A Study of TD-9855 in Adults With Attention-Deficit/Hyperactivity Disorder (ADHD)

Study Overview
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Brief Summary
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The safety and efficacy of multiple dosages of TD-9855, administered once daily, will be evaluated in adult males with ADHD.

Official Title
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A Phase 2 Multicenter, Randomized, Double-Blind, Parallel, Placebo-Controlled Proof-of-Concept Study of TD-9855 in Adults With Attention-Deficit/Hyperactivity Disorder (ADHD)

Conditions
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Attention-Deficit/Hyperactivity Disorder, ADHD

Intervention / Treatment
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* Drug: TD-9855
* Drug: TD-9855
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects must meet the following ADHD diagnostic and inclusion criteria: Subjects must meet Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) criteria for current ADHD subtypes (ADHD combined type, ADHD predominately inattentive type, ADHD predominately hyperactive-impulsive type) as assessed by the clinical interview and confirmed by Adult Attention-Deficit/Hyperactivity Disorder Clinical Diagnostic Scale (ACDS V1.2). Subjects must have a total score of 24 or greater on the AISRS at both the Screening and Baseline Visits AND the Baseline Visit AISRS scores must not vary by more than 20% from Screening. Subjects are required to have CGI-S score ≥4 (moderate) at both the Screening and Baseline Visits. Subjects should have at least moderate severity for ADHD symptoms. For women of childbearing potential, documentation of a negative serum pregnancy test at Screening and a negative urine pregnancy test on Day 0. All female subjects of childbearing potential must be using a highly effective method of birth control during the study and for at least 1 month after completion of study drug dosing. A highly effective method of birth control is defined as one that results in a low failure rate (i.e., <1% per year) when used consistently and correctly, such as condom + diaphragm, condom + spermicide, diaphragm + spermicide, or intrauterine device [IUD] with documented failure rate of <1% per year, or oral/injectable/implanted hormonal contraceptives used in combination with a barrier method. Women are considered to be not of childbearing potential if they have had a total hysterectomy or bilateral tubal ligation (documentation for either must be provided before enrollment) or are at least 2 years postmenopausal. Female subjects cannot be breast-feeding. Exclusion Criteria: Any current psychiatric disorder other than ADHD as defined in DSM-IV-TR as assessed by Mini International Neuropsychiatric Interview (MINI). Subjects with dysthymia that does not require pharmacological treatment will not be excluded. MADRS total score >15. A diagnosis of ADHD NOS. Any diagnosis of lifetime bipolar disorder or psychotic disorder A current diagnosis of any severe comorbid Axis II disorder Any history of mental retardation, organic mental disorders due to general medical condition or pervasive developmental disorder as defined by DSM-IV-TR.-

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TD-9855 Dose 1<br> | Drug: TD-9855<br>* Once daily<br>|
| Experimental: Placebo<br> | Drug: Placebo<br>* Once daily<br>|
| Experimental: TD-9855 Dose 2<br> | Drug: TD-9855<br>* Once daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in AISRS Total Score at Day 42 | The AISRS is a modified version of the ADHD Rating Scale that more accurately reflects the impact and severity of ADHD among adults. It is a clinician-administered scale that measures all 18 symptoms of adult ADHD using a Likert scale from 0 (not present) to 3 (severe). The total score ranges from 0 to 54 with a negative change from baseline indicating an improvement in severity/reduction in symptoms. | Baseline and Day 42 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in BDEFS-SF: Self Report Total Score at Day 42 | The BDEFS-SF: Self-Report is an empirically based tool for evaluating dimensions of adult executive functioning in daily life. The BDEFS-SF is used to score how frequently the participants experience problems involved in time management; organization and problem solving; self restraint; self motivation; and self-regulation of emotions. The score for each item ranges from 1 (never) to 4 (very often). The total score on the BDEFS-SF ranges from 20 to 80 with a negative change from baseline indicating an improvement in functioning. | Baseline and Day 42 | 
| Change From Baseline in AISRS Inattentive Subscale at Day 42 | The AISRS is a modified version of the ADHD Rating Scale that more accurately reflects the impact and severity of ADHD among adults. The AISRS inattentive subscale that measures all 9 inattentive symptoms of adult ADHD using a Likert scale from 0 (not present) to 3 (severe). The AISRS inattentive subscale score ranges from 0 to 27 with a negative change from baseline indicating an improvement in severity/reduction in symptoms. | Baseline and Day 42 | 
| Change From Baseline in AISRS Hyperactive-impulsive Subscale at Day 42 | The AISRS is a modified version of the ADHD Rating Scale that more accurately reflects the impact and severity of ADHD among adults. The AISRS hyperactive-impulsive subscale measures all 9 hyperactive/impulsive symptoms of adult ADHD using a Likert scale from 0 (not present) to 3 (severe). The AISRS hyperactive-impulsive subscale score ranges from 0 to 27 with a negative change from baseline indicating an improvement in severity/reduction in symptoms. | Baseline and Day 42 | 
| Percentage of Participants With an AISRS Response at Day 42 | The AISRS is a modified version of the ADHD Rating Scale that more accurately reflects the impact and severity of ADHD among adults. The AISRS total scale measures all 18 symptoms of adult ADHD using a Likert scale from 0 (not present) to 3 (severe). The total score ranges from 0 to 54. A responder is defined as a participant with >=30% reduction from baseline in AISRS total score. | Day 42 | 
| Change From Baseline in Clinical Global Impression - Severity of Illness (CGI-S) Score at Day 42 | The CGI-S is a 7-point scale that requires the clinician to rate the severity of the participants' illness at the time of assessment, relative to the clinician's past experience with patients who have the same diagnosis. Considering total clinical experience, a participant is assessed on severity of mental illness at the time of rating 1=normal, not at all ill; 2, borderline mentally ill; 3, mildly ill; 4, moderately ill; 5, markedly ill; 6, severely ill; or 7,extremely ill. A negative change from baseline indicates a reduction in illness. | Baseline and Day 42 | 
| Change From Baseline in Adult ADHD Self-Report Scale (ASRS) Total Score at Day 42 | The ASRS is a checklist consisting of the 18 Diagnostic and Statistical Manual of Mental Disorders 4th edition (DSM-IV-TR) criteria in which participants rank frequency of each criterion from never (0) to very often (4). The ASRS total score ranges from 0-72 with a negative change from baseline indicating a reduction in frequency of symptoms. | Baseline and Day 42 | 
| Change From Baseline in ASRS Inattentive Subscale at Day 42 | The ASRS inattentive subscale is a checklist consisting of 9 DSM-IV-TR inattentive criteria in which participants rank frequency of each criterion from never (0) to very often (4). The ASRS inattentive subscale score ranges from 0-36 with a negative change from baseline indicating a reduction in frequency of symptoms. | Baseline and Day 42 | 
| Change From Baseline in ASRS Hyperactive-impulsive Subscale at Day 42 | The ASRS hyperactive-impulsive subscale is a checklist consisting of 9 DSM-IV-TR hyperactive/impulsive criteria in which participants rank frequency of each criterion from never (0) to very often (4). The ASRS hyperactive-impulsive subscale score ranges from 0-36 with a negative change from baseline indicating a reduction in frequency of symptoms. | Baseline and Day 42 | 
| Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score at Day 42 | MADRS is a 10-item investigator-rated scale that assesses the range of symptoms that are most frequently observed in patients with major depression. The 10 selected items are rated on a scale of 0 (no depression) to 6 (highest level of depression) with anchors at 2-point intervals. Total scores on the MADRS range from 0 to 60 with a negative change from baseline indicating an improvement in levels of depression. | Baseline and Day 42 | 
| Percentage of Participants With a Reliable Change on the BDEFS-SF at Day 42 | The BDEFS-SF is used to score how frequently the participants experience problems involved in time management; organization and problem solving; self restraint; self motivation; and self-regulation of emotions. The score for each item ranges from 1 (never) to 4 (very often). The total score on the BDEFS-SF ranges from 20 to 80. A reliable change is defined as a decrease in total BDEFS-SF score of 12 or more relative to the baseline value. | Baseline and Day 42 | 
| Percentage of Participants With a Reliable Change and Normalized Score on the BDEFS-SF at Day 42 | The BDEFS-SF is used to score how frequently the participants experience problems involved in time management; organization and problem solving; self restraint; self motivation; and self-regulation of emotions. The score for each item ranges from 1 (never) to 4 (very often). The total score on the BDEFS-SF ranges from 20 to 80. A reliable change is defined as a decrease in total BDEFS-SF score of 12 or more relative to the baseline value. Normalization is defined as a post-baseline BDEFS-SF total score <45. | Baseline and Day 42 | 
| Change From Baseline in BDEFS-SF Symptom Count at Day 42 | The BDEFS-SF is used to score how frequently the participants experience problems involved in time management; organization and problem solving; self restraint; self motivation; and self-regulation of emotions. A negative change from baseline in symptom count indicates an improvement in functioning. Only symptoms rated as occurring often or very often on the BDEFS-SF are included in the symptom count. Mean change from baseline in symptom count is reported | Baseline and Day 42 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Adult ADHD, Attention-Deficit/Hyperactivity Disorder