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The time course of response following one dose of a new methylphenidate hydrochloride extended release capsule is studied in children 6-12 years in a simulated laboratory classroom setting. Biphentin methylphenidate hydrochloride extended release capsule has been formulated for daily dosing to provide treatment of a child with Attention deficit hyperactivity disorder (ADHD) for the substantial day.
Biphentin methylphenidate hydrochloride (HCl) extended release (ER) capsules is provided in multiple strengths of 10, 15, 20, 30, 40, 50, and 60 mg to be administered once daily. Once daily dosing is intended to provide treatment for the substantial day.
For current analog classroom study each eligible subject will be optimized at 15, 20, 30, or 40 mg in a timeframe of five weekly periods. In the sixth week each subject will be randomized double-blind to receive either active comparator at the optimized dose or placebo comparator treatment. The first classroom session will be held at the end of the week, when efficacy measurements including Swanson, Kotkin, Agler, M-Flynn, Pelham Rating Scale (SKAMP) and Permanent Product Measure of Performance (PERMP) tests will be administered. At the beginning of the following week, the subjects will be crossed-over to the corresponding active comparator or placebo comparator treatment. The second classroom session will be held at the end of the second double-blind week, when the same efficacy measurements will be administered.
Various safety and tolerability, and quality of life assessments will be conducted.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Open Label Phase Then 2-week Double Blind Phase (Placebo First, Then Methylphenidate HCl ER Capsule) | Experimental | 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) | Experimental | 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 |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Methylphenidate Hydrochloride Extended Release Capsule | Drug | An optimized dose of Methylphenidate Hydrochloride Extended Release Capsules 15, 20, 30 or 40 mg to be dosed once daily |
| Measure | Description | Time Frame |
|---|---|---|
| Comparison Following Treatment Between Drug and Placebo Using Evaluation by SKAMP Combined, Attention, and Deportment Scales | 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. | 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) |
| Measure | Description | Time Frame |
|---|---|---|
| Comparison Following Treatment With Drug or Placebo Using PERMP (Permanent Product of Arithmetic) Evaluations | 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Wei-wei Chang, Ph.D. | NuTec Incorporated | Study Director |
| Sharon B. Wigal, Ph.D. | University of California, Irvine / Child Development Center | Principal Investigator |
| Robert Kupper, Ph.D. | Rhodes Pharmaceuticals, L.P. | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of California, Irvine/Child Development Center | Irvine | California | 92612 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 25470572 | Derived | Wigal SB, Greenhill LL, Nordbrock E, Connor DF, Kollins SH, Adjei A, Childress A, Stehli A, Kupper RJ. A randomized placebo-controlled double-blind study evaluating the time course of response to methylphenidate hydrochloride extended-release capsules in children with attention-deficit/hyperactivity disorder. J Child Adolesc Psychopharmacol. 2014 Dec;24(10):562-9. doi: 10.1089/cap.2014.0100. |
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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
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)
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| ID | Title | Description |
|---|---|---|
| FG000 | 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 |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| First Intervention |
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All subjects entered the Open-Label Dose optimization phase and were titrated until an optimized dose of Methylphenidate hydrochloride Extended Release capsule was achieved. Completing subjects then entered the randomized Double-blind Phase (crossover).
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| Placebo | Drug | Capsule without active drug |
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| 12 hours post-dose |
| FG001 | 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 |
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| NOT COMPLETED |
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| Second Intervention |
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| Third Intervention |
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Subjects enrolled in the open-label dose optimization phase and received at least one dose of study drug; 4 subjects withdrew from the study during this phase
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| ID | Title | Description |
|---|---|---|
| BG000 | Safety Population | All subjects entering open label dose optimization phase (Safety Population) and received at least one dose of study drug |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
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| Age, Continuous | Mean | Standard Deviation | Years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Comparison Following Treatment Between Drug and Placebo Using Evaluation by SKAMP Combined, Attention, and Deportment Scales | 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. | 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. | Posted | Mean | Standard Deviation | units on a scale | 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) |
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| Secondary | Comparison Following Treatment With Drug or Placebo Using PERMP (Permanent Product of Arithmetic) Evaluations | 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 | 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. | Posted | Least Squares Mean | Standard Deviation | Number of Problems | 12 hours post-dose |
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11 weeks
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Methylphenidate HCl ER During Open Label Phase | 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. | 0 | 26 | 23 | 26 | ||
| EG001 | Methylphenidate HCl ER Capsules During Double Blind Phase | 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 | 0 | 21 | 7 | 21 | ||
| EG002 | Capsule Without Active Drug During Double Blind | 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 | 0 | 22 | 3 | 22 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Emesis | Gastrointestinal disorders | Non-systematic Assessment |
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| Abdominal pain | Gastrointestinal disorders | Non-systematic Assessment |
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| Pyrexia | General disorders | Non-systematic Assessment |
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| Influenza | Infections and infestations | Non-systematic Assessment |
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| Otitis Media | Infections and infestations | Non-systematic Assessment |
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| Respiratory Tract Infection | Infections and infestations | Non-systematic Assessment |
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| Sinusitis | Infections and infestations | Non-systematic Assessment |
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| Decreased Appetite | Metabolism and nutrition disorders | Non-systematic Assessment |
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| Headache | Nervous system disorders | Non-systematic Assessment |
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| Insomnia | Nervous system disorders | Non-systematic Assessment |
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| Somnolence | Nervous system disorders | Non-systematic Assessment |
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| Emotional Distress | Psychiatric disorders | Non-systematic Assessment |
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| Irritability | Psychiatric disorders | Non-systematic Assessment |
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| Mood Swings | Psychiatric disorders | Non-systematic Assessment |
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| Cough | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
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| Nasal Congestion | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
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| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
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| Rash | Skin and subcutaneous tissue disorders | Non-systematic Assessment |
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PI is restricted from using, disclosing, presenting, or publishing trial information without the prior written consent from the Sponsor
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Inder Chaudhary, PhD | Rhodes Pharmaceuticals L.P. | 401-262-9272 | inder.chaudhary@rhodespharma.com |
| ID | Term |
|---|---|
| D001289 | Attention Deficit Disorder with Hyperactivity |
| D013035 | Spasm |
| D007175 | Impulsive Behavior |
| ID | Term |
|---|---|
| D019958 | Attention Deficit and Disruptive Behavior Disorders |
| D065886 | Neurodevelopmental Disorders |
| D001523 | Mental Disorders |
| D020879 | Neuromuscular Manifestations |
| D009461 | Neurologic Manifestations |
| D009422 | Nervous System Diseases |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D001519 | Behavior |
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| Unknown or Not Reported |
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| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
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| More than one race |
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| Unknown or Not Reported |
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| OG001 | Capsule Without Active Drug | Double blind crossover assignment of the placebo comparator. Placebo: Capsule without active drug |
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