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

NCT03706898 | Completed Phase 1

• 1 other identifier: HIV-VM1500-07
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

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.

Conditions

HIV-1-infection; Hepatic Impairment

Outcome Measures

Primary Outcomes (5)

• Plasma concentration of elsulfavirine

  42 days

• Plasma concentration of VM-1500A

  42 days

• Plasma concentration of daclatasvir

  42 days

• Plasma concentration of sofosbuvir

  42 days

• Plasma concentration of dolutegravir

  42 days

Secondary Outcomes (1)

• AEs and SAEs frequency

  42 days

Study Arms (6)

Elpida® fasting

EXPERIMENTAL

Elpida® 20 mg single dose fasting

Drug: Elpida®

Elpida® after meal

EXPERIMENTAL

Elpida® 20 mg single dose after meals

Drug: Elpida®

Elpida® (in subjects with mild hepatic impairment)

EXPERIMENTAL

Elpida® 20 mg single dose fasting - subjects with mild hepatic impairment (Child - Pugh Class А)

Drug: Elpida®

Elpida® (in subjects with moderate hepatic impairment)

EXPERIMENTAL

Elpida® 20 mg single dose fasting - subjects with moderate hepatic impairment (Child - Pugh Class B)

Drug: Elpida®

Elpida® & sofosbuvir & daclatasvir

EXPERIMENTAL

Drug-drug interactions of sofosbuvir 400 mg + daclatasvir 60 mg and Elpida® 20 mg, single dose fasting

Drug: Elpida®; Drug: Sofosbuvir; Drug: Daclatasvir

Elpida® & dolutegravir

EXPERIMENTAL

Drug-drug interactions of dolutegravir 50 mg and Elpida® 20 mg, single dose fasting

Drug: Elpida®; Drug: Dolutegravir

Interventions

Elpida® DRUG

Elpida® capsules, 20mg

Also known as: Elsulfavirine, VM1500, VM-1500

Elpida® & dolutegravir; Elpida® & sofosbuvir & daclatasvir; Elpida® (in subjects with mild hepatic impairment); Elpida® (in subjects with moderate hepatic impairment); Elpida® after meal; Elpida® fasting

Dolutegravir DRUG

Dolutegravir, film-coated tablets, 50mg

Also known as: TIVICAY®

Elpida® & dolutegravir

Sofosbuvir DRUG

Sofosbuvir, film-coated tablets, 400mg

Also known as: Sovaldi

Elpida® & sofosbuvir & daclatasvir

Daclatasvir DRUG

Daclatasvir, film-coated tablets, 60mg

Also known as: Daklinza®

Elpida® & sofosbuvir & daclatasvir

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Non-smoking male or female subjects between the ages of 18 and 45 years (inclusive);
• Verified "healthy" diagnosis according to standard clinical, laboratory and instrumental examination methods;
• Body Mass Index ranges between 18.5 kg/m2 and 30.0 kg/m2 and a body weight not less than 50 kg;
• Negative alcohol and drug tests;
• 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;
• Signed Patient Information Sheet and form of Informed Consent to participate in the study.
• Non-smoking male or female subjects between the ages of 18 and 45 years (inclusive);
• 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;
• 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;
• 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;
• Negative alcohol and drug tests;
• 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;
• Signed Patient Information Sheet and form of Informed Consent to participate in the study.

You may not qualify if:

• Chronic diseases of cardiovascular, bronchopulmonary, neuroendocrine, musculoskeletal system, as well as diseases of the gastrointestinal tract, liver, kidneys, blood;
• Variables of standard laboratory and instrumental parameters are beyond the normal limits (taking into account the acceptable limits of laboratory parameters);
• Surgical interventions on the gastrointestinal tract in medical history (except appendectomy);
• 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;
• 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;
• Presence of antibodies to HIV and hepatitis C virus, presence of hepatitis В surface antigen, a positive syphilis test;
• 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);
• 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;
• 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;
• Lactase deficiency, lactose intolerance, glucose-galactose malabsorption;
• Blood/plasma donation (450 ml of blood or plasma and more) less than 2 months prior to screening;
• Participation in other clinical studies or taking other study drugs 1 months prior to screening;
• Acute infectious diseases less than 4 weeks prior to screening;
• Inhibitors or inducers of CYP3A4/5, drugs that cause QTс prolongation () within 30 days prior to Study Drug administration;
• For women - positive result of pregnancy test or breastfeeding;

Sponsors & Collaborators

• Viriom: lead

Study Sites (1)

Regional State Budgetary Healthcare Institution "Smolensk Regional Clinical Hospital"

Smolensk, 214018, Russia

Location

MeSH Terms

Interventions

elsulfavirine; dolutegravir; Sofosbuvir; daclatasvir

Intervention Hierarchy (Ancestors)

Uridine Monophosphate; Uracil Nucleotides; Pyrimidine Nucleotides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleotides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleotides

Study Officials

• Alla Andreeva, PhD

  Regional State Budgetary Healthcare Institution "Smolensk Regional Clinical Hospital"

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 11, 2018
• First Posted: October 16, 2018
• Study Start: October 1, 2018
• Primary Completion: April 10, 2019
• Study Completion: April 10, 2019
• Last Updated: January 11, 2022

Record last verified: 2020-05

Data Sharing

• IPD Sharing: Will not share

Locations

RU (1)