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

Evaluation of Pharmacokinetics and Profile of Clinical Response of Subacute Lisdexamfetamine Dimesylate (Vyvanse) Treatment vs. Clinical Response to Subacute Immediate Release Mixed Amphetamine Salt Therapy in Adult ADHD

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.

Study Overview

• Status: Completed
• Conditions: Attention Deficit Hyperactivity Disorder
• Intervention / Treatment: Drug: LDX Treatment

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.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10016
      • NYU School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

EXPERIMENTAL: LDX Treatment; 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.

Drug: LDX Treatment; 30 mg, 50mg, or 70 mg. Oral capsule, once a day, for 12 weeks.; Other Names: Vyvanse

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Week 0 to Week 12
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).	Visits 0 and 12
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.	Visits 0 and 12
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.	Visits 0 and 12
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.	Baseline to Week 12
Psychometric Validation of AMRS	To perform secondary psychometric validations of the AMRS using Cronbach's alpha coefficients.	Weeks 0-12
Psychometric Validation of AMSES	To perform secondary psychometric validations of the AMSES using Cronbach's alpha coefficients.	Weeks 0-12

Collaborators and Investigators

• Sponsor: NYU Langone Health
• Collaborators: Shire

Publications and helpful links

General Publications

• Adler LA, Alperin S, Leon T, Faraone S. Clinical effects of lisdexamfetamine and mixed amphetamine salts immediate release in adult ADHD: results of a crossover design clinical trial. Postgrad Med. 2014 Sep;126(5):17-24. doi: 10.3810/pgm.2014.09.2796.
• Mattingly GW, Weisler RH, Young J, Adeyi B, Dirks B, Babcock T, Lasser R, Scheckner B, Goodman DW. Clinical response and symptomatic remission in short- and long-term trials of lisdexamfetamine dimesylate in adults with attention-deficit/hyperactivity disorder. BMC Psychiatry. 2013 Jan 29;13:39. doi: 10.1186/1471-244X-13-39.

Study record dates

Study Major Dates

• Study Start: February 1, 2010
• Primary Completion (ACTUAL): July 1, 2012
• Study Completion (ACTUAL): July 1, 2012

Study Registration Dates

• First Submitted: February 16, 2010
• First Submitted That Met QC Criteria: February 17, 2010
• First Posted (ESTIMATE): February 18, 2010

Study Record Updates

• Last Update Posted (ACTUAL): April 3, 2018
• Last Update Submitted That Met QC Criteria: March 5, 2018
• Last Verified: March 1, 2018

More Information

Terms related to this study

• Keywords: ADHD; Lisdexamfetamine Dimesylate; Amphetamine
• Additional Relevant MeSH Terms: Mental Disorders; Nervous System Diseases; Neurologic Manifestations; Dyskinesias; Attention Deficit and Disruptive Behavior Disorders; Neurodevelopmental Disorders; Attention Deficit Disorder with Hyperactivity; Hyperkinesis; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Dopamine Agents; Dopamine Uptake Inhibitors; Central Nervous System Stimulants; Lisdexamfetamine Dimesylate
• Other Study ID Numbers: 10-00510

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No