Study to Evaluate Safety & Efficacy of d-Amphetamine Transdermal System vs Placebo in Children & Adolescents With ADHD

Noven Pharmaceuticals

Status and phase: Completed; Phase 2

Conditions: Attention Deficit Hyperactivity Disorder

Treatments: Drug: Placebo patch; Drug: d-Amphetamine Transdermal Patch

Study type: Interventional

Funder types: Industry

Identifiers

NCT01711021

N25-006

Details and patient eligibility

About

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

Full 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.

Enrollment: 110 patients

Sex: All

Ages: 6 to 17 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: Triple Blind

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110 participants in 2 patient groups, including a placebo group

d-Amphetamine Transdermal patch

Active Comparator group

Description:

The study was conducted in 2 parts: a 5-week, open-label, step-wise Dose Optimization Period and a 2-week, randomized, cross-over Double-Blind Treatment Period. Subjects who reached the optimal dose by end of dose optimization treatment period were randomized to receive double-blind treatment. Participants first received study patches everyday for one week, then subjects were crossed-over to receive the placebo treatment. d-Amphetamine Transdermal System: Patches will be worn for 9 hours every day. After 9 hours the patch will be removed. Every day a new patch will be applied.

Treatment:

Drug: d-Amphetamine Transdermal Patch

Placebo patch

Placebo Comparator group

Description:

The study was conducted in 2 parts: a 5-week, open-label, step-wise Dose Optimization Period and a 2-week, randomized, cross-over Double-Blind Treatment Period. Subjects who reached the optimal dose by end of dose optimization treatment period were randomized to receive double-blind treatment. Participants first received placebo patches everyday for one week, then subjects were crossed-over to receive the study treatment. Placebo patch: Patches will be worn for 9 hours every day. After 9 hours the patch will be removed. Every day a new patch will be applied.

Treatment:

Drug: Placebo patch