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A Flexible-Dose Titration Study of Aptensio XR in Children Ages 4 to Under 6 Years Diagnosed With ADHD (EF003)

Primary Purpose

Attention Deficit Disorder With Hyperactivity

Status

Completed

Phase

Phase 4

Locations

United States

Study Type

Interventional

Intervention

Aptensio XR

Placebo

About this trial

This is an interventional other trial for Attention Deficit Disorder With Hyperactivity

Eligibility Criteria

4 Years - 6 Years (Child)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Male and female subjects ages 48 months to 68 months inclusive at time of consent
Met Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) criteria for ADHD, combined, hyperactive/impulsive or inattentive presentation made during a clinical interview by an experienced clinician and confirmed with Kiddie-Sads-Present and Lifetime Version (K-SADS-PL)
ADHD symptoms must have been present for at least 6 months
Age- and sex-adjusted ratings of ≥ 90th percentile Total Score on the ADHD-RS-IV Preschool Version
Score of < 65 on the Child Global Assessment Scale (CGAS)
Must have had a CGI-S score of ≥ 4 at Visit 2 (subjects who were granted a waiver to bypass parental training, and did not have a Visit 2, were still qualified to continue in the study based on their CGI-S score at screening)
Estimated intelligence quotient (IQ) ≥ 80 on the Kaufman Brief Intelligence Test, 2nd edition (KBIT-2). If results from the KBIT-2 were deemed invalid because of significant ADHD symptomatology, the PI could submit additional documentation to support average cognitive functioning. This documentation could include progress reports from preschool or other previous testing. These exceptions were evaluated by the Medical Monitor and Study PIs on a case-by-case basis for inclusion.
The subject had a parent or legal guardian who would give written informed consent for the subject to participate in the study
Subject and parent or legal guardian must have been able to speak and understand English
Subject must live with primary caretaker/rater and have been living with primary caretaker for at least 6 months
Subject and parent/guardian must have been willing and able to comply with all requirements of the protocol
Systolic and diastolic blood pressure below the 95th percentile for age and gender

Exclusion Criteria:

The subject had a lack of response to a trial of adequate dose and duration of MPH or intolerance to previous methylphenidate (MPH) treatment
The subject was using any other current psychotropic medication except clonidine, guanfacine, atomoxetine and/or stimulants or had taken an investigational drug in the 30 days prior to screening
The subject had used monoamine oxidase inhibitors (MAOIs) within 14 days of the screening visit
The subject planned to use prohibited drugs or agents at any point between the screening visit and the end of the study
Use of anticonvulsants, antidepressants, or antipsychotics in the 30 days prior to screening
The subject should not plan to start any additional psychotherapy outside of the trial during the duration of the study
The subject had a history of chronic vocal or motor tics or Tourette's syndrome
The subject had any clinically significant ECG abnormalities at screening
The subject had any major medical conditions that would have interfered with involvement in the study or could have been affected negatively by methylphenidate
The subject had chronic medical illnesses including a seizure disorder (excluding a history of febrile seizures), severe hypertension, untreated thyroid disease, known structural cardiac abnormalities, serious arrhythmias, cardiomyopathy, glaucoma, or a family history of sudden death
History (in the past 12 months) or presence of clinically-significant cardiovascular, cerebrovascular, renal, hepatic, gastrointestinal, pulmonary, immunological, hematological, endocrine, or neurological disease that in the opinion of the investigator could have put the subject at risk if he/she participated in the trial or which could have confounded study results
Family history (parent or sibling) of structural cardiovascular disease
Current or recent (past 12 months) history of drug abuse in someone living in the subject's home
Current symptoms or history of major psychiatric illness (for example schizophrenia, psychosis, bipolar disorder, post-traumatic stress disorder, depression, severe anxiety disorder, obsessive compulsive disorder or autistic spectrum disorder) in addition to ADHD that required treatment with additional medication or, in the opinion of the PI, would have contraindicated study participation
History or presence of suicidal ideation or significant self-injurious behavior
The subject showed evidence of current physical, sexual, or emotional abuse
Both biological parents of the subject had a history of bipolar disorder

Sites / Locations

Center for Psychiatry and Behavioral Medicine Inc.
Duke University Medical Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Aptensio XR

Placebo comparator

Arm Description

Optimized dose of Aptensio XR (10, 15, 20, 30 or 40 mg Aptensio XR)

Placebo capsules

Outcomes

Primary Outcome Measures

Attention Deficit Hyperactivity Disorder Rating Scale - 4th Edition (ADHD-RS-IV) Preschool Version Total Score Change From End of Open Label Phase (Baseline) to End of Double Blind.

ADHD-RS-IV is 18-item scale incorporates each of the ADHD symptoms listed in the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision (DSM-IV-TR) regardless of assigned subtype. Scoring was based on the universally accepted symptom severity as recommended in the DSM-IV-TR manual 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) for each administration per subject. Higher score means higher frequency and severity of symptoms. Trained clinicians administered the questionnaire to parents. The ADHD-RS-IV Preschool Version was used to determine eligibility, optimal dosing and the efficacy of double blind treatment.

Secondary Outcome Measures

Attention Deficit Hyperactivity Disorder Rating Scale - 4th Edition (ADHD-RS-IV) Preschool Version Hyperactivity-Impulsivity Subscale Score Change From End of Open Label Phase (Baseline) to End of Double Blind.

This 18-item scale incorporates each of the ADHD symptoms listed in the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision (DSM-IV-TR) regardless of assigned subtype. Scoring was based on the universally accepted symptom severity as recommended in the DSM-IV-TR manual on a 4-point scale: 0=never or rarely, 1=sometimes, 2=often, and 3=very often. The Hyperactivity-Impulsivity even items. The Hyperactivity-Impulsivity subscale score was the sum of the scores for the 9 even items and could range from 0 (no impairment) to 27 (maximal impairment) for each administration per subject. Higher score means higher frequency and severity of symptoms. Trained clinicians administered the questionnaire to parents.

Attention Deficit Hyperactivity Disorder Rating Scale - 4th Edition (ADHD-RS-IV) Preschool Version Inattention Subscale Score Change From End of Open Label Phase (Baseline) to End of Double Blind.

This 18-item scale incorporates each of the ADHD symptoms listed in the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision (DSM-IV-TR) regardless of assigned subtype. Scoring was based on the universally accepted symptom severity as recommended in the DSM-IV-TR manual on a 4-point scale: 0=never or rarely, 1=sometimes, 2=often, and 3=very often. The Inattention subscales were based upon the sum of the odd items. The Inattention subscale score was the sum of the scores for the 9 odd items and could range from 0 (no impairment) to 27 (maximal impairment) for each administration per subject. Higher score means higher frequency and severity of symptoms. Trained clinicians administered the questionnaire to parents.

Summary of Clinical Global Impression Scale of Severity (CGI-S) Score From End of Open Label Phase (Baseline) to End of Double Blind.

The scale provides a global rating of illness severity during the trial. The subject is rated relative to the clinician's past experience with other subjects who have the same diagnosis. The CGI-S scale is 1 question and rated on a 7-point scale, with the severity of illness scale using a range of responses from 1 (normal) through to 7 (amongst the most severely ill subjects). A lower value a better the outcome.

Clinical Global Impression Scale of Improvement (CGI-I) Score at End of Double Blind Phase Relative to End of Open Label Phase (Baseline).

The scale provides a global rating of illness improvement during the trial. The subject is rated relative to the clinician's past experience with other subjects who have the same diagnosis. The CGI-I scale is 1 question, and rates improvement compared with a baseline visit using a 7-point scale. The range of responses are from 1 (very much improved) through 7 (very much worse). A lower value is a better the outcome.

Conners Early Childhood Behavior - Parent (Short) (EC BEH-P(S)) Change in T-score From End of Open Label Phase (Baseline) to End of Double Blind

Conners EC BEH-P(S) is an assessment tool used to obtain a parent's observations about his/her child's behavior. This tool is designed to assess a range of behavioral, emotional, & social issues in young children. The tool consists of 47 items, responses to which are summarized in 6 behavioral scales & 2 validity scales. Items on Conners assessment are rated on a Likert scale ranging from 0-3. The ratings were converted to raw item scores. Raw item scores were grouped, standardized, and/or compared to lookup tables for interpretation. Assessments were presented as T-scores: item raw scores for a given scale are added together; this raw sum is compared to age- and gender-matched normative data and converted to a T-score. Higher scores indicate higher concerns. T-score is a standard score with a mean of 50 and standard deviation of 10. Note that Conners assessments do not use T-scores greater than 90; raw scores that produce extremely high T-scores are reported as ''T-score >= 90."

Full Information

NCT ID

NCT02683265

First Posted

February 5, 2016

Last Updated

January 24, 2023

Sponsor

Rhodes Pharmaceuticals, L.P.

1. Study Identification

Unique Protocol Identification Number

NCT02683265

Brief Title

A Flexible-Dose Titration Study of Aptensio XR in Children Ages 4 to Under 6 Years Diagnosed With ADHD

Acronym

EF003

Official Title

A Randomized, Double-Blind, Placebo-Controlled, Flexible-Dose Titration Study of Aptensio XR® in Children Ages 4 to Under 6 Years Diagnosed With Attention Deficit-Hyperactivity Disorder (ADHD)

Study Type

Interventional

2. Study Status

Record Verification Date

January 2023

Overall Recruitment Status

Completed

Study Start Date

April 25, 2016 (Actual)

Primary Completion Date

November 2, 2017 (Actual)

Study Completion Date

March 27, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Rhodes Pharmaceuticals, L.P.

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

This randomized, double-blind, flexible-dose, placebo-controlled, parallel group study is designed to evaluate Aptensio XR® compared to placebo in preschool age children with ADHD. Male and female children ages 4 years, 0 months to 5 years, 8 months with a diagnosis of ADHD (combined, inattentive or hyperactive/impulsive) will be enrolled. There will be 6 phases in this study: a screening phase of up to 4 weeks, which will include washout if applicable, an enrollment & parent training phase lasting 2-4 weeks, an eligibility phase of up to 2 weeks to determine eligibility for the open-label phase, a 6-week open-label dose titration phase, a 2 week double-blind phase for Aptensio XR® responders, and a two-week follow-up call after study completion or early discontinuation to assess for ongoing adverse events and concomitant medications. Up to 150 subjects will be enrolled in this trial to allow for subjects who improve significantly during the behavior training phase and drop-outs. Once 74 subjects have completed the double-blind phase, no additional subjects will be enrolled in the trial. Subjects who are already enrolled at that time will be allowed to complete the trial. The primary objective of this study is to establish that an optimal dose of Aptensio XR® will result in a significant reduction in ADHD symptoms compared with placebo in children ages 4 to under 6 years.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Attention Deficit Disorder With Hyperactivity

7. Study Design

Primary Purpose

Other

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

Model Description

Randomized, Double-Blind, Placebo-Controlled, Flexible-Dose Titration Study

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Masking Description

Blinded active capsules looked identical to the same strength placebo capsules

Allocation

Randomized

Enrollment

158 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Aptensio XR

Arm Type

Experimental

Arm Description

Optimized dose of Aptensio XR (10, 15, 20, 30 or 40 mg Aptensio XR)

Arm Title

Placebo comparator

Arm Type

Placebo Comparator

Arm Description

Placebo capsules

Intervention Type

Drug

Intervention Name(s)

Aptensio XR

Other Intervention Name(s)

methylphenidate, extended release

Intervention Description

Optimized dose of Aptensio XR (10, 15, 20, 30 or 40 mg) administered orally, once daily

Intervention Type

Drug

Intervention Name(s)

Placebo

Other Intervention Name(s)

Dose-matched placebo

Intervention Description

Placebo capsules

Primary Outcome Measure Information:

Title

Attention Deficit Hyperactivity Disorder Rating Scale - 4th Edition (ADHD-RS-IV) Preschool Version Total Score Change From End of Open Label Phase (Baseline) to End of Double Blind.

Description

Time Frame