Attention-Deficit Hyperactivity Disorder
Conditions
Keywords
Concerta, Adults, Attention-Deficit/Hyperactivity Disorder, ADHD, Methylphenidate hydrochloride
Brief summary
The main purpose of this study is to evaluate the efficacy of JNS001 titrated to daily doses of 18 to 72 mg in adults with attention-deficit hyperactivity disorder (ADHD) relative to placebo.
Detailed description
This is a randomized (the study drug is assigned by chance), double-blind (DB, neither physician nor patient knows the name of the assigned drug), multicenter, placebo-controlled, parallel group (each group of patients will be treated at the same time), dose-titration study. This study consists of a screening period, a DB phase (titration period and efficacy assessment period), and post-study phase. The study includes a 1 to 2-week screening period for wash-out of prohibited drugs, and screening for eligibility. Eligible patients will be randomly assigned to receive JNS001 or placebo in a ratio of 1:1. The study also includes a 4-week titration period. Patients will be titrated from a starting dose of 18 mg/day or matching placebo for 7 days (+/- 2 days), and continue with a weekly (+/- 2 days) increment of 18 mg until an individualized dose is achieved. Once an individualized dose is achieved, patients will remain on that dose for the rest of the titration period as far as tolerable. Doses can be tapered down only once during the titration period in the study, and their dose cannot be up-titrated again for the rest of the period. The 4-week titration period will be followed by the 4-week efficacy assessment period. The post-study phase for collection of additional safety data will be scheduled for 1 week after a patient's final study treatment. The study drug will be administered with water once daily in the morning at doses of 18 mg, 36 mg, 54 mg, 72 mg per day or the matching placebo. The study treatment period is 8 weeks (titration period of 4 weeks and efficacy assessment period of 4 weeks).
Interventions
DRUGJNS001
Participants will receive JNS001 (18 mg, 36 mg, 54 mg or 72 mg per day) orally once daily for 8 weeks.
DRUGPlacebo
Participants will receive matching placebo orally once daily for 8 weeks.
Sponsors
Janssen Pharmaceutical K.K.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 64 Years
Healthy volunteers
No
Inclusion criteria
* Patients who meet the criteria of ADHD (predominantly inattentive type \[314.00\], predominantly hyperactive-impulsive type \[314.01\], and combined type \[314.01\]) of DSM-IV-TR both at present and in childhood, based on Conners' Adult ADHD Diagnostic Interview for DSM-IV (CAADID) at screening * DSM-IV Total ADHD Symptoms scores (18 items) of CAARS-O: SV score of = 24 as determined by investigator or co-investigator at baseline * Healthy on the basis of physical examination, medical history, vital signs, 12-lead ECG and clinical laboratory tests performed at screening * Women of childbearing potential must have a negative urine pregnancy test at screening * Patients (and their legally-acceptable representative if patients are 18 or 19 years of age) must have signed an informed consent form (ICF), indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study.
Exclusion criteria
* Presence or history of co-morbid psychiatric diagnosis per DSM-IV-TR criteria of bipolar I disorder, schizophrenia, schizoaffective disorder, or severe obsessive compulsive disorders * Presence of co-morbid psychiatric diagnosis per DSM-IV-TR criteria of pervasive developmental disorder (including autistic disorder or Asperger's disorder), suicidality, or any other diagnosis that in the judgment the investigator or co-investigator would exclude the patient from the study * Presence of motor tics, history of Tourette's disorder, or family history of Tourette's disorder * Known or suspected mental retardation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Endpoint in the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) Total Attention Deficit-Hyperactivity Disorder (ADHD) Symptoms Scores of Conners' Adult ADHD Rating Scale - Observer Screening Version (CAARS-O: SV) | Baseline (Day 0) to Endpoint (Week 8) | CAARS-O: SV evaluates DSM-IV-oriented inattention, impulsivity and hyperactivity as well as measures of self-concept. The CAARS-O:SV comprises 30 items to measure symptoms for ADHD in adults. Each item is scored from 0 (not at all, never) to 3 (very much, very frequently) with higher scores corresponding to worse symptoms. The total score can range from 0 (best) to 90 (worst). Lower score indicates improvement in ADHD symptoms. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline to Endpoint in the Conners' Adult ADHD Rating Scale - Observer Screening Version (CAARS-O: SV) Total Score Other Than Total Attention Deficit-Hyperactivity Disorder (ADHD) Symptoms Score | Baseline (Day 0) to Endpoint (Week 8) | CAARS-O: SV evaluates DSM-IV-oriented inattention, impulsivity and hyperactivity as well as measures of self-concept. The CAARS-O: SV comprises 30 items to measure symptoms for ADHD in adults. Each item is scored from 0 (not at all, never) to 3 (very much, very frequently) with higher scores corresponding to worse symptoms. The total score can range from 0 (best) to 90 (worst). Lower score indicates improvement in ADHD symptoms. |
| Change From Baseline to Endpoint in Clinical Global Impression - Severity (CGI-S) Scores | Baseline (Day 0) to Endpoint (Week 8) | The CGI-S rating scale is used to rate the severity of a patient's psychotic condition on a 7-point scale. It is rated as follows: 1=Normal, not at all ill, 2=Borderline mentally ill, 3=Mildly ill, 4=Moderately ill, 5=Markedly ill, 6=Severely ill, and 7=Among the most extremely ill. Higher scores indicate worsening. |
| Clinical Global Impression of Change (CGI-C) Scores | Endpoint (Week 8) | The CGI-C is a assessment of change in global clinical status, defined as a sense of well-being and ability to function in daily activities. CGI-C scores range from 1 (very much improved) through to 7 (very much worse). Higher scores indicate worsening. |
| Mean Change From Baseline to Endpoint in the Conners' Adult Attention Deficit-Hyperactivity Disorder (ADHD) Rating Scales-Self Report: Screening Version (CAARS-S:SV) Score | Baseline (Day 0) to Endpoint (Week 8) | CAARS-S:SV evaluates DSM-IV-oriented inattention, impulsivity and hyperactivity as well as measures of self-concept. The CAARS-S:SV comprises 30 items to measure symptoms for ADHD in adults. Each item is scored from 0 (not at all, never) to 3 (very much, very frequently) with higher scores corresponding to worse symptoms. The total score can range from 0 (best) to 90 (worst). Lower score indicates improvement in ADHD symptoms. |
| Mean Change From Baseline to Endpoint in Quality of Life Enjoyment and Satisfaction Questionnaire - Short Form (Q-LES-Q-SF) Total Scores | Baseline (Day 0) to Endpoint (Week 8) | Q-LES-Q-SF is a 16-item questionnaire in which each question is rated on a 5-point scale with scores ranging from 1 = very poor to 5 = very good. The total raw score is calculated by summing up the scores for the 16 items. The raw total score is transformed into a percentage maximum possible score using the following formula:(raw total score -minimum score) / (maximum possible raw score -minimum score). The minimum raw score on the Q-LES-Q-SF is 16 (worst), and the maximum score is 80 (best). A higher score indicates a better quality of life. |
Countries
Japan
Participant flow
Recruitment details
The study was conducted at 39 study sites in Japan.
Pre-assignment details
284 participants were randomly assigned and treated with JNS001 or placebo in this study. One participant in the placebo group was excluded from the full analysis set because no post-dose efficacy data was available.
Participants by arm
| Arm | Count |
|---|---|
| JNS001 Participants received JNS001 (18 mg, 36 mg, 54 mg or 72 mg per day) orally once daily for 8 weeks. | 143 |
| Placebo Participants received matching placebo orally once daily for 8 weeks. | 141 |
| Total | 284 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 6 | 1 |
| Overall Study | Noncompliance with study medication | 0 | 3 |
| Overall Study | Nonmedical reasons | 0 | 1 |
| Overall Study | Withdrawal by Subject | 3 | 1 |
Baseline characteristics
| Characteristic | JNS001 | Placebo | Total |
|---|---|---|---|
| Age, Customized 18-24 years of age | 24 Participants | 19 Participants | 43 Participants |
| Age, Customized 25-35 years of age | 60 Participants | 65 Participants | 125 Participants |
| Age, Customized 36-49 years of age | 55 Participants | 51 Participants | 106 Participants |
| Age, Customized 50-64 years of age | 4 Participants | 6 Participants | 10 Participants |
| Race/Ethnicity, Customized Asian | 143 Participants | 139 Participants | 282 Participants |
| Race/Ethnicity, Customized Other | 0 Participants | 2 Participants | 2 Participants |
| Sex: Female, Male Female | 72 Participants | 73 Participants | 145 Participants |
| Sex: Female, Male Male | 71 Participants | 68 Participants | 139 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 117 / 143 | 76 / 141 |
| serious Total, serious adverse events | 2 / 143 | 0 / 141 |
Outcome results
Primary
Change From Baseline to Endpoint in the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) Total Attention Deficit-Hyperactivity Disorder (ADHD) Symptoms Scores of Conners' Adult ADHD Rating Scale - Observer Screening Version (CAARS-O: SV)
CAARS-O: SV evaluates DSM-IV-oriented inattention, impulsivity and hyperactivity as well as measures of self-concept. The CAARS-O:SV comprises 30 items to measure symptoms for ADHD in adults. Each item is scored from 0 (not at all, never) to 3 (very much, very frequently) with higher scores corresponding to worse symptoms. The total score can range from 0 (best) to 90 (worst). Lower score indicates improvement in ADHD symptoms.
Time frame: Baseline (Day 0) to Endpoint (Week 8)
Population: Full analysis set: All participants who received at least 1 dose of study medication; and had baseline and at least 1 post-dose efficacy assessment. One participant in the placebo group was excluded from the full analysis set because no post-dose efficacy data was available.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| JNS001 | Change From Baseline to Endpoint in the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) Total Attention Deficit-Hyperactivity Disorder (ADHD) Symptoms Scores of Conners' Adult ADHD Rating Scale - Observer Screening Version (CAARS-O: SV) | -12.5 Scores on a scale | Standard Deviation 9.27 |
| Placebo | Change From Baseline to Endpoint in the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) Total Attention Deficit-Hyperactivity Disorder (ADHD) Symptoms Scores of Conners' Adult ADHD Rating Scale - Observer Screening Version (CAARS-O: SV) | -7.9 Scores on a scale | Standard Deviation 9.61 |
p-value: <0.000195% CI: [-6.7, -2.4]ANCOVA
Secondary
Change From Baseline to Endpoint in Clinical Global Impression - Severity (CGI-S) Scores
The CGI-S rating scale is used to rate the severity of a patient's psychotic condition on a 7-point scale. It is rated as follows: 1=Normal, not at all ill, 2=Borderline mentally ill, 3=Mildly ill, 4=Moderately ill, 5=Markedly ill, 6=Severely ill, and 7=Among the most extremely ill. Higher scores indicate worsening.
Time frame: Baseline (Day 0) to Endpoint (Week 8)
Population: Full analysis set: All participants who received at least 1 dose of study medication; and had baseline and at least 1 post-dose efficacy assessment. One participant in the placebo group was excluded from the full analysis set because no post-dose efficacy data was available.
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| JNS001 | Change From Baseline to Endpoint in Clinical Global Impression - Severity (CGI-S) Scores | -1.0 Scores on a scale | Full Range 16.45 |
| Placebo | Change From Baseline to Endpoint in Clinical Global Impression - Severity (CGI-S) Scores | -1.0 Scores on a scale | Full Range 16.55 |
p-value: <0.0001ANCOVA
Secondary
Clinical Global Impression of Change (CGI-C) Scores
The CGI-C is a assessment of change in global clinical status, defined as a sense of well-being and ability to function in daily activities. CGI-C scores range from 1 (very much improved) through to 7 (very much worse). Higher scores indicate worsening.
Time frame: Endpoint (Week 8)
Population: Full analysis set: All participants who received at least 1 dose of study medication; and had baseline and at least 1 post-dose efficacy assessment. One participant in the placebo group was excluded from the full analysis set because no post-dose efficacy data was available.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| JNS001 | Clinical Global Impression of Change (CGI-C) Scores | 3 Scores on a scale |
| Placebo | Clinical Global Impression of Change (CGI-C) Scores | 3 Scores on a scale |
p-value: <0.0001ANOVA
Secondary
Mean Change From Baseline to Endpoint in Quality of Life Enjoyment and Satisfaction Questionnaire - Short Form (Q-LES-Q-SF) Total Scores
Q-LES-Q-SF is a 16-item questionnaire in which each question is rated on a 5-point scale with scores ranging from 1 = very poor to 5 = very good. The total raw score is calculated by summing up the scores for the 16 items. The raw total score is transformed into a percentage maximum possible score using the following formula:(raw total score -minimum score) / (maximum possible raw score -minimum score). The minimum raw score on the Q-LES-Q-SF is 16 (worst), and the maximum score is 80 (best). A higher score indicates a better quality of life.
Time frame: Baseline (Day 0) to Endpoint (Week 8)
Population: Full analysis set: All participants who received at least 1 dose of study medication; and had baseline and at least 1 post-dose efficacy assessment. One participant in the placebo group was excluded from the full analysis set because no post-dose efficacy data was available.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| JNS001 | Mean Change From Baseline to Endpoint in Quality of Life Enjoyment and Satisfaction Questionnaire - Short Form (Q-LES-Q-SF) Total Scores | 2.4 Scores on a scale | Standard Deviation 14 |
| Placebo | Mean Change From Baseline to Endpoint in Quality of Life Enjoyment and Satisfaction Questionnaire - Short Form (Q-LES-Q-SF) Total Scores | 0.8 Scores on a scale | Standard Deviation 12.69 |
p-value: 0.4041ANCOVA
Secondary
Mean Change From Baseline to Endpoint in the Conners' Adult ADHD Rating Scale - Observer Screening Version (CAARS-O: SV) Total Score Other Than Total Attention Deficit-Hyperactivity Disorder (ADHD) Symptoms Score
CAARS-O: SV evaluates DSM-IV-oriented inattention, impulsivity and hyperactivity as well as measures of self-concept. The CAARS-O: SV comprises 30 items to measure symptoms for ADHD in adults. Each item is scored from 0 (not at all, never) to 3 (very much, very frequently) with higher scores corresponding to worse symptoms. The total score can range from 0 (best) to 90 (worst). Lower score indicates improvement in ADHD symptoms.
Time frame: Baseline (Day 0) to Endpoint (Week 8)
Population: Full analysis set: All participants who received at least 1 dose of study medication; and had baseline and at least 1 post-dose efficacy assessment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| JNS001 | Mean Change From Baseline to Endpoint in the Conners' Adult ADHD Rating Scale - Observer Screening Version (CAARS-O: SV) Total Score Other Than Total Attention Deficit-Hyperactivity Disorder (ADHD) Symptoms Score | -19.5 Scores on a scale | Standard Deviation 15.42 |
| Placebo | Mean Change From Baseline to Endpoint in the Conners' Adult ADHD Rating Scale - Observer Screening Version (CAARS-O: SV) Total Score Other Than Total Attention Deficit-Hyperactivity Disorder (ADHD) Symptoms Score | -12.5 Scores on a scale | Standard Deviation 15.87 |
p-value: 0.0002ANCOVA
Secondary
Mean Change From Baseline to Endpoint in the Conners' Adult Attention Deficit-Hyperactivity Disorder (ADHD) Rating Scales-Self Report: Screening Version (CAARS-S:SV) Score
CAARS-S:SV evaluates DSM-IV-oriented inattention, impulsivity and hyperactivity as well as measures of self-concept. The CAARS-S:SV comprises 30 items to measure symptoms for ADHD in adults. Each item is scored from 0 (not at all, never) to 3 (very much, very frequently) with higher scores corresponding to worse symptoms. The total score can range from 0 (best) to 90 (worst). Lower score indicates improvement in ADHD symptoms.
Time frame: Baseline (Day 0) to Endpoint (Week 8)
Population: Full analysis set: All participants who received at least 1 dose of study medication; and had baseline and at least 1 post-dose efficacy assessment. One participant in the placebo group was excluded from the full analysis set because no post-dose efficacy data was available.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| JNS001 | Mean Change From Baseline to Endpoint in the Conners' Adult Attention Deficit-Hyperactivity Disorder (ADHD) Rating Scales-Self Report: Screening Version (CAARS-S:SV) Score | -18.0 Scores on a scale | Standard Deviation 16.45 |
| Placebo | Mean Change From Baseline to Endpoint in the Conners' Adult Attention Deficit-Hyperactivity Disorder (ADHD) Rating Scales-Self Report: Screening Version (CAARS-S:SV) Score | -10.9 Scores on a scale | Standard Deviation 16.55 |
p-value: 0.0003ANCOVA