Study to Evaluate the Safety and PK of Elpida® in Healthy Subjects and Patients With Hepatic Impairment and to Assess the Impact of Food Intake and Drug-Drug Interactions With Other Antiviral Drugs

Phase 1

Completed

• Conditions: Hepatic Impairment; HIV-1-infection
• Interventions: Drug: Elpida®; Drug: Sofosbuvir; Drug: Dolutegravir; Drug: Daclatasvir

• Registration Number: NCT03706898
• Lead Sponsor: Viriom

Brief Summary

This is open label, phase 1 clinical study to evaluate the safety, tolerability and pharmacokinetics of Elpida® in healthy subjects and patients with hepatic impairment (Child - Pugh Class А and B), as well as to assess the impact of food intake and drug-drug interactions in case of Co-administration with other antiviral drugs in healthy subjects.

Detailed Description

In medical practice HIV infection is often found associated with viral hepatitis, especially chronic hepatitis C virus (HCV). This, as well as a possible change in PK parameters in case of co-administration of Elpida® and HIV integrase inhibitors, necessitates the study of PK and safety of co-administration of Elpida® with a combination of Sofosbuvir + Daclatasvir and Dolutegravir in healthy subjects. Thus, the study to evaluates safety and pharmacokinetics of Elpida® in healthy subjects and patients with hepatic impairment, as well as assesses the impact of food intake and drug-drug interactions in case of co-administration with other antiviral drugs in healthy subjects.

Study Timeline

• Study Start: 2018-10-01
• Study First Submitted: 2018-10-11
• Study First Submitted QC: 2018-10-15
• Study First Posted: 2018-10-16
• Primary Completion: 2019-04-10
• Study Completion: 2019-04-10
• Status Verified: 2020-05
• Last Update Submitted: 2022-01-10
• Last Update Posted: 2022-01-11

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 36

Inclusion Criteria

Not provided

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 В 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 QTс 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 QTс 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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: FACTORIAL

Arm && Interventions

Group	Intervention	Description
Elpida® & dolutegravir	Elpida®	Drug-drug interactions of dolutegravir 50 mg and Elpida® 20 mg, single dose fasting
Elpida® fasting	Elpida®	Elpida® 20 mg single dose fasting
Elpida® after meal	Elpida®	Elpida® 20 mg single dose after meals
Elpida® (in subjects with mild hepatic impairment)	Elpida®	Elpida® 20 mg single dose fasting - subjects with mild hepatic impairment (Child - Pugh Class А)
Elpida® (in subjects with moderate hepatic impairment)	Elpida®	Elpida® 20 mg single dose fasting - subjects with moderate hepatic impairment (Child - Pugh Class B)
Elpida® & sofosbuvir & daclatasvir	Elpida®	Drug-drug interactions of sofosbuvir 400 mg + daclatasvir 60 mg and Elpida® 20 mg, single dose fasting
Elpida® & sofosbuvir & daclatasvir	Daclatasvir	Drug-drug interactions of sofosbuvir 400 mg + daclatasvir 60 mg and Elpida® 20 mg, single dose fasting
Elpida® & sofosbuvir & daclatasvir	Sofosbuvir	Drug-drug interactions of sofosbuvir 400 mg + daclatasvir 60 mg and Elpida® 20 mg, single dose fasting
Elpida® & dolutegravir	Dolutegravir	Drug-drug interactions of dolutegravir 50 mg and Elpida® 20 mg, single dose fasting

Primary Outcome Measures

Name	Time	Method
Plasma concentration of elsulfavirine	42 days
Plasma concentration of daclatasvir	42 days
Plasma concentration of VM-1500A	42 days
Plasma concentration of sofosbuvir	42 days
Plasma concentration of dolutegravir	42 days

Secondary Outcome Measures

Name	Time	Method
AEs and SAEs frequency	42 days	Adverse events (AE) and serious adverse events (SAE) frequency of varying severity according to subjective complaints, physical examination, instrumental and laboratory studies

Trial Locations

Locations (1)

Regional State Budgetary Healthcare Institution "Smolensk Regional Clinical Hospital"; 🇷🇺 Smolensk, Russian Federation