Attention Deficit Hyperactivity Disorder
Conditions
Keywords
Attention Deficit Hyperactivity Disorder, Methylphenidate, Concerta, CONQoL
Brief summary
The purpose of this study is to evaluate the efficacy, safety and to assess the impact of the treatment on quality of life of long-acting methylphenidate in adult participants with Attention Deficit Hyperactivity Disorder (ADHD). ADHD is a clinical condition beginning in childhood and is characterized by inadequate levels of attention, hyperactivity and impulsiveness.
Detailed description
This is an open-label (all people know the identity of the intervention), multi-center (when more than one hospital or medical school team work on a medical research study), single arm study of multiple doses of long-acting methylphenidate in participants with ADHD. The study will consist of 2 phases; a screening phase and a treatment phase. The duration of participation in the study for an individual participant will be up to 12 weeks. Participants will be given 18 milligram (mg) of long-acting methylphenidate daily in the morning and titrated up (slow increase in drug dosage guided by participant's responses) to 36 mg per day (mg/day) on Day 8. Depending on response, tolerability and clinician's judgment, the dose could be escalated to the next dose level of 54 mg/day on Day 28 to a maximum of 72 mg/day on Day 56, until each participant achieved optimal dose. Participant's safety will be monitored throughout the study.
Interventions
DRUGLong-Acting Methylphenidate
Long-Acting Methylphenidate within the range of 18, 36, 54 and 76 milligram will be orally administered once daily up to Day 56.
Sponsors
Janssen-Cilag Farmaceutica Ltda.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosis of Attention Deficient Hyperactivity Disorder (ADHD) according to the Diagnostic and Statistical Manual of Mental Diseases, Fourth Edition (DSM-IV), obtained via interview with an adapted version of the Kiddie-Schedule of Affective Disorders and Schizophrenia-Epidemiologic Version (K-SADS E) module for ADHD * Described chronic course of ADHD symptomatology from childhood to adulthood, with some symptoms present before age 7 years, which continue to meet DSM-IV criteria at the time of assessment. ADHD is not diagnosed if the symptoms are better accounted for by another psychiatric disorder \[e.g. mood disorder (especially bipolar disorder), anxiety disorder, psychotic disorder, personality disorder\] * Clinical Global Impression-Severity (CGI-Severity) baseline score greater than or equal to (\>=) 4 (at least moderate severity) * Female participants must be postmenopausal (after the time in life when a woman stops having a menstrual period) for at least 1year, surgically sterile, or practicing an effective method of birth control (e.g., prescription oral contraceptives\[compounds, usually hormonal, taken orally in order to block ovulation and prevent the occurrence of pregnancy\], contraceptive injections \[chemical substances that prevent or reduce the probability of pregnancy\], intrauterine device \[contraceptive devices placed high in the uterine fundus\], double-barrier method, contraceptive patch, male partner sterilization) before entry and throughout the study; have a negative urine pregnancy test at baseline * Participant agrees to take only the supplied study drug as treatment for ADHD during the study
Exclusion criteria
* Participant having allergy or hypersensitivity to methylphenidate * Participants who are non-responder to methylphenidate in adequate doses (i.e., 0.8 - 1.0 milligram per kilogram \[mg/kg\]) * Participant treated with any methylphenidate or amphetamine containing medication within 4 weeks of the screening visit * Participant having Hamilton's Depression Scale, suicide item higher than 2 * Participant having any psychiatric condition including the following, but not limited to: acute mood disorder (disorders that have a disturbance in mood as their main feature), schizophrenia (a mixed psychiatric disorder relating to a complex psychotic state that has features of both schizophrenia and a mood disorder such as bipolar disorder), bipolar disorder I (disorder marked by severe mood swings (manic or major depressive episodes) and a tendency to remission \[when a medical problem gets better or goes away at least for a while\] and recurrence \[happen again\]), obsessive compulsive disorder (OCD) (an anxiety disorder characterized by recurrent, persistent obsessions or compulsions, anti-social personality disorder ( personality disorder whose essential feature is a pervasive pattern of disregard for, and violation of, the rights of others that begins in childhood or early adolescence and continues into adulthood)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Adult ADHD Quality of Life (AAQoL) Scale Score at Week 12 | Baseline and Week 12 | The AAQoL is a validated 29-item scale consisting of 4 subscales:life productivity (11 items), psychological health (6 items), life outlook (7 items) and relationships (5 items). Participants rate each item on a 5-point Likert - like scale ranging from 1 (not at all/never) to 5 (extremely/very often). These scores are then transformed to a 0-100 point scale, higher scores indicating better quality of life. Total score=average of individual 29 item scores (range= 0-100, where higher total score indicates better quality of life). Change from baseline in total score for AAQoL is reported. |
| Change From Baseline in Adult Attention Deficit Hyperactivity Disorder (ADHD) Self-Report Scale (ASRS) Total Score at Week 4 | Baseline and Week 4 | Adult ASRS assesses 18 core ADHD symptoms corresponding to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) diagnostic symptoms for adult participant based on the participant's own rating for each of the symptoms using a 4 point scale (0=none, 1=mild, 2=moderate, 3=severe). If a single item is missing the score is imputed and if more than one item is missing, the total score is treated as missing. The ASRS total score is derived by summing the score assigned to each of the 18 symptoms (low=0, high=54, a higher score signifies a greater severity of symptoms). |
| Change From Baseline in Adult Attention Deficit Hyperactivity Disorder (ADHD) Self-Report Scale (ASRS) Total Score at Week 8 | Baseline and Week 8 | Adult ASRS assesses 18 core ADHD symptoms corresponding to DSM-IV diagnostic symptoms for adult participant based on the participant's own rating for each of the symptoms using a 4 point scale (0=none, 1=mild, 2=moderate, 3=severe). If a single item is missing the score is imputed and if more than one item is missing, the total score is treated as missing. The ASRS total score is derived by summing the score assigned to each of the 18 symptoms (low=0, high=54, a higher score signifies a greater severity of symptoms). |
| Change From Baseline in Adult Attention Deficit Hyperactivity Disorder (ADHD) Self-Report Scale (ASRS) Total Score at Week 12 | Baseline and Week 12 | Adult ASRS assesses 18 core ADHD symptoms corresponding to DSM-IV diagnostic symptoms for adult participant based on the participant's own rating for each of the symptoms using a 4 point scale (0=none, 1=mild, 2=moderate, 3=severe). If a single item is missing the score is imputed and if more than one item is missing, the total score is treated as missing. The ASRS total score is derived by summing the score assigned to each of the 18 symptoms (low=0, high=54, a higher score signifies a greater severity of symptoms). |
| Change From Baseline in Adult ADHD Quality of Life (AAQoL) Scale Score at Week 4 | Baseline and Week 4 | The AAQoL is a validated 29-item scale consisting of 4 subscales:life productivity (11 items), psychological health (6 items), life outlook (7 items) and relationships (5 items). Participants rate each item on a 5-point Likert - like scale ranging from 1 (not at all/never) to 5 (extremely/very often). These scores are then transformed to a 0-100 point scale, higher scores indicating better quality of life. Total score=average of individual 29 item scores (range= 0-100, where higher total score indicates better quality of life). Change from baseline in total score for AAQoL is reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Global Impression-Improvement (CGI-I) Score | Week 4, 8 and 12 | The CGI-I is a 7-point scale that requires the clinician to assess how much the participant's illness has improved or worsened relative to a baseline state at the beginning of the intervention and rated as (1=very much improved; 2=much improved; 3=minimally improved; 4=no change; 5=minimally worse; 6=much worse; 7=very much worse). |
| Change From Baseline in the State-Trait Anxiety Inventory (STAI) Scale | Baseline, Week 4, 8 and 12 | The STAI scale consists of total 40 items on separate scales measuring state (20 items) and trait (20 items) anxiety. The participant reports how they feel right now at this moment for state anxiety and how they generally feel for trait anxiety. The state items are scored as: 1 (not at all), 2 (somewhat true), 3 (moderately true), 4 (very true). The trait items are scored as: 1 (almost never), 2 (sometimes), 3 (often), 4 (almost always). The total scores range from 4-80 for each scale. Higher scores indicate more impaired participants. |
| Change From Screening in the Hamilton Depression Rating (HAM-D) Scale Score at Week 4 and 12 | Screening (Week -2), 4 and 12 | It is a 21-item clinician-rated scale that evaluates depressed mood as well as the vegetative and cognitive symptoms of depression. 11 items are scored on a 3 point scale (0=none/absent to 2=most severe), 2 items are scored on a 4 point scale (0=none/absent to 3=most severe) and 8 items are scored on a 5 point scale (0=none/absent to 4=most severe). The individual items are summed to yield the HAM-D total score that ranges from 0-60, where higher scores indicate worsening. |
| Change From Screening in Clinical Global Impression-Severity of Illness (CGI-S) Score at Weeks 4, 8 and 12 | Screening (Week -2), 4, 8 and 12 | The CGI-S rating scale is a 7 point global assessment that measures the clinician's impression of the severity of illness exhibited by a participant. A rating of 1 = Normal, not at all ill and a rating of 7 = Among the most extremely ill participants. Higher scores indicate worsening. |
Countries
Brazil
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Methylphenidate Oral long acting methylphenidate tablets were administered daily at a starting dose of 18 milligram (mg) and slowly increased to 36 mg on Day 8. Depending on response, tolerability and clinician's discretion, the dose could be increased to 54 mg on Day 28 to a maximum of 72 mg per day on Day 56, until each participant achieved optimal dose. | 60 |
| Total | 60 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 3 |
| Overall Study | Lost to Follow-up | 1 |
| Overall Study | Medical Criteria | 1 |
| Overall Study | Participant not Adherent | 3 |
| Overall Study | Withdrawal by Subject | 2 |
Baseline characteristics
| Characteristic | Methylphenidate |
|---|---|
| Age Continuous | 31.1 Years STANDARD_DEVIATION 9.6 |
| Sex: Female, Male Female | 20 Participants |
| Sex: Female, Male Male | 40 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 48 / 60 |
| serious Total, serious adverse events | 0 / 60 |
Outcome results
Primary
Change From Baseline in Adult ADHD Quality of Life (AAQoL) Scale Score at Week 12
The AAQoL is a validated 29-item scale consisting of 4 subscales:life productivity (11 items), psychological health (6 items), life outlook (7 items) and relationships (5 items). Participants rate each item on a 5-point Likert - like scale ranging from 1 (not at all/never) to 5 (extremely/very often). These scores are then transformed to a 0-100 point scale, higher scores indicating better quality of life. Total score=average of individual 29 item scores (range= 0-100, where higher total score indicates better quality of life). Change from baseline in total score for AAQoL is reported.
Time frame: Baseline and Week 12
Population: ITTe included all participants who received at least 1 dose of study medication and provided at least 1 post-baseline measure of effectiveness.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Methylphenidate | Change From Baseline in Adult ADHD Quality of Life (AAQoL) Scale Score at Week 12 | 21.9 Unit on a scale | Standard Error 2.3 |
Primary
Change From Baseline in Adult ADHD Quality of Life (AAQoL) Scale Score at Week 4
The AAQoL is a validated 29-item scale consisting of 4 subscales:life productivity (11 items), psychological health (6 items), life outlook (7 items) and relationships (5 items). Participants rate each item on a 5-point Likert - like scale ranging from 1 (not at all/never) to 5 (extremely/very often). These scores are then transformed to a 0-100 point scale, higher scores indicating better quality of life. Total score=average of individual 29 item scores (range= 0-100, where higher total score indicates better quality of life). Change from baseline in total score for AAQoL is reported.
Time frame: Baseline and Week 4
Population: ITTe included all participants who received at least 1 dose of study medication and provided at least 1 post-baseline measure of effectiveness.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Methylphenidate | Change From Baseline in Adult ADHD Quality of Life (AAQoL) Scale Score at Week 4 | Baseline | 39.6 Unit on a scale | Standard Error 2.1 |
| Methylphenidate | Change From Baseline in Adult ADHD Quality of Life (AAQoL) Scale Score at Week 4 | Change at Week 4 | 19.4 Unit on a scale | Standard Error 2.3 |
Primary
Change From Baseline in Adult Attention Deficit Hyperactivity Disorder (ADHD) Self-Report Scale (ASRS) Total Score at Week 12
Adult ASRS assesses 18 core ADHD symptoms corresponding to DSM-IV diagnostic symptoms for adult participant based on the participant's own rating for each of the symptoms using a 4 point scale (0=none, 1=mild, 2=moderate, 3=severe). If a single item is missing the score is imputed and if more than one item is missing, the total score is treated as missing. The ASRS total score is derived by summing the score assigned to each of the 18 symptoms (low=0, high=54, a higher score signifies a greater severity of symptoms).
Time frame: Baseline and Week 12
Population: ITTe included all participants who received at least 1 dose of study medication and provided at least 1 post-baseline measure of effectiveness.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Methylphenidate | Change From Baseline in Adult Attention Deficit Hyperactivity Disorder (ADHD) Self-Report Scale (ASRS) Total Score at Week 12 | -20.6 Unit on a scale | Standard Error 1.7 |
Primary
Change From Baseline in Adult Attention Deficit Hyperactivity Disorder (ADHD) Self-Report Scale (ASRS) Total Score at Week 4
Adult ASRS assesses 18 core ADHD symptoms corresponding to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) diagnostic symptoms for adult participant based on the participant's own rating for each of the symptoms using a 4 point scale (0=none, 1=mild, 2=moderate, 3=severe). If a single item is missing the score is imputed and if more than one item is missing, the total score is treated as missing. The ASRS total score is derived by summing the score assigned to each of the 18 symptoms (low=0, high=54, a higher score signifies a greater severity of symptoms).
Time frame: Baseline and Week 4
Population: Intent to treat efficacy evaluation (ITTe) included all participants who received at least 1 dose of study medication and provided at least 1 post-baseline measure of effectiveness.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Methylphenidate | Change From Baseline in Adult Attention Deficit Hyperactivity Disorder (ADHD) Self-Report Scale (ASRS) Total Score at Week 4 | Change at Week 4 | -10.9 Unit on a scale | Standard Error 1.6 |
| Methylphenidate | Change From Baseline in Adult Attention Deficit Hyperactivity Disorder (ADHD) Self-Report Scale (ASRS) Total Score at Week 4 | Baseline | 52.6 Unit on a scale | Standard Error 1.6 |
Primary
Change From Baseline in Adult Attention Deficit Hyperactivity Disorder (ADHD) Self-Report Scale (ASRS) Total Score at Week 8
Adult ASRS assesses 18 core ADHD symptoms corresponding to DSM-IV diagnostic symptoms for adult participant based on the participant's own rating for each of the symptoms using a 4 point scale (0=none, 1=mild, 2=moderate, 3=severe). If a single item is missing the score is imputed and if more than one item is missing, the total score is treated as missing. The ASRS total score is derived by summing the score assigned to each of the 18 symptoms (low=0, high=54, a higher score signifies a greater severity of symptoms).
Time frame: Baseline and Week 8
Population: ITTe included all participants who received at least 1 dose of study medication and provided at least 1 post-baseline measure of effectiveness.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Methylphenidate | Change From Baseline in Adult Attention Deficit Hyperactivity Disorder (ADHD) Self-Report Scale (ASRS) Total Score at Week 8 | -16.2 Unit on a scale | Standard Error 1.6 |
Secondary
Change From Baseline in the State-Trait Anxiety Inventory (STAI) Scale
The STAI scale consists of total 40 items on separate scales measuring state (20 items) and trait (20 items) anxiety. The participant reports how they feel right now at this moment for state anxiety and how they generally feel for trait anxiety. The state items are scored as: 1 (not at all), 2 (somewhat true), 3 (moderately true), 4 (very true). The trait items are scored as: 1 (almost never), 2 (sometimes), 3 (often), 4 (almost always). The total scores range from 4-80 for each scale. Higher scores indicate more impaired participants.
Time frame: Baseline, Week 4, 8 and 12
Population: ITTe included all participants who received at least 1 dose of study medication and provided at least 1 post-baseline measure of effectiveness.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Methylphenidate | Change From Baseline in the State-Trait Anxiety Inventory (STAI) Scale | State Anxiety Score: Change at Week 4 | -6.1 Unit on a scale | Standard Error 1.2 |
| Methylphenidate | Change From Baseline in the State-Trait Anxiety Inventory (STAI) Scale | State Anxiety Score: Change at Week 12 | -9.4 Unit on a scale | Standard Error 1.3 |
| Methylphenidate | Change From Baseline in the State-Trait Anxiety Inventory (STAI) Scale | Trait Anxiety Score: Change at Week 4 | -8.4 Unit on a scale | Standard Error 1.3 |
| Methylphenidate | Change From Baseline in the State-Trait Anxiety Inventory (STAI) Scale | State Anxiety Score: Baseline | 50.4 Unit on a scale | Standard Error 1.4 |
| Methylphenidate | Change From Baseline in the State-Trait Anxiety Inventory (STAI) Scale | Trait Anxiety Score: Baseline | 52.7 Unit on a scale | Standard Error 1.5 |
| Methylphenidate | Change From Baseline in the State-Trait Anxiety Inventory (STAI) Scale | State Anxiety Score: Change at Week 8 | -7.8 Unit on a scale | Standard Error 1.3 |
| Methylphenidate | Change From Baseline in the State-Trait Anxiety Inventory (STAI) Scale | Trait Anxiety Score: Change at Week 8 | -8.4 Unit on a scale | Standard Error 1.3 |
| Methylphenidate | Change From Baseline in the State-Trait Anxiety Inventory (STAI) Scale | Trait Anxiety Score: Change at Week 12 | -10.7 Unit on a scale | Standard Error 1.3 |
Secondary
Change From Screening in Clinical Global Impression-Severity of Illness (CGI-S) Score at Weeks 4, 8 and 12
The CGI-S rating scale is a 7 point global assessment that measures the clinician's impression of the severity of illness exhibited by a participant. A rating of 1 = Normal, not at all ill and a rating of 7 = Among the most extremely ill participants. Higher scores indicate worsening.
Time frame: Screening (Week -2), 4, 8 and 12
Population: ITTe included all participants who received at least 1 dose of study medication and provided at least 1 post-baseline measure of effectiveness.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Methylphenidate | Change From Screening in Clinical Global Impression-Severity of Illness (CGI-S) Score at Weeks 4, 8 and 12 | Screening (Week -2) | 4.6 Unit on a scale | Standard Error 0.1 |
| Methylphenidate | Change From Screening in Clinical Global Impression-Severity of Illness (CGI-S) Score at Weeks 4, 8 and 12 | Change at Week 4 | -1.0 Unit on a scale | Standard Error 0.1 |
| Methylphenidate | Change From Screening in Clinical Global Impression-Severity of Illness (CGI-S) Score at Weeks 4, 8 and 12 | Change at Week 8 | -1.3 Unit on a scale | Standard Error 0.1 |
| Methylphenidate | Change From Screening in Clinical Global Impression-Severity of Illness (CGI-S) Score at Weeks 4, 8 and 12 | Change at Week 12 | -1.7 Unit on a scale | Standard Error 0.1 |
Secondary
Change From Screening in the Hamilton Depression Rating (HAM-D) Scale Score at Week 4 and 12
It is a 21-item clinician-rated scale that evaluates depressed mood as well as the vegetative and cognitive symptoms of depression. 11 items are scored on a 3 point scale (0=none/absent to 2=most severe), 2 items are scored on a 4 point scale (0=none/absent to 3=most severe) and 8 items are scored on a 5 point scale (0=none/absent to 4=most severe). The individual items are summed to yield the HAM-D total score that ranges from 0-60, where higher scores indicate worsening.
Time frame: Screening (Week -2), 4 and 12
Population: ITTe included all participants who received at least 1 dose of study medication and provided at least 1 post-baseline measure of effectiveness.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Methylphenidate | Change From Screening in the Hamilton Depression Rating (HAM-D) Scale Score at Week 4 and 12 | Screening (Week -2) | 5.9 Unit on a scale | Standard Error 0.6 |
| Methylphenidate | Change From Screening in the Hamilton Depression Rating (HAM-D) Scale Score at Week 4 and 12 | Change at Week 4 | -2.8 Unit on a scale | Standard Error 0.6 |
| Methylphenidate | Change From Screening in the Hamilton Depression Rating (HAM-D) Scale Score at Week 4 and 12 | Change at Week12 | -3.3 Unit on a scale | Standard Error 0.6 |
Secondary
Clinical Global Impression-Improvement (CGI-I) Score
The CGI-I is a 7-point scale that requires the clinician to assess how much the participant's illness has improved or worsened relative to a baseline state at the beginning of the intervention and rated as (1=very much improved; 2=much improved; 3=minimally improved; 4=no change; 5=minimally worse; 6=much worse; 7=very much worse).
Time frame: Week 4, 8 and 12
Population: ITTe included all participants who received at least 1 dose of study medication and provided at least 1 post-baseline measure of effectiveness.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Methylphenidate | Clinical Global Impression-Improvement (CGI-I) Score | Week 4 | 2.7 Unit on a scale | Standard Error 0.1 |
| Methylphenidate | Clinical Global Impression-Improvement (CGI-I) Score | Week 8 | 2.4 Unit on a scale | Standard Error 0.1 |
| Methylphenidate | Clinical Global Impression-Improvement (CGI-I) Score | Week 12 | 2.2 Unit on a scale | Standard Error 0.1 |