| Eligibility |
Inclusion Criteria for healthy volunteers:
1. Non-smoking male or female subjects between the ages of 18 and 45 years (inclusive);
2. Verified "healthy" diagnosis according to standard clinical, laboratory and
instrumental examination methods;
3. Body Mass Index ranges between 18.5 kg/m2 and 30.0 kg/m2 and a body weight not less
than 50 kg;
4. Negative alcohol and drug tests;
5. Consent to use two adequate and reliable methods of contraception throughout the study
and up to 3 months after its completion: a condom with spermicide (foam, gel, cream,
suppositories), or a diaphragm with spermicide, or a condom and diaphragm, or a condom
and an intrauterine device;
6. Signed Patient Information Sheet and form of Informed Consent to participate in the
study.
Inclusion Criteria for patients with hepatic impairment:
1. Non-smoking male or female subjects between the ages of 18 and 45 years (inclusive);
2. Mild and moderate hepatic impairment (Child - Pugh Class A or B), including viral
nature (Hepatitis C virus, etc.). At the same time, there were no changes in the
diagnosis of the patient according to Child - Pugh Class not less than 1 month prior
to screening;
3. Increase in the concentration of aspartate aminotransferase (AST )and (or) alanine
aminotransferase (ALT) in blood plasma by 1.25 times or more from the upper limit of
the norm (ULN), but not more than 5 times ULN at the time of screening;
4. Body Mass Index ranges between 18.0 kg/m2 and 36.0 kg/m2 and a body weight not less
than 50 kg, but not more than 120 kg;
5. Negative alcohol and drug tests;
6. Consent to use two adequate and reliable methods of contraception throughout the study
and up to 3 months after its completion: a condom with spermicide (foam, gel, cream,
suppositories), or a diaphragm with spermicide, or a condom and diaphragm, or a condom
and an intrauterine device;
7. Signed Patient Information Sheet and form of Informed Consent to participate in the
study.
Exclusion Criteria:
1. Chronic diseases of cardiovascular, bronchopulmonary, neuroendocrine, musculoskeletal
system, as well as diseases of the gastrointestinal tract, liver, kidneys, blood;
2. Variables of standard laboratory and instrumental parameters are beyond the normal
limits (taking into account the acceptable limits of laboratory parameters);
3. Surgical interventions on the gastrointestinal tract in medical history (except
appendectomy);
4. Systolic pressure below 90 mmHg or above 130 mmHg, diastolic pressure below 60 mmHg or
above 85 mmHg, heart rate less than 60 BPM or more than 90 BPM at screening;
5. Regular intake of drugs less than 2 weeks prior to screening (including herbal
preparations and dietary supplements); intake of drugs that have a pronounced effect
on hemodynamics, hepatic function, etc. (for example, barbiturates, omeprazole,
cimetidine, etc.) less than 30 days prior to screening;
6. Presence of antibodies to HIV and hepatitis C virus, presence of hepatitis ? surface
antigen, a positive syphilis test;
7. An unstable sleep structure (e.g., night work, sleep disorders, insomnia, recent
return from another time zone, etc.), extreme physical activity (e.g. weight lifting),
a special diet (e.g. vegetarian, vegan);
8. Signs of alcohol (intake of more than 10 units of alcohol per week ) or drug
addiction; alcohol or drugs consumption within 4 days prior to screening; cigarettes
smoking 3 months prior to screening; positive drug and/or alcohol test;
9. Drug allergies in medical history (including drug intolerance, including
hypersensitivity to active / excipient substances of study drugs - elsulfavirine,
sofosbuvir, daclatasvir, dolutegravir as well as any other substance of study drugs )
as well as food allergy;
10. Lactase deficiency, lactose intolerance, glucose-galactose malabsorption;
11. Blood/plasma donation (450 ml of blood or plasma and more) less than 2 months prior to
screening;
12. Participation in other clinical studies or taking other study drugs 1 months prior to
screening;
13. Acute infectious diseases less than 4 weeks prior to screening;
14. Inhibitors or inducers of CYP3A4/5, drugs that cause QT? prolongation () within 30
days prior to Study Drug administration;
15. For women - positive result of pregnancy test or breastfeeding;
16. Inability to read or write; unwillingness to understand and adhere to the study
protocol procedures; non-compliance with the drugs intake regimen or execution of
procedures, which as the Investigator believes may affect the study results or
subject's safety and prevent the subject from further participation in the study; any
other associated medical or serious psychological conditions making the subject not
eligible to participate in the clinical study, restricting legality of obtaining the
Informed Consent or affecting the subject's ability to participate in the study.
Exclusion criteria for patients with hepatic impairment:
1. Severe hepatic impairment (Child - Pugh Class C); other hepatic disorders or
conditions that do not allow according to the Investigator to include the patient in
the study without increased threat to his safety - including (but not limited to)
signs of severe ascites requiring regular abdominal laparocentesis, the level of total
bilirubin in blood plasma > 100 µmol/l, etc.;
2. Chronic diseases of cardiovascular, bronchopulmonary, neuroendocrine, musculoskeletal
system, as well as diseases of the gastrointestinal tract, kidneys, blood, requiring
medical treatment and preventing, according to the Investigator the subject's
participation in the study;
3. Surgical interventions on the gastrointestinal tract in medical history including
liver transplantation (except appendectomy);
4. Regular intake of drugs less than 2 weeks prior to study drug administration
(including herbal preparations and dietary supplements); intake of drugs that have a
pronounced effect on hemodynamics, hepatic function, etc. (for example, barbiturates,
omeprazole, cimetidine, etc.) less than 30 days prior to study drug administration;
5. Antibodies to HIV, a positive syphilis test;
6. An unstable sleep structure (e.g., night work, sleep disorders, insomnia, recent
return from another time zone, etc.), extreme physical activity (e.g. weight lifting),
a special diet (e.g. vegetarian, vegan);
7. Signs of alcohol (taking more than 10 units of alcohol per week) or drug addiction;
alcohol or drugs consumption within 4 days prior to screening; cigarettes smoking 3
months prior to screening; positive drug and/or alcohol test;
8. Drug allergies in medical history (including drug intolerance, including
hypersensitivity to active / excipient substances of Elpida®) as well as food allergy;
9. Lactase deficiency, lactose intolerance, glucose-galactose malabsorption;
10. Participation in other clinical studies or taking other study drugs 1 months prior to
screening;
11. Acute infectious diseases less than 4 weeks prior to screening;
12. Any prescribed pharmacotherapy aimed at restoring hepatic function, eradication of
hepatitis viruses, or otherwise focused on the compensation of hepatic impairment;
13. Administration of inhibitors or inducers of CYP3A4/5, drugs that cause QT?
prolongation within 30 days prior to StD administration; ongoing therapy with
immunosuppressive agents;
14. For women - positive result of pregnancy test or breastfeeding;
15. Inability to read or write; unwillingness to understand and adhere to the study
protocol procedures; non-compliance with the drugs intake regimen or execution of
procedures, which as the Investigator believes may affect the study results or
subject's safety and prevent the subject from further participation in the study; any
other associated medical or serious psychological conditions making the subject not
eligible to participate in the clinical study, restricting legality of obtaining the
Informed Consent or affecting the subject's ability to participate in the study.
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