Journal Frontiers in Psychiatry Publishes Analysis of Open Label Safety Study Showing Improvements in Sleep Habits for Children With ADHD After Treatment With AZSTARYS® (serdexmethylphenidate and dexmethylphenidate)

Sleep domain score improvements were statistically significant and observed throughout the twelve-month study

BOSTON, June 26, 2023 /PRNewswire/ -- Corium, LLC, a commercial-stage biopharmaceutical company leading the development and commercialization of novel central nervous system (CNS) therapies, announced today that the peer-reviewed journal Frontiers in Psychiatry published an analysis of a yearlong open-label safety study of Corium’s attention-deficit hyperactivity disorder (ADHD) medicine AZSTARYS (serdexmethylphenidate [SDX] and dexmethylphenidate [d-MPH]). AZSTARYS was approved by the U.S. Food and Drug Administration in 2021 for the treatment of ADHD symptoms in people aged 6 years through adulthood. The analysis showed that study participants, children aged 6 to 12 years with ADHD and treated with AZSTARYS for up to twelve months, had statistically significant and lasting improvements in their sleep as assessed by the Children’s Sleep Habits Questionnaire (CSHQ), a caregiver-reported screening survey designed to assess behavioral and medically based sleep problems in school children.

Almost three in four children with ADHD have some sleep impairment, according to Children and Adults with Attention-Deficit/Hyperactivity Disorder (CHADD), a national nonprofit organization serving people affected by ADHD. They commonly have trouble falling asleep and staying asleep. Some stimulant medications used to treat ADHD also can disrupt sleep and may cause insomnia.

“Given how common sleep problems are for those with ADHD, the sleep improvements identified in this analysis of the AZSTARYS long-term safety study are meaningful and relevant safety information about this novel medicine,” said Greg W. Mattingly, M.D., lead author, associate clinical professor of psychiatry at Washington University School of Medicine, and president elect of the American Professional Society for ADHD and Related Disorders.

“Publication of this encouraging sleep data on AZSTARYS reinforces why AZSTARYS is an important treatment option for providing clinically meaningful ADHD symptom control,” said Charles Oh, MD, Chief Medical Officer of Corium. “Our continued examination of the safety and efficacy of AZSTARYS is an example of Corium’s strong commitment to deliver innovative solutions that transform care for patients with CNS disorders.”

AZSTARYS is the first and only medicine for ADHD symptoms that contains SDX, the prodrug of d-MPH, along with immediate-release d-MPH. SDX is a prodrug that is pharmacologically inactive until reaching a patient’s lower gastrointestinal tract where, by design, it gradually converts to d-MPH throughout the day. This formulation provides rapid control of ADHD symptoms with the immediate- release d-MPH and extended duration of control with the SDX. AZSTARYS is a Schedule II controlled substance because it contains 30% immediate release d-MPH. The SDX component of AZSTARYS (±comprising 70% of the active ingredient) is a Schedule IV controlled substance.

Trial Design

In the yearlong open label classroom study (NCT03460652), investigators used the validated CSHQ to evaluate sleep, a pre-specified secondary trial endpoint, in 238 children aged 6 to 12 years who received AZSTARYS. The CSHQ uses a total of 33 questions for caregivers about a child’s sleep behavior across eight domains using a three-point scale of “usually”, “sometimes” and “rarely.” The eight sleep behaviors are bedtime resistance, sleep onset delay, sleep duration, sleep anxiety, night wakings, parasomnias (abnormal movement or speech as one falls asleep), sleep-disordered breathing and daytime sleepiness. Total CSHQ scores can range from 33 to 99, with any score of 41 or higher indicating a sleep disorder. At the study start, all but two children had CSHQ total scores in the range of 42 to 79, and those two participants scored 37 and 40.

In the year-long study, after screening and a three-week dose-optimization for the new participants, the children received once-daily AZSTARYS doses of 26.1/5.2 milligrams (mg), 39.2/7.8 mg, or 52.3/10.4 mg of SDX/d-MPH, which delivered 20-, 30-, and 40-mg molar equivalent doses of total d-MPH HCl.

AZSTARYS Treatment Yielded Sustained Overall Sleep Improvements Over 12 Months

After one month of AZSTARYS treatment, the children’s average CSHQ total sleep disturbance score significantly decreased, indicating improved sleep. Specifically, their scores declined from 53.4 to 50.5, a reduction of 2.9 points [95% CI: −3.5 to −2.4; p < 0.0001]. Moreover, after 12 months of treatment their average CSHQ total score remained in the 48.9 to 50.1 range, indicating the children sustained overall sleep improvements while receiving AZSTARYS.

About AZSTARYS

AZSTARYS, approved for patients ages 6 years through adulthood, is the first and only once-daily treatment for ADHD symptoms containing SDX, the prodrug of d-MPH. SDX is designed specifically to be pharmacologically inactive until reaching a patient’s lower gastrointestinal tract, where, by design, the prodrug gradually converts to d-MPH throughout the day. This formulation provides control of ADHD symptoms both rapidly with the immediate-release d-MPH and for an extended duration with SDX. Once-daily AZSTARYS is available in the U.S. in three SDX/d-MPH dose strengths of

26.1/5.2 mg, 39.2/7.8 mg, and 52.3/10.4 mg.

Indication and Important Safety Information for AZSTARYS (serdexmethylphenidate and dexmethylphenidate)

INDICATION

AZSTARYS is a central nervous system (CNS) stimulant indicated for the treatment of Attention Deficit Hyperactivity Disorder (ADHD) in patients aged 6 years and older.

IMPORTANT SAFETY INFORMATION

WARNING: ABUSE AND DEPENDENCE

• CNS stimulants, including AZSTARYS, other methylphenidate-containing products, and amphetamines, have a high potential for abuse and dependence. Assess the risk of abuse prior to prescribing, and monitor for signs of abuse and dependence while on therapy.

CONTRAINDICATIONS

• Known hypersensitivity to serdexmethylphenidate, methylphenidate, or other product components. Bronchospasm, rash, and pruritus have occurred with AZSTARYS. Hypersensitivity reactions such as angioedema and anaphylactic reactions have occurred with other methylphenidate products.
  
• Concomitant treatment with a monoamine oxidase inhibitor (MAOI) or use of an MAOI within the preceding 14 days, because of the risk of hypertensive crisis.

WARNINGS AND PRECAUTIONS

• Sudden death has been reported in association with CNS stimulant treatment at recommended doses in pediatric patients with structural cardiac abnormalities or other serious heart problems. In adults, sudden death, stroke, and myocardial infarction have been reported at recommended doses. Avoid use in patients with known structural cardiac abnormalities, cardiomyopathy, serious heart arrhythmias, coronary artery disease, or other serious heart problems.
  
• CNS stimulants cause an increase in blood pressure and heart rate. Monitor all patients for hypertension and tachycardia.
  
• Exacerbation of Pre-existing Psychosis: May exacerbate symptoms of behavior disturbance and thought disorder in patients with a pre-existing psychotic disorder. Induction of a Manic Episode in Patients with Bipolar Disorder: May induce a mixed/manic episode in patients with bipolar disorder. Prior to initiating treatment, screen for risk factors for developing a manic episode (e.g., comorbid or history of depressive symptoms, or a family history of suicide, bipolar disorder, or depression). New Psychotic or Manic Symptoms: At recommended doses, may cause psychotic or manic symptoms (e.g., hallucinations, delusional thinking, or mania) in patients without a history of psychotic illness or mania. Discontinue if symptoms occur.
  
• Cases of painful and prolonged penile erections and priapism have been reported with methylphenidate products. Immediate medical attention should be sought if signs or symptoms of prolonged penile erections or priapism are observed.
  
• CNS stimulants, including AZSTARYS, are associated with peripheral vasculopathy, including Raynaud’s phenomenon. Signs and symptoms are usually intermittent and mild; very rare sequelae include digital ulceration and/or soft tissue breakdown. Carefully observe patients during treatment for digital changes. Further evaluation may be required, including referral.
  
• CNS stimulants have been associated with weight loss and slowing of growth rate in pediatric patients. Monitor height and weight at appropriate intervals in pediatric patients. Treatment may need to be interrupted in children not growing or gaining weight as expected.

ADVERSE REACTIONS

• Based on accumulated data from other methylphenidate products, the most common (>5 percent and twice the rate of placebo) adverse reactions are appetite decreased, insomnia, nausea, vomiting, dyspepsia, abdominal pain, weight decreased, anxiety, dizziness, irritability, affect lability, tachycardia, and blood pressure increased.

DRUG INTERACTIONS

• Adjust dosage of antihypertensive drug as needed. Monitor blood pressure.
  
• Avoid use of AZSTARYS on the day of surgery if halogenated anesthetics will be used.

For additional safety information, click here for Prescribing Information and Medication Guide, including BOXED WARNING.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch, or call 1-800-FDA-1088.

About Corium

Corium, LLC, is a commercial-stage biopharmaceutical company that is leading the development and commercialization of CNS therapies that provide physicians with innovative treatment options for patients, their families, and their caregivers. Corium is commercializing two FDA approved products, ADLARITY and AZSTARYS. For further information, please visit https://www.corium.com.

References

1. Mattingly GW, Childress AC, Cutler AJ, et al. Serdexmethylphenidate/dexmethylphenidate effects on sleep in children with attention-deficit/hyperactivity disorder. Front Psychiatry. 2023 . Volume 14. doi: 10.3389/fpsyt.2023.1193455, available at https://www.frontiersin.org/articles/10.3389/fpsyt.2023.1193455/full.
   
2. Kollins SH, Braeckman R, Guenther S, et al. A Randomized, Controlled Laboratory Classroom Study of Serdexmethylphenidate and d-Methylphenidate Capsules in Children with Attention-Deficit/Hyperactivity Disorder. J Child Adolesc Psychopharmacol. 2021;31(9):597-609. doi:10.1089/cap.2021.0077.

Contact: Corium, LLC
Gartmanpr@gmail.com
202-413-4226

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