Oral Compound Seen to Ease Daytime Sleepiness in Phase 2 Trial

Theranexus’ lead candidate THN102 significantly lowers excessive daytime sleepiness in people with Parkinson’s disease, according to final data from a Phase 2 clinical trial.

“The symptom addressed by THN102 … affects around 40% of patients. It is particularly debilitating and represents one of the primary risk factors for accidents, with considerable medical and economic consequences,” Jean-Christophe Corvol, MD, PhD, a Parkinson’s specialist, professor of neurology at the Pitié-Salpêtrière Hospital in Paris, and the trial’s principal investigator, said in a press release.

With no currently approved treatments, “the positive results achieved with THN102 in this trial are a tremendous step forward in treating this debilitating symptom,” Corvol added.

THN102 is an oral investigational therapy that combines modafinil (sold under the brand name Provigil) — a treatment for narcolepsy, a disorder characterized by excessive sleepiness — and flecainide, a treatment for irregular heartbeats repurposed to boost modafinil’s benefits.

Flecainide enhances modafinil’s effects on glial cells, non-neuronal cells of the nervous system that support and protect nerve cells and are involved in sleep regulation.

Previous data from a Phase 1 clinical trial (NCT03182413) showed that the therapy was safe in healthy volunteers deprived of sleep.

The Phase 2 trial (NCT03624920; 2017-004475-31) evaluated the safety and effectiveness of THN102 in 75 people with excessive daytime sleepiness due to Parkinson’s disease. Patients were recruited across 30 sites in France, Hungary, Czech Republic, Germany, and the U.S.

Participants were randomly assigned to three successive, two-week treatment periods: THN102 at 200 mg modafinil and 2 mg flecainide, THN102 at 200 mg modafinil and 18 mg flecainide, or to a placebo. Treatment periods were separated by a one-week washout period (no treatment).

Treatment effectiveness, with safety as a main study goal, was measured by changes in daytime sleepiness — assessed through the Epworth Sleepiness Scale (ESS). ESS is a self-administered questionnaire with scores ranging from zero to 24; scores greater than 10 indicate higher-than-normal levels of daytime sleepiness.

Secondary goals included changes in attention and alertness — assessed with the Psychomotor Vigilance Test — and in cognitive function — through the Montreal Cognitive Assessment scale.

A total of 72 patients (48 men and 24 women), with a mean age of 63.3 (range 38–80), completed the three treatment periods.

Results showed that patients had severe excessive daytime sleepiness at study’s start, and that THN102 (200 mg modafinil/2 mg of flecainide) significantly lowered their daytime sleepiness (by 3.9 points in ESS), compared with a placebo (a drop of 2.4 points).

The proportion of patients without excessive daytime sleepiness for the duration of the treatment was higher with both THN102 doses. But only the 200 mg modafinil/2 mg flecainide dose reached statistical significance when compared to placebo (27.5% vs 16.2%).

No significant changes were observed in attention/alertness and cognitive function with either dose of THN102. Importantly, the therapy was not seen to affect Parkinson’s motor and other symptoms (assessed using the Unified Parkinson’s Disease Rating Scale).

THN102 was well-tolerated, with few treatment-related adverse events — most mild to moderate severity — and no treatment-related serious adverse events reported. THN102’s safety profile was consistent with the known profile of modafinil, the researchers noted.

“To our knowledge, THN102 is the only pharmaceutical development with demonstrated efficacy for this indication, affecting about 2 million patients,” said Franck Mouthon, Theranexus’ CEO.

Mouthon added that the company now plans to “join forces with an industrial partner to continue developing THN102.”

More detailed data from the Phase 2 trial are expected to be presented at an upcoming scientific conference.

Theranexus is also evaluating THN102’s efficacy in people with narcolepsy, and it has completed a Phase 2 trial (NCT02821715) in people with this disorder in France.