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

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 an intact capsule after a high-fat meal. The analysis showed that LDX may be taken in solution or as an intact capsule with or without food, without affecting the overall extent of absorption.

Like all phase I clinical trials, this was followed by phase II and phase III studies to confirm LDX’s pharmacokinetic variability and to evaluate its long-term efficacy and safety. Two more abuse liability studies supported LDX’s reduced abuse potential compared to the standard immediate-release stimulant treatments for ADHD.

It’s exciting developments like this that motivate Worldwide Clinical Trials’s neuroscience clinical trials—finding effective new treatments for conditions that affect millions of people around the world, from ADHD to Alzheimer’s Disease to Multiple Sclerosis and beyond.

Learn more about Worldwide’s 30 years of experience in neuroscience.

 

Kenneth Williams, M.D., is Senior Medical Director, Medical & Scientific Affairs at Worldwide Clinical Trials.