Trial Outcomes & Findings for A Pivotal Efficacy Trial to Evaluate HLD200 in Children With ADHD in a Classroom Setting (NCT NCT02493777)
NCT ID: NCT02493777
Last Updated: 2021-07-23
Results Overview
The SKAMP is a validated, 13-item, observer-rated scale designed to assess the level of impairment of classroom-observed behaviors (Wigal and Wigal, 2006). Items 1 through 4 assess subject attention; items 5 through 8 assess deportment; items 9 through 11 assess quality of work; while items 12 and 13 assess subject compliance with teacher/classroom rules. Each individual item is rated on a 7-point scale from 0 (normal, no impairment) to 6 (maximal impairment). When all individual item scores are summed together, they produce a 13-item combined score that ranges from 0 to 78, with higher scores signifying greater impairment. In the present study, the SKAMP rating scale was utilized across 9 sessions occuring at 8:00 am, 9:00 am, 10:00 am, 12:00 pm, 2:00 pm, 4:00 pm, 6:00 pm, 7:00 pm, and 8:00 pm of the laboratory classroom day. Successful training of qualified individuals on the SKAMP scale was required before raters were allowed to perform study assessments.
COMPLETED
PHASE3
125 participants
12-hours from 8:00 am to 8:00 pm
2021-07-23
Participant Flow
A total of 125 participants were enrolled in this study, of which 119 were randomized to double-blind, placebo-controlled treatment at 6 sites in the United States from 28 July, 2015 to 04 March, 2015.
The study consisted of a screening period of up-to 4-weeks, followed by a 6-week open-label HLD200 treatment-optimization period that was followed by a 1-week randomized (1:1), placebo-controlled, double-blind period.
Participant milestones
| Measure |
HLD200 (Methylphenidate)
Participants received HLD200 capsules (containing beads with methylphenidate in a dual-coated drug-layered core; optimzed at 20, 40, 60, 80 or 100 mg) orally once daily in the evening during a 1-week randomized (1:1), placebo-controlled, double-blind-period that followed a 6-week open-label HLD200 treatment-optimization period.
|
Placebo
Participants recieved placebo (matched to their dose-optimzed HLD200 capsules, but containing microcrystalline cellulose beads in place of methylphenidate) orally once daily in the evening during a 1-week randomized (1:1), placebo-controlled, double-blind period that followed a 6-week open-label HLD200 treatment-optimization period.
|
|---|---|---|
|
Overall Study
STARTED
|
65
|
54
|
|
Overall Study
COMPLETED
|
65
|
53
|
|
Overall Study
NOT COMPLETED
|
0
|
1
|
Reasons for withdrawal
| Measure |
HLD200 (Methylphenidate)
Participants received HLD200 capsules (containing beads with methylphenidate in a dual-coated drug-layered core; optimzed at 20, 40, 60, 80 or 100 mg) orally once daily in the evening during a 1-week randomized (1:1), placebo-controlled, double-blind-period that followed a 6-week open-label HLD200 treatment-optimization period.
|
Placebo
Participants recieved placebo (matched to their dose-optimzed HLD200 capsules, but containing microcrystalline cellulose beads in place of methylphenidate) orally once daily in the evening during a 1-week randomized (1:1), placebo-controlled, double-blind period that followed a 6-week open-label HLD200 treatment-optimization period.
|
|---|---|---|
|
Overall Study
Lost to Follow-up
|
0
|
1
|
Baseline Characteristics
A Pivotal Efficacy Trial to Evaluate HLD200 in Children With ADHD in a Classroom Setting
Baseline characteristics by cohort
| Measure |
HLD200 (Methylphenidate)
n=64 Participants
|
Placebo
n=53 Participants
|
Total
n=117 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
9.6 Years
STANDARD_DEVIATION 1.58 • n=5 Participants
|
9.3 Years
STANDARD_DEVIATION 1.68 • n=7 Participants
|
9.4 Years
STANDARD_DEVIATION 1.63 • n=5 Participants
|
|
Sex: Female, Male
Female
|
22 Participants
n=5 Participants
|
15 Participants
n=7 Participants
|
37 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
42 Participants
n=5 Participants
|
38 Participants
n=7 Participants
|
80 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 12-hours from 8:00 am to 8:00 pmPopulation: Intent-to-Treat
The SKAMP is a validated, 13-item, observer-rated scale designed to assess the level of impairment of classroom-observed behaviors (Wigal and Wigal, 2006). Items 1 through 4 assess subject attention; items 5 through 8 assess deportment; items 9 through 11 assess quality of work; while items 12 and 13 assess subject compliance with teacher/classroom rules. Each individual item is rated on a 7-point scale from 0 (normal, no impairment) to 6 (maximal impairment). When all individual item scores are summed together, they produce a 13-item combined score that ranges from 0 to 78, with higher scores signifying greater impairment. In the present study, the SKAMP rating scale was utilized across 9 sessions occuring at 8:00 am, 9:00 am, 10:00 am, 12:00 pm, 2:00 pm, 4:00 pm, 6:00 pm, 7:00 pm, and 8:00 pm of the laboratory classroom day. Successful training of qualified individuals on the SKAMP scale was required before raters were allowed to perform study assessments.
Outcome measures
| Measure |
HLD200 (Methylphenidate)
n=64 Participants
|
Placebo
n=53 Participants
|
|---|---|---|
|
Swanson, Kotkin, Agler, M-Flynn and Pelham Combined Score (SKAMP CS) - Model-adjusted Average of All Post-dose Time Points Assessed During a Laboratory Classroom Test Day (Visit 9).
|
14.8 SKAMP CS (12-hour average)
Standard Error 1.17
|
20.7 SKAMP CS (12-hour average)
Standard Error 1.22
|
SECONDARY outcome
Timeframe: PREMB-R AM mean subscale score for the 2-days prior to Visit 9.Population: Intent-to-Treat
The PREMB-R is an 11-item rating scale designed to assess at-home functional impairments in children with ADHD during both early morning (AM) and late afternoon/evening (PM) time periods. With demonstrated validity and reliablility (Faraone et al., 2015), the AM subscale total score (sum of items 1 to 3) was designated in this study as a key secondary endpoint. Items are scored from 0 (none) to 3 (a lot), with higher scores signifying greater impairment of function. The PREMB-R rating scale was completed by parents during the 2-days prior to study visits at the beginning and end of the open-label period (Visits 2 and 8, respectively), as well as at the end of the randomized, double-blind period (Visit 9). At each visit, these ratings were used only for review by the clinician (MD, PhD, DO, licensed social worker, or any trained mental health professional approved by the sponsor) as part of a structured interview to enable collection of a clinician-rated PREMB-R AM subscale score.
Outcome measures
| Measure |
HLD200 (Methylphenidate)
n=64 Participants
|
Placebo
n=53 Participants
|
|---|---|---|
|
Parent Rating of Evening and Morning Behavior Revised, Morning Subscale (PREMB-R AM).
|
0.9 PREMB-R AM subscale total score
Standard Error 0.27
|
2.7 PREMB-R AM subscale total score
Standard Error 0.27
|
Adverse Events
HLD200 (Methylphenidate)
Placebo
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
HLD200 (Methylphenidate)
n=65 participants at risk
|
Placebo
n=54 participants at risk
|
|---|---|---|
|
Psychiatric disorders
Any Insomnia
|
7.7%
5/65 • Adverse events were collected across the duration of the study (up to 13-weeks). However, an adverse event is considered treatment-emergent during the randomized, placebo-controlled phase only if it started on or after the first dose of double-blind study medication, but before the last dose of double blind study medication plus 72 hours as reflected in the table below.
Adverse events were recorded by study staff at every post-screening study visit based on spontaneous report from subjects/parents, regardless of causality. However, sleep-related adverse event were directly solicited from subjects/parents by study staff using a structured interview format to assessing sleep disturbances (e.g., issues with sleep onset, quality and quantity), rather than obtained from spontaneous reporting.
|
9.3%
5/54 • Adverse events were collected across the duration of the study (up to 13-weeks). However, an adverse event is considered treatment-emergent during the randomized, placebo-controlled phase only if it started on or after the first dose of double-blind study medication, but before the last dose of double blind study medication plus 72 hours as reflected in the table below.
Adverse events were recorded by study staff at every post-screening study visit based on spontaneous report from subjects/parents, regardless of causality. However, sleep-related adverse event were directly solicited from subjects/parents by study staff using a structured interview format to assessing sleep disturbances (e.g., issues with sleep onset, quality and quantity), rather than obtained from spontaneous reporting.
|
|
Investigations
Blood pressure diastolic increased
|
13.8%
9/65 • Adverse events were collected across the duration of the study (up to 13-weeks). However, an adverse event is considered treatment-emergent during the randomized, placebo-controlled phase only if it started on or after the first dose of double-blind study medication, but before the last dose of double blind study medication plus 72 hours as reflected in the table below.
Adverse events were recorded by study staff at every post-screening study visit based on spontaneous report from subjects/parents, regardless of causality. However, sleep-related adverse event were directly solicited from subjects/parents by study staff using a structured interview format to assessing sleep disturbances (e.g., issues with sleep onset, quality and quantity), rather than obtained from spontaneous reporting.
|
13.0%
7/54 • Adverse events were collected across the duration of the study (up to 13-weeks). However, an adverse event is considered treatment-emergent during the randomized, placebo-controlled phase only if it started on or after the first dose of double-blind study medication, but before the last dose of double blind study medication plus 72 hours as reflected in the table below.
Adverse events were recorded by study staff at every post-screening study visit based on spontaneous report from subjects/parents, regardless of causality. However, sleep-related adverse event were directly solicited from subjects/parents by study staff using a structured interview format to assessing sleep disturbances (e.g., issues with sleep onset, quality and quantity), rather than obtained from spontaneous reporting.
|
Additional Information
Chief Scientific Officer
Ironshore Pharmaceuticals and Development, Inc.
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place