Attention Deficit/Hyperactivity Disorder
Conditions
Keywords
Attention Deficit /Hyperactivity Disorder,, hyperactivity
Brief summary
This study will evaluate the long-term safety of methylphenidate hydrochloride extended release in adults with attention deficit/hyperactivity disorder
Interventions
DRUGRitalin LA (methylphenidate hydrochloride extended release)
Ritalin LA 20 mg or 30 mg (a racemic mixture of d- and l-thre-Methylphenidate Hydrocloride (MPH), Extended release hard capsules) taken orally once daily in doses of 40, 60, or 80 mg. For 40mg dose patients took (2) Ritalin LA 20mg daily, for 60mg patients took (2) Ritalin LA 30mg daily and for 80mg patients took (2) Ritalin LA 30mg daily + (1) Ritalin LA 20mg daily for their optimal dose.
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
1\. Completion of the 40-week core study CRIT124D2302 and Week 40 (End of Study) assessments or Patients who meet predefined criteria for treatment failure, were withdrawn from the core study, and have completed core-study week 40 assessments (Premature Discontinuation Visit)
Exclusion criteria
1. Patients who, during the core study, developed any psychiatric condition that requires treatment with medication or that may interfere with study participation and /or study assessments. 2. Patients who during the core study developed cardiovascular disorders. 3. Pregnant women. 4. Patients who developed seizures during the core study. 5. Diagnosis of glaucoma, hyperthyroidism, pheochromocytoma. 6. Diagnosis or family history of Tourette's syndrome. 7. Patients who during the core study developed cerebrovascular disorders such as cerebral aneurysm, vascular abnormalities including vasculitis and stroke Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events, Serious Adverse Events and Deaths. | Week 40 - Week 66 | Adverse Events, Serious Adverse Events and Deaths were monitored from week 40 to week 66. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Extension Baseline (Week 40) to End of Study (Week 66) in on DSM-IV Attention-Deficit/Hyperactivity Disorder Rating Scale (DSM-IV ADHD RS) Total Score. | week 40 - week 66 | Attention-Deficit/Hyperactivity Disorder Rating Scale (DSM-IV ADHD RS) total score consists of 18 items directly adapted from the ADHD symptom list according to the DSM-IV. The DSM-IV ADHD RS total score was calculated as the sum of the Inattentive and the Hyperactive-Impulsive subscores. The 18 items are rated from 0 (rarely or never) to 3 (Very often). The total score ranges from 0 to 54. Decrease in the DSM-IV ADHD RS total score indicates improvement, therefore a greater decrease (change at Final Visit compared to baseline) indicates a greater improvement in ADHD symptoms. Last Observation Carried Forward (LOCF) applied for each patient with data in extension period. If no post-baseline is available, it is considered as missing. |
| Change From Extension Baseline (Week 40) to End of Study (Week 66) on Sheehan Disability Scale (SDS) Total Score | week 40 - week 66 | SDS,5-self-rated questionnaire to measure the extent a pt's disability due to an illness/health problem interferes with work/school,social life/leisure,family life/home. First 3 items, pts are asked how their symptoms disrupted their regular activities over the past 7d in each using a scale from 0(not at all)-10(extremely) Each subscale(work disability, social life disability, family life disability)can be scored independently or combined into a total score(sum of the non-missing responses for items 1-3)from 0-30,higher scores indicate significant functional impairment. Subscale scores\>5 suggest impairment in that subscale area. Final 2 items ask pts about the # of days their symptoms caused them to miss school/work and # of days their symptoms caused them to be underproductive at school/work.(These items were not included in the total score.) Before responding to SDS items 1-3, pts were verbally instructed to recall the past 7d, items 4-5 refer to the last week w/in the item wording. |
Countries
Belgium, Colombia, Denmark, Germany, Sweden, United States
Participant flow
Recruitment details
Actual enrolment was 299 but one patient entered the extension but did not receive a single dose of the study medication and was subsequently excluded from the All Extension Patients Population
Participants by arm
| Arm | Count |
|---|---|
| Ritalin LA All participants started with Ritalin LA 20 mg/day and increased at weekly intervals in increments of 20 mg/day until reaching the patient's optimal dose 40, 60 or 80 mg/day). | 298 |
| Total | 298 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Administrative problems | 3 |
| Overall Study | Adverse Event | 8 |
| Overall Study | Lack of Efficacy | 5 |
| Overall Study | Lost to Follow-up | 4 |
| Overall Study | no longer require study drug | 1 |
| Overall Study | Protocol Deviation | 4 |
| Overall Study | Withdrawal by Subject | 11 |
Baseline characteristics
| Characteristic | Ritalin LA |
|---|---|
| Age, Continuous | 36.3 years STANDARD_DEVIATION 11.4 |
| Sex: Female, Male Female | 138 Participants |
| Sex: Female, Male Male | 160 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 163 / 298 |
| serious Total, serious adverse events | 2 / 298 |
Outcome results
Primary
Number of Participants With Adverse Events, Serious Adverse Events and Deaths.
Adverse Events, Serious Adverse Events and Deaths were monitored from week 40 to week 66.
Time frame: Week 40 - Week 66
Population: All Extension Patients(AEP) analysis set was used for all efficacy and safety analyses of the extension study. AEP was ALL patients who had entered the extension study \& received at least 1 dose of Ritalin LA. Enrolment was 299, but 1 pt entered the extension but didn't receive 1 dose of Ritalin LA and was excluded from AEP Population analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ritalin LA | Number of Participants With Adverse Events, Serious Adverse Events and Deaths. | Adverse Events (Serious and Non Serious) | 208 participants |
| Ritalin LA | Number of Participants With Adverse Events, Serious Adverse Events and Deaths. | Serious Adverse Events | 2 participants |
| Ritalin LA | Number of Participants With Adverse Events, Serious Adverse Events and Deaths. | Deaths | 0 participants |
Secondary
Change From Extension Baseline (Week 40) to End of Study (Week 66) in on DSM-IV Attention-Deficit/Hyperactivity Disorder Rating Scale (DSM-IV ADHD RS) Total Score.
Attention-Deficit/Hyperactivity Disorder Rating Scale (DSM-IV ADHD RS) total score consists of 18 items directly adapted from the ADHD symptom list according to the DSM-IV. The DSM-IV ADHD RS total score was calculated as the sum of the Inattentive and the Hyperactive-Impulsive subscores. The 18 items are rated from 0 (rarely or never) to 3 (Very often). The total score ranges from 0 to 54. Decrease in the DSM-IV ADHD RS total score indicates improvement, therefore a greater decrease (change at Final Visit compared to baseline) indicates a greater improvement in ADHD symptoms. Last Observation Carried Forward (LOCF) applied for each patient with data in extension period. If no post-baseline is available, it is considered as missing.
Time frame: week 40 - week 66
Population: All Extension Patients(AEP) analysis set was used for all efficacy and safety analyses of the extension study. AEP was ALL patients who had entered the extension study \& received at least 1 dose of Ritalin LA. Enrolment was 299, but 1 pt entered the extension but didn't receive 1 dose of Ritalin LA and was excluded from AEP Population analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ritalin LA | Change From Extension Baseline (Week 40) to End of Study (Week 66) in on DSM-IV Attention-Deficit/Hyperactivity Disorder Rating Scale (DSM-IV ADHD RS) Total Score. | -7.2 scores on a scale | Standard Deviation 11 |
Secondary
Change From Extension Baseline (Week 40) to End of Study (Week 66) on Sheehan Disability Scale (SDS) Total Score
SDS,5-self-rated questionnaire to measure the extent a pt's disability due to an illness/health problem interferes with work/school,social life/leisure,family life/home. First 3 items, pts are asked how their symptoms disrupted their regular activities over the past 7d in each using a scale from 0(not at all)-10(extremely) Each subscale(work disability, social life disability, family life disability)can be scored independently or combined into a total score(sum of the non-missing responses for items 1-3)from 0-30,higher scores indicate significant functional impairment. Subscale scores\>5 suggest impairment in that subscale area. Final 2 items ask pts about the # of days their symptoms caused them to miss school/work and # of days their symptoms caused them to be underproductive at school/work.(These items were not included in the total score.) Before responding to SDS items 1-3, pts were verbally instructed to recall the past 7d, items 4-5 refer to the last week w/in the item wording.
Time frame: week 40 - week 66
Population: All Extension Patients(AEP) analysis set was used for all efficacy and safety analyses of the extension study. AEP was ALL patients who had entered the extension study \& received at least 1 dose of Ritalin LA. Enrolment was 299, but 1 pt entered the extension but didn't receive 1 dose of Ritalin LA and was excluded from AEP Population analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ritalin LA | Change From Extension Baseline (Week 40) to End of Study (Week 66) on Sheehan Disability Scale (SDS) Total Score | -4.8 Scores on a scale | Standard Deviation 6.88 |