Phase I Clinical Trials for LDX: How Do We Treat ADHD?

attention deficit hyperactivity disorder; Lisdexamfetamine dimesylate
By Kenneth Williams, M.D.,

  One of the most common behavioral disorders in childhood, attention deficit hyperactivity disorder (ADHD) affects an estimated 8-12% of children worldwide and follows an estimated 10-70% of patients into adolescence and adulthood. The most common treatment for ADHD is stimulants—but concerns about the association between ADHD and substance use disorder, tampering, and other forms of misuse have prompted research into new, nonabusable treatments for ADHD. One potential solution lies in prodrugs—compounds that are pharmacologically inactive until metabolized in the body. By undergoing biotransformation before exhibiting its therapeutic effect, a prodrug can be administered once-daily, providing prolonged delivery, more consistent clinical effects, and less abuse potential. Today, there is only one prodrug stimulant: Lisdexamfetamine dimesylate (LDX, marketed as Vyvanse™ by Shire U.S. Inc.), which is indicated for the treatment of ADHD in children aged 6 to 12 years. Therapeutically inactive before ingestion, LDX is converted into naturally-occurring l-lysine and active d-amphetamine after ingestion. Studying the Efficacy of LDX After an in-vitro study, a Phase 1 clinical study determined the pharmacokinetic profile of the LDX formulation. With three 1-week study periods, with a 7-day washout between doses, eighteen healthy volunteers—9 men and 9 women, aged 18 to 55 years old—received a single 70 mg LDX dose under three dose conditions: Fasting, with capsule only; a solution containing the capsule contents; and...

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