Trial Outcomes & Findings for A Pivotal Efficacy Trial to Evaluate HLD200 in Children With ADHD in a Naturalistic Setting (NCT NCT02520388)
NCT ID: NCT02520388
Last Updated: 2021-07-23
Results Overview
The ADHD-RS-IV was developed to measure the behaviors of children with ADHD (DuPaul et al., 1998). The scale consists of 18 items designed to reflect current symptomatology of ADHD. Each item is scored in a range from 0 (reflecting no symptoms or a frequency of never or rarely) to 3 (reflecting severe symptoms or a frequency of almost always), with a range of total scores ranging from 0 to 54. In this study, a site clinican (required to be an MD, PhD, DO, licensed social worker, or any trained mental health professional approved by the sponsor) completed ADHD-RS-IV assessments at each visit using a structured interview format.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
163 participants
Primary outcome timeframe
Last week of 3-week treatment period assessed at Visit 5.
Results posted on
2021-07-23
Participant Flow
The study was conducted at 22 sites in the United States. First subject enrolled was on 13 August, 2015 and last subject completed was on 13 May, 2016.
In total, 163 particpants were enrolled in the study (completed the Baseline Visit).
Participant milestones
| Measure |
HLD200 (Methylphenidate)
Participantas recieved HLD200 capsules (containing beads with methylphenidate in a dual-coated drug-layered core; 40, 60 or 80 mg) orally once daily in the evening for 3 weeks.
|
Placebo
Participants recieved placebo (matched to HLD200 capsules, but containing microcrystalline cellulose beads in place of methylphenidate) orally once daily in the evening for 3 weeks.
|
|---|---|---|
|
Overall Study
STARTED
|
82
|
81
|
|
Overall Study
Treated
|
81
|
80
|
|
Overall Study
COMPLETED
|
73
|
65
|
|
Overall Study
NOT COMPLETED
|
9
|
16
|
Reasons for withdrawal
| Measure |
HLD200 (Methylphenidate)
Participantas recieved HLD200 capsules (containing beads with methylphenidate in a dual-coated drug-layered core; 40, 60 or 80 mg) orally once daily in the evening for 3 weeks.
|
Placebo
Participants recieved placebo (matched to HLD200 capsules, but containing microcrystalline cellulose beads in place of methylphenidate) orally once daily in the evening for 3 weeks.
|
|---|---|---|
|
Overall Study
Physician Decision
|
1
|
0
|
|
Overall Study
Subject or parent/guardian request
|
0
|
6
|
|
Overall Study
Adverse Event
|
1
|
4
|
|
Overall Study
Lost to Follow-up
|
3
|
2
|
|
Overall Study
Other (reason not defined)
|
4
|
4
|
Baseline Characteristics
A Pivotal Efficacy Trial to Evaluate HLD200 in Children With ADHD in a Naturalistic Setting
Baseline characteristics by cohort
| Measure |
HLD200 (Methylphenidate)
n=81 Participants
At the start of the Randomized Placebo-controlled Test Phase (Visit 2), subjects were randomized to receive either HLD200 or placebo. Subjects instructed to begin dosing at 40mg each evening (8:00 pm ±30 minutes) for 1 week, with scheduled titration, as medically indicated and tolerated, over the subsequent 2 weeks to 60 mg (Visit 3) and 80 mg (Visit 4) and/or a dose not to exceed 3.7 mg/kg (based on the subject's most recently assessed weight). Following dose escalation above 40 mg (i.e., after Visit 3), subjects were permitted to reduce the dose by 1 step (i.e., from 60 to 40 mg or from 80 to 60 mg) if necessary for safety or tolerability. Subjects who were unable to tolerate a dose of at least 40 mg during the final (third) week of treatment, from Visit 4 to 5, were discontinued. Subjects were also permitted to adjust the timing of the evening dosing at Visits 3 and 4 in increments of 30 to 60 minutes/week to achieve optimal morning control of observed ADHD symptoms; however, the dose was not to be taken any later than 9:30 pm or any earlier than 6:30 pm, regardless of the ±30-minute dosing window.
|
Placebo
n=80 Participants
At the start of the randomized placebo-controlled Test Phase (Visit 2), subjects were randomized to receive either HLD200 or placebo. Placebo capsules were colour and weight matched to the active HLD200 capsules.
Subjects instructed to begin dosing at 40mg each evening (8:00 pm ±30 minutes) for 1 week, with scheduled titration, as medically indicated and tolerated, over the subsequent 2 weeks to 60 mg (Visit 3) and 80 mg (Visit 4) and/or a dose not to exceed 3.7 mg/kg (based on the subject's most recently assessed weight). Following dose escalation above 40 mg (i.e., after Visit 3), subjects were permitted to reduce the dose by 1 step (i.e., from 60 to 40 mg or from 80 to 60 mg) if necessary for safety or tolerability. Subjects who were unable to tolerate a dose of at least 40 mg during the final (third) week of treatment, from Visit 4 to 5, were discontinued. Subjects were also permitted to adjust the timing of the evening dosing at Visits 3 and 4 in increments of 30 to 60 minutes/week to achieve optimal morning control of observed ADHD symptoms; however, the dose was not to be taken any later than 9:30 pm or any earlier than 6:30 pm, regardless of the ±30-minute dosing window.
|
Total
n=161 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
9.6 Years
STANDARD_DEVIATION 1.79 • n=5 Participants
|
9.0 Years
STANDARD_DEVIATION 1.73 • n=7 Participants
|
9.3 Years
STANDARD_DEVIATION 1.79 • n=5 Participants
|
|
Sex: Female, Male
Female
|
26 Participants
n=5 Participants
|
22 Participants
n=7 Participants
|
48 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
55 Participants
n=5 Participants
|
58 Participants
n=7 Participants
|
113 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Last week of 3-week treatment period assessed at Visit 5.Population: Intent-to-Treat
The ADHD-RS-IV was developed to measure the behaviors of children with ADHD (DuPaul et al., 1998). The scale consists of 18 items designed to reflect current symptomatology of ADHD. Each item is scored in a range from 0 (reflecting no symptoms or a frequency of never or rarely) to 3 (reflecting severe symptoms or a frequency of almost always), with a range of total scores ranging from 0 to 54. In this study, a site clinican (required to be an MD, PhD, DO, licensed social worker, or any trained mental health professional approved by the sponsor) completed ADHD-RS-IV assessments at each visit using a structured interview format.
Outcome measures
| Measure |
HLD200 (Methylphenidate)
n=78 Participants
|
Placebo
n=67 Participants
|
|---|---|---|
|
Attention Deficit Hyperactivity Disorder Rating Scale Based on DSM-IV Criteria (ADHD-RS-IV) Total Score.
|
24.1 ADHD-RS-IV total score
Standard Error 1.5
|
31.2 ADHD-RS-IV total score
Standard Error 1.6
|
SECONDARY outcome
Timeframe: Last week of 3-week treatment period assessed at Visit 5.Population: Intent-to-Treat
The BSFQ was developed as a hybrid measure completed by a clinician or parent/legal guardian to assess commonly reported areas of morning dysfunction - both behaviors and functions associated with the post-waking, early morning period (from approximately 6:00 am to 9:00 am) - in children and adolescents with ADHD (Wilens et al., 2010; Wilens et al., 2013). Symptom severity and functional impairment were rated from 0 (none) to 3 (severe - different from peers all days, all settings) with total scores ranging from 0 to 60. Ratings were completed by a site clinician (MD, PhD, DO, licensed social worker, or trained mental health professional approved by the sponsor) at Visits 2 through 5 using a structured interview format.
Outcome measures
| Measure |
HLD200 (Methylphenidate)
n=78 Participants
|
Placebo
n=67 Participants
|
|---|---|---|
|
Before School Functioning Questionnaire (BSFQ) Total Score
|
18.7 BSFQ total score
Standard Error 1.63
|
28.4 BSFQ total score
Standard Error 1.73
|
Adverse Events
HLD200 (Methylphenidate)
Serious events: 0 serious events
Other events: 27 other events
Deaths: 0 deaths
Placebo
Serious events: 0 serious events
Other events: 24 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
HLD200 (Methylphenidate)
n=81 participants at risk
|
Placebo
n=80 participants at risk
|
|---|---|---|
|
Psychiatric disorders
Any Insomnia
|
33.3%
27/81 • Treatment emergent adverse events were collected from the start of study treatment up to the safety follow-up assessment (35 days)
Assessment of adverse events by study staff occurred at every study visit and were recorded based on spontaneous reports 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 assess sleep disturbance (including sleep onset, quality and quantity), rather than obtained from spontaneous reporting.
|
8.8%
7/80 • Treatment emergent adverse events were collected from the start of study treatment up to the safety follow-up assessment (35 days)
Assessment of adverse events by study staff occurred at every study visit and were recorded based on spontaneous reports 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 assess sleep disturbance (including sleep onset, quality and quantity), rather than obtained from spontaneous reporting.
|
|
Psychiatric disorders
Affect lability/mood swings
|
6.2%
5/81 • Treatment emergent adverse events were collected from the start of study treatment up to the safety follow-up assessment (35 days)
Assessment of adverse events by study staff occurred at every study visit and were recorded based on spontaneous reports 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 assess sleep disturbance (including sleep onset, quality and quantity), rather than obtained from spontaneous reporting.
|
1.2%
1/80 • Treatment emergent adverse events were collected from the start of study treatment up to the safety follow-up assessment (35 days)
Assessment of adverse events by study staff occurred at every study visit and were recorded based on spontaneous reports 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 assess sleep disturbance (including sleep onset, quality and quantity), rather than obtained from spontaneous reporting.
|
|
Metabolism and nutrition disorders
Decreased appetite
|
18.5%
15/81 • Treatment emergent adverse events were collected from the start of study treatment up to the safety follow-up assessment (35 days)
Assessment of adverse events by study staff occurred at every study visit and were recorded based on spontaneous reports 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 assess sleep disturbance (including sleep onset, quality and quantity), rather than obtained from spontaneous reporting.
|
3.8%
3/80 • Treatment emergent adverse events were collected from the start of study treatment up to the safety follow-up assessment (35 days)
Assessment of adverse events by study staff occurred at every study visit and were recorded based on spontaneous reports 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 assess sleep disturbance (including sleep onset, quality and quantity), rather than obtained from spontaneous reporting.
|
|
Nervous system disorders
Headache
|
9.9%
8/81 • Treatment emergent adverse events were collected from the start of study treatment up to the safety follow-up assessment (35 days)
Assessment of adverse events by study staff occurred at every study visit and were recorded based on spontaneous reports 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 assess sleep disturbance (including sleep onset, quality and quantity), rather than obtained from spontaneous reporting.
|
5.0%
4/80 • Treatment emergent adverse events were collected from the start of study treatment up to the safety follow-up assessment (35 days)
Assessment of adverse events by study staff occurred at every study visit and were recorded based on spontaneous reports 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 assess sleep disturbance (including sleep onset, quality and quantity), rather than obtained from spontaneous reporting.
|
|
Nervous system disorders
Psychomotor hyperactivity
|
4.9%
4/81 • Treatment emergent adverse events were collected from the start of study treatment up to the safety follow-up assessment (35 days)
Assessment of adverse events by study staff occurred at every study visit and were recorded based on spontaneous reports 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 assess sleep disturbance (including sleep onset, quality and quantity), rather than obtained from spontaneous reporting.
|
1.2%
1/80 • Treatment emergent adverse events were collected from the start of study treatment up to the safety follow-up assessment (35 days)
Assessment of adverse events by study staff occurred at every study visit and were recorded based on spontaneous reports 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 assess sleep disturbance (including sleep onset, quality and quantity), rather than obtained from spontaneous reporting.
|
|
Gastrointestinal disorders
Vomiting
|
8.6%
7/81 • Treatment emergent adverse events were collected from the start of study treatment up to the safety follow-up assessment (35 days)
Assessment of adverse events by study staff occurred at every study visit and were recorded based on spontaneous reports 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 assess sleep disturbance (including sleep onset, quality and quantity), rather than obtained from spontaneous reporting.
|
0.00%
0/80 • Treatment emergent adverse events were collected from the start of study treatment up to the safety follow-up assessment (35 days)
Assessment of adverse events by study staff occurred at every study visit and were recorded based on spontaneous reports 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 assess sleep disturbance (including sleep onset, quality and quantity), rather than obtained from spontaneous reporting.
|
|
Gastrointestinal disorders
Nausea
|
6.2%
5/81 • Treatment emergent adverse events were collected from the start of study treatment up to the safety follow-up assessment (35 days)
Assessment of adverse events by study staff occurred at every study visit and were recorded based on spontaneous reports 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 assess sleep disturbance (including sleep onset, quality and quantity), rather than obtained from spontaneous reporting.
|
0.00%
0/80 • Treatment emergent adverse events were collected from the start of study treatment up to the safety follow-up assessment (35 days)
Assessment of adverse events by study staff occurred at every study visit and were recorded based on spontaneous reports 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 assess sleep disturbance (including sleep onset, quality and quantity), rather than obtained from spontaneous reporting.
|
|
Psychiatric disorders
Sleep disorder
|
2.5%
2/81 • Treatment emergent adverse events were collected from the start of study treatment up to the safety follow-up assessment (35 days)
Assessment of adverse events by study staff occurred at every study visit and were recorded based on spontaneous reports 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 assess sleep disturbance (including sleep onset, quality and quantity), rather than obtained from spontaneous reporting.
|
5.0%
4/80 • Treatment emergent adverse events were collected from the start of study treatment up to the safety follow-up assessment (35 days)
Assessment of adverse events by study staff occurred at every study visit and were recorded based on spontaneous reports 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 assess sleep disturbance (including sleep onset, quality and quantity), rather than obtained from spontaneous reporting.
|
|
Infections and infestations
Upper respiratory tract infection
|
1.2%
1/81 • Treatment emergent adverse events were collected from the start of study treatment up to the safety follow-up assessment (35 days)
Assessment of adverse events by study staff occurred at every study visit and were recorded based on spontaneous reports 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 assess sleep disturbance (including sleep onset, quality and quantity), rather than obtained from spontaneous reporting.
|
5.0%
4/80 • Treatment emergent adverse events were collected from the start of study treatment up to the safety follow-up assessment (35 days)
Assessment of adverse events by study staff occurred at every study visit and were recorded based on spontaneous reports 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 assess sleep disturbance (including sleep onset, quality and quantity), rather than obtained from spontaneous reporting.
|
Additional Information
Chief Scientific Officer
Ironshore Pharmaceuticals and Development, Inc.
Phone: 13457498174
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place