Clinical trial NCT01711021: Study to Evaluate Safety & Efficacy of d-Amphetamine Transdermal System vs Placebo in Children & Adolescents With ADHD
Official title: A Randomized, Double-Blind, Placebo-Controlled, Crossover, Laboratory Classroom Study to Evaluate the Safety and Efficacy of d-Amphetamine Transdermal Drug Delivery System (d-ATS) Compared to Placebo in Children and Adolescents With ADHD
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Attention Deficit Hyperactivity Disorder
Keywords: ADHD
Lead sponsor: Noven Therapeutics
Sponsor class: INDUSTRY
First posted: 2012-10-22
Enrollment: 110
Sex: ALL
Minimum age (years): 6
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: This study will evaluate safety and efficacy of d-Amphetamine Transdermal System for the treatment of Attention Deficit Hyperactivity Disorder in children and adolescents.

Detailed description: The study will consist of a four-week screening period, a 3-day wash-out period (if applicable), a five-week open-label, step-wise dose optimization period and two-week double blind randomized crossover treatment period with weekly classroom assessments and a safety follow-up by telephone 7 - 10 days after last dose of study drug.

Eligibility criteria: Inclusion Criteria:

1. Gender: Male or female
2. Age: Between 6 and 17 years of age (inclusive)
3. Race: All eligible
4. Females of child-bearing potential must have agreed to practice a clinically accepted method of contraception during the study and for at least 1 month prior to study dosing and 1 month following completion of the study. Acceptable contraceptive methods included abstinence, oral contraception, surgical sterilization (bilateral tubal ligation, bilateral oophorectomy, or hysterectomy), intrauterine device, diaphragm in addition to spermicidal foam and condom on male partner, or systemic contraception (e.g., Norplant System)
5. Must have met Diagnostic and Statistical Manual of Mental Disorders, 4th edition - Text Revision (DSM-IV-TR) criteria for a primary diagnosis of ADHD combined, hyperactive/impulsive subtype, or predominately inattentive subtype
6. The Screening and Baseline visit ADHD-RS-IV total score must have been ≥90% of the general population of children by age and gender
7. Able to wear a patch for 9 hours (for children and, if applicable, for adolescents, parent or caregiver must be present to apply and remove the patches and maintain the used and unused patches in a secure, controlled area of the home)
8. Functioning at an age-appropriate level intellectually as determined by an intelligence quotient (IQ) of ≥80 on the Wechsler Abbreviated Scale of Intelligence II™ (WASI II™) vocabulary and matrix reasoning components
9. Must have been able to complete PERMP assessment
10. Must have provided parental consent (signed ICF) and obtained written/verbal assent from the subject
11. Subject and parent(s)/ caregiver must have been willing and able to comply with all the protocol requirements and parent(s) or caregiver must be able to provide transportation for the subject to and from the analog classroom sessions

Exclusion Criteria:

1. Blood pressure outside the 95th percentile for age and gender
2. Pulse of \<50 (age 6 - 17), or \>120 (age 6 - 12), or \>125 (age 13 - 17)
3. Known non-responder to amphetamine treatment
4. Documented allergy, intolerance, or hypersensitivity to amphetamine
5. Currently taking an ADHD medication that is providing symptom control with no residual impairment at home or school and has acceptable tolerability and adherence
6. Recent history (within the past 6 months) of suspected substance abuse or dependence disorder (including nicotine)
7. History of seizures during the last 2 years (excluding infantile febrile seizures), a tic disorder (exclusive of transient tic disorder), a current diagnosis, and/or a family history of Tourette's Disorder. Mild medication-induced tics were not exclusionary
8. Any psychiatric disorder that could interfere with study participation or the safety of the subject or other participants, such as conduct disorder (CD) or oppositional defiant disorder (ODD) with a history of prominent aggressive outbursts. Children meeting CD or ODD but without prominent aggression will be allowed to enroll at the discretion of the Investigator
9. Autism or Asperger's Disorder
10. Family history (first degree relatives) of sudden cardiac death
11. Current controlled (requiring medication) or uncontrolled comorbid psychiatric conditions such as post-traumatic stress disorder, psychosis, bipolar illness, severe obsessive compulsive disorder, severe depressive or severe anxiety disorder, was considered a suicide risk, had recent (last 6 months) suicidal ideation, or any lifetime self-harm event
12. History of abnormal thyroid function
13. Has a body mass index (BMI) for age greater than 95th percentile per Centers for Disease Control BMI (for gender-specific charts)
14. Known history of symptomatic cardiovascular disease, advanced arteriosclerosis, structural cardiac abnormality, cardiomyopathy, serious heart rhythm abnormalities, coronary artery disease, or other serious cardiac problems that may place them at increased vulnerability to the sympathomimetic effects of a stimulant drug
15. Any skin abnormality present at the potential application site (i.e., infection, rash, atrophy, excessive fragility or dryness, any cut or abrasion, or tattoo)
16. History of hypersensitivity, allergy to topical medication, preparation, or adhesive dressings
17. Concurrent chronic or significant acute illnesses (such as severe allergic rhinitis or an infectious process requiring antibiotics, unless expected to resolve or has resolved by Day 0) disability or any unstable medical condition that in the Investigator's opinion would lead to difficulty complying with the protocol requirements
18. Used any investigational drug within 30 days of the Screening visit
19. History of physical, sexual, or emotional abuse in the last year
20. Medical history of hepatitis A/B/C or HIV
21. Positive urine drug screen for drugs of abuse

Primary outcomes:
measure: Mean Swanson, Kotkin, Agler, M-Flynn, and Pelham (SKAMP) Total Score During the Double-Blind Treatment Period
timeFrame: Mean SKAMP Total Score of SKAMP Total Scores from 9 different time points including (1, 2, 3, 4.5, 6, 7, 9, 10, 12 hours post-dose)
Secondary outcomes:
measure: Onset of Efficacy Measured by Swanson, Kotkin, Agler, M-Flynn, and Pelham (SKAMP) Total Score
timeFrame: Onset of efficacy defined as the time of the first assessment time showing statistical significance between d-ATS and placebo. 2 hours post-dose in Double-Blind Treatment Period
measure: Duration of Effect for d-Amphetamine and Placebo Treatment
timeFrame: Duration of Effect was from onset (2 hours post-dose) and up to 12 hours post-dose (p<0.001)
measure: Permanent Product Measure of Performance (PERMP) Scores Including PREMP-C and PREMP-A From Different Timepoints Post-dose
timeFrame: 1,2, 3, 4.5,6,7,9,10 and 12 hours post-dose from double-blind treatment period
measure: Change in the Clinician-rated Scale of ADHD Symptoms Based on DSM-IV-TR Criteria (ADHD-RS-IV).
timeFrame: Averaged from week 6 and week 7 results during the Double-Blind Cross-Over treatment period.
measure: Conners Parent Rating Scale Revised Short Form (CPRS-R:S) Total Scores From Week 6 and Week 7
timeFrame: Combined analysis by treatment groups from week 6 and week 7 (averaged)
measure: Number of Responders Evaluated by Clinical Global Impression (CGI-I) Scale by Treatments From the Double-blind Treatment Period
timeFrame: the double-blind treatment period
Other outcomes:
Locations:
city: Irvine
country: United States
facility: University of California - Irvine
state: California
city: Miami
country: United States
facility: Florida International University Center for Children and Families
state: Florida
city: Las Vegas
country: United States
facility: Center for Psychiatry and Behavioral Medicine Inc.
state: Nevada
Study officials:
affiliation: Not Affiliated
name: James Waxmonsky, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Cutler AJ, Suzuki K, Starling B, Balakrishnan K, Komaroff M, Castelli M, Meeves S, Childress AC. Efficacy and Safety of Dextroamphetamine Transdermal System for the Treatment of Attention-Deficit/Hyperactivity Disorder in Children and Adolescents: Results from a Pivotal Phase 2 Study. J Child Adolesc Psychopharmacol. 2022 Mar;32(2):89-97. doi: 10.1089/cap.2021.0107. Epub 2022 Jan 11.