Study of the Effect of Food Intake on the Bioavailability of XC221 100 mg Tablets

An Open-label, Randomized, Cross-over Study With 2 Treatments (Fasting and After Meals), 3 Periods, 2 Sequences, and an Adaptive, Two-stage Design to Evaluate the Effect of Food Intake on the Bioavailability of XC221 100 mg Tablets at a Single Dose in Healthy Volunteers

Primary objective of the study: evaluation of the effect of food intake on the bioavailability of XC221 100 mg tablets after a single oral administration in fed or fasted condition.

Additional objective of the study: evaluation of pharmacokinetic parameters, safety and tolerability of XC221 100 mg tablets in healthy volunteers after single oral administration in fed or fasted condition.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: XC221 100 mg tablets

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• Russian Federation
  • Saint Petersburg, Russian Federation, 196143
    • Limited Liability Company "Research Center Eco-safety"

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 43 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Healthy male and female volunteers aged 18 to 45 years (inclusive).
2. Presence of written consent of the volunteer to participate in the study in accordance with applicable law.
3. Body mass index (BMI) within the range of 18.5 ≤ BMI ≤ 30 kg/m2 with a body weight not less than 45 kg and not more than 100 kg.
4. Verified diagnosis "healthy": no deviations from the reference values of the data of standard clinical, laboratory and instrumental methods of examination.
5. The consent of the volunteer (including the partner) to use adequate methods of contraception during the study and 3 weeks after its completion.
6. Hemodynamic and other vital signs within normal limits (reference intervals are 60-90 bpm at rest for heart rate (HR), 16-20 breaths/min for respiratory rate (RR), 35.5 to 36.9°C for body temperature, normal blood pressure (BP) is considered to be systolic blood pressure (SBP) in the range of 110-130 mmHg; diastolic blood pressure (DBP) is 60-85 mmHg).

Exclusion Criteria:

1. Hypersensitivity to the active substance XC221 (N-[2-(1H-imidazol-4-yl)-ethyl]-6-oxo-δ-lactam) and/or any other component of the drug product.
2. A history of allergy.
3. A history of bronchial asthma, recurrent nasal or paranasal sinus polyposis, allergic rhinitis.
4. Hereditary lactose intolerance, lactase deficiency and glucose-galactose malabsorption syndrome.
5. Chronic diseases of the cardiovascular, bronchopulmonary, neuroendocrine, digestive, urinary, hematopoietic, immune and musculoskeletal systems, mental illness in the history.
6. Acute infectious diseases (including influenza, acute respiratory infections) within 30 days prior to the study.
7. Surgical interventions on the gastrointestinal tract in the anamnesis (except appendectomy).
8. Taking any medications, including vitamins, herbal preparations, and dietary supplements within 14 days prior to screening.
9. Taking medications that have significant effects on hemodynamics or liver function (barbiturates, omeprazole, cimetidine, etc.) for less than 30 days before screening.
10. Vital signs outside the reference intervals: SBP less than 110 mmHg or greater than 130 mmHg; DBP less than 60 mmHg or greater than 85 mmHg; HR less than 60 bpm or greater than 90 bpm; body temperature less than 35.5 or greater than 36.9° C, RR less than 16 or greater than 20 bpm.
11. Laboratory values outside the reference intervals.
12. Intake of more than 10 units of alcohol per week (where each unit equals 30 ml of spirits or 120 ml of wine or 330 ml of beer) or anamnestic evidence of alcoholism, drug addiction, substance abuse, drug abuse.
13. Smoking more than 10 cigarettes per day and failure to abstain from smoking 48 hours before the study and during the hospital stay.
14. Special diet (e.g., vegetarian, vegan, restricted salt intake) or lifestyle (night work, extreme physical activity).
15. Consumption of alcohol, caffeine, and xanthine-containing products 72 hours before taking the drug product.
16. Consumption of citrus fruits, cranberries and products containing them, preparations or products containing St. John's wort - 7 days before taking the IP. 17.
17. Dehydration due to diarrhea, vomiting, or other reason within the last 24 hours prior to IP administration.
18. Positive result of examination for antibodies to HIV type 1 and 2, syphilis, markers of hepatitis B and C.
19. Positive result of rapid test for COVID-19.
20. Positive breath alcohol test.
21. Positive urine drug test (cocaine, marijuana, amphetamine, methamphetamine, morphine, barbiturates).
22. Pregnancy, breastfeeding, positive urine pregnancy test (for women of preserved reproductive potential).
23. Use of hormonal contraceptives (oral, transdermal, injectable, implantable) by a female volunteer for 2 months prior to the drug administration.
24. Donation of blood (450 ml or more) within 30 days prior to the study.
25. Participation in a clinical drug study of any phase within 90 days prior to the start of the study.
26. Unavailability for observation during the study, inability to keep the visit schedule, inability to be hospitalized for the required duration, high likelihood of problems with successful insertion of a venous catheter or performing a forearm vein puncture.
27. Belonging to a vulnerable group of volunteers (minors; incapacitated; people with limited free will or possibly participating under compulsion (serving a sentence in prison, being in custody in detention centers, military personnel)), as well as law enforcement officers.
28. Other reasons that, in the opinion of the researcher, prevent the participation of the volunteer in the research or create an unreasonable risk.

Withdrawal criteria:

1. Withdrawal of consent to participate in the study.
2. SAE, irrespective of causal relationship to drug intake.
3. Any other AE if the researcher believes it is in the best interest of the volunteer to discontinue participation in the study.
4. Missing two consecutive or four or more blood sampling points to determine pharmacokinetic parameters during the same period of the pharmacokinetics study.
5. Violation of study protocol requirements (including because the volunteer refuses to cooperate with the investigator, is late to the clinic, etc.).
6. Volunteer is undergoing or requires treatment that may affect the pharmacokinetic parameters of the drug.
7. Volunteer requires inpatient treatment while participating in the study.
8. Vomiting and/or diarrhea in volunteer within 24 hours prior to the drug administration or within 3 hours (2 maximum Tmax for XC221) after the drug administration.
9. Positive urine drug test result.
10. Positive breath alcohol test.
11. Positive urine pregnancy test.
12. Positive test for COVID-19.
13. Discontinuation of the study at the discretion of the Sponsor or regulatory agency.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: XC221, fasted; Administration of XC221 in fasted state in Dosing Periods 1 and 2 followed by administration of XC221 in fasted state in Dosing Period 3	Drug: XC221 100 mg tablets; XC221, 3 discrete doses separated by 7-day wash-out periods
Experimental: XC221, fed; Administration of XC221 in fed state in Dosing Periods 1 and 2 followed by administration of XC221 in fasted state in Dosing Period 3	Drug: XC221 100 mg tablets; XC221, 3 discrete doses separated by 7-day wash-out periods

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics - Cmax	Maximum plasma concentration (Cmax) of XC221GI (active ingridient) and XC221A (metabolite)	From 0 to 12 hours after dosing on Day 1, Day 8, and Day 15
Pharmacokinetics - AUC0-t	Area under the plasma concentration-time curve from time 0 to t (AUC0-t) of XC221GI (active ingridient) and XC221A (metabolite)	From 0 to 12 hours after dosing on Day 1, Day 8, and Day 15
Pharmacokinetics - AUC0-inf	Area under the plasma concentration-time curve from time 0 to infinity (AUC0-inf) of XC221GI (active ingridient) and XC221A (metabolite)	From 0 to 12 hours after dosing on Day 1, Day 8, and Day 15

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and Tolerability: adverse event (AE) number and frequency	Number and frequency of adverse events (AEs) or serious AEs (SAEs)	From the screening (and signing informed consent form) to Day 16 of the study or to an early termination visit within the time frame of the study (from Day -1 to Day 16)
Safety and Tolerability: adverse event (AE) characteristics	Description and severity of AEs or serious AEs (SAEs), concomitant therapy for AEs/SAEs, causal relationship with XC221, outcomes.	From the screening (and signing informed consent form) to Day 16 of the study or to an early termination visit within the time frame of the study (from Day -1 to Day 16)
Safety and Tolerability: vital signs - systolic blood pressure (SBP)	SBP, mmHg	Screening, from Day -1 to Day 2, from Day 7 to Day 9, from Day 14 to Day 16 and/or on early termination visit within the time frame of the study (from Day -1 to Day 16)
Safety and Tolerability: vital signs - diastolic blood pressure (DBP)	DBP, mmHg	Screening, from Day -1 to Day 2, from Day 7 to Day 9, from Day 14 to Day 16 and/or on early termination visit within the time frame of the study (from Day -1 to Day 16)
Safety and Tolerability: vital signs - respiratory rate (RR)	RR, breaths per minute	Screening, from Day -1 to Day 2, from Day 7 to Day 9, from Day 14 to Day 16 and/or on early termination visit within the time frame of the study (from Day -1 to Day 16)
Safety and Tolerability: vital signs - heart rate (HR)	HR, beats per minute	Screening, from Day -1 to Day 2, from Day 7 to Day 9, from Day 14 to Day 16 and/or on early termination visit within the time frame of the study (from Day -1 to Day 16)
Safety and Tolerability: vital signs - body temperature	Body temperature, centigrade scale	Screening, from Day -1 to Day 2, from Day 7 to Day 9, from Day 14 to Day 16 and/or on early termination visit within the time frame of the study (from Day -1 to Day 16)
Safety and Tolerability: physical examination results	Physical examination results	Screening, from Day -1 to Day 2, from Day 7 to Day 9, from Day 14 to Day 16 and/or on early termination visit within the time frame of the study (from Day -1 to Day 16)
Safety and Tolerability: urinalysis - color	Color of the urine	Screening and Day 16 or on early termination visit within the time frame of the study (from Day -1 to Day 16)
Safety and Tolerability: urinalysis - transparency	Transparency of the urine	Screening and Day 16 or on early termination visit within the time frame of the study (from Day -1 to Day 16)
Safety and Tolerability: urinalysis - pH	pH of the urine	Screening and Day 16 or on early termination visit within the time frame of the study (from Day -1 to Day 16)
Safety and Tolerability: urinalysis - specific gravity	Specific gravity of the urine	Screening and Day 16 or on early termination visit within the time frame of the study (from Day -1 to Day 16)
Safety and Tolerability: urinalysis - nitrites	Nitrites in the urine (+/-)	Screening and Day 16 or on early termination visit within the time frame of the study (from Day -1 to Day 16)
Safety and Tolerability: urinalysis - protein	Protein in the urine (g/L)	Screening and Day 16 or on early termination visit within the time frame of the study (from Day -1 to Day 16)
Safety and Tolerability: urinalysis - glucose	Glucose in the urine (mmol/L)	Screening and Day 16 or on early termination visit within the time frame of the study (from Day -1 to Day 16)
Safety and Tolerability: urinalysis - ketones	Ketones in the urine (mmol/L)	Screening and Day 16 or on early termination visit within the time frame of the study (from Day -1 to Day 16)
Safety and Tolerability: urinalysis - urobilinogen	Urobilinogen in the urine (mmol/L)	Screening and Day 16 or on early termination visit within the time frame of the study (from Day -1 to Day 16)
Safety and Tolerability: urinalysis - bilirubin	Bilirubin in the urine (+/-)	Screening and Day 16 or on early termination visit within the time frame of the study (from Day -1 to Day 16)
Safety and Tolerability: urinalysis (microscopy) - red blood cells	Red blood cells in the urine (number in sight)	Screening and Day 16 or on early termination visit within the time frame of the study (from Day -1 to Day 16)
Safety and Tolerability: urinalysis (microscopy) - white blood cells	White blood cells in the urine (number in sight)	Screening and Day 16 or on early termination visit within the time frame of the study (from Day -1 to Day 16)
Safety and Tolerability: urinalysis (microscopy) - cylinders (except hyaline)	Cylinders (except hyaline) in the urine (number in sight)	Screening and Day 16 or on early termination visit within the time frame of the study (from Day -1 to Day 16)
Safety and Tolerability: urinalysis (microscopy) - bacteria	Bacteria in the urine (number in sight)	Screening and Day 16 or on early termination visit within the time frame of the study (from Day -1 to Day 16)
Safety and Tolerability: complete bood count - hemoglobin	Hemoglobin, g/dL	Screening and Day 16 or on early termination visit within the time frame of the study (from Day -1 to Day 16)
Safety and Tolerability: complete bood count - red blood cells	Red blood cells, 10^6/uL	Screening and Day 16 or on early termination visit within the time frame of the study (from Day -1 to Day 16)
Safety and Tolerability: complete bood count - hematocrit	Hematocrit, %	Screening and Day 16 or on early termination visit within the time frame of the study (from Day -1 to Day 16)
Safety and Tolerability: complete bood count - platelets	Platelets, 10^3/uL	Screening and Day 16 or on early termination visit within the time frame of the study (from Day -1 to Day 16)
Safety and Tolerability: complete bood count - white blood cells	White blood cells, 10^3/uL	Screening and Day 16 or on early termination visit within the time frame of the study (from Day -1 to Day 16)
Safety and Tolerability: complete bood count - erythrocyte sedimentation rate	Erythrocyte sedimentation rate, mm per hour	Screening and Day 16 or on early termination visit within the time frame of the study (from Day -1 to Day 16)
Safety and Tolerability: complete bood count - neutrophils	Neutrophils, %	Screening and Day 16 or on early termination visit within the time frame of the study (from Day -1 to Day 16)
Safety and Tolerability: complete bood count - lymphocytes	Lymphocytes, %	Screening and Day 16 or on early termination visit within the time frame of the study (from Day -1 to Day 16)
Safety and Tolerability: complete bood count - eosinophils	Eosinophils, %	Screening and Day 16 or on early termination visit within the time frame of the study (from Day -1 to Day 16)
Safety and Tolerability: complete bood count - monocytes	Monocytes, %	Screening and Day 16 or on early termination visit within the time frame of the study (from Day -1 to Day 16)
Safety and Tolerability: complete bood count - basophils	Basophils, %	Screening and Day 16 or on early termination visit within the time frame of the study (from Day -1 to Day 16)
Safety and Tolerability: blood test results - total protein	Total protein in blood serum, g/L	Screening and Day 16 or on early termination visit within the time frame of the study (from Day -1 to Day 16)
Safety and Tolerability: blood test results - creatinine	Creatinine in blood serum, umol/L	Screening and Day 16 or on early termination visit within the time frame of the study (from Day -1 to Day 16)
Safety and Tolerability: blood test results - urea	Urea in blood serum, mmol/L	Screening and Day 16 or on early termination visit within the time frame of the study (from Day -1 to Day 16)
Safety and Tolerability: blood test results - glucose	Glucose in blood serum, mmol/L	Screening and Day 16 or on early termination visit within the time frame of the study (from Day -1 to Day 16)
Safety and Tolerability: blood test results - total bilirubin	Total bilirubin in blood serum, umol/L	Screening and Day 16 or on early termination visit within the time frame of the study (from Day -1 to Day 16)
Safety and Tolerability: blood test results - direct bilirubin	Direct bilirubin in blood serum, umol/L	Screening and Day 16 or on early termination visit within the time frame of the study (from Day -1 to Day 16)
Safety and Tolerability: blood test results - total cholesterol	Total cholesterol in blood serum, mmol/L	Screening and Day 16 or on early termination visit within the time frame of the study (from Day -1 to Day 16)
Safety and Tolerability: blood test results - triglycerides	Triglycerides in blood serum, mmol/L	Screening and Day 16 or on early termination visit within the time frame of the study (from Day -1 to Day 16)
Safety and Tolerability: blood test results - alanine transaminase (ALT)	ALT in blood serum, U/L	Screening and Day 16 or on early termination visit within the time frame of the study (from Day -1 to Day 16)
Safety and Tolerability: blood test results - aspartate transaminase (AST)	AST in blood serum, U/L	Screening and Day 16 or on early termination visit within the time frame of the study (from Day -1 to Day 16)
Safety and Tolerability: blood test results - alkaline phosphatase (ALP)	ALP in blood serum, U/L	Screening and Day 16 or on early termination visit within the time frame of the study (from Day -1 to Day 16)
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 and Day 16 or on early termination visit within the time frame of the study (from Day -1 to Day 16)
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 and Day 16 or on early termination visit within the time frame of the study (from Day -1 to Day 16)
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 and Day 16 or on early termination visit within the time frame of the study (from Day -1 to Day 16)
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 and Day 16 or on early termination visit within the time frame of the study (from Day -1 to Day 16)

Collaborators and Investigators

• Sponsor: Valenta Pharm JSC

Study record dates

Study Major Dates

• Study Start (Actual): February 10, 2022
• Primary Completion (Actual): February 22, 2022
• Study Completion (Actual): March 17, 2022

Study Registration Dates

• First Submitted: January 28, 2022
• First Submitted That Met QC Criteria: March 14, 2022
• First Posted (Actual): March 24, 2022

Study Record Updates

• Last Update Posted (Actual): July 27, 2023
• Last Update Submitted That Met QC Criteria: July 25, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Other Study ID Numbers: XC221-01-04-2021

Drug and device information, study documents

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