Project Description:
The present study is designed to evaluate the efficacy, safety, and tolerability of SPN-810 in patients aged 6 to 12 years with ADHD and comorbid IA, when taken in conjunction with a standard ADHD treatment. In this patient population, IA behaviors persist, despite monotherapy treatment with an FDA-approved ADHD medication, stimulant or non-stimulant, at an FDA-approved optimized dose.
A titration schedule will be followed to ensure a safe escalation to each dose level. The titration rate and dose range under investigation in the present study were demonstrated to be safe, efficacious, and well tolerated in a similar patient population in the previous Phase 2b study. Administration of study medication will be recorded using an electronic dosing diary.
The IA diary will serve as the primary assessment tool for efficacy. The IA diary is a new electronic observer-reported outcome (eObsRO) instrument developed by the Sponsor to record behaviors associated with IA. Secondary measures of efficacy will include the effect of SPN-810 on the Clinical Global Impression Improvement Scale (CGI-I), the effect of SPN-810 on the Clinical Global Impression Severity Scale (CGI-S), the effect of SPN-810 on the childs overall health as measured by the Child Health Questionnaire Parent Form 28-item (CHQ-PF28), and the effect of treating the child with SPN-810 on the parent-child relationship as measured by the Parenting Stress Index Short Form (PSI-4-SF). The childs ADHD symptoms will be measured using the Swanson, Nolan and Pelham Rating Scale - Revised (SNAP-IV). Safety will be assessed by the monitoring of AEs, concomitant medications, vital signs, clinical laboratory tests, physical examinations, and ECGs, as well as by the Simpson-Angus Scale, the Barnes Akathisia Scale, and the Abnormal Involuntary Movement Scale (AIMS). The scales were chosen to specifically monitor EPS, since youth treated with antipsychotics are at greater risk for EPS side effects than adults (Findling 2005). These scales were utilized in Phase 2 studies and have been used in other clinical studies of atypical antipsychotics in children.
Protocol 810P301 is a randomized, placebo-controlled, double blind, multicenter, parallel group, fixed dose study to demonstrate the efficacy, safety, and tolerability of SPN-810 in the treatment of IA in patients aged 6-12 years with ADHD in conjunction with standard ADHD treatment. The study is presented schematically in Figure 1 and Figure 2. The study is divided into three phases: Pre-Treatment, Treatment, and Conversion/Taper.
Following screening, eligible subjects will enter a two-week baseline period, at which time the IA diary will be issued to the subjects primary caregiver. At the end of the two-week baseline period, eligible subjects whose primary caregiver has maintained at least 80% compliance with the IA diary will be randomized 1:1:1 to 18 mg/day SPN-810, 36 mg/day SPN-810, or placebo. A dose titration schedule will be followed, with dosing in the active treatment groups initiated at 3 mg/day and increased approximately every 3 days until the target dose is reached. After completing the two-week titration period and the three-week maintenance period, subjects will enter the conversion or tapering phase prior to discontinuing SM, at which time subjects will have the option to enter an open label extension (OLE) study. A subject who discontinues during the maintenance period prior to Visit 6 may be allowed to participate in the OLE on a case-by-case basis only after consultation between the Investigator, the Medical Monitor and the Sponsor. The OLE study will be conducted under a separate protocol. Subjects who choose to participate in the OLE will enter that study at a dose of 18 mg/day SPN-810.
Keyword(s):
ADHD, Aggression, Molindone, Medication, ADD
Target Audience:
Professionals and Para-Professionals, Family Members/Caregivers, Children/Adolescents with Disabilities/SHCN, General Public
Unserved or Under-served Populations:
Racial or Ethnic Minorities, Disadvantaged Circumstances, Geographic Areas, Rural/Remote, Urban, Specific Groups
Primary Target Audience Geographic Descriptor:
State, Regional, National
