A Pivotal Efficacy Trial to Evaluate HLD200 in Children With ADHD in a Classroom Setting

NCT02493777 | Completed Phase 3 Results

• 1 other identifier: HLD200-107
• Study Type: interventional
• Target: 125
• Locations: 1 country
• Sites: 7

Brief Summary

This Phase 3 pivotal efficacy trial will examine the effects of HLD200 (methylphenidate) in patients aged 6-12 years with ADHD in a laboratory classroom setting. This study has a 6-week open-label treatment optimization period followed by a one week randomized, double-blind, placebo-controlled test phase.

Conditions

Attention Deficit Hyperactivity Disorder

Outcome Measures

Primary Outcomes (1)

• Swanson, Kotkin, Agler, M-Flynn and Pelham Combined Score (SKAMP CS) - Model-adjusted Average of All Post-dose Time Points Assessed During a Laboratory Classroom Test Day (Visit 9).

  The SKAMP is a validated, 13-item, observer-rated scale designed to assess the level of impairment of classroom-observed behaviors (Wigal and Wigal, 2006). Items 1 through 4 assess subject attention; items 5 through 8 assess deportment; items 9 through 11 assess quality of work; while items 12 and 13 assess subject compliance with teacher/classroom rules. Each individual item is rated on a 7-point scale from 0 (normal, no impairment) to 6 (maximal impairment). When all individual item scores are summed together, they produce a 13-item combined score that ranges from 0 to 78, with higher scores signifying greater impairment. In the present study, the SKAMP rating scale was utilized across 9 sessions occuring at 8:00 am, 9:00 am, 10:00 am, 12:00 pm, 2:00 pm, 4:00 pm, 6:00 pm, 7:00 pm, and 8:00 pm of the laboratory classroom day. Successful training of qualified individuals on the SKAMP scale was required before raters were allowed to perform study assessments.

  12-hours from 8:00 am to 8:00 pm

Secondary Outcomes (1)

• Parent Rating of Evening and Morning Behavior Revised, Morning Subscale (PREMB-R AM).

  PREMB-R AM mean subscale score for the 2-days prior to Visit 9.

Study Arms (2)

HLD200 (methylphenidate)

EXPERIMENTAL

The investigational drug for this study is HLD200 MPH MR capsules comprised of the active pharmaceutical ingredient (MPH) in a dual-coated drug-layered core. Following open-label treatment optimization, subjects will be randomized (1:1) to double-blind HLD200 to be taken once daily during the evening for a period of 1-week prior to testing.

Drug: HLD200 methylphenidate hydrochloride (MPH) Capsules

Placebo

PLACEBO COMPARATOR

Placebo capsules will be composed of microcrystalline cellulose beads in place of MPH containing beads found in the HLD200 capsules. Following open-label treatment optimization, subjects will be randomized (1:1) to double-blind placebo to be taken once daily during the evening for a period of 1-week prior to testing.

Drug: Placebo

Interventions

HLD200 methylphenidate hydrochloride (MPH) Capsules DRUG

HLD200 doses: 20, 40, 60, 80 or 100 mg

Also known as: methylphenidate

HLD200 (methylphenidate)

Placebo DRUG

Placebo

Eligibility Criteria

• Age: 6 Years - 12 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Subjects must be male or female children (6 to 12 years at the time of consent).
• Subjects must have a diagnosis of ADHD as defined by DSM5 criteria and confirmation using the Mini International Neuropsychiatric Interview for Children and Adolescents (MINI-KID).
• Subjects must have a Baseline ADHD-RS-IV score at or above the 90th percentile normalized for sex and age in at least 1 of the following categories: 1) Hyperactive Impulse; 2) Inattentive; or 3) Total Score. In addition, this ADHD-RS-IV Total Score must be greater or equal to 26.
• Subjects must have a Clinical Global Impression of Severity (CGI-S) score greater than or equal to 4 and a CGI-P score \>10 at the Baseline Visit.
• Subjects who are not currently on MPH treatment must either 1) have prior experience with MPH treatment and have shown clinical response to therapy during that time; or 2) be treated with the same dose of MPH and show a clinical response with acceptable tolerability to MPH for ≥2 weeks prior to screening.
• Parental or legal guardian confirmation of before-school function impairment and difficulties performing morning routine.
• Regular weekday morning routine of no less than 30 minutes.
• Subject must be considered clinically appropriate for treatment with MPH and HLD200, including ability to swallow treatment capsules.
• Subject must be in general good health based upon medical history, physical examination, and laboratory results (including urine drug screen).
• Subject and parent or legal guardian must be able to read, write, and/or understand at a level sufficient to provide informed consent (parent/legal guardian) and assent (subject) prior to study participation and to complete study-related materials. Subject and a parent/legal guardian must plan to be available for the entire study period.
• Female subjects of childbearing potential (i.e., post-menarche) are required to have a negative result on urine pregnancy testing at screening (and will be given specific instructions for avoiding pregnancy during the study).
• A medically highly effective form of birth control must be used during the study and for 90 days thereafter for subjects of either sex of childbearing potential. Examples of medically highly effective forms of birth control are as follows:
• No sexual activity
• Use of acceptable methods of birth control including intra-uterine device, oral, implantable, or injectable contraceptives.

You may not qualify if:

• History of, or current, medical condition or laboratory result which, 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.
• Serious structural cardiac abnormalities, cardiomyopathy, serious heart rhythm abnormalities, or other cardiac problems that may place the subject at increased vulnerability to the sympathomimetic effects of a stimulant drug.
• History of seizure disorder (except febrile seizures prior to age 5 and at least 1 year prior to study participation), Tourette's disorder, or intellectual disability of minor severity or greater (DSM5 criteria).
• History of psychosis, bipolar disorder, anorexia nervosa, bulimia, or suicide attempt. Current depression, anxiety, conduct/behavior disorder, substance use disorder, or other psychiatric condition which, in the investigator's opinion, may jeopardize subject safety or may interfere with the satisfactory completion of the study and study-related procedures.
• Active suicidal ideation as evidenced by an ideation score of 2 or greater on the C-SSRS.
• History of severe allergic reaction to MPH.
• History of no response or intolerance to the adverse effects of MPH;
• History of alcohol abuse or illicit drug use.
• Use of prescription medications (except allowed medications; see Section 8.1.2) within 7 days of Baseline (Visit 2), except for ADHD stimulant medication (5 days) and monoamine oxidase inhibitors (MAOIs) (14 days), and over-the-counter medications (except birth control and allowed medications) within the 3 days preceding Baseline (Visit 2). Medications not covered in allowed medications or prohibited medications (Section 8.1.1) must be cleared by the medical monitor prior to enrolling the subject.
• Participation in a clinical study with an investigational drug within the 30 days preceding study enrollment.
• Previous treatment experience with HLD200.
• Positive screening for illicit drug use or nicotine and/or current health conditions or use of medications that might confound the results of the study or increase risk to the subject.
• In the opinion of the investigator, the subject may have problems complying with the protocol or the procedures of the protocol, or could face unnecessary safety risks from the study. This includes current health conditions or use of medications that might confound the results of the study or increase risk to the subject.
• Subject's systolic or diastolic blood pressure measurement exceeds the 95th percentile for age, sex, and height at the Baseline visit.
• Subject is significantly underweight based on Centers for Disease Control and Prevention body mass index (BMI)-for-age sex-specific values at the Screening Visit. Significantly underweight is defined as a BMI \<5th percentile.

Sponsors & Collaborators

• Ironshore Pharmaceuticals and Development, Inc: lead

Study Sites (7)

AVIDA Inc.

Newport Beach, California, 92660, United States

Location

Florida Clinical Research Center, LLC

Bradenton, Florida, 34201, United States

Location

Florida Clinical Research Center, LLC

Maitland, Florida, 32751, United States

Location

South Shore Psychiatric Services, PC

Marshfield, Massachusetts, 02050, United States

Location

Center for Psychiatry and Behavioral Medicine, Inc.

Las Vegas, Nevada, 89128, United States

Location

Bayou City Research, Ltd

Houston, Texas, 77007, United States

Location

Westex Clinical Investigations

Lubbock, Texas, 79423, United States

Location

Related Publications (8)

• Storebo OJ, Storm MRO, Pereira Ribeiro J, Skoog M, Groth C, Callesen HE, Schaug JP, Darling P, Huus CL, Zwi M, Kirubakaran R, Simonsen E, Gluud C. Methylphenidate for children and adolescents with attention deficit hyperactivity disorder (ADHD). Cochrane Database Syst Rev. 2025 Dec 4;12(12):CD009885. doi: 10.1002/14651858.CD009885.pub4.

  PMID: 41342306 DERIVED

• Katzman MA, Otcheretko V, Po MD, Uchida CL, Incledon B. 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. Clin Ther. 2023 Dec;45(12):1212-1221. doi: 10.1016/j.clinthera.2023.09.009. Epub 2023 Sep 27.

  PMID: 37770309 DERIVED

• Storebo OJ, Storm MRO, Pereira Ribeiro J, Skoog M, Groth C, Callesen HE, Schaug JP, Darling Rasmussen P, Huus CL, Zwi M, Kirubakaran R, Simonsen E, Gluud C. Methylphenidate for children and adolescents with attention deficit hyperactivity disorder (ADHD). Cochrane Database Syst Rev. 2023 Mar 27;3(3):CD009885. doi: 10.1002/14651858.CD009885.pub3.

  PMID: 36971690 DERIVED

• Goldberg JF. Adjunctive Mood Stabilizers Are Not the Same as a Placebo-Only Arm in Bipolar Depression Trials: Reply to Terao. J Clin Psychiatry. 2021 Jun 22;82(4):21lr13919b. doi: 10.4088/JCP.21lr13919b. No abstract available.

  PMID: 34166589 DERIVED

• Terao T. Antidepressant Effects of Combined Mood Stabilizers May Account for High Placebo Response Rates. J Clin Psychiatry. 2021 Jun 22;82(4):21lr13919. doi: 10.4088/JCP.21lr13919. No abstract available.

  PMID: 34166588 DERIVED

• Childress AC, Cutler AJ, Po MD, DeSousa NJ, Warrington LE, Sallee FR, Incledon B. Symptomatic and Functional Response and Remission From the Open-Label Treatment-Optimization Phase of a Study With DR/ER-MPH in Children With ADHD. J Clin Psychiatry. 2021 Jun 22;82(4):21m13914. doi: 10.4088/JCP.21m13914.

  PMID: 34166587 DERIVED

• Childress AC, Uchida CL, Po MD, DeSousa NJ, Incledon B. A Post Hoc Comparison of Prior ADHD Medication Dose and Optimized Delayed-release and Extended-release Methylphenidate Dose in a Pivotal Phase III Trial. Clin Ther. 2020 Dec;42(12):2332-2340. doi: 10.1016/j.clinthera.2020.10.004. Epub 2020 Nov 7.

  PMID: 33168234 DERIVED

• Childress AC, Cutler AJ, Marraffino A, McDonnell MA, Turnbow JM, Brams M, DeSousa NJ, Incledon B, Sallee FR, Wigal SB. 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. J Child Adolesc Psychopharmacol. 2020 Feb;30(1):2-14. doi: 10.1089/cap.2019.0070. Epub 2019 Aug 29.

  PMID: 31464511 DERIVED

MeSH Terms

Conditions

Attention Deficit Disorder with Hyperactivity

Interventions

5,10-dihydro-5-methylphenazine; Capsules; Methylphenidate

Condition Hierarchy (Ancestors)

Attention Deficit and Disruptive Behavior Disorders; Neurodevelopmental Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Dosage Forms; Pharmaceutical Preparations; Phenylacetates; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Chief Scientific Officer
• Organization: Ironshore Pharmaceuticals and Development, Inc.

bev@ironshorepharma.com

13457498174

Study Officials

• Ann Childress, MD

  Center for Psychiatry And Behavioral Medicine Inc.

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 7, 2015
• First Posted: July 10, 2015
• Study Start: July 1, 2015
• Primary Completion: February 1, 2016
• Study Completion: March 1, 2016
• Last Updated: July 23, 2021
• Results First Posted: October 3, 2018

Record last verified: 2021-07

Locations

US (7)