Clinical Trial of Efficacy and Safety of Prospekta in the Treatment of Attention Deficit/Hyperactivity Disorder in Children

Design: a multicenter double-blind placebo-controlled parallel-group randomized clinical trial.

The study will enroll children of either age from 7 to 12 years old with diagnosis of attention deficit/hyperactivity disorder (ADHD) verified by Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, American Psychiatric Association" [DSM-V]).

After signing patient information sheet and informed consent form by the subject's parent/adoptive parent collection of complaints, medical examination of the children, filling Attention Deficit Hyperactivity Disorder-Rating Scale-V [ADHD-RS-V]) scale by the parent/adoptive parent will be performed, concomitant therapy will be recorded and laboratory tests will be carried out.

The study will enroll children with total score ADHD-RS-V ≥ 22. If the inclusion criteria were met and there were no exclusion criteria (Day 1), the patient will be randomized to one of the two groups: group 1 will receive Prospekta at 1 tablet twice daily; group 2 will receive Placebo using the study drug dosing regimen.

Treatment period will be 8 weeks, the key examination stages (collection of complaints, recording objective examination findings, repeated filling ADHD-RS-V by parent/adoptive parent) will be made at Visit 1 (Day 1), further in 4 weeks (visit 2) and in 8 weeks (visit 3). Each visit to the research center will be made by the subject accompanied by his/her parent/adoptive parent. Two weeks later (visit 1.1, week 2±3 days) after randomization and initiation of the study therapy and between visits 2 and 3 (visits 2.2, week 6±3 days) the investigator will examine the patient's clinical status (during phone calls). Based on complaints, monitoring of the prescribed therapy therapeutic safety will be assessed. At visit 2 (week 4±3 days) and visit 3 (week 8±3 days) the investigator will collect complaints, record objective examination findings, monitor repeated ADHD-RS-V filling by parent/adoptive parent, the prescribed and concomitant therapy, evaluate therapeutic safety and compliance. In addition at Visit 3 the investigator will complete the Clinical Global Impression Efficacy Index [CGI-EI] scale and collect samples for laboratory testing. The study treatments will be completed.

The total length of the observation period is 8 weeks. During the study the treatment for underlying conditions will be allowed with the exception of the drugs indicated in the section "Prohibited concomitant therapy".

Inclusion criteria

• Male and female children aged 7-12 years old inclusive.
• Children with verified diagnosis of ADHD.
• Presence of all ADHD criteria according to DSM-V (see appendix 1):

A. persistent pattern of inattention and/or hyperactivity-impulsivity that interferes with functioning or development, as characterized by (1) and/or (2):

• Attention deficit: Six (or more) of the following symptoms have persisted for at least 6 months to a degree that is inconsistent with developmental level and that negatively impacts directly on social and academic/occupational activities:

• Often fails to give close attention to details or makes careless mistakes in schoolwork, at work, or during other activities (e.g., overlooks or misses details, work is inaccurate).
• Often has difficulty sustaining attention in tasks or play activities (e.g., has difficulty remaining focused during lectures, conversations, or lengthy reading).
• Often does not seem to listen when spoken to directly (e.g., mind seems elsewhere, even in the absence of any obvious distraction).
• Often does not follow through on instructions and fails to finish schoolwork, chores, or duties in the workplace (e.g., starts tasks but quickly loses focus and is easily sidetracked).
• Often has difficulty organizing tasks and activities (e.g., difficulty managing sequential tasks; difficulty keeping materials and belongings in order; messy, disorganized work; has poor time management; fails to meet deadlines).
• Often avoids, dislikes, or is reluctant to engage in tasks that require sustained mental effort (e.g., schoolwork or homework).
• Often loses things necessary for tasks or activities (e.g., school materials, pencils, books, tools, wallets, keys, eyeglasses).
• Is often easily distracted by extraneous stimuli.
• Is often forgetful in daily activities (e.g., doing chores, running errands).
• Hyperactivity/impulsivity: Six (or more) of the following symptoms have persisted for at least 6 months to a degree that is inconsistent with developmental level and that negatively impacts directly on social and academic/occupational activities. Note. The symptoms are not solely a manifestation of oppositional behavior, defiance, hostility, or failure to understand tasks or instructions.

• Often fidgets with or taps hands or feet or squirms in seat.
• Often leaves seat in situations when remaining seated is expected (e.g., leaves his or her place in the classroom, in the office or other workplace, or in other situations that require remaining in place).
• Often runs about or climbs in situations where it is inappropriate.
• Often unable to play or take part in leisure activities quietly.
• Is often "on the go" acting as if "driven by a motor" (e.g., is unable to be or uncomfortable being still for extended time).
• Often talks excessively.
• Often blurts out an answer before a question has been completed (e.g., completes people's sentences; cannot wait for turn in conversation).
• Often has trouble waiting his/her turn (e.g., while waiting in line).
• Often interrupts or intrudes on others (e.g., butts into conversations, games, or activities; may start using other people's things without asking or receiving permission).

B. Several inattentive or hyperactive-impulsive symptoms were present before age 12 years.

C. Several inattentive or hyperactive-impulsive symptoms are present in two or more settings, (e.g., at home, school or work; with friends or relatives).

D. There is clear evidence that the symptoms interfere with, or reduce the quality of, social, school, or work functioning.

E. The symptoms do not occur exclusively during the course of schizophrenia or another psychotic disorder and are not better explained by another mental disorder (e.g., mood disorder, anxiety disorder, dissociative disorder, personality disorder, substance intoxication or withdrawal).

• ADHD-RS-V ≥ 22. 5. Availability of signed information sheet and informed consent form for the parents/adoptive parents for the subject's participation in the clinical trial.

Exclusion criteria

• History of central nervous system (CNS) diseases including:

• Inflammatory diseases of the central nervous system (G00-G09).
• Systemic atrophies primarily affecting the CNS (G10-G13).
• Extrapyramidal and movement disorders (G20-G26).
• Other degenerative diseases of the nervous system (G30-G32).
• Demyelinating diseases of the CNS (G35-G37).
• Epilepsy (G40-41).
• Hydrocephalus (G91).
• Childhood autism (F84.0), atypical autism • (F84.1).
• Mental retardation (F70-79).
• Disorders of psychological development (F80-F89).
• History of hyperthyroidism (thyrotoxicosis).
• History/suspicion of oncology of any location (except for benign neoplasms).
• Any other comorbidity which, in the opinion of the investigator, may affect patient participation in the clinical trial.
• Patients allergic to/intolerant of any constituent of the medications used in the treatment.
• Hereditary lactose intolerance, malabsorption due to lactose intolerance including congenital or acquired lactase (or other disaccharide) deficiency, galactosemia.
• Patients whose parents/adoptive parents will not fulfill the requirements during the study or follow the order of administration of the study drug (SD) products, from the Investigator's point of view.
• History of treatment noncompliance, mental diseases, alcoholism or drug abuse in parents/adoptive parents which, according to the investigator, will prevent from following the study procedures.
• Administration of the products outlined in section "Prohibited concomitant therapy" within 1 month prior to enrollment.
• Patients who have participated in other clinical trials in the past 3 months.
• The patient's parent/adoptive parent is a study specialist of the center and is directly involved in the study, or is an immediate family member of the Investigator. Spouses, parents, children, or siblings, regardless of whether they are siblings or adopted are considered immediate family members.
• The patient's parent/adoptive parent works at Materia Medica Holding, i.e. they are employees of the Company, temporary employees on a contract basis or appointed officials responsible for conduction of the study or their immediate family members.