Jornay PM (methylphenidate extended release) / Highland Therapeutics - LARVOL DELTA

Real-World Dose Titration Patterns in Children, Adolescents, and Young Adults Treated With Delayed-Release/Extended-Release Methylphenidate (AACAP 2024) - "Objectives: DR/ER-MPH (JORNAY PM®; formerly HLD200) is the first evening-dosed delayed-release and extended-release methylphenidate approved for individuals ≥6 years with ADHD. These real-world data demonstrated that in clinical practice, with patients aged 6 to 29, DR/ER-MPH dose titration patterns differed from those in a phase 3 clinical trial of participants aged 6 to 12. In the trial, participants achieved significant and clinically relevant improvements in ADHD symptoms and reductions in functional impairment from waking to bedtime, with a safety profile consistent with other methylphenidates. These findings suggest an opportunity to improve outcomes by titrating similarly to the clinical trial, in which all-day duration was achieved within 6 weeks.ADHD, STIM, TREAT"

Clinical • Real-world • Real-world evidence • ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • CNS Disorders • Psychiatry

Ph3 Multicenter, 3wk RDBPC Efficacy, Safety & PK Study of Evening Dosed MPH HCl ER Capsules (HLD200) in Children 4-5 Yr With ADHD (clinicaltrials.gov) - P3 | N=168 | Recruiting | Sponsor: Ironshore Pharmaceuticals and Development, Inc | Not yet recruiting ➔ Recruiting

Enrollment open • ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • CNS Disorders • Psychiatry

Real-World Utilization of Delayed-Release/Extended-Release Methylphenidate: Demographic and Dosing Data from a Large US Claims Database Analysis (CADDRA ADHD 2024) - "Research Funded By: Ironshore Pharmaceuticals, manufacturer of JORNAY PM® (formerly HLD200). A total of 5,501 patients (mean age: 20.2y; 55% male) were included; 17.4% and 24.1% had experience with amphetamine and methylphenidate, respectively, in the prior six months. Most common psychiatric comorbidities were anxiety disorders (26.3%), mood disorders (19.3%), autism spectrum disorder (6.7%), and oppositional defiant disorder (6.7%). For patients with ≥4 DR/ER-MPH prescriptions (N=2,831), mean starting strength was 33.2 mg and 60.2% initiated at 20 mg; mean strength increased to 49.4 mg by prescription four."

Claims database • Clinical • Real-world • Real-world evidence • ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • Autism Spectrum Disorder • Behavior Disorders • CNS Disorders • Genetic Disorders • Mood Disorders • Psychiatry

An Open-Label Treatment With Randomization Observation, Investigator-Initiated Study, on the Duration and Efficacy of Jornay PM (Methylphenidate Hydrochloride Extended-Release Capsules) on Adult ADHD Symptoms and Executive Function and Emotional Regulation Throughout the Day Into Early Evening (clinicaltrials.gov) - P4 | N=30 | Recruiting | Sponsor: NYU Langone Health

New P4 trial • ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • CNS Disorders • Psychiatry

Ph3 Multicenter, 3wk RDBPC Efficacy, Safety & PK Study of Evening Dosed MPH HCl ER Capsules (HLD200) in Children 4-5 Yr With ADHD (clinicaltrials.gov) - P3 | N=168 | Not yet recruiting | Sponsor: Ironshore Pharmaceuticals and Development, Inc

New P3 trial • ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • CNS Disorders • Psychiatry

Methylphenidate for the Treatment of Epilepsy-related Cognitive Deficits (clinicaltrials.gov) - P4 | N=226 | Recruiting | Sponsor: VA Office of Research and Development | Trial completion date: Mar 2028 ➔ Sep 2027 | Trial primary completion date: Jun 2027 ➔ Sep 2027

Trial completion date • Trial primary completion date • CNS Disorders • Cognitive Disorders • Epilepsy

A Post-Hoc Analysis of Emotional Lability With Delayed-Release/Extended-Release Methylphenidate in Children Aged 6 to 12 Years of Age Participating in Two Phase 3 Clinical Trials. (PubMed, J Atten Disord) - P3 | "DR/ER-MPH (formerly HLD200) is an evening-dosed delayed-release and extended-release methylphenidate approved for the treatment of ADHD in patients ≥6 years. Few emotional adverse events (AEs) were reported. DR/ER-MPH treatment resulted in statistically significant improvements in EL to the level of non-ADHD peers as contextualized by T-scores."

Journal • P3 data • Retrospective data • ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • CNS Disorders • Psychiatry

Adult and preadolescent methylphenidate leads to changes in sleep/wake activity rhythms in rats (Neuroscience 2023) - "Adult MPH exposure produce circadian rhythm disturbance with shifts in acrophase and amplitude. Additionally, increases in fragmentation of rest-activity during the light period occurred after prolonged withdrawal."

Preclinical • ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • CNS Disorders • Psychiatry • Sleep Disorder

Pooled Post Hoc Analysis of Permanent Product Measure of Performance (PERMP) Scores in Children With ADHD Treated With DR/ER-MPH from Two Phase 3 Studies (AACAP 2023) - P3 | "Delayed-release and extended-release methylphenidate (DR/ER-MPH, trade name: JORNAY PM®) is an evening-dosed formulation that provides a dose-dependent duration of effect for individuals aged ≥6 years with ADHD. Significance at the 8 AM time point demonstrates that participants in the DR/ER-MPH group were medicated prior to the start of the classroom study day. Conclusions In a pooled post hoc analysis, DR/ER-MPH significantly improved mean PERMP-CS from 8 AM to 8 PM vs placebo, demonstrating consistent improvement in classroom performance from morning until evening."

Clinical • P3 data • Retrospective data • ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • CNS Disorders • Psychiatry

Development of an Interactive Pharmacokinetic Dose-Dependent Duration Model for Delayed-Release and Extended-Release Methylphenidate (AACAP 2023) - "Objectives Evening-administered delayed-release and extended-release methylphenidate (DR/ER-MPH, trade name: JORNAY PM ® ) is approved for the treatment of ADHD in patients 6 years and older, with efficacy coinciding with awakening and lasting until evening. The HCPs reported that the 3 thresholds were appropriate to capture the durations of effect for the majority of patients, and that patients tended to follow along a given threshold as doses were up-titrated. Conclusions An interactive PK dashboard appropriately illustrated the concept of dose-dependent duration with DR/ER-MPH by applying literature-based thresholds of effective MPH concentrations to an established population PK model."

PK/PD data • ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • CNS Disorders • Psychiatry

A Convolution-based In Vitro-In Vivo Correlation (IVIVC) Model for Methylphenidate Hydrochloride Delayed-release and Extended-release Capsule. (PubMed, CPT Pharmacometrics Syst Pharmacol) - No abstract available

Journal • Preclinical

Effects of adolescent methylphenidate administration on methamphetamine conditioned place preference in an animal model of attention-deficit/hyperactivity disorder: Examination of potential sex differences. (PubMed, Drug Alcohol Depend) - "These results demonstrate the importance of considering biological sex when prescribing psychostimulant medications for ADHD as long-term MPH administration may increase the risk of continued drug use in females with ADHD following a period of abstinence."

Journal • Preclinical • ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • CNS Disorders • Psychiatry

Adverse Events During Dosing of Delayed-Release/Extended-Release Methylphenidate: Learnings From the Open-Label Phase of a Registration Trial and a Real-World Postmarketing Surveillance Program. (PubMed, Clin Ther) - P3 | "No new safety concerns were revealed in this real-world setting compared with the safety profile identified in DR/ER-MPH trial data. In real-world practices, clinicians tended to discontinue DR/ER-MPH treatment after AE onset, whereas trial investigators continued to optimize treatment and found that AEs were generally tolerable, suggesting that health care practitioners may consider developing strategies to manage tolerability issues with DR/ER-MPH treatment on AE emergence rather than immediately discontinuing use of the drug to provide optimal therapeutic benefit."

Adverse events • Journal • P4 data • Real-world • Real-world evidence • ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • CNS Disorders • Psychiatry

Methylphenidate for the Treatment of Epilepsy-related Cognitive Deficits (clinicaltrials.gov) - P4 | N=226 | Recruiting | Sponsor: VA Office of Research and Development | Not yet recruiting ➔ Recruiting

Enrollment open • CNS Disorders • Cognitive Disorders • Epilepsy

Methylphenidate for the Treatment of Epilepsy-related Cognitive Deficits (clinicaltrials.gov) - P4 | N=226 | Not yet recruiting | Sponsor: VA Office of Research and Development | Trial completion date: Dec 2027 ➔ Mar 2028 | Trial primary completion date: Dec 2026 ➔ Jun 2027

Trial completion date • Trial primary completion date • CNS Disorders • Cognitive Disorders • Epilepsy

Methylphenidate for the Treatment of Epilepsy-related Cognitive Deficits (clinicaltrials.gov) - P4 | N=226 | Not yet recruiting | Sponsor: VA Office of Research and Development | N=77 ➔ 226 | Trial completion date: Mar 2027 ➔ Dec 2027 | Trial primary completion date: Mar 2026 ➔ Dec 2026

Enrollment change • Trial completion date • Trial primary completion date • CNS Disorders • Cognitive Disorders • Epilepsy

Growth Trajectories of Children and Adolescents With ADHD Treated With Delayed-Release/Extended-Release Methylphenidate (JORNAY PM®): A Pilot Study of Real-World Data From a Large US Claims Database (AACAP 2022) - "Herein, we report real-world weight and height changes in patients newly prescribed DR/ER-MPH in its first year of availability vs patients treated with 2 established branded stimulants, osmotic release oral system (OROS) MPH (Concerta®) and lisdexamfetamine dimesylate (LDX; Vyvanse®)...Differences in weight and height trajectories were modeled with repeated measures mixed effects models (DR/ER-MPH vs OROS MPH or LDX); covariates were baseline weight (height models), baseline height (weight models), age, sex, and prior amphetamine or methylphenidate use...Conclusions Of patients newly prescribed DR/ER-MPH in its first year of availability, growth trajectories after 1 year of treatment numerically increased relative to OROS MPH and LDX, with the weight trajectory significantly increased compared to LDX. Reasons for these growth improvements remain to be investigated."

Clinical • Real-world evidence • ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • CNS Disorders • Pediatrics • Psychiatry

Quantitative Characterization of the Smoothness of Extended-release Methylphenidate Pharmacokinetic Profiles. (PubMed, Innov Clin Neurosci) - "DR/ER-MPH demonstrated a smoother PK profile compared to the highest dose of other ER-MPH formulations. While the benefits of a smooth PK profile remain to be tested clinically, having fewer peaks and troughs has been hypothesized to reduce waxing and waning of therapeutic effects throughout the day, and more gradual changes in MPH plasma levels have been hypothesized to lower the risk of likeability and potentially abate afternoon symptom rebound."

Journal • PK/PD data • ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • CNS Disorders • Psychiatry

Higher Persistence with DR/ER-MPH over Other Extended-Release Stimulants for the Management of ADHD: Real World Evidence from a Large Us Claims Database Analysis (CADDRA ADHD 2022) - "DR/ER-MPH (formerly HLD200) is an evening-dosed, delayed-release and extended-release methylphenidate (MPH) that is released in the colon; it has no immediate-release component and provides a dose-dependent duration of effect for individuals with ADHD...Results were stratified by age (6–12y, 13–17y, ≥18y) and prior extended-release (ER) stimulant medication use (amphetamine [AMP], MPH, both, neither)... Persistence over 12 fills was highest with DR/ER-MPH (20% from 19,697 episodes) compared to AMP prodrug (16% from 726,083 episodes), generic ER AMP (15% from 950,593 episodes), branded ER MPH/AMP analogs (11% from 147,440 episodes), and generic ER MPH (8% from 770,454 episodes) (P<0.01 for DR/ER-MPH compared to all other treatments). Age was found to be an important moderator of persistence patterns. Although not adjusted for baseline characteristics, and despite differences in sample sizes, individuals showed higher overall persistence rates over 12 prescription..."

Clinical • HEOR • Real-world evidence • ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • CNS Disorders • Psychiatry

Effect of Colonic Absorption on the Pharmacokinetic Properties of Delayed-Release and Extended-Release Methylphenidate: In Vivo, In Vitro, and Modeling Evaluations. (PubMed, Clin Pharmacol Drug Dev) - "DR/ER-MPH (formerly HLD200), an evening-dosed delayed-release and extended-release methylphenidate, is predicted to be absorbed in the proximal colon. Safety profiles fell within the expectations for methylphenidate products. Modeled PK profiles were similar between the small intestine formulation and a morning-dosed extended-release methylphenidate (both predicted to release methylphenidate in the upper gastrointestinal tract), providing additional evidence that the PK profile of DR/ER-MPH is shaped by colonic absorption."

Journal • PK/PD data • Preclinical • ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • CNS Disorders • Gastrointestinal Disorder • Psychiatry

Improvements In Emotional Lability With Delayed-Release And Extended-Release Methylphenidate Treatment In Children With Adhd (AACAP 2021) - P3 | "This post hoc analysis examined the effect of HLD200, an evening-dosed delayed-release and extended-release methylphenidate (DR/ER-MPH; tradename: JORNAY PM®), on EL in children (6-12 years) with ADHD in 2 randomized, double-blind, phase 3 trials (HLD200-107 [NCT02493777] and HLD200-108 [NCT02520388]).Methods EL was measured with the 3-item Connors’ Global Index–Parent (CGI-P) EL subscale, which was recorded weekly in the 6-week, open-label phase of HLD200-107, and at baseline and study endpoint (Week 3) in HLD200-108. EL was positively correlated with ADHD symptoms and functional impairment in children with ADHD and with strain on caregivers. Due to its pharmacokinetic profile and dose-dependent duration of effect that can provide consistent treatment effects from early morning to late afternoon/evening, DR/ER-MPH is predicted to be an effective treatment for ADHD patients with EL."

Clinical • ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • CNS Disorders • Psychiatry

Higher Persistence And Adherence With Dr/Er-Mph Over Other Extended-Release Stimulants For The Management Of Adhd: Real-World Evidence From A Large U.S. Claims Database Analysis (AACAP 2021) - "The evening-dosed, delayed-release and extended-release methylphenidate ([DR/ER-MPH]; JORNAY PM®; formerly HLD200) is released in the colon and provides a dose-dependent duration of effect for individuals with ADHD...Persistence and adherence rates for DR/ER-MPH were compared to other extended-release (ER) stimulants using a 2-proportion hypothesis test and right-tailed 2-sample t test, respectively, both with α = 0.01.Results The persistence rate over the 9-month period was highest with DR/ER-MPH at 33% (n = 10,371), compared to 26% for lisdexamfetamine dimesylate (LDX) (n = 384,144), 22% for generic ER amphetamine (ER AMP) (n = 463,429), 20% for branded ER MPH or ER AMP analogs (n = 79,663), and 17% for generic ER MPH (n = 427,396; p < 0.01 for all). Adherence was also highest with DR/ER-MPH at 92%, compared to 89% for LDX, 89% for generic ER AMP, 88% for branded analogs, and 88% for generic MPH (p < 0.01 for all).Conclusions Although not adjusted for..."

Clinical • HEOR • Real-world evidence • ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • CNS Disorders • Psychiatry

[VIRTUAL] Real-World Safety Profile of DR/ER-MPH for ADHD in Children, Adolescents, and Adults in the US (CADDRA ADHD 2021) - P3 | "Objectives: HLD200 is the first evening-dosed delayed-release and extended-release methylphenidate (DR/ER-MPH), which provides a dose-dependent duration of effect for individuals with attention-deficit/hyperactivity disorder (ADHD). Post-marketing surveillance of approximately 44,000 patients exposed to DR/ER-MPH revealed a consistent safety profile with observations from phase 3 trials of DR/ER-MPH and with AEs seen with other methylphenidate formulations. Differences between the number of AEs reported here and in the US Package Insert for DR/ER-MPH may be partially explained by differences in reporting between pharmacovigilance data and clinical trials. Three Learning Objectives After this presentation, participants should be better able to: 1."

Clinical • Real-world evidence • ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • CNS Disorders • Psychiatry

Symptomatic and Functional Response and Remission From the Open-Label Treatment-Optimization Phase of a Study With DR/ER-MPH in Children With ADHD. (PubMed, J Clin Psychiatry) - P3 | "Delayed-release and extended-release methylphenidate (DR/ER-MPH), the first stimulant predicted to be absorbed primarily in the colon, demonstrated significant improvements in attention-deficit/hyperactivity disorder (ADHD) symptoms and functional impairment from awakening until evening versus placebo in clinical trials...Trial Registration:Data used in this post hoc analysis came from the study with ClinicalTrials.gov identifier: NCT02493777."

Clinical • Journal • ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • CNS Disorders • Psychiatry

Clinically Meaningful Improvements in Early Morning and Late Afternoon/Evening Functional Impairment in Children with ADHD Treated with Delayed-Release and Extended-Release Methylphenidate. (PubMed, J Atten Disord) - P3 | "More children achieved clinically meaningful improvements with DR/ER-MPH versus placebo (all p < .05). DR/ER-MPH increased proportions of children achieving clinically meaningful improvements in BSFQ and PREMB-R."

Clinical • Journal • ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • CNS Disorders • Psychiatry