Adding a low dose of the anti-arrhythmic drug flecainide to modafinil alleviated excessive daylight sleepiness (EDS) in some patients with Parkinson’s disease (PD), a serene peek suggests.
“This affiliation would possibly well maybe improve wakefulness and cognition presumably by modifying the interplay between neuronal and glial networks in the mind,” said lead author Jean-Christophe Corvol, MD, PhD, of Sorbonne College, Paris.
The outcomes had been provided at a late-breaking poster presentation at the Straggle Issues Society virtual congress.
Corvol said all over his presentation of the peek that modafinil on my own had previously shown inconsistent outcomes in PD patients with EDS.
The aggregate, being developed as THN102, incorporates modafinil 200 mg/day plus a low dose of flecainide, either 2 mg (THN200/2) or 18 mg (THN200/18) day after day. In a section 2, global, double-blind, 3-interval crossover trial, investigators randomly assigned PD patients with EDS to placebo or either energetic dose of the drug. EDS turn out to be as soon as outlined as an Epworth Sleepiness Scale (ESS) total rating of ? 14, which signifies moderate to severe daylight sleepiness.
Each intervention interval lasted 2 weeks, separated by a 1- to 2-week washout interval, followed by crossover to a various intervention. “The efficacy evaluation showed no elevate-over absorb,” between the sessions, Corvol reported.
Of 77 randomly assigned patients, 75 had been uncovered to therapy, and 72 had been evaluable for efficacy. The mean age of the cohort turn out to be as soon as 63.5 ± 9.35 years, 50 had been male, and the ESS at baseline turn out to be as soon as 16.5 ± 2.
The predominant dreams of the trial had been efficacy as assessed with the ESS and security. Sufferers had been additionally evaluated for vigilance as measured by the Psychomotor Vigilance Take a look at (PVT) and for cognition the exercise of the Montreal Cognitive Evaluation (MoCA).
THN200/2 reduced ESS rankings (least squares methodology ± typical error) by 3.84 ± 0.5 facets from baseline when put next with a low cost of two.44 ± 0.5 facets with placebo (P = .012). Interestingly, THN200/18 turn out to be as soon as less effective, reducing ESS rankings by 3.18 ± 0.5 facets, which didn’t reach statistical significance when put next with placebo (P = .177).
“So that is kind of extraordinary that there isn’t in point of fact a dose-dependent absorb,” Alberto Espay, MD, MSc, director of the Parkinson’s Illness and Straggle Issues Middle at the College of Cincinnati, Ohio, commented to Medscape Clinical News. Given the modest outcomes, “I absorb no longer know whether it’s a ways going to translate into scientific significance.”
There turn out to be as soon as a pattern in remission of sleepiness, outlined as ESS < 11, in 27.5% of the patients on THN200/2 and in 25.4% on THN200/18 vs 16.2% on placebo (P = .052 and P = .102, respectively).
The reality that handiest about one quarter of patients showed remission of EDS would possibly well maybe demonstrate the rather modest reduction in total ESS rankings for the reason that nonresponders would possibly well maybe want skewed the total ESS rating. The responders would possibly well maybe want completed better than the cohort as a total.
Espay said it’s a ways going to be attention-grabbing to notion if the investigators “gawk anything else in the knowledge they easy that would focus on predictors of response, as effectively as predictors of lack of response, so as that they will most definitely dazzling-tune the collection of patients most at risk of encourage for the next peek.”
Appropriate Security and No Destructive Effects
“The safety evaluation showed no therapy-linked serious negative events,” Corvol said. Many of the negative events happened in the increased dosage sessions, with four occurrences of headache, three each and every of nausea and nasopharyngitis, and two each and every of insomnia, confusional direct, nightmare, and dry mouth. Within the THN200/2 phases, there had been two stories of nausea and undoubtedly one of insomnia. Six contributors discontinued the peek (three in each and every THN102 dosage therapy interval). No negative outcomes had been illustrious everywhere in the placebo sessions.
There had been no adjustments in the cognitive assessments as measured by the PVT and MoCA tests. There had been additionally no necessary adjustments in Parkinson’s symptoms as measured on Parts I-IV of the Straggle Issues Society–Unified Parkinson’s Illness Score Scale, nor had been there any disorders referring to a would possibly want to gain indicators, cardiac, or laboratory assessments.
When requested if placebo turn out to be as soon as the most appropriate alter, Espay said a peek against modafinil on my own would be that you shall be ready to deem, “and in point of fact, a truly noteworthy ask to answer to isn’t any longer whether or no longer you gain something that entails modafinil that is better than placebo, however something in precept positively that works better than…modafinil on my own.”
He puzzled the different of placebo as a alter and urged that for “an organization that desires to acquire these out in the market, it be simpler to narrate efficacy against placebo than it’s a ways to narrate efficacy against an already present energetic remedy.”
Theranexus Pharma sponsored the trial. Corvol served on an advisory board for Theranexus Pharma for the invent and conduct of the trial, has an advisory relationship with CleveXel Pharma, and has bought honoraria from Biogen. Espay has disclosed no relevant monetary relationships.
MDS Virtual Congress 2020: Abstract LBA3. Presented September 12, 2020.
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