Clinical Trials

MainTitle

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

This study is currently recruiting participants. (see Contacts and Locations)

Verified October 2018 by Viriom

Sponsor
Viriom


Information provided by (Responsible Party)
Viriom
ClinicalTrials.gov Identifier
NCT03706898

First received: October 11, 2018
Last updated: October 15, 2018
Last Verified: October 2018
History of Changes
Purpose

Purpose

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.

Condition Intervention Phase
HIV-1-infection
Hepatic Impairment

Drug : Elpida®
Drug : Dolutegravir
Drug : Sofosbuvir
Drug : Daclatasvir
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Open Label Study to Evaluate the Safety and Pharmacokinetics of Elpida® in Healthy Subjects and Patients With Hepatic Impairment, 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

Further study details as provided by Viriom:

Primary Outcome Measures

  • Plasma concentration of elsulfavirine [ Time Frame: 42 days ]
  • Plasma concentration of VM-1500A [ Time Frame: 42 days ]
  • Plasma concentration of daclatasvir [ Time Frame: 42 days ]
  • Plasma concentration of sofosbuvir [ Time Frame: 42 days ]
  • Plasma concentration of dolutegravir [ Time Frame: 42 days ]
Secondary Outcome Measures:
  • AEs and SAEs frequency [ Time Frame: 42 days ]
    Adverse events (AE) and serious adverse events (SAE) frequency of varying severity according to subjective complaints, physical examination, instrumental and laboratory studies

Estimated Enrollment: 36
Study Start Date: October 1, 2018
Estimated Study Completion Date: December 10, 2018
Estimated Primary Completion Date: December 10, 2018 (Final data collection date for primary outcome measure)

Arms Assigned Interventions
Experimental: Elpida® fasting
Elpida® 20 mg single dose fasting
Drug: Elpida®

Elpida® capsules, 20mg

Other Name:
  • Elsulfavirine
  • VM1500
  • VM-1500

Experimental: Elpida® after meal
Elpida® 20 mg single dose after meals
Drug: Elpida®

Elpida® capsules, 20mg

Other Name:
  • Elsulfavirine
  • VM1500
  • VM-1500

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

Elpida® capsules, 20mg

Other Name:
  • Elsulfavirine
  • VM1500
  • VM-1500

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

Elpida® capsules, 20mg

Other Name:
  • Elsulfavirine
  • VM1500
  • VM-1500

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

Elpida® capsules, 20mg

Other Name:
  • Elsulfavirine
  • VM1500
  • VM-1500

Drug: Sofosbuvir

Sofosbuvir, film-coated tablets, 400mg

Other Name: Sovaldi
Drug: Daclatasvir

Daclatasvir, film-coated tablets, 60mg

Other Name: Daklinza®
Experimental: Elpida® & dolutegravir
Drug-drug interactions of dolutegravir 50 mg and Elpida® 20 mg, single dose fasting
Drug: Elpida®

Elpida® capsules, 20mg

Other Name:
  • Elsulfavirine
  • VM1500
  • VM-1500

Drug: Dolutegravir

Dolutegravir, film-coated tablets, 50mg

Other Name: TIVICAY®

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.

Eligibility

Eligibility

Ages Eligible for Study: 18 Years to 45 Years  
Sexes Eligible for Study: All  
Accepts Healthy Volunteers: Yes  

Criteria

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 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.

contacts and locations

Contacts and Locations

Choosing to participate in a study is an important personal decision.Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT03706898

Contacts

Contact:   Elena Yakubova, PhD +7 (495) 995 49 44 eyakubova@viriom.com
Contact:   Natalia Vostokova, PhD +7 (495) 276 11 43 nv@ipharma.ru

Locations

Russian Federation
Regional State Budgetary Healthcare Institution "Smolensk Regional Clinical Hospital" Recruiting
Smolensk, Russian Federation, 214018
Contact: Alla Andreeva, PhD    +7 4812 611 301 ext 114    alla@antibiotic.ru

Sponsors and Collaborators

Viriom

Investigators

Principal Investigator: Alla Andreeva, PhD Regional State Budgetary Healthcare Institution "Smolensk Regional Clinical Hospital"
More Information

More Information


Responsible Party: Viriom  
ClinicalTrials.gov Identifier: NCT03706898   History of Changes  
Other Study ID Numbers: HIV-VM1500-07  
Study First Received: October 11, 2018  
Last Updated: October 15, 2018  
Individual Participant Data    
Plan to Share IPD: No  

Studies a U.S. FDA-regulated Drug Product: No  
Studies a U.S. FDA-regulated Device Product: No  

Additional relevant MeSH terms:
Liver Diseases
Antiviral Agents
Sofosbuvir
Dolutegravir

ClinicalTrials.gov processed this data on October 15, 2019
This information is provided by ClinicalTrials.gov.