpat, an approved but immediate-release version of the medication, Adamas Pharmaceuticals reports. The modified formulation may allow for once-daily dosing.
The results, from a Phase 1a study, were presented at the recent 14th Antiepileptic Drug and Device Trials Conference.
ADS-4101 is being developed as a high-strength lacosamide capsule designed to be taken at bedtime, so as to deliver optimal concentrations of the medicine during the day when seizures primarily occur.
The trial compared the safety and drug properties profile (pharmacokinetics) of four 400 mg oral formulations of ADS-4010 with Vimpat — a twice-daily oral form of lacosamide for partial-onset seizures, marked by UCB — in 24 healthy volunteers. The study also aimed to select an ADS-4101 formulation to be tested in further clinical trials.
At the conference, Adamas reported that all four formulations of ADS-4101 were safe and well-tolerated when compared to Vimpat. The results also showed that single 400 mg doses of ADS-4101 were better tolerated than the equivalent dose of Vimpat.
The most common adverse events experienced by participants were dizziness and oral hypoesthesia (reduced sense of touch or sensation).
All four ADS-4101 formulations were also seen to have a slower rise and prolonged time to maximum plasma concentrations — 15 hours— compared to Vimpat tablets.
Based on these results, Adamas started a new Phase 1b study.
This study will assess the tolerability and profile of three doses of ADS-4101 (200, 400 and 600 mg) given once daily at bedtime, compared to ascending twice-daily doses (100, 150, and 200 mg) of Vimpat. Twenty-four healthy volunteers will be treated for three weeks. The trial aims to establish the pharmacokinetic limits of the dose levels of ADS-4101 and Vimpat tablets, as well as the safety and tolerability of ADS-4101 compared to Vimpat. Results are expected this year.
ADS-4101 is a modified-release formulation of lacosamide, an active ingredient with anti-epileptic properties. Vimpat was approved by the U.S. Food and Drug Administration (FDA) in September 2014 and in the European Union in December 2016 to treat partial-onset seizures in adult and adolescent patients with epilepsy.
“With this positive data in hand, coupled with our understanding that epileptic seizures primarily occur during the day, we have advanced our program to evaluate three ascending doses of ADS-4101 in healthy volunteers,” Rajiv Patni, MD, chief medical officer of Adamas Pharmaceuticals, said in a press release. “The ongoing Phase 1b steady state study is designed to establish the dose and titration schedule of ADS-4101 given once daily at bedtime. We look forward to topline data from this study in the third quarter, with the goal of advancing to clinical studies in epilepsy patients following a meeting with FDA.”
“We have successfully confirmed our hypothesis that the rapid initial rise in blood levels contributes to the adverse event profile of lacosamide, allowing us to advance ADS-4101 forward in clinical development,” Gregory T. Went, PhD, chairman and CEO of Adamas Pharmaceuticals, said. “The goal of this program is to achieve higher levels of lacosamide throughout the day, when we believe patients with epilepsy are most prone to seizures, with similar or better tolerability than Vimpat (lacosamide).”
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