A Randomized, Controlled Laboratory Classroom Study of Serdexmethylphenidate and d-Methylphenidate Capsules in Children with Attention-Deficit/Hyperactivity Disorder

Kollins, Scott H.; Braeckman, René; Guenther, Sven; Barrett, Andrew C.; Mickle, Travis; Oh, Charles; Marraffino, Andrea; Cutler, Andrew J.; Brams, Matthew

doi:10.1089/cap.2021.0077

Cited by 25 publications

(18 citation statements)

References 51 publications

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“…Serdexmethylphenidate is converted to active dexmethylphenidate in the intestine, which leads to a pharmacokinetic profile with an extended duration of action at once-daily dosing. Serdexmethylphenidate/dexmethylphenidate was well tolerated (Kollins et al 2021 ). While serdexmethylphenidate/dexmethylphenidate combines the benefits of the rapid onset of the immediate-release and of the long duration of action of the marketed extended-release formulation, its clinical benefit compared to these two formulations remains to be established.…”

Section: Methodsmentioning

confidence: 99%

A year in pharmacology: new drugs approved by the US Food and Drug Administration in 2021

Kaykı-Mutlu

Aksoyalp

Wojnowski

et al. 2022

Naunyn-Schmiedeberg's Arch Pharmacol

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The second year of the COVID-19 pandemic had no adverse effect on the number of new drug approvals by the US Food and Drug Administration (FDA). Quite the contrary, with a total of 50 new drugs, 2021 belongs to the most successful FDA years. We assign these new drugs to one of three levels of innovation: (1) first drug against a condition (“first-in-indication”), (2) first drug using a novel molecular mechanism (“first-in-class”), and (3) “next-in-class”, i.e., a drug using an already exploited molecular mechanism. We identify 21 first-in-class, 28 next-in-class, and only one first-in-indication drugs. By treatment area, the largest group is once again cancer drugs, many of which target specific genetic alterations. Every second drug approved in 2021 targets an orphan disease, half of them being cancers. Small molecules continue to dominate new drug approvals, followed by antibodies and non-antibody biopharmaceuticals. In 2021, the FDA continued to approve drugs without strong evidence of clinical effects, best exemplified by the aducanumab controversy.

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Section: Methodsmentioning

confidence: 99%

A year in pharmacology: new drugs approved by the US Food and Drug Administration in 2021

Kaykı-Mutlu

Aksoyalp

Wojnowski

et al. 2022

Naunyn-Schmiedeberg's Arch Pharmacol

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“…Although SDX is a novel prodrug of d-methylphenidate (d-MPH) and is pharmacologically inactive until gradually converted to active d-MPH in the lower intestinal tract, FDA has not approved it as a single entity for any indication [ 237 ]. As the immediate-release d-MPH component accounts for the rapid increase in plasma MPH concentrations, while the SDX component increases the MPH concentration through the evening hours, a multicenter, randomized, double-blind, placebo-controlled laboratory classroom study, SDX/d-MPH was shown to be efficacious and well tolerated in children aged 6–12 years with ADHD [ 238 ]. Therefore, SDX/d-MPH has been approved by FDA.…”

Section: Adhd and Epilepsy: Challenges And Opportunitiesmentioning

confidence: 99%

Epilepsy and Attention Deficit Hyperactivity Disorder: Connection, Chance, and Challenges

Fan

Chiang

Chang

et al. 2023

IJMS

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Comorbidities are common in children with epilepsy, with nearly half of the patients having at least one comorbidity. Attention deficit hyperactivity disorder (ADHD) is a psychiatric disorder characterized by hyperactivity and inattentiveness level disproportional to the child’s developmental stage. The burden of ADHD in children with epilepsy is high and can adversely affect the patients’ clinical outcomes, psychosocial aspects, and quality of life. Several hypotheses were proposed to explain the high burden of ADHD in childhood epilepsy; the well-established bidirectional connection and shared genetic/non-genetic factors between epilepsy and comorbid ADHD largely rule out the possibility of a chance in this association. Stimulants are effective in children with comorbid ADHD, and the current body of evidence supports their safety within the approved dose. Nonetheless, safety data should be further studied in randomized, double-blinded, placebo-controlled trials. Comorbid ADHD is still under-recognized in clinical practice. Early identification and management of comorbid ADHD are crucial to optimize the prognosis and reduce the risk of adverse long-term neurodevelopmental outcomes. The identification of the shared genetic background of epilepsy and ADHD can open the gate for tailoring treatment options for these patients through precision medicine.

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“…SDX/d-MPH contains a fixed molar ratio of 70% SDX, a novel prodrug of d-MPH, and 30% d-MPH. After oral intake of an SDX/d-MPH capsule, early exposure to MPH is governed primarily by d-MPH in the formulation, and mid- to late-day exposure is governed by the gradual conversion of SDX to d-MPH (Kollins et al, 2021 ). SDX is designed to be pharmacologically inactive until it is gradually converted to active d-MPH in the lower intestinal tract.…”

Section: Introductionmentioning

confidence: 99%

“…Results of a pivotal, 1-month, randomized, placebo-controlled, double-blind (DB), dose-optimized, laboratory classroom study of children aged 6–12 years with ADHD demonstrated that SDX/d-MPH was well tolerated, with adverse events (AEs) that were comparable with those of other stimulant treatments (Kollins et al, 2021 ). In addition, significant improvements in ADHD symptoms were seen versus placebo in children aged 6–12 years.…”

Section: Introductionmentioning

confidence: 99%

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Safety and Tolerability of Serdexmethylphenidate/Dexmethylphenidate Capsules in Children with Attention-Deficit/Hyperactivity Disorder: A 12-Month, Open-Label Safety Study

Childress

Marraffino²,

Cutler

et al. 2023

Journal of Child and Adolescent Psychopharmacology

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Objective: Serdexmethylphenidate/dexmethylphenidate (SDX/d-MPH) is approved for the treatment of patients aged ≥6 years with attention-deficit/hyperactivity disorder (ADHD). A pivotal double-blind (DB) study of children aged 6–12 years with ADHD demonstrated efficacy for ADHD with good tolerability. In this study, we assessed the safety and tolerability of daily oral SDX/d-MPH for up to 1 year in children with ADHD. Methods: This was a dose-optimized, open-label safety study with SDX/d-MPH in children aged 6–12 years with ADHD that included subjects who successfully completed the DB study (rollover) and new subjects. The study consisted of a 30-day screening phase, a dose optimization phase for new subjects only, a 360-day treatment phase, and follow-up. Adverse events (AEs) were assessed from the first day of SDX/d-MPH administration to the end of the study. During the treatment phase, ADHD Rating Scale-5 (ADHD-RS-5) and Clinical Global Impressions–Severity (CGI-S) scale assessments were used to evaluate ADHD severity. Results: Of the 282 subjects enrolled (70 rollover; 212 new), 28 discontinued treatment in the dose optimization phase and 254 entered the treatment phase. By study completion, 127 had discontinued and 155 had completed the study. The treatment-phase safety population included all enrolled subjects who received ≥1 dose of study drug and had ≥1 postdose safety assessment. Of 238 subjects assessed in the treatment-phase safety population, 143 (60.1%) had ≥1 treatment-emergent adverse events (TEAEs), and 36 (15.1%), 95 (39.9%), and 12 (5.0%) had mild, moderate, or severe TEAEs, respectively. The most common TEAEs were decreased appetite (18.5%), upper respiratory tract infection (9.7%), nasopharyngitis (8.0%), decreased weight (7.6%), and irritability (6.7%). There were no clinically meaningful trends in electrocardiograms, cardiac events, or blood pressure events, and none led to discontinuation. Two subjects had eight serious AEs that were unrelated to treatment. There were overall reductions in ADHD symptoms and severity as assessed by ADHD-RS-5 and CGI-S during the treatment phase. Conclusions: In this 1-year study, SDX/d-MPH was found to be safe and well tolerated and comparable with other methylphenidate products, with no unexpected safety findings. SDX/d-MPH also showed sustained efficacy during the 1-year treatment period. identifier: NCT03460652.

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A Randomized, Controlled Laboratory Classroom Study of Serdexmethylphenidate and d-Methylphenidate Capsules in Children with Attention-Deficit/Hyperactivity Disorder

Cited by 25 publications

References 51 publications

A year in pharmacology: new drugs approved by the US Food and Drug Administration in 2021

A year in pharmacology: new drugs approved by the US Food and Drug Administration in 2021

Epilepsy and Attention Deficit Hyperactivity Disorder: Connection, Chance, and Challenges

Safety and Tolerability of Serdexmethylphenidate/Dexmethylphenidate Capsules in Children with Attention-Deficit/Hyperactivity Disorder: A 12-Month, Open-Label Safety Study

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