The investigational drug consistently increased the proportion of patients no longer suffering from daytime sleepiness during treatment.
Results from a placebo-controlled, double-blind, randomized 3-way crossover study demonstrated that THN102 (Theranexus), a combination of modafinil and low-dose flecainide, was well tolerated and significant improved excessive daytime sleepiness (EDS) in patients with Parkinson disease (PD).1
The study included 75 subjects (mean age, 63.5 years [±9.35]; male participants, n = 50; Epworth sleepiness scale [ESS] score, 16.2 [±2]) in the safety population and was presented at the 2020 MDS Virtual Congress, September 12–16, 2020, by lead investigator Jean-Christophe Corvol, MD, PhD, Parkinson disease specialist, Pitié Salpêtrière Hospital and the Brain Institute, and colleagues.
Patients were treated with THN102 in 2 dosing groups: 200-mg modafinil/2-mg flecainide (THN102-200/2), and 200-mg modafinil/18-mg flecainide (THN102-200/18), or placebo for 2 weeks each separated by a 1- to 2-week wash-out period. The efficacy population, which included 72 subjects, showed no significant treatment period interaction while those treated with THN102-200/2 significantly improved sleepiness compared to placebo (THN102-200/2: least square-mean [LS-mean], –3.84 [±0.5]; placebo: LS-mean, –2.44 [±0.5]; P = .012).
Corvol and colleagues noted that THN102-200/18 also improved ESS but did not reach statistical significance (LS-mean, –3.18 [±0.5]; P = .177).
Overall, there was no treatment-related serious adverse events (TEAEs) reported, but there were 6 patients, 3 from each treatment group, that discontinued due to AEs. Headache, nausea, and nasopharyngitis, all of which were found in the THN102-200/18 group were among the most frequent AEs observed and occurred in 4, 3, and 3, patients respectively.
The proportion of patients no longer presenting EDS for the duration of treatment was considerably higher with THN102-200/2 than in the placebo group (27.5% vs 16.2; P = .05). Investigators noted that the other exploratory efficacy parameters used in the trial did not show a difference between THN102 and the placebo.2
Theranexus originally announced the success of the phase 2 trial in March, at which time Corvol noted that “the symptom addressed by THN102—excessive daytime sleepiness in Parkinson’s disease—affects around 40% of patients. It is particularly debilitating and represents 1 of the primary risk factors for accidents, with considerable medical and economic consequences. There is currently no approved treatment to mitigate these major impacts. The positive results achieved with THN102 in this trial are a tremendous step forward in treating this debilitating symptom.”
The patient population all had ESS score of 14 or higher and Hoehn and Yahr scale score ≤4. Investigators of the study used treatment tolerance as the primary end point, with secondary end points that evaluated sleepiness, vigilance, and cognition.
Investigators noted that THN102’s success in improving excessive daytime sleepiness warrants future clinical trials.
For more coverage of MDS 2020, click here.