Biliary Dyskinesia, Chronic Cholecystitis
Conditions
Brief summary
This open-label study will evaluate the effect of food on the bioavailability of a single dose of 4-MUST, tablets, 128 mg. Additionally, the study will assess the pharmacokinetics, safety, and tolerability of 4-MUST, tablets, 128 mg following both single and multiple oral dose administration.
Interventions
DRUG4-MUST
128 mg tablets containing trimebutine 4-methylumbelliferyl sulfate (4-MUST)
Sponsors
Valenta Pharm JSC
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* Voluntary, personally signed ICF obtained prior to any study procedures; * Males and females aged 18 to 45 years (inclusive) of Caucasian race; * Confirmed healthy status based on the absence of clinically significant abnormalities in clinical, laboratory, and diagnostic assessments specified in the protocol; * Blood pressure (BP): systolic blood pressure (SBP) from 99 to 129 mmHg (inclusive), diastolic blood pressure (DBP) from 70 to 89 mmHg (inclusive); * Heart rate (HR) from 60 to 89 beats/min (inclusive); * Respiratory rate (RR) from 12 to 20 per 1 minute (inclusive); * Body temperature from 36.0°C to 36.9°C (inclusive); * Body mass index (BMI) of 18.5 kg/m2 ≤ BMI ≤ 30 kg/m2, with body weight ≥ 55 kg for males and ≥ 45 kg for females; * Commitment to adhere to highly effective contraceptive methods during the study participation period and for 30 days thereafter; documentation of negative urine pregnancy test for women of childbearing potential. Noninclusion Criteria: * History of clinically significant allergic reactions; * Hypersensitivity to hymecromone and trimebutine and/or excipients included in the study drug in anamnesis; * Drug intolerance to hymecromone and trimebutine and/or excipients included in the study drug in the anamnesis; * Hereditary galactose intolerance, lactase deficiency or glucose-galactose malabsorption in the anamnesis; * Chronic diseases of the kidney, liver, gastrointestinal tract (GIT), cardiovascular, lymphatic, respiratory, nervous, endocrine, musculoskeletal, genitourinary and immune systems, as well as skin, hematopoietic and visual organs; * History of GI surgery (except for appendectomy at least 1 year prior to screening); * Diseases/conditions that, in the opinion of the investigator, may affect the absorption, distribution, metabolism, or excretion of the study drug; * Acute infectious diseases less than 4 weeks prior to screening; * Intake of drugs that have a significant effect on hemodynamics and drugs that affect liver function (barbiturates, omeprazole, cimetidine, etc.) less than 2 months before screening; * Regular intake of a medicine less than 2 weeks prior to screening and single intake of a medicine less than 7 days prior to screening (including over-the-counter medicines, vitamins, supplements, herbs); * Blood or plasma donation less than 3 months prior to screening; * Use of hormonal contraceptives (in women) less than 2 months prior to screening; * Use of depot injections of any medicine less than 3 months prior to screening; * Pregnancy or lactation period; positive pregnancy test for women of childbearing potential; * Women of childbearing potential who have had unprotected sexual intercourse with a non-sterilized male partner within 30 days prior to administration of the study drug; * Participation in another clinical trial less than 3 months prior to screening or concurrent with the present study; * Consumption of more than 10 units of alcohol per week during the month prior to study enrollment (1 unit of alcohol is equivalent to 500 mL of beer, 200 mL of wine, or 50 mL of spirits), or a history of alcoholism, drug dependence, or abuse of medicinal products; * Smoking more than 10 cigarettes per day currently, or a history of smoking the indicated number of cigarettes in the 6 months preceding screening; failure to agree to abstain from smoking for the duration of the hospital stay; * Consumption of alcohol, caffeine, and xanthine-containing products in the 7 days prior to taking the study drug; * Consumption of citrus fruits, cranberries, rose hips and products containing them, preparations or products containing St. John's wort - 7 days before taking the study drug; * Dehydration due to diarrhea, vomiting, or other cause within the last 24 hours prior to taking the study drug; * Positive blood test result 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; * Clinically significant abnormalities on electrocardiogram (ECG) in the medical history and/or at screening; * Positive urinalysis for narcotics and potent drugs at screening; * Positive breath alcohol vapor test at screening; * Scheduling a hospital stay during the study period, for any reason other than hospitalization required by this protocol; * Failure or inability to comply with protocol requirements, follow protocol procedures, diet and activity regimen. * Belonging to a vulnerable population, including: students enrolled in medical, pharmaceutical, or dental educational institutions, clinical and laboratory assistants, pharmaceutical company employees, military personnel and prisoners, persons residing in residential care facilities, low-income and unemployed, minorities, homeless, vagrants, refugees, persons in foster care, persons unable to consent, and law enforcement officers; * Any other condition that, in the judgement of the Investigator, would preclude the volunteer's enrollment in the study or could lead to premature withdrawal from the study, including adherence to fasting regimens or special diets (e.g., vegetarian, vegan, or sodium-restricted diets) or lifestyle factors (e.g., night-shift work or extreme physical exertion)
Exclusion criteria
* Voluntary withdrawal of the subject from the study; * Failure to comply with protocol requirements by the volunteer (e.g., missing scheduled study procedures, unauthorized use of prohibited medications, or violation of dietary or lifestyle restrictions); * Occurrence of any event or condition during the study that, in the investigator's judgement, may compromise the volunteer's safety (e.g., hypersensitivity reactions); * Volunteers selected for participation in the study in violation of the inclusion/non-inclusion criteria; * Development of severe adverse event and/or a serious adverse event in a volunteer during the course of the study; * Volunteer is receiving or requires treatment that may affect the pharmacokinetic parameters of the study drug; * Missing collection of 2 or more consecutive blood samples or 3 x or more blood samples during the same Study Period; * Occurrence of vomiting/diarrhea within 6 h after administration of study drug; * Positive urine test for narcotics and potent drugs; * Positive breath alcohol test; * Positive pregnancy test in women; * Occurrence of any other circumstance that precludes conduct of the study in accordance with the protocol.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics - Cmax | From 0 to 48 hours (days 1-3 and 8-10) | Maximum plasma concentration (Cmax) of 4-MUST metabolites: trimebutine, N-desmethyltrimebutine, 3,4,5-trimethoxybenzoic acid, 4-methylumbelliferone sulfate, 4-methylumbelliferone and 4-methylumbelliferone glucuronide |
| Pharmacokinetics - tmax | From 0 to 48 hours (days 1-3 and 8-10) | Time to reach Cmax (tmax) of trimebutine, N-desmethyltrimebutine, 3,4,5-trimethoxybenzoic acid, 4-methylumbelliferone sulfate, 4-methylumbelliferone and 4-methylumbelliferone glucuronide |
| Pharmacokinetics - AUC0-t | From 0 to 48 hours (days 1-3 and 8-10) | Area under the plasma concentration-time curve from time 0 to t (AUC0-t) of trimebutine, N-desmethyltrimebutine, 3,4,5-trimethoxybenzoic acid, 4-methylumbelliferone sulfate, 4-methylumbelliferone and 4-methylumbelliferone glucuronide |
| Pharmacokinetics - AUC0-inf | From 0 to 48 hours (days 1-3 and 8-10) | Area under the plasma concentration-time curve from time 0 to infinity (AUC0-inf) of trimebutine, N-desmethyltrimebutine, 3,4,5-trimethoxybenzoic acid, 4-methylumbelliferone sulfate, 4-methylumbelliferone and 4-methylumbelliferone glucuronide |
| Pharmacokinetics - AUC ratio | From 0 to 48 hours (days 1-3 and 8-10) | The ratio of the area under the concentration-time curve over the observation time to the calculated area under the concentration-time curve from zero to infinity |
| Pharmacokinetics - t1/2 | From 0 to 48 hours (days 1-3 and 8-10) | Elimination half-life (t1/2) of trimebutine, N-desmethyltrimebutine, 3,4,5-trimethoxybenzoic acid, 4-methylumbelliferone sulfate, 4-methylumbelliferone and 4-methylumbelliferone glucuronide |
| Pharmacokinetics - kel | From 0 to 48 hours (days 1-3 and 8-10) | Elimination constant (kel) of of trimebutine, N-desmethyltrimebutine, 3,4,5-trimethoxybenzoic acid, 4-methylumbelliferone sulfate, 4-methylumbelliferone and 4-methylumbelliferone glucuronide |
| Pharmacokinetics - MRT | From 0 to 48 hours (days 1-3 and 8-10) | Mean residence time (MRT) of of trimebutine, N-desmethyltrimebutine, 3,4,5-trimethoxybenzoic acid, 4-methylumbelliferone sulfate, 4-methylumbelliferone and 4-methylumbelliferone glucuronide |
| Pharmacokinetics - Vd | From 0 to 48 hours (days 1-3 and 8-10) | Volume of distribution of trimebutine, N-desmethyltrimebutine, 3,4,5-trimethoxybenzoic acid, 4-methylumbelliferone sulfate, 4-methylumbelliferone and 4-methylumbelliferone glucuronide |
| Pharmacokinetics - Cmax/AUC0-t | From 0 to 48 hours (days 1-3 and 8-10) | The ratio of the maximum concentration to the area under the concentration-time curve during the observation period |
| Pharmacokinetics - f' | From 0 to 48 hours (days 1-3 and 8-10) | f' - relative bioavailability (AUC(0-t)(fed)/AUC(0- t)(fasting)) |
| Pharmacokinetics - f'' | From 0 to 48 hours (days 1-3 and 8-10) | f'' is the relative absorption rate (Cmax(fed)/Cmax(fasting)) |
| Bioavailability - ratio of Cmax | From 0 to 48 hours (days 1-3 and 8-10) | Ratio of geometric mean Cmax for trimebutine, N-desmethyltrimebutine, 3,4,5-trimethoxybenzoic acid, 4-methylumbelliferone sulfate, 4-methylumbelliferone and 4-methylumbelliferone glucuronide under fasted and fed conditions (with 90% confidence intervals) |
| Bioavailability - ratio of AUC0-t | From 0 to 48 hours (days 1-3 and 8-10) | Ratio of geometric mean AUC0-t for of trimebutine, N-desmethyltrimebutine, 3,4,5-trimethoxybenzoic acid, 4-methylumbelliferone sulfate, 4-methylumbelliferone and 4-methylumbelliferone glucuronide under fasted and fed conditions (with 90% confidence intervals) |
| Bioavailability - ratio of AUC0-inf | From 0 to 48 hours (days 1-3 and 8-10) | Ratio of geometric mean AUC0-inf for of trimebutine, N-desmethyltrimebutine, 3,4,5-trimethoxybenzoic acid, 4-methylumbelliferone sulfate, 4-methylumbelliferone and 4-methylumbelliferone glucuronide under fasted and fed conditions (with 90% confidence intervals) |
| Pharmacokinetics (multiple dosing) - number of terminal timepoints | From 72 to 120 hours | number of points in the terminal logarithmic phase used to estimate the terminal elimination rate constant of of trimebutine, N-desmethyltrimebutine, 3,4,5-trimethoxybenzoic acid, 4-methylumbelliferone sulfate, 4-methylumbelliferone and 4-methylumbelliferone glucuronide |
| Pharmacokinetics (multiple dosing) - Cmax | From 72 to 120 hours | Maximum plasma concentration (Cmax) of trimebutine, N-desmethyltrimebutine, 3,4,5-trimethoxybenzoic acid, 4-methylumbelliferone sulfate, 4-methylumbelliferone and 4-methylumbelliferone glucuronide |
| Pharmacokinetics (multiple dosing) - tmax | From 72 to 120 hours | Time to reach Cmax (tmax) of trimebutine, N-desmethyltrimebutine, 3,4,5-trimethoxybenzoic acid, 4-methylumbelliferone sulfate, 4-methylumbelliferone and 4-methylumbelliferone glucuronide |
| Pharmacokinetics (multiple dosing) - AUC0-t | From 72 to 120 hours | Area under the plasma concentration-time curve from time 0 to t (AUC0-t) of trimebutine, N-desmethyltrimebutine, 3,4,5-trimethoxybenzoic acid, 4-methylumbelliferone sulfate, 4-methylumbelliferone and 4-methylumbelliferone glucuronide |
| Pharmacokinetics (multiple dosing) - AUC0-inf | From 72 to 120 hours | Area under the plasma concentration-time curve from time 0 to infinity (AUC0-inf) of trimebutine, N-desmethyltrimebutine, 3,4,5-trimethoxybenzoic acid, 4-methylumbelliferone sulfate, 4-methylumbelliferone and 4-methylumbelliferone glucuronide |
| Pharmacokinetics (multiple dosing) - AUCextr | From 72 to 120 hours | Extrapolated AUC of trimebutine, N-desmethyltrimebutine, 3,4,5-trimethoxybenzoic acid, 4-methylumbelliferone sulfate, 4-methylumbelliferone and 4-methylumbelliferone glucuronide |
| Pharmacokinetics (multiple dosing) - t1/2 | From 72 to 120 hours | Elimination half-life (t1/2) of trimebutine, N-desmethyltrimebutine, 3,4,5-trimethoxybenzoic acid, 4-methylumbelliferone sulfate, 4-methylumbelliferone and 4-methylumbelliferone glucuronide |
| Pharmacokinetics (multiple dosing) - kel | From 72 to 120 hours | Elimination constant (kel) of trimebutine, N-desmethyltrimebutine, 3,4,5-trimethoxybenzoic acid, 4-methylumbelliferone sulfate, 4-methylumbelliferone and 4-methylumbelliferone glucuronide |
| Pharmacokinetics (multiple dosing) - MRT | From 72 to 120 hours | Mean residence time (MRT) of trimebutine, N-desmethyltrimebutine, 3,4,5-trimethoxybenzoic acid, 4-methylumbelliferone sulfate, 4-methylumbelliferone and 4-methylumbelliferone glucuronide |
| Pharmacokinetics (multiple dosing) - Vd | From 72 to 120 hours | Volume of distribution of trimebutine, N-desmethyltrimebutine, 3,4,5-trimethoxybenzoic acid, 4-methylumbelliferone sulfate, 4-methylumbelliferone and 4-methylumbelliferone glucuronide |
| Pharmacokinetics (multiple dosing) - CL | From 72 to 120 hours | Clearance (CL) of trimebutine, N-desmethyltrimebutine, 3,4,5-trimethoxybenzoic acid, 4-methylumbelliferone sulfate, 4-methylumbelliferone and 4-methylumbelliferone glucuronide |
| Pharmacokinetics (multiple dosing) - Cmax,ss | From 0 to 72 hours | Maximum plasma concentration at steady state of trimebutine, N-desmethyltrimebutine, 3,4,5-trimethoxybenzoic acid, 4-methylumbelliferone sulfate, 4-methylumbelliferone and 4-methylumbelliferone glucuronide |
| Pharmacokinetics (multiple dosing) - tmax,ss | From 0 to 72 hours | Time to reach maximum plasma concentration at steady state of trimebutine, N-desmethyltrimebutine, 3,4,5-trimethoxybenzoic acid, 4-methylumbelliferone sulfate, 4-methylumbelliferone and 4-methylumbelliferone glucuronide |
| Pharmacokinetics (multiple dosing) - tmin,ss | From 0 to 72 hours | Time to reach minimum plasma concentration at steady state of trimebutine, N-desmethyltrimebutine, 3,4,5-trimethoxybenzoic acid, 4-methylumbelliferone sulfate, 4-methylumbelliferone and 4-methylumbelliferone glucuronide |
| Pharmacokinetics (multiple dosing) - Cmin,ss | From 0 to 72 hours | Minimum plasma concentration at steady state of trimebutine, N-desmethyltrimebutine, 3,4,5-trimethoxybenzoic acid, 4-methylumbelliferone sulfate, 4-methylumbelliferone and 4-methylumbelliferone glucuronide |
| Pharmacokinetics (multiple dosing) - Cavg,ss | From 0 to 72 hours | Average plasma concentration at steady state of trimebutine, N-desmethyltrimebutine, 3,4,5-trimethoxybenzoic acid, 4-methylumbelliferone sulfate, 4-methylumbelliferone and 4-methylumbelliferone glucuronide |
| Pharmacokinetics (multiple dosing) - CL,ss | From 0 to 72 hours | Clearance at steady state of trimebutine, N-desmethyltrimebutine, 3,4,5-trimethoxybenzoic acid, 4-methylumbelliferone sulfate, 4-methylumbelliferone and 4-methylumbelliferone glucuronide |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Adverse event type | From day -14 - day -1 (screening) to day 16 ± 1 (end of the study) | Adverse events will be assessed by complaints, results of physical examination, results of heart rate and blood pressure assessment, results of respiratory rate assessment, body temperature, laboratory monitoring (clinical blood count, biochemical blood count, urinalysis), electrocardiography; adverse events will be classified in accordance to MedDRA. |
| Adverse event frequency | From day -14 - day -1 (screening) to day 16 ± 1 (end of the study) | Number and frequency of adverse events registered during the study |
| Adverse event severety | From day -14 - day -1 (screening) to day 16 ± 1 (end of the study) | Severity of adverse events registered during the study, assessed using the Common Terminology Criteria for Adverse Events (CTCAE) |
| Drop-outs associated with adverse events | From day -14 - day -1 (screening) to day 16 ± 1 (end of the study) | The number of cases of early termination of participation in the study due to the development of adverse events and/or serious adverse events associated with the study drug |
| Physical examination results - cardiovascular system | From day -14 - day -1 (screening) to day 16 ± 1 (end of the study) | An assessment of the condition of the cardiovascular system on physical examination (normal condition or list of abnormal conditions, if any) |
| Physical examination results - respiratory system | From day -14 - day -1 (screening) to day 16 ± 1 (end of the study) | An assessment of the condition of the respiratory system on physical examination (normal condition or list of abnormal conditions, if any) |
| Physical examination results - digestive tract | From day -14 - day -1 (screening) to day 16 ± 1 (end of the study) | An assessment of the condition of the digestive tract on physical examination (normal condition or list of abnormal conditions, if any) |
| Physical examination results - endocrine system | From day -14 - day -1 (screening) to day 16 ± 1 (end of the study) | An assessment of the condition of the endocrine system on physical examination (normal condition or list of abnormal conditions, if any) |
| Physical examination results - musculoskeletal system | From day -14 - day -1 (screening) to day 16 ± 1 (end of the study) | An assessment of the condition of the musculoskeletal system on physical examination (normal condition or list of abnormal conditions, if any) |
| Physical examination results - nervous system | From day -14 - day -1 (screening) to day 16 ± 1 (end of the study) | An assessment of the condition of the nervous system on physical examination (normal condition or list of abnormal conditions, if any) |
| Physical examination results - sensory systems | From day -14 - day -1 (screening) to day 16 ± 1 (end of the study) | An assessment of the condition of the sensory systems on physical examination (normal condition or list of abnormal conditions, if any) |
| Physical examination results - skin/visible mucous membranes | From day -14 - day -1 (screening) to day 16 ± 1 (end of the study) | An assessment of the condition of the skin/visible mucous membranes on physical examination (normal condition or list of abnormal conditions, if any) |
| Physical examination results - genitourinary system | From day -14 - day -1 (screening) to day 16 ± 1 (end of the study) | An assessment of the condition of the genitourinary system on physical examination (normal condition or list of abnormal conditions, if any) |
| Safety and Tolerability: vital signs - systolic blood pressure | From day -14 - day -1 (screening) to day 16 ± 1 (end of the study) | Systolic blood pressure (SBP, mmHg) |
| Safety and Tolerability: vital signs - diastolic blood pressure | From day -14 - day -1 (screening) to day 16 ± 1 (end of the study) | Diastolic blood pressure (DBP, mmHg) |
| Safety and Tolerability: vital signs - heart rate | From day -14 - day -1 (screening) to day 16 ± 1 (end of the study) | Heart rate (HR, bpm) |
| Safety and Tolerability: vital signs - respiratory rate | From day -14 - day -1 (screening) to day 16 ± 1 (end of the study) | Respiratory rate (breaths per minute) |
| Safety and Tolerability: vital signs - body temperature (Celsius temperature scale) | From day -14 - day -1 (screening) to day 16 ± 1 (end of the study) | Body temperature (Celsius temperature scale) |
| Safety and Tolerability: 12-lead electrocardiogram (ECG) - heart rate | From day -14 - day -1 (screening) to day 16 ± 1 (end of the study) | 12-lead ECG (I, II, III, aVR-enhanced unipolar abduction from the right arm , aVL-enhanced unipolar abduction from the left arm, aVF - enhanced unipolar abduction from the left leg, V1-V6): heart rate (beats per minute) |
| Safety and Tolerability: 12-lead electrocardiogram (ECG) - PQ interval | From day -14 - day -1 (screening) to day 16 ± 1 (end of the study) | 12-lead ECG (I, II, III, aVR-enhanced unipolar abduction from the right arm , aVL-enhanced unipolar abduction from the left arm, aVF - enhanced unipolar abduction from the left leg, V1-V6): PQ interval (is the period, measured in milliseconds, that extends from the beginning of the P wave (the onset of atrial depolarization) until the beginning of the QRS complex) |
| Safety and Tolerability: 12-lead electrocardiogram (ECG) - QRS complex | From day -14 - day -1 (screening) to day 16 ± 1 (end of the study) | 12-lead ECG (I, II, III, aVR-enhanced unipolar abduction from the right arm , aVL-enhanced unipolar abduction from the left arm, aVF - enhanced unipolar abduction from the left leg, V1-V6) taken while lying down: QRS complex (the QRS complex is the combination of three of the graphical deflections seen on a typical electrocardiogram) |
| Safety and Tolerability: 12-lead electrocardiogram (ECG) - QT interval | From day -14 - day -1 (screening) to day 16 ± 1 (end of the study) | 12-lead ECG (I, II, III, aVR-enhanced unipolar abduction from the right arm , aVL-enhanced unipolar abduction from the left arm, aVF - enhanced unipolar abduction from the left leg, V1-V6) taken while lying down: QT interval (distance from the beginning of the QRS complex to the end of the T wave) |
| Safety and Tolerability: clinical blood test - hemoglobin | From day -14 - day -1 (screening) to day 16 ± 1 (end of the study) | Hemoglobin (g/L) |
| Safety and Tolerability: clinical blood test - hematocrit | From day -14 - day -1 (screening) to day 16 ± 1 (end of the study) | Hematocrit (%) |
| Safety and Tolerability: clinical blood test - red blood cell count | From day -14 - day -1 (screening) to day 16 ± 1 (end of the study) | Red blood cell count (cells/L) |
| Safety and Tolerability: clinical blood test - platelet count | From day -14 - day -1 (screening) to day 16 ± 1 (end of the study) | Platelet count (cells/L) |
| Safety and Tolerability: clinical blood test - leukocyte count | From day -14 - day -1 (screening) to day 16 ± 1 (end of the study) | Leukocyte count (cells/L) |
| Safety and Tolerability: clinical blood test - erythrocyte sedimentation rate | From day -14 - day -1 (screening) to day 16 ± 1 (end of the study) | Erythrocyte sedimentation rate (mm/h) |
| Safety and Tolerability: clinical blood test - myelocytes | From day -14 - day -1 (screening) to day 16 ± 1 (end of the study) | Leukocyte formula (myelocytes, %) |
| Safety and Tolerability: clinical blood test - band neutrophils | From day -14 - day -1 (screening) to day 16 ± 1 (end of the study) | Leukocyte formula (band neutrophils, %) |
| Safety and Tolerability: clinical blood test - segmented neutrophils | From day -14 - day -1 (screening) to day 16 ± 1 (end of the study) | Leukocyte formula (segmented neutrophils, %) |
| Safety and Tolerability: clinical blood test - eosinophils | From day -14 - day -1 (screening) to day 16 ± 1 (end of the study) | Leukocyte formula (eosinophils, %) |
| Safety and Tolerability: clinical blood test - basophils | From day -14 - day -1 (screening) to day 16 ± 1 (end of the study) | Leukocyte formula (basophils, %) |
| Safety and Tolerability: clinical blood test - monocytes | From day -14 - day -1 (screening) to day 16 ± 1 (end of the study) | Leukocyte formula (monocytes, %) |
| Safety and Tolerability: clinical blood test - lymphocytes | From day -14 - day -1 (screening) to day 16 ± 1 (end of the study) | Leukocyte formula (lymphocytes, %) |
| Safety and Tolerability: blood chemistry - glucose | From day -14 - day -1 (screening) to day 16 ± 1 (end of the study) | Glucose concentration (mmol/L) |
| Safety and Tolerability: blood chemistry - cholesterol | From day -14 - day -1 (screening) to day 16 ± 1 (end of the study) | Total cholesterol concentration (mmol/L) |
| Safety and Tolerability: blood chemistry - total protein | From day -14 - day -1 (screening) to day 16 ± 1 (end of the study) | Total protein in blood serum (g/L) |
| Safety and Tolerability: blood chemistry - bilirubin | From day -14 - day -1 (screening) to day 16 ± 1 (end of the study) | Total bilirubin concentration (micromol/L) |
| Safety and Tolerability: blood chemistry - creatinine | From day -14 - day -1 (screening) to day 16 ± 1 (end of the study) | Creatinine concentration (micromol/L) |
| Safety and Tolerability: blood chemistry - alkaline phosphatase | From day -14 - day -1 (screening) to day 16 ± 1 (end of the study) | Alkaline phosphatase activity (U/L) |
| Safety and Tolerability: blood chemistry - alanine transaminase | From day -14 - day -1 (screening) to day 16 ± 1 (end of the study) | Alanine transaminase activity (U/L) |
| Safety and Tolerability: blood chemistry - aspartate transaminase | From day -14 - day -1 (screening) to day 16 ± 1 (end of the study) | Aspartate transaminase activity (U/L) |
| Safety and Tolerability: urinalysis - specific gravity | From day -14 - day -1 (screening) to day 16 ± 1 (end of the study) | Specific gravity of the urine |
| Safety and Tolerability: urinalysis - color | From day -14 - day -1 (screening) to day 16 ± 1 (end of the study) | Color of the urine |
| Safety and Tolerability: urinalysis - transparency | From day -14 - day -1 (screening) to day 16 ± 1 (end of the study) | Transparency of the urine |
| Safety and Tolerability: urinalysis - pH | From day -14 - day -1 (screening) to day 16 ± 1 (end of the study) | pH of the urine |
| Safety and Tolerability: urinalysis - protein | From day -14 - day -1 (screening) to day 16 ± 1 (end of the study) | Protein concentration (g/L) |
| Safety and Tolerability: urinalysis - glucose | From day -14 - day -1 (screening) to day 16 ± 1 (end of the study) | Glucose concentration (mmol/L) |
| Safety and Tolerability: urinalysis - red blood cells | From day -14 - day -1 (screening) to day 16 ± 1 (end of the study) | Red blood cell content (number in sight) |
| Safety and Tolerability: urinalysis - white blood cells | From day -14 - day -1 (screening) to day 16 ± 1 (end of the study) | White blood cell content (number in sight) |
| Safety and Tolerability: urinalysis - casts | From day -14 - day -1 (screening) to day 16 ± 1 (end of the study) | Presence of casts (Yes/No) |
| Safety and Tolerability: urinalysis - mucus | From day -14 - day -1 (screening) to day 16 ± 1 (end of the study) | Presence of mucus (Yes/No) |
| Safety and Tolerability: urinalysis - bacteria | From day -14 - day -1 (screening) to day 16 ± 1 (end of the study) | Presence of bacteria (Yes/No) |
Countries
Russia
Outcome results
None listed