ADHD :: Shire bioequivalence study results of SPD465, investigational drug for adults with ADHD

Shire plc (LSE: SHP, NASDAQ: SHPGY, TSX: SHQ) announced today that a single once-daily morning dose of the investigational amphetamine compound SPD465, extended release triple-bead mixed amphetamine salts, designed to reduce symptoms of Attention-Deficit/Hyperactivity Disorder (ADHD) in adults for up to 16 hours, was bioequivalent to a dose of ADDERALL XR (mixed salts of a single-entity amphetamine product) followed by a dose of mixed amphetamine salts immediate release (“MAS IR”) eight hours later.

The results of this phase I clinical trial in healthy adults were presented today at the 2006 U.S. Psychiatric & Mental Health Congress (USPMHC) annual meeting in New Orleans.

“Adults with ADHD are particularly challenged by a normal day’s activities that often extend into the evening, and SPD465 offers the possibility of full-day symptom control,” said Lenard A. Adler, M.D., director of the Adult ADHD Program in the Departments of Psychiatry and Neurology at New York University (NYU) School of Medicine and author of Scattered Minds: Hope and Help for Adults with ADHD (Putnam).

On July 21, 2006, Shire submitted a New Drug Application for SPD465, which is now under FDA review. If approved, SPD465 would be the first and only ADHD stimulant product designed to control inattention, hyperactivity and impulsivity in adults for up to 16 hours with one daily dose, thus potentially eliminating the need for augmenting a long-acting stimulant medication with a short-acting stimulant during the latter part of the day. More than nine million American adults currently exhibit symptoms of ADHD.

About the Study In the study, investigators randomized 20 healthy adults (average age of 30 years), to either of two treatments, once-daily SPD465 37.5 mg or 25 mg ADDERALL XR followed by 12.5 mg of MAS IR administered eight hours later. The researchers dispensed the assigned medication regimen to the participants after an overnight fast and collected blood plasma samples before dosing; hourly thereafter through the first 10 hours after dosing; and then periodically for the next two and a half days. After a washout period of seven days, each participant was crossed over to receive the alternate treatment.

Bioequivalency of the two medication regimens is supported by the pharmacokinetic data collected for both d-amphetamine and l-amphetamine. Maximum plasma concentrations for both d-amphetamine and l-amphetamine were similar between the SPD465 group and the ADDERALL XR plus MAS IR group (50.3 ng/ML and 49.3 ng/mL, respectively). Both d-amphetamine and l-amphetamine were quantifiable in plasma at one hour after dosing in both treatment groups. Mean plasma concentration profiles of d-amphetamine and l-amphetamine were similar throughout the day and into the evening hours for both SPD465 and ADDERALL XR augmented with MAS IR.

No clinically meaningful differences occurred between the two study groups regarding adverse events. The reported adverse events were generally considered mild and resolved before study end, except one reported case of acne. The most frequently reported adverse events in the SPD465 group of healthy adults were hypervigilance, decreased appetite, headache, eye irritation, back pain, increased energy and anorexia.

About ADHDADHD is one of the most common psychiatric disorders in children and adolescents. Although many people tend to think of ADHD as a childhood problem, up to 80 percent of children with ADHD may exhibit symptoms into adolescence and up to 65 percent of children with ADHD may still exhibit symptoms into adulthood. In fact, ADHD affects approximately 9 million adults. ADHD is a neurobiological psychiatric disorder that manifests as a persistent pattern of inattention and/or hyperactivity-impulsivity that is more frequent and severe than is typically observed in individuals at a comparable level of development. A diagnosis of Attention-Deficit Hyperactivity Disorder in adults (ADHD; DSM-IV) implies the presence of hyperactive-impulsive and/or inattentive symptoms that cause impairment and were present before the age of 7 years. The symptoms must cause clinically significant impairment, e.g., in social, academic, or occupational functioning, and be present in two or more settings, e.g., work (or school) and at home. The symptoms must not be better accounted for by another mental disorder.

Although there is no “cure” for ADHD, there are accepted treatments that specifically target its symptoms. The most common standard treatments include educational approaches, psychological or behavioral modification, and medication.

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