Addrenex Pharmaceuticals Announces Positive Phase III Clinical Results For Clonicel To Treat ADHD

A drug that diminishes the body's hyper-reactivity to stress has been shown to significantly reduce symptoms of attention-deficit hyperactivity disorder (ADHD) in children, according to a phase 3 clinical trial conducted by Addrenex Pharmaceuticals.

The study showed that the new drug, Clonicel, achieved statistically significant improvement over placebo in reducing an aggregate of 18 ADHD symptoms listed by the American Psychiatric Association and used by physicians to diagnose and classify the condition.

"This is the first study to validate the potential for a long-acting version of clonidine -- a widely used hypertension drug -- as a safe and effective treatment for ADHD," said Moise Khayrallah, Ph.D., CEO of Addrenex Pharmaceuticals, a small Durham start-up that initiated and coordinated the multicenter trial.

Previous studies of clonidine have indicated that the drug diminishes select symptoms of ADHD, but these studies have been small and inconclusive, Khayrallah said. Moreover, clonidine carries bothersome side effects that have limited its use, including a peak of drowsiness when the drug is absorbed and a subsequent rebound of symptoms when drug levels subside.

Addrenex scientists developed Clonicel to reduce these side effects and treat specific ADHD symptoms that may occur when the body's adrenergic system is in overdrive, producing excessive levels of the stress hormone adrenaline. Such symptoms include emotional outbursts, mood swings, insomnia and hyperreactivity to stress.

"We conducted a well-powered, randomized clinical trial to demonstrate that Clonicel may be effective on its own in treating a multitude of ADHD symptoms, with a favorable side effect profile," said Khayrallah. "We're very excited with the positive data we obtained, and we intend for this study to serve as part of the basis for review and approval by the FDA, hopefully by next year."

The study showed that Clonicel was statistically superior to placebo on the primary endpoint, the ADHD Rating Scale of 18 symptoms. Clonicel was also statistically superior to placebo on several secondary scales completed by clinicians and parents, including a scale that assesses adrenergic dysregulation. The scale was designed by Joseph Horacek, M.D., a Charlotte neuropsychiatrist and cofounder of Addrenex. Side effects were generally mild to moderate in severity, and no serious adverse events were reported in the study.

A total of 228 children between the ages of 6 and 17 with a diagnosis of ADHD participated in the randomized, double-blind, placebo-controlled trial that compared two doses of Clonicel, 0.2 mg per day and 0.4 mg per day, with placebo. Children received either study medication or placebo for eight weeks at one of 13 study centers nationwide.

If Clonicel is approved by the Food and Drug Administration, the new drug will be marketed by Sciele Pharma under an agreement signed with Addrenex in July 2007.

The introduction of Clonicel into the ADHD market would fill a void that currently exists in the treatment of ADHD, Khayrallah said. While stimulants play an important role in treating ADHD, they do not address all of the symptoms associated with the disorder and may result in unacceptable side effects in some patients.

Because Clonicel targets receptors within the body's stress response center -- the adrenergic system -- it may be more effective in alleviating lesser-known symptoms that accompany ADHD, such as emotional outbursts, mood swings, irritability and hyperreactivity to stress, Horacek said.

"We believe that Clonicel is normalizing the excess of the adrenergic hormones that contribute to many of the symptoms of ADHD," said Horacek.

Stress hormones produce a rapid heart rate, elevated blood pressure, sweating, temperature increases, heightened anxiety, stress and fear, he said. Scientists have implicated an excessive stress response to a wide array of disorders, from ADHD and Tourette's syndrome to post-traumatic stress disorder and migraines.

Addrenex is currently developing a cadre of drugs focused on treating these and other conditions arising from adrenergic excess, including hypertension, menopausal flushing, pain and sleep disturbance. By mining a library of 400 adrenergic compounds at the University of Nebraska Medical Center, Addrenex scientists have already identified one new drug candidate, a compound code named ADX415, to treat hypertension and other conditions.

"With the extremely positive data from our first study, we are well under way toward our goal of regulating adrenergic excess and helping to ameliorate medical conditions that arise from this physiologic imbalance," said Khayrallah.

The company is also midway through a second ADHD clinical trial testing the effects of Clonicel together with stimulants. The goal is to determine if the two treatments together alleviate a broader range of symptoms than either drug alone.