Excessive Daytime Sleepiness Therapy in Patients With Parkinson Disease Meets Phase 2 Primary Efficacy End Point

Theranexus announced this week that its phase 2 trial for THN102 (modafinil/flecainide) in patients with Parkinson disease (PD) met its primary efficacy end point of significantly increasing the proportion of patients no longer suffering from excessive daytime sleepiness (EDS).

Patients with PD (PwP) are at a higher risk of developing EDS than the general population—it affects approximately 40% of those with the disease. As noted in Theranexus’ press release, finding effective therapeutic interventions in PwP can prove difficult, as therapies require a delicate balance to maintain control over motor symptoms.

In the double-blind, placebo-controlled, crossover phase 2 trial, researchers recruited 75 PwP with EDS, characterized by a score of 14 or more (out of 24) on the Epworth Sleepiness Scale (ESS). Participants were derived from centers in Europe and the United States, with a 1-week washout period between each successive 2-week period of randomly administered THN102 (200mg modafinil/2mg flecainide), THN102 (200mg modafinil/18mg flecainide), or placebo.

The primary end point of the trial was tolerability and the primary efficacy end point was EDS.

In the phase 2 trial findings, THN102 administered in doses of 200mg modafinil/2mg flecainide (THN102-200/2) was associated with significant improvements in the ESS by 3.9 points (P = .01) compared with placebo (2.4 points). Additionally, the proportion of patients no longer presenting EDS for the duration of the treatment (ESS <11) was notably higher with THN102-200/2 than in the placebo group (27.5% vs 16.2%; P = .05).

Tolerability, examined through sections of the Unified Parkinson’s Disease Rating Scale, was achieved in both doses administered of THN102, with no effect seen on the motor disorders or other symptoms that occur in PwP.

“With aging populations and increasing numbers of elderly people, the number of patients affected by Parkinson disease will continue to rise,” stressed principal trial investigator Jean-Christophe Corvol, PD specialist and professor at Pitié Salpêtrière Hospital and the Brain Institute.

Corvol noted that as EDS represents 1 of the primary risk factors for accidents, with considerable medical and economic consequences, finding an approved treatment to mitigate these issues would be crucial. “The positive results achieved with THN102 in this trial are a tremendous step forward in treating this debilitating symptom,” said Corvol.