Pharmacokinetics Study to Evaluate Drug-Drug Interactions and Safety of Elpida® in Co-Administration With Other Drugs

Open-Label Pharmacokinetics Study to Evaluate Drug-Drug Interactions and Safety of ELPIDA® in Co-Administration With Other Drugs in Healthy Volunteers

The study assesses PK and safety of other drugs, such as some antibiotics, proton pump inhibitors, statins, and combined oral contraceptives when co-administered with Elpida®

Study Overview

• Status: Completed
• Conditions: HIV-1-infection
• Intervention / Treatment: Drug: Elpida®; Drug: Rifampin; Drug: Rifabutin; Drug: Clarithromycin; Drug: Omeprazole; Drug: Atorvastatin; Drug: Levonorgestrel+Ethinylestradiol

Detailed Description

This study evaluates the drug-drug interaction of Elpida® and other drugs (Rifampin, Rifabutin, Clarithromycin, Omeprazole, Atorvastatin and combinations of Levonorgestrel and Ethinylestradiol) according to changes in the PK parameters of the study substances in their single co-administration in healthy subjects

• Study Type: Interventional
• Enrollment (Actual): 56
• Phase: Phase 1

Contacts and Locations

Study Locations

• Russian Federation
  • Moscow Region
    • Reutov, Moscow Region, Russian Federation, 143964
      • Central Clinical City Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 43 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Healthy subjects must meet the following criteria to be enrolled in the study:

1. Non-smoking men and women between the ages of 18 and 45 years (inclusive) (only women in Group 7);
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 NLT 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.

Exclusion Criteria:

A subject will be considered not eligible to participate in the study if one or more of the following criteria is met:

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 mm Mercury or above 130 mm Mercury, diastolic pressure below 60 mm Mercury or above 85 mm Mercury, 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 any components of study drugs) as well as food allergy;
10. Lactase deficiency, lactose intolerance, glucose-galactose malabsorption;
11. Individual intolerance to any components of study drugs;
12. Blood/plasma donation (450 ml of blood or plasma and more) less than 2 months prior to screening;
13. Treatment with a study drug in framework of other clinical trials within 1 month prior to screening (including follow-up visits);
14. Acute infectious diseases less than 4 weeks prior to screening;
15. Inhibitors or inducers of CYP3A4/5, drugs that cause QT prolongation within 30 days prior to StD administration;
16. For women - positive result of pregnancy test or breastfeeding; 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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: None (Open Label)

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Elpida® single dose; Single dose of Elpida® (capsule 20 mg)	Drug: Elpida®; Elpida® capsules, 20mg; Other Names: elsulfavirine; VM1500; VM-1500
Experimental: Rifampin & Elpida®; Single dose of Rifampin (capsule 150 mg), Rifampin + Elpida® 20mg single dose	Drug: Elpida®; Elpida® capsules, 20mg; Other Names: elsulfavirine; VM1500; VM-1500; Drug: Rifampin; Rifampin capsules, 150mg
Experimental: Rifabutin & Elpida®; Single dose of Rifabutin capsule 150 mg, Rifabutin + Elpida® 20mg single dose	Drug: Elpida®; Elpida® capsules, 20mg; Other Names: elsulfavirine; VM1500; VM-1500; Drug: Rifabutin; Rifabutin capsules, 150mg
Experimental: Clarithromycin & Elpida®; Single dose of Clarithromycin capsule 250 mg, Clarithromycin + Elpida® 20mg single dose	Drug: Elpida®; Elpida® capsules, 20mg; Other Names: elsulfavirine; VM1500; VM-1500; Drug: Clarithromycin; Clarithromycin Film-coated tablets, 250mg
Experimental: Omeprazole & Elpida®; Single dose of Omeprazole capsule 20 mg, Omeprazole + Elpida® 20mg single dose	Drug: Elpida®; Elpida® capsules, 20mg; Other Names: elsulfavirine; VM1500; VM-1500; Drug: Omeprazole; Omeprazole Film-coated tablets 20mg
Experimental: Atorvastatin & Elpida®; Single dose of Atorvastatin tablet 80 mg, Atorvastatin + Elpida® 20mg single dose	Drug: Elpida®; Elpida® capsules, 20mg; Other Names: elsulfavirine; VM1500; VM-1500; Drug: Atorvastatin; Atorvastatin Film-coated tablets, 80mg
Experimental: Levonorgestrel+Ethinylestradiol & Elpida®; Single dose of Levonorgestrel 150 µg + Ethinylestradiol 150 µg tablet, Levonorgestrel + Ethinylestradiol + Elpida® 20mg single dose	Drug: Elpida®; Elpida® capsules, 20mg; Other Names: elsulfavirine; VM1500; VM-1500; Drug: Levonorgestrel+Ethinylestradiol; Levonorgestrel 150 μg + Ethinylestradiol 30 μg, Film-coated tablets
Active Comparator: Elpida® multiple dose; Elpida® QD dosing for 14 days	Drug: Elpida®; Elpida® capsules, 20mg; Other Names: elsulfavirine; VM1500; VM-1500

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Plasma concentration of elsulfavirine	42 days
Plasma concentration of VM1500A	42 days
Plasma concentration of rifampicin	42 days
Plasma concentration of rifabutin	49 days
Plasma concentration of clarithromycin	42 days
Plasma concentration of atorvastatin	42 days
Plasma concentration of levonorgestrel	42 days
Plasma concentration of ethinylestradiol	42 days

Secondary Outcome Measures

Outcome Measure	Time Frame
The incidence of AEs and SAEs	49 days

Collaborators and Investigators

• Sponsor: Viriom
• Investigators: Principal Investigator: Elena Smolyarchuk, PhD, I.M. Sechenov First Medical State University; Principal Investigator: Alla Andreeva, PhD, Smolensk Region Clinical Hospital

Study record dates

Study Major Dates

• Study Start (Actual): November 14, 2018
• Primary Completion (Actual): September 6, 2019
• Study Completion (Actual): September 6, 2019

Study Registration Dates

• First Submitted: October 11, 2018
• First Submitted That Met QC Criteria: October 15, 2018
• First Posted (Actual): October 17, 2018

Study Record Updates

• Last Update Posted (Actual): January 26, 2022
• Last Update Submitted That Met QC Criteria: January 10, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Keywords: HIV-1
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Antimetabolites; Gastrointestinal Agents; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Estrogens; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Anti-Bacterial Agents; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Leprostatic Agents; Protein Synthesis Inhibitors; Cytochrome P-450 Enzyme Inducers; Contraceptive Agents, Hormonal; Contraceptive Agents; Reproductive Control Agents; Contraceptives, Oral, Combined; Contraceptives, Oral; Contraceptive Agents, Female; Anti-Ulcer Agents; Proton Pump Inhibitors; Cytochrome P-450 CYP3A Inducers; Contraceptives, Oral, Synthetic; Antitubercular Agents; Contraceptives, Oral, Hormonal; Antibiotics, Antitubercular; Cytochrome P-450 CYP2B6 Inducers; Cytochrome P-450 CYP2C8 Inducers; Cytochrome P-450 CYP2C19 Inducers; Cytochrome P-450 CYP2C9 Inducers; Atorvastatin; Levonorgestrel; Ethinyl Estradiol; Rifampin; Rifabutin; Clarithromycin; Omeprazole; Ethinyl estradiol, levonorgestrel drug combination; Elsulfavirine
• Other Study ID Numbers: HIV-VM1500-08

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No