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

NCT02520388 | Completed Phase 3 Results

• 1 other identifier: HLD200-108
• Study Type: interventional
• Target: 163
• Locations: 1 country
• Sites: 21

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 naturalistic setting. Following a screening/washout period (Visit 1), subjects will randomized to double-blind placebo or HLD200 for a period of 3 weeks (Visits 2-5) before assessing clinical study endpoints at last study visit.

Conditions

Attention Deficit Hyperactivity Disorder

Outcome Measures

Primary Outcomes (1)

• Attention Deficit Hyperactivity Disorder Rating Scale Based on DSM-IV Criteria (ADHD-RS-IV) Total Score.

  The ADHD-RS-IV was developed to measure the behaviors of children with ADHD (DuPaul et al., 1998). The scale consists of 18 items designed to reflect current symptomatology of ADHD. Each item is scored in a range from 0 (reflecting no symptoms or a frequency of never or rarely) to 3 (reflecting severe symptoms or a frequency of almost always), with a range of total scores ranging from 0 to 54. In this study, a site clinican (required to be an MD, PhD, DO, licensed social worker, or any trained mental health professional approved by the sponsor) completed ADHD-RS-IV assessments at each visit using a structured interview format.

  Last week of 3-week treatment period assessed at Visit 5.

Secondary Outcomes (1)

• Before School Functioning Questionnaire (BSFQ) Total Score

  Last week of 3-week treatment period assessed at Visit 5.

Study Arms (2)

HLD200 (methylphenidate)

EXPERIMENTAL

Experimental: HLD200 (methylphenidate) 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 a minimum 72-hour washout, subjects will be randomized (1:1) to double-blind HLD200 to be taken once daily during the evening for a period of 3-weeks 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 a minimum 72-hour washout, subjects will be randomized (1:1) to double-blind placebo to be taken once daily during the evening for a period of 3-weeks prior to testing.

Drug: Placebo

Interventions

HLD200 methylphenidate hydrochloride (MPH) Capsules DRUG

HLD200 Doses: 40, 60 or 80 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 total score. In addition, this ADHD-RS-IV total score must be ≥26 at Baseline.
• Subjects must have a Clinical Global Impression of Severity (CGI-S) score ≥4 and a CGI-P score \>10 at the Baseline Visit.
• Subjects have demonstrated, in the judgment of the investigator, at least a partial clinical response to MPH.
• Parental or legal guardian confirmation of the child's before-school functional impairment and/or difficulties performing a morning routine of at least 30 minutes minimum duration occurring between 6:00 and 9:00 am.
• Subject body weight must be ≥20 kg.
• 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 the medical history, physical, and laboratory examinations (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 parent or 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 with last occurrence 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 or intolerance to MPH.
• History of alcohol abuse or illicit drug use.
• Use of prescription medications (except per protocol allowed medications) within 7 days of Baseline (Visit 2), except for ADHD stimulant medication (72 hours) 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 must be cleared by the medical monitor prior to enrolling the subject.
• Use of psychotropic medications including antidepressants, mood stabilizers, and antipsychotics.
• Participation in a clinical trial 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 for which the study could pose unnecessary safety risks. This includes current health conditions or use of medications that might confound the results of the study or increase risk to the subject.
• A sibling or step-sibling that is concurrently participating in this study who resides with and is cared for by the same parent/legal guardian as the subject.

Sponsors & Collaborators

• Ironshore Pharmaceuticals and Development, Inc: lead

Study Sites (21)

AVIDA

Newport Beach, California, 92660, United States

Location

Florida Clinical Research Center, LLC

Bradenton, Florida, 34201, United States

Location

Sarkis Clinical Trials

Gainesville, Florida, 32607, United States

Location

Clinical Neuroscience Solutions, Inc

Jacksonville, Florida, 32256, United States

Location

Florida Clinical Research Center, LLC

Maitland, Florida, 32751, United States

Location

Scientific Clinical Research, Inc.

North Miami, Florida, 33161, United States

Location

Medical Research Group of Central Florida

Orange City, Florida, 32763, United States

Location

Clinical Neuroscience Solutions, Inc.

Orlando, Florida, 32801, United States

Location

QPS MRA, dba Miami Research Associates, LLC

South Miami, Florida, 33143, United States

Location

Children's Developmental Center, P.A.

Winter Park, Florida, 32792, United States

Location

Pedia Research, LLC

Owensboro, Kentucky, 42301, United States

Location

Duke University Medical Center, Duke Child and Family Study Center

Durham, North Carolina, 27705, United States

Location

IPS Research Company

Oklahoma City, Oklahoma, 73103, United States

Location

Cutting Edge Research Group

Oklahoma City, Oklahoma, 73116, United States

Location

Clinical Neuroscience Solutions, Inc.

Memphis, Tennessee, 38119, United States

Location

Bayou City Research, Ltd

Houston, Texas, 77007, United States

Location

Red Oak Psychiatry Associates, PA

Houston, Texas, 77090, United States

Location

Westex Clinical Investigations

Lubbock, Texas, 79423, United States

Location

University of Texas Health Science Center at San Antonio

San Antonio, Texas, 78229, United States

Location

Ericksen Research and Development

Clinton, Utah, 84015, United States

Location

Seattle Children's Hospital

Seattle, Washington, 98105, United States

Location

Related Publications (4)

• 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

• 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

• Wilens TE, Faraone SV, Hammerness PG, Pliszka SR, Uchida CL, DeSousa NJ, Sallee FR, Incledon B, Newcorn JH. Clinically Meaningful Improvements in Early Morning and Late Afternoon/Evening Functional Impairment in Children with ADHD Treated with Delayed-Release and Extended-Release Methylphenidate. J Atten Disord. 2022 Mar;26(5):696-705. doi: 10.1177/10870547211020073. Epub 2021 Jun 4.

  PMID: 34085581 DERIVED

• Lopez FA, Faraone SV, Newcorn JH, Doll HA, Rhoten S, Lewis HB, Khan TF, DeSousa NJ, Sallee FR, Incledon B. Effect of Delayed-Release and Extended-Release Methylphenidate on Caregiver Strain and Validation of Psychometric Properties of the Caregiver Strain Questionnaire: Results from a Phase 3 Trial in Children with Attention-Deficit/Hyperactivity Disorder. J Child Adolesc Psychopharmacol. 2021 Apr;31(3):179-186. doi: 10.1089/cap.2020.0159. Epub 2021 Apr 1.

  PMID: 33797983 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

• Newcorn Jeffrey, MD

  Icahn School of Medicine at Mount Sinai

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

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: August 7, 2015
• First Posted: August 11, 2015
• Study Start: August 1, 2015
• Primary Completion: April 1, 2016
• Study Completion: May 1, 2016
• Last Updated: July 23, 2021
• Results First Posted: October 3, 2018

Record last verified: 2021-07

Locations

US (21)