Pharmacokinetics of HLD200 in Children and Adolescents With ADHD
Primary Purpose
Attention-Deficit Hyperactivity Disorder
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
HLD200 (methylphenidate hydrochloride)
Sponsored by
About this trial
This is an interventional treatment trial for Attention-Deficit Hyperactivity Disorder
Eligibility Criteria
Inclusion Criteria:
- Male and female adolescents (13-17 years) and children (6-12 years).
- Previous diagnosis of ADHD and confirmation using the Mini International Neuropsychiatric Interview for Children and Adolescents (MINI-KID).
- ADHD symptoms controlled on a stable dose of ADHD medication. Subjects should be on MPH or have previous history of symptom control during treatment with MPH.
- Physical examination free of clinically significant findings, unless deemed NCS by the Investigator and Medical Monitor;
- Able to swallow treatment capsules;
- Available for entire study period;
- Provision of informed consent (from the parent[s] and/or legal representative[s]) and assent (from the subject); and
- Female subjects of childbearing potential (i.e., post-menarche) required to have a negative result on urine pregnancy testing (and will be given specific instructions on avoiding pregnancy during trial)
Exclusion Criteria:
- Any known history or presence of significant cardiovascular, pulmonary, hepatic, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic, ophthalmologic disease, unless deemed NCS by the Investigator and the Medical Monitor;
- Presence of any significant physical or organ abnormality;
- Any illness during the 4 weeks before this study, unless deemed NCS by the Investigator and the Clinical and/or Medical Monitor;
- Severe comorbid psychiatric diagnosis that may affect subject safety or confound results (e.g., psychosis, bipolar disorder);
- Known history of moderate to severe asthma;
- Known history of severe allergic reaction (including drugs, food, insect bites, environmental allergens);
- Known history of seizures (except febrile seizures prior to age 5), anorexia nervosa, bulimia or current diagnosis or family history of Tourette's disorder;
- Subject who are severely underweight or overweight.
- Clinical value outside of the acceptable ranges, unless deemed NCS significant per the Investigator;
- Positive history for hepatitis B, hepatitis C and Human Immunodeficiency Virus (HIV);
- Positive screening for illicit drug use, and/or current health conditions or use of medications that might confound the results of the study or increase risk to the subject;
- Use of prescription medications (except ADHD medications) within 7 days and over-the counter medications (except birth control) within the 3 days preceding study enrollment, unless deemed acceptable by the Investigator and Clinical and/or Medical Monitor;
- Blood draws of 50 ml to 249 ml within the 30 days, 250 ml to 449 ml within the 45 days and ≥ 450 ml within the 60 days preceding study enrollment;
- Participation in clinical trial with an investigational drug within the 30 days preceding study enrollment;
- Intolerance to venipuncture; and
- Current suicidal ideation or history of suicidality determined as a significant finding on the Columbia-Suicide Severity Rating Scale (C-SSRS) by the investigator (Baseline C-SSRS for adolescents; Pediatric Baseline C-SSRS for children).
Sites / Locations
- Centre for Psychiatry & Behavioral Medicine, Inc.
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
HLD200 (methylphenidate hydrochloride) in Adolescents
HLD200 (methylphenidate hydrochloride) in Children
Arm Description
HLD200 (B formulation, 54 mg, oral capsules) administered as a single treatment in the evening to children aged 13-17 years.
HLD200 (B formulation, 54 mg, oral capsules) administered as a single treatment in the evening to children aged 6-12 years.
Outcomes
Primary Outcome Measures
PK Parameters for Rate and Extent of Absorption of MPH: Lag Time
The absorption lag time for methylphenidate in plasma expressed in hours is the difference in time between the drug administration and the last time point where the drug concentration was below the limit of assay quantitation.
PK Parameters for Rate and Extent of Absorption of MPH: Cmax
The maximum drug concentration of methylphenidate in plasma.
PK Parameters for Rate and Extent of Absorption of MPH: Tmax
The time to reach maximum concentration of methylphenidate in plasma.
PK Parameters for Rate and Extent of Absorption of MPH: AUC0-tz
Area under the methylphenidate plasma concentration-time curve to time point tz (AUC0-tz), where tz was the last time point over the time interval with a measurable drug concentration
PK Parameters for Rate and Extent of Absorption of MPH: AUC0-inf
The area under the methylphenidate plasma concentration-time curve to infinite time
Secondary Outcome Measures
Full Information
NCT ID
NCT01907360
First Posted
July 12, 2013
Last Updated
November 22, 2021
Sponsor
Ironshore Pharmaceuticals and Development, Inc
1. Study Identification
Unique Protocol Identification Number
NCT01907360
Brief Title
Pharmacokinetics of HLD200 in Children and Adolescents With ADHD
Official Title
A Phase I/II, Single Center, Single-Treatment, Open-Label, Adaptive Clinical Trial Design Examining the Pharmacokinetic Effects of up to Two Separate HLD200 Modified Release Formulations of Methylphenidate in Adolescent and Pediatric Subjects With ADHD
Study Type
Interventional
2. Study Status
Record Verification Date
November 2021
Overall Recruitment Status
Completed
Study Start Date
August 2013 (undefined)
Primary Completion Date
October 2013 (Actual)
Study Completion Date
October 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Ironshore Pharmaceuticals and Development, Inc
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This study was designed to assess the pharmacokinetic effects of a single dose of HLD200 (methylphenidate hydrochloride) in children and adolescents with ADHD.
Detailed Description
This study utilized a single-center, open-label, single-treatment, fasted design to examine the rate and extent of absorption of evening-administered HLD200 in children (6-12 years) and adolescents (13-17 years) with ADHD.
Following a screening period that included five days washout to allow for clearance of any prior ADHD medications, subjects were domiciled in-clinic and administered HLD200 (B-formulation; 54 mg; oral capsule) at 9 pm under fasted conditions. Subjects were then observed for safety and tolerability and a total of 18 blood samples collected during a 48 hour period (at t=0, 4, 6, 8, 9, 10, 11, 12, 13, 14, 15, 16, 18, 20, 22, 24, 36 and 48 hours post-dosing). These samples were then assayed for methylphenidate plasma concentrations and this data used for calculation of pharmacokinetic parameters.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Attention-Deficit Hyperactivity Disorder
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Sequential Assignment
Model Description
Open-label, single-treatment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
29 (Actual)
8. Arms, Groups, and Interventions
Arm Title
HLD200 (methylphenidate hydrochloride) in Adolescents
Arm Type
Experimental
Arm Description
HLD200 (B formulation, 54 mg, oral capsules) administered as a single treatment in the evening to children aged 13-17 years.
Arm Title
HLD200 (methylphenidate hydrochloride) in Children
Arm Type
Experimental
Arm Description
HLD200 (B formulation, 54 mg, oral capsules) administered as a single treatment in the evening to children aged 6-12 years.
Intervention Type
Drug
Intervention Name(s)
HLD200 (methylphenidate hydrochloride)
Other Intervention Name(s)
JORNAY PM
Primary Outcome Measure Information:
Title
PK Parameters for Rate and Extent of Absorption of MPH: Lag Time
Description
The absorption lag time for methylphenidate in plasma expressed in hours is the difference in time between the drug administration and the last time point where the drug concentration was below the limit of assay quantitation.
Time Frame
48hrs
Title
PK Parameters for Rate and Extent of Absorption of MPH: Cmax
Description
The maximum drug concentration of methylphenidate in plasma.
Time Frame
48hrs
Title
PK Parameters for Rate and Extent of Absorption of MPH: Tmax
Description
The time to reach maximum concentration of methylphenidate in plasma.
Time Frame
48hrs
Title
PK Parameters for Rate and Extent of Absorption of MPH: AUC0-tz
Description
Area under the methylphenidate plasma concentration-time curve to time point tz (AUC0-tz), where tz was the last time point over the time interval with a measurable drug concentration
Time Frame
48hrs
Title
PK Parameters for Rate and Extent of Absorption of MPH: AUC0-inf
Description
The area under the methylphenidate plasma concentration-time curve to infinite time
Time Frame
48hrs
Other Pre-specified Outcome Measures:
Title
PK Parameters for Rate and Extent of Absorption of MPH in Plasma: Plasma Concentration-time Curve
Description
To determine the rate and extent of absorption of methylphenidate following a single treatment of HLD200 (B formulation; 54 mg) in children and adolescents with ADHD, plasma samples were collected at t=0, 4, 6, 8, 9, 10, 11, 12, 13, 14, 15, 16, 18, 20, 22, 24, 36 and 48 hours post-HLD200 treatment and methylphenidate concentrations were determined.
Time Frame
48hrs
10. Eligibility
Sex
All
Minimum Age & Unit of Time
6 Years
Maximum Age & Unit of Time
17 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Male and female adolescents (13-17 years) and children (6-12 years).
Previous diagnosis of ADHD and confirmation using the Mini International Neuropsychiatric Interview for Children and Adolescents (MINI-KID).
ADHD symptoms controlled on a stable dose of ADHD medication. Subjects should be on MPH or have previous history of symptom control during treatment with MPH.
Physical examination free of clinically significant findings, unless deemed NCS by the Investigator and Medical Monitor;
Able to swallow treatment capsules;
Available for entire study period;
Provision of informed consent (from the parent[s] and/or legal representative[s]) and assent (from the subject); and
Female subjects of childbearing potential (i.e., post-menarche) required to have a negative result on urine pregnancy testing (and will be given specific instructions on avoiding pregnancy during trial)
Exclusion Criteria:
Any known history or presence of significant cardiovascular, pulmonary, hepatic, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic, ophthalmologic disease, unless deemed NCS by the Investigator and the Medical Monitor;
Presence of any significant physical or organ abnormality;
Any illness during the 4 weeks before this study, unless deemed NCS by the Investigator and the Clinical and/or Medical Monitor;
Severe comorbid psychiatric diagnosis that may affect subject safety or confound results (e.g., psychosis, bipolar disorder);
Known history of moderate to severe asthma;
Known history of severe allergic reaction (including drugs, food, insect bites, environmental allergens);
Known history of seizures (except febrile seizures prior to age 5), anorexia nervosa, bulimia or current diagnosis or family history of Tourette's disorder;
Subject who are severely underweight or overweight.
Clinical value outside of the acceptable ranges, unless deemed NCS significant per the Investigator;
Positive history for hepatitis B, hepatitis C and Human Immunodeficiency Virus (HIV);
Positive screening for illicit drug use, and/or current health conditions or use of medications that might confound the results of the study or increase risk to the subject;
Use of prescription medications (except ADHD medications) within 7 days and over-the counter medications (except birth control) within the 3 days preceding study enrollment, unless deemed acceptable by the Investigator and Clinical and/or Medical Monitor;
Blood draws of 50 ml to 249 ml within the 30 days, 250 ml to 449 ml within the 45 days and ≥ 450 ml within the 60 days preceding study enrollment;
Participation in clinical trial with an investigational drug within the 30 days preceding study enrollment;
Intolerance to venipuncture; and
Current suicidal ideation or history of suicidality determined as a significant finding on the Columbia-Suicide Severity Rating Scale (C-SSRS) by the investigator (Baseline C-SSRS for adolescents; Pediatric Baseline C-SSRS for children).
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ann Childress, M.D.
Organizational Affiliation
Centre for Psychiatry & Behavioral Medicine, Inc.
Official's Role
Principal Investigator
Facility Information:
Facility Name
Centre for Psychiatry & Behavioral Medicine, Inc.
City
Las Vegas
State/Province
Nevada
ZIP/Postal Code
89128
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
29039979
Citation
Childress A, Mehrotra S, Gobburu J, McLean A, DeSousa NJ, Incledon B. 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. J Child Adolesc Psychopharmacol. 2018 Feb;28(1):10-18. doi: 10.1089/cap.2017.0044. Epub 2017 Oct 17.
Results Reference
derived
Learn more about this trial
Pharmacokinetics of HLD200 in Children and Adolescents With ADHD
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