Attention Deficit Hyperactivity Disorder
Conditions
Keywords
Attention Deficit Hyperactivity Disorder, ADHD, Adult, Methylphenidate Transdermal System, Daytrana
Brief summary
This study will look at the effectiveness of Methylphenidate Transdermal System (MTS) in treating adult ADHD. MTS has received FDA approval for childhood ADHD but this is the first trial for adult ADHD. Subjects will experience two screening visits and one baseline visit. Those who meet admission criteria will enter the double-blind phase. This will involve two 4-week treatment periods one of which will involve the use of MTS and the other a placebo patch. Subjects who complete the double-blind phase will be allowed to enter a 180-day, open-label MTS phase designed to assess long-term effects.
Detailed description
ADHD affects from 3 to 5% of children, persists into adolescence in 40 to 70% of these children and continues into adulthood in at least 50% of affected adolescents. Methylphenidate was the first medication shown to be effective in treatment for adults with ADHD and continues to be widely used. While the extended release formulations represent an improvement over the immediate release versions, significant problems remain for many patients. In particular, most have been designed with the goal of providing medication only during school hours and a short time period after school. In adults, there is a frequent need for much more extended duration of treatment. MTS is a new form of methylphenidate that provides medication in a transdermal patch delivery system. It has a very even, slowly ascending pharmacokinetic profile. MTS's very stable slowly increasing blood level should overcome the problems noted above with a delivery system that is more convenient for many patients. It is currently approved for treatment of childhood ADHD, with effectiveness and safety profiles similar to other forms of methylphenidate. This study will be the first to evaluate the effectiveness and safety of MTS in adult ADHD. This is a double-blind, placebo-controlled, randomized, crossover trial comparing MTS with placebo patch. The double-blind trial will be preceded by an enrollment period consisting of two screening visits followed as quickly as possible by a baseline visit. Patients who continue to meet admission criteria at baseline will be randomized into the first of two 4-week treatment periods. We will attempt to reach the highest tolerated dose size of MTS within 2 weeks and then observe the response over the last two weeks of each crossover phase. The double-blind period will be followed by a 180 day open-treatment, flexible-dose phase designed to assess long-term effects.
Interventions
DRUGMethylphenidate Transdermal System (MTS)
MTS is an advanced patch product that provides methylphenidate evenly mixed with the adhesive. This formulation allows good adhesion and a wide range of dose sizes. MTS patch sizes of 12.5, 18.75, 25 and 37.5cm2 are equivalent to nominal doses over a 9-hour wear time of 10, 15, 20 and 30mg of MPH.
OTHERplacebo patch
This patch is designed to appear identical to the actual intervention patch
Sponsors
Shire
University of Utah
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
Adults meeting DSM-IV-Text Revision criteria for ADHD, the Utah Criteria for ADHD, and experiencing at least moderate impairment (a score of 4 or greater on the CGI-Severity Scale for ADHD at both Screening and Baseline visits) will be enrolled. Other criteria include: 1. Subjects ages 18 to 65, inclusive; 2. Female subjects are eligible to enter and participate in this study only if: 1. She is of non-childbearing potential; has a male sexual partner who is surgically sterilized; is on implant of levonorgestrel, injectable progesterone, or an oral contraceptive; has an intrauterine device (IUD); or is sexually inactive with a male partner. 2. Or agrees to use a double barrier method of contraception (any combination of physical and chemical methods) and has a negative urine pregnancy test at screening interview. 3. Subject must be in general good health as determined by medical history, ECG, and other analysis that, in the judgment of the study physician, would confirm the patient's good health. 4. Subjects must read and write at a level sufficient to provide written informed consent and complete study-related materials.
Exclusion criteria
* Subjects will not be eligible for inclusion in this study if any of the following criteria apply: 1. Subjects with other current DSM-IV Axis I Disorders including Current or lifetime history of psychosis, current bipolar disorder type I, current Major Depressive Disorder, and Current Anxiety Disorder (unless in the opinion of clinic physician ADHD is the primary disorder and causes the disability seen in the patient); 2. Subjects with any other DSM-IV Axis II diagnosis so severe that it would suggest non-responsiveness to pharmacotherapy for ADHD or noncompliance with the protocol; 3. Subjects at risk for suicide or a risk to harm others; 4. History of Substance Dependence according to DSM-IV criteria within 3 months of screening; 5. Subjects currently abusing illegal drugs or alcohol are excluded from the study; 6. Positive urine screen for drugs of abuse at screening for patients who have a significant history of substance use but still meet criteria 4 and 5. Patients not at risk for substance abuse will not be given a urine drug screen; 7. Subjects in whom stimulants would represent a risk such as those with a history of stimulant abuse, 8. History of uncontrolled hypertension or significant cardiovascular disease; 9. Any known or suspected significant medical or psychiatric illnesses (e.g., hepatic or renal insufficiency, pulmonary (asthma, COPD, etc), gastrointestinal, endocrine, neurological or metabolic disturbances that, in the judgment of the investigator, may impair interpretation of study results or constitute a significant safety concern in the context of the clinical trial; 10. Medications, including health food supplements judged by the investigator to be likely to have central nervous system activity (for example, St John's Wort, gingko leaf, and melatonin), are not permitted during the study. If the subject is taking the medication prior to study entry, there must be a 7 day washout period prior to Visit 2. We will ask for an honest report of all medications consumed between visits. In the event a medication with psychoactive properties is consumed, the patient will be counseled regarding the use of prohibited medications; 11. Use of any medication not considered acceptable by the clinical investigator or the medical monitor during the 7-day period before the start of the study (Day 1); 12. Subjects with high BMI (\>38) and those with high adipose tissue concentrations in the hip as judged by the clinician.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Wender Reimherr Adult Attention Deficit Disorder Scale | Double-blind endpoints during MTS and placebo arms | This scale measures the 7 domains of the Utah Criteria for Adult ADHD. Total scores run from 0 to 28. Normative samples average below 5. The worst possible score is 28. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Conners' Adult ADHD Rating Scales (CAARS) | Double-blind endpoints for MTS and placebo arms | Measures the DSM based ADHD criteria of Inattention and Hyperactivity/Impulsivity. There are 30 items scored 0-3 for a minimum score of 0 (no symptoms) and a maximum score of 90 worst possible symptoms. |
Countries
United States
Participant flow
Recruitment details
Subjects (n=92) were recruited from 4-16-2007 through 10-24-2008. They were seen at the Psychiatry Research Clinic at the University of Utah School of Medicine.
Pre-assignment details
There were 3 screening visits. Subjects met DSM-IV &/or Utah criteria for adult ADHD, experiencing at least moderate impairment. Most DSM-IV axis-I disorders were excluded. Of 92 subjects enrolled, 65 were randomized and produced double-blind data. The assessment procedure was more extensive than normal, leading to a high dropout rate.
Participants by arm
| Arm | Count |
|---|---|
| a) Methylphenidate Transdermal System Was Taken First Subjects took Methylphenidate Transdermal System in the first treatment arm and placebo patch in the second treatment arm | 29 |
| B Placebo Patch Was Used First Placebo patch was used in the first treatment arm and MTS in the second treatment arm. | 36 |
| Total | 65 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| 3 Week Screening Phase | Withdrawal by Subject | 17 | 10 |
| 6-month Open Label Phase | Lost to Follow-up | 1 | 7 |
| 6-month Open Label Phase | Withdrawal by Subject | 9 | 5 |
| Double Blind Cross-Over Phase | Lost to Follow-up | 5 | 2 |
| Double Blind Cross-Over Phase | Withdrawal by Subject | 4 | 3 |
Baseline characteristics
| Characteristic | a) Methylphenidate Transdermal System Was Taken First | Total | B Placebo Patch Was Used First |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 29 Participants | 65 Participants | 36 Participants |
| Age, Continuous | 30.4 years STANDARD_DEVIATION 9.5 | 35.2 years STANDARD_DEVIATION 11.8 | 40.4 years STANDARD_DEVIATION 11.8 |
| Region of Enrollment United States | 29 participants | 65 participants | 36 participants |
| Sex: Female, Male Female | 8 Participants | 21 Participants | 13 Participants |
| Sex: Female, Male Male | 21 Participants | 44 Participants | 23 Participants |
| Wender-Reimherr Adult Attention Deficit Disorder Scale | 21.5 units on a scale STANDARD_DEVIATION 4.2 | 21.4 units on a scale STANDARD_DEVIATION 4.2 | 21.3 units on a scale STANDARD_DEVIATION 4.1 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 24 / 61 | 10 / 58 |
| serious Total, serious adverse events | 0 / 61 | 0 / 58 |
Outcome results
Primary
Wender Reimherr Adult Attention Deficit Disorder Scale
This scale measures the 7 domains of the Utah Criteria for Adult ADHD. Total scores run from 0 to 28. Normative samples average below 5. The worst possible score is 28.
Time frame: Double-blind endpoints during MTS and placebo arms
Population: All subjects given active treatment last observation carried forward using a mixed models design.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Scores in MTS Arm | Wender Reimherr Adult Attention Deficit Disorder Scale | 11.0 units on a scale | Standard Deviation 7.4 |
| Scores in Placebo Arm | Wender Reimherr Adult Attention Deficit Disorder Scale | 17.9 units on a scale | Standard Deviation 6.6 |
p-value: 0.001Mixed Models Analysis
Secondary
Conners' Adult ADHD Rating Scales (CAARS)
Measures the DSM based ADHD criteria of Inattention and Hyperactivity/Impulsivity. There are 30 items scored 0-3 for a minimum score of 0 (no symptoms) and a maximum score of 90 worst possible symptoms.
Time frame: Double-blind endpoints for MTS and placebo arms
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Scores in MTS Arm | Conners' Adult ADHD Rating Scales (CAARS) | 30.8 units on a scale | Standard Deviation 19.1 |
| Scores in Placebo Arm | Conners' Adult ADHD Rating Scales (CAARS) | 49.5 units on a scale | Standard Deviation 18.8 |
p-value: 0.001Mixed Models Analysis