Comparative Study of PK and BE of VM-1500FDC (Fixed-dose Combination) and Elpida® With Truvada® сo-administrated 1 Daily Fasting in Healthy Subjects

Study Overview
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Brief Summary
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Open-label, randomized, parallel-group, comparative study of pharmacokinetics and bioequivalence of VM-1500FDC (elsulfavirine/emtricitabine/tenofovir fixed-dose combination) and Elpida® with Truvada® (emtricitabine/tenofovir) co-administered by healthy male subjects. The study will also assess safety profile of study drugs.

Detailed Description
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The study assesses PK and bioequivalence of the developed new drug VM-1500FDC - a fixed combination of three active substances: elsulfavirine (NNRTI), emtricitabine (NRTI) and tenofovir (NRTI) to Elpida® and Truvada® co-administered. The combination is intended for once daily administration (1 tablet) for the treatment of HIV-1 infection in adult patients. Thus, the purpose of this combination is to simplify the dosage regimen and improve patient compliance

Official Title
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Open-Label, Randomized, Parallel-group, Comparative Study of Pharmacokinetics and Bioequivalence of VM-1500FDC (Viriom Ltd, Russia) and Elpida® (Viriom Ltd, Russia) and Truvada® (Gilead Sciences Ireland UC, UK) When сo-administrated Once Daily Fasting in Healthy Subjects

Conditions
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HIV-1-infection

Intervention / Treatment
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* Drug: VM-1500FDC
* Drug: Elpida®
* Drug: Truvada®


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Non-smoking male subjects between the ages of 20 and 40 years (inclusive); Verified diagnosis of healthy according to standard clinical, laboratory and instrumental examination methods; Body weight from 60 to 95 kg and Body Mass Index from 19.0 to 27.0 kg/m; A negative result in tests for alcohol and drugs; The subject's consent to use adequate contraception methods during the study and 3 month after end of study: condom with spermicide (foam, gel, cream, suppositories); Signed the Participant Explanation Sheet and the Informed Consent Form. Exclusion Criteria: 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 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 less than 90 mm Mercury or above 130 mm Mercury, diastolic pressure less than 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, liver 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 (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; Burdened allergic medical history (including drug intolerance and food allergy); Lactase deficiency, lactose intolerance, glucose-galactose malabsorption; Hypersensitivity to tenofovir, elsulfavirine or emtricitabine, as well as any other component of the 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 30 days prior to screening (including follow-up visits); Acute infectious diseases less than 4 weeks prior to screening; Incapable of reading or writing; no desire to understand and adhere to the study protocol procedures; non-compliance with the drugs intake regimen or execution of procedures, which as the Investigator may think 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 take part in the study.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: VM-1500FDC<br>VM-1500FDC (tenofovir 300 mg/elsulfavirine 20 mg/emtricitabine 200 mg), once daily fasting | Drug: VM-1500FDC<br>* A fixed-dose combination of three active substances: tenofovir 300 mg + elsulfavirine 20 mg + emtricitabine 200 mg, film-coated tablets<br>* Other names: VM1500FDC;|
| Active Comparator: Elpida® & Truvada®<br>Elpida®, 20 mg + Truvada® (tenofovir 300 mg / emtricitabine 200 mg), once daily fasting | Drug: Elpida®<br>* Elpida®, capsules, elsulfavirine 20 mg<br>* Other names: Elsulfavirine;Drug: Truvada®<br>* Truvada® (tenofovir 300 mg / emtricitabine 200 mg), film-coated tablets<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma concentration of VM1500A |  | 29 days | 
| Plasma concentration of elsulfavirine |  | 29 days | 
| Plasma concentration of emtricitabine |  | 29 days | 
| Plasma concentration of tenofovir |  | 29 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency and severity of AEs and SAEs | Frequency and severity of AE, recorded after administration of the drug according to subjective complaints, changes in vital signs, ECG, laboratory results and physical examination compared to the baseline | 29 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV -1, elsulfavirine fixed-dose combination