Dose-Optimization Study Evaluating the Efficacy, Safety and Tolerability of Vyvanse (Lisdexamfetamine Dimesylate) in Children Aged 6-12 Diagnosed With ADHD

• Sponsor: Shire (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00500071
• Collaborator: (none)
• Enrollment: 318
• Locations: 46
• Arm: 1
• Actual Duration (Months): 6.2
• Patients Per Site: 6.9
• Patients Per Site Per Month: 1.1

Study Details

Study Description

Brief Summary

Assess the efficacy & tolerability of Vyvanse when children aged 6-12 years diagnosed with ADHD are dosed to optimal effect.

Condition or Disease	Intervention/Treatment	Phase
Attention Deficit Hyperactivity Disorder (ADHD)	Drug: Vyvanse (lisdexamfetamine dimesylate)	Phase 4

Detailed Description

Dose-Optimization Study Evaluating the Efficacy, Safety and Tolerability of Vyvanse (lisdexamfetamine dimesylate) in Children aged 6-12 Diagnosed with ADHD

Study Design

• Study Type: Interventional
• Actual Enrollment: 318 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Prospective, Open-Label, Multi-Center, Dose-Optimization Study Evaluating the Efficacy, Safety and Tolerability of Vyvanse (Lisdexamfetamine Dimesylate) 20-70mg in Children Aged 6-12 Diagnosed With ADHD
• Actual Study Start Date: Jun 28, 2007
• Actual Primary Completion Date: Jan 2, 2008
• Actual Study Completion Date: Jan 2, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1	Drug: Vyvanse (lisdexamfetamine dimesylate); Vyvanse™ 20mg once daily at 7 a.m.; dose increased weekly by 10mg until an acceptable response is achieved. Titration may proceed to a maximum daily dose 70mg/day.

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Total Attention Deficit Hyperactivity Disorder Rating Scale-fourth Edition (ADHD-RS-IV) Score at 7 Weeks [Baseline and 7 weeks]

   Change in the Attention Deficit Hyperactivity Disorder Rating Scale-fourth edition (ADHD-RS-IV) total score from baseline. The ADHD-RS-IV consists of 18 items scored on a 4-point scale ranging from 0 (no symptoms) to 3 (severe symptoms) with total score ranging from 0 to 54.

Secondary Outcome Measures

1. Weekly Change From Baseline in Total ADHD-RS-IV Score [Baseline and 1, 2, 3, 4, 5, 6, and 7 weeks]

   Change in the Attention Deficit Hyperactivity Disorder Rating Scale-fourth edition (ADHD-RS-IV) total score from baseline. The ADHD-RS-IV consists of 18 items scored on a 4-point scale ranging from 0 (no symptoms) to 3 (severe symptoms) with total score ranging from 0 to 54.

2. Number of Participants With Improvement on Clinical Global Impression-Improvement (CGI-I) [7 weeks]

   Clinical Global Impression-Improvement (CGI-I) consists of a 7-point scale ranging from 1 (very much improved) to 7 (very much worse). Improvement is defined as a score of 1 or 2 on the scale.

3. Number of Participants With Improvement onParent Global Assessment (PGA) [7 weeks]

   Parent Global Assessment (PGA) consists of a 7-point scale ranging from 1 (very much improved) to 7 (very much worse). Improvement is defined as a score of 1 (very much improved) or 2 (much improved) on the scale.

4. Change From Baseline in Expression and Emotional Scale for Children (EESC) Scores at 7 Weeks [Baseline and 7 weeks]

   Expression and Emotional Scale for Children (EESC) consists of 29 items rated on a scale from 1 (not true at all) to 5 (very much true). Lower scores reflect better emotional outcomes.

5. Changes From Baseline in Behavior Rating Inventory of Executive Function (BRIEF) Scores at 7 Weeks [Baseline and 7 weeks]

   Behavior Rating Inventory of Executive Function (BRIEF) is an 86-item questionnaire composed of three scales (Global Executive Composite, Behavioral Recognition Index, and Metacognition Index). Items are rated 1 (never), 2 (sometimes), and 3 (often). Lower scores reflect better functioning.

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 based on a detailed psychiatric evaluation.

4. Subjects must have a baseline ADHD-RS-IV total score ≥28.

5. Subject is functioning at an age-appropriate level intellectually.

6. comply with all the testing and requirements.

7. Subject is able to swallow a capsule.

8. Subject has blood pressure measurements within the 95th percentile for age, gender, and height.

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, psychosis, bipolar illness, pervasive developmental disorder, severe obsessive compulsive disorder, severe depressive or severe anxiety disorder or other symptomatic manifestations.

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.

6. Subject has a positive urine drug result.

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

8. Subject is significantly overweight.

9. Subject has a history of seizures (exclusive of febrile seizures), a tic disorder, a current diagnosis and/or family history of Tourette's Disorder.

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

11. Subject has taken another investigational product or taken part in a clinical trial within 30 days prior to Screening.

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. The female subject is pregnant or lactating.

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Melmed Center	Scottsdale	Arizona	United States
2	Valley Clinical Research	El Centro	California	United States
3	Peninsula Research Assoc, Inc	Rolling Hills Estates	California	United States
4	UCSF-Langely Porter Psych Institute	San Francisco	California	United States
5	Encompass Clinical Research	Spring Valley	California	United States
6	Shire Clinical Research Site	Wildomar	California	United States
7	Sarkis Clinical Trials	Gainesville	Florida	United States
8	Shire Clinical Research Site	Hialeah	Florida	United States
9	CNS Research Institute, Inc	Jacksonville	Florida	United States
10	CORE Research, Inc	Maitland	Florida	United States
11	Miami Research Associates	Miami	Florida	United States
12	Clinical Neuroscience Solutions, Inc	Orlando	Florida	United States
13	Janus Center for Psychiatric Research	West Palm Beach	Florida	United States
14	Children's Development Center	Winter Park	Florida	United States
15	Capstone Clinical Research	Libertyville	Illinois	United States
16	Indiana University School of Medicine	Indianapolis	Indiana	United States
17	Shire Clinical Research Site	Terre Haute	Indiana	United States
18	Shire Clinical Research Site	Newton	Kansas	United States
19	Psychiatric Associates	Overland Park	Kansas	United States
20	Kentucky Pediatric/Adult Research	Bardstown	Kentucky	United States
21	Shire Clinical Research Site	Lexington	Kentucky	United States
22	Pedia Research	Owensboro	Kentucky	United States
23	Four Rivers Clinical Research, Inc.	Paducah	Kentucky	United States
24	Shire Clinical Research Site	Troy	Michigan	United States
25	University of Rochester, School of Medicine and Dentistry	Rochester	New York	United States
26	Piedmont Neuropsychiatry	Charlotte	North Carolina	United States
27	University Commons Office Park	Durham	North Carolina	United States
28	University Hospitals of Cleveland	Cleveland	Ohio	United States
29	BHI, Inc.	Moore	Oklahoma	United States
30	Shire Clinical Research Site	Oklahoma City	Oklahoma	United States
31	Oregon Center for Clinical Investigations, Inc	Eugene	Oregon	United States
32	Oregon Center For Clinical Investigations, Inc.	Portland	Oregon	United States
33	Summit Research Network	Portland	Oregon	United States
34	Oregon Center for Clinical Investigations, Inc.	Salem	Oregon	United States
35	ADHD Program, Western Psychiatric Institute and Clinic	Pittsburgh	Pennsylvania	United States
36	The Jackson Clinic	Jackson	Tennessee	United States
37	Clinical Neuroscience Solutions, Inc	Memphis	Tennessee	United States
38	FutureSearch Trials	Austin	Texas	United States
39	Claghorn-Lesem Research Clinic Inc.	Bellaire	Texas	United States
40	Red Oak Psychiatry Associates P.A.	Houston	Texas	United States
41	R/D Clinical Research, Inc.	Lake Jackson	Texas	United States
42	ADHD Clinic of San Antonio	San Antonio	Texas	United States
43	NeuroScience, Inc	Herndon	Virginia	United States
44	Dominion Clinical Research	Midlothian	Virginia	United States
45	International Clinical Research Associates, LLC	Richmond	Virginia	United States
46	Eastside Therapeutic Resource	Kirkland	Washington	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: NCT00500071
• Other Study ID Numbers: SPD489-310
• First Posted: Jul 12, 2007
• Last Update Posted: Mar 10, 2022
• Last Verified: Feb 1, 2022

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

Study Results

Participant Flow

Pre-assignment Detail	The study had three phases; 1)screening and wash-out; 2) dose-optimization (5 weeks) and maintenance (2 weeks); 3) 30-day safety follow-up. Dosing ranged from 20-70 mg once daily of Vyvanse.

Arm/Group Title	Vyvanse
Arm/Group Description	Lisdexamfetamine dimesylate (LDX)
Period Title: Screening and Washout Phase
STARTED	318
COMPLETED	317
NOT COMPLETED	1
Period Title: Screening and Washout Phase
STARTED	317
COMPLETED	295
NOT COMPLETED	22
Period Title: Screening and Washout Phase
STARTED	295
COMPLETED	278
NOT COMPLETED	17

Baseline Characteristics

Arm/Group Title	Vyvanse
Arm/Group Description	Lisdexamfetamine dimesylate (LDX)
Overall Participants	318
Age (Count of Participants)
<=18 years	318 100%
Between 18 and 65 years	0 0%
>=65 years	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	9.1 (1.9)
Sex: Female, Male (Count of Participants)
Female	93 29.2%
Male	225 70.8%
Region of Enrollment (Count of Participants)
United States	318 100%

Outcome Measures

1. Secondary Outcome

Title	Weekly Change From Baseline in Total ADHD-RS-IV Score
Description	Change in the Attention Deficit Hyperactivity Disorder Rating Scale-fourth edition (ADHD-RS-IV) total score from baseline. The ADHD-RS-IV consists of 18 items scored on a 4-point scale ranging from 0 (no symptoms) to 3 (severe symptoms) with total score ranging from 0 to 54.
Time Frame	Baseline and 1, 2, 3, 4, 5, 6, and 7 weeks

Outcome Measure Data

Analysis Population Description

ITT

Arm/Group Title	Vyvanse
Arm/Group Description	Lisdexamfetamine dimesylate (LDX)
Measure Participants	316
Week 1	-11.3 (0.62)
Week 2	-17.8 (0.63)
Week 3	-21.7 (0.61)
Week 4	-25.4 (0.61)
Week 5	-27.0 (0.60)
Week 6	-28.9 (0.60)
Week 7	-29.8 (0.58)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Vyvanse
	Comments	Week 1
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments
	Method	t-test, 1 sided
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Vyvanse
	Comments	Week 2
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments
	Method	t-test, 1 sided
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Vyvanse
	Comments	Week 3
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments
	Method	t-test, 1 sided
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Vyvanse
	Comments	Week 4
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments
	Method	t-test, 1 sided
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Vyvanse
	Comments	Week 5
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments
	Method	t-test, 1 sided
	Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Vyvanse
	Comments	Week 6
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments
	Method	t-test, 1 sided
	Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Vyvanse
	Comments	Week 7
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments
	Method	t-test, 1 sided
	Comments

2. Primary Outcome

Title	Change From Baseline in Total Attention Deficit Hyperactivity Disorder Rating Scale-fourth Edition (ADHD-RS-IV) Score at 7 Weeks
Description	Change in the Attention Deficit Hyperactivity Disorder Rating Scale-fourth edition (ADHD-RS-IV) total score from baseline. The ADHD-RS-IV consists of 18 items scored on a 4-point scale ranging from 0 (no symptoms) to 3 (severe symptoms) with total score ranging from 0 to 54.
Time Frame	Baseline and 7 weeks

Outcome Measure Data

Analysis Population Description

Intent-to-treat (ITT). ITT population defined as all subjects who took at least one dose of drug and had at least one ADHD-RS-IV total score available.

Arm/Group Title	Vyvanse
Arm/Group Description	Lisdexamfetamine dimesylate (LDX)
Measure Participants	316
Mean (Standard Error) [Units on a scale]	-28.6 (0.61)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Vyvanse
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments
	Method	t-test, 1 sided
	Comments

3. Secondary Outcome

Title	Number of Participants With Improvement on Clinical Global Impression-Improvement (CGI-I)
Description	Clinical Global Impression-Improvement (CGI-I) consists of a 7-point scale ranging from 1 (very much improved) to 7 (very much worse). Improvement is defined as a score of 1 or 2 on the scale.
Time Frame	7 weeks

Outcome Measure Data

Analysis Population Description

ITT

Arm/Group Title	Vyvanse
Arm/Group Description	Lisdexamfetamine dimesylate (LDX)
Measure Participants	316
Number [Participants]	284 89.3%

4. Secondary Outcome

Title	Number of Participants With Improvement onParent Global Assessment (PGA)
Description	Parent Global Assessment (PGA) consists of a 7-point scale ranging from 1 (very much improved) to 7 (very much worse). Improvement is defined as a score of 1 (very much improved) or 2 (much improved) on the scale.
Time Frame	7 weeks

Outcome Measure Data

Analysis Population Description

ITT

Arm/Group Title	Vyvanse
Arm/Group Description	Lisdexamfetamine dimesylate (LDX)
Measure Participants	316
Number [Participants]	267 84%

5. Secondary Outcome

Title	Change From Baseline in Expression and Emotional Scale for Children (EESC) Scores at 7 Weeks
Description	Expression and Emotional Scale for Children (EESC) consists of 29 items rated on a scale from 1 (not true at all) to 5 (very much true). Lower scores reflect better emotional outcomes.
Time Frame	Baseline and 7 weeks

Outcome Measure Data

Analysis Population Description

ITT

Arm/Group Title	Vyvanse
Arm/Group Description	Lisdexamfetamine dimesylate (LDX)
Measure Participants	316
Mean (Standard Deviation) [Units on a scale]	-7.4 (18.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Vyvanse
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments
	Method	t-test, 1 sided
	Comments

6. Secondary Outcome

Title	Changes From Baseline in Behavior Rating Inventory of Executive Function (BRIEF) Scores at 7 Weeks
Description	Behavior Rating Inventory of Executive Function (BRIEF) is an 86-item questionnaire composed of three scales (Global Executive Composite, Behavioral Recognition Index, and Metacognition Index). Items are rated 1 (never), 2 (sometimes), and 3 (often). Lower scores reflect better functioning.
Time Frame	Baseline and 7 weeks

Outcome Measure Data

Analysis Population Description

ITT

Arm/Group Title	Vyvanse
Arm/Group Description	Lisdexamfetamine dimesylate (LDX)
Measure Participants	316
Global Executive Composite	-17.9 (12.5)
Behavioral Recognition Index	-15.4 (12.6)
Metacognition Index	-17.6 (12.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Vyvanse
	Comments	Global Executive Composite
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments
	Method	t-test, 1 sided
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Vyvanse
	Comments	Behavioral Recognition Index
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments
	Method	t-test, 1 sided
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Vyvanse
	Comments	Metacognition Index
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments
	Method	t-test, 1 sided
	Comments

Adverse Events

Arm/Group Title	Vyvanse
Arm/Group Description	Lisdexamfetamine dimesylate (LDX)
All Cause Mortality
	Vyvanse
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Vyvanse
	Affected / at Risk (%)	# Events
Total	2/317 (0.6%)
Cardiac disorders
Syncope	1/317 (0.3%)	1
Sinus arrest	1/317 (0.3%)	1
Other (Not Including Serious) Adverse Events
	Vyvanse
	Affected / at Risk (%)	# Events
Total	269/317 (84.9%)
Gastrointestinal disorders
Abdominal pain upper	42/317 (13.2%)
Nausea	17/317 (5.4%)
Vomiting	17/317 (5.4%)
General disorders
Irritability	51/317 (16.1%)
Investigations
Weight decreased	54/317 (17%)
Metabolism and nutrition disorders
Decreased appetite	137/317 (43.2%)
Nervous system disorders
Headache	44/317 (13.9%)
Initial insomnia	36/317 (11.4%)
Insomnia	51/317 (16.1%)
Psychiatric disorders
Affect liability	23/317 (7.3%)

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.