Conditions: Attention Deficit Hyperactivity Disorder
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 125
Healthy volunteers: no

Brief summary:
This Phase 3 pivotal efficacy trial will examine the effects of HLD200 (methylphenidate) in patients aged 6-12 years with ADHD in a laboratory classroom setting. This study has a 6-week open-label treatment optimization period followed by a one week randomized, double-blind, placebo-controlled test phase.

Detailed description:
To address the unmet need for early morning ADHD symptom control, Ironshore has developed a novel drug delivery system that incorporates the active MPH ingredient in a delayed release/extended release formulation. This formulation provides a controlled, approximately 8-hour delay in initial drug release, followed by a subsequent controlled rate of drug release throughout the day. The goal of this system is to enable nighttime dosing of MPH to provide control of ADHD symptoms at the beginning of the next morning and throughout the remainder of the day.

The phase 3 study used an open-label treatment-optimization phase followed by a double-blind, placebo-controlled, 1-week, parallel-group treatment phase to assess safety and tolerability, as well as the time course of treatment effect, of evening-dosed HLD200 in pediatric subjects with a diagnosis of ADHD. At Visit 2, subjects began daily evening (8:00 pm ±30 minutes) treatment with 20 or 40 mg HLD200 (based on prior treatment history) for a period of 1 week and then had up to 4 additional weekly visits (Visits 3 to 6) for treatment adjustments to achieve both a) an optimal daily dose and b) an optimal treatment time prior to beginning the Double-blind Placebo-controlled Test Phase.

During Visits 3, 4, 5, and 6, investigators were permitted to titrate the dose of study drug (up or down) in 20 to 40 mg increments until either achieving the "optimal" daily dose or reaching a maximum daily dose of 100 mg/day and/or a maximum dose not exceeding 3.7 mg/kg (based on Visit 2 \[baseline\] weight). The final permitted dose level change was at Visit 6, after which, that dose was to be continued through Visit 7 to randomization at Visit 8. The subject underwent an assessment of study drug tolerability and, if necessary, could have his/her dose reduced. In concert with dose strength adjustments, treatment time adjustments were permitted during Visits 3, 4, 5, and 6 in increments of ±0.5 to 1.0 hour until an "optimal" treatment time was achieved (between 6:30 pm to 9:30 pm; at least 1 hour following completion of dinner). The time for changing final dose timing was at Visit 6 and continued through Visit 7 to randomization at Visit 8.

During the 1-week parallel-group phase, at Visit 8 subjects were randomly assigned (1:1 ratio) in double-blind fashion to either HLD200 or placebo treatments over the next 7 evenings. The placebo group received matching placebo at their optimal treatment time, while the HLD200 group received HLD200 at their optimal daily dose and treatment time.

Arms:
arm 1: The investigational drug for this study is HLD200 MPH MR capsules comprised of the active pharmaceutical ingredient (MPH) in a dual-coated drug-layered core. Following open-label treatment optimization, subjects will be randomized (1:1) to double-blind HLD200 to be taken once daily during the evening for a period of 1-week prior to testing. arm 2: Placebo capsules will be composed of microcrystalline cellulose beads in place of MPH containing beads found in the HLD200 capsules. Following open-label treatment optimization, subjects will be randomized (1:1) to double-blind placebo to be taken once daily during the evening for a period of 1-week prior to testing.

Interventions: intervention 1: HLD200 methylphenidate hydrochloride (MPH) Capsules intervention 2: Placebo
Intervention descriptions: intervention 1: HLD200 doses: 20, 40, 60, 80 or 100 mg intervention 2: None

Protocol document: