Evening Dosed Methylphenidate for ADHD

No longer recruiting at 24 trial locations

Overseen By Collegium Pharmaceutical

Age: < 18

Sex: Any

Trial Phase: Phase 3

Sponsor: Ironshore Pharmaceuticals and Development, Inc

Must not be taking: Antidepressants, Mood stabilizers, Antipsychotics

Disqualifiers: Cardiac conditions, Seizure disorder, Psychosis, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 3 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness and safety of an evening dose of HLD200, a form of methylphenidate, for treating ADHD in young children. The study compares two different doses of the medication and a placebo to determine which works best. It targets children aged 4 to 5 diagnosed with ADHD who seek new treatment options. Participants should exhibit noticeable ADHD symptoms affecting daily life, and their caregivers must be prepared to assist with study requirements. As a Phase 3 trial, this study represents the final step before potential FDA approval, offering participants a chance to contribute to a promising ADHD treatment option.

Will I have to stop taking my current medications?

The trial requires stopping certain medications before participating. You must stop using prescription medications (except allowed ones) 7 days before the baseline visit, ADHD stimulant medication 72 hours before, clonidine and guanfacine 5 days before, atomoxetine 7 days before, and MAO inhibitors 14 days before. Psychotropic medications must be stopped 14 days before the baseline visit.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that HLD200, a medication similar to Ritalin, has been generally well tolerated in past studies. One study found that after three weeks of treatment, patients showed noticeable improvements in ADHD symptoms compared to those who took a placebo. This indicates that the treatment is effective and manageable for users. However, HLD200 can be misused, potentially leading to addiction. Overall, evidence suggests that while HLD200 effectively treats ADHD, users should exercise caution due to its potential for misuse. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for ADHD?

Researchers are excited about HLD200 methylphenidate capsules for ADHD because they offer a unique evening dosing option. Unlike most ADHD medications that are taken in the morning, HLD200 is designed to be taken at night, potentially providing smoother symptom control from the start of the next day. This could be particularly beneficial for individuals who struggle with morning symptoms or have inconsistent medication effects throughout the day. Additionally, while standard treatments like immediate-release and extended-release methylphenidate focus on managing symptoms during the day, HLD200 may offer a more consistent 24-hour coverage, improving overall daily functioning for those with ADHD.

What evidence suggests that this treatment might be an effective treatment for ADHD?

In this trial, participants will receive either HLD200, a special form of the medication methylphenidate, or a placebo. Studies have shown that HLD200 effectively improves ADHD symptoms in children. Research indicates that HLD200 significantly reduces problems with daily activities compared to a placebo. Previous findings also show that this treatment is generally well tolerated, causing few side effects. Importantly, HLD200 aids in managing both ADHD symptoms and functioning at home, making it a promising option for young children with ADHD. ^{1 2 5 6 7}

Are You a Good Fit for This Trial?

This trial is for children aged 4-5 with ADHD, who have a vocabulary score within the normal range and meet specific criteria for ADHD severity. They must be in good health, with normal heart rate and blood pressure, and not undergoing other treatments that could interfere. Parents or guardians must consent to the study's duration.

Inclusion Criteria

My guardian(s) and I can participate fully and understand the study consent.

My child is between 4 and 5 years old.

I have been diagnosed with ADHD according to DSM-5 and confirmed by MINI KID.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

Up to 4 weeks

Treatment

Participants receive HLD200 or placebo for 3 weeks

3 weeks

Visits at Day 1, Day 8, Day 15, and Day 22

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 weeks

What Are the Treatments Tested in This Trial?

Interventions

• HLD200 methylphenidate hydrochloride capsules

Trial Overview The trial tests HLD200 methylphenidate hydrochloride capsules (20 mg & 40 mg) against placebo capsules to assess their effectiveness, safety, and how the body processes them in young children with ADHD when taken in the evening.

How Is the Trial Designed?

Group I: HLD200 40 mg Experimental Treatment 1 Intervention

HLD200 20 mg placebo capsule (×1) and HLD200 20 mg active capsule (×1) for the first week (prescribed at Visit 2), with up-titration for the final 2 weeks to HLD200 20 mg active capsules (×2) (prescribed at Visits 3 and 4)

Group II: HLD200 20 mg Experimental Treatment 1 Intervention

HLD200 20 mg placebo capsule (×1) and HLD200 20 mg active capsule (×1) for 3 weeks (prescribed at Visits 2, 3, and 4)

Group III: Placebo Comparator Placebo Group 1 Intervention

Matching placebo to HLD200 20 mg capsule (×2) for 3 weeks (prescribed at Visits 2, 3, and 4)

HLD200 methylphenidate hydrochloride capsules is already approved in United States for the following indications:

Approved in United States as Jornay PM for:

• Attention Deficit Hyperactivity Disorder (ADHD)

Who Is Running the Clinical Trial?

Ironshore Pharmaceuticals and Development, Inc

Lead Sponsor

Trials

7

Recruited

570+

Collegium Pharmaceutical, Inc.

Industry Sponsor

Trials

3

Recruited

920+

Published Research Related to This Trial

HLD200, a delayed-release and extended-release methylphenidate, showed dose proportionality in pharmacokinetics between 20 mg and 100 mg doses, indicating consistent efficacy across different dosages.

The drug can be taken with or without food, as meal content did not significantly affect its pharmacokinetics, and there is negligible accumulation with multiple dosing, suggesting a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics of HLD200, a Delayed-Release and Extended-Release Methylphenidate: Evaluation of Dose Proportionality, Food Effect, Multiple-Dose Modeling, and Comparative Bioavailability with Immediate-Release Methylphenidate in Healthy Adults. Liu, T., Gobburu, JVS., Po, MD., et al.[2020]

PRC-063, an extended-release formulation of methylphenidate, significantly improved attention and reduced ADHD symptoms in children compared to placebo, with effects lasting up to 13 hours after dosing.

The treatment was well-tolerated, with adverse events similar to those seen with other methylphenidate treatments, including decreased appetite and insomnia, indicating a safety profile consistent with existing ADHD medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Multilayer, Extended-Release Methylphenidate (PRC-063) in Children 6-12 Years of Age with Attention-Deficit/Hyperactivity Disorder: A Laboratory Classroom Study. Childress, AC., Brams, MN., Cutler, AJ., et al.[2021]

HLD200, a delayed-release and extended-release formulation of methylphenidate, shows a predictable pharmacokinetic profile with an 8- to 10-hour delay in medication release, effectively targeting early morning ADHD symptoms.

The pharmacokinetics of HLD200 were consistent across healthy adults and children/adolescents with ADHD, indicating its potential for broad use in managing ADHD symptoms throughout the day.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single-Dose Pharmacokinetics of HLD200, a Delayed-Release and Extended-Release Methylphenidate Formulation, in Healthy Adults and in Adolescents and Children with Attention-Deficit/Hyperactivity Disorder. Childress, A., Mehrotra, S., Gobburu, J., et al.[2019]

HLD200, a delayed-release and extended-release methylphenidate, is designed to provide therapeutic effects for children with ADHD from morning through evening, with optimal dosing predicted to be 12 hours before school.

The pharmacokinetic and pharmacodynamic models suggest that higher doses of HLD200 lead to longer durations of clinical response, which aligns with trial data showing improvements in daily functioning.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Model-Based Approach for Establishing the Predicted Clinical Response of a Delayed-Release and Extended-Release Methylphenidate for the Treatment of Attention-Deficit/Hyperactivity Disorder. Gomeni, R., Komolova, M., Incledon, B., et al.[2022]

In a phase 3 trial involving 117 children aged 6-12 with ADHD, the delayed-release and extended-release methylphenidate (DR/ER-MPH) significantly improved functional impairment throughout the day, including early morning and late afternoon/evening, compared to placebo.

The treatment was well tolerated, with no significant differences in treatment-emergent adverse events between DR/ER-MPH and placebo, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Randomized, Double-Blind, Placebo-Controlled Study of HLD200, a Delayed-Release and Extended-Release Methylphenidate, in Children with Attention-Deficit/Hyperactivity Disorder: An Evaluation of Safety and Efficacy Throughout the Day and Across Settings. Childress, AC., Cutler, AJ., Marraffino, A., et al.[2021]

In a study involving 59 adults with ADHD, multilayer-release methylphenidate (PRC-063) significantly improved performance scores compared to placebo, with effects starting within 1 hour and lasting for 16 hours.

Common side effects included decreased appetite, headache, and insomnia, but there was no significant impact on overall sleep quality, indicating that PRC-063 is generally well-tolerated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Time Course of Effect of Multilayer-Release Methylphenidate Hydrochloride Capsules: A Randomized, Double-Blind Study of Adults With ADHD in a Simulated Adult Workplace Environment. Wigal, SB., Wigal, T., Childress, A., et al.[2022]

HLD200, a delayed-release and extended-release methylphenidate, is designed to provide consistent treatment effects for ADHD throughout the day and evening, with optimized doses being higher than those of previous ADHD medications.

In a Phase III study involving children aged 6-12, the dose conversion ratios indicated that transitioning to DR/ER-MPH from other ADHD medications requires significantly higher doses, but the safety profile remains consistent with other methylphenidate formulations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Post Hoc Comparison of Prior ADHD Medication Dose and Optimized Delayed-release and Extended-release Methylphenidate Dose in a Pivotal Phase III Trial. Childress, AC., Uchida, CL., Po, MD., et al.[2021]

Controlled-delivery methylphenidate (methylphenidate CD) is effective and well tolerated for treating ADHD in children aged 6 and older, showing superior control of symptoms compared to osmotic release methylphenidate during a typical school day.

In clinical trials lasting 3 weeks, methylphenidate CD was found to be more effective than a placebo and equally effective as immediate-release methylphenidate, making it a strong option for managing ADHD symptoms during school hours.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Methylphenidate controlled-delivery capsules (EquasymXL, Metadate CD): a review of its use in the treatment of children and adolescents with attention-deficit hyperactivity disorder. Anderson, VR., Keating, GM.[2018]

In a 3-week phase 3 study involving 161 children aged 6-12 with ADHD, the evening-dosed DR/ER-MPH formulation significantly improved ADHD symptoms compared to placebo, as measured by the ADHD rating scale-IV.

DR/ER-MPH also enhanced at-home functioning in the early morning and late afternoon/evening, while being generally well tolerated, with common side effects including insomnia and decreased appetite.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of HLD200, Delayed-Release and Extended-Release Methylphenidate, in Children with Attention-Deficit/Hyperactivity Disorder. Pliszka, SR., Wilens, TE., Bostrom, S., et al.[2018]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7041320/

A Randomized, Double-Blind, Placebo-Controlled Study of ... Conclusion: DR/ER-MPH was well tolerated and demonstrated significant improvements versus placebo in functional impairment throughout the day across different ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT01907360

Pharmacokinetics of HLD200 in Children and Adolescents ... This study was designed to assess the pharmacokinetic effects of a single dose of HLD200 (methylphenidate hydrochloride) in children and adolescents with ADHD.

3. sciencedirect.com sciencedirect.com/science/article/pii/S0149291820304719

A Post Hoc Comparison of Prior ADHD Medication Dose ... Bostrom, et al. Efficacy and safety of HLD200, delayed-release and extended-release methylphenidate, in children with attention-deficit/hyperactivity disorder.

4. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2018/209311Orig1s000MedR.pdf

209311Orig1s000 HLD200, tradename Jornay PM, contains methylphenidate, a known psychostimulant for the treatment of Attention Deficit and Hyperactivity Disorder ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5567875/

Efficacy and Safety of HLD200, Delayed-Release ... Conclusions: DR/ER-MPH was generally well tolerated and demonstrated significant improvements versus placebo in ADHD symptoms and at-home functional impairments ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT01907360

Pharmacokinetics of HLD200 in Children and Adolescents ... This study was designed to assess the pharmacokinetic effects of a single dose of HLD200 (methylphenidate hydrochloride) in children and adolescents with ADHD.

7. jornaypm-pro.com jornaypm-pro.com/safety

Learn Safety & Side Effects of JORNAY PM (methylphenidate ... JORNAY PM has a high potential for abuse and misuse, which can lead to the development of a substance use disorder, including addiction.