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Comparison of Lisdexamfetamine Dimesylate With Atomoxetine HCl in Attention-Deficit/Hyperactivity Disorder (ADHD) Subjects With an Inadequate Response to Methylphenidate

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ClinicalTrials.gov Identifier: NCT01106430
Recruitment Status : Completed
First Posted : April 19, 2010
Results First Posted : June 24, 2013
Last Update Posted : June 12, 2014
Sponsor:
Information provided by (Responsible Party):
Shire

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Attention-Deficit/Hyperactivity Disorder
Interventions Drug: Lisdexamfetamine Dimesylate
Drug: Atomoxetine Hydrochloride
Enrollment 267
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Lisdexamfetamine Dimesylate Atomoxetine Hydrochloride
Hide Arm/Group Description Lisdexamfetamine Dimesylate (LDX, Vyvanse, SPD489) was administered orally once-daily at approximately 7:00am for 9 weeks (4-week dose optimization period and a 5-week dose maintenance period) at doses of either 30, 50, or 70 mg. Atomoxetine Hydrochloride (Strattera) was administered orally once-daily at approximately 7:00am for 9 weeks (4-week dose optimization period and a 5-week dose maintenance period) at weight adjusted doses of 10 mg to 100 mg.
Period Title: Overall Study
Started 133 134
Completed 100 101
Not Completed 33 33
Reason Not Completed
Adverse Event             8             10
Lack of Efficacy             2             13
Lost to Follow-up             5             1
Early Termination Requested By Sponsor             1             0
Moved Out Of State             0             1
Refused To Take Medication             0             1
Noncompliance             0             1
Hard Time Swallowing The Pills             1             0
Previous Use Of Marijuana             1             0
Protocol Violation             7             2
Withdrawal by Subject             8             4
Arm/Group Title Lisdexamfetamine Dimesylate Atomoxetine Hydrochloride Total
Hide Arm/Group Description Lisdexamfetamine Dimesylate (LDX, Vyvanse, SPD489) was administered orally once-daily at approximately 7:00am for 9 weeks (4-week dose optimization period and a 5-week dose maintenance period) at doses of either 30, 50, or 70 mg. Atomoxetine Hydrochloride (Strattera) was administered orally once-daily at approximately 7:00am for 9 weeks (4-week dose optimization period and a 5-week dose maintenance period) at weight adjusted doses of 10 mg to 100 mg. Total of all reporting groups
Overall Number of Baseline Participants 128 134 262
Hide Baseline Analysis Population Description
Safety Population was used for baseline characteristics (n = 262). Defined as all subjects who were randomized and who had taken at least 1 dose of investigational product. Five randomized subjects did not take any investigational product.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 128 participants 134 participants 262 participants
10.9  (3.01) 10.4  (2.84) 10.6  (2.93)
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 128 participants 134 participants 262 participants
13 - 17 years 34 34 68
6 - 12 years 94 100 194
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 128 participants 134 participants 262 participants
Female
34
  26.6%
31
  23.1%
65
  24.8%
Male
94
  73.4%
103
  76.9%
197
  75.2%
Region of Enrollment   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 128 participants 134 participants 262 participants
BELGIUM 0 2 2
CANADA 17 18 35
GERMANY 20 22 42
HUNGARY 10 10 20
ITALY 1 0 1
POLAND 0 1 1
SPAIN 12 10 22
SWEDEN 3 3 6
UNITED STATES 70 68 138
[1]
Measure Description: All enrolled subjects defined as all randomized subjects (n = 267).
1.Primary Outcome
Title Time to First Response
Hide Description Time to first response was defined as a Clinical Global Impression-Improvement (CGI-I) value of 1 (very much improved) or 2 (much improved) first recorded following first dose of investigational product. CGI-I consists of a 7-point scale ranging from 1 (very much improved) to 7 (very much worse).
Time Frame 9 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set defined as all subjects who were randomized and who had taken at least 1 dose of investigational product. One subject was randomized to receive Strattera, but actually received Lisdexamfetamine Dimesylate. For all efficacy analyses this subject is included in the Strattera arm per the intention to treat principle.
Arm/Group Title Lisdexamfetamine Dimesylate Atomoxetine Hydrochloride
Hide Arm/Group Description:
Lisdexamfetamine Dimesylate (LDX, Vyvanse, SPD489) was administered orally once-daily at approximately 7:00am for 9 weeks (4-week dose optimization period and a 5-week dose maintenance period) at doses of either 30, 50, or 70 mg.
Atomoxetine Hydrochloride (Strattera) was administered orally once-daily at approximately 7:00am for 9 weeks (4-week dose optimization period and a 5-week dose maintenance period) at weight adjusted doses of 10 mg to 100 mg.
Overall Number of Participants Analyzed 127 135
Median (95% Confidence Interval)
Unit of Measure: Days
12.0
(8.0 to 16.0)
21.0
(15.0 to 23.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Lisdexamfetamine Dimesylate, Atomoxetine Hydrochloride
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.001
Comments [Not Specified]
Method Peto-Peto-Prentice Wilcoxon Test
Comments [Not Specified]
2.Secondary Outcome
Title Percent of Participants With Improvement on Clinical Global Impression-Improvement (CGI-I) Scores - Last Observation Carried Forward (LOCF)
Hide 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 (very much improved) or 2 (much improved) on the scale.
Time Frame 9 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set defined as all subjects who were randomized and who had taken at least 1 dose of investigational product.
Arm/Group Title Lisdexamfetamine Dimesylate Atomoxetine Hydrochloride
Hide Arm/Group Description:
Lisdexamfetamine Dimesylate (LDX, Vyvanse, SPD489) was administered orally once-daily at approximately 7:00am for 9 weeks (4-week dose optimization period and a 5-week dose maintenance period) at doses of either 30, 50, or 70 mg.
Atomoxetine Hydrochloride (Strattera) was administered orally once-daily at approximately 7:00am for 9 weeks (4-week dose optimization period and a 5-week dose maintenance period) at weight adjusted doses of 10 mg to 100 mg.
Overall Number of Participants Analyzed 126 132
Measure Type: Number
Unit of Measure: percentage of participants
81.7 63.6
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Lisdexamfetamine Dimesylate, Atomoxetine Hydrochloride
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 18.1
Confidence Interval (2-Sided) 95%
7.5 to 28.7
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Change From Baseline in Attention Deficit Hyperactivity Disorder Rating Scale-Fourth Edition (ADHD-RS-IV) Total Score at 9 Weeks - LOCF
Hide Description ADHD-RS-IV consists of 18 items scored on a 4-point scale from 0 (no symptoms) to 3 (severe symptoms) with total score ranging from 0 to 54. A decrease in score indicates an improvement in ADHD symptomology.
Time Frame Baseline and 9 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set defined as all subjects who were randomized and who had taken at least 1 dose of investigational product.
Arm/Group Title Lisdexamfetamine Dimesylate Atomoxetine Hydrochloride
Hide Arm/Group Description:
Lisdexamfetamine Dimesylate (LDX, Vyvanse, SPD489) was administered orally once-daily at approximately 7:00am for 9 weeks (4-week dose optimization period and a 5-week dose maintenance period) at doses of either 30, 50, or 70 mg.
Atomoxetine Hydrochloride (Strattera) was administered orally once-daily at approximately 7:00am for 9 weeks (4-week dose optimization period and a 5-week dose maintenance period) at weight adjusted doses of 10 mg to 100 mg.
Overall Number of Participants Analyzed 126 133
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-26.1  (1.16) -19.7  (1.13)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Lisdexamfetamine Dimesylate, Atomoxetine Hydrochloride
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in LS Means
Estimated Value -6.5
Confidence Interval (2-Sided) 95%
-9.3 to -3.6
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Change From Baseline in the Weiss Functional Impairment Rating Scale - Parent Report (WFIRS-P) Global Score at Up to 9 Weeks
Hide Description The WFIRS-P is a 50-item scale with each item scored from 0 (never/not at all) to 3 (very often/very much). Mean scores range from 0 to 3. Higher scores indicate greater functional impairment.
Time Frame Baseline and up to 9 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set defined as all subjects who were randomized and who had taken at least 1 dose of investigational product.
Arm/Group Title Lisdexamfetamine Dimesylate Atomoxetine Hydrochloride
Hide Arm/Group Description:
Lisdexamfetamine Dimesylate (LDX, Vyvanse, SPD489) was administered orally once-daily at approximately 7:00am for 9 weeks (4-week dose optimization period and a 5-week dose maintenance period) at doses of either 30, 50, or 70 mg.
Atomoxetine Hydrochloride (Strattera) was administered orally once-daily at approximately 7:00am for 9 weeks (4-week dose optimization period and a 5-week dose maintenance period) at weight adjusted doses of 10 mg to 100 mg.
Overall Number of Participants Analyzed 107 113
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-0.35  (0.034) -0.27  (0.032)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Lisdexamfetamine Dimesylate, Atomoxetine Hydrochloride
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.046
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in LS Means
Estimated Value -0.09
Confidence Interval (2-Sided) 95%
-0.17 to -0.00
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Health Utilities Index-2 (HUI-2) Scores at Up to 9 Weeks
Hide Description HUI is used to describe health status and to obtain utility scores by collecting data using one or more questionnaires in formats selected to match the specific study design criteria. Scoring ranges from 0.00 (dead) to 1.00 (perfect health). Higher scores represent better health status.
Time Frame up to 9 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set defined as all subjects who were randomized and who had taken at least 1 dose of investigational product.
Arm/Group Title Lisdexamfetamine Dimesylate Atomoxetine Hydrochloride
Hide Arm/Group Description:
Lisdexamfetamine Dimesylate (LDX, Vyvanse, SPD489) was administered orally once-daily at approximately 7:00am for 9 weeks (4-week dose optimization period and a 5-week dose maintenance period) at doses of either 30, 50, or 70 mg.
Atomoxetine Hydrochloride (Strattera) was administered orally once-daily at approximately 7:00am for 9 weeks (4-week dose optimization period and a 5-week dose maintenance period) at weight adjusted doses of 10 mg to 100 mg.
Overall Number of Participants Analyzed 116 123
Mean (Standard Deviation)
Unit of Measure: units on a scale
0.920  (0.0961) 0.922  (0.0937)
6.Secondary Outcome
Title Change From Baseline in Brief Psychiatric Rating Scale for Children (BPRS-C) Total Score at Up to 9 Weeks
Hide Description The BPRS-C characterizes psychopathology. A total of 21 items are rated on a scale from 0 (not present) to 6 (extremely severe) with a total score ranging from 0 to 126. A decrease in score indicates a reduction in psychopathology.
Time Frame Baseline and up to 9 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety Population defined as all subjects who were randomized and who had taken at least 1 dose of investigational product.
Arm/Group Title Lisdexamfetamine Dimesylate Atomoxetine Hydrochloride
Hide Arm/Group Description:
Lisdexamfetamine Dimesylate (LDX, Vyvanse, SPD489) was administered orally once-daily at approximately 7:00am for 9 weeks (4-week dose optimization period and a 5-week dose maintenance period) at doses of either 30, 50, or 70 mg.
Atomoxetine Hydrochloride (Strattera) was administered orally once-daily at approximately 7:00am for 9 weeks (4-week dose optimization period and a 5-week dose maintenance period) at weight adjusted doses of 10 mg to 100 mg.
Overall Number of Participants Analyzed 117 123
Mean (Standard Deviation)
Unit of Measure: units on a scale
-10.7  (9.27) -7.9  (9.07)
7.Secondary Outcome
Title Columbia-Suicide Severity Rating Scale (C-SSRS)
Hide Description C-SSRS is a semi-structured interview that captures the occurence, severity, and frequency of suicide-related thoughts and behaviors during the assessment period. The interview includes definitions and suggested questions to solicit the type of information needed to determine if a suicide-related thought or behaviour occurred. The assessment is done by the nature of the responses, not by a numbered scale.
Time Frame 9 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety Population defined as all subjects who were randomized and who had taken at least 1 dose of investigational product.
Arm/Group Title Lisdexamfetamine Dimesylate Atomoxetine Hydrochloride
Hide Arm/Group Description:
Lisdexamfetamine Dimesylate (LDX, Vyvanse, SPD489) was administered orally once-daily at approximately 7:00am for 9 weeks (4-week dose optimization period and a 5-week dose maintenance period) at doses of either 30, 50, or 70 mg.
Atomoxetine Hydrochloride (Strattera) was administered orally once-daily at approximately 7:00am for 9 weeks (4-week dose optimization period and a 5-week dose maintenance period) at weight adjusted doses of 10 mg to 100 mg.
Overall Number of Participants Analyzed 127 132
Measure Type: Number
Unit of Measure: participants
Suicidal ideation 0 0
Suicidal behavior 0 0
8.Secondary Outcome
Title Udvalg for Kliniske Undersogelser Side Effect Rating Scale - Clinician (UKU-SERS-Clin) With Side Effects Scores >=1
Hide Description UKU-SERS-Clin is composed of 48 items each of which asks about a single side effect. Each side effect is rated based on a 4-point scale ranging from 0 (no or doubtful presence) to 3 (the least favorable rating). The rating is independent of whether the symptom is regarded as related to the investigational product.
Time Frame 9 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety Population defined as all subjects who were randomized and who had taken at least 1 dose of investigational product.
Arm/Group Title Lisdexamfetamine Dimesylate Atomoxetine Hydrochloride
Hide Arm/Group Description:
Lisdexamfetamine Dimesylate (LDX, Vyvanse, SPD489) was administered orally once-daily at approximately 7:00am for 9 weeks (4-week dose optimization period and a 5-week dose maintenance period) at doses of either 30, 50, or 70 mg.
Atomoxetine Hydrochloride (Strattera) was administered orally once-daily at approximately 7:00am for 9 weeks (4-week dose optimization period and a 5-week dose maintenance period) at weight adjusted doses of 10 mg to 100 mg.
Overall Number of Participants Analyzed 127 132
Measure Type: Number
Unit of Measure: participants
Weight Loss 46 19
Reduced Duration of Sleep 29 16
Asthenia/Lassitude/Increased Fatigability 25 29
Tension/Inner Unrest 20 22
Nausea/Vomiting 19 26
Sleepiness/Sedation 16 35
Reduced Salivation 16 6
Headache-Tension Headache 15 17
Concentration Difficulties 75 92
Failing Memory 10 21
Depression 6 10
Increased Duration of Sleep 12 12
Increased Dream Activity 3 8
Emotional Indifference 12 10
Dystonia 0 1
Rigidity 0 1
Hypokinesia/Akinesia 1 0
Hyperkinesia Logic 2 3
Tremor 3 1
Akathisia 0 2
Paraesthesias 1 0
Accomodation Disturbances 0 2
Increased Salivation 1 2
Diarrhea 6 9
Constipation 9 5
Micturition Disturbances 0 1
Polyuria/Polydipsia 3 2
Orthostatic Dizziness 10 9
Palpitations/Tachycardia 1 5
Increased Tendency to Sweating 3 5
Rash-Morbiliform 0 1
Rash-Petechial 1 0
Rash-Urticarial 1 1
Rash-Cannot be Classified 1 2
Pruritus 4 7
Weight Gain 1 0
Headache-Migraine 2 2
Headache-Other Forms 11 10
Time Frame [Not Specified]
Adverse Event Reporting Description Safety Population defined as all subjects who were randomized and who had taken at least 1 dose of investigational product.
 
Arm/Group Title Lisdexamfetamine Dimesylate Atomoxetine Hydrochloride
Hide Arm/Group Description Lisdexamfetamine Dimesylate (LDX, Vyvanse, SPD489) was administered orally once-daily at approximately 7:00am for 9 weeks (4-week dose optimization period and a 5-week dose maintenance period) at doses of either 30, 50, or 70 mg. Atomoxetine Hydrochloride (Strattera) was administered orally once-daily at approximately 7:00am for 9 weeks (4-week dose optimization period and a 5-week dose maintenance period) at weight adjusted doses of 10 mg to 100 mg.
All-Cause Mortality
Lisdexamfetamine Dimesylate Atomoxetine Hydrochloride
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Lisdexamfetamine Dimesylate Atomoxetine Hydrochloride
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/128 (0.00%)      0/134 (0.00%)    
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Lisdexamfetamine Dimesylate Atomoxetine Hydrochloride
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   92/128 (71.88%)      95/134 (70.90%)    
Gastrointestinal disorders     
ABDOMINAL PAIN  3/128 (2.34%)  3 8/134 (5.97%)  10
ABDOMINAL PAIN UPPER  3/128 (2.34%)  3 10/134 (7.46%)  12
CONSTIPATION  8/128 (6.25%)  9 2/134 (1.49%)  2
DIARRHOEA  2/128 (1.56%)  3 9/134 (6.72%)  11
DRY MOUTH  8/128 (6.25%)  8 4/134 (2.99%)  4
NAUSEA  16/128 (12.50%)  16 21/134 (15.67%)  27
VOMITING  6/128 (4.69%)  6 13/134 (9.70%)  17
General disorders     
FATIGUE  12/128 (9.38%)  14 14/134 (10.45%)  16
IRRITABILITY  8/128 (6.25%)  8 3/134 (2.24%)  3
Infections and infestations     
NASOPHARYNGITIS  8/128 (6.25%)  9 8/134 (5.97%)  9
UPPER RESPIRATORY TRACT INFECTION  3/128 (2.34%)  3 8/134 (5.97%)  8
Investigations     
WEIGHT DECREASED  28/128 (21.88%)  30 9/134 (6.72%)  9
Metabolism and nutrition disorders     
DECREASED APPETITE  33/128 (25.78%)  36 14/134 (10.45%)  14
Nervous system disorders     
HEADACHE  17/128 (13.28%)  25 22/134 (16.42%)  29
SEDATION  5/128 (3.91%)  5 8/134 (5.97%)  9
SOMNOLENCE  4/128 (3.13%)  4 16/134 (11.94%)  23
Psychiatric disorders     
INSOMNIA  15/128 (11.72%)  16 8/134 (5.97%)  8
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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.
Results Point of Contact
Name/Title: Study Physician
Organization: Shire Development LLC
Phone: +1 866 842 5335
Responsible Party: Shire
ClinicalTrials.gov Identifier: NCT01106430     History of Changes
Other Study ID Numbers: SPD489-317
2009-011745-94 ( EudraCT Number )
First Submitted: April 14, 2010
First Posted: April 19, 2010
Results First Submitted: May 3, 2013
Results First Posted: June 24, 2013
Last Update Posted: June 12, 2014