A Classroom Study to Assess the Time of Onset of Vyvanse (Lisdexamfetamine Dimesylate) in Pediatric Subjects Aged 6-12 With Attention Deficit/Hyperactivity Disorder (ADHD)

• Sponsor: Shire (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00500149
• Collaborator: (none)
• Enrollment: 129
• Locations: 9
• Arms: 2
• Actual Duration (Months): 5.7
• Patients Per Site: 14.3
• Patients Per Site Per Month: 2.5

Study Details

Study Description

Brief Summary

The primary objective of this study is to assess the time of onset of Vyvanse compared to placebo, in the analog classroom as measured by the Swanson, Kotkin, Agler, M. Flynn and Pelham (SKAMP) deportment scale in children (aged 6-12) diagnosed with Attention-Deficit/Hyperactivity Disorder (ADHD).

Condition or Disease	Intervention/Treatment	Phase
ADHD	Drug: Vyvanse (lisdexamfetamine dimesylate); Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 129 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase IIIb, Randomized, Double-Blind, Multi-Center, Placebo- Controlled, Dose-Optimization, Cross-Over, Analog Classroom Study to Assess the Time of Onset of Vyvanse (Lisdexamfetamine Dimesylate) in Pediatric Subjects Aged 6-12 With Attention-Deficit/Hyperactivity Disorder
• Actual Study Start Date: Jun 13, 2007
• Actual Primary Completion Date: Dec 5, 2007
• Actual Study Completion Date: Dec 5, 2007

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1	Drug: Vyvanse (lisdexamfetamine dimesylate); Following completion of the open-label dose optimization period and successful titration to an optimal dose of Vyvanse™, subjects will take their optimized dose of Vyvanse™ (30, 50 or 70 mg/day).
Placebo Comparator: 2	Drug: Placebo; Placebo

Outcome Measures

Primary Outcome Measures

1. Onset of Effect of Vyvanse [Evaluations were conducted at 1.5, 2.5, 5.0, 7.5, 10.0, 12.0, and 13.0 hours post-dose.]

   The onset of effect will be defined as the first assessment time showing statistical significance between Vyvanse and placebo as measured by the Swanson, Kotkin, Agler, M-Flynn, and Pelham (SKAMP) Deportment scale. The degree of impairment is rated from 0 (normal) to 6 (maximal).

Secondary Outcome Measures

1. Duration of Effect of Vyvanse [Evaluations were conducted at 1.5, 2.5, 5.0, 7.5, 10.0, 12.0, and 13.0 hours post-dose.]

   Duration of effect will be defined as the first time point at which there is a non-significant difference between Vyvanse and placebo after a time point at which there is a significant difference between the two treatment groups as measured by SKAMP Deportment Scores. The degree of impairment is rated from 0 (normal) to 6 (maximal).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 6 Years to 12 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Subject is a male or female aged 6-12 years inclusive at the time of consent.

2. Females of Child-bearing Potential (FOCP) must have a negative serum beta Human Chorionic Gonadotropin (HCG) pregnancy test at Screening and a negative urine pregnancy test at Baseline and agree to comply with any applicable contraceptive requirements of the protocol.

3. Primary diagnosis of ADHD: combined sub-type or predominantly hyperactive impulsive sub-type based on a detailed psychiatric evaluation.

4. Subject has a baseline ADHD-RS-IV score ≥ 28.

5. Intelligent Quotient (IQ) score of 80 or above on the Kaufman Brief Intelligence Test (KBIT).

6. Subject must be able to complete at least the Basic Test of the PERMP assessment.

Exclusion Criteria:

1. Subject has a current, controlled (requiring a restricted medication) or uncontrolled, comorbid psychiatric diagnosis with significant symptoms such as Post Traumatic Stress Disorder (PTSD), psychosis, bipolar illness, pervasive developmental disorder, severe obsessive compulsive disorder, severe depressive or severe anxiety disorder

2. Subject has Conduct Disorder.

3. Subject has a documented allergy, hypersensitivity or intolerance to amphetamines.

4. Subject has failed to respond to one or more adequate courses (dose and duration) of amphetamine therapy.

5. The subject has a recent history (within the past 6 months) of suspected substance abuse or dependence disorder (excluding nicotine) in accordance with DSM-IV-TR criteria.

6. Subject weighs less than 50 pounds (22.7kg).

7. Subject is significantly overweight

8. Subject had a history of seizures during the last two years (exclusive of febrile seizures), a tic disorder, a current diagnosis and/or family history of Tourette's Disorder.

9. Subject has any reported history of abnormal thyroid function.

10. Subject has taken another investigational drug or taken part in a clinical trial within the last 30 days prior to Screening.

11. Subject has a known history of structural cardiac abnormality, as well as any other condition(s) that may affect cardiac performance.

12. Subject has a concurrent chronic or acute illness (such as severe allergic rhinitis or an infectious process requiring antibiotics), disability, or other condition that might confound the results of safety assessments

13. Subject is taking other medications that have central nervous system (CNS) effects or affect performance, such as sedating antihistamines and decongestant sympathomimetics (bronchodilators are not exclusionary).

14. The female subject is pregnant or lactating.

15. Subject is well controlled on their current ADHD medication with acceptable tolerability.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Clinical Study Centers, LLC	Little Rock	Arkansas	United States
2	Univ. of CA, Irvine Child Development Center	Irvine	California	United States
3	Shire Clinical Research Site	Wildomar	California	United States
4	Vince and Associates Clinical Research	Overland Park	Kansas	United States
5	Center for Psychiatry & Behavioral Medicine Inc	Las Vegas	Nevada	United States
6	Duke Child & Family Study Center	Durham	North Carolina	United States
7	Duke University Medical Center	Durham	North Carolina	United States
8	Shire Clinical Research Site	Houston	Texas	United States
9	Shire Clinical Research Site	Lubbock	Texas	United States

Sponsors and Collaborators

• Shire

Investigators

• Study Director: Study Director, Takeda

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• FDA Recall Information
• FDA-approved label

Publications

None provided.

• Responsible Party: Shire
• ClinicalTrials.gov Identifier: NCT00500149
• Other Study ID Numbers: SPD489-311
• First Posted: Jul 12, 2007
• Last Update Posted: Jun 14, 2021
• Last Verified: Jun 1, 2021

• Additional relevant MeSH terms: Attention Deficit Disorder with Hyperactivity; Lisdexamfetamine Dimesylate

Study Results

Participant Flow

Recruitment Details	129 subjects were enrolled for dose optimization phase, 12 discontinued, and 117 were randomized to the cross-over phase.
Pre-assignment Detail	The study consisted of an open-label dose-optimization phase (4 weeks), followed by a randomized, placebo-controlled, 2-way crossover phase (1 week each).

Arm/Group Title	Vyvanse First	Placebo First
Arm/Group Description	Vyvanse was dosed orally once daily at either 30, 50 or 70 mg (depending on the outcome of the dose optimization phase)for 1 week in the first intervention and matching placebo was given orally once daily for 1 week in the second intervention	Matching placebo was given orally once daily for 1 week in the first intervention and Vyvanse was dosed orally once daily at either 30, 50 or 70 mg (depending on the outcome of the dose optimization phase)for 1 week in the second intervention
Period Title: Enrolled (Dose-optimization Phase)
STARTED	129	0
COMPLETED	117	0
NOT COMPLETED	12	0
Period Title: Enrolled (Dose-optimization Phase)
STARTED	58	59
COMPLETED	56	57
NOT COMPLETED	2	2
Period Title: Enrolled (Dose-optimization Phase)
STARTED	56	57
COMPLETED	54	57
NOT COMPLETED	2	0

Baseline Characteristics

Arm/Group Title	Entire Study Population
Arm/Group Description
Overall Participants	129
Age (Count of Participants)
<=18 years	129 100%
Between 18 and 65 years	0 0%
>=65 years	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	10.1 (1.5)
Sex: Female, Male (Count of Participants)
Female	31 24%
Male	98 76%
Region of Enrollment (Count of Participants)
United States	129 100%

Outcome Measures

1. Primary Outcome

Title	Onset of Effect of Vyvanse
Description	The onset of effect will be defined as the first assessment time showing statistical significance between Vyvanse and placebo as measured by the Swanson, Kotkin, Agler, M-Flynn, and Pelham (SKAMP) Deportment scale. The degree of impairment is rated from 0 (normal) to 6 (maximal).
Time Frame	Evaluations were conducted at 1.5, 2.5, 5.0, 7.5, 10.0, 12.0, and 13.0 hours post-dose.

Outcome Measure Data

Analysis Population Description

Analysis on the intention-to-treat (ITT) population.

Arm/Group Title	Vyvanse	Placebo
Arm/Group Description	Lisdexamfetamine dimesylate (LDX)	Matching placebo
Measure Participants	113	113
1.5 hours	0.70 (0.09)	1.14 (0.09)
2.5 hours	0.45 (0.09)	1.42 (0.09)
5 hours	0.44 (0.10)	1.60 (0.10)
7.5 hours	0.54 (0.09)	1.56 (0.09)
10 hours	0.60 (0.09)	1.43 (0.09)
12 hours	0.90 (0.10)	1.41 (0.10)
13 hours	1.05 (0.10)	1.31 (0.10)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Vyvanse, Placebo
	Comments	Statistical analysis of SKAMP scores at 1.5 hours post-dose
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	The primary efficacy variable will be onset of effect, which will be determined from the results of inferential analyses across multiple time points. No adjustment will be made to the levels of significance as a result of the multiple comparisons.
	Method	ANCOVA
	Comments	Using a linear mixed model that includes sequence, period, and treatment group as fixed effects and subject-within-sequence as a random effect.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Vyvanse, Placebo
	Comments	Statistical analysis of SKAMP scores at 2.5 hours post-dose
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	The primary efficacy variable will be onset of effect, which will be determined from the results of inferential analyses across multiple time points. No adjustment will be made to the levels of significance as a result of the multiple comparisons.
	Method	ANCOVA
	Comments	Using a linear mixed model that includes sequence, period, and treatment group as fixed effects and subject-within-sequence as a random effect.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Vyvanse, Placebo
	Comments	Statistical analysis of SKAMP scores at 5.0 hours post-dose
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	The primary efficacy variable will be onset of effect, which will be determined from the results of inferential analyses across multiple time points. No adjustment will be made to the levels of significance as a result of the multiple comparisons.
	Method	ANCOVA
	Comments	Using a linear mixed model that includes sequence, period, and treatment group as fixed effects and subject-within-sequence as a random effect.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Vyvanse, Placebo
	Comments	Statistical analysis of SKAMP scores at 7.5 hours post-dose
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	The primary efficacy variable will be onset of effect, which will be determined from the results of inferential analyses across multiple time points. No adjustment will be made to the levels of significance as a result of the multiple comparisons.
	Method	ANCOVA
	Comments	Using a linear mixed model that includes sequence, period, and treatment group as fixed effects and subject-within-sequence as a random effect.

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Vyvanse, Placebo
	Comments	Statistical analysis of SKAMP scores at 10.0 hours post-dose
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	The primary efficacy variable will be onset of effect, which will be determined from the results of inferential analyses across multiple time points. No adjustment will be made to the levels of significance as a result of the multiple comparisons.
	Method	ANCOVA
	Comments	Using a linear mixed model that includes sequence, period, and treatment group as fixed effects and subject-within-sequence as a random effect.

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Vyvanse, Placebo
	Comments	Statistical analysis of SKAMP scores at 12.0 hours post-dose
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	The primary efficacy variable will be onset of effect, which will be determined from the results of inferential analyses across multiple time points. No adjustment will be made to the levels of significance as a result of the multiple comparisons.
	Method	ANCOVA
	Comments	Using a linear mixed model that includes sequence, period, and treatment group as fixed effects and subject-within-sequence as a random effect.

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Vyvanse, Placebo
	Comments	Statistical analysis of SKAMP scores at 13.0 hours post-dose
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	The primary efficacy variable will be onset of effect, which will be determined from the results of inferential analyses across multiple time points. No adjustment will be made to the levels of significance as a result of the multiple comparisons.
	Method	ANCOVA
	Comments	Using a linear mixed model that includes sequence, period, and treatment group as fixed effects and subject-within-sequence as a random effect.

2. Secondary Outcome

Title	Duration of Effect of Vyvanse
Description	Duration of effect will be defined as the first time point at which there is a non-significant difference between Vyvanse and placebo after a time point at which there is a significant difference between the two treatment groups as measured by SKAMP Deportment Scores. The degree of impairment is rated from 0 (normal) to 6 (maximal).
Time Frame	Evaluations were conducted at 1.5, 2.5, 5.0, 7.5, 10.0, 12.0, and 13.0 hours post-dose.

Outcome Measure Data

Analysis Population Description

Analysis on intention-to-treat (ITT) population.

Arm/Group Title	Vyvanse	Placebo
Arm/Group Description	Lisdexamfetamine dimesylate (LDX)	Matching placebo
Measure Participants	113	113
1.5 hours	0.70 (0.09)	1.14 (0.09)
2.5 hours	0.45 (0.09)	1.42 (0.09)
5 hours	0.44 (0.10)	1.60 (0.10)
7.5 hours	0.54 (0.09)	1.56 (0.09)
10 hours	0.60 (0.09)	1.43 (0.09)
12 hours	0.90 (0.10)	1.41 (0.10)
13 hours	1.05 (0.10)	1.31 (0.10)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Vyvanse, Placebo
	Comments	Statistical analysis of SKAMP scores at 1.5 hours post-dose
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments
	Method	ANCOVA
	Comments	Using a linear mixed model that includes sequence, period, and treatment group as fixed effects and subject-within-sequence as a random effect.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Vyvanse, Placebo
	Comments	Statistical analysis of SKAMP scores at 2.5 hours post-dose
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments	Using a linear mixed model that includes sequence, period, and treatment group as fixed effects and subject-within-sequence as a random effect.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Vyvanse, Placebo
	Comments	Statistical analysis of SKAMP scores at 5.0 hours post-dose
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments	Using a linear mixed model that includes sequence, period, and treatment group as fixed effects and subject-within-sequence as a random effect.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Vyvanse, Placebo
	Comments	Statistical analysis of SKAMP scores at 7.5 hours post-dose
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments	Using a linear mixed model that includes sequence, period, and treatment group as fixed effects and subject-within-sequence as a random effect.

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Vyvanse, Placebo
	Comments	Statistical analysis of SKAMP scores at 10.0 hours post-dose
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments	Using a linear mixed model that includes sequence, period, and treatment group as fixed effects and subject-within-sequence as a random effect.

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Vyvanse, Placebo
	Comments	Statistical analysis of SKAMP scores at 12.0 hours post-dose
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments	Using a linear mixed model that includes sequence, period, and treatment group as fixed effects and subject-within-sequence as a random effect.

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Vyvanse, Placebo
	Comments	Statistical analysis of SKAMP scores at 13.0 hours post-dose
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments	Using a linear mixed model that includes sequence, period, and treatment group as fixed effects and subject-within-sequence as a random effect.

Adverse Events

Adverse Event Reporting Description	The Randomized Population is defined as all subjects who are randomized and received at least one dose of study medication during the Cross-Over Phase of the study.
Arm/Group Title	Vyvanse		Placebo
Arm/Group Description
All Cause Mortality
	Vyvanse		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Vyvanse		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/115 (0%)		0/115 (0%)
Other (Not Including Serious) Adverse Events
	Vyvanse		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	13/115 (11.3%)		3/115 (2.6%)
Metabolism and nutrition disorders
Decreased Appetite	7/115 (6.1%)		1/115 (0.9%)
Nervous system disorders
Headache	6/115 (5.2%)		2/115 (1.7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

If a multicenter publication is not submitted within twelve (12) months after conclusion, abandonment or termination of the Study at all sites, or after SPONSOR confirms there shall be no multicenter Study publication, the INSTITUTION and/or such PRINCIPAL INVESTIGATOR may publish the results from the INSTITUTION site individually.