ZX008 Is Well-tolerated and Unaffected by Food Intake, Study of Healthy Participants Shows

Ana Pena, PhD avatar

by Ana Pena, PhD |

Share this article:

Share article via email
Sunovion FDA

ZX008, an experimental therapy for Dravet syndrome, was found to be well-tolerated and can be administered regardless of food intake, according to clinical results of a study in healthy volunteers.

The findings mean that ZX008 likely will be easier to administer than other antiepileptic treatments, as caregivers will not have to tightly control its delivery in conjunction with meal times.

The study, “The Lack of Effect of Food on the Pharmacokinetics of ZX008 (Fenfluramine Oral Solution): Results of a Single-dose, Two-period Crossover Study,” was published in the journal Clinical Therapeutics.

ZX008 is an oral, low-dose solution of fenfluramine hydrochloride currently under development by Zogenix to treat seizures in patients with Dravet syndrome and other epileptic conditions, including Lennox-Gastaut syndrome.

Several Phase 3 clinical trials are underway in the U.S. and Europe testing different doses of ZX008, including its safety and absorption by the body. One such trial (NCT02826863), taking place across Europe and in Australia, is currently recruiting patients ages 2 to 18.

Most Dravet patients take multiple antiepileptic medications, which makes it difficult for caregivers to keep track of correct administration times and conditions. For example, stiripentol must be given with a meal, but should not be taken with milk or dairy products.

Food can affect several aspects of drug pharmacokinetics — how the medication is absorbed, distributed, metabolized, and eliminated by the body. It can delay and reduce, accelerate and increase, or have no effect at all on absorption.

For patients receiving several antiepileptic medications, food makes it even more challenging to maintain a correct administration schedule for all medicines.

Researchers conducted a Phase 1, open-label, randomized study in healthy subjects to evaluate both the safety and food effect on ZX008’s pharmacokinetics.

Blood levels of ZX008’s active ingredient fenfluramine, along with its active form after being metabolized by the body (called norfenfluramine), were compared between adults either after eating or after a period of fasting.

Fourteen healthy nonsmoking individuals, ages 18 to 50, received a 0.8-mg/kg dose of ZX008 following a 10-hour overnight fast. After a “washout” period of nine days in which the medicine was not administered, participants received another ZX008 dose half an hour after eating a high-fat breakfast.

Blood samples were taken before each dose, and periodically for 72 hours after each dose, to determine the concentrations of fenfluramine and norfenfluramine.

Fenfluramine was absorbed equally well in both fed or fasted participants. Food had no effect on both ZX008 absorption or the amount reaching the blood (called bioavailability). Additionally, food did not have an impact on blood concentrations of norfenfluramine.

A single oral dose of 0.8 mg/kg of ZX008 was generally well-tolerated in both a fasted and a fed state.

No severe or serious adverse events were reported. Seven subjects reported at least one adverse event due to treatment, but all were mild.

Although the study tested only a single dose of ZX008, researchers said that the compound has high solubility and high permeability, meaning it is unlikely to be significantly affected by food at any dose.

“The results of the present study support the recommendation that fenfluramine (ZX008) can be administered without regard to meals,” the study’s authors concluded.

ZX008 has received orphan drug designation in the U.S. by the FDA and in Europe by the EMA, which provides developmental incentives to companies. Recently, the investigational treatment also received breakthrough therapy designation by the FDA.