Trial Outcomes & Findings for Comparing the Effectiveness of New Versus Older Treatments for Attention Deficit Hyperactivity Disorder (The NOTA Study) (NCT NCT00889915)
NCT ID: NCT00889915
Last Updated: 2013-09-30
Results Overview
The CGI-E is the value at which the participant's Therapeutic Benefit and Adverse Impact to the study drug intersect. This number is determined by combining each participant's scores for the degree of Therapeutic Benefit versus the degree to which problems with Tolerability and/or Acceptability adversely impact the subject. Participants are then determined to be Responders or Non-responders to the study medication. For example, a subject who is very much improved (CGI-I=1) or much improved (CGI-I=2) therapeutically and whose adverse impact rating is none (score 1,5) or mild (score 2,6) will be categorized as a Responder. All others whose adverse impact rating is moderate (score 3,7,11,15)or outweighs therapeutic effect (score 4,8,12,16) will be categorized as Non-responders to study medication. The CGI scores are totaled for each participant and a mean score is calculated. A median total score was calculated for each treatment group.
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
228 participants
Primary outcome timeframe
Measured at each participant's last visit, which can occur at or before Week 6
Results posted on
2013-09-30
Participant Flow
Recruitment period was April to October 2009. Recruitment occurred at Child and Adolescent Psychiatry clinics in the USA.
Participant milestones
| Measure |
Daytrana (Methylphenidate Transdermal System
Participants will receive methylphenidate transdermal system.
Methylphenidate transdermal system : Not specified in protocol; determined by local standard of care.
|
Vyvanse (Lisdexamfetamine Dimesylate)
Participants will receive lisdexamfetamine dimesylate.
Lisdexamfetamine dimesylate : Not specified in protocol; determined by local standard of care.
|
Concerta (Osmotic-release Oral System Methylphenidate)
Participants will receive osmotic-release oral system methylphenidate (OROS MPH).
Osmotic-release oral system methylphenidate (OROS MPH) : Not specified in protocol; determined by local standard of care.
|
Adderall (Mixed Amphetamine Salts Extended Release)
Participants will receive mixed amphetamine salts extended release.
Mixed amphetamine salts extended release : Not specified in protocol; determined by local standard of care.
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
37
|
76
|
67
|
48
|
|
Overall Study
COMPLETED
|
35
|
71
|
54
|
40
|
|
Overall Study
NOT COMPLETED
|
2
|
5
|
13
|
8
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Comparing the Effectiveness of New Versus Older Treatments for Attention Deficit Hyperactivity Disorder (The NOTA Study)
Baseline characteristics by cohort
| Measure |
Daytrana (Methylphenidate Transdermal System
n=37 Participants
Participants will receive methylphenidate transdermal system. Although not specified by protocol, rather determined by local standard of care, the typical doses and strategies are as follows:
Dose form as 10, 15, 20, 30 mg patches. Typical starting dose is 10 mg patch every day then titrate up by patch strength.
The FDA maximum dose per day is 30 mg and the off label maximum dose per day is 40 mg.
The patch should be applied to the hip area, avoiding the waistline and the patch application should be alternated between hips.
|
Vyvanse (Lisdexamfetamine Dimesylate)
n=76 Participants
Participants will receive lisdexamfetamine dimesylate.
Although not specified by protocol, rather determined by local standard of care, the typical doses and strategies are as follows:
Dose form is 20, 30, 40, 50, 60, 70 mg ivory body/ivory cap. The typical starting dose is 30 mg every day in the morning; dosage may be adjusted in increments of 10 mg or 20 mg at approximately weekly intervals.
The FDA maximum dose per day is 70 mg. Afternoon doses should be avoided because of the potential for insomnia. Vyvanse may be taken with or without food. Vyvanse capsules may be taken whole, or the capsule may be opened and the entire contents dissolved in a glass of water. The solution should be consumed immediately and should not be stored. The dose of a single capsule should not be divided.
|
Concerta (Osmotic-release Oral System Methylphenidate)
n=67 Participants
Participants will receive osmotic-release oral system methylphenidate (OROS MPH).
Although not specified by protocol, rather determined by local standard of care, the typical doses and strategies are as follows:
Dose form is 18, 27, 36, 54 mg capsules. The typical starting dose is 18 mg every morning. The FDA maximum dose per day is 54 mg in children or 72 mg in adolescents. The off label maximum dose is 108 mg. Longer acting stimulants offer greater convenience, confidentiality, and compliance with single daily dosing, but may have greater problematic effects on evening appetite and sleep. Its nonabsorbable tablet shell may appear in the stool.
Osmotic-release oral system methylphenidate (OROS MPH) : Not specified in protocol; determined by local standard of care.
|
Adderall (Mixed Amphetamine Salts Extended Release)
n=48 Participants
Participants will receive mixed amphetamine salts extended release.
Although not specified by protocol, rather determined by local standard of care, the typical doses and strategies are as follows:
The dose form for is 5, 10, 15, 20, 25, 30 mg capsules. The typical starting dose for children greater than or equal to 6 years of age is 10 mg every day.
The FDA maximum dose per day is 30 mg if weight is greater than 50 kilograms. The off label maximum dose per day is 60 mg. The capsule may be opened and sprinkled on soft foods.
|
Total
n=228 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Categorical
<=18 years
|
37 Participants
n=5 Participants
|
76 Participants
n=7 Participants
|
67 Participants
n=5 Participants
|
48 Participants
n=4 Participants
|
228 Participants
n=21 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Age Continuous
|
10.3 years
STANDARD_DEVIATION 3.2 • n=5 Participants
|
10.6 years
STANDARD_DEVIATION 3.1 • n=7 Participants
|
10.0 years
STANDARD_DEVIATION 3.2 • n=5 Participants
|
10.4 years
STANDARD_DEVIATION 3.0 • n=4 Participants
|
10.3 years
STANDARD_DEVIATION 3.1 • n=21 Participants
|
|
Sex: Female, Male
Female
|
10 Participants
n=5 Participants
|
21 Participants
n=7 Participants
|
25 Participants
n=5 Participants
|
16 Participants
n=4 Participants
|
72 Participants
n=21 Participants
|
|
Sex: Female, Male
Male
|
27 Participants
n=5 Participants
|
55 Participants
n=7 Participants
|
42 Participants
n=5 Participants
|
32 Participants
n=4 Participants
|
156 Participants
n=21 Participants
|
|
Region of Enrollment
United States
|
37 participants
n=5 Participants
|
76 participants
n=7 Participants
|
67 participants
n=5 Participants
|
48 participants
n=4 Participants
|
228 participants
n=21 Participants
|
PRIMARY outcome
Timeframe: Measured at each participant's last visit, which can occur at or before Week 6The CGI-E is the value at which the participant's Therapeutic Benefit and Adverse Impact to the study drug intersect. This number is determined by combining each participant's scores for the degree of Therapeutic Benefit versus the degree to which problems with Tolerability and/or Acceptability adversely impact the subject. Participants are then determined to be Responders or Non-responders to the study medication. For example, a subject who is very much improved (CGI-I=1) or much improved (CGI-I=2) therapeutically and whose adverse impact rating is none (score 1,5) or mild (score 2,6) will be categorized as a Responder. All others whose adverse impact rating is moderate (score 3,7,11,15)or outweighs therapeutic effect (score 4,8,12,16) will be categorized as Non-responders to study medication. The CGI scores are totaled for each participant and a mean score is calculated. A median total score was calculated for each treatment group.
Outcome measures
| Measure |
Daytrana (Methylphenidate Transdermal System
n=35 Participants
Participants will receive methylphenidate transdermal system.
Methylphenidate transdermal system : Not specified in protocol; determined by local standard of care.
|
Vyvanse (Lisdexamfetamine Dimesylate)
n=71 Participants
Participants will receive lisdexamfetamine dimesylate.
Lisdexamfetamine dimesylate : Not specified in protocol; determined by local standard of care.
|
Concerta (Osmotic-release Oral System Methylphenidate)
n=54 Participants
Participants will receive osmotic-release oral system methylphenidate (OROS MPH).
Osmotic-release oral system methylphenidate (OROS MPH) : Not specified in protocol; determined by local standard of care.
|
Adderall (Mixed Amphetamine Salts Extended Release)
n=40 Participants
Participants will receive mixed amphetamine salts extended release.
Mixed amphetamine salts extended release : Not specified in protocol; determined by local standard of care.
|
|---|---|---|---|---|
|
Dichotomized Clinical Global Impression-Effectiveness (CGI-E) Scale
|
7.0 Units on a scale
Full Range 16.0 • Interval 1.0 to 16.0
|
5.0 Units on a scale
Full Range 16.0 • Interval 1.0 to 16.0
|
6.0 Units on a scale
Full Range 16.0 • Interval 1.0 to 16.0
|
6.0 Units on a scale
Full Range 16.0 • Interval 1.0 to 16.0
|
SECONDARY outcome
Timeframe: Measured at each participant's last visit, which can occur at or before Week 6The CGI-I score at the subject's last study visit at or before Week 6, is one of the 3 secondary endpoints that contribute to the primary endpoint (CGI-E). The CGI-I scale will be used to rate improvement in the subject's condition (benefits) since baseline using the following 7-point scale: 1=very much improved, 2=much improved, 3=minimally improved, 4=not changed, 5=minimally worse, 6=much worse; 7=very much worse.
Outcome measures
| Measure |
Daytrana (Methylphenidate Transdermal System
n=35 Participants
Participants will receive methylphenidate transdermal system.
Methylphenidate transdermal system : Not specified in protocol; determined by local standard of care.
|
Vyvanse (Lisdexamfetamine Dimesylate)
n=71 Participants
Participants will receive lisdexamfetamine dimesylate.
Lisdexamfetamine dimesylate : Not specified in protocol; determined by local standard of care.
|
Concerta (Osmotic-release Oral System Methylphenidate)
n=54 Participants
Participants will receive osmotic-release oral system methylphenidate (OROS MPH).
Osmotic-release oral system methylphenidate (OROS MPH) : Not specified in protocol; determined by local standard of care.
|
Adderall (Mixed Amphetamine Salts Extended Release)
n=40 Participants
Participants will receive mixed amphetamine salts extended release.
Mixed amphetamine salts extended release : Not specified in protocol; determined by local standard of care.
|
|---|---|---|---|---|
|
Clinical Global Impressions-Improvement (CGI-I) Scale
|
2.0 Units on a scale
Interval 1.0 to 5.0
|
2.0 Units on a scale
Interval 1.0 to 5.0
|
2.0 Units on a scale
Interval 1.0 to 7.0
|
2.0 Units on a scale
Interval 1.0 to 5.0
|
SECONDARY outcome
Timeframe: Measured at each participant's last visit, which can occur at or before Week 6The CGI-A score at the subject's last study visit at or before Week 6 is one of the 3 secondary endpoints that contribute to the primary endpoint (CGI-E). The CGI-A will be used to assess the acceptability of the study medication with respect to the subject's experience with the formulation of medication. The 7-point rating for the CGI-A will be: 1=very high acceptability, 2=high acceptability, 3=above average acceptability, 4=average acceptability, 5=low acceptability, 6=very low acceptability, 7=extremely low acceptability
Outcome measures
| Measure |
Daytrana (Methylphenidate Transdermal System
n=35 Participants
Participants will receive methylphenidate transdermal system.
Methylphenidate transdermal system : Not specified in protocol; determined by local standard of care.
|
Vyvanse (Lisdexamfetamine Dimesylate)
n=71 Participants
Participants will receive lisdexamfetamine dimesylate.
Lisdexamfetamine dimesylate : Not specified in protocol; determined by local standard of care.
|
Concerta (Osmotic-release Oral System Methylphenidate)
n=54 Participants
Participants will receive osmotic-release oral system methylphenidate (OROS MPH).
Osmotic-release oral system methylphenidate (OROS MPH) : Not specified in protocol; determined by local standard of care.
|
Adderall (Mixed Amphetamine Salts Extended Release)
n=40 Participants
Participants will receive mixed amphetamine salts extended release.
Mixed amphetamine salts extended release : Not specified in protocol; determined by local standard of care.
|
|---|---|---|---|---|
|
Clinical Global Improvements-Acceptability (CGI-A) Scale
|
3.0 Units on a scale
Interval 1.0 to 7.0
|
2.0 Units on a scale
Interval 1.0 to 6.0
|
2.0 Units on a scale
Interval 1.0 to 7.0
|
2.0 Units on a scale
Interval 1.0 to 6.0
|
Adverse Events
Daytrana (Methylphenidate Transdermal System
Serious events: 2 serious events
Other events: 16 other events
Deaths: 0 deaths
Vyvanse (Lisdexamfetamine Dimesylate)
Serious events: 0 serious events
Other events: 33 other events
Deaths: 0 deaths
Concerta (Osmotic-release Oral System Methylphenidate)
Serious events: 1 serious events
Other events: 18 other events
Deaths: 0 deaths
Adderall (Mixed Amphetamine Salts Extended Release)
Serious events: 0 serious events
Other events: 15 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Daytrana (Methylphenidate Transdermal System
n=33 participants at risk
Participants will receive methylphenidate transdermal system.
Methylphenidate transdermal system : Not specified in protocol; determined by local standard of care.
|
Vyvanse (Lisdexamfetamine Dimesylate)
n=67 participants at risk
Participants will receive lisdexamfetamine dimesylate.
Lisdexamfetamine dimesylate : Not specified in protocol; determined by local standard of care.
|
Concerta (Osmotic-release Oral System Methylphenidate)
n=53 participants at risk
Participants will receive osmotic-release oral system methylphenidate (OROS MPH).
Osmotic-release oral system methylphenidate (OROS MPH) : Not specified in protocol; determined by local standard of care.
|
Adderall (Mixed Amphetamine Salts Extended Release)
n=39 participants at risk
Participants will receive mixed amphetamine salts extended release.
Mixed amphetamine salts extended release : Not specified in protocol; determined by local standard of care.
|
|---|---|---|---|---|
|
Cardiac disorders
Tachycardia / arrhythmia
|
3.0%
1/33 • Number of events 1 • Adverse events were collected from baseline through the participant's last visit. The participant's last visit can can occur at or before 6 weeks after study medication was started.
|
0.00%
0/67 • Adverse events were collected from baseline through the participant's last visit. The participant's last visit can can occur at or before 6 weeks after study medication was started.
|
0.00%
0/53 • Adverse events were collected from baseline through the participant's last visit. The participant's last visit can can occur at or before 6 weeks after study medication was started.
|
0.00%
0/39 • Adverse events were collected from baseline through the participant's last visit. The participant's last visit can can occur at or before 6 weeks after study medication was started.
|
|
Psychiatric disorders
Assaultive/Aggressive behavior
|
0.00%
0/33 • Adverse events were collected from baseline through the participant's last visit. The participant's last visit can can occur at or before 6 weeks after study medication was started.
|
0.00%
0/67 • Adverse events were collected from baseline through the participant's last visit. The participant's last visit can can occur at or before 6 weeks after study medication was started.
|
1.9%
1/53 • Number of events 1 • Adverse events were collected from baseline through the participant's last visit. The participant's last visit can can occur at or before 6 weeks after study medication was started.
|
0.00%
0/39 • Adverse events were collected from baseline through the participant's last visit. The participant's last visit can can occur at or before 6 weeks after study medication was started.
|
|
Nervous system disorders
Hypersomnia
|
3.0%
1/33 • Number of events 1 • Adverse events were collected from baseline through the participant's last visit. The participant's last visit can can occur at or before 6 weeks after study medication was started.
|
0.00%
0/67 • Adverse events were collected from baseline through the participant's last visit. The participant's last visit can can occur at or before 6 weeks after study medication was started.
|
0.00%
0/52 • Adverse events were collected from baseline through the participant's last visit. The participant's last visit can can occur at or before 6 weeks after study medication was started.
|
0.00%
0/39 • Adverse events were collected from baseline through the participant's last visit. The participant's last visit can can occur at or before 6 weeks after study medication was started.
|
Other adverse events
| Measure |
Daytrana (Methylphenidate Transdermal System
n=33 participants at risk
Participants will receive methylphenidate transdermal system.
Methylphenidate transdermal system : Not specified in protocol; determined by local standard of care.
|
Vyvanse (Lisdexamfetamine Dimesylate)
n=67 participants at risk
Participants will receive lisdexamfetamine dimesylate.
Lisdexamfetamine dimesylate : Not specified in protocol; determined by local standard of care.
|
Concerta (Osmotic-release Oral System Methylphenidate)
n=53 participants at risk
Participants will receive osmotic-release oral system methylphenidate (OROS MPH).
Osmotic-release oral system methylphenidate (OROS MPH) : Not specified in protocol; determined by local standard of care.
|
Adderall (Mixed Amphetamine Salts Extended Release)
n=39 participants at risk
Participants will receive mixed amphetamine salts extended release.
Mixed amphetamine salts extended release : Not specified in protocol; determined by local standard of care.
|
|---|---|---|---|---|
|
Psychiatric disorders
Irritability
|
3.0%
1/33 • Number of events 9 • Adverse events were collected from baseline through the participant's last visit. The participant's last visit can can occur at or before 6 weeks after study medication was started.
|
7.5%
5/67 • Number of events 9 • Adverse events were collected from baseline through the participant's last visit. The participant's last visit can can occur at or before 6 weeks after study medication was started.
|
1.9%
1/53 • Number of events 9 • Adverse events were collected from baseline through the participant's last visit. The participant's last visit can can occur at or before 6 weeks after study medication was started.
|
5.1%
2/39 • Number of events 9 • Adverse events were collected from baseline through the participant's last visit. The participant's last visit can can occur at or before 6 weeks after study medication was started.
|
|
Psychiatric disorders
Insomnia
|
15.2%
5/33 • Number of events 18 • Adverse events were collected from baseline through the participant's last visit. The participant's last visit can can occur at or before 6 weeks after study medication was started.
|
9.0%
6/67 • Number of events 18 • Adverse events were collected from baseline through the participant's last visit. The participant's last visit can can occur at or before 6 weeks after study medication was started.
|
9.4%
5/53 • Number of events 18 • Adverse events were collected from baseline through the participant's last visit. The participant's last visit can can occur at or before 6 weeks after study medication was started.
|
5.1%
2/39 • Number of events 18 • Adverse events were collected from baseline through the participant's last visit. The participant's last visit can can occur at or before 6 weeks after study medication was started.
|
|
Psychiatric disorders
Angry or hostile mood
|
3.0%
1/33 • Number of events 9 • Adverse events were collected from baseline through the participant's last visit. The participant's last visit can can occur at or before 6 weeks after study medication was started.
|
4.5%
3/67 • Number of events 9 • Adverse events were collected from baseline through the participant's last visit. The participant's last visit can can occur at or before 6 weeks after study medication was started.
|
3.8%
2/53 • Number of events 9 • Adverse events were collected from baseline through the participant's last visit. The participant's last visit can can occur at or before 6 weeks after study medication was started.
|
7.7%
3/39 • Number of events 9 • Adverse events were collected from baseline through the participant's last visit. The participant's last visit can can occur at or before 6 weeks after study medication was started.
|
|
General disorders
Weight loss
|
6.1%
2/33 • Number of events 10 • Adverse events were collected from baseline through the participant's last visit. The participant's last visit can can occur at or before 6 weeks after study medication was started.
|
4.5%
3/67 • Number of events 10 • Adverse events were collected from baseline through the participant's last visit. The participant's last visit can can occur at or before 6 weeks after study medication was started.
|
5.7%
3/53 • Number of events 10 • Adverse events were collected from baseline through the participant's last visit. The participant's last visit can can occur at or before 6 weeks after study medication was started.
|
5.1%
2/39 • Number of events 10 • Adverse events were collected from baseline through the participant's last visit. The participant's last visit can can occur at or before 6 weeks after study medication was started.
|
|
General disorders
Decreased appetite
|
15.2%
5/33 • Number of events 25 • Adverse events were collected from baseline through the participant's last visit. The participant's last visit can can occur at or before 6 weeks after study medication was started.
|
16.4%
11/67 • Number of events 25 • Adverse events were collected from baseline through the participant's last visit. The participant's last visit can can occur at or before 6 weeks after study medication was started.
|
7.5%
4/53 • Number of events 25 • Adverse events were collected from baseline through the participant's last visit. The participant's last visit can can occur at or before 6 weeks after study medication was started.
|
12.8%
5/39 • Number of events 25 • Adverse events were collected from baseline through the participant's last visit. The participant's last visit can can occur at or before 6 weeks after study medication was started.
|
|
Psychiatric disorders
Emotional lability
|
6.1%
2/33 • Number of events 9 • Adverse events were collected from baseline through the participant's last visit. The participant's last visit can can occur at or before 6 weeks after study medication was started.
|
6.0%
4/67 • Number of events 9 • Adverse events were collected from baseline through the participant's last visit. The participant's last visit can can occur at or before 6 weeks after study medication was started.
|
3.8%
2/53 • Number of events 9 • Adverse events were collected from baseline through the participant's last visit. The participant's last visit can can occur at or before 6 weeks after study medication was started.
|
2.6%
1/39 • Number of events 9 • Adverse events were collected from baseline through the participant's last visit. The participant's last visit can can occur at or before 6 weeks after study medication was started.
|
|
Nervous system disorders
Tics
|
6.1%
2/33 • Number of events 2 • Adverse events were collected from baseline through the participant's last visit. The participant's last visit can can occur at or before 6 weeks after study medication was started.
|
1.5%
1/67 • Number of events 2 • Adverse events were collected from baseline through the participant's last visit. The participant's last visit can can occur at or before 6 weeks after study medication was started.
|
1.9%
1/53 • Number of events 2 • Adverse events were collected from baseline through the participant's last visit. The participant's last visit can can occur at or before 6 weeks after study medication was started.
|
5.1%
2/39 • Number of events 2 • Adverse events were collected from baseline through the participant's last visit. The participant's last visit can can occur at or before 6 weeks after study medication was started.
|
|
Skin and subcutaneous tissue disorders
Rash
|
18.2%
6/33 • Number of events 6 • Adverse events were collected from baseline through the participant's last visit. The participant's last visit can can occur at or before 6 weeks after study medication was started.
|
9.0%
6/67 • Number of events 6 • Adverse events were collected from baseline through the participant's last visit. The participant's last visit can can occur at or before 6 weeks after study medication was started.
|
11.3%
6/53 • Number of events 6 • Adverse events were collected from baseline through the participant's last visit. The participant's last visit can can occur at or before 6 weeks after study medication was started.
|
15.4%
6/39 • Number of events 6 • Adverse events were collected from baseline through the participant's last visit. The participant's last visit can can occur at or before 6 weeks after study medication was started.
|
Additional Information
John S. March, MD, MPH
Duke Clinical Research Institute - Duke University School of Medicine
Phone: 919-668-7818
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place