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Adlon Therapeutics L.P. and Purdue Pharma L.P. Will Present Data from Adhansia XR™ (methylphenidate HCl) Studies Examining Sleep Quality Outcomes, Functional Outcomes and Executive Functioning at the 2020 APSARD Annual Meeting

January 16, 2020 Off By BusinessWire

STAMFORD, Conn.–(BUSINESS WIRE)–Adlon Therapeutics L.P. and Purdue Pharma L.P. will present data from three studies evaluating PRC-063 at the 2020 American Professional Society of ADHD and Related Disorders (APSARD) Annual Meeting in Washington D.C. PRC-063 was approved by the U.S. Food and Drug Administration (FDA) for the treatment of Attention-Deficit/Hyperactivity Disorder (ADHD) in patients six years and older and is currently available as Adhansia XR™ (methylphenidate hydrochloride) extended-release capsules CII.

The Full Prescribing Information for Adhansia XR contains a boxed warning for abuse and dependence. CNS stimulants, including Adhansia XR, other methylphenidate-containing products, and amphetamines have a high potential for abuse and dependence. Healthcare professionals should assess the risk of abuse prior to prescribing Adhansia XR and monitor for signs of abuse and dependence while patients are on therapy.¹

Information from the three posters highlighting the effect of Adhansia XR on sleep quality outcomes in adults and adolescents with ADHD, the effect of Adhansia XR on functional outcomes in adults with ADHD, and the effect of Adhansia XR on executive functioning in adolescents with ADHD is summarized below.

“These studies demonstrate Adlon Therapeutics’ ongoing efforts to inform the scientific community about Adhansia XR following its FDA approval and introduction in 2019,” said Mike Ronning, vice president, sales and marketing, and general manager, Adlon Therapeutics. “We are pleased to present relevant medical and disease state studies at this scientific forum.”

Adhansia XR is not appropriate for all patients, and healthcare professionals should work with their patients to determine the most appropriate treatment option. Adhansia XR is contraindicated in patients with a known hypersensitivity to methylphenidate or product components, as well as patients receiving concurrent treatment with a monoamine oxidase inhibitor (MAOI) or who have used an MAOI within the preceding 14 days.¹

The Full Prescribing Information for Adhansia XR, including Boxed Warning, is available at this link. Please see Important Safety Information for Adhansia XR below, including the Boxed Warning, Contraindications, Warnings and Precautions including the potential for abuse and dependence, serious cardiovascular events, blood pressure and heart rate increases, psychiatric adverse reactions, priapism, peripheral vasculopathy, long-term suppression of growth, allergic-type reactions, and Adverse Reactions.¹

Poster #5 (Poster Session 1): Sleep Quality Outcomes in Adults and Adolescents with ADHD Treated with PRC-063 in Two Randomized, Double-Blind, Placebo-Controlled, Multi-Center Studies with Six-Month Open Label Extensions

The Phase 3 program included two randomized, double-blind, placebo-controlled studies and a six-month open-label extension to examine the efficacy and safety of Adhansia XR in adolescent and adult patients with ADHD and assess the effects of Adhansia XR on sleep quality as a secondary endpoint. At screening, baseline, end of double-blind studies, and during monthly open label visits, patients completed the Pittsburgh Sleep Quality Index (PSQI), which is used to measure indicators such as overall sleep quality, sleep latency, duration of sleep, sleep efficiency, sleep disturbances, requiring medication to sleep, and daytime disfunction due to sleepiness.

The studies enrolled 375 adults and 354 adolescents; 333 adults and 323 adolescents completed the double-blind study; 184 adults and 178 adolescents entered the open-label study. In these adult and adolescent studies, patients with a DSM-5 ADHD diagnosis were randomly assigned to a fixed daily dose of Adhansia XR at 25, 45, 70, 85, or 100 mg for four weeks. During a six-month open-label extension, daily doses were titrated to a patient’s optimal dose (25, 35, 45, 55, 70, 85 or 100 mg). The studies evaluated a maximum of 85 mg/day for adolescent patients and 100 mg/day for adult patients.

In the double-blind studies, PSQI Global Scores in adults and adolescents using Adhansia XR remained similar to placebo (Adults: Baseline, 8.8±3.7; End of Double-Blind Placebo, 7.3±4.1; End of Double-Blind Adhansia XR, 8.1±3.6, p=.0972; Adolescents: Baseline, 5.7±3.3; End of Double-Blind Placebo, 5.4±3.7; End of Double-Blind Adhansia XR, 5.4±3.4, p=.6110). During the open-label extension where patients were titrated to their optimum dose, the PSQI Global Scores decreased further from the baseline (Adults: 5.4±3.2, Adolescents: 4.4±3.3). A lower PSQI Global score indicates better sleep quality.

The most common sleep-related adverse events in the double-blind studies were headache (Adults: 17.5%; Adolescents: 15%), insomnia (Adults: 15.8%; Adolescents: 6.5%) and decreased appetite (Adults: 11.1%; Adolescents: 20.1%) In the six month open label continuation, the most frequent adverse events among adults and adolescents were headache (12.9%), insomnia (12.9%), and decreased appetite (11.3%).

Poster #6 (Poster Session 2): Functional Outcomes in Adults with ADHD Treated with PRC-063 in a Randomized, Double-Blind, Placebo-Controlled, Multi-Center Study with a Six-Month Open-Label Extension

The randomized, double-blind, fixed-dose study of Adhansia XR and placebo, followed by a six-month open-label extension, sought to identify domain-specific and overall functional improvement in adults with ADHD as a secondary endpoint. The Weiss Functional Impairment Rating Scale (WFIRS), a scale that measures impairment in areas including family, life skills, and social activities, was performed at the beginning of the study, as well as at the end of the double-blind and open-label portions.

The study enrolled 375 adults (≥18 years) with a DSM-5 ADHD diagnosis, of which 333 completed the double-blind portion and 184 entered a six-month open-label extension. Patients were randomly assigned to either a daily dose of Adhansia XR (25, 45, 70 or 100 mg) or placebo. Patients underwent blinded titration to a fixed dose over a two-week period, followed by two weeks at their assigned dose. During the open-label extension, patients were titrated to their optimal dose (25, 35, 45, 55, 70, 85 or 100 mg/day).

During the double-blind portion, WFIRS Total Scores for patients treated with Adhansia XR decreased (least-squares [LS] mean change from baseline [cfb]: -0.24 for Adhansia XR vs. -0.15 for placebo; p=.056), as did specific scores around work (-0.30 for Adhansia XR vs. -0.11 for placebo; p=.01), self-concept (-0.40 for Adhansia XR vs. -0.19 for placebo; p=.04), and risky activities (-0.12 for Adhansia XR vs. -0.04 for placebo; p=.03). A decreased WFIRS score indicates less impairment. These results were seen during the fixed-dose double-blind portion of the study despite approximately 90% of patients being either over or under-dosed. In the open-label portion, on optimized doses, there were significant differences in functional outcomes (p<.0001) across all domains and in the Total Score of the WFIRS.

Adverse effects (AEs) seen in greater than 10% of cases during the double-blind portion included headache (17.5%), insomnia (15.8%), and decreased appetite (11.1%). AEs seen in greater than 10% of cases during the open-label portion included insomnia (15.1%), initial insomnia (11.9%), and headache (10.8%).

Poster #9 (Poster Session 1): Effect of PRC-063 on Executive Functioning in Adolescents with ADHD in a Randomized, Double-Blind, Placebo-Controlled, Multi-Center Study with a Six-Month Open Label Extension

The randomized, double-blind, fixed-dose, placebo-controlled study of the clinical efficacy and safety of Adhansia XR, including a six-month open-label extension, assessed executive functioning in adolescents with ADHD as a secondary endpoint. Executive functioning, a mental process that enables individuals to focus attention, remember instructions, and juggle multiple tasks successfully, was evaluated using the Behavior Rating Inventory of Executive Function (BRIEF) at baseline and at the end of both the double-blind and open-label periods.²

Patients randomly assigned to Adhansia XR 25, 45, 70 or 85 mg, or placebo per day underwent two weeks of titration to their fixed dose followed by a two-week assessment period. During six month open-label extension, patients were titrated to their optimal dose (Adhansia XR 25, 35, 45, 55, 70 or 85 mg, or placebo per day). 354 adolescents (12-17 years) with a DSM-5 ADHD diagnosis were enrolled, 323 completed the double-blind study and 178 entered the open-label study.

In the double-blind study, the mean Global Executive Complex (GEC) T-Score (SD) of patients who were randomized to Adhansia XR was 67 (SD 11.57), indicating a change from baseline (cfb) of -6.5. This is in comparison to a mean GEC T-Score of 68.4 (SD 14.1) and cfb of -4 in patients who received placebo (p=.0630). A lower score equals less dysfunction. A greater change was seen during the open-label extension where patients were able to titrate to an optimal dose of Adhansia XR (GEC T-Score: 62.5 [SD 11.75]; p<.0001). These results reached the measure of statistical significance according to the protocol-defined statistical analysis.

The most common adverse events (AEs) during the double-blind study were decreased appetite (16.1%), headache (13.9%), and irritability (8.4%). During the open-label extension, 98% of AEs were mild to moderate in severity and the most common included headache (15.2%), decreased appetite (14.6%), and insomnia (10.7%). Eight patients discontinued treatment during the open-label extension due to an AE.

About Adhansia XR™

Adhansia XR was developed by Purdue Pharma (Canada). The medication was granted marketing authorization from Health Canada in December 2017 and is currently marketed in Canada as FOQUEST™ for the treatment of ADHD. In the U.S., the medication was approved by the U.S. Food and Drug Administration (FDA) for the treatment of Attention-Deficit/Hyperactivity Disorder (ADHD) in patients six years and older in February 2019.

Adhansia XR capsules contain multilayered beads, which are composed of an immediate-release layer which contains approximately 20 percent of the methylphenidate dose, and a controlled-release layer which contains approximately 80 percent of the methylphenidate dose, for oral administration. The MLR™ (multi-layer release) technology is a controlled-release delivery system patented by Purdue Pharma.

Please see Important Safety Information, including Boxed Warning, Warnings & Precautions, and Adverse Reactions below.

IMPORTANT SAFETY INFORMATION

WARNING: ABUSE AND DEPENDENCE

CNS stimulants, including Adhansia XR, 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

Adhansia XR is contraindicated in patients with a known hypersensitivity to methylphenidate or other components of Adhansia XR. Hypersensitivity reactions such as angioedema and anaphylactic reactions have been reported in patients treated with other methylphenidate products. Adhansia XR is also contraindicated in patients receiving concomitant treatment with monoamine oxidase inhibitors (MAOIs), and also within 14 days following discontinuation of treatment with a MAOI, because of the risk of hypertensive crisis.

WARNINGS AND PRECAUTIONS

Potential for Abuse and Dependence

Serious Cardiovascular Events

Sudden death, stroke and myocardial infarction have occurred in adults treated with CNS stimulant treatment at recommended doses. Sudden death has occurred in pediatric patients with structural cardiac abnormalities and other serious cardiac problems taking CNS stimulants at recommended doses for ADHD. Avoid use in patients with known structural cardiac abnormalities, cardiomyopathy, serious heart arrhythmia, coronary artery disease, and other serious heart problems. Further evaluate patients who develop exertional chest pain, unexplained syncope, or arrhythmias during Adhansia XR treatment.

Blood Pressure and Heart Rate Increases

CNS stimulants cause an increase in blood pressure (mean increase approximately 2 to 4 mmHg) and heart rate (mean increase approximately 3 to 6 bpm). Individuals may have larger increases. Monitor all patients for hypertension and tachycardia.

Psychiatric Adverse Reactions

CNS stimulants may exacerbate symptoms of behavior disturbance and thought disorder in patients with a pre-existing psychotic disorder.

CNS stimulants may induce a manic or mixed episode in patients. Prior to initiating treatment, screen patients 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).

CNS stimulants, at recommended doses, may cause psychotic or manic symptoms (e.g., hallucinations, delusional thinking, or mania) in patients without a prior history of psychotic illness or mania. If such symptoms occur, consider discontinuing Adhansia XR. In a pooled analysis of multiple short-term, placebo-controlled studies of CNS stimulants, psychotic or manic symptoms occurred in approximately 0.1% of CNS stimulant-treated patients, compared to 0% in placebo-treated patients.

Priapism

Prolonged and painful erections, sometimes requiring surgical intervention, have been reported with methylphenidate products, in both pediatric and adult patients. Priapism was not reported with drug initiation but developed after some time on the drug, often subsequent to an increase in dose. Priapism has also appeared during a period of drug withdrawal (drug holidays or during discontinuation). Patients who develop abnormally sustained or frequent and painful erections should seek immediate medical attention.

Peripheral Vasculopathy, including Raynaud’s Phenomenon

CNS stimulants, including Adhansia XR, used to treat ADHD are associated with peripheral vasculopathy, including Raynaud’s phenomenon. Signs and symptoms are usually intermittent and mild; however, very rare sequelae include digital ulceration and/or soft tissue breakdown. Effects of peripheral vasculopathy, including Raynaud’s phenomenon, were observed in post-marketing reports at different times and at therapeutic doses in all age groups throughout the course of treatment. Signs and symptoms generally improve after reduction in dose or discontinuation of drug. Careful observation for digital changes is necessary during treatment with ADHD stimulants. Further clinical evaluation (e.g., rheumatology referral) may be appropriate for certain patients.

Long-Term Suppression of Growth

CNS stimulants have been associated with weight loss and slowing of growth rate in pediatric patients.

Careful follow-up of weight and height in pediatric patients ages 7 to 10 years who were randomized to either methylphenidate or non-medication treatment groups over 14 months, as well as in naturalistic subgroups of newly methylphenidate-treated and non-medication treated pediatric patients over 36 months (to the ages of 10 to 13 years), suggests that consistently medicated pediatric patients (i.e., treatment for 7 days per week throughout the year) have a temporary slowing in growth rate (on average, a total of about 2 cm less growth in height and 2.7 kg less growth in weight over 3 years), without evidence of growth rebound during this period of development.

Closely monitor growth (weight and height) in pediatric patients treated with CNS stimulants, including Adhansia XR. Patients who are not growing or gaining height or weight as expected may need to have their treatment interrupted.

Allergic-Type Reactions: FD&C Yellow No. 5

Adhansia XR 45 mg capsules contain FD&C Yellow No. 5 (tartrazine) which may cause allergic-type reactions (including bronchial asthma) in certain susceptible persons. Although the overall incidence of FD&C Yellow No. 5 (tartrazine) sensitivity in the general population is low, it is frequently seen in patients who also have aspirin hypersensitivity.

ADVERSE REACTIONS

The most common (≥5% and twice the rate of placebo) adverse reactions occurring with Adhansia XR in adults are insomnia, dry mouth, and decreased appetite.

The most common (≥5% and twice the rate of placebo) adverse reactions occurring with Adhansia XR in pediatric patients are decreased appetite, insomnia, and weight decreased.

PREGNANCY EXPOSURE REGISTRY

There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to Adhansia XR during pregnancy. Healthcare providers are encouraged to register patients by calling the National Pregnancy Registry for Psychostimulants at 1-866-961-2388.

To report SUSPECTED ADVERSE REACTIONS, contact Purdue Pharma L.P. at 1-888-726-7535 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch

Please read Full Prescribing Information, including Boxed Warning.

About Adlon Therapeutics L.P.

Adlon Therapeutics L.P. is a biopharmaceutical company dedicated to developing and providing treatment options for Attention-Deficit/Hyperactivity Disorder (ADHD) and related disorders. Our initial focus is on adults and adolescents who have been diagnosed with ADHD. Adlon is a subsidiary of Purdue Pharma L.P. For more information, please visit www.adlontherapeutics.com.

About Purdue Pharma L.P.

Purdue Pharma and its subsidiaries are physician-founded and physician-led companies that develop, manufacture and market medications and consumer health products to meet the evolving needs of healthcare professionals, patients, consumers and caregivers. Purdue Pharma is also committed to supporting national, regional and local collaborations to drive innovations in patient care while continuing our efforts to address the opioid addiction crisis.

Purdue’s subsidiaries include: Adlon Therapeutics L.P., focused on treatment options for Attention-Deficit/Hyperactivity Disorder (ADHD) and related disorders; Avrio Health L.P., a consumer wellness company that provides over-the-counter products to fight infection, promote digestive regularity and support muscle and brain function; Imbrium Therapeutics L.P., established to develop and commercialize non-opioid pain medications and therapies for select oncology and CNS disorders; Rhodes Pharmaceuticals L.P., which develops and supplies primarily solid oral-dose and transdermal medications; Rhodes Technologies, which develops and manufactures active pharmaceutical ingredients; and Greenfield Bioventures L.P., an investment vehicle focused on compounds in the early stages of clinical development.

For more information, visit www.purduepharma.com.

References:

Purdue Pharma L.P. Adhansia XR Full Prescribing Information. May 2019. Accessed January 2020. Retrieved from http://app.adlontherapeutics.com/adhansia-xr/fpi.pdf.
Harvard.edu. Executive Function & Self-Regulation. Accessed January 2020. Retrieved from: https://developingchild.harvard.edu/science/key-concepts/executive-function/.

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