Study of the Safety, Tolerability, Pharmacokinetics of NIOCH-14 in Volunteers Aged 18-50 Years

The Aim:

To study safety, tolerability and pharmacokinetics of NIOCH-14 when administered orally using a set of clinical and laboratory-instrumental methods.

The research tasks are to:

* to assess the safety and tolerability of different single doses of the drug;
* to assess the safety and tolerability of different repeated doses of the drug;
* to study pharmacokinetics of single and repeated administration of the drug;
* to assess the data on safety and tolerability to select the optimal drug dosing schedule to resolve the issue of conducting phase II clinical trial in an expanded cohort of volunteers.

An open, simple, randomized study of the safety, tolerability, and pharmacokinetics of NIOCH-14 in volunteers aged 18-50 years in parallel groups will be conducted.

The study included 90 healthy volunteers of both sexes aged 18-50 years who met the inclusion criteria, had no exclusion criteria and underwent all screening procedures.

Grouping of the volunteers:

1) For a single dose of the drug, three groups will be formed: group 1 - 15 volunteers, single 200-mg oral dose; group 2 - 15 volunteers, single 600-mg oral dose; group 3 - 15 volunteers, single 1200-mg oral dose. Before drug administration, volunteers should be hospitalized for a day in the hospital of Federal State Budgetary Healthcare Institution "Medical and Sanitary Unit No. 163 of the Federal Medical and Biological Agency" (FGBUZ MSCH-163, FMBA Russia).

The drug will be first given to 5 healthy volunteers in Group 1. The volunteers will be followed up daily by a clinical investigator for 7 days. In the absence of changes in clinical analyzes and adverse events and the approval of the findings by the IDMC, the remaining subjects in Group 1 will begin to receive the drug.

After 7 days of the follow-up, the first 5 volunteers in Group 2 (600 mg) will start receiving the drug. After 7 days, the remaining 10 volunteers in Group 2 will receive the drug.

The first 5 volunteers in Group 3 will start receiving the drug after obtaining the results for the volunteers in Group 2.

If the volunteers feel satisfactory, they will be discharged on the 2nd day, and then will have to visit the clinical site for examination and identification of adverse events daily for 7 days, after which all volunteers will be given self- monitoring diaries for self-completion to record all adverse events. The volunteers have to present for examination and clinical testing on the 10th, 20th, 30th and 90th day after receiving the drug.

Eligibility Criteria:
Inclusion Criteria:

1. Signed and dated informed consent of a volunteer to participate in the clinical study, obtained prior to any of the study procedures.
2. A verified diagnosis "healthy" based on findings of standard clinical, laboratory and instrumental methods of examination.
3. Age from 18 to 50 years inclusive.
4. Body mass index from 18.5 to 30 kg/m3.
5. Ability to attend all scheduled visits and all scheduled procedures and examinations.
6. Consent of volunteers to use effective methods of contraception throughout the study.

Exclusion Criteria:

1. Known hypersensitivity to any component of the studied drug.
2. Aggravated history of allergies.
3. Drug intolerance.
4. Pregnancy and the period of breastfeeding.
5. Military personnel.
6. Persons in custody in pre-trial detention centers and serving sentences in penitentiaries.
7. Children's age under 18.
8. Acute infectious diseases less than 4 weeks before the start of the study.
9. Acute or chronic diseases of the cardiovascular, bronchopulmonary, neuroendocrine system, as well as diseases of the gastrointestinal tract, liver, blood, kidneys, surgical interventions to the gastrointestinal tract (with the exception of appendectomy).
10. Immunosuppressive conditions: congenital or acquired immunodeficiency syndrome (including HIV infection), leukemia, malignant tumors, organ transplantation, cellular and humoral immunodeficiencies.
11. Immunosuppressive therapy: treatment with antimetabolites, high doses of corticosteroids for 14 days or more, radio and x-ray therapy, etc.
12. Regular medication intake less than 2 weeks prior to the start of the study.
13. Taking medications that have a pronounced effect on hemodynamics, liver function, etc. (barbiturates, omeprazole, cimetidine, etc.) less than 30 days before the start of the study.
14. Donation (450 ml of blood or plasma or more) less than 2 months before the start of the study.
15. Participation in other clinical trials less than 3 months prior to study enrollment.
16. Drinking more than 10 units of alcohol per week (1 unit of alcohol is equivalent to ½ liter of beer, 200 ml of wine or 50 ml of alcohol) or a history of alcoholism, drug addiction, drug abuse.
17. Smoking of more than 10 cigarettes a day.
18. Failure to meet inclusion criteria.
19. Premenopausal women (last menstrual period ≤ 1 year prior to signing of informed consent) who are not surgically sterile.
20. Women with a childbearing potential not using or planning to use acceptable means of contraception during the study and give no consent to urine pregnancy testing during the study. Acceptable means of contraception include ectopic devices, oral, implanted, or injectable contraceptives.
21. Nervous and mental diseases: central nervous system (CNS) traumas with residual effects, encephalitis and encephalomyelitis (including post-vaccination), meningitis, polyradiculoneuritis (including a history of polyradiculoneuritis), epilepsy, hydrocephalus in the stage of decompensation or subcompensation, demyelinating and degenerative nervous system damage (muscle degeneration, etc.), stroke; compensated hydrocephalus, Down's disease, Little's disease, CNS damage without residual effects, history of febrile convulsions, mental illnesses.

Early (premature) exclusion of subjects from the study (reasons for discontinuation of the studied drug administration):

After randomization and the start of the clinical phase, a clinical investigator may exclude a subject early from the study if:

* The decision of the clinical investigator to exclude a volunteer is in the best interests of the volunteer.
* Erroneous inclusion (inclusion and non-inclusion criteria were not allowed for) or the appearance of non-inclusion criteria during the study.
* Investigator's or Client's decision to exclude a volunteer from the study due to a clinically significant protocol deviation/violation of the protocol.
* Any adverse event requiring the prescription of drugs that are not permitted by the protocol of the study (exacerbation of chronic diseases of the liver, kidneys, pancreas, heart; occurrence of infectious (influenza and other acute respiratory viral infections, tonsillitis, hepatitis, etc.) or oncological diseases during the study.
* Volunteer's refusal to continue participation in the study or his indiscipline.
* Volunteer's desire to terminate the study early for any reason.
* Failure of a volunteer to attend a scheduled visit without notifying the clinical investigator, and loss of communication with a volunteer.
* Positive urine drug test and/or alcohol breath test at visits.
* Pregnancy. Identification of reasons for premature termination of the study in enrolled subjects leads to their exclusion from the study at the stage when these reasons were identified. In each case of premature termination of the study by a volunteer/exclusion of a volunteer from the study, the clinical investigator must make an appropriate entry in the Individual Registration Card (IRC) with the obligatory indication of the reason for the premature termination or exclusion of a volunteer from the study, and inform the authorized representative of the Customer.