Trial Outcomes & Findings for Double-blind, Placebo-controlled, Randomised Withdrawal, Extension, Safety and Efficacy Study of LDX in Children and Adolescents Aged 6-17 (NCT NCT00784654)
NCT ID: NCT00784654
Last Updated: 2021-06-09
Results Overview
Treatment failure defined as 50% increase (worsening) in Attention Deficit Hyperactivity Disorder Rating Scale (ADHD-RS-IV) total score and \>= 2 point increase (worsening) in the Clinical Global Impression-Severity of Illness (CGI-S) score observed at any visit during the randomized withdrawal period compared to the respective scores at baseline of randomized withdrawal period. Subjects without an endpoint value were classed as treatment failures.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
276 participants
Primary outcome timeframe
Baseline of the randomized withdrawal period and its relevant endpoint (Up to 6 weeks)
Results posted on
2021-06-09
Participant Flow
In the Open-label period, 8 subjects completed the Open-label period and were not randomized. Therefore, 157 subjects were randomized in the Randomized Withdrawal Period.
Participant milestones
| Measure |
Lisdexamfetamine Dimesylate (LDX)(Open-label Period)
Consists of at least 26 weeks where subjects are titrated to an optimal dose of LDX (either 30, 50 or 70 mg once-daily orally at approximately 7:00 AM +/- 2 hours) and then maintained on their optimal dose of LDX (either 30, 50 or 70 mg once-daily orally at approximately 7:00 AM +/- 2 hours).
|
Lisdexamfetamine Dimesylate (LDX)(Randomized Period)
After the Open-label Period, subjects were randomized to receive their optimal dose of LDX at either 30, 50, or 70 mg once-daily orally at approximately 7:00 AM +/- 2 hours for up to 6 weeks.
|
Placebo (Randomized Period)
After the Open-label Period, subjects were randomized to receive placebo once-daily orally at approximately 7:00 AM +/- 2 hours for up to 6 weeks.
|
|---|---|---|---|
|
Open-Label Period (Non-Randomized)
STARTED
|
276
|
0
|
0
|
|
Open-Label Period (Non-Randomized)
COMPLETED
|
165
|
0
|
0
|
|
Open-Label Period (Non-Randomized)
NOT COMPLETED
|
111
|
0
|
0
|
|
Randomized Withdrawal Period
STARTED
|
0
|
78
|
79
|
|
Randomized Withdrawal Period
COMPLETED
|
0
|
60
|
16
|
|
Randomized Withdrawal Period
NOT COMPLETED
|
0
|
18
|
63
|
Reasons for withdrawal
| Measure |
Lisdexamfetamine Dimesylate (LDX)(Open-label Period)
Consists of at least 26 weeks where subjects are titrated to an optimal dose of LDX (either 30, 50 or 70 mg once-daily orally at approximately 7:00 AM +/- 2 hours) and then maintained on their optimal dose of LDX (either 30, 50 or 70 mg once-daily orally at approximately 7:00 AM +/- 2 hours).
|
Lisdexamfetamine Dimesylate (LDX)(Randomized Period)
After the Open-label Period, subjects were randomized to receive their optimal dose of LDX at either 30, 50, or 70 mg once-daily orally at approximately 7:00 AM +/- 2 hours for up to 6 weeks.
|
Placebo (Randomized Period)
After the Open-label Period, subjects were randomized to receive placebo once-daily orally at approximately 7:00 AM +/- 2 hours for up to 6 weeks.
|
|---|---|---|---|
|
Open-Label Period (Non-Randomized)
Adverse Event
|
44
|
0
|
0
|
|
Open-Label Period (Non-Randomized)
Withdrawal by Subject
|
22
|
0
|
0
|
|
Open-Label Period (Non-Randomized)
Lack of Efficacy
|
21
|
0
|
0
|
|
Open-Label Period (Non-Randomized)
Lost to Follow-up
|
11
|
0
|
0
|
|
Open-Label Period (Non-Randomized)
Protocol Violation
|
7
|
0
|
0
|
|
Open-Label Period (Non-Randomized)
Mother is a drug addict
|
1
|
0
|
0
|
|
Open-Label Period (Non-Randomized)
Decision of medical monitor
|
1
|
0
|
0
|
|
Open-Label Period (Non-Randomized)
Home situation intolerable
|
1
|
0
|
0
|
|
Open-Label Period (Non-Randomized)
ADHD-RS score too high for Random Phase
|
1
|
0
|
0
|
|
Open-Label Period (Non-Randomized)
Met stopping criteria for CGI-S score
|
1
|
0
|
0
|
|
Open-Label Period (Non-Randomized)
Did not provide end of study page
|
1
|
0
|
0
|
|
Randomized Withdrawal Period
Met relapse criteria per investigator
|
0
|
8
|
35
|
|
Randomized Withdrawal Period
Lack of Efficacy
|
0
|
5
|
18
|
|
Randomized Withdrawal Period
Withdrawal by Subject
|
0
|
1
|
7
|
|
Randomized Withdrawal Period
Protocol Violation
|
0
|
2
|
1
|
|
Randomized Withdrawal Period
Adverse Event
|
0
|
1
|
1
|
|
Randomized Withdrawal Period
Did not complete a visit
|
0
|
1
|
0
|
|
Randomized Withdrawal Period
Family reasons
|
0
|
0
|
1
|
Baseline Characteristics
Double-blind, Placebo-controlled, Randomised Withdrawal, Extension, Safety and Efficacy Study of LDX in Children and Adolescents Aged 6-17
Baseline characteristics by cohort
| Measure |
All Enrolled Subjects
n=276 Participants
|
|---|---|
|
Age, Continuous
|
10.9 years
STANDARD_DEVIATION 2.82 • n=99 Participants
|
|
Age, Customized
6-12 years
|
191 Participants
n=99 Participants
|
|
Age, Customized
13-17 years
|
85 Participants
n=99 Participants
|
|
Sex: Female, Male
Female
|
64 Participants
n=99 Participants
|
|
Sex: Female, Male
Male
|
212 Participants
n=99 Participants
|
|
Region of Enrollment
United States
|
40 Participants
n=99 Participants
|
|
Region of Enrollment
Italy
|
20 Participants
n=99 Participants
|
|
Region of Enrollment
United Kingdom
|
16 Participants
n=99 Participants
|
|
Region of Enrollment
France
|
11 Participants
n=99 Participants
|
|
Region of Enrollment
Hungary
|
28 Participants
n=99 Participants
|
|
Region of Enrollment
Belgium
|
9 Participants
n=99 Participants
|
|
Region of Enrollment
Poland
|
8 Participants
n=99 Participants
|
|
Region of Enrollment
Germany
|
95 Participants
n=99 Participants
|
|
Region of Enrollment
Sweden
|
49 Participants
n=99 Participants
|
PRIMARY outcome
Timeframe: Baseline of the randomized withdrawal period and its relevant endpoint (Up to 6 weeks)Population: Randomized Full Analysis Set (Randomized FAS) includes all subjects who were randomized and received at least 1 dose of investigational product during the Randomized Withdrawal Period.
Treatment failure defined as 50% increase (worsening) in Attention Deficit Hyperactivity Disorder Rating Scale (ADHD-RS-IV) total score and \>= 2 point increase (worsening) in the Clinical Global Impression-Severity of Illness (CGI-S) score observed at any visit during the randomized withdrawal period compared to the respective scores at baseline of randomized withdrawal period. Subjects without an endpoint value were classed as treatment failures.
Outcome measures
| Measure |
Lisdexamfetamine Dimesylate (LDX)(Randomized Period)
n=76 Participants
Subjects receive their optimal dose of LDX at either 30, 50, or 70 mg once-daily orally at approximately 7:00 AM +/- 2 hours for 6 weeks.
|
Placebo (Randomized Period)
n=77 Participants
Subjects receive placebo once-daily orally at approximately 7:00 AM +/- 2 hours for 6 weeks.
|
|---|---|---|
|
Percent of Participants With Treatment Failures at End of The Randomized Withdrawal Period
|
15.8 percentage of participants
|
67.5 percentage of participants
|
SECONDARY outcome
Timeframe: Open-label baseline and Endpoint (Week-26)Population: Open-label Full Analysis set (Open-label FAS) includes all subjects who received at least 1 dose of investigational product during the Open-label Period.
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.
Outcome measures
| Measure |
Lisdexamfetamine Dimesylate (LDX)(Randomized Period)
n=257 Participants
Subjects receive their optimal dose of LDX at either 30, 50, or 70 mg once-daily orally at approximately 7:00 AM +/- 2 hours for 6 weeks.
|
Placebo (Randomized Period)
Subjects receive placebo once-daily orally at approximately 7:00 AM +/- 2 hours for 6 weeks.
|
|---|---|---|
|
Change From Open-Label Baseline in The Attention Deficit Hyperactivity Disorder Rating Scale-Fourth Edition (ADHD-RS-IV) Total Score at Endpoint (Week-26) of The Open-label Period
|
-26.6 Scores on a scale
Standard Deviation 11.39
|
—
|
SECONDARY outcome
Timeframe: Baseline of the randomized withdrawal period and its relevant endpoint (Up to 6 weeks)Population: Randomized FAS
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.
Outcome measures
| Measure |
Lisdexamfetamine Dimesylate (LDX)(Randomized Period)
n=73 Participants
Subjects receive their optimal dose of LDX at either 30, 50, or 70 mg once-daily orally at approximately 7:00 AM +/- 2 hours for 6 weeks.
|
Placebo (Randomized Period)
n=73 Participants
Subjects receive placebo once-daily orally at approximately 7:00 AM +/- 2 hours for 6 weeks.
|
|---|---|---|
|
Change From Randomized Withdrawal Baseline in The ADHD-RS-IV Total Score at Endpoint of The Randomized Withdrawal Period
|
1.2 Scores on a scale
Standard Error 1.09
|
13.8 Scores on a scale
Standard Error 1.06
|
SECONDARY outcome
Timeframe: At Week 26Population: Open-label FAS
CGI-S assesses the severity of the subject's condition on a 7-point scale ranging from 1 (normal, not at all ill) to 7 (among the most extremely ill)
Outcome measures
| Measure |
Lisdexamfetamine Dimesylate (LDX)(Randomized Period)
n=198 Participants
Subjects receive their optimal dose of LDX at either 30, 50, or 70 mg once-daily orally at approximately 7:00 AM +/- 2 hours for 6 weeks.
|
Placebo (Randomized Period)
Subjects receive placebo once-daily orally at approximately 7:00 AM +/- 2 hours for 6 weeks.
|
|---|---|---|
|
Percent of Participants With Clinical Global Impression - Severity of Illness (CGI-S) at Endpoint (Week-26) of The Open-label Period
Normal, not at all ill
|
39.9 percentage of participants
|
—
|
|
Percent of Participants With Clinical Global Impression - Severity of Illness (CGI-S) at Endpoint (Week-26) of The Open-label Period
Borderline mentally ill
|
46.5 percentage of participants
|
—
|
|
Percent of Participants With Clinical Global Impression - Severity of Illness (CGI-S) at Endpoint (Week-26) of The Open-label Period
Mildly ill
|
1.5 percentage of participants
|
—
|
|
Percent of Participants With Clinical Global Impression - Severity of Illness (CGI-S) at Endpoint (Week-26) of The Open-label Period
Moderately ill
|
6.6 percentage of participants
|
—
|
|
Percent of Participants With Clinical Global Impression - Severity of Illness (CGI-S) at Endpoint (Week-26) of The Open-label Period
Markedly ill
|
4.5 percentage of participants
|
—
|
|
Percent of Participants With Clinical Global Impression - Severity of Illness (CGI-S) at Endpoint (Week-26) of The Open-label Period
Severely ill
|
0.5 percentage of participants
|
—
|
|
Percent of Participants With Clinical Global Impression - Severity of Illness (CGI-S) at Endpoint (Week-26) of The Open-label Period
Among the most extremely ill
|
0.5 percentage of participants
|
—
|
SECONDARY outcome
Timeframe: At endpoint of the randomized withdrawal period (Up to 6 weeks)Population: Randomized FAS
CGI-S assesses the severity of the subject's condition on a 7-point scale ranging from 1 (normal, not at all ill) to 7 (among the most extremely ill)
Outcome measures
| Measure |
Lisdexamfetamine Dimesylate (LDX)(Randomized Period)
n=75 Participants
Subjects receive their optimal dose of LDX at either 30, 50, or 70 mg once-daily orally at approximately 7:00 AM +/- 2 hours for 6 weeks.
|
Placebo (Randomized Period)
n=73 Participants
Subjects receive placebo once-daily orally at approximately 7:00 AM +/- 2 hours for 6 weeks.
|
|---|---|---|
|
Percent of Participants With CGI-S at Endpoint of The Randomized Withdrawal Period, Last Observation Carried Forward (LOCF)
Among the most extremely ill
|
0 percentage of participants
|
0 percentage of participants
|
|
Percent of Participants With CGI-S at Endpoint of The Randomized Withdrawal Period, Last Observation Carried Forward (LOCF)
Normal, not at all ill
|
40.0 percentage of participants
|
8.2 percentage of participants
|
|
Percent of Participants With CGI-S at Endpoint of The Randomized Withdrawal Period, Last Observation Carried Forward (LOCF)
Borderline mentally ill
|
41.3 percentage of participants
|
19.2 percentage of participants
|
|
Percent of Participants With CGI-S at Endpoint of The Randomized Withdrawal Period, Last Observation Carried Forward (LOCF)
Mildly ill
|
8.0 percentage of participants
|
11.0 percentage of participants
|
|
Percent of Participants With CGI-S at Endpoint of The Randomized Withdrawal Period, Last Observation Carried Forward (LOCF)
Moderately ill
|
10.7 percentage of participants
|
39.7 percentage of participants
|
|
Percent of Participants With CGI-S at Endpoint of The Randomized Withdrawal Period, Last Observation Carried Forward (LOCF)
Markedly ill
|
0 percentage of participants
|
15.1 percentage of participants
|
|
Percent of Participants With CGI-S at Endpoint of The Randomized Withdrawal Period, Last Observation Carried Forward (LOCF)
Severely ill
|
0 percentage of participants
|
6.8 percentage of participants
|
SECONDARY outcome
Timeframe: At Week 26Population: Open-label FAS
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. Improvement includes CGI-I categories of very much improved and much improved. No improvement includes all other assessed categories.
Outcome measures
| Measure |
Lisdexamfetamine Dimesylate (LDX)(Randomized Period)
n=257 Participants
Subjects receive their optimal dose of LDX at either 30, 50, or 70 mg once-daily orally at approximately 7:00 AM +/- 2 hours for 6 weeks.
|
Placebo (Randomized Period)
Subjects receive placebo once-daily orally at approximately 7:00 AM +/- 2 hours for 6 weeks.
|
|---|---|---|
|
Percent of Participants With Improvement on Clinical Global Impression - Improvement (CGI-I) at Endpoint (Week-26) of The Open-label Period
|
79.8 percentage of improved participants
|
—
|
SECONDARY outcome
Timeframe: At open-label baseline and endpoint (Week-26) of the open-label periodPopulation: Open-label FAS
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.
Outcome measures
| Measure |
Lisdexamfetamine Dimesylate (LDX)(Randomized Period)
n=223 Participants
Subjects receive their optimal dose of LDX at either 30, 50, or 70 mg once-daily orally at approximately 7:00 AM +/- 2 hours for 6 weeks.
|
Placebo (Randomized Period)
Subjects receive placebo once-daily orally at approximately 7:00 AM +/- 2 hours for 6 weeks.
|
|---|---|---|
|
Change From Open-label Baseline in The Health Utilities Index-2 (HUI-2) Scores at Endpoint (Week-26) of The Open-label Period, LOCF
|
0.087 scores on a scale
Standard Deviation 0.1307
|
—
|
SECONDARY outcome
Timeframe: Baseline of the randomized withdrawal period and its relevant endpoint (Up to 6 weeks)Population: Randomized FAS
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.
Outcome measures
| Measure |
Lisdexamfetamine Dimesylate (LDX)(Randomized Period)
n=59 Participants
Subjects receive their optimal dose of LDX at either 30, 50, or 70 mg once-daily orally at approximately 7:00 AM +/- 2 hours for 6 weeks.
|
Placebo (Randomized Period)
n=62 Participants
Subjects receive placebo once-daily orally at approximately 7:00 AM +/- 2 hours for 6 weeks.
|
|---|---|---|
|
Change From Randomized Withdrawal Baseline in The HUI-2 Scores at Endpoint of The Randomized Withdrawal Period
|
-0.005 Scores on a scale
Standard Deviation 0.0772
|
-0.046 Scores on a scale
Standard Deviation 0.1098
|
SECONDARY outcome
Timeframe: At open-label baseline and endpoint (Week-26) of the open-label periodPopulation: Open-label FAS
The CHIP-CE:PRF evaluates health-related quality of life. It is composed of 5 domains (satisfaction, comfort, resilience, avoidance, and achievement) consisting of a total of 76 items. The global score is an average of the scores for the 5 domains. The majority of items assess frequency of events using a 5-point response format. There is no range for a total score. Raw scale scores are used to generate T-scores. Higher scores indicate better health.
Outcome measures
| Measure |
Lisdexamfetamine Dimesylate (LDX)(Randomized Period)
n=207 Participants
Subjects receive their optimal dose of LDX at either 30, 50, or 70 mg once-daily orally at approximately 7:00 AM +/- 2 hours for 6 weeks.
|
Placebo (Randomized Period)
Subjects receive placebo once-daily orally at approximately 7:00 AM +/- 2 hours for 6 weeks.
|
|---|---|---|
|
Change From Open-label Baseline in The Child Health and Illness Profile, Child Edition: Parent Report Form (CHIP-CE:PRF) Global T-score at Endpoint (Week-26) of The Open-label Period
|
10.2 T-scores
Standard Deviation 10.71
|
—
|
SECONDARY outcome
Timeframe: Baseline of the randomized withdrawal period and its relevant endpoint (Up to 6 weeks)Population: Randomized FAS
The CHIP-CE:PRF evaluates health-related quality of life. It is composed of 5 domains (satisfaction, comfort, resilience, avoidance, and achievement) consisting of a total of 76 items. The global score is an average of the scores for the 5 domains. The majority of items assess frequency of events using a 5-point response format. There is no range for a total score. Raw scale scores are used to generate T-scores. Higher scores indicate better health.
Outcome measures
| Measure |
Lisdexamfetamine Dimesylate (LDX)(Randomized Period)
n=52 Participants
Subjects receive their optimal dose of LDX at either 30, 50, or 70 mg once-daily orally at approximately 7:00 AM +/- 2 hours for 6 weeks.
|
Placebo (Randomized Period)
n=60 Participants
Subjects receive placebo once-daily orally at approximately 7:00 AM +/- 2 hours for 6 weeks.
|
|---|---|---|
|
Change From Randomized Withdrawal Baseline in The CHIP-CE:PRF Global T-score at Endpoint of The Randomized Withdrawal Period
|
1.1 T-scores
Standard Error 1.17
|
-5.4 T-scores
Standard Error 1.10
|
SECONDARY outcome
Timeframe: At open-label baseline and endpoint (Week-26) of the open-label periodPopulation: Open-label FAS
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.
Outcome measures
| Measure |
Lisdexamfetamine Dimesylate (LDX)(Randomized Period)
n=223 Participants
Subjects receive their optimal dose of LDX at either 30, 50, or 70 mg once-daily orally at approximately 7:00 AM +/- 2 hours for 6 weeks.
|
Placebo (Randomized Period)
Subjects receive placebo once-daily orally at approximately 7:00 AM +/- 2 hours for 6 weeks.
|
|---|---|---|
|
Change From Open-Label Baseline in The Weiss Functional Impairment Rating Scale - Parent Report (WFIRS-P) Global Score at Endpoint (Week-26) of The Open-label Period
|
-0.43 scores on a scale
Standard Deviation 0.42
|
—
|
SECONDARY outcome
Timeframe: Baseline of the randomized withdrawal period and its relevant endpoint (Up to 6 weeks)Population: Randomized FAS
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.
Outcome measures
| Measure |
Lisdexamfetamine Dimesylate (LDX)(Randomized Period)
n=58 Participants
Subjects receive their optimal dose of LDX at either 30, 50, or 70 mg once-daily orally at approximately 7:00 AM +/- 2 hours for 6 weeks.
|
Placebo (Randomized Period)
n=61 Participants
Subjects receive placebo once-daily orally at approximately 7:00 AM +/- 2 hours for 6 weeks.
|
|---|---|---|
|
Change From Randomized Withdrawal Baseline in The WFIRS-P Global Score at Endpoint of The Randomized Withdrawal Period
|
0.01 Scores on a scale
Standard Error 0.03
|
0.20 Scores on a scale
Standard Error 0.03
|
SECONDARY outcome
Timeframe: At open-label baseline and endpoint (Week-26) of the open-label periodPopulation: Open-label Safety Population includes all subjects who received at least 1 dose of investigational product in the Open-label period.
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.
Outcome measures
| Measure |
Lisdexamfetamine Dimesylate (LDX)(Randomized Period)
n=84 Participants
Subjects receive their optimal dose of LDX at either 30, 50, or 70 mg once-daily orally at approximately 7:00 AM +/- 2 hours for 6 weeks.
|
Placebo (Randomized Period)
Subjects receive placebo once-daily orally at approximately 7:00 AM +/- 2 hours for 6 weeks.
|
|---|---|---|
|
Change From Open-Label Baseline in The Brief Psychiatric Rating Scale for Children (BPRS-C) Total Score at Endpoint (Week-26) of The Open-label Period
|
-13.9 Scores on a scale
Standard Deviation 12.58
|
—
|
SECONDARY outcome
Timeframe: Baseline of the randomized withdrawal period and its relevant endpoint (Up to 6 weeks)Population: Randomized Safety Population includes all subjects who received at least 1 dose of any investigational product during the Randomized Withdrawal Period
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.
Outcome measures
| Measure |
Lisdexamfetamine Dimesylate (LDX)(Randomized Period)
n=23 Participants
Subjects receive their optimal dose of LDX at either 30, 50, or 70 mg once-daily orally at approximately 7:00 AM +/- 2 hours for 6 weeks.
|
Placebo (Randomized Period)
n=27 Participants
Subjects receive placebo once-daily orally at approximately 7:00 AM +/- 2 hours for 6 weeks.
|
|---|---|---|
|
Change From Randomized Withdrawal Baseline in BPRS-C Total Score at Endpoint of The Randomized Withdrawal Period
|
-17.1 Scores on a scale
Standard Deviation 11.17
|
-9.1 Scores on a scale
Standard Deviation 11.26
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Open-label baselinePopulation: Open-label FAS
CGI-S assesses the severity of the subject's condition on a 7-point scale ranging from 1 (normal, not at all ill) to 7 (among the most extremely ill).
Outcome measures
| Measure |
Lisdexamfetamine Dimesylate (LDX)(Randomized Period)
n=261 Participants
Subjects receive their optimal dose of LDX at either 30, 50, or 70 mg once-daily orally at approximately 7:00 AM +/- 2 hours for 6 weeks.
|
Placebo (Randomized Period)
Subjects receive placebo once-daily orally at approximately 7:00 AM +/- 2 hours for 6 weeks.
|
|---|---|---|
|
Percent of Participants With CGI-S at Open-label Baseline
Mildly ill
|
1.5 percentage of participants
|
—
|
|
Percent of Participants With CGI-S at Open-label Baseline
Normal, not at all ill
|
0 percentage of participants
|
—
|
|
Percent of Participants With CGI-S at Open-label Baseline
Borderline mentally ill
|
0 percentage of participants
|
—
|
|
Percent of Participants With CGI-S at Open-label Baseline
Moderately ill
|
27.2 percentage of participants
|
—
|
|
Percent of Participants With CGI-S at Open-label Baseline
Markedly ill
|
50.2 percentage of participants
|
—
|
|
Percent of Participants With CGI-S at Open-label Baseline
Severely ill
|
17.6 percentage of participants
|
—
|
|
Percent of Participants With CGI-S at Open-label Baseline
Among the most extremely ill
|
3.4 percentage of participants
|
—
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Randomized withdrawal baselinePopulation: Randomized FAS
CGI-S assesses the severity of the subject's condition on a 7-point scale ranging from 1 (normal, not at all ill) to 7 (among the most extremely ill)
Outcome measures
| Measure |
Lisdexamfetamine Dimesylate (LDX)(Randomized Period)
n=74 Participants
Subjects receive their optimal dose of LDX at either 30, 50, or 70 mg once-daily orally at approximately 7:00 AM +/- 2 hours for 6 weeks.
|
Placebo (Randomized Period)
n=77 Participants
Subjects receive placebo once-daily orally at approximately 7:00 AM +/- 2 hours for 6 weeks.
|
|---|---|---|
|
Percent of Participants With CGI-S at Randomized Withdrawal Baseline
Normal, not at all ill
|
50.0 percentage of participants
|
46.8 percentage of participants
|
|
Percent of Participants With CGI-S at Randomized Withdrawal Baseline
Borderline mentally ill
|
50.0 percentage of participants
|
53.2 percentage of participants
|
|
Percent of Participants With CGI-S at Randomized Withdrawal Baseline
Mildly ill
|
0 percentage of participants
|
0 percentage of participants
|
|
Percent of Participants With CGI-S at Randomized Withdrawal Baseline
Moderately ill
|
0 percentage of participants
|
0 percentage of participants
|
|
Percent of Participants With CGI-S at Randomized Withdrawal Baseline
Markedly ill
|
0 percentage of participants
|
0 percentage of participants
|
|
Percent of Participants With CGI-S at Randomized Withdrawal Baseline
Severely ill
|
0 percentage of participants
|
0 percentage of participants
|
|
Percent of Participants With CGI-S at Randomized Withdrawal Baseline
Among the most extremely ill
|
0 percentage of participants
|
0 percentage of participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: From open-label baseline to Week-26Population: Open-label Safety Population
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.
Outcome measures
| Measure |
Lisdexamfetamine Dimesylate (LDX)(Randomized Period)
n=118 Participants
Subjects receive their optimal dose of LDX at either 30, 50, or 70 mg once-daily orally at approximately 7:00 AM +/- 2 hours for 6 weeks.
|
Placebo (Randomized Period)
Subjects receive placebo once-daily orally at approximately 7:00 AM +/- 2 hours for 6 weeks.
|
|---|---|---|
|
Columbia-Suicide Severity Rating Scale (C-SSRS) During The Open-label Period
Suicidal ideation
|
1 participants
|
—
|
|
Columbia-Suicide Severity Rating Scale (C-SSRS) During The Open-label Period
Suicidal behavior
|
0 participants
|
—
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline of the randomized withdrawal period to end of the study (Up to 6 weeks)Population: Randomized Safety Population
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.
Outcome measures
| Measure |
Lisdexamfetamine Dimesylate (LDX)(Randomized Period)
n=45 Participants
Subjects receive their optimal dose of LDX at either 30, 50, or 70 mg once-daily orally at approximately 7:00 AM +/- 2 hours for 6 weeks.
|
Placebo (Randomized Period)
n=41 Participants
Subjects receive placebo once-daily orally at approximately 7:00 AM +/- 2 hours for 6 weeks.
|
|---|---|---|
|
C-SSRS During the Randomized Withdrawal Period
Suicidal behavior
|
0 participants
|
0 participants
|
|
C-SSRS During the Randomized Withdrawal Period
Suicidal ideation
|
0 participants
|
0 participants
|
Adverse Events
Lisdexamfetamine Dimesylate (LDX)(Open-label Period)
Serious events: 12 serious events
Other events: 227 other events
Deaths: 0 deaths
Lisdexamfetamine Dimesylate (LDX)(Randomized Period)
Serious events: 0 serious events
Other events: 31 other events
Deaths: 0 deaths
Placebo (Randomized Period)
Serious events: 1 serious events
Other events: 20 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Lisdexamfetamine Dimesylate (LDX)(Open-label Period)
n=276 participants at risk
Consists of at least 26 weeks where subjects are titrated to an optimal dose of LDX (either 30, 50 or 70 mg once-daily orally at approximately 7:00 AM) and then maintained on their optimal dose of LDX (either 30, 50 or 70 mg once-daily orally at approximately 7:00 AM).
|
Lisdexamfetamine Dimesylate (LDX)(Randomized Period)
n=78 participants at risk
After the Open-label Period, subjects were randomized to receive their optimal dose of LDX at either 30, 50, or 70 mg once-daily orally at approximately 7:00 AM for up to 6 weeks.
|
Placebo (Randomized Period)
n=79 participants at risk
After the Open-label Period, subjects were randomized to receive placebo once-daily orally at approximately 7:00 AM for up to 6 weeks.
|
|---|---|---|---|
|
Nervous system disorders
Syncope
|
0.72%
2/276 • Number of events 2 • 33 weeks
|
0.00%
0/78 • 33 weeks
|
0.00%
0/79 • 33 weeks
|
|
Psychiatric disorders
Aggression
|
0.72%
2/276 • Number of events 2 • 33 weeks
|
0.00%
0/78 • 33 weeks
|
0.00%
0/79 • 33 weeks
|
|
Gastrointestinal disorders
Abdominal pain
|
0.36%
1/276 • Number of events 1 • 33 weeks
|
0.00%
0/78 • 33 weeks
|
0.00%
0/79 • 33 weeks
|
|
Gastrointestinal disorders
Vomiting
|
0.36%
1/276 • Number of events 1 • 33 weeks
|
0.00%
0/78 • 33 weeks
|
0.00%
0/79 • 33 weeks
|
|
Infections and infestations
Cellulitis
|
0.36%
1/276 • Number of events 1 • 33 weeks
|
0.00%
0/78 • 33 weeks
|
0.00%
0/79 • 33 weeks
|
|
Infections and infestations
Gastric infection
|
0.36%
1/276 • Number of events 1 • 33 weeks
|
0.00%
0/78 • 33 weeks
|
0.00%
0/79 • 33 weeks
|
|
Injury, poisoning and procedural complications
Wound
|
0.36%
1/276 • Number of events 1 • 33 weeks
|
0.00%
0/78 • 33 weeks
|
0.00%
0/79 • 33 weeks
|
|
Metabolism and nutrition disorders
Dehydration
|
0.36%
1/276 • Number of events 1 • 33 weeks
|
0.00%
0/78 • 33 weeks
|
0.00%
0/79 • 33 weeks
|
|
Psychiatric disorders
Abnormal behavior
|
0.36%
1/276 • Number of events 1 • 33 weeks
|
0.00%
0/78 • 33 weeks
|
0.00%
0/79 • 33 weeks
|
|
Psychiatric disorders
Anger
|
0.36%
1/276 • Number of events 1 • 33 weeks
|
0.00%
0/78 • 33 weeks
|
0.00%
0/79 • 33 weeks
|
|
Psychiatric disorders
Oppositional defiant disorder
|
0.36%
1/276 • Number of events 1 • 33 weeks
|
0.00%
0/78 • 33 weeks
|
0.00%
0/79 • 33 weeks
|
|
Social circumstances
Treatment noncompliance
|
0.36%
1/276 • Number of events 1 • 33 weeks
|
0.00%
0/78 • 33 weeks
|
0.00%
0/79 • 33 weeks
|
|
Psychiatric disorders
Attention deficit/hyperactivity disorder
|
0.00%
0/276 • 33 weeks
|
0.00%
0/78 • 33 weeks
|
1.3%
1/79 • Number of events 1 • 33 weeks
|
Other adverse events
| Measure |
Lisdexamfetamine Dimesylate (LDX)(Open-label Period)
n=276 participants at risk
Consists of at least 26 weeks where subjects are titrated to an optimal dose of LDX (either 30, 50 or 70 mg once-daily orally at approximately 7:00 AM) and then maintained on their optimal dose of LDX (either 30, 50 or 70 mg once-daily orally at approximately 7:00 AM).
|
Lisdexamfetamine Dimesylate (LDX)(Randomized Period)
n=78 participants at risk
After the Open-label Period, subjects were randomized to receive their optimal dose of LDX at either 30, 50, or 70 mg once-daily orally at approximately 7:00 AM for up to 6 weeks.
|
Placebo (Randomized Period)
n=79 participants at risk
After the Open-label Period, subjects were randomized to receive placebo once-daily orally at approximately 7:00 AM for up to 6 weeks.
|
|---|---|---|---|
|
Metabolism and nutrition disorders
Decreased appetite
|
27.5%
76/276 • Number of events 91 • 33 weeks
|
3.8%
3/78 • Number of events 3 • 33 weeks
|
0.00%
0/79 • 33 weeks
|
|
Nervous system disorders
Headache
|
21.0%
58/276 • Number of events 80 • 33 weeks
|
7.7%
6/78 • Number of events 6 • 33 weeks
|
6.3%
5/79 • Number of events 7 • 33 weeks
|
|
Investigations
Weight decreased
|
16.7%
46/276 • Number of events 60 • 33 weeks
|
2.6%
2/78 • Number of events 2 • 33 weeks
|
1.3%
1/79 • Number of events 1 • 33 weeks
|
|
Infections and infestations
Nasopharyngitis
|
15.6%
43/276 • Number of events 64 • 33 weeks
|
9.0%
7/78 • Number of events 7 • 33 weeks
|
3.8%
3/79 • Number of events 3 • 33 weeks
|
|
Metabolism and nutrition disorders
Anorexia
|
14.9%
41/276 • Number of events 48 • 33 weeks
|
0.00%
0/78 • 33 weeks
|
0.00%
0/79 • 33 weeks
|
|
Psychiatric disorders
Insomnia
|
14.1%
39/276 • Number of events 44 • 33 weeks
|
1.3%
1/78 • Number of events 1 • 33 weeks
|
1.3%
1/79 • Number of events 1 • 33 weeks
|
|
Gastrointestinal disorders
Vomiting
|
11.6%
32/276 • Number of events 43 • 33 weeks
|
2.6%
2/78 • Number of events 2 • 33 weeks
|
1.3%
1/79 • Number of events 1 • 33 weeks
|
|
Gastrointestinal disorders
Nausea
|
9.8%
27/276 • Number of events 36 • 33 weeks
|
2.6%
2/78 • Number of events 2 • 33 weeks
|
0.00%
0/79 • 33 weeks
|
|
Gastrointestinal disorders
Abdominal pain upper
|
8.3%
23/276 • Number of events 25 • 33 weeks
|
5.1%
4/78 • Number of events 4 • 33 weeks
|
2.5%
2/79 • Number of events 2 • 33 weeks
|
|
Gastrointestinal disorders
Abdominal pain
|
7.2%
20/276 • Number of events 25 • 33 weeks
|
2.6%
2/78 • Number of events 2 • 33 weeks
|
0.00%
0/79 • 33 weeks
|
|
Psychiatric disorders
Initial insomnia
|
7.2%
20/276 • Number of events 22 • 33 weeks
|
1.3%
1/78 • Number of events 1 • 33 weeks
|
0.00%
0/79 • 33 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
6.9%
19/276 • Number of events 25 • 33 weeks
|
2.6%
2/78 • Number of events 2 • 33 weeks
|
0.00%
0/79 • 33 weeks
|
|
General disorders
Fatigue
|
6.5%
18/276 • Number of events 22 • 33 weeks
|
1.3%
1/78 • Number of events 1 • 33 weeks
|
0.00%
0/79 • 33 weeks
|
|
General disorders
Pyrexia
|
6.5%
18/276 • Number of events 25 • 33 weeks
|
1.3%
1/78 • Number of events 1 • 33 weeks
|
1.3%
1/79 • Number of events 1 • 33 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
5.4%
15/276 • Number of events 18 • 33 weeks
|
3.8%
3/78 • Number of events 3 • 33 weeks
|
5.1%
4/79 • Number of events 4 • 33 weeks
|
|
Infections and infestations
Upper respiratory tract infection
|
5.1%
14/276 • Number of events 21 • 33 weeks
|
1.3%
1/78 • Number of events 1 • 33 weeks
|
1.3%
1/79 • Number of events 1 • 33 weeks
|
|
General disorders
Irritability
|
4.7%
13/276 • Number of events 17 • 33 weeks
|
0.00%
0/78 • 33 weeks
|
0.00%
0/79 • 33 weeks
|
|
Gastrointestinal disorders
Diarrhea
|
4.3%
12/276 • Number of events 12 • 33 weeks
|
1.3%
1/78 • Number of events 1 • 33 weeks
|
0.00%
0/79 • 33 weeks
|
|
Psychiatric disorders
Depressed mood
|
4.0%
11/276 • Number of events 16 • 33 weeks
|
0.00%
0/78 • 33 weeks
|
0.00%
0/79 • 33 weeks
|
|
Psychiatric disorders
Anxiety
|
3.3%
9/276 • Number of events 9 • 33 weeks
|
0.00%
0/78 • 33 weeks
|
0.00%
0/79 • 33 weeks
|
|
Infections and infestations
Gastroenteritis
|
3.3%
9/276 • Number of events 11 • 33 weeks
|
1.3%
1/78 • Number of events 1 • 33 weeks
|
2.5%
2/79 • Number of events 2 • 33 weeks
|
|
Nervous system disorders
Dizziness
|
2.9%
8/276 • Number of events 8 • 33 weeks
|
0.00%
0/78 • 33 weeks
|
0.00%
0/79 • 33 weeks
|
|
Psychiatric disorders
Tic
|
2.9%
8/276 • Number of events 11 • 33 weeks
|
0.00%
0/78 • 33 weeks
|
0.00%
0/79 • 33 weeks
|
|
Psychiatric disorders
Aggression
|
2.5%
7/276 • Number of events 7 • 33 weeks
|
2.6%
2/78 • Number of events 2 • 33 weeks
|
0.00%
0/79 • 33 weeks
|
|
Infections and infestations
Sinusitis
|
2.5%
7/276 • Number of events 7 • 33 weeks
|
1.3%
1/78 • Number of events 1 • 33 weeks
|
1.3%
1/79 • Number of events 1 • 33 weeks
|
|
Ear and labyrinth disorders
Ear pain
|
2.2%
6/276 • Number of events 6 • 33 weeks
|
0.00%
0/78 • 33 weeks
|
0.00%
0/79 • 33 weeks
|
|
Infections and infestations
Tonsillitis
|
2.2%
6/276 • Number of events 6 • 33 weeks
|
1.3%
1/78 • Number of events 2 • 33 weeks
|
0.00%
0/79 • 33 weeks
|
|
Injury, poisoning and procedural complications
Accidental overdose
|
1.1%
3/276 • Number of events 3 • 33 weeks
|
2.6%
2/78 • Number of events 2 • 33 weeks
|
0.00%
0/79 • 33 weeks
|
|
Infections and infestations
Rhinitis
|
0.36%
1/276 • Number of events 2 • 33 weeks
|
2.6%
2/78 • Number of events 2 • 33 weeks
|
0.00%
0/79 • 33 weeks
|
|
Psychiatric disorders
Attention deficit/hyperactivity disorder
|
0.72%
2/276 • Number of events 2 • 33 weeks
|
0.00%
0/78 • 33 weeks
|
2.5%
2/79 • Number of events 2 • 33 weeks
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee 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.
- Publication restrictions are in place
Restriction type: OTHER