Placebo-Controlled, Double-Blind, Study to Determine the Safety and Efficacy of SDX in Patients With IH

SDX is a prodrug of dexmethylphenidate (d‐MPH). SDX behaves as a prototypical prodrugthat is devoid of pharmacological effects until metabolized to active d‐MPH. Centralnervous system (CNS) stimulants, including d‐MPH products, are being used off‐label bypatients with IH. The potential advantage of SDX‐derived d‐MPH is its unique PK profilewith rising d‐MPH plasma concentrations at approximately 3 hours postdose followed by abroad peak from approximately 8 to 12 hours postdose (without sharp exposure spikes), anda gradual decline after the peak.The optimal dose of SDX will be determined for each participant by titration based onindividual tolerability and response during the 5‐week SDX‐only Open‐Label Titrationperiod (OLTP), after which 2/3 of the participants will continue to receive SDX and 1/3of the participants will receive placebo (withdrawal design) in the 2‐week Double‐BlindWithdrawal Period (DBWP).The study will evaluate safety (primary endpoint), efficacy and PK in patients with IHafter daily oral administration of SDX either once per day in the evening (qd pm) ortwice per day (morning and evening: bid). The study is expected to inform about theoptimal SDX dose range and the best dose regimen (nighttime dosing or twice‐per‐day) forfurther studies in patients with IH and narcolepsy. The evening dosing regimen (justbefore bedtime) is of interest since there is little or no exposure to d‐MPH for thefirst several hours post‐dose and the mean peak d‐MPH concentration occurs at 10‐12 hourspost‐dose (ie, in the morning after a nighttime dose).