Pharmacokinetics and Bioequivalence of XC8 10 mg and 40 mg Tablets in Fasted Volunteers

Influenza Clinical Trial

Official title:

A Randomized, Open-label, Cross-over Study in Two Periods and Two Sequences to Evaluate the Comparative Pharmacokinetics and Bioavailability of XC8, 10 mg Film-coated Tablets, and XC8, 40 mg Film-coated Tablets, When Taken Once in Equal Doses (40 mg) on an Empty Stomach in Healthy Volunteers

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05558462
• Other study ID #: XC8-05-04-2022
• Status: Completed
• Phase: N/A
• Start date: August 22, 2022
• Est. completion date: December 7, 2022

Study information

• Verified date: October 2023
• Source: Valenta Pharm JSC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Comparative study of the pharmacokinetics of XC8, film-coated tablets, 10 mg and XC8, film-coated tablets, 40 mg, when administered once in equal doses (40 mg) on an empty stomach in healthy volunteers.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: December 7, 2022
• Est. primary completion date: November 11, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 45 Years

Eligibility

Inclusion Criteria:

1. Voluntary and handwritten informed consent form signed by a healthy volunteer to participate in the study prior to any of the study procedures;

2. Men and women between the ages of 18 and 45 years (inclusive) of Caucasian race;

3. Verified diagnosis "healthy" (absence of abnormalities according to clinical, laboratory, instrumental methods of examination, stipulated by the protocol);

4. Blood pressure (BP): systolic blood pressure (SBP) of 99 to 129 mmHg (inclusive), diastolic blood pressure (DBP) of 70 to 89 mmHg (inclusive);

5. Heart rate (HR) from 60 to 89 beats/min (inclusive);

6. Respiratory rate (HR) from 12 to 20 per minute (inclusive);

7. Body temperature from 36°C to 36.9°C (inclusive);

8. Body mass index (BMI) of 18.5 kg/m2 = BMI = 30 kg/m2, with a body weight of = 55 kg for men and = 45 kg for women;

9. Consent to use adequate methods of contraception throughout the study and for 30 days after completion; for women of preserved reproductive potential, a negative urine pregnancy test result.

Exclusion Criteria:

1. A history of allergy;

2. Drug intolerance to the active substance XC8 (N-[2-(1H-imidazol-4-yl)-ethyl]-6-oxo-d-lactam) and/or excipients contained in the studied drug in the anamnesis;

3. Chronic diseases of the kidneys, liver, gastrointestinal tract (GIT), cardiovascular, lymphatic, respiratory, nervous, endocrine, musculoskeletal, genitourinary and immune systems, as well as skin, blood and vision;

4. History of gastrointestinal surgery (except appendectomy at least 1 year prior to screening);

5. Diseases/conditions that, in the opinion of the investigator, may affect absorption, distribution, metabolism or excretion of the investigational drugs;

6. Acute infectious disease less than 4 weeks prior to screening;

7. Taking medications that significantly affect hemodynamics and medications that affect liver function (barbiturates, omeprazole, cimetidine, etc.) less than 2 months prior to screening;

8. Regularly taking an medicine less than 2 weeks before screening and taking a single medicine less than 7 days before screening;

9. Donating blood or plasma less than 3 months before screening;

10. Use of hormonal contraceptives (in women) less than 2 months before screening;

11. The use of depot injections of any drug less than 3 months before screening;

12. Pregnancy or lactation; positive urine pregnancy test for women of preserved reproductive potential;

13. Women of preserved reproductive potential with a history of unprotected intercourse within 30 days prior to study drug administration with an unsterilized partner;

14. Participation in another clinical trial less than 3 months prior to screening or concurrently with the present study;

15. Taking more than 10 units of alcohol (1 unit of alcohol is equivalent to 330 mL of beer, 150 mL of wine or 40 mL of spirits) in the week in the last month before inclusion in the study or anamnestic evidence of alcoholism, drug addiction, drug abuse;

16. Smoking more than 10 cigarettes per day currently, or a history of smoking the specified number of cigarettes during the 6 months prior to screening; disagreement to abstain from smoking for the duration of the hospital stay;

17. Consumption of alcohol, caffeine, and xanthine-containing products 7 days prior to the study drug admission;

18. Consumption of citrus fruits, cranberries and products containing them, preparations or products containing St. John's wort - 7 days before admission to the study drug;

19. Dehydration due to diarrhea, vomiting, or other reason within the last 24 hours prior to study drug administration.

20. Positive blood tests for antibodies to human immunodeficiency virus (HIV) 1 and 2, antibodies to Treponema pallidum antigens, hepatitis B surface antigen (HBsAg), antibodies to hepatitis C virus antigens at screening;

21. Rapid tests of biomaterial (nasopharyngeal and/or oropharyngeal swab) for Severe Acute Respiratory Syndrome Coronavirus 2 antigen (SARS-CoV-2), Coronavirus Disease 2019 (COVID-19) at screening;

22. Clinically significant abnormalities on an electrocardiogram (ECG) history and/or at screening;

23. Positive urinalysis for narcotics and powerful drugs at screening;

24. Positive breath alcohol vapor test at screening.

25. Scheduling an inpatient stay at the time of the study, for any reason other than hospitalization required by this protocol;

26. Inability or inability to meet the requirements of the protocol, perform the procedures prescribed by the protocol, follow the diet, activity regimen.

27. Belonging to a vulnerable group of volunteers: students of higher and secondary medical, pharmaceutical and dental schools, junior staff of clinics and laboratories, employees of pharmaceutical companies, servicemen and prisoners, persons in nursing homes, low-income and unemployed, national minorities, homeless people, vagrants, refugees, persons under guardianship or custody, and persons unable to give consent, and law enforcement officers;

28. Other conditions that, in the opinion of the Researcher, prevent the inclusion of the volunteer in the study or that might lead to early withdrawal of the volunteer from the study, including fasting or a special diet (e.g. vegetarian, vegan, restricted salt intake) or a special lifestyle (night work, extreme physical activity).

Withdrawal Criteria:

1. The volunteer's refusal to further participate in the study;

2. Failure of the volunteer to comply with the rules of participation in the study (skipping study procedures, independent use of drugs prohibited in the study, violation of dietary and lifestyle restrictions, etc.);

3. Occurrence of causes/occurrence during the study of situations that threaten the safety of the volunteer (e.g., hypersensitivity reactions, etc.);

4. Volunteers selected for the study in violation of the inclusion/inclusion criteria;

5. Development of severe adverse event in the volunteer during the study;

6. The volunteer is undergoing or requires treatment that may affect the pharmacokinetic parameters;

7. Missing 2 or more consecutive blood samples or 3 or more blood samples during the same Study Period;

8. Occurrence of vomiting/diarrhea within 4 hours of study drug administration;

9. Positive urine test for narcotics and powerful drugs;

10. Positive breath alcohol vapor test.

11. Positive pregnancy test in women;

12. Positive test for COVID-19;

13. The occurrence in the course of the study of other reasons that prevent the study according to the protocol.

Related Conditions & MeSH terms

• Influenza
• Respiratory Viral Infection
• Virus Diseases

Intervention

Drug:
• XC8
A single dose of R or T drug in each of 2 periods of the study in fasted conditions

Locations

Country	Name	City	State
Russian Federation	I.M. Sechenov First Moscow State Medical University	Moscow

Sponsors (1)

Lead Sponsor	Collaborator
Valenta Pharm JSC

Country where clinical trial is conducted

Russian Federation, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pharmacokinetics - Cmax	Maximum plasma concentration (Cmax)	From 0 to 24 hours (Day 1-2 and Day 8-9)
Primary	Pharmacokinetics - tmax	Time to reach Cmax (tmax)	From 0 to 24 hours (Day 1-2 and Day 8-9)
Primary	Pharmacokinetics - AUC0-t	Area under the plasma concentration-time curve from time 0 to t (AUC0-t)	From 0 to 24 hours (Day 1-2 and Day 8-9)
Primary	Pharmacokinetics - AUC0-inf	Area under the plasma concentration-time curve from time 0 to infinity (AUC0-inf)	From 0 to 24 hours (Day 1-2 and Day 8-9)
Primary	Pharmacokinetics - AUCextr	Extrapolated AUC, defined as (AUC0-inf - AUC0-t)/AUC0-inf	From 0 to 24 hours (Day 1-2 and Day 8-9)
Primary	Pharmacokinetics - t1/2	Elimination half-life (t1/2)	From 0 to 24 hours (Day 1-2 and Day 8-9)
Primary	Pharmacokinetics - kel	Elimination constant (kel)	From 0 to 24 hours (Day 1-2 and Day 8-9)
Primary	Pharmacokinetics - MRT	Mean residence time (MRT)	From 0 to 24 hours (Day 1-2 and Day 8-9)
Primary	Bioequivalence - ratio of Cmax	Ratio of geometric mean Cmax after intake of R or T (with 90% confidence intervals)	From 0 to 24 hours (Day 1-2 and Day 8-9)
Primary	Bioequivalence - ratio of AUC0-t	Ratio of geometric mean AUC0-t after intake of R or T (with 90% confidence intervals)	From 0 to 24 hours (Day 1-2 and Day 8-9)
Primary	Bioequivalence - ratio of AUC0-inf	Ratio of geometric mean AUC0-inf after intake of R or T (with 90% confidence intervals)	From 0 to 24 hours (Day 1-2 and Day 8-9)
Secondary	Safety and Tolerability: adverse event (AE) number and frequency	Number and frequency of adverse events (AEs)	From the screening (and signing informed consent form) to Day 14 of the study or to an early termination visit within the time frame of the study (from Day 0 to Day 14)
Secondary	Safety and Tolerability: serious adverse event (SAE) number and frequency	Number and frequency of serious AEs (SAEs)	From the screening (and signing informed consent form) to Day 14 of the study or to an early termination visit within the time frame of the study (from Day 0 to Day 14)
Secondary	Safety and Tolerability: vital signs - systolic blood pressure (SBP)	SBP, mmHg	Screening, from Day 0 to Day 2, from Day 7 to Day 9, and/or on early termination visit within the time frame of the study (from Day 0 to Day 14)
Secondary	Safety and Tolerability: vital signs - diastolic blood pressure (DBP)	DBP, mmHg	Screening, from Day 0 to Day 2, from Day 7 to Day 9, and/or on early termination visit within the time frame of the study (from Day 0 to Day 14)
Secondary	Safety and Tolerability: vital signs - respiratory rate (RR)	RR, breaths per minute	Screening, from Day 0 to Day 2, from Day 7 to Day 9, and/or on early termination visit within the time frame of the study (from Day 0 to Day 14)
Secondary	Safety and Tolerability: vital signs - heart rate (HR)	HR, beats per minute	Screening, from Day 0 to Day 2, from Day 7 to Day 9, and/or on early termination visit within the time frame of the study (from Day 0 to Day 14)
Secondary	Safety and Tolerability: vital signs - body temperature	Body temperature, centigrade scale	Screening, from Day 0 to Day 2, from Day 7 to Day 9, and/or on early termination visit within the time frame of the study (from Day 0 to Day 14)
Secondary	Safety and Tolerability: physical examination results	Physical examination will follow the general rules of internal medicine: general examination, examination of mucous membranes and skin, including palpation of lymph nodes, evaluation of the musculoskeletal system, palpation, percussion, and auscultation of the main organ systems (cardiovascular, respiratory, digestive, and urinary systems) will be performed sequentially. The findings (if any) will be reported as the rate of clinically significant findings by each system level assessed.	Screening, from Day 0 to Day 2, from Day 7 to Day 9, and/or on early termination visit within the time frame of the study (from Day 0 to Day 14)
Secondary	Safety and Tolerability: 12-lead electrocardiogram (ECG) - heart rate	12-lead ECG (I, II, III, aVR, aVL, aVF, V1-V6) taken while lying down: heart rate (beats per minute)	Screening, Day 2, Day 9 or on early termination visit within the time frame of the study (from Day 0 to Day 14)
Secondary	Safety and Tolerability: 12-lead electrocardiogram (ECG) - PQ interval	12-lead ECG (I, II, III, aVR, aVL, aVF, V1-V6) taken while lying down: PQ interval (ms)	Screening, Day 2, Day 9 or on early termination visit within the time frame of the study (from Day 0 to Day 14)
Secondary	Safety and Tolerability: 12-lead electrocardiogram (ECG) - QRS complex	12-lead ECG (I, II, III, aVR, aVL, aVF, V1-V6) taken while lying down: QRS complex (ms)	Screening, Day 2, Day 9 or on early termination visit within the time frame of the study (from Day 0 to Day 14)
Secondary	Safety and Tolerability: 12-lead electrocardiogram (ECG) - corrected QT interval (QTc)	12-lead ECG (I, II, III, aVR, aVL, aVF, V1-V6) taken while lying down: QTc (ms)	Screening, Day 2, Day 9 or on early termination visit within the time frame of the study (from Day 0 to Day 14)
Secondary	Safety and Tolerability: urinalysis - color	Color of the urine	Screening, Day 2, Day 9 or on early termination visit within the time frame of the study (from Day 0 to Day 14)
Secondary	Safety and Tolerability: urinalysis - transparency	Transparency of the urine	Screening, Day 2, Day 9 or on early termination visit within the time frame of the study (from Day 0 to Day 14)
Secondary	Safety and Tolerability: urinalysis - pH	pH of the urine	Screening, Day 2, Day 9 or on early termination visit within the time frame of the study (from Day 0 to Day 14)
Secondary	Safety and Tolerability: urinalysis - specific gravity	Specific gravity of the urine	Screening, Day 2, Day 9 or on early termination visit within the time frame of the study (from Day 0 to Day 14)
Secondary	Safety and Tolerability: urinalysis - protein	Protein in the urine (g/L)	Screening, Day 2, Day 9 or on early termination visit within the time frame of the study (from Day 0 to Day 14)
Secondary	Safety and Tolerability: urinalysis - glucose	Glucose in the urine (mmol/L)	Screening, Day 2, Day 9 or on early termination visit within the time frame of the study (from Day 0 to Day 14)
Secondary	Safety and Tolerability: urinalysis (microscopy) - red blood cells	Red blood cells in the urine (number in sight)	Screening, Day 2, Day 9 or on early termination visit within the time frame of the study (from Day 0 to Day 14)
Secondary	Safety and Tolerability: urinalysis (microscopy) - white blood cells	White blood cells in the urine (number in sight)	Screening, Day 2, Day 9 or on early termination visit within the time frame of the study (from Day 0 to Day 14)
Secondary	Safety and Tolerability: urinalysis (microscopy) - epithelial cells	Epithelial cells in the urine (number in sight)	Screening, Day 2, Day 9 or on early termination visit within the time frame of the study (from Day 0 to Day 14)
Secondary	Safety and Tolerability: urinalysis (microscopy) - cylinders	Cylinders in the urine (number in sight)	Screening, Day 2, Day 9 or on early termination visit within the time frame of the study (from Day 0 to Day 14)
Secondary	Safety and Tolerability: urinalysis (microscopy) - mucus	Mucus in the urine (presence in sight)	Screening, Day 2, Day 9 or on early termination visit within the time frame of the study (from Day 0 to Day 14)
Secondary	Safety and Tolerability: urinalysis (microscopy) - bacteria	Bacteria in the urine (number in sight)	Screening, Day 2, Day 9 or on early termination visit within the time frame of the study (from Day 0 to Day 14)
Secondary	Safety and Tolerability: complete blood count - hemoglobin	Hemoglobin, g/dL	Screening, Day 2, Day 9 or on early termination visit within the time frame of the study (from Day 0 to Day 14)
Secondary	Safety and Tolerability: complete blood count - red blood cells	Red blood cells, 10^6/uL	Screening, Day 2, Day 9 or on early termination visit within the time frame of the study (from Day 0 to Day 14)
Secondary	Safety and Tolerability: complete blood count - hematocrit	Hematocrit, %	Screening, Day 2, Day 9 or on early termination visit within the time frame of the study (from Day 0 to Day 14)
Secondary	Safety and Tolerability: complete blood count - platelets	Platelets, 10^3/uL	Screening, Day 2, Day 9 or on early termination visit within the time frame of the study (from Day 0 to Day 14)
Secondary	Safety and Tolerability: complete blood count - white blood cells	White blood cells, 10^3/uL	Screening, Day 2, Day 9 or on early termination visit within the time frame of the study (from Day 0 to Day 14)
Secondary	Safety and Tolerability: complete blood count - erythrocyte sedimentation rate	Erythrocyte sedimentation rate, mm per hour	Screening, Day 2, Day 9 or on early termination visit within the time frame of the study (from Day 0 to Day 14)
Secondary	Safety and Tolerability: complete blood count - neutrophils	Neutrophils, %	Screening, Day 2, Day 9 or on early termination visit within the time frame of the study (from Day 0 to Day 14)
Secondary	Safety and Tolerability: complete blood count - lymphocytes	Lymphocytes, %	Screening, Day 2, Day 9 or on early termination visit within the time frame of the study (from Day 0 to Day 14)
Secondary	Safety and Tolerability: complete blood count - eosinophils	Eosinophils, %	Screening, Day 2, Day 9 or on early termination visit within the time frame of the study (from Day 0 to Day 14)
Secondary	Safety and Tolerability: complete blood count - monocytes	Monocytes, %	Screening, Day 2, Day 9 or on early termination visit within the time frame of the study (from Day 0 to Day 14)
Secondary	Safety and Tolerability: complete blood count - basophils	Basophils, %	Screening, Day 2, Day 9 or on early termination visit within the time frame of the study (from Day 0 to Day 14)
Secondary	Safety and Tolerability: blood test results - total protein	Total protein in blood serum, g/L	Screening, Day 2, Day 9 or on early termination visit within the time frame of the study (from Day 0 to Day 14)
Secondary	Safety and Tolerability: blood test results - creatinine	Creatinine in blood serum, umol/L	Screening, Day 2, Day 9 or on early termination visit within the time frame of the study (from Day 0 to Day 14)
Secondary	Safety and Tolerability: blood test results - glucose	Glucose in blood serum, mmol/L	Screening, Day 2, Day 9 or on early termination visit within the time frame of the study (from Day 0 to Day 14)
Secondary	Safety and Tolerability: blood test results - total bilirubin	Total bilirubin in blood serum, umol/L	Screening, Day 2, Day 9 or on early termination visit within the time frame of the study (from Day 0 to Day 14)
Secondary	Safety and Tolerability: blood test results - total cholesterol	Total cholesterol in blood serum, mmol/L	Screening, Day 2, Day 9 or on early termination visit within the time frame of the study (from Day 0 to Day 14)
Secondary	Safety and Tolerability: blood test results - alanine transaminase (ALT)	ALT in blood serum, U/L	Screening, Day 2, Day 9 or on early termination visit within the time frame of the study (from Day 0 to Day 14)
Secondary	Safety and Tolerability: blood test results - aspartate transaminase (AST)	AST in blood serum, U/L	Screening, Day 2, Day 9 or on early termination visit within the time frame of the study (from Day 0 to Day 14)
Secondary	Safety and Tolerability: blood test results - alkaline phosphatase (ALP)	ALP in blood serum, U/L	Screening, Day 2, Day 9 or on early termination visit within the time frame of the study (from Day 0 to Day 14)