Pharmacokinetics, Safety and Efficacy Study of GP30341 (GEROPHARM, Russia)

Multicenter open two-stage study of pharmacokinetics, safety and efficacy of GP30341, 200 mg capsules (GEROPHARM LLC, Russia) involving healthy volunteers and patients with novel coronavirus infection 2019 (COVID-19) with a high risk of adverse outcome.

I stage: An open non-comparative study of pharmacokinetics and safety of GP30341 studied at different dosing regimens with an escalation of the daily dose in healthy volunteers.

II stage: Open randomized study efficacy and safety of GP30341, 200 mg capsules with active control - comparison with standard therapy - in patients with COVID-19 infection with a high risk of adverse outcome.

Stage 1

Inclusion criteria

• Signed informed consent to participate in the study.
• Males with a verified diagnosis "healthy" according to the data of standard clinical, laboratory and instrumental examination methods.
• Age 18-45 years old inclusive.
• Body mass index 18.5 - 30 kg/m2.
• Agree to use an adequate method of contraception (double barrier method) during the entire period of participation in the study and for 3 weeks after its completion.
• Consent to all restrictions imposed during the study.
• Citizenship of the Russian Federation.

Exclusion criteria

• Burdened allergic history, drug intolerance.
• Hypersensitivity to heparin, molnupiravir and any of the excipients of the study drug.
• Any acute and chronic diseases, incl. but not limited to:

• diseases of the cardiovascular, bronchopulmonary, neuroendocrine systems, as well as diseases of the gastrointestinal tract (including diseases of the colon), liver, kidneys, blood;
• positive test results for hepatitis C (antibodies) or hepatitis B (surface antigen), HIV (antibodies to HIV-1/2), syphilis (antibodies to Treponema pallidum).
• Deviations from normal values of heart rate (60-89), SBP (90-130 mm Hg), DBP (60-89 mm Hg), NPV (12-20), body temperature (35.7 - 37.0 °C).
• ECG Deviations, according to a specialist, during screening.
• laboratory tests results deviations from the normal values.
• Hard-to-reach veins of the upper extremities, vein thrombosis, thrombophlebitis in a family history of close relatives, "compromised" veins due to frequent previous venipunctures.
• Surgical interventions on the gastrointestinal tract (with the exception of appendectomy) in history.
• Acute infectious diseases less than 4 weeks prior to screening.
• Presence of at least one of the epidemic signs:

• return from overseas travel 14 days prior to screening and no test results for SARS-CoV-2 RNA or SARS-CoV-2 antigen;
• close contact in the last 14 days prior to screening with a person under observation for COVID-19 who subsequently fell ill;
• close contact in the past 14 days prior to screening with individuals who have laboratory-confirmed case of COVID-19;
• Occupational contacts in the past 14 days prior to screening with individuals who have a suspected or confirmed case of COVID-I9.
• Regular intake of any medications, including vitamins, herbal preparations, and dietary supplements, less than 2 weeks before screening.
• Significant blood loss (more than 450 ml of blood or plasma) within 3 months prior to screening, due to, including, but not limited to, blood donation, blood loss during advanced surgery or trauma.
• Drinking alcohol in quantities exceeding 10 units per week (on average) (1 unit of alcohol is equivalent to 500 ml of beer, 200 ml of dry wine or 50 ml of strong alcoholic drinks) or anamnestic information about alcoholism, drug addiction, abuse of strong drugs.
• Positive test results for alcohol, drug use and the use of strong drugs.
• Nicotine addiction (regular tobacco use, including smoking of all types of electronic cigarettes, hookahs, snuff, etc. less than 6 months prior to screening).
• Participation in a clinical trial of any drugs (including experimental drugs) or experimental medical devices for 3 months or 5 half-lives prior to Screening, whichever is longer.
• Dehydration due to diarrhea, vomiting, or other cause within the last 24 hours prior to screening.
• Any diet (eg vegetarian, fasting, etc.) or lifestyle (including night work and extreme physical activity such as heavy lifting) that may interfere with the study.
• Taking drugs that have a pronounced effect on hemodynamics, liver function, etc. (barbiturates, omeprazole, cimetidine, etc.) less than 30 days before screening.
• Mental diseases, history of epilepsy, seizures.
• Volunteers who are obviously or likely, in the opinion of the investigator, unable to understand and evaluate the information on this study as part of the informed consent process, in particular regarding expected risks and possible discomfort.

Stage2:

Inclusion criteria

• Signed informed consent to participate in the study.
• Male and female patients aged ≥18 years at the time of providing informed consent.
• Laboratory confirmation of COVID-19 infection ≤5 days prior to randomization1, defined as a positive RT-PCR test for SARS-CoV-2 RNA and/or a positive antigen test for SARS-CoV-2 in a nasal swab.
• Clinical onset of COVID-19 infection (as ≥1 symptom consistent with COVID-19) ≤5 days prior to randomization.
• Presence of ≥1 symptom consistent with COVID-19 at time of randomization3.
• Mild to moderate COVID-19 infection with ≥1 risk factor for adverse outcome.
• WHO (World Health Organization) Clinical Progression Scale score ≥3 at screening 6.
• Consent and ability to take oral medications.
• Agree to use reliable contraceptive measures throughout the study and for 3 weeks after - Negative pregnancy test in women capable of childbearing.
• Consent and ability to comply with the Protocol's procedures, prohibitions and restrictions.

Exclusion criteria

• Hypersensitivity or intolerance reactions to any of the components of the test drug or the proposed standard therapy drugs according to the anamnesis.
• Vaccination to prevent COVID-19 within 6 months prior to screening or planning vaccination during the study period.
• Vaccination with any vaccine within 4 weeks prior to screening.
• Use of drugs from the list of prohibited therapy (section 5.3.3 of the Study Protocol) in the anamnesis or their planned use during the study period.
• Past infection with COVID-19 within 6 months prior to screening.
• Current hospitalization or, in the opinion of the Investigator, expected hospitalization within 48 hours after randomization.
• Dysfunction of organs that affect the absorption and metabolism of the test drug, which include, but are not limited to the following:

• diseases of the gastrointestinal tract, which, in the opinion of the researcher, may interfere with the absorption of the contents of the capsules;
• Kidney Disease Outcomes Quality Initiative (KDOQI) stage 4 or 5 chronic kidney disease;
• Signs of significant uncontrolled comorbidity, such as disorders of the nervous, respiratory, cardiovascular, kidney, liver, endocrine, or gastrointestinal tract, that persist at the time of screening and, in the opinion of the Investigator, significantly increase the risk of adverse outcome and preclude participation patient in the study.
• Acute pancreatitis or exacerbation of chronic pancreatitis ≤3 months prior to randomization.
• Severe immunodeficiency states, which include, but are not limited to, the following:

• HIV infection, syphilis;
• chemotherapy within 5 weeks prior to screening;
• absolute number of neutrophils in blood <500/mm3;
• history of hematopoietic stem cell transplantation.
• Signs of severe or extremely severe COVID-19 infection at the time of screening and randomization.
• Heart rate less than 50 beats per minute at rest at screening.
• Platelet count <100,000/µl or platelet transfusion within 5 days prior to randomization12.
• Pregnancy or lactation in women.
• Alcoholism or alcohol consumption in excess of:

• for men: 14 units per week (on average);
• for women: 7 units per week (on average).
• Addiction and/or substance abuse.
• Participation in other clinical trials within 28 days prior to screening, or planned participation during the period of this study.