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

Study Overview
=================
Brief Summary
-----------------
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®

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

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

Conditions
-----------------
HIV-1-infection

Intervention / Treatment
-----------------
* Drug: Elpida®
* Drug: Rifampin
* Drug: Rifabutin
* Drug: Clarithromycin
* Drug: Omeprazole
* Drug: Atorvastatin
* Drug: Levonorgestrel+Ethinylestradiol


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Healthy subjects must meet the following criteria to be enrolled in the study: Non-smoking men and women between the ages of 18 and 45 years (inclusive) (only women in Group 7); 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 NLT 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. Exclusion Criteria: A subject will be considered not eligible to participate in the study if one or more of the following criteria is met: 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 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; 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 any components of study drugs) as well as food allergy; Lactase deficiency, lactose intolerance, glucose-galactose malabsorption; Individual intolerance to any components of study drugs; Blood/plasma donation (450 ml of blood or plasma and more) less than 2 months prior to screening; Treatment with a study drug in framework of other clinical trials within 1 month prior to screening (including follow-up visits); Acute infectious diseases less than 4 weeks prior to screening; Inhibitors or inducers of CYP3A4/5, drugs that cause QT prolongation within 30 days prior to StD administration; 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.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

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

What is the study measuring?
-----------------
Primary Outcome Measures

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

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
HIV-1