Evening Dosed Methylphenidate for ADHD

Recruiting at 12 trial locations

Overseen By Collegium Pharmaceutical

Age: < 18

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

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)

Prior Safety Data

Approved in 1 Jurisdiction

Trial Summary

What is the purpose of this trial?

This study will evaluate the efficacy, safety and pharmacokinetics of HLD200 (20 mg and 40 mg) in children aged 4 to 5 years with ADHD.

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.

What data supports the effectiveness of the drug HLD200 methylphenidate hydrochloride capsules for ADHD?

Research shows that HLD200, a delayed-release and extended-release form of methylphenidate taken in the evening, significantly improves daily functioning in children with ADHD. It helps reduce symptoms from morning through evening, with studies indicating better performance in school and at home compared to a placebo. ^{1 2 3 4 5}

Is evening-dosed methylphenidate (HLD200) safe for humans?

In a study with children, evening-dosed methylphenidate (HLD200) was well tolerated, with no serious side effects reported compared to a placebo. Common side effects in similar treatments include decreased appetite, stomach pain, mood changes, weight loss, headache, irritability, and trouble sleeping. ^{2 3 4 6 7}

What makes the drug HLD200 unique for treating ADHD?

HLD200 is unique because it is taken in the evening and is designed to release the medication gradually, starting to work when the person wakes up and lasting throughout the day and into the evening. This delayed-release and extended-release formulation helps manage ADHD symptoms from morning to night, unlike other treatments that are typically taken in the morning. ^{1 4 6 8 9}

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• HLD200 methylphenidate hydrochloride capsules (Stimulant)

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.

Participant Groups

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)

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of HLD200, Delayed-Release and Extended-Release Methylphenidate, in Children with Attention-Deficit/Hyperactivity Disorder. [2018]

2. United States 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. [2022]

3. United States 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. [2020]

4. United States 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. [2021]

5. Switzerland 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. [2018]

6. United States 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. [2021]

7. United States 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. [2021]

8. United States 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. [2019]

9. United States 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. [2022]