Clinical trial NCT00468143: A Within-Subject Cross-Over Comparison Between Immediate Release and Extended Release Adderall
Official title: A Within-Subject Cross-Over Comparison Between Immediate Release and Extended Release Adderall
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Attention Deficit Hyperactivity Disorder
Lead sponsor: NYU Langone Health
Sponsor class: OTHER
First posted: 2007-05-02
Enrollment: 62
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: The purpose of this pilot study is to compare Adderall ® and Adderall XR ® in terms of their effectiveness and side effects for the treatment of ADHD in adults.

Detailed description: This will be a randomized, cross-over study in which adults with ADHD will receive three weeks of treatment with Adderall (IR) (15, 30, or 45 mg TID) and three weeks of treatment of Adderall XR (XR) (15, 30, or 45 mg QD) for evaluation of dosing adherence and treatment efficacy. The order of the two conditions (TID-QD or QD-TID) will be counterbalanced across subjects, with a washout period in between treatment periods. Participants will be required to come to the site for 9 visits over approximately an 8-week period.

The study will consist of the following four phases:

* Phase 1

  * Screening Visit (Visit 1)
  * Treatment "A" Baseline Visit (Visit 2)
* Phase 2

  o Treatment Period "A" - participants will take either Adderall or Adderall XR for 3 weeks (Visits 3-5)
* Phase 3

  * 7-Day Washout Period - participants will be off Treatment "A" medication
  * Treatment "B" Baseline visit (Visit 6)
* Phase 4 o Treatment Period "B" - participants will take either Adderall or Adderall XR for 3 weeks (Visits 7-9)

Eligible participants will be randomized in a 1:1 ratio to one of two schedules of treatment, Adderall IR followed by Adderall XR, or Adderall XR followed by Adderall IR. Within both schedules, each treatment will consist of a 3-week dose optimization titration evaluation period with a washout week prior to switching to the second respective treatment. The maximum total daily dose will be 45mg, with 15mg TID for IR or 45mg QD for XR. Throughout the medication treatment periods, participants will visit the clinic weekly for evaluations of efficacy, tolerance, and adherence. Medical evaluations will also be conducted at each treatment visit, including assessment of weight, blood pressure, and pulse. Efficacy and adherence data will collected by separate research staff, so that the rater evaluating efficacy will be blinded to the adherence results. The clinician evaluating efficacy will also be blinded to the participants' treatment assignment.

Eligibility criteria: 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 previous amphetamine or methylphenidate treatment for 1 week prior to baseline (visit 2). Must be off past non-stimulant ADHD medication (i.e., atomoxetine) for 3 weeks prior to baseline (visit 2).
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. Lifetime or present history of bipolar disorder, schizophrenia or schizoaffective disorder.
2. Uncontrolled comorbid major depressive disorder, anxiety disorder or dysthymia. Participants with controlled depressive or anxiety disorders may participate if their medications have been stabilized for a minimum of four weeks and, in the opinion of the Principal Investigator, will not interfere with adherence, safety, or efficacy assessments.
3. Anyone who meets current DSM-IV-TR criteria for alcohol or any non-alcohol substance abuse or dependence disorder (excluding nicotine).
4. Have organic brain disease (such as dementia) or traumatic brain injury residua. Have a history of seizure disorder (other than febrile seizures) or participants who have taken (or are currently taking) anticonvulsants for seizure control.
5. Females who are currently pregnant or breast feeding, and women of child-bearing potential who are not currently using an adequate form of birth control.
6. Participants with clinically significant ECG or laboratory abnormalities at screening that are deemed exclusionary in the opinion of the Principal Investigator.
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 with a positive urine drug result at Screening.
9. 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. Subjects who have a history of mental retardation or severe learning disability will be excluded.
10. Participants with a history of structural cardiac abnormalities as well as any other condition that may affect cardiac performance.
11. Participants with documented history of allergy, intolerance, or non-responsivity to methylphenidate or amphetamines. This includes a history of two or more failed stimulant treatment trials, as deemed by the Principal Investigator.
12. Participants who in the investigator's opinion meet any of the exclusionary criteria specified on the FDA label of either Adderall or Adderall XR.

Primary outcomes:
measure: Medication Event Monitoring System (MEMS®) Dosage Adherence
timeFrame: The MEMS information was noted at clinic visit 3, 4, 5, 7, 8, and 9 (over 8 weeks)
measure: Medication Event Monitoring System (MEMS®) Regimen Adherence
timeFrame: The MEMS information was noted at clinic visit 3, 4, 5, 7, 8, and 9 (over 8 weeks)
measure: Medication Event Monitoring System (MEMS®) Time Adherence
timeFrame: The MEMS information was noted at clinic visit 3, 4, 5, 7, 8, and 9 (over 8 weeks)
Secondary outcomes:
measure: Pill Count
timeFrame: At clinic visit 3, 4, 5, 7, 8, and 9 (over 8 weeks)
measure: Self Report
timeFrame: At clinic visit 3, 4, 5, 7, 8, and 9 (over 8 weeks)
Other outcomes:
Locations:
city: New York
country: United States
facility: VANYHHS
state: New York
Study officials:
affiliation: NYU School of Medicine
name: Lenard Adler, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Adler LA, Lynch LR, Shaw DM, Wallace SP, Ciranni MA, Briggie AM, Kulaga A, O'Donnell KE, Faraone SV. Medication adherence and symptom reduction in adults treated with mixed amphetamine salts in a randomized crossover study. Postgrad Med. 2011 Sep;123(5):71-9. doi: 10.3810/pgm.2011.09.2461.