Efficacy and Safety of Methylphenidate HCl ER Capsules in Children and Adolescents With ADHD

A Randomized, Parallel, Double-Blind Efficacy and Safety Study of Biphentin Methylphenidate HCl Extended Release Capsules Compared to Placebo in Children and Adolescents 6 to 18 Years With Attention Deficit Hyperactivity Disorder (ADHD)

This multi-center parallel study is designed to study the efficacy and safety of fixed doses of methylphenidate extended release (ER) capsules of four dose levels compared with a placebo group in pediatric patients with Attention Deficit Hyperactivity Disorder (ADHD) who are between 6 and 18 years old.

Study Overview

• Status: Completed
• Conditions: ADHD; Attention Deficit Hyperactivity Disorder
• Intervention / Treatment: Drug: Placebo; Drug: Methylphenidate Hydrochloride Extended Release Capsules

Detailed Description

This is a parallel, randomized, double-blind, multi-center, placebo-controlled, forced dose, phase 3 study to evaluate the safety and efficacy of Biphentin® methylphenidate hydrochloride (HCl) extended release (ER) capsules in the treatment of Attention Deficit Hyperactivity Disorder (ADHD) in pediatric and adolescent patients aged 6 up to 18 years.

The primary objective was to assess the efficacy of Biphentin compared to placebo, in the clinic setting, as measured by the clinician-administered parent version of the ADHD-RS-IV.

Subjects who met study entry criteria were enrolled in the Double-blind Phase and were randomized to either a fixed dose of Biphentin (!0, 15, 20, or 40 mg/day) or placebo capsule taken daily in the morning for 1 week. Subjects then continued into an Open-label Phase that included dose optimization with doses starting at 10 mg and allowed up to 60 mg. The open-label period following the one double-blind fixed dose week provides additional opportunity for subjects to receive treatment with Biphentin. Extra unscheduled dose optimization visits are allowed as needed for additional dose titration visits during the open-label period.

The safety and tolerability, and efficacy assessments will be conducted throughout the study.

Biphentin® is designed to be a single daily dose alternative to separate doses of immediate release methylphenidate by providing a biphasic plasma profile. It achieves a first Cmax more similar to immediate release methylphenidate.

• Study Type: Interventional
• Enrollment (Actual): 230
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • Clinical Study Centers, LLC
  • California
    • Irvine, California, United States, 92612
      • University of California, Irvine/Child Development Center
    • National City, California, United States, 91950
      • Synergy Research
  • Florida
    • Bradenton, Florida, United States, 34201
      • Florida Clinical Research Center, LLC
    • Lauderhill, Florida, United States, 33319
      • Behavioral Clinical Research, Inc.
    • Maitland, Florida, United States, 32751
      • Martin Kane, DO
    • North Miami, Florida, United States, 33161
      • Segal Institute for clinical Research, North Miami Outpatient Clinic
  • Massachusetts
    • Marshfield, Massachusetts, United States, 02050
      • South Shore Psychiatric Services, PC
  • Mississippi
    • Madison, Mississippi, United States, 39110
      • Precise Research Center
  • Nevada
    • Las Vegas, Nevada, United States, 89128
      • Center for Psychiatry and Behavioural Medicine Inc
  • New York
    • New York, New York, United States, 10032
      • New York State Psychiatric Institute/Columbia University
  • North Carolina
    • Durham, North Carolina, United States, 27705
      • Department of Psychiatry, Duke University Medical Center
    • New Bern, North Carolina, United States, 28562
      • CTMG
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • University of Cincinnati College of Medicine/PPSI
    • Cleveland, Ohio, United States, 44106
      • University Hospital Case Medical Center
  • Texas
    • Wharton, Texas, United States, 77488
      • Wharton Research Center, Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Males and females ages 6 up to 18
• ADHD diagnosis with ADHD Rating Scale - 4th Edition scores ≥ 90th percentile
• In need of treatment for ADHD and able to have 2-day washout from previous medication
• Females of child-bearing potential not pregnant and practice birth control
• Subject and parent/guardian willing to comply with protocol
• Signed consent and assent

Exclusion Criteria:

• Estimated Full Scale intellectual level below 80 using Wechsler Abbreviated Scale of Intelligence (WASI)
• Current primary psychiatric diagnosis of other listed disorders
• Chronic medical illnesses: seizure, hypertension, thyroid disease, cardiac, family history of sudden death, glaucoma
• Use of psychotropic central nervous system (CNS) meds having effect exceeding 14 days from screening
• Planned use of prohibited drugs
• Is pregnant or breast-feeding
• Significant ECG or laboratory abnormalities
• Experimental drug or medical device within 30 days prior to screening
• Hypersensitivity to methylphenidate
• Inability or unwillingness to comply with protocol
• Well controlled on current ADHD treatment
• Inability to take oral capsules

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Placebo capsules	Drug: Placebo; Placebo capsules; Other Names: Placebo capsules
Active Comparator: 10 mg; Biphentin Methylphenidate Hydrochloride Extended Release Capsules 10 mg	Drug: Methylphenidate Hydrochloride Extended Release Capsules; Biphentin Methylphenidate ER Once-A-Day Capsules; Other Names: Biphentin
Active Comparator: 15 mg; Biphentin Methylphenidate Hydrochloride Extended Release Capsules 15 mg	Drug: Methylphenidate Hydrochloride Extended Release Capsules; Biphentin Methylphenidate ER Once-A-Day Capsules; Other Names: Biphentin
Active Comparator: 20 mg; Biphentin Methylphenidate Hydrochloride Extended Release Capsules 20 mg	Drug: Methylphenidate Hydrochloride Extended Release Capsules; Biphentin Methylphenidate ER Once-A-Day Capsules; Other Names: Biphentin
Active Comparator: 40 mg; Biphentin Methylphenidate Hydrochloride Extended Release Capsules 40 mg	Drug: Methylphenidate Hydrochloride Extended Release Capsules; Biphentin Methylphenidate ER Once-A-Day Capsules; Other Names: Biphentin
Experimental: Methylphenidate HCl ER Capsules (10, 15, 20, 40, 50 or 60 mg); Biphentin Methylphenidate Hydrochloride Extended Release Capsules (10, 15, 20, 40, 50 or 60 mg) - Open Label Phase	Drug: Methylphenidate Hydrochloride Extended Release Capsules; Biphentin Methylphenidate ER Once-A-Day Capsules; Other Names: Biphentin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in ADHD-RS-IV Total Score From Baseline (Visit 2) to the End of the Double-Blind Phase (Visit 3)	Change in ADHD-RS-IV Total Score from Baseline (Visit 2) to end of Double Blind Phase (Visit 3); [Calculations of baseline values (Visit 2) minus end of Double Blind values (Visit 3), higher differences means better outcomes]. Attention Deficit Hyperactivity Disorder Rating Scale-IV (ADHD-RS-IV): The home version of the ADHD-RS-IV comprising symptoms of ADHD was used. This 18-item scale incorporates each of the ADHD symptoms regardless of assigned subtype. Trained clinicians administered questionnaire to parents. Scoring was based on symptom severity on a 4-point scale: 0=never or rarely, 1=sometimes, 2=often, and 3=very often. The Total Score is the sum of the scores for all 18 items, and could range from 0 (no impairment) to 54 (maximal impairment).	From baseline (visit 2) to end of of Double-Blind phase (visit 3)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Adverse Events as a Measure of Safety and Tolerability	Incidence of adverse findings using various measures of safety, tolerability, and quality of life assessments following administration of once daily Biphentin	During the 12-week study period

Collaborators and Investigators

• Sponsor: Rhodes Pharmaceuticals, L.P.
• Investigators: Study Director: Wei-wei Chang, Ph.D., NuTec Incorporated; Principal Investigator: Sharon B. Wigal, Ph.D., University of California, Irvine / Child Development Center; Principal Investigator: Laurence Greenhill, M.D., New York State Psychiatric Institute / Columbia University; Study Chair: Robert J. Kupper, Ph.D., Rhodes Phamaceuticals, L.P.

Publications and helpful links

General Publications

• Wigal SB, Nordbrock E, Adjei AL, Childress A, Kupper RJ, Greenhill L. Efficacy of Methylphenidate Hydrochloride Extended-Release Capsules (Aptensio XR) in Children and Adolescents with Attention-Deficit/Hyperactivity Disorder: A Phase III, Randomized, Double-Blind Study. CNS Drugs. 2015 Apr;29(4):331-40. doi: 10.1007/s40263-015-0241-3.

Study record dates

Study Major Dates

• Study Start: November 1, 2010
• Primary Completion (Actual): February 1, 2012
• Study Completion (Actual): March 1, 2012

Study Registration Dates

• First Submitted: November 3, 2010
• First Submitted That Met QC Criteria: November 9, 2010
• First Posted (Estimate): November 11, 2010

Study Record Updates

• Last Update Posted (Estimate): February 22, 2023
• Last Update Submitted That Met QC Criteria: January 26, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Keywords: ADHD; inattention; hyperactivity; impulsivity
• Additional Relevant MeSH Terms: Mental Disorders; Nervous System Diseases; Neurologic Manifestations; Dyskinesias; Attention Deficit and Disruptive Behavior Disorders; Neurodevelopmental Disorders; Attention Deficit Disorder with Hyperactivity; Hyperkinesis; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Dopamine Agents; Dopamine Uptake Inhibitors; Central Nervous System Stimulants; Methylphenidate
• Other Study ID Numbers: RP-BP-EF002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO