Attention Deficit Hyperactivity Disorder
Conditions
Keywords
ADHD, Lisdexamfetamine Dimesylate, Amphetamine
Brief summary
The purpose of this study is to examine the effectiveness and length of effect of Vyvanse on lessening Attention-Deficit/Hyperactivity Disorder symptoms in adults. The study will also investigate the safety and tolerability of Vyvanse in adults with ADHD.
Detailed description
Protocol Summary: Effectiveness and Duration of Effect of Open Treatment in Adult ADHD Patients Treated with Lisdexamfetamine Dimesylate- LDX (Vyvanse) The primary objective of this study is to evaluate the effectiveness and duration of effect of LDX for the treatment of ADHD symptoms in adults. The study will be a 12-week open label extension with 25 adult participants who completed a cross-over study of adherence/efficacy of Adderall Immediate Release (IR) vs. Adderall Extended Release (XR). The secondary objective is to provide information regarding tolerability, dosing and titration of LDX in the adult population with ADHD. An additional fifteen participants will be recruited using advertising and previous Mental Health and Addictive Behaviour Research Program (MHADRP) studies will be offered treatment with LDX. All participants will be diagnosed with ADHD using the Adult Clinician Diagnostic Scale (ACDS). We will be collecting demographic information, administering the Scheduled Clinical Interview for DSM Disorders (SCID), collecting medical history, previous drug therapy, and the participant will have a physical with the physician. A coordinator will give an electrocardiogram (ECG), and collect a blood sample for blood chemistry and hematology. Schedule of Events: Vyvanse Extension Screening Visit * Consent * Demographics (needs to be added?) * Physical * Medical history (needs to be added?) * Previous drug therapy * Vitals (Blood Pressure-BP, Heart Rate-HR, Respiration, weight) * Urine Drug screen * Urine pregnancy test * ECG * Blood sample * SCID * ACDS Visits at week 0,1,2,3,4,6,8,10,12 (every visit) * ADHD-Rating Scale (ADHD-RS) * Adult ADHD Self-Report Scale (ASRS) * Clinical Global Impression (CGI) * Vitals * Pill count * Adverse Events (AE)/ Concomitant Medications (CM) Visits at week 0,1,4,6,12 also administer * Adult ADHD Medication Rebound Scale (AMRS) (AM/PM) * Adult ADHD Medication Smoothness of Effect Scale (AMSES) (AM/PM) * Wender-Reimherr Adult Attention Deficit Disorder Scale (WRAADS) (AM/PM) First 4 weeks of treatment is a dose adjustment period (30-70 mg po qAM), after those 4 weeks established dose is remained for remaining 8 weeks of treatment.
Interventions
DRUGLDX Treatment
30 mg, 50mg, or 70 mg. Oral capsule, once a day, for 12 weeks.
Sponsors
Shire
NYU Langone Health
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
No
Inclusion criteria
1. At the time of consent, are between the ages of 18-55, inclusive. 2. Meet DSM-IV criteria for ADHD as assessed by the Adult ADHD Clinician Diagnostic Scale (ACDS) v1.2. 3. Female participants of childbearing potential must test negative for pregnancy at the time of enrollment based on a urine pregnancy test and agree to use a reliable method of birth control during the study. Females of childbearing potential are defined as women not surgically sterilized and are between menarche and 2 years post-menopause. 4. Must have a satisfactory medical assessment with no clinically significant abnormalities as determined by medical history, physical exam, ECG, and clinical laboratory testing. 5. Must be able to swallow capsules. 6. Must be able to begin the daily dose of study medication in the morning. 7. Must be off all ADHD therapies for one week (psychostimulants) and three weeks (non-stimulants). 8. In the opinion of the investigator, the subject must understand and be able, willing and likely to fully comply with the study procedures and restrictions. 9. Must have given signed and dated informed consent in accordance with Good Clinical Practice (GCP) Guidelines.
Exclusion criteria
1. Participants with a positive urine drug result at Screening. 2. Anyone who meets current DSM-IV-TR criteria for alcohol or any non-alcohol substance abuse or dependence disorder (excluding nicotine). 3. Participants with controlled depressive or anxiety disorders may not participate if, in the opinion of the Principal Investigator, their medications will interfere with safety or efficacy assessments. 4. Participants with any concurrent chronic or acute illness or unstable medical condition that could, in the opinion of the study physician, confound the results of safety assessments, increase risk to the subject or lead to difficulty complying with the protocol. 5. Participants with hypertension at screening, indicated by a blood pressure reading of 135/90 and heart rate above 120bmp. 6. Female participants of childbearing potential who test positive for pregnancy at the time of enrollment based on a urine pregnancy test, or who do not agree to use a reliable method of birth control during the study. Females of childbearing potential are defined as women not surgically sterilized and are between menarche and 2 years post-menopause. 7. Participants who work the night shift or another schedule that would preclude beginning the daily dose of study medication in the morning. 8. Participants who in the investigator's opinion meet any of the exclusionary criteria specified on the FDA label of Vyvanse.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Attention Deficit Hyperactivity Disorder- Rating Scale (ADHS-RS) | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Measure of Smoothness of Effect Using Adult ADHD Medications Smoothness of Effect Scale (AMSES) | 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). |
| Correlation Between AMRS (In Clinic) and ADHD-RS | 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. |
| Change in Correlation Between AMRS and TASS | 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. |
| Change in Symptom Rebound Score Using the Adult ADHD Medication Rebound Scale (AMRS). | 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. |
| Psychometric Validation of AMRS | Weeks 0-12 | To perform secondary psychometric validations of the AMRS using Cronbach's alpha coefficients. |
| Psychometric Validation of AMSES | Weeks 0-12 | To perform secondary psychometric validations of the AMSES using Cronbach's alpha coefficients. |
| Correlation Between In-Clinic AMRS and ASRS v.1.1 Symptom Checklist | 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. |
Countries
United States
Participant flow
Recruitment details
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.
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| LDX Treatment 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. | 33 |
| Total | 33 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 6 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | LDX Treatment |
|---|---|
| Age, Continuous | 36.4 years STANDARD_DEVIATION 8.9 |
| Race/Ethnicity, Customized Asian | 3 participants |
| Race/Ethnicity, Customized Black or African-American | 5 participants |
| Race/Ethnicity, Customized Caucasian | 21 participants |
| Race/Ethnicity, Customized Hispanic | 2 participants |
| Race/Ethnicity, Customized Other/Mixed Ethnicity | 2 participants |
| Sex: Female, Male Female | 12 Participants |
| Sex: Female, Male Male | 21 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 33 / 40 |
| serious Total, serious adverse events | 0 / 40 |
Outcome results
Primary
Attention Deficit Hyperactivity Disorder- Rating Scale (ADHS-RS)
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
Time frame: 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Overall Study | Attention Deficit Hyperactivity Disorder- Rating Scale (ADHS-RS) | 13.9 units on a scale | Standard Deviation 2.31 |
p-value: 0.001GEE regression model
Secondary
Change in Correlation Between AMRS and TASS
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.
Time frame: Visits 0 and 12
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Overall Study | Change in Correlation Between AMRS and TASS | In Clinic | .96 Pearson's correlation coefficient |
| Overall Study | Change in Correlation Between AMRS and TASS | Evening | .96 Pearson's correlation coefficient |
p-value: <0.001GEE regression model
Secondary
Change in Measure of Smoothness of Effect Using Adult ADHD Medications Smoothness of Effect Scale (AMSES)
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).
Time frame: Visits 0 and 12
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Overall Study | 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 3.7 |
| Overall Study | 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 |
p-value: 0.569GEE regression model
Comparison: The following p-value is for AMSES In-Clinic, a subset of the overall AMSESp-value: 0.827Generalized Estimating Equation
Comparison: The following p-value is for AMSES, Evening, a subset of the AMSESp-value: 0.569Generalized Estimating Equation
Secondary
Change in Symptom Rebound Score Using the Adult ADHD Medication Rebound Scale (AMRS).
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.
Time frame: Week 0 to Week 12
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Overall Study | 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 |
| Overall Study | Change in Symptom Rebound Score Using the Adult ADHD Medication Rebound Scale (AMRS). | Evening | 26.9 units on a scale | Standard Deviation 5.29 |
p-value: <0.001GEE regression model
Secondary
Correlation Between AMRS (In Clinic) and ADHD-RS
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.
Time frame: Visits 0 and 12
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Overall Study | Correlation Between AMRS (In Clinic) and ADHD-RS | .66 Pearson's correlation coefficient |
p-value: 0.001GEE regression model
Secondary
Correlation Between In-Clinic AMRS and ASRS v.1.1 Symptom Checklist
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.
Time frame: Baseline to Week 12
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Overall Study | Correlation Between In-Clinic AMRS and ASRS v.1.1 Symptom Checklist | .83 Pearson's correlation coefficient |
p-value: <0.0001GEE regression model
Secondary
Psychometric Validation of AMRS
To perform secondary psychometric validations of the AMRS using Cronbach's alpha coefficients.
Time frame: Weeks 0-12
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Overall Study | Psychometric Validation of AMRS | In Clinic | .99 Cronbach's alpha coefficients |
| Overall Study | Psychometric Validation of AMRS | Evening | .97 Cronbach's alpha coefficients |
Secondary
Psychometric Validation of AMSES
To perform secondary psychometric validations of the AMSES using Cronbach's alpha coefficients.
Time frame: Weeks 0-12
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Overall Study | Psychometric Validation of AMSES | In Clinic | .92 Cronbach's alpha coefficients |
| Overall Study | Psychometric Validation of AMSES | Evening | .87 Cronbach's alpha coefficients |