A Study to Evaluate the Efficacy, Safety and Tolerability of Oral AK0901 in Children With ADHD

The study consists of an approximately 28-day screening period, a 28-day double-blind treatment period, and a follow-up period for 5±2 days.

During the screening period, all subjects must sign an informed consent form and complete all assessment items at the screening visit prior to the screening. Study drug is started within 28 days of signing the informed consent form.

During the double-blind treatment period, all eligible subjects are randomized 1:1 to receive AK0901 or placebo once daily for 4 weeks. During the first week, all subjects are given a starting dose of 39.2 mg/7.8 mg AK0901 or matching placebo; from the second week, the dose drug can be increased or decreased, or maintained at the original dose level at weekly follow-up depending on tolerability and optimal individual dose response at the investigator's discretion.

After the last dose in the double-blind treatment period, subjects will enter a 5 ± 2 day follow-up period for safety assessments. The primary analysis will be performed after all subjects have completed the study.

Inclusion criteria

• At the time of signing informed consent form, subjects must be between 6 and 12 years of age (inclusive) and of any gender.
• Subjects meet the diagnostic criteria for ADHD (attention deficit or hyperactivityj/impulsivity or combined attention deficit and hyperactivity/impulsivity manifestations) in the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) as medically evaluated and confirmed by the Chinese version of Kiddie-schedule for affective disorders and schizophrenia-present and lifetime version DSM-5 (K-SADS-PL-C DSM-5).
• An ADHD-RS-5 total score of at least 28. For subjects requiring washout of ADHD medications, this criterion refers to a score following washout.
• A score of at least 3 (mildly ill) on the Clinical Global Impressions - Severity (CGI-S) scale as assessed by clinician. For subjects requiring washout of ADHD medications, this criterion refers to a score following washout.
• Weight exceeds the median weight for the appropriate age and sex minus two times the standard deviation (2SD) .
• Able to sign the ICF, including compliance with the requirements and limitations specified in the ICF and this protocol.
• Understand the importance of adhering to study medication requirements and completing all assessments on time throughout the study, and agree to strictly follow the requirements as specified in the protocol, including restrictions on concomitant medications during the study.
• The subject's parent/legal guardian must ensure that the subject: has washed out ongoing stimulants for ADHD and herbal/Chinese patent medicines for the treatment of ADHD 5 days prior to the first dose and is abstained from these medications until the end of the study or early termination of the study; and must wash out ongoing non-stimulants for ADHD 14 days prior to the first dose and is abstained from these medications until the end of the study or early termination of the study.

Exclusion criteria

Medical disorders

• Pre-existing or current clinically significant disease or any condition that, in the opinion of the investigator, would jeopardize the safety of the subject or the validity of study results, or would result in the subject's inability to complete study in accordance with the protocol.
• Presence of evidence of central nervous system (CNS) diseases (e.g., tumor, inflammation, epilepsy, vascular disease), or neuromuscular disorder that may have occurred in childhood (e.g., Duchenne muscular dystrophy, myasthenia gravis), or history of persistent neurological symptoms that can be attributed to severe head injury, or other serious nervous system disorders. Simple febrile seizure is allowed. Patients with electroencephalogram suggesting epileptiform discharge or seizure susceptibility will be excluded.
• History of mental illness including, but not limited to, a diagnosis of bipolar disorder, major depressive disorder, conduct disorder, obsessive-compulsive disorder, childhood schizophrenia, autism spectrum disorder, disruptive mood dysregulation disorder (DMDD), intellectual developmental disorder, tic disorders, generalized anxiety disorder or panic disorder, severe sleep disorder, and genetic disorders associated with cognitive and/or behavioral disorder. Oppositional defiant disorder (ODD) is permitted if the condition is mild-moderate, not a current treatment priority, and the investigator assesses that the subject is appropriate and cooperative.
• Subject has any history of attempted suicide or clinically significant suicidal ideation based on the Columbia-Suicide Severity Rating Scale (C-SSRS) assessment, in the opinion of the investigator, at screening or Day 1.
• Cardiovascular system , digestive system , endocrine system, ophthalmology , respiratory system, and hepatic or renal system, or any other clinically significant concomitant diseases that could jeopardize the safety of the subject or affect the results of the study.
• Active malignancy and/or history of malignancy.
• History of allergy or suspected allergy to methylphenidate, serdexmethylphenidate, or AK0901 excipients.
• History of serious allergy to any drug, or known history of allergy to more than one drug.

Previous therapies/concomitant treatment

• Have received or are receiving systematic cognitive behavioral therapy (CBT), behavioral therapy, or other non-drug therapies for ADHD within 1 month prior to screening.
• Subject has taken ADHD medications from more than one class within 30 days prior to screening. Subjects on a stable dose of one ADHD medication with occasional use of ADHD medications from another class are exceptional at the discretion of the investigator.
• Subjects with lack of response or intolerability to previous adequate dose and duration of treatment with methylphenidate products in the opinion of the investigator.
• Use of monoamine oxidase inhibitors within 14 days prior to the first dose; use of the following medications within 21 days prior to the first dose: antidepressants, mood stabilizers, antipsychotics, coumarin anticoagulants, anticonvulsants, halogenated anesthetics, phenylbutazone, and sedative hypnotics.
• Planned use of prohibited drugs or non-drug therapies as specified in the protocol during the study.

Clinical study experience of prior/concomitant medications

• Subject has participated in clinical study of any other investigational product within 90 days or 5 half-lives, whichever is longer, prior to screening, or is currently participating in another drug clinical trial.

Diagnostic assessments

• At the discretion of the investigator, has a clinically significant abnormal finding in the physical examination, neurological examination, vital signs, ECG, or clinical laboratory tests at screening.
• Mean systolic or diastolic blood pressure measurements ≥ 95th percentile for corresponding age, gender, and height at screening or Day 1.
• Electrocardiogram shows QTcF interval ≥ 450 ms at screening [QTcF = QT/(RR^0.33)].
• Glutamic-pyruvate transaminase (SGPT) or glutamic-oxaloacetic transferase (SGOT) ≥ 1.5 × the upper limit of normal (ULN) or blood creatinine > ULN at screening.
• Thyroid stimulating hormone (TSH), free thyroxine (FT4), or free tri-iodothyronine (FT3) abnormality at screening.

Other exclusion criteria

• Subjects with a history of drug or alcohol abuse within 1 year prior to screening; positive alcohol or drug screen at screening or Day 1 ;
• Positive screening for methylphenidate at screening or Day 1.
• Use of tobacco or other nicotine-containing products at screening.
• Family history (parents and siblings) of sudden cardiac death, severe ventricular arrhythmia, or QT prolongation.
• The subject's parent/legal guardian is an investigator of this study, employee of the study site with direct involvement in this study or any other studies under the direction of the investigator, sponsor's employee, or any family members of the investigator of this study, employee of study site or sponsor's employee.
• Subject and parent/legal guardian are unable to communicate well with the investigator.
• Any other reason that, in the opinion of the investigator, would make subject's participation inappropriate.