Trial Outcomes & Findings for Effectiveness and Duration of Effect of Open Treatment in Attention Deficit Hyperactivity Disorder (ADHD) Patients Treated With Lisdexamfetamine Dimesylate(Vyvanse) (NCT NCT01070394)

Results Overview

The ADHD-RS with adult ADHD prompts is a semi-structured scale that consists of 18 items that directly correspond to the 18 DSM-IV symptoms of ADHD, and is designed to assess current symptomatology19. Each item is scored on a 4-point scale ranging from 0 (none) to 3 (severe).Each item on the 18-item measure is scored on a 4-point scale ranging from 0 (no symptoms) to 3 (severe symptoms), yielding a possible total score of 0-54. A score of 0-16 means "Unlikely to have ADHD"; a score of 17-23 "Likely to Have ADHD" ; 24 or greater-Highly Likely to have ADHD

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

40 participants

Primary outcome timeframe

12 weeks

Results posted on

2018-04-03

Participant Flow

The first 25 participants enrolled consisted of adults who had recently completed a randomized, cross-over, open label study (MAS Adherence Study) that examined adherence to ADHD treatment with MAS IR vs. MAS XR. An additional 15 adults were recruited from local advertising and from the pool of participants at the MHADRP at the NYU SoM.

Participants taking prohibited concomitant medications, including ADHD medications, will be required to washout of their medication during the screening phase.The washout period will be one week for psychostimulants and three weeks for non-stimulants.

Participant milestones

Participant milestones
Measure	Overall Study: Lisdexamfetamine Treatment The treatment arm will receive 12 weeks of Lisdexamfetamine Dimesylate-LDX treatment. At baseline, participants were initiated on LDX at a dose of 30 mg/day and began a 4-week dose optimization phase with weekly clinic visits. The dose optimization phase was followed by an 8-week dose maintenance phase, which included clinic visits every 2 weeks for the assessment of safety and efficacy. At visits 3-6, the dose of LDX was increased by 20 mg/day until an optimal dose or the maximum dose of 80 mg/day was reached. An optimal dose was determined by clinical efficacy, defined as a \>= 30% reduction in the baseline ADHD Rating Scale, and tolerability. At the discretion of the investigator, the dose could be down-titrated by 20 mg/day at visits 4-6. When an optimal dose was reached, the participant remained at this level for the duration of the study.
Overall Study STARTED	40
Overall Study COMPLETED	33
Overall Study NOT COMPLETED	7

Reasons for withdrawal

Reasons for withdrawal
Measure	Overall Study: Lisdexamfetamine Treatment The treatment arm will receive 12 weeks of Lisdexamfetamine Dimesylate-LDX treatment. At baseline, participants were initiated on LDX at a dose of 30 mg/day and began a 4-week dose optimization phase with weekly clinic visits. The dose optimization phase was followed by an 8-week dose maintenance phase, which included clinic visits every 2 weeks for the assessment of safety and efficacy. At visits 3-6, the dose of LDX was increased by 20 mg/day until an optimal dose or the maximum dose of 80 mg/day was reached. An optimal dose was determined by clinical efficacy, defined as a \>= 30% reduction in the baseline ADHD Rating Scale, and tolerability. At the discretion of the investigator, the dose could be down-titrated by 20 mg/day at visits 4-6. When an optimal dose was reached, the participant remained at this level for the duration of the study.
Overall Study Adverse Event	6
Overall Study Withdrawal by Subject	1

Baseline Characteristics

Effectiveness and Duration of Effect of Open Treatment in Attention Deficit Hyperactivity Disorder (ADHD) Patients Treated With Lisdexamfetamine Dimesylate(Vyvanse)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	LDX Treatment n=33 Participants Prospective participants will be evaluated for ADHD and study inclusion/exclusion criteria. Eligible participants will begin open-label lisdexamfetamine dimesylate for 12 weeks. Those who were able to complete all 12 weeks of the treatment were evaluated for data purposes.
Age, Continuous	36.4 years STANDARD_DEVIATION 8.9 • n=5 Participants
Sex: Female, Male Female	12 Participants n=5 Participants
Sex: Female, Male Male	21 Participants n=5 Participants
Race/Ethnicity, Customized Caucasian	21 participants n=5 Participants
Race/Ethnicity, Customized Black or African-American	5 participants n=5 Participants
Race/Ethnicity, Customized Hispanic	2 participants n=5 Participants
Race/Ethnicity, Customized Asian	3 participants n=5 Participants
Race/Ethnicity, Customized Other/Mixed Ethnicity	2 participants n=5 Participants

PRIMARY outcome

Timeframe: 12 weeks

The ADHD-RS with adult ADHD prompts is a semi-structured scale that consists of 18 items that directly correspond to the 18 DSM-IV symptoms of ADHD, and is designed to assess current symptomatology19. Each item is scored on a 4-point scale ranging from 0 (none) to 3 (severe).Each item on the 18-item measure is scored on a 4-point scale ranging from 0 (no symptoms) to 3 (severe symptoms), yielding a possible total score of 0-54. A score of 0-16 means "Unlikely to have ADHD"; a score of 17-23 "Likely to Have ADHD" ; 24 or greater-Highly Likely to have ADHD

Outcome measures

Outcome measures
Measure	Overall Study n=33 Participants Eligible participants received 12 weeks of open-label treatment. Those on treatment prior to baseline underwent a 7-day (for amphetamine or methylphenidate) or 28-day (for atomoxetine or other medications) washout period prior to initiating LDX treatment. The starting dose was 30mg/day, which could be titrated up by 20mg/day during visits 2-6 (for a maximum dose of 70mg/day). At discretion of investigator, the dose could be down-titrated by 20mg/day during visits 4-6. Once the dose was optimized (after visit 6), the dose was maintained for 8 weeks. LDX Treatment: 30 mg, 50mg, or 70 mg. Oral capsule, once a day, for 12 weeks.
Attention Deficit Hyperactivity Disorder- Rating Scale (ADHS-RS)	13.9 units on a scale Standard Deviation 2.31

SECONDARY outcome

Timeframe: Week 0 to Week 12

To evaluate the symptom rebound throughout a single day (assessed via the AMRS) with LDX treatment. Scoring on the AMRS based on 38 items, each scored 0 (None), 1 (Mild), 2 (Moderate), 3 (Severe). The lowest scored units on a scale for 1 individual is 0, the highest 114. The scores reported below are Mean scores for 33 patients analyzed.

Outcome measures

Outcome measures
Measure	Overall Study n=33 Participants Eligible participants received 12 weeks of open-label treatment. Those on treatment prior to baseline underwent a 7-day (for amphetamine or methylphenidate) or 28-day (for atomoxetine or other medications) washout period prior to initiating LDX treatment. The starting dose was 30mg/day, which could be titrated up by 20mg/day during visits 2-6 (for a maximum dose of 70mg/day). At discretion of investigator, the dose could be down-titrated by 20mg/day during visits 4-6. Once the dose was optimized (after visit 6), the dose was maintained for 8 weeks. LDX Treatment: 30 mg, 50mg, or 70 mg. Oral capsule, once a day, for 12 weeks.
Change in Symptom Rebound Score Using the Adult ADHD Medication Rebound Scale (AMRS). In Clinic	27.99 units on a scale Standard Deviation 4.17
Change in Symptom Rebound Score Using the Adult ADHD Medication Rebound Scale (AMRS). Evening	26.9 units on a scale Standard Deviation 5.29

SECONDARY outcome

Timeframe: Visits 0 and 12

The Adult ADHD Medication Smoothness of Effect Scale (AMSES) is a 6-item, frequency-based, self-report scale that was recently developed to assess the consistency and duration of effect of ADHD medication throughout the day. The AMSES compares the effectiveness of ADHD medication shortly after dosing with the effectiveness later in the day. Respondents are asked to rate how frequently the effective-ness of their medication was the same 2 hr post-dose as it was 4, 6, 8, 10, and 12 hr post-dose on a 0 to 4 scale (0 = never, 1 = rarel, 2 = sometimes, 3 = often, 4 = very often). In addition, respondents rate how frequently the delivery of their medication was consistent and smooth throughout the day on a visual analog scale ranging from 0 (never) to 100 (very often).

Outcome measures

Outcome measures
Measure	Overall Study n=33 Participants Eligible participants received 12 weeks of open-label treatment. Those on treatment prior to baseline underwent a 7-day (for amphetamine or methylphenidate) or 28-day (for atomoxetine or other medications) washout period prior to initiating LDX treatment. The starting dose was 30mg/day, which could be titrated up by 20mg/day during visits 2-6 (for a maximum dose of 70mg/day). At discretion of investigator, the dose could be down-titrated by 20mg/day during visits 4-6. Once the dose was optimized (after visit 6), the dose was maintained for 8 weeks. LDX Treatment: 30 mg, 50mg, or 70 mg. Oral capsule, once a day, for 12 weeks.
Change in Measure of Smoothness of Effect Using Adult ADHD Medications Smoothness of Effect Scale (AMSES) In Clinic	1.31 units on a scale Standard Deviation 3.70
Change in Measure of Smoothness of Effect Using Adult ADHD Medications Smoothness of Effect Scale (AMSES) Evening	-3.34 units on a scale Standard Deviation 3.47

SECONDARY outcome

Timeframe: Visits 0 and 12

To correlate symptom rebound through a single day (assessed via the AMRS) with a global (ADHD-RS) measure of efficacy of LDX treatment. AMRS and ADHD-RD scores obtained on Day 0 and Day 12 will be correlated. The Pearson's correlation coefficients for the In-Clinic assessment will be presented for Visits 0 and 12.

Outcome measures

Outcome measures
Measure	Overall Study n=33 Participants Eligible participants received 12 weeks of open-label treatment. Those on treatment prior to baseline underwent a 7-day (for amphetamine or methylphenidate) or 28-day (for atomoxetine or other medications) washout period prior to initiating LDX treatment. The starting dose was 30mg/day, which could be titrated up by 20mg/day during visits 2-6 (for a maximum dose of 70mg/day). At discretion of investigator, the dose could be down-titrated by 20mg/day during visits 4-6. Once the dose was optimized (after visit 6), the dose was maintained for 8 weeks. LDX Treatment: 30 mg, 50mg, or 70 mg. Oral capsule, once a day, for 12 weeks.
Correlation Between AMRS (In Clinic) and ADHD-RS	.66 Pearson's correlation coefficient

SECONDARY outcome

Timeframe: Visits 0 and 12

To correlate symptom rebound through a single day (assessed via the AMRS) with a time-sensitive (TASS) measure of efficacy of LDX treatment. A Pearson's correlation coefficient will be presented. AMRS and TASS scores obtained on Day 0 and Day 12 will be correlated. The Pearson's correlation coefficients for the In-Clinic assessment will be presented for Visits 0 and 12.

Outcome measures

Outcome measures
Measure	Overall Study n=33 Participants Eligible participants received 12 weeks of open-label treatment. Those on treatment prior to baseline underwent a 7-day (for amphetamine or methylphenidate) or 28-day (for atomoxetine or other medications) washout period prior to initiating LDX treatment. The starting dose was 30mg/day, which could be titrated up by 20mg/day during visits 2-6 (for a maximum dose of 70mg/day). At discretion of investigator, the dose could be down-titrated by 20mg/day during visits 4-6. Once the dose was optimized (after visit 6), the dose was maintained for 8 weeks. LDX Treatment: 30 mg, 50mg, or 70 mg. Oral capsule, once a day, for 12 weeks.
Change in Correlation Between AMRS and TASS In Clinic	.96 Pearson's correlation coefficient
Change in Correlation Between AMRS and TASS Evening	.96 Pearson's correlation coefficient

SECONDARY outcome

Timeframe: Baseline to Week 12

To correlate symptom rebound through a single day (assessed via the AMRS) with a self assessment of ADHD Symptoms. A Pearson's correlation coefficient will be presented. AMRS and self assessment of ADHD scores obtained on Day 0 and Day 12 will be correlated. The Pearson's correlation coefficients for the In-Clinic assessment will be presented for Visits 0 and 12.

Outcome measures

Outcome measures
Measure	Overall Study n=33 Participants Eligible participants received 12 weeks of open-label treatment. Those on treatment prior to baseline underwent a 7-day (for amphetamine or methylphenidate) or 28-day (for atomoxetine or other medications) washout period prior to initiating LDX treatment. The starting dose was 30mg/day, which could be titrated up by 20mg/day during visits 2-6 (for a maximum dose of 70mg/day). At discretion of investigator, the dose could be down-titrated by 20mg/day during visits 4-6. Once the dose was optimized (after visit 6), the dose was maintained for 8 weeks. LDX Treatment: 30 mg, 50mg, or 70 mg. Oral capsule, once a day, for 12 weeks.
Correlation Between In-Clinic AMRS and ASRS v.1.1 Symptom Checklist	.83 Pearson's correlation coefficient

SECONDARY outcome

Timeframe: Weeks 0-12

To perform secondary psychometric validations of the AMRS using Cronbach's alpha coefficients.

Outcome measures

Outcome measures
Measure	Overall Study n=33 Participants Eligible participants received 12 weeks of open-label treatment. Those on treatment prior to baseline underwent a 7-day (for amphetamine or methylphenidate) or 28-day (for atomoxetine or other medications) washout period prior to initiating LDX treatment. The starting dose was 30mg/day, which could be titrated up by 20mg/day during visits 2-6 (for a maximum dose of 70mg/day). At discretion of investigator, the dose could be down-titrated by 20mg/day during visits 4-6. Once the dose was optimized (after visit 6), the dose was maintained for 8 weeks. LDX Treatment: 30 mg, 50mg, or 70 mg. Oral capsule, once a day, for 12 weeks.
Psychometric Validation of AMRS In Clinic	.99 Cronbach's alpha coefficients
Psychometric Validation of AMRS Evening	.97 Cronbach's alpha coefficients

SECONDARY outcome

Timeframe: Weeks 0-12

To perform secondary psychometric validations of the AMSES using Cronbach's alpha coefficients.

Outcome measures

Outcome measures
Measure	Overall Study n=33 Participants Eligible participants received 12 weeks of open-label treatment. Those on treatment prior to baseline underwent a 7-day (for amphetamine or methylphenidate) or 28-day (for atomoxetine or other medications) washout period prior to initiating LDX treatment. The starting dose was 30mg/day, which could be titrated up by 20mg/day during visits 2-6 (for a maximum dose of 70mg/day). At discretion of investigator, the dose could be down-titrated by 20mg/day during visits 4-6. Once the dose was optimized (after visit 6), the dose was maintained for 8 weeks. LDX Treatment: 30 mg, 50mg, or 70 mg. Oral capsule, once a day, for 12 weeks.
Psychometric Validation of AMSES In Clinic	.92 Cronbach's alpha coefficients
Psychometric Validation of AMSES Evening	.87 Cronbach's alpha coefficients

Adverse Events

LDX Treatment

Serious events: 0 serious events

Other events: 33 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	LDX Treatment n=40 participants at risk The treatment arm will receive 12 weeks of Lisdexamfetamine Dimesylate-LDX treatment. At baseline, participants were initiated on LDX at a dose of 30 mg/day and began a 4-week dose optimization phase with weekly clinic visits. The dose optimization phase was followed by an 8-week dose maintenance phase, which included clinic visits every 2 weeks for the assessment of safety and efficacy. At visits 3-6, the dose of LDX was increased by 20 mg/day until an optimal dose or the maximum dose of 80 mg/day was reached. An optimal dose was determined by clinical efficacy, defined as a \>= 30% reduction in the baseline ADHD Rating Scale, and tolerability. At the discretion of the investigator, the dose could be down-titrated by 20 mg/day at visits 4-6. When an optimal dose was reached, the participant remained at this level for the duration of the study.
General disorders Insomnia	80.0% 32/40 • Number of events 34
Vascular disorders Headache	52.5% 21/40 • Number of events 22
Gastrointestinal disorders Loss of Appetite	52.5% 21/40 • Number of events 21
General disorders Dry Mouth	42.5% 17/40 • Number of events 17

Additional Information

Dr. Lenard Adler

NYU School of Medicine

Phone: (212) 263-3580

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place