Attention Deficit/Hyperactivity Disorder
Conditions
Keywords
Attention Deficit /Hyperactivity Disorder, hyperactivity
Brief summary
This study will evaluate efficacy and safety of methylphenidate hydrochloride extended release compared to placebo in adult patients with childhood-onset attention deficit/hyperactivity disorder (ADHD).
Interventions
DRUGPlacebo
Placebo Comparator: Placebo
DRUGRitalin LA 20 mg
Ritalin LA (a racemic mixture of d- and l-thre-Methylphenidate Hydrochloride (MPH), extended release hard capsules) taken orally once daily in doses of 40, 60, or 80 mg.
DRUGRitalin LA 30 mg
Ritalin LA (a racemic mixture of d- and l-thre-Methylphenidate Hydrochloride (MPH), extended release hard capsules) taken orally once daily in doses of 60, or 80 mg.
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
1. Diagnosis of attention deficit/hyperactivity disorder (ADHD) which started in childhood 2. Female patients of childbearing potential must be practicing an acceptable method of contraception.
Exclusion criteria
1. Patients with body mass index (BMI) less than 18.5 kg/m2 or more than 35 kg/m2 2. History of alcohol or substance abuse within the last six months. 3. History of seizures or use of anticonvulsant medication. 4. Any psychiatric condition that requires medication or may interfere with study participation. 5. Pre-existing cardiovascular disorders including severe hypertension, heart failure, myocardial infraction, etc. 6. Significant respiratory, hepatic, gastrointestinal, renal, hematological or oncologic disorder 7. Diagnosis of glaucoma, hyperthyroidism, pheochromocytoma 8. Diagnosis or family history of Tourette's syndrome 9. Pre-existing cerebrovascular disorders such as cerebral aneurysm, vascular abnormalities including vasculitis or stroke Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline of Period 1 (Baseline 1) to End of Period 1 on Attention-Deficit/Hyperactivity Disorder Rating Scale (DSM-IV ADHD RS) Total Score by Treatment | Baseline 1 to End of Period 1 (Week 9) | 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 (Never) to 4 (Very often). The total score ranges from 0(least symptomatic) to 72 (most symptomatic). 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. 30% improvement: 100×(DSM-IV ADHD RS total score during Period 1 - DSM-IV ADHD RS total score at randomization(visit 2))/DSM-IV ADHD RS total score at randomization (visit 2) \<= - 30%. |
| Change From Baseline Period 1 (Baseline 1) to End of Period 1 on Sheehan Disability Scale (SDS) Total Score by Treatment | Baseline 1 to End of Period 1 (Week 9) | SDS, a 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 reg. activities over the past 7d in ea. using a scale from 0(not at all)-10(extremely) Ea. 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 impairmt. 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. |
| Percentage of Participants With Treatment Failures During Period 3 | Baseline Period 1 (Baseline 1) and Baseline Period 3 (Baseline 2) to End of Week 40 | Treatment failure is defined as: 100×(DSM-IV ADHD RS total score during Period 3 - DSM-IV ADHD RS total score at re-randomization (visit 13))/DSM-IV ADHD RS total score at re-randomization (visit 13) \>= 30% AND 100×(DSM-IV ADHD RS total score during Period 3 - DSM-IV ADHD RS total score at randomization (visit 2))/DSM-IV ADHD RS total score at randomization (visit 2) \> - 30%. The ADHD-RS-IV is an 180item clinician rated scale to assess ADHD by DSM-IV-TR, defined criteria using symptom terminology appropriate for the adult population. Each item pertains to inattention (odd-numbered) or hyperactivity/impulsivity (even-numbered) and is scored on a scale of 0 (no symptoms) to 3 (severe symptoms). A total added score can range from 0-54 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Clinical Global Impression - Improvement Scale Severity of Illness (CGI-S) Rating at the End of Period 2 (Visit 13/ Week 14) | Baseline 1 to End of Period 2 (Week 14) | CGI-S assesses the patient's current illness state. CGI-S consists of 7 ratings that range from 1 = normal, not at all ill , 2 = borderline mentally ill, 3 = mildly ill, 4 = moderately ill, 5 = markedly ill, 6 = severely ill, 7 = among the most extremely ill patients |
| Change From Baseline Period 3 (Baseline 2) to End of Period 3 on DSM-IV Attention-Deficit/Hyperactivity Disorder Rating Scale ADHD RS Total Score by Treatment | Baseline 2 to end of Period 3 (end of withdrawal period 40 weeks) | The ADHD-RS-IV is an 180 item clinician rated scale to assess ADHD by DSM-IV-TR, defined criteria using symptom terminology appropriate for the adult population. Each item pertains to inattention (odd-numbered) or hyperactivity/impulsivity (even-numbered) and is scored on a scale of 0 (no symptoms) to 3 (severe symptoms). A total added score can range from 0-54. |
| Change From Baseline Period 3 (Baseline 2) to End of Period 3 on SDS Total Score by Treatment | Baseline 2 to end of Period 3 (end of withdrawal period 40 weeks) | The Sheehan Disability Scale (SDS) is a self-rating scale designed to assess the extent to which the patient's work social life/leisure activities and home life are impaired by his or her symptoms. The scale generates 4 scores: a work disability score, a social life disability score, a family life disability score and a total score. To get a total score the 3 individual scores (work: social life: family life) are totaled. The maximum possible score is 30 The higher the score, the more impaired a patient's work, social life, family life is. |
| Percentage of Patients With Improvement on Clinical Global Impression - Improvement Scale (CGI-I) From Baseline Period 1 (Baseline 1) to End of Period 1 | Baseline 1 to End of Period 1 (Week 9) | On the CGI-I scale, a lower score reflects greater improvement between 1 and 3, a score of 4 is no change, scores higher than 4 reflect worsening. The CGI-I consists of 7 ratings that range from 1 = Very much improved to 7 =Very much worse. Improvement on the CGI-I scale is defined as a visit rating of 1 very much improved or 2 much improved on the CGI-I scale. Percentage has been calculated from the evaluable patients (N) as Percentage = n/N \* 100. |
| Number of Patients With Worsening on CGI-S Scale From Baseline Period 3 (Baseline 2) to End of Period 3 by Treatment | Baseline 2 to end of Period 3 (end of withdrawal period 40 weeks) | CGI-S assesses the patient's current illness state. CGI-S consists of 7 ratings that range from 1 = normal, not at all ill , 2 = borderline mentally ill, 3 = mildly ill, 4 = moderately ill, 5 = markedly ill, 6 = severely ill, 7 = among the most extremely ill patients |
| Change From Baseline Period 3 (Baseline 2) to End of Period 3 in Conners Adult ADHD Rating Scales Observer: Short Version (CAARS-O:S:) Total Score by Treatment | Baseline 2 to end of Period 3 (end of withdrawal period 40 weeks) | CAARS is an instrument to assess ADHD symptoms and behaviors in adults. This study utilizes the Observer Short Version (CAARS-O: S), consisting of 26 items and 6 subscales: Inattention/Memory Problems, Hyperactivity/Restlessness, Impulsivity/Emotional Lability, Problems with Self-Concept, ADHD Index (to distinguish ADHD adults from non-clinical adults), and Inconsistency Index (to identify random or careless responding) and is rated by someone close to the patient in their daily life such as a spouse, friend, or coworker. The observer is asked to notice the patient carefully and decide how much or how frequently each of the 26 items of the scale describes the patient recently. The response to every question in increasing order of severity is not at all, never = 0; Just a little, once in a while = 1; Pretty much, often = 2; Very much, very frequently = 3. The total score combined from all the 26 items ranges from 0 to 88. |
| Change From Baseline Period 3 (Baseline 2) to End of Period 3 in ASRS Total Score by Treatment | Baseline 2 to end of Period 3 (end of withdrawal period 40 weeks) | The ASRS is a self-rating scale designed to assess ADHD symptoms in adults and is now part of the World Health Organization Composite International Diagnostic Interview. It consists of 18 items written to reflect the DSM-IV diagnostic criteria for ADHD and are rated from 0 (Never) to 4 (Very often). The total score ranges from 0 to 72. |
| Number of Patients With Worsening on CGI-I Scale From Baseline Period 3 (Baseline 2) to End of Period 3 by Treatment | Baseline 2 to end of Period 3 (end of withdrawal period 40 weeks) | On the CGI-I scale, a lower score reflects greater improvement between 1 and 3, a score of 4 is no change, scores higher than 4 reflect worsening. The CGI-I consists of 7 ratings that range from 1 = Very much improved to 7 =Very much worse. Improvement on the CGI-I scale is defined as a visit rating of 1 very much improved or 2 much improved on the CGI-I scale. |
| Change From Baseline 1 in DSM-IVADHD RS Total Score, SDS Total Score, The Conners' Adult ADHD Rating Scale Observer Short Version (CAARS-O:S) Total Score and Adult Self-Report Scale (ASRS) Total Score at the End of Period 2 (Visit 13/ Week 14) | Baseline 1 to End of Period 2 (Week 14) | DSM-IV ADHD RS consists of 18 items directly adapted from the ADHD symptom list according to the DSM-IV. The SDS is a five-item, self-rated questionnaire that has been used widely in clinical trials and observational studies. CAARS-O: S consists of 26 items and 6 subscales: Inattention/Memory Problems, Hyperactivity/Restlessness, Impulsivity/Emotional Lability, Problems with Self-Concept, ADHD Index, and Inconsistency Index and is rated by someone close to the patient in their daily life such as a spouse, friend, or coworker. The Adult Self-Report Scale (ASRS) is a self-rating scale designed to assess Attention-Deficit/Hyperactivity Disorder (ADHD) symptoms. The 18 items are written to reflect the DSM-IV diagnostic criteria for ADHD and are rated from 0 (Never) to 4 (Very often). |
| Number of Participants With Clinical Global Impression - Improvement Scale (CGI-I) Rating at the End of Period 2 (Visit 13/ Week 14) | Baseline 1 to End of Period 2 (Week 14) | CGI-I assesses the overall change of illness relative to baseline. CGI-I consists of 7 ratings that range from 1 = very much improved, 2 = much improved, 3 = minimally improved, 4 = no change from baseline, 5 = minimally worse, 6 = much worse 7 = very much worse |
Countries
Belgium, Colombia, Denmark, Germany, Norway, Singapore, South Africa, Sweden, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Ritalin LA 40 mg In period 1 patients were given Ritalin LA 20 mg and up titrated to 40 mg at week 2, continued in same dose till week 9. Period 2- The dose of study medication was re-titrated for all patients (including those in the Placebo arm during Period 1) starting at 20 mg/day Ritalin LA and increased at weekly intervals in increments of 20 mg/day until reaching the patient's optimal dose 40 mg. Optimal dose was defined as the dose at which the investigator considered an optimal balance between control of symptoms and side effects was maintained for a period of at least one week prior to Week 14. In period 3, patients were re- randomized to either their optimal dose of medication (40, 60, or 80 mg/day) or Placebo from beginning of week 15 to end of week 40. | 181 |
| Ritalin LA 60 mg In period 1 patients were given Ritalin LA 20 mg and up titrated to 40 mg at week 2 and to 60 mg at week 3. Period 2- The dose of study medication was re-titrated for all patients (including those in the Placebo arm during Period 1) starting at 20 mg/day Ritalin LA and increased at weekly intervals in increments of 20 mg/day until reaching the patient's optimal dose 60 mg. Optimal dose was defined as the dose at which the investigator considered an optimal balance between control of symptoms and side effects was maintained for a period of at least one week prior to Week 14.In period 3, patients were re- randomized to either their optimal dose of medication (40, 60, or 80 mg/day) or Placebo from beginning of week 15 to end of week 40. | 182 |
| Ritalin LA 80 mg In period 1 patients were given Ritalin LA 20 mg and up titrated to 40 mg at week 2 and to 60 mg at week 3 and to 80 mg at week 4. Period 2- The dose of study medication was re-titrated for all patients (including those in the Placebo arm during Period 1) starting at 20 mg/day Ritalin LA and increased at weekly intervals in increments of 20 mg/day until reaching the patient's optimal dose 60 mg. Optimal dose was defined as the dose at which the investigator considered an optimal balance between control of symptoms and side effects was maintained for a period of at least one week prior to Week 14. In period 3, patients were re- randomized to either their optimal dose of medication (40, 60, or 80 mg/day) or Placebo from beginning of week 15 to end of week 40. | 181 |
| Placebo Period 1- Placebo controlled Period 2 - The dose of study medication was re-titrated for all patients (including those in the Placebo arm during Period 1) starting at 20 mg/day Ritalin LA and increased at weekly intervals in increments of 20 mg/day until reaching the patient's optimal dose (40, 60 or 80 mg). In period 3, patients were re- randomized to either their optimal dose of medication (40, 60, or 80 mg/day) or Placebo from beginning of week 15 to end of week 40. | 181 |
| Total | 725 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Period 1 (9 Weeks) | Administrative Problems | 0 | 1 | 1 | 2 |
| Period 1 (9 Weeks) | Adverse Event | 13 | 18 | 26 | 3 |
| Period 1 (9 Weeks) | Lack of Efficacy | 2 | 2 | 4 | 11 |
| Period 1 (9 Weeks) | Lost to Follow-up | 4 | 6 | 3 | 4 |
| Period 1 (9 Weeks) | Protocol Violation | 5 | 6 | 3 | 1 |
| Period 1 (9 Weeks) | Withdrawal by Subject | 5 | 8 | 6 | 7 |
| Period 2 (Week 10 to Week 14) | Adverse Event | 3 | 4 | 7 | 8 |
| Period 2 (Week 10 to Week 14) | Lack of Efficacy | 13 | 7 | 7 | 13 |
| Period 2 (Week 10 to Week 14) | Lost to Follow-up | 3 | 3 | 1 | 3 |
| Period 2 (Week 10 to Week 14) | Protocol Violation | 0 | 2 | 1 | 0 |
| Period 2 (Week 10 to Week 14) | Withdrawal by Subject | 6 | 2 | 8 | 4 |
| Period 3 (Week 15 to End of Week 40) | Abnormal Lab value(s) | 0 | 0 | 0 | 1 |
| Period 3 (Week 15 to End of Week 40) | Abnormal Test Procedure Result(s) | 0 | 0 | 1 | 0 |
| Period 3 (Week 15 to End of Week 40) | Administrative Problems | 0 | 0 | 1 | 0 |
| Period 3 (Week 15 to End of Week 40) | Adverse Event | 5 | 11 | 6 | 5 |
| Period 3 (Week 15 to End of Week 40) | Lack of Efficacy | 28 | 42 | 29 | 62 |
| Period 3 (Week 15 to End of Week 40) | Lost to Follow-up | 3 | 4 | 6 | 3 |
| Period 3 (Week 15 to End of Week 40) | Patient no longer requires study drug | 1 | 0 | 0 | 0 |
| Period 3 (Week 15 to End of Week 40) | Protocol Violation | 5 | 6 | 3 | 7 |
| Period 3 (Week 15 to End of Week 40) | Withdrawal by Subject | 12 | 6 | 4 | 3 |
Baseline characteristics
| Characteristic | Ritalin LA 40 mg | Ritalin LA 60 mg | Ritalin LA 80 mg | Placebo | Total |
|---|---|---|---|---|---|
| Age, Customized 18-30 | 72 Participants | 78 Participants | 71 Participants | 66 Participants | 287 Participants |
| Age, Customized 31-40 | 19 Participants | 45 Participants | 40 Participants | 38 Participants | 162 Participants |
| Age, Customized 41-50 | 56 Participants | 41 Participants | 45 Participants | 31 Participants | 149 Participants |
| Age, Customized 51-60 | 10 Participants | 14 Participants | 13 Participants | 30 Participants | 71 Participants |
| Gender Female | 60 Participants | 58 Participants | 46 Participants | 52 Participants | 216 Participants |
| Gender Male | 54 Participants | 74 Participants | 74 Participants | 71 Participants | 273 Participants |
| Sex: Female, Male Female | 87 Participants | 77 Participants | 86 Participants | 80 Participants | 330 Participants |
| Sex: Female, Male Male | 94 Participants | 105 Participants | 95 Participants | 101 Participants | 395 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 517 / 695 | 104 / 275 |
| serious Total, serious adverse events | 9 / 695 | 4 / 275 |
Outcome results
Primary
Change From Baseline of Period 1 (Baseline 1) to End of Period 1 on Attention-Deficit/Hyperactivity Disorder Rating Scale (DSM-IV ADHD RS) Total Score by Treatment
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 (Never) to 4 (Very often). The total score ranges from 0(least symptomatic) to 72 (most symptomatic). 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. 30% improvement: 100×(DSM-IV ADHD RS total score during Period 1 - DSM-IV ADHD RS total score at randomization(visit 2))/DSM-IV ADHD RS total score at randomization (visit 2) \<= - 30%.
Time frame: Baseline 1 to End of Period 1 (Week 9)
Population: Full Analysis Set for Period 1 (FAS P1) - all randomized patients who take one dose of study medication in period 1. Patients will be assigned to their randomized fixed dose. Patients with both baseline and post-baseline (end of week 9) assessments were included.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ritalin LA 40 mg | Change From Baseline of Period 1 (Baseline 1) to End of Period 1 on Attention-Deficit/Hyperactivity Disorder Rating Scale (DSM-IV ADHD RS) Total Score by Treatment | 16.0 Units on a Scale | Standard Deviation 12.18 |
| Ritalin LA 60 mg | Change From Baseline of Period 1 (Baseline 1) to End of Period 1 on Attention-Deficit/Hyperactivity Disorder Rating Scale (DSM-IV ADHD RS) Total Score by Treatment | 14.7 Units on a Scale | Standard Deviation 10.12 |
| Ritalin LA 80 mg | Change From Baseline of Period 1 (Baseline 1) to End of Period 1 on Attention-Deficit/Hyperactivity Disorder Rating Scale (DSM-IV ADHD RS) Total Score by Treatment | 16.8 Units on a Scale | Standard Deviation 11.36 |
| Placebo | Change From Baseline of Period 1 (Baseline 1) to End of Period 1 on Attention-Deficit/Hyperactivity Disorder Rating Scale (DSM-IV ADHD RS) Total Score by Treatment | 9.7 Units on a Scale | Standard Deviation 11.05 |
Primary
Change From Baseline Period 1 (Baseline 1) to End of Period 1 on Sheehan Disability Scale (SDS) Total Score by Treatment
SDS, a 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 reg. activities over the past 7d in ea. using a scale from 0(not at all)-10(extremely) Ea. 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 impairmt. 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: Baseline 1 to End of Period 1 (Week 9)
Population: Full Analysis Set for Period 1 (FAS P1) - all randomized patients who take one dose of study medication in period 1. Patients will be assigned to their randomized fixed dose. Patients with both baseline and post-baseline (end of week 9) assessments were included.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ritalin LA 40 mg | Change From Baseline Period 1 (Baseline 1) to End of Period 1 on Sheehan Disability Scale (SDS) Total Score by Treatment | 6.4 Units on a Scale | Standard Deviation 7.54 |
| Ritalin LA 60 mg | Change From Baseline Period 1 (Baseline 1) to End of Period 1 on Sheehan Disability Scale (SDS) Total Score by Treatment | 4.7 Units on a Scale | Standard Deviation 7.08 |
| Ritalin LA 80 mg | Change From Baseline Period 1 (Baseline 1) to End of Period 1 on Sheehan Disability Scale (SDS) Total Score by Treatment | 6.1 Units on a Scale | Standard Deviation 7.31 |
| Placebo | Change From Baseline Period 1 (Baseline 1) to End of Period 1 on Sheehan Disability Scale (SDS) Total Score by Treatment | 2.9 Units on a Scale | Standard Deviation 7.47 |
Primary
Percentage of Participants With Treatment Failures During Period 3
Treatment failure is defined as: 100×(DSM-IV ADHD RS total score during Period 3 - DSM-IV ADHD RS total score at re-randomization (visit 13))/DSM-IV ADHD RS total score at re-randomization (visit 13) \>= 30% AND 100×(DSM-IV ADHD RS total score during Period 3 - DSM-IV ADHD RS total score at randomization (visit 2))/DSM-IV ADHD RS total score at randomization (visit 2) \> - 30%. The ADHD-RS-IV is an 180item clinician rated scale to assess ADHD by DSM-IV-TR, defined criteria using symptom terminology appropriate for the adult population. Each item pertains to inattention (odd-numbered) or hyperactivity/impulsivity (even-numbered) and is scored on a scale of 0 (no symptoms) to 3 (severe symptoms). A total added score can range from 0-54
Time frame: Baseline Period 1 (Baseline 1) and Baseline Period 3 (Baseline 2) to End of Week 40
Population: Full Analysis Set for Period 3 (FAS P3) - all re-randomized patients who take one dose of study medication in period 3. One patient in Ritalin LA 80mg did not have post baseline 2 measurements and was not included in the categories under without imputation.
| Arm | Measure | Group | Value (NUMBER) | Dispersion |
|---|---|---|---|---|
| Ritalin LA 40 mg | Percentage of Participants With Treatment Failures During Period 3 | With Imputation - Treatment failure | 16.4 Percentage of participants | — |
| Ritalin LA 40 mg | Percentage of Participants With Treatment Failures During Period 3 | Without Imputation - Not treatment failure | 54.5 Percentage of participants | — |
| Ritalin LA 40 mg | Percentage of Participants With Treatment Failures During Period 3 | With Imputation - Not treatment failure | 83.6 Percentage of participants | — |
| Ritalin LA 40 mg | Percentage of Participants With Treatment Failures During Period 3 | Without Imputation missing failure status | 33.6 Percentage of participants | — |
| Ritalin LA 40 mg | Percentage of Participants With Treatment Failures During Period 3 | Without Imputation - Treatment failure | 11.8 Percentage of participants | 7.54 |
| Ritalin LA 60 mg | Percentage of Participants With Treatment Failures During Period 3 | Without Imputation missing failure status | 29.7 Percentage of participants | — |
| Ritalin LA 60 mg | Percentage of Participants With Treatment Failures During Period 3 | With Imputation - Treatment failure | 26.6 Percentage of participants | — |
| Ritalin LA 60 mg | Percentage of Participants With Treatment Failures During Period 3 | With Imputation - Not treatment failure | 73.4 Percentage of participants | — |
| Ritalin LA 60 mg | Percentage of Participants With Treatment Failures During Period 3 | Without Imputation - Not treatment failure | 50.0 Percentage of participants | — |
| Ritalin LA 60 mg | Percentage of Participants With Treatment Failures During Period 3 | Without Imputation - Treatment failure | 20.3 Percentage of participants | 7.08 |
| Ritalin LA 80 mg | Percentage of Participants With Treatment Failures During Period 3 | Without Imputation missing failure status | 25.4 Percentage of participants | — |
| Ritalin LA 80 mg | Percentage of Participants With Treatment Failures During Period 3 | Without Imputation - Treatment failure | 17.5 Percentage of participants | 7.31 |
| Ritalin LA 80 mg | Percentage of Participants With Treatment Failures During Period 3 | Without Imputation - Not treatment failure | 56.1 Percentage of participants | — |
| Ritalin LA 80 mg | Percentage of Participants With Treatment Failures During Period 3 | With Imputation - Treatment failure | 20.2 Percentage of participants | — |
| Ritalin LA 80 mg | Percentage of Participants With Treatment Failures During Period 3 | With Imputation - Not treatment failure | 79.8 Percentage of participants | — |
| Placebo | Percentage of Participants With Treatment Failures During Period 3 | With Imputation - Treatment failure | 49.6 Percentage of participants | — |
| Placebo | Percentage of Participants With Treatment Failures During Period 3 | Without Imputation - Not treatment failure | 31.3 Percentage of participants | — |
| Placebo | Percentage of Participants With Treatment Failures During Period 3 | Without Imputation - Treatment failure | 43.5 Percentage of participants | 7.47 |
| Placebo | Percentage of Participants With Treatment Failures During Period 3 | Without Imputation missing failure status | 25.2 Percentage of participants | — |
| Placebo | Percentage of Participants With Treatment Failures During Period 3 | With Imputation - Not treatment failure | 50.4 Percentage of participants | — |
Secondary
Change From Baseline 1 in DSM-IVADHD RS Total Score, SDS Total Score, The Conners' Adult ADHD Rating Scale Observer Short Version (CAARS-O:S) Total Score and Adult Self-Report Scale (ASRS) Total Score at the End of Period 2 (Visit 13/ Week 14)
DSM-IV ADHD RS consists of 18 items directly adapted from the ADHD symptom list according to the DSM-IV. The SDS is a five-item, self-rated questionnaire that has been used widely in clinical trials and observational studies. CAARS-O: S consists of 26 items and 6 subscales: Inattention/Memory Problems, Hyperactivity/Restlessness, Impulsivity/Emotional Lability, Problems with Self-Concept, ADHD Index, and Inconsistency Index and is rated by someone close to the patient in their daily life such as a spouse, friend, or coworker. The Adult Self-Report Scale (ASRS) is a self-rating scale designed to assess Attention-Deficit/Hyperactivity Disorder (ADHD) symptoms. The 18 items are written to reflect the DSM-IV diagnostic criteria for ADHD and are rated from 0 (Never) to 4 (Very often).
Time frame: Baseline 1 to End of Period 2 (Week 14)
Population: Full Analysis Set for Period 2 (FAS P2) - all randomized patients who took one dose of study medication in Period 2
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ritalin LA 40 mg | Change From Baseline 1 in DSM-IVADHD RS Total Score, SDS Total Score, The Conners' Adult ADHD Rating Scale Observer Short Version (CAARS-O:S) Total Score and Adult Self-Report Scale (ASRS) Total Score at the End of Period 2 (Visit 13/ Week 14) | DSM-IV ADHD RS total score n=494 | 24.8 Score on Scale | Standard Deviation 8.97 |
| Ritalin LA 40 mg | Change From Baseline 1 in DSM-IVADHD RS Total Score, SDS Total Score, The Conners' Adult ADHD Rating Scale Observer Short Version (CAARS-O:S) Total Score and Adult Self-Report Scale (ASRS) Total Score at the End of Period 2 (Visit 13/ Week 14) | SDS total score n=480 | 10.1 Score on Scale | Standard Deviation 7.25 |
| Ritalin LA 40 mg | Change From Baseline 1 in DSM-IVADHD RS Total Score, SDS Total Score, The Conners' Adult ADHD Rating Scale Observer Short Version (CAARS-O:S) Total Score and Adult Self-Report Scale (ASRS) Total Score at the End of Period 2 (Visit 13/ Week 14) | CAARS-O:S total score n=411 | 15.5 Score on Scale | Standard Deviation 15.25 |
| Ritalin LA 40 mg | Change From Baseline 1 in DSM-IVADHD RS Total Score, SDS Total Score, The Conners' Adult ADHD Rating Scale Observer Short Version (CAARS-O:S) Total Score and Adult Self-Report Scale (ASRS) Total Score at the End of Period 2 (Visit 13/ Week 14) | ASRS total score n=490 | 23.2 Score on Scale | Standard Deviation 14.16 |
Secondary
Change From Baseline Period 3 (Baseline 2) to End of Period 3 in ASRS Total Score by Treatment
The ASRS is a self-rating scale designed to assess ADHD symptoms in adults and is now part of the World Health Organization Composite International Diagnostic Interview. It consists of 18 items written to reflect the DSM-IV diagnostic criteria for ADHD and are rated from 0 (Never) to 4 (Very often). The total score ranges from 0 to 72.
Time frame: Baseline 2 to end of Period 3 (end of withdrawal period 40 weeks)
Population: Full Analysis Set for Period 3 (FAS P3) - all re-randomized patients who take one dose of study medication in period 3. Patients will be assigned to their re-randomized treatment; Ritalin (pooled doses) or placebo.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ritalin LA 40 mg | Change From Baseline Period 3 (Baseline 2) to End of Period 3 in ASRS Total Score by Treatment | 3.0 Units on a scale | Standard Deviation 12.64 |
| Ritalin LA 60 mg | Change From Baseline Period 3 (Baseline 2) to End of Period 3 in ASRS Total Score by Treatment | 3.8 Units on a scale | Standard Deviation 12.66 |
| Ritalin LA 80 mg | Change From Baseline Period 3 (Baseline 2) to End of Period 3 in ASRS Total Score by Treatment | 3.0 Units on a scale | Standard Deviation 11.54 |
| Placebo | Change From Baseline Period 3 (Baseline 2) to End of Period 3 in ASRS Total Score by Treatment | 8.0 Units on a scale | Standard Deviation 16.39 |
Secondary
Change From Baseline Period 3 (Baseline 2) to End of Period 3 in Conners Adult ADHD Rating Scales Observer: Short Version (CAARS-O:S:) Total Score by Treatment
CAARS is an instrument to assess ADHD symptoms and behaviors in adults. This study utilizes the Observer Short Version (CAARS-O: S), consisting of 26 items and 6 subscales: Inattention/Memory Problems, Hyperactivity/Restlessness, Impulsivity/Emotional Lability, Problems with Self-Concept, ADHD Index (to distinguish ADHD adults from non-clinical adults), and Inconsistency Index (to identify random or careless responding) and is rated by someone close to the patient in their daily life such as a spouse, friend, or coworker. The observer is asked to notice the patient carefully and decide how much or how frequently each of the 26 items of the scale describes the patient recently. The response to every question in increasing order of severity is not at all, never = 0; Just a little, once in a while = 1; Pretty much, often = 2; Very much, very frequently = 3. The total score combined from all the 26 items ranges from 0 to 88.
Time frame: Baseline 2 to end of Period 3 (end of withdrawal period 40 weeks)
Population: Full Analysis Set for Period 3 (FAS P3) - all re-randomized patients who take one dose of study medication in period 3. Patients will be assigned to their re-randomized treatment; Ritalin (pooled doses) or placebo.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ritalin LA 40 mg | Change From Baseline Period 3 (Baseline 2) to End of Period 3 in Conners Adult ADHD Rating Scales Observer: Short Version (CAARS-O:S:) Total Score by Treatment | -2.7 Units on a scale | Standard Deviation 11.74 |
| Ritalin LA 60 mg | Change From Baseline Period 3 (Baseline 2) to End of Period 3 in Conners Adult ADHD Rating Scales Observer: Short Version (CAARS-O:S:) Total Score by Treatment | 1.7 Units on a scale | Standard Deviation 12 |
| Ritalin LA 80 mg | Change From Baseline Period 3 (Baseline 2) to End of Period 3 in Conners Adult ADHD Rating Scales Observer: Short Version (CAARS-O:S:) Total Score by Treatment | -0.2 Units on a scale | Standard Deviation 14.23 |
| Placebo | Change From Baseline Period 3 (Baseline 2) to End of Period 3 in Conners Adult ADHD Rating Scales Observer: Short Version (CAARS-O:S:) Total Score by Treatment | 2.9 Units on a scale | Standard Deviation 15.26 |
Secondary
Change From Baseline Period 3 (Baseline 2) to End of Period 3 on DSM-IV Attention-Deficit/Hyperactivity Disorder Rating Scale ADHD RS Total Score by Treatment
The ADHD-RS-IV is an 180 item clinician rated scale to assess ADHD by DSM-IV-TR, defined criteria using symptom terminology appropriate for the adult population. Each item pertains to inattention (odd-numbered) or hyperactivity/impulsivity (even-numbered) and is scored on a scale of 0 (no symptoms) to 3 (severe symptoms). A total added score can range from 0-54.
Time frame: Baseline 2 to end of Period 3 (end of withdrawal period 40 weeks)
Population: Full Analysis Set for Period 3 (FAS P3) - all re-randomized patients who take one dose of study medication in period 3. Patients will be assigned to their re-randomized treatment; Ritalin (pooled doses) or placebo.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ritalin LA 40 mg | Change From Baseline Period 3 (Baseline 2) to End of Period 3 on DSM-IV Attention-Deficit/Hyperactivity Disorder Rating Scale ADHD RS Total Score by Treatment | 3.0 Units on a Scale | Standard Deviation 10.07 |
| Ritalin LA 60 mg | Change From Baseline Period 3 (Baseline 2) to End of Period 3 on DSM-IV Attention-Deficit/Hyperactivity Disorder Rating Scale ADHD RS Total Score by Treatment | 5.1 Units on a Scale | Standard Deviation 10.85 |
| Ritalin LA 80 mg | Change From Baseline Period 3 (Baseline 2) to End of Period 3 on DSM-IV Attention-Deficit/Hyperactivity Disorder Rating Scale ADHD RS Total Score by Treatment | 2.6 Units on a Scale | Standard Deviation 8.67 |
| Placebo | Change From Baseline Period 3 (Baseline 2) to End of Period 3 on DSM-IV Attention-Deficit/Hyperactivity Disorder Rating Scale ADHD RS Total Score by Treatment | 9.3 Units on a Scale | Standard Deviation 11.95 |
Secondary
Change From Baseline Period 3 (Baseline 2) to End of Period 3 on SDS Total Score by Treatment
The Sheehan Disability Scale (SDS) is a self-rating scale designed to assess the extent to which the patient's work social life/leisure activities and home life are impaired by his or her symptoms. The scale generates 4 scores: a work disability score, a social life disability score, a family life disability score and a total score. To get a total score the 3 individual scores (work: social life: family life) are totaled. The maximum possible score is 30 The higher the score, the more impaired a patient's work, social life, family life is.
Time frame: Baseline 2 to end of Period 3 (end of withdrawal period 40 weeks)
Population: Full Analysis Set for Period 3 (FAS P3) - all re-randomized patients who take one dose of study medication in period 3. Patients will be assigned to their re-randomized treatment; Ritalin (pooled doses) or placebo.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ritalin LA 40 mg | Change From Baseline Period 3 (Baseline 2) to End of Period 3 on SDS Total Score by Treatment | 2.1 Units on a Scale | Standard Deviation 6.34 |
| Ritalin LA 60 mg | Change From Baseline Period 3 (Baseline 2) to End of Period 3 on SDS Total Score by Treatment | 2.3 Units on a Scale | Standard Deviation 7.19 |
| Ritalin LA 80 mg | Change From Baseline Period 3 (Baseline 2) to End of Period 3 on SDS Total Score by Treatment | 2.0 Units on a Scale | Standard Deviation 6.81 |
| Placebo | Change From Baseline Period 3 (Baseline 2) to End of Period 3 on SDS Total Score by Treatment | 5.0 Units on a Scale | Standard Deviation 8.15 |
Secondary
Number of Participants With Clinical Global Impression - Improvement Scale (CGI-I) Rating at the End of Period 2 (Visit 13/ Week 14)
CGI-I assesses the overall change of illness relative to baseline. CGI-I consists of 7 ratings that range from 1 = very much improved, 2 = much improved, 3 = minimally improved, 4 = no change from baseline, 5 = minimally worse, 6 = much worse 7 = very much worse
Time frame: Baseline 1 to End of Period 2 (Week 14)
Population: Full Analysis Set for Period 2 (FAS P2) - all randomized patients who took one dose of study medication in Period 2 Patients with CGI-I assessment both at Baseline 1 and Period 2 was included.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ritalin LA 40 mg | Number of Participants With Clinical Global Impression - Improvement Scale (CGI-I) Rating at the End of Period 2 (Visit 13/ Week 14) | very much improved | 195 number of participants |
| Ritalin LA 40 mg | Number of Participants With Clinical Global Impression - Improvement Scale (CGI-I) Rating at the End of Period 2 (Visit 13/ Week 14) | much improved | 230 number of participants |
| Ritalin LA 40 mg | Number of Participants With Clinical Global Impression - Improvement Scale (CGI-I) Rating at the End of Period 2 (Visit 13/ Week 14) | minimally improved | 42 number of participants |
| Ritalin LA 40 mg | Number of Participants With Clinical Global Impression - Improvement Scale (CGI-I) Rating at the End of Period 2 (Visit 13/ Week 14) | no change | 16 number of participants |
| Ritalin LA 40 mg | Number of Participants With Clinical Global Impression - Improvement Scale (CGI-I) Rating at the End of Period 2 (Visit 13/ Week 14) | minimally worse | 7 number of participants |
| Ritalin LA 40 mg | Number of Participants With Clinical Global Impression - Improvement Scale (CGI-I) Rating at the End of Period 2 (Visit 13/ Week 14) | much worse | 2 number of participants |
| Ritalin LA 40 mg | Number of Participants With Clinical Global Impression - Improvement Scale (CGI-I) Rating at the End of Period 2 (Visit 13/ Week 14) | very much worse | 0 number of participants |
Secondary
Number of Participants With Clinical Global Impression - Improvement Scale Severity of Illness (CGI-S) Rating at the End of Period 2 (Visit 13/ Week 14)
CGI-S assesses the patient's current illness state. CGI-S consists of 7 ratings that range from 1 = normal, not at all ill , 2 = borderline mentally ill, 3 = mildly ill, 4 = moderately ill, 5 = markedly ill, 6 = severely ill, 7 = among the most extremely ill patients
Time frame: Baseline 1 to End of Period 2 (Week 14)
Population: Full Analysis Set for Period 2 (FAS P2) - all randomized patients who took one dose of study medication in Period 2; Patients with CGI-S assessment both at Baseline 1 and Period 2 was included.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ritalin LA 40 mg | Number of Participants With Clinical Global Impression - Improvement Scale Severity of Illness (CGI-S) Rating at the End of Period 2 (Visit 13/ Week 14) | Normal, not ill at all | 91 number of participants |
| Ritalin LA 40 mg | Number of Participants With Clinical Global Impression - Improvement Scale Severity of Illness (CGI-S) Rating at the End of Period 2 (Visit 13/ Week 14) | borderline mentally ill | 151 number of participants |
| Ritalin LA 40 mg | Number of Participants With Clinical Global Impression - Improvement Scale Severity of Illness (CGI-S) Rating at the End of Period 2 (Visit 13/ Week 14) | mildly ill | 193 number of participants |
| Ritalin LA 40 mg | Number of Participants With Clinical Global Impression - Improvement Scale Severity of Illness (CGI-S) Rating at the End of Period 2 (Visit 13/ Week 14) | moderately ill | 50 number of participants |
| Ritalin LA 40 mg | Number of Participants With Clinical Global Impression - Improvement Scale Severity of Illness (CGI-S) Rating at the End of Period 2 (Visit 13/ Week 14) | markedly ill | 7 number of participants |
| Ritalin LA 40 mg | Number of Participants With Clinical Global Impression - Improvement Scale Severity of Illness (CGI-S) Rating at the End of Period 2 (Visit 13/ Week 14) | severely ill | 0 number of participants |
| Ritalin LA 40 mg | Number of Participants With Clinical Global Impression - Improvement Scale Severity of Illness (CGI-S) Rating at the End of Period 2 (Visit 13/ Week 14) | among the most extremely ill patients | 0 number of participants |
Secondary
Number of Patients With Worsening on CGI-I Scale From Baseline Period 3 (Baseline 2) to End of Period 3 by Treatment
On the CGI-I scale, a lower score reflects greater improvement between 1 and 3, a score of 4 is no change, scores higher than 4 reflect worsening. The CGI-I consists of 7 ratings that range from 1 = Very much improved to 7 =Very much worse. Improvement on the CGI-I scale is defined as a visit rating of 1 very much improved or 2 much improved on the CGI-I scale.
Time frame: Baseline 2 to end of Period 3 (end of withdrawal period 40 weeks)
Population: Full Analysis Set for Period 3 (FAS P3) - all re-randomized patients who take one dose of study medication in period 3. Patients will be assigned to their re-randomized treatment; Ritalin (pooled doses) or placebo. Evaluable patients with both baseline 2 and post-baseline (end of week 40) assessments were included.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ritalin LA 40 mg | Number of Patients With Worsening on CGI-I Scale From Baseline Period 3 (Baseline 2) to End of Period 3 by Treatment | 6 participants |
| Ritalin LA 60 mg | Number of Patients With Worsening on CGI-I Scale From Baseline Period 3 (Baseline 2) to End of Period 3 by Treatment | 13 participants |
| Ritalin LA 80 mg | Number of Patients With Worsening on CGI-I Scale From Baseline Period 3 (Baseline 2) to End of Period 3 by Treatment | 5 participants |
| Placebo | Number of Patients With Worsening on CGI-I Scale From Baseline Period 3 (Baseline 2) to End of Period 3 by Treatment | 21 participants |
Secondary
Number of Patients With Worsening on CGI-S Scale From Baseline Period 3 (Baseline 2) to End of Period 3 by Treatment
CGI-S assesses the patient's current illness state. CGI-S consists of 7 ratings that range from 1 = normal, not at all ill , 2 = borderline mentally ill, 3 = mildly ill, 4 = moderately ill, 5 = markedly ill, 6 = severely ill, 7 = among the most extremely ill patients
Time frame: Baseline 2 to end of Period 3 (end of withdrawal period 40 weeks)
Population: Full Analysis Set for Period 3 (FAS P3) - all re-randomized patients who take one dose of study medication in period 3. Patients will be assigned to their re-randomized treatment; Ritalin (pooled doses) or placebo. Evaluable patients with both baseline 2 and post-baseline (end of week 40) assessments were included.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ritalin LA 40 mg | Number of Patients With Worsening on CGI-S Scale From Baseline Period 3 (Baseline 2) to End of Period 3 by Treatment | 39 Participants |
| Ritalin LA 60 mg | Number of Patients With Worsening on CGI-S Scale From Baseline Period 3 (Baseline 2) to End of Period 3 by Treatment | 50 Participants |
| Ritalin LA 80 mg | Number of Patients With Worsening on CGI-S Scale From Baseline Period 3 (Baseline 2) to End of Period 3 by Treatment | 35 Participants |
| Placebo | Number of Patients With Worsening on CGI-S Scale From Baseline Period 3 (Baseline 2) to End of Period 3 by Treatment | 72 Participants |
Secondary
Percentage of Patients With Improvement on Clinical Global Impression - Improvement Scale (CGI-I) From Baseline Period 1 (Baseline 1) to End of Period 1
On the CGI-I scale, a lower score reflects greater improvement between 1 and 3, a score of 4 is no change, scores higher than 4 reflect worsening. The CGI-I consists of 7 ratings that range from 1 = Very much improved to 7 =Very much worse. Improvement on the CGI-I scale is defined as a visit rating of 1 very much improved or 2 much improved on the CGI-I scale. Percentage has been calculated from the evaluable patients (N) as Percentage = n/N \* 100.
Time frame: Baseline 1 to End of Period 1 (Week 9)
Population: Full Analysis Set for Period 1 (FAS P1) - all randomized patients who take one dose of study medication in period 1. Patients will be assigned to their randomized fixed dose. Evaluable patients with both baseline and post-baseline (end of week 9) assessments were included.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ritalin LA 40 mg | Percentage of Patients With Improvement on Clinical Global Impression - Improvement Scale (CGI-I) From Baseline Period 1 (Baseline 1) to End of Period 1 | 56.3 Percentage of Patients |
| Ritalin LA 60 mg | Percentage of Patients With Improvement on Clinical Global Impression - Improvement Scale (CGI-I) From Baseline Period 1 (Baseline 1) to End of Period 1 | 54.8 Percentage of Patients |
| Ritalin LA 80 mg | Percentage of Patients With Improvement on Clinical Global Impression - Improvement Scale (CGI-I) From Baseline Period 1 (Baseline 1) to End of Period 1 | 57.1 Percentage of Patients |
| Placebo | Percentage of Patients With Improvement on Clinical Global Impression - Improvement Scale (CGI-I) From Baseline Period 1 (Baseline 1) to End of Period 1 | 31.7 Percentage of Patients |