Trial Outcomes & Findings for Time Course of Response to Methylphenidate HCl ER Capsules in Children 6 to 12 Years With ADHD in Classroom Setting (NCT NCT01269463)

Last Updated: 2022-12-13

Results Overview

Comparison of Swanson, Kotkin, Alger, M-Flynn and Pelham (SKAMP) Combined, Attention, and Deportment Scales following drug dose versus placebo. The SKAMP scale is a validated rating scale that assesses behavioral symptoms of ADHD in a classroom setting using a 7-point impairment scale (0 = none through 6 = maximal impairment). The SKAMP total score comprises 13 items, with individual total scores ranging from 0 to 78 (lower scores mean better outcome). The SKAMP-D subscale evaluates deportment, including interacting with other children, interacting with adults, remaining quiet according to classroom rules, and staying seated according to classroom rules. The SKAMP-A subscale is a measure of attention and evaluates getting started on assignments, sticking with tasks, attending to an activity, and making activity transitions. The SKAMP quality of work subscale includes 3 items: completing assigned work, performing work accurately, and being careful and neat while writing or drawing.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

26 participants

Primary outcome timeframe

Average over all post-dose time points (1.0, 2.0, 3.0, 4.5, 6.0, 7.5, 9.0, 10.5, and 12 hours)

Results posted on

2022-12-13

Participant Flow

Study Start Date: 19 January 2011 (First subject screened) Double-Blind Phase Completion Date: 18 June 2011 (Last subject visit in Double-Blind phase) Compassionate Use Phase Completion Date: 13 March 2013 (Last subject visit in Compassionate Use phase)

Approximately 27 otherwise healthy pediatric subjects (aged 6 to 12) diagnosed with ADHD by DSM-IV-TR™ criteria were planned to participate in the study so that approximately 24 subjects would complete the Double-Blind phase. Subjects were to be randomized into 2 sequences with approximately 12 subjects in each sequence

Participant milestones

Participant milestones
Measure	Open Label Phase Then 2-week Double Blind Phase (Placebo First, Then Methylphenidate HCl ER Capsule) Open Label Phase: Subjects were dose optimized over a 2 to 4 week period. All subjects began at an initial Methylphenidate hydrochloride extended release capsules dose of 15 mg and were titrated weekly to an optimal dose using strengths of 15, 20, 30, up to the maximum of 40 mg/day. Double Blind Phase (2-weeks): Placebo: Capsule without active drug for 1 week Methylphenidate HCl ER Capsule: An optimized dose of Methylphenidate hydrochloride extended release capsules (15, 20, 30, or 40 mg) for 1 week Dosed once daily in the morning	Open Label Phase Then 2-week Double Blind Phase (Methylphenidate HCl ER Capsule First, Then Placebo) Open Label Phase: Subjects were dose optimized over a 2 to 4 week period. All subjects began at an initial Methylphenidate hydrochloride extended release capsules dose of 15 mg and were titrated weekly to an optimal dose using strengths of 15, 20, 30, up to the maximum of 40 mg/day. Double Blind Phase (2-weeks): Methylphenidate HCl ER Capsule: An optimized dose of Methylphenidate hydrochloride extended release capsules (15, 20, 30, or 40 mg) for 1 week Placebo: Capsule without active drug for 1 week Dosed once daily in the morning
First Intervention STARTED	13	13
First Intervention COMPLETED	11	11
First Intervention NOT COMPLETED	2	2
Second Intervention STARTED	11	11
Second Intervention COMPLETED	11	11
Second Intervention NOT COMPLETED	0	0
Third Intervention STARTED	11	11
Third Intervention COMPLETED	11	11
Third Intervention NOT COMPLETED	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Open Label Phase Then 2-week Double Blind Phase (Placebo First, Then Methylphenidate HCl ER Capsule) Open Label Phase: Subjects were dose optimized over a 2 to 4 week period. All subjects began at an initial Methylphenidate hydrochloride extended release capsules dose of 15 mg and were titrated weekly to an optimal dose using strengths of 15, 20, 30, up to the maximum of 40 mg/day. Double Blind Phase (2-weeks): Placebo: Capsule without active drug for 1 week Methylphenidate HCl ER Capsule: An optimized dose of Methylphenidate hydrochloride extended release capsules (15, 20, 30, or 40 mg) for 1 week Dosed once daily in the morning	Open Label Phase Then 2-week Double Blind Phase (Methylphenidate HCl ER Capsule First, Then Placebo) Open Label Phase: Subjects were dose optimized over a 2 to 4 week period. All subjects began at an initial Methylphenidate hydrochloride extended release capsules dose of 15 mg and were titrated weekly to an optimal dose using strengths of 15, 20, 30, up to the maximum of 40 mg/day. Double Blind Phase (2-weeks): Methylphenidate HCl ER Capsule: An optimized dose of Methylphenidate hydrochloride extended release capsules (15, 20, 30, or 40 mg) for 1 week Placebo: Capsule without active drug for 1 week Dosed once daily in the morning
First Intervention Withdrawal by Subject	1	0
First Intervention Adverse Event	1	0
First Intervention Lack of Efficacy	0	1
First Intervention Physician Decision	0	1

Baseline Characteristics

Time Course of Response to Methylphenidate HCl ER Capsules in Children 6 to 12 Years With ADHD in Classroom Setting

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Safety Population n=26 Participants All subjects entering open label dose optimization phase (Safety Population) and received at least one dose of study drug
Age, Categorical <=18 years	26 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Age, Continuous	8.7 Years STANDARD_DEVIATION 1.89 • n=5 Participants
Sex: Female, Male Female	12 Participants n=5 Participants
Sex: Female, Male Male	14 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	6 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	20 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	3 Participants n=5 Participants
Race (NIH/OMB) White	21 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants
Region of Enrollment United States	26 participants n=5 Participants

PRIMARY outcome

Timeframe: Average over all post-dose time points (1.0, 2.0, 3.0, 4.5, 6.0, 7.5, 9.0, 10.5, and 12 hours)

Population: 20 subjects were in the evaluable population, defined as subjects who completed SKAMP assessments for all the study time points on study days 35 and 42, and who received the scheduled treatment in both periods during the double-blind phase. Two (2) subjects were excluded from the evaluable population due to protocol deviations.

Outcome measures

Outcome measures
Measure	Methylphenidate HCl ER Capsules n=20 Participants Methylphenidate hydrochloride extended release capsules Methylphenidate Hydrochloride Extended Release Capsules: Methylphenidate Hydrochloride Extended Release Capsules to be dosed once daily	Capsule Without Active Drug n=20 Participants Double blind crossover assignment of the placebo comparator. Placebo: Capsule without active drug
Comparison Following Treatment Between Drug and Placebo Using Evaluation by SKAMP Combined, Attention, and Deportment Scales	1.46 units on a scale Standard Deviation 0.52	2.03 units on a scale Standard Deviation 0.92

SECONDARY outcome

Timeframe: 12 hours post-dose

Population: 20 subjects were in the evaluable population, defined as subjects who completed PERMP assessments for all the study time points on study days 35 and 42, and who received the scheduled treatment in both periods during the double-blind phase. Two (2) subjects were excluded from the evaluable population due to protocol deviations.

Comparison of PERMP measurement scores following drug dose versus placebo (math-correct). The Permanent Product Measure of Performance (PERMP), is a 5-page test consisting of 80 math problems per page (total of 400 problems) and evaluates effortful performance in the classroom as a measure of efficacy. Participants are instructed to work at their seats and to complete as many problems as possible in 10 minutes. The appropriate level of difficulty for each student was determined previously based on results of a math pretest administered at screening. Performance was evaluated using PERMP-A) and PERMP-C scores. Measures obtained from these tests include the number of problems attempted (Math-Attempted; PERMP-A) and the number of problems answered correctly (Math-Correct; PERMP-C). Higher scores are better. The responses are reviewed by comparing them to an answer template, and they are triple-checked for accuracy

Outcome measures

Outcome measures
Measure	Methylphenidate HCl ER Capsules n=20 Participants Methylphenidate hydrochloride extended release capsules Methylphenidate Hydrochloride Extended Release Capsules: Methylphenidate Hydrochloride Extended Release Capsules to be dosed once daily	Capsule Without Active Drug n=20 Participants Double blind crossover assignment of the placebo comparator. Placebo: Capsule without active drug
Comparison Following Treatment With Drug or Placebo Using PERMP (Permanent Product of Arithmetic) Evaluations PERMP-A	92.85 Number of Problems Standard Deviation 48.01	80.30 Number of Problems Standard Deviation 55.31
Comparison Following Treatment With Drug or Placebo Using PERMP (Permanent Product of Arithmetic) Evaluations PERMP-C	86.85 Number of Problems Standard Deviation 49.29	74.80 Number of Problems Standard Deviation 57.41

Adverse Events

Methylphenidate HCl ER During Open Label Phase

Serious events: 0 serious events

Other events: 23 other events

Deaths: 0 deaths

Methylphenidate HCl ER Capsules During Double Blind Phase

Serious events: 0 serious events

Other events: 7 other events

Deaths: 0 deaths

Capsule Without Active Drug During Double Blind

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Methylphenidate HCl ER During Open Label Phase n=26 participants at risk Open Label Phase (Period 1): Subjects were dose optimized over a 2 to 4 week period. All subjects began at an initial Methylphenidate hydrochloride extended release capsules dose of 15 mg and were titrated weekly to an optimal dose using strengths of 15, 20, 30, up to the maximum of 40 mg/day.	Methylphenidate HCl ER Capsules During Double Blind Phase n=21 participants at risk Double blind crossover assignment of Methylphenidate hydrochloride extended release capsules Double Blind Phase (2-week crossover): patients receiving Methylphenidate hydrochloride extended release capsules (15, 20, 30, or 40 mg) for 1 week either on period 2 or period 3 depending on randomization. Dosed once daily in the morning	Capsule Without Active Drug During Double Blind n=22 participants at risk Double blind crossover assignment of the placebo comparator. Double Blind Phase (2-week crossover): patients receiving Placebo for 1 week either on period 2 or period 3 depending on randomization. Dosed once daily in the morning Placebo: Capsule without active drug
Gastrointestinal disorders Emesis	11.5% 3/26 • 11 weeks	4.8% 1/21 • 11 weeks	0.00% 0/22 • 11 weeks
Gastrointestinal disorders Abdominal pain	11.5% 3/26 • 11 weeks	9.5% 2/21 • 11 weeks	4.5% 1/22 • 11 weeks
General disorders Pyrexia	15.4% 4/26 • 11 weeks	9.5% 2/21 • 11 weeks	0.00% 0/22 • 11 weeks
Infections and infestations Influenza	7.7% 2/26 • 11 weeks	0.00% 0/21 • 11 weeks	0.00% 0/22 • 11 weeks
Infections and infestations Otitis Media	7.7% 2/26 • 11 weeks	0.00% 0/21 • 11 weeks	0.00% 0/22 • 11 weeks
Infections and infestations Respiratory Tract Infection	7.7% 2/26 • 11 weeks	0.00% 0/21 • 11 weeks	0.00% 0/22 • 11 weeks
Infections and infestations Sinusitis	7.7% 2/26 • 11 weeks	0.00% 0/21 • 11 weeks	0.00% 0/22 • 11 weeks
Metabolism and nutrition disorders Decreased Appetite	23.1% 6/26 • 11 weeks	0.00% 0/21 • 11 weeks	0.00% 0/22 • 11 weeks
Nervous system disorders Headache	23.1% 6/26 • 11 weeks	14.3% 3/21 • 11 weeks	0.00% 0/22 • 11 weeks
Nervous system disorders Insomnia	30.8% 8/26 • 11 weeks	0.00% 0/21 • 11 weeks	4.5% 1/22 • 11 weeks
Nervous system disorders Somnolence	7.7% 2/26 • 11 weeks	0.00% 0/21 • 11 weeks	0.00% 0/22 • 11 weeks
Psychiatric disorders Emotional Distress	7.7% 2/26 • 11 weeks	4.8% 1/21 • 11 weeks	0.00% 0/22 • 11 weeks
Psychiatric disorders Irritability	19.2% 5/26 • 11 weeks	0.00% 0/21 • 11 weeks	4.5% 1/22 • 11 weeks
Psychiatric disorders Mood Swings	7.7% 2/26 • 11 weeks	0.00% 0/21 • 11 weeks	0.00% 0/22 • 11 weeks
Respiratory, thoracic and mediastinal disorders Cough	15.4% 4/26 • 11 weeks	0.00% 0/21 • 11 weeks	0.00% 0/22 • 11 weeks
Respiratory, thoracic and mediastinal disorders Nasal Congestion	11.5% 3/26 • 11 weeks	0.00% 0/21 • 11 weeks	0.00% 0/22 • 11 weeks
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	11.5% 3/26 • 11 weeks	0.00% 0/21 • 11 weeks	0.00% 0/22 • 11 weeks
Skin and subcutaneous tissue disorders Rash	7.7% 2/26 • 11 weeks	4.8% 1/21 • 11 weeks	0.00% 0/22 • 11 weeks

Additional Information

Inder Chaudhary, PhD

Rhodes Pharmaceuticals L.P.

Phone: 401-262-9272

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee PI is restricted from using, disclosing, presenting, or publishing trial information without the prior written consent from the Sponsor
Publication restrictions are in place

Restriction type: OTHER