## Protocol Section
### Identification Module
**NCT ID:** NCT06431256

**Brief Title:** Ph3 Multicenter, 3wk RDBPC Efficacy, Safety & PK Study of Evening Dosed MPH HCl ER Capsules (HLD200) in Children 4-5 Yr With ADHD

**Official Title:** Phase 3, Multicenter, 3-Week Fixed-dose, Randomized, Double-blind, Placebo-controlled, Parallel-group Efficacy, Safety and Pharmacokinetic Study of Evening Dosed Methylphenidate Hydrochloride Extended-Release Capsules (HLD200) in Children Aged 4 to 5 Years With ADHD

#### Organization Study ID Info
**ID:** HLD200-112
#### Organization
**Class:** OTHER
**Full Name:** Ironshore Pharmaceuticals and Development, Inc
### Status Module
#### Completion Date
**Date:** 2026-07

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-29

**Type:** ACTUAL

**Last Update Submit Date:** 2024-05-27

**Overall Status:** NOT_YET_RECRUITING

#### Primary Completion Date
**Date:** 2026-07

**Type:** ESTIMATED

#### Start Date
**Date:** 2024-08

**Type:** ESTIMATED

**Status Verified Date:** 2024-05

#### Study First Post Date
**Date:** 2024-05-28
**Type:** ACTUAL
**Study First Submit Date:** 2024-05-22
**Study First Submit QC Date:** 2024-05-22
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** OTHER

**Name:** Ironshore Pharmaceuticals and Development, Inc

#### Responsible Party

**Type:** SPONSOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** True

### Description Module

**Brief Summary:** 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.

**Detailed Description:** This is a multicenter, 3 week fixed dose, randomized, double-blind, placebo-controlled, parallel group study to evaluate the efficacy, safety and pharmacokinetics of HLD200 (20 mg and 40 mg) in children aged 4 to 5 years with ADHD.

Participants will be screened for eligibility for up to 4 weeks. Eligible participants will be treated with study medication for 3 weeks followed by a 2 week safety follow-up following the end of study treatment. The total duration of the study is up to 9 weeks. A single pharmacokinetic (PK) sample will be taken from each participant, in a prespecified PK sampling window at visit 5, for population PK analysis.

A total of 168 participants (56 per treatment arm) will be randomized at Visit 2.

### Conditions Module

**Conditions:**

- Attention Deficit Hyperactivity Disorder

### Design Module

#### Design Info

**Allocation:** RANDOMIZED

**Intervention Model:** PARALLEL

##### Masking Info

**Masking:** QUADRUPLE

**Who Masked:**

- PARTICIPANT

- CARE_PROVIDER

- INVESTIGATOR

- OUTCOMES_ASSESSOR

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 168

**Type:** ESTIMATED

**Phases:**

- PHASE3

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

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

**Intervention Names:**

- Drug: Placebo HLD200 capsules

**Label:** Placebo Comparator

**Type:** PLACEBO_COMPARATOR

#### Arm Group 2

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

**Intervention Names:**

- Drug: HLD200 methylphenidate hydrochloride capsules

**Label:** HLD200 20 mg

**Type:** EXPERIMENTAL

#### Arm Group 3

**Description:** 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)

**Intervention Names:**

- Drug: HLD200 methylphenidate hydrochloride capsules

**Label:** HLD200 40 mg

**Type:** EXPERIMENTAL

### Interventions

#### Intervention 1

**Arm Group Labels:**

- HLD200 20 mg

- HLD200 40 mg

**Description:** Doses: 20mg capsules

**Name:** HLD200 methylphenidate hydrochloride capsules

**Other Names:**

- methylphenidate

**Type:** DRUG

#### Intervention 2

**Arm Group Labels:**

- Placebo Comparator

**Description:** Doses: 20mg capsules

**Name:** Placebo HLD200 capsules

**Other Names:**

- placebo

**Type:** DRUG

### Outcomes Module

#### Primary Outcomes

**Description:** The change in ADHD Rating Scale-IV (ADHD RS IV) Preschool Version Total Score from Baseline (Visit 2) to Visit 5 for participants receiving HLD200 compared to participants receiving placebo in ITT population

**Measure:** Primary Efficacy Endpoint

**Time Frame:** 3 weeks

#### Secondary Outcomes

**Description:** The change in Clinical Global Impression - Severity (CGI-S) score from Baseline (Visit 2) to Visit 5 for participants receiving HLD200 compared to participants receiving placebo in ITT population

**Measure:** Secondary Efficacy Endpoint

**Time Frame:** 3 weeks

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

1. Subject and the subject's parent(s)/legal guardian(s) must be available for the duration of the study. The subject's parent(s)/legal guardian(s) must be able to read, write, and/or understand at a level sufficient to provide signed and dated informed consent. In accordance with ICH GCP Guideline E6 and other applicable regulations, the Investigator, or a person designated by the Investigator, will obtain written informed consent from each subject's parent(s)/legal guardian(s) (and the subject's assent, if applicable) before any study-specific activity is performed. The Investigator will retain the original copy of each signed consent/assent document.
2. Subjects must be male or female children 4 to 5 years of age at the time of consent and assent (if applicable).
3. Subjects must have a diagnosis of ADHD as defined by the DSM-5 criteria with confirmation using the Mini - International Neuropsychiatric Interview for Children and Adolescents (MINI KID).
4. Subjects must meet the criteria for the therapeutic need for control of mild to moderate symptoms of ADHD at Screening (Visit 1) and/or Baseline (Visit 2) as determined by a medical evaluation and by an ADHD-RS-IV Preschool Version Parent score ≥ 93rd percentile cut-off normalized for sex in ≥ 1 of the following: Hyperactivity/Impulsivity subscale score (≥17 for boys; ≥14 for girls), Inattention subscale score (≥14 for boys; ≥12 for girls), or Total Score (≥32 for boys; ≥24 for girls); and a Clinical Global Impression - Severity (CGI-S) score ≥4.
5. Subjects must have a Peabody Picture Vocabulary Test 4 (PPVT-4) Standard Score ≥70 at Screening.
6. Subject has undergone an adequate course of nonpharmacologic treatment or has a severe enough condition in the opinion of the Investigator to consider enrollment without undergoing prior nonpharmacological treatment.
7. Subject's height and weight at Screening are between the 5th and 95th percentiles according to the Centers for Disease Control and Prevention growth charts by age and sex.
8. Subject must have a resting pulse less than 127 bpm, systolic and diastolic blood pressure below the 95th percentile for age and gender according to the 2017 American Academy of Pediatrics guidelines7 based on the average of 3 measurements 2 to 5 minutes apart at Visit 1 and Visit 2, (only a single measurement is required at Visit 2 unless an elevated excursion is noted which requires the averaged value of triplicate measurements).
9. Subject must be considered clinically appropriate for treatment with HLD200.
10. Subject must be in general good health based upon medical history, physical examination, clinical laboratory examinations, vital signs, and 12-lead electrocardiogram (ECG) assessment

Exclusion Criteria:

1. History of, or current, medical condition, including gastrointestinal disorders (e.g., surgery, malabsorption syndrome, and other similar conditions), open-angle glaucoma, abnormally increased intraocular pressure (IOP), or laboratory result that, in the opinion of the Investigator, unfavorably alters the risk-benefit of study participation, may jeopardize subject safety, or may interfere with the satisfactory completion of the study and study related procedures.
2. Serious structural cardiac abnormalities, cardiomyopathy, serious heart rhythm abnormalities, severe hypertension, untreated thyroid disease, peripheral vasculopathy, known structural cardiac disorders, serious cardiac conditions, serious arrhythmias, known family history of sudden death, or other cardiac problems that may place the subject at increased vulnerability to the sympathomimetic effects of a stimulant drug.
3. History of seizure disorder (except febrile seizures prior to age 4 and with last occurrence at least 1 year prior to study participation), Tourette's disorder, or intellectual disability of minor severity or greater (DSM-5 criteria).
4. Subject has any diagnosis of psychosis, bipolar I or II disorder, major depressive disorder, anxiety disorder, eating disorder, conduct disorder, obsessive-compulsive disorder, any history of psychosis, autism spectrum disorder, tic disorders, disruptive mood dysregulation disorder, intellectual disability, Tourette's Syndrome, confirmed genetic disorder with cognitive and/or behavioral disturbances. Subjects with oppositional defiant disorder (ODD) are permitted to enroll in the study as long as ODD is not the primary focus of treatment, and, in the opinion of the Investigator, the ODD is mild to moderate, and eligible subjects with ODD are appropriate and cooperative during screening. Additionally, subject has any other conditions that, in the Investigator's opinion, may jeopardize subject safety or may interfere with the satisfactory completion of the study and study-related procedures.
5. Subject is currently considered at risk of suicide in the opinion of the Investigator, has previously made a suicide attempt, or has a history of, or is currently demonstrating active suicidal ideation or behavior.
6. History of severe allergic reaction or intolerance to MPH.
7. Alanine aminotransferase, aspartate aminotransferase, total bilirubin, or creatinine greater than 1.5 times the upper limit of normal. Elevated bilirubin due to Gilbert's syndrome is not exclusionary.
8. Use of prescription medications (except allowed medications) within 7 days of Baseline (Visit 2), except for ADHD stimulant medication (within 72 hours \[3 days\] of Baseline Visit 2), clonidine and guanfacine (5 days of Baseline Visit 2), atomoxetine (7 days of Baseline Visit 2), monoamine oxidase (MAO) inhibitors (14 days of Baseline Visit 2), and nonprescription/over-the-counter medications (except allowed medications) within the 3 days preceding Baseline (Visit 2). Medications not covered in allowed medications or prohibited medications must be cleared by the Medical Monitor prior to enrolling the subject.
9. Use of psychotropic medications including antidepressants, mood stabilizers, and antipsychotics within 14 days of Baseline.
10. Participation in a clinical trial with an investigational drug within the 30 days preceding study enrollment.
11. Initiation of non-pharmacological treatment within 30 days prior to Baseline (Visit 2). Subject may not initiate any new non-pharmacological treatment during the study.
12. Use of any other medications that might confound the results of the study or increase risk to the subject.
13. Subject is well-controlled on his/her current ADHD medication with acceptable tolerability.
14. In the opinion of the Investigator, the subject may have potential problems complying with the protocol or the procedures of the protocol, or for which the study could pose unnecessary safety risks.
15. Subject has a sibling or step-sibling that is concurrently participating in this study or who has previously participated in this study
16. Subject or caregiver is a participating Investigator, Sub-investigator, study coordinator, or employee of a participating Investigator, or is an immediate family member of the aforementioned.
17. Any factor, which in the opinion of the Investigator would jeopardize the evaluation or safety or be associated with poor adherence to the protocol

**Maximum Age:** 5 Years

**Minimum Age:** 4 Years

**Sex:** ALL

**Standard Ages:**

- CHILD

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000019958

- Term: Attention Deficit and Disruptive Behavior Disorders

- ID: D000065886

- Term: Neurodevelopmental Disorders

- ID: D000001523

- Term: Mental Disorders

### Condition Browse Module - Browse Branches

- Abbrev: BC10

- Name: Nervous System Diseases

- Abbrev: BC23

- Name: Symptoms and General Pathology

- Abbrev: All

- Name: All Conditions

- Abbrev: BXM

- Name: Behaviors and Mental Disorders

### Condition Browse Module - Browse Leaves

- ID: M9999

- Name: Hyperkinesis

- Relevance: LOW

- As Found: Unknown

- ID: M4594

- Name: Attention Deficit Disorder with Hyperactivity

- Relevance: HIGH

- As Found: Attention Deficit Hyperactivity Disorder

- ID: M21830

- Name: Attention Deficit and Disruptive Behavior Disorders

- Relevance: LOW

- As Found: Unknown

- ID: M30644

- Name: Neurodevelopmental Disorders

- Relevance: LOW

- As Found: Unknown

- ID: M4815

- Name: Mental Disorders

- Relevance: LOW

- As Found: Unknown

- ID: M14473

- Name: Psychotic Disorders

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000001289

- Term: Attention Deficit Disorder with Hyperactivity

### Intervention Browse Module - Ancestors

- ID: D000000697

- Term: Central Nervous System Stimulants

- ID: D000045505

- Term: Physiological Effects of Drugs

- ID: D000018765

- Term: Dopamine Uptake Inhibitors

- ID: D000014179

- Term: Neurotransmitter Uptake Inhibitors

- ID: D000049990

- Term: Membrane Transport Modulators

- ID: D000045504

- Term: Molecular Mechanisms of Pharmacological Action

- ID: D000015259

- Term: Dopamine Agents

- ID: D000018377

- Term: Neurotransmitter Agents

### Intervention Browse Module - Browse Branches

- Abbrev: CNSSti

- Name: Central Nervous System Stimulants

- Abbrev: All

- Name: All Drugs and Chemicals

- Abbrev: CaAg

- Name: Cardiotonic Agents

### Intervention Browse Module - Browse Leaves

- ID: M11748

- Name: Methylphenidate

- Relevance: HIGH

- As Found: Fed

- ID: M4029

- Name: Central Nervous System Stimulants

- Relevance: LOW

- As Found: Unknown

- ID: M7473

- Name: Dopamine

- Relevance: LOW

- As Found: Unknown

- ID: M20832

- Name: Dopamine Uptake Inhibitors

- Relevance: LOW

- As Found: Unknown

- ID: M17962

- Name: Dopamine Agents

- Relevance: LOW

- As Found: Unknown

- ID: M20504

- Name: Neurotransmitter Agents

- Relevance: LOW

- As Found: Unknown

### Intervention Browse Module - Meshes

- ID: D000008774

- Term: Methylphenidate

### Misc Info Module

- Version Holder: 2024-05-31
