A Phase 3 Study of S-877503 in Adult Patients with Attention-deficit/Hyperactivity Disorder (long term extension study)

Patients who met the following criteria were included in the study. [Continuing Patients]

Patients who have completed 12-week administration in the preceding phase 3 study of S-877503 in adult patients with ADHD (Study ID 1522A3132).

Patients who hope to continue treatment with S-877503 after the preceding study.

Patients themselves gave written consent or assent for voluntary participation in the study. In the case of patients aged under 20 years, written informed consent was obtained also from a legally acceptable representative.

[For men] Patients who have azoospermia, and if not so, patients who agreed to use an appropriate method of contraception (including a condom in combination use with spermatocidal agent) from the date of informed consent until 3 months after the last dose of investigational product.

[For women] Patients who agreed to use the following contraception measures from the day of informed consent until 3 months after the last dose of investigational product except for patients who were postmenopausal (defined as cessation of regular menstrual periods for 2 years or more and confirmed by a follicle-stimulating hormone test) or who were surgically sterile by hysterectomy and/or bilateral oophorectomy, which can be confirmed by appropriate documentation. Progestogen-only oral hormonal contraception (where inhibition of ovulation is not the primary mode of action), male or female condom with or without spermatocidal agent, cervical cap, diaphragm or sponge in combination use with spermatocidal agent.

Male or female outpatients aged 18 years or more at the time of signing the informed consent or assent form.

Patients themselves who could give written consent or assent for voluntary

Participation in the study. In the case of patients aged under 20 years, a written informed consent was obtained also from a legally acceptable representative.

At Visit pre, patients were interviewed using Japanese version of Conners' Adult ADHD Diagnostic Interview for DSM-IV™ (CAADID), and judged as having ADHD as a principal diagnosis* by the DSM-5 criteria both at present and in childhood.

In evaluation by Japanese version of ADHD-RS-IV with adult prompts at Visit 1, patients in whom subscales of inattention or hyperactivity/impulsivity subscale were scored 2 or more in 5 or more items and the total score was 24 or more.

Patients whose CGI-S was scored 4 (moderately ill) or over at Visit 1.

Patient who have both a thyroid stimulating hormone (TSH) level and a free thyroxine (free T4) level within the reference ranges. Among patients who are using a medication to treat thyroid function abnormality and having TSH and free T4 within the reference ranges, those who used the same medication without changing the dosage for at least 90 days before Visit 1 are considered eligible.

[For men] Patients who has azoospermia, and if not so, patients who agreed to use an appropriate method of contraception (including a condom in combination use with spermatocidal agent) from the date of informed consent until 3 months after the last dose of investigational product.

[For women] Patients who agreed to use the following contraception measures from the day of informed consent until 3 months after the last dose of investigational product except for patients who are postmenopausal (defined as a condition without menstruation for 2 years or more and confirmed by a follicle-stimulating hormone test) or who were surgically sterile by hysterectomy and/or bilateral oophorectomy, which can be confirmed by appropriate documentation. - Progestogen-only oral hormonal contraception (where inhibition of ovulation is not the primary mode of action), male or female condom with or without spermatocidal agent, cervical cap, diaphragm or sponge in combination use with spermatocidal agent.

Patients who met any of the following criteria were excluded from the study. [Continuing Patients]

Patients who have serious hepatic disorder, renal disorder, heart disease, lung disease, hematological disease, or metabolic disease. Second-degree atrioventricular block is included in the serious heart disease.

Patients who suggested suicide risk and met either of the followings: Have previously made a suicide attempt Have a history of or are currently demonstrating active suicidal ideation. Patients who answered “Yes” to any of questions 1 to 5 about suicidal ideation or any question about suicidal behavior in Columbia-Suicide Severity Rating Scale (C-SSRS). Among patients who answered “Yes” to the question relating to non-suicidal self-injurious behavior among questions relating to suicidal behavior, only patients who have committed a self-injurious behavior within the previous 6 months should be excluded from this study. female patient during lactation, or male patient who wishes pregnancy of his partner.

Patients who the investigator or subinvestigator judged inappropriate to participate in the study.

Female patient who is pregnant or wishes to be pregnant during the study period.

Patients who have serious hepatic disorder, renal disorder, heart disease, lung disease, hematological disease, or metabolic disease.

Patients who have psychiatric disease such as schizophrenia spectrum or bipolar disorder.

Patients who have personality disorder or mental retardation.

Patients who have a moderate or severe psychiatric disease prescribed in DSM-5 which requires medicine or therapy (excluding counseling).

Patients who have HAM-A total score greater than or equal to 17.

Patients who have HAM-D total score greater than or equal to 12.

Patients who have a history of seizures (other than infantile febrile seizures), a chronic or current tic disorder, or a current diagnosis and/or a known family history of Tourette’s Disorder.

QTc interval (Fridericia adjusted) is over 450 msec

Patients who have orthostatic hypotension.

Patients who have persistent bradycardia

Patients who are receiving any medical treatment for clinically significant ECG or laboratory abnormality in the prescribed test in this study at the time of Visit pre. Patients who have any clinically significant ECG or laboratory abnormality in the prescribed test in this study which requires additional examination or medical treatment at the time of Visit 1, with the exception of cases in which the investigator or subinvestigator judged that the abnormality is transient or associated with an allergic disease.

Patients who are using medications which affect blood pressure or cardiac rate or need to use these medicines after enrollment.

Patients who suggested a suicide risk meeting some of the following conditions: Have previously made a suicide attempt Have a history of or are currently demonstrating active suicidal ideation. Patients who answered “Yes” to any of questions 1 to 5 about suicidal ideation or any question about suicidal behavior in Columbia-Suicide Severity Rating Scale (C-SSRS). Of the questions about suicidal behavior to which the patient answered “Yes,” self-injurious behavior without suicidal ideation should have occurred within 6 months.

Patients who used any prohibited drug for 14 days until Visit 1.

Patients who deviated from the provision for restricted concomitant drugs/therapies between Visits pre and 1.

Patients who have a history of substance use disorder group d) prescribed in DSM-5.

Patients who had a positive urine drug result at the screening tests (with the exception of patient’s current ADHD therapy). ○

Female patients who are pregnant or want to be pregnant during the study period; female patients who are lactating;, or male patients who want his partner to be pregnant.

Patients who have been exposed to an investigational drug for 30 days before Visit pre.

Patients who have received S-877503 or guanfacine before.

Patients who have disability or other conditions likely to confound assessment of the safety results in this study or to increase a risk for the patient. In addition, patients who are under other conditions which make it inappropriate to evaluate the efficacy or safety at discretion of the investigator or subinvestigator or hinder the study to be completed. Other conditions are those which are likely to make it difficult to comply with the protocol.