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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02493777
Recruitment Status : Completed
First Posted : July 10, 2015
Results First Posted : October 3, 2018
Last Update Posted : October 3, 2018
Information provided by (Responsible Party):
Ironshore Pharmaceuticals and Development, Inc

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.

Condition or disease Intervention/treatment Phase
Attention Deficit Hyperactivity Disorder Drug: HLD200 methylphenidate hydrochloride (MPH) Capsules Drug: Placebo Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 125 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 3, Multicenter, Open-label Treatment-optimized, Double-blind, Randomized, Placebo-controlled, Forced-withdrawal, Parallel Group Study to Evaluate the Safety and Efficacy of Evening Dosed HLD200, a Novel Delayed and Extended Release Formulation (DELEXIS) of Methylphenidate Hydrochloride, in Children Aged 6-12 With Attention Deficit Hyperactivity Disorder (ADHD) in a Laboratory Classroom Setting
Study Start Date : July 2015
Actual Primary Completion Date : February 2016
Actual Study Completion Date : March 2016

Arm Intervention/treatment
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 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
HLD200 doses: 20, 40, 60, 80 or 100 mg
Other Name: methylphenidate

Placebo Comparator: Placebo
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

Primary Outcome Measures :
  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). [ Time Frame: 12-hours from 8:00 am to 8:00 pm ]
    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.

Secondary Outcome Measures :
  1. Parent Rating of Evening and Morning Behavior Revised, Morning Subscale (PREMB-R AM). [ Time Frame: PREMB-R AM mean subscale score for the 2-days prior to Visit 9. ]
    The PREMB-R is an 11-item rating scale designed to assess at-home functional impairments in children with ADHD during both early morning (AM) and late afternoon/evening (PM) time periods. With demonstrated validity and reliablility (Faraone et al., 2015), the AM subscale total score (sum of items 1 to 3) was designated in this study as a key secondary endpoint. Items are scored from 0 (none) to 3 (a lot), with higher scores signifying greater impairment of function. The PREMB-R rating scale was completed by parents during the 2-days prior to study visits at the beginning and end of the open-label period (Visits 2 and 8, respectively), as well as at the end of the randomized, double-blind period (Visit 9). At each visit, these ratings were used only for review by the clinician (MD, PhD, DO, licensed social worker, or any trained mental health professional approved by the sponsor) as part of a structured interview to enable collection of a clinician-rated PREMB-R AM subscale score.

Information from the National Library of Medicine

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Ages Eligible for Study:   6 Years to 12 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Subjects must be male or female children (6 to 12 years at the time of consent).
  2. 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).
  3. 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.
  4. 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.
  5. 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.
  6. Parental or legal guardian confirmation of before-school function impairment and difficulties performing morning routine.
  7. Regular weekday morning routine of no less than 30 minutes.
  8. Subject must be considered clinically appropriate for treatment with MPH and HLD200, including ability to swallow treatment capsules.
  9. Subject must be in general good health based upon medical history, physical examination, and laboratory results (including urine drug screen).
  10. 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.
  11. 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).
  12. 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.

Exclusion Criteria:

  1. 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.
  2. 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.
  3. 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).
  4. 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.
  5. Active suicidal ideation as evidenced by an ideation score of 2 or greater on the C-SSRS.
  6. History of severe allergic reaction to MPH.
  7. History of no response or intolerance to the adverse effects of MPH;
  8. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin, or creatinine greater than 1.5x the upper limit of normal. Elevated bilirubin due only to Gilbert's syndrome is not exclusionary.
  9. History of alcohol abuse or illicit drug use.
  10. 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.
  11. Participation in a clinical study with an investigational drug within the 30 days preceding study enrollment.
  12. Previous treatment experience with HLD200.
  13. 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.
  14. 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.
  15. Subject's systolic or diastolic blood pressure measurement exceeds the 95th percentile for age, sex, and height at the Baseline visit.
  16. 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.
  17. Subject is significantly overweight based on Centers for Disease Control and Prevention BMI-for-age sex specific values at the Screening Visit. Significantly overweight is defined as a BMI >95th percentile.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02493777

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United States, California
Newport Beach, California, United States, 92660
United States, Florida
Florida Clinical Research Center, LLC
Bradenton, Florida, United States, 34201
Florida Clinical Research Center, LLC
Maitland, Florida, United States, 32751
United States, Massachusetts
South Shore Psychiatric Services, PC
Marshfield, Massachusetts, United States, 02050
United States, Nevada
Center for Psychiatry and Behavioral Medicine, Inc.
Las Vegas, Nevada, United States, 89128
United States, Texas
Bayou City Research, Ltd
Houston, Texas, United States, 77007
Westex Clinical Investigations
Lubbock, Texas, United States, 79423
Sponsors and Collaborators
Ironshore Pharmaceuticals and Development, Inc
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Principal Investigator: Ann Childress, MD Center for Psychiatry And Behavioral Medicine Inc.
Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: Ironshore Pharmaceuticals and Development, Inc Identifier: NCT02493777    
Other Study ID Numbers: HLD200-107
First Posted: July 10, 2015    Key Record Dates
Results First Posted: October 3, 2018
Last Update Posted: October 3, 2018
Last Verified: September 2018
Additional relevant MeSH terms:
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Attention Deficit Disorder with Hyperactivity
Attention Deficit and Disruptive Behavior Disorders
Neurodevelopmental Disorders
Mental Disorders
Neurologic Manifestations
Nervous System Diseases
Central Nervous System Stimulants
Physiological Effects of Drugs
Dopamine Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Dopamine Agents
Neurotransmitter Agents