Back to resultsPA Tolerability, Safety and Pharmacokinetics in Healthy Volunteers (PA)
Primary Purpose
Infections, Respiratory
Status
Completed
Phase
Phase 1
Locations
Kazakhstan
Study Type
Interventional
Intervention
Potentiator of antibiotics (PA)
Placebo PA
Sponsored by
About this trial
This is an interventional other trial for Infections, Respiratory focused on measuring Safety, Iodine complex, Pharmacokinetics, Antibiotic potentiator
Eligibility Criteria
Inclusion Criteria:
- Age 18 to 55 years
- Body mass index 16 to 30
- Subjects should be in good physical and mental health based on medical history, clinical examination and laboratory investigations
- Subjects should have signed informed consent prior to screening and the clinical study after they have read and understood the objective, conduct, risks related to the study, and their rights as study participants
- Subjects should have signed informed consent for being tested for HIV
- Subjects should have signed informed consent to be tested for alcoholemia, use of cannabinoids, cocaine, morphine, benzodiazepines, barbiturates and amphetamine
Exclusion Criteria:
- Subjects should not have evidence of any physical and/or mental health issues at screening and/or results of any clinical, laboratory and/or technical procedures at screening outside of the normal range
- Subjects should not be taking any concomitant medication
- Subjects should not have a history of allergies, hypersensitivity or intolerance to iodine or iodide or to medicines containing iodine such as contrast media used for radiologic examinations
- Subjects should not have a history of addiction or abuse of drugs or alcohol
- Subjects should not be in a position of subordination or other dependence on persons involved in the study such as sponsor, investigators, or any other person or institution interested in its results
- Subjects should not be members of the armed forces or prison inmates
- Subjects should not have positive serology for Hepatitis B, Hepatitis C or HIV
- Subjects should not have any apparent functional and/or physical defects which may or interfere with the study or distort results
Sites / Locations
- Institute Of Cardiology & Internal Diseases
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Potentiator of antibiotics (PA)
Patients taking placebo PA
Arm Description
Potenciator of antibiotics (PA) , albumin complex of tetraiodid was given per os, single and multiple doses for the different periods (but not exceeding 14 days)
Placebo without any active pharmaceutical ingredients was given per os dosed for the patients in same periods of time as per experimental group, single and multiple doses for the different periods (but not exceeding 14 days)
Outcomes
Primary Outcome Measures
Adverse Events (AE)
The safety of ascending single and multiple doses of Study Drug in healthy male subjects will be assessed by adverse event and serious adverse event monitoring.
Secondary Outcome Measures
Area under plasma concentration time curve (AUC∞)
AUC∞ characterizes the total concentration of a drug in serum during the entire observation time. AUC0-∞ is area under the сurve concentration of a drug in blood versus time during the entire observation time. It is calculated on the basis of experimental data. It is measured in μg*hours/liter.
Maximum concentration of drug in the blood (Cmax)
Maximum concentration of drug in the blood after its intake. It is measured in μg /liter.
Time to reach maximum drug concentration (Tmax)
The time required to reach maximum concentration of the drug in blood. Determined by measurements. It is measured in hours.
Half-life time (T1/2)
The interval of time required to eliminate the half of drug dose from blood. It is calculated on the basis of experimental data. It is measured in hours.
Total clearance (СL)
The total clearance is the volume of plasma from which a substance is completely removed per the unit of time. It is calculated on the basis of experimental data. Clearance is measured in liters / hour * kg of body weight.
Mean residence time of drug (MRT)
MRT is the average time of the drug molecules stays in the body. It is calculated on the basis of experimental data. It is measured in hours.
Drug excretion (%)
Drug excretion with urine over specified periods of time. It is calculated on the basis of experimental data. It is defined as a percentage (%) of single dose or of the total drug amount during its multiple use.It is measured in percents (%).
Volume of distribution (Vλz)
Volume of distribution is the theoretical volume that would be necessary to contain the total amount of an administered drug at the same concentration that it is observed in the blood plasma. Volume of distribution of the drug in blood is calculated base on terminal phase of drug pharmacokinetic curve. Volume of distribution is an apparent volume that would be necessary to contain the total amount of an administered drug at the same concentration that it is observed in the blood plasma. It is evaluated on the basis of experimental data. It is measured in liters / kg.
Drug elimination rate constant (Lambda-z (λz))
Drug elimination rate constant in the terminal phase of the pharmacokinetic curve. Elimination rate constant characterizes absorption and excretion. It is measured in 1/hours.
Accumulation index (Rac)
The degree of accumulation of the drug in the blood at multiple-dose administration. It is evaluated on basis experimental data.
Change in thyroid stimulating hormone (TSH)
TSH stimulates the thyroid gland to synthesize and secrete thyroid hormone. TSH serum measurements are used to detect primary hypo- and hyperthyroidism. The capability of a TSH assay to distinguish between normal and subnormal concentrations is essential for thyroid testing strategy. It is measured in milli international units per liter (mlU/L). Normal range for the study: 0.5-4.8 mlU/L.
Change in total triiodothyronine (TT3)
Total triiodothyronine measured in serum and used to diagnose thyroid diseases such as hyperthyroidism and T3-thyrotoxicosis. It is measured in nmol/L. Normal range for the study: 0.85-2.62 nmol/L.
Change in free triiodothyronine (FT3)
The FT3 is not bound to transport proteins in the circulating blood (unbound T3). It is metabolically active. T3 plays an important role in regulating metabolism. The Free T3 test helps determine whether the thyroid is functioning properly. It is to help diagnose hyperthyroidism and monitor the progress of a patient with a thyroid disorder. It is measured in pmol/L. Normal range for the study: 3.5-6.5 pmol/L.
Change in total thyroxine (TT4)
Total thyroxine is a hormone used to help diagnose hyper- and hypothyroidism. The TT4 test is usually used with a TSH test to help determine whether the thyroid hormone feedback system is functioning properly, and the results help to distinguish between causes of hyper- and hypothyroidism. It is measured in nmol/L. Normal range for the study: 54 -167 nmol/L.
Change in free thyroxine (FT4)
The FT4 is an unbound fraction of thyroxine. It is not bound to transport proteins, free in the circulation. The free T4 is metabolically active. It is used in combination with TSH for the diagnosis of thyroid disorders and follow-up of patients with thyroid disorders. It is measured in pmol/L. Normal range for the study: 10-22 pmol/L.
Change in anti-thyroglobulin antibody
Thyroglobulin (Tg) is a glycoprotein found in thyroid follicular cells that plays a critical role in the biosynthesis of key thyroid hormones. The measurement of anti-TG antibody has been shown to be an aid in the diagnosis of thyroid disorders. It is measured in kilo international units per liter (klU/L). Normal range for the study: up to 40 klU/L.
Change in anti-thyroid peroxidase antibody
Anti-thyroid peroxidase antibody is a protein found in thyroid follicular cells, is a catalyst in the synthesis of key thyroid hormones. Elevated levels of anti-TPO antibody are a risk factor for autoimmune thyroid diseases. It is measured in klU/L. Normal range for the study: up to 35 klU/L.
Change from baseline in thyroid ultrasound
Thyroid Ultrasound is used to assess the size of the Thyroid gland and to find out if there are nodules or lesions within the gland. Also the test is used to suspect thyroid disease at screening visit to not include volunteer into the trial.
Change from baseline in electrocardiogram (ECG)
A 12-lead resting ECG with a 10 second rhythm strip to be recorded, which includes PR, QT, and QTc intervals as well as QRS interval duration. ECG will be interpreted as "normal", "abnormal, not clinically significant", or "abnormal, clinically significant". Findings classified as "abnormal, clinically significant" will be registered as adverse events if evaluated after dosing.
Change in Respiratory Rate
Respiratory rate is an essential vital sign and a fundamental element of patient assessment. It is assessed in combination with heart rate, blood pressure, body temperature. It is measured by counting the breaths (number of times the chest moves up and down) for a full minute in relaxed condition. Normal range for the study is 12-20 breaths per minute.
Change in Heart Rate
The heart rate is one of the vital signs. It measures the number of times the heart beats per minute. It is measured in relaxed condition by checking the pulse. To calculate the beats per minute, the patient's pulse is counted for 15 seconds and multiplied by four. Normal range for the study is 60-90 beats per minute.
Change in Blood Pressure
Blood Pressure is measured with a sphygmomanometer in a resting condition in three hours after study drug intake, before blood sampling. Subjects should abstain from eating, drinking, smoking one hour before measurement. The bladder should have been emptied. Subject should have been sitting quietly for about 5 minutes before the measurement. Tight clothes should have been removed. Measurements should be taken in sitting position so that the arm and back are supported. Blood Pressure is measured in millimeters of mercury (mm Hg). The systolic and diastolic blood pressure is recorded.
Change in Body Temperature
Body Temperature is measured with a mercury thermometer in the armpit in a resting condition three hours after study drug intake, before blood sampling.
Symptoms of musculoskeletal system
The symptoms are recorded as a score on a scale. If there are no symptoms the result is reported as "Normal" (score=0). If there are any musculoskeletal symptoms the result is reported as "Abnormal". Each symptom will be estimated as "Clinically non-significant" (score=1) or "Clinically significant"(score=2) and described. The relationship of symptoms with the study drug is assessed as:"Definitely related"(score=3); "Probably related"(score=2); "Possibly related"(score=1); "Not related"(score=0). The scores of clinical significance are summarized with the score of the drug relation. The higher scores mean a worse outcome.
Symptoms of cardiovascular system
The symptoms are recorded as a score on a scale. If there are no symptoms the result is reported as "Normal" (score=0). If there are any cardiovascular symptoms the result is reported as "Abnormal". Each symptom will be estimated as "Clinically non-significant" (score=1) or "Clinically significant"(score=2) and described. The relationship of symptoms with the study drug is assessed as:"Definitely related"(score=3); "Probably related"(score=2); "Possibly related"(score=1); "Not related"(score=0). The scores of clinical significance are summarized with the score of the drug relation. The higher scores mean a worse outcome.
Symptoms of lymphatic system
The symptoms are recorded as a score on a scale. If there are no symptoms the result is reported as "Normal" (score=0). If there are any lymphatic symptoms the result is reported as "Abnormal". Each symptom will be estimated as "Clinically non-significant" (score=1) or "Clinically significant"(score=2) and described. The relationship of symptoms with the study drug is assessed as:"Definitely related"(score=3); "Probably related"(score=2); "Possibly related"(score=1); "Not related"(score=0). The scores of clinical significance are summarized with the score of the drug relation. The higher scores mean a worse outcome.
Symptoms of nervous system
The symptoms are recorded as a score on a scale. If there are no symptoms the result is reported as "Normal" (score=0). If there are any nervous symptoms the result is reported as "Abnormal". Each symptom will be estimated as "Clinically non-significant" (score=1) or "Clinically significant"(score=2) and described. The relationship of symptoms with the study drug is assessed as:"Definitely related"(score=3); "Probably related"(score=2); "Possibly related"(score=1); "Not related"(score=0). The scores of clinical significance are summarized with the score of the drug relation. The higher scores mean a worse outcome.
Symptoms of Respiratory system
The symptoms are recorded as a score on a scale. If there are no symptoms the result is reported as "Normal" (score=0). If there are any Respiratory symptoms the result is reported as "Abnormal". Each symptom will be estimated as "Clinically non-significant" (score=1) or "Clinically significant"(score=2) and described. The relationship of symptoms with the study drug is assessed as:"Definitely related"(score=3); "Probably related"(score=2); "Possibly related"(score=1); "Not related"(score=0). The scores of clinical significance are summarized with the score of the drug relation. The higher scores mean a worse outcome.
Symptoms of Gastrointestinal system
The symptoms are recorded as a score on a scale. If there are no symptoms the result is reported as "Normal" (score=0). If there are any gastrointestinal symptoms the result is reported as "Abnormal". Each symptom will be estimated as "Clinically non-significant" (score=1) or "Clinically significant"(score=2) and described. The relationship of symptoms with the study drug is assessed as:"Definitely related"(score=3); "Probably related"(score=2); "Possibly related"(score=1); "Not related"(score=0). The scores of clinical significance are summarized with the score of the drug relation. The higher scores mean a worse outcome.
Symptoms of urinary system
The symptoms are recorded as a score on a scale. If there are no symptoms the result is reported as "Normal" (score=0). If there are any urinary symptoms the result is reported as "Abnormal". Each symptom will be estimated as "Clinically non-significant" (score=1) or "Clinically significant"(score=2) and described. The relationship of symptoms with the study drug is assessed as:"Definitely related"(score=3); "Probably related"(score=2); "Possibly related"(score=1); "Not related"(score=0). The scores of clinical significance are summarized with the score of the drug relation. The higher scores mean a worse outcome.
Symptoms of Endocrine system
The symptoms are recorded as a score on a scale. If there are no symptoms the result is reported as "Normal" (score=0). If there are any endocrine system symptoms the result is reported as "Abnormal". Each symptom will be estimated as "Clinically non-significant" (score=1) or "Clinically significant"(score=2) and described. The relationship of symptoms with the study drug is assessed as:"Definitely related"(score=3); "Probably related"(score=2); "Possibly related"(score=1); "Not related"(score=0). The scores of clinical significance are summarized with the score of the drug relation. The higher scores mean a worse outcome.
Symptoms of Skin and subcutaneous tissue
The symptoms are recorded as a score on a scale. If there are no symptoms the result is reported as "Normal" (score=0). If there are any skin and subcutaneous tissue symptoms the result is reported as "Abnormal". Each symptom will be estimated as "Clinically non-significant" (score=1) or "Clinically significant"(score=2) and described. The relationship of symptoms with the study drug is assessed as:"Definitely related"(score=3); "Probably related"(score=2); "Possibly related"(score=1); "Not related"(score=0). The scores of clinical significance are summarized with the score of the drug relation. The higher scores mean a worse outcome.
Change in Alanine transaminase (ALT)
The ALT test measures the amount of ALT in the blood. High levels of ALT in the blood can indicate a liver problem, even before clinical signs of liver disease. It is measured in IU/L. Normal range for the study: ≤ 45 IU/L.
Change in Aspartate aminotransferase (AST)
The AST blood test measures the amount of AST in the blood. AST is an enzyme that is found mostly in the liver. AST releases into bloodstream when liver is damaged. The test can help to diagnose liver damage or disease. It is measured in IU/L. Normal range for the study: ≤ 41 IU/L.
Change in Bilirubin / bilirubin fractions
The level of bilirubin is measured in the blood by the bilirubin blood test. Direct bilirubin is water-soluble form of bilirubin. Indirect bilirubin is fat-soluble form of bilirubin.
Direct and indirect are measured solely. Total and direct bilirubin levels can be measured from the blood, but indirect bilirubin is calculated from the total and direct bilirubin. It is measured in μmol/L. Normal range for the study: 8,6-20,5 μmol/L.
Change in Creatinine
Serum creatinine is measured in the blood. Creatinine measurements are used in the trial as the indicator of kidney function. Elevated creatinine level signifies impaired kidney function or kidney disease. As the kidneys become impaired for any reason, the creatinine level in the blood will rise due to poor clearance of creatinine by the kidneys. Abnormally high levels of creatinine thus warn of possible malfunction or failure of the kidneys. It is measured in μmol/L. Normal range for the study: ≤133 μmol/L.
Change in Alkaline phosphatase
The alkaline phosphatase is measured in the blood. High levels of alkaline phosphatase may indicate the liver damage. It is measured in IU/L. Normal range for the study: 40-129 IU/L.
Change in Blood Urea Nitrogen
The amount of urea nitrogen is measured in the blood. The urea is produced by liver in the urea cycle as a waste product of the digestion of proteins. The elevated levels of Blood Urea Nitrogen may be a sign that that kidneys aren't working efficiently. The accumulation of urea and other nitrogen-containing compounds in the blood due to renal failure leads to uremia. The main causes of an increase in Blood Urea Nitrogen are: high protein diet, decrease in glomerular filtration rate (suggestive of renal failure), decrease in blood volume (hypovolemia), congestive heart failure, gastrointestinal hemorrhage,[4] fever, and increased catabolism. Hypothyroidism can cause both decreased glomerular filtration rate and hypovolemia, but Blood Urea Nitrogen -to-creatinine ratio has been found to be lowered in hypothyroidism and raised in hyperthyroidism. It is measured in mmol/L. Normal range for the study: ≤8.3 mmol/L.
Change in Uric acid
Uric acid is a product of the metabolic breakdown of purine nucleotides, and it is a normal component of urine. High blood concentrations of uric acid may be caused by study drug, hypothyroidism, kidney damage and called hyperuricemia. It can lead to gout and are associated with other medical conditions, including diabetes and the formation of ammonium acid urate kidney stones.
Uric acid in blood is measured in mmol/L. Normal range for the study: ≤480 mmol/L.
Change in Alpha-amylase (α-amylase)
α-amylase is an enzyme that catalyze the hydrolysis of starch into smaller carbohydrate molecules.
The alpha-amylase is produced by the salivary glands, whereas pancreatic amylase is secreted by the pancreas into the small intestine. Both the salivary and pancreatic amylases are α-amylases.
Blood serum amylase may be increased in case of the pancreas damage by the study drug. α-amylase in blood is measured in mmol/L. Normal range for the study: 28-100 U/L
Change in Serum total protein
Protein in the serum consists of albumin and globulin. Protein fractions are determined using electrophoresis. Total protein levels in the blood give a general indication of the state of hydration, nutrition or proper functioning of certain major organs such as the liver, kidneys or bone marrow. Total protein in blood is measured in g/L. Normal range for the study: 64-83 g/L. Concentrations below the reference range may be a sign of low albumin concentration, liver damage, acute inflammation, or a problem of malnutrition or malabsorption of amino acids necessary for protein formation. It may be also a sign of immunodeficiency. Too much protein loss from the kidneys or too much water in the blood can also cause hypoproteinemia. Concentrations above the reference range (hyperproteinemia) may indicate dehydration or an increase in the gammaglobulin fraction, as found in chronic inflammatory diseases, certain viral infections or bone marrow disorders.
Change in Albumin level in blood
Albumin is a protein made by the liver. Albumin is measured in the blood. Albumin carries substances such as hormones, medicines, and enzymes throughout the body. Low albumin levels can indicate a problem with the liver or kidneys. Albumin in blood is measured in g/L. Normal range for the study: 35-55 g/L.
Change in Glucose level in blood
Measuring blood glucose levels is primarily used to monitor blood sugar levels to diagnose hyperglycemia or hypoglycemia caused by study drug. It is measured in fasting condition. Glucose in blood is measured in mmol/L. Normal range for the study: 4,11-5,89 mmol/L.
Change in Total cholesterol
It is measured in the blood. It includes all the cholesterol in all the lipoprotein particles: high-density lipoprotein cholesterol (HDL) and low-density lipoprotein cholesterol (LDL).
Total cholesterol in blood is measured in mmol/L. Normal range for the study: ≤5.2 mmol/L. It is used to diagnose the metabolism of lipids and the liver function.
Change in Potassium in blood
Measurement of the amount of potassium in the blood helps to diagnose an electrolyte imbalance caused by study drug. Changed potassium level (hypokaliemia, hyperkaliemia) may cause such problems as muscle weakness or contractions, nerve signals transmission, cardiac arrhythmia, hypertension, may affect the kidney function and hormone release. Potassium in the blood is measured in mmol/L. Normal range for the study: 3.5 - 5.3 mmol/L
Change in Serum calcium
Measurement of the amount of calcium in the blood helps to diagnose an electrolyte imbalance caused by study drug. Changed calcium level (hypocalcaemia, hypercalcaemia) may influence the proper functioning of muscles, nerves, and the heart, coagulation, maintenance of bones and teeth.Calcium in the blood is measured in mmol/L. Normal range for the study: 2,15-2,55 mmol/L.
Change in Serum magnesium
Measurement of the amount of magnesium in the blood helps to diagnose an electrolyte imbalance caused by study drug. Abnormal levels of magnesium may influence the proper functioning of muscles, nerves, and the heart, helps control blood pressure and blood sugar. Low level of magnesium in the body may cause numerous symptoms: poor coordination, muscle spasms, loss of appetite, personality changes, and nystagmus. Magnesium in the blood is measured in mmol/L. Normal range for the study: 0,65- 1,5 mmol/L.
Change in erythrocytes number in blood
The influence of the study drug on the number and morphology of erythrocytes will be assessed. Normal range for the study: 3,9-5,5 х10^12 per liter.
Change in hemoglobin
The influence of the study drug on to the amount of hemoglobin will be assessed. Normal range for the study: 130-180 g/L.
Change in leucocytes number in the blood
The influence of the study drug on the number and morphology of leucocytes will be assessed. Normal range for the study: 4,0-9,0 х10^9 per liter.
Change in thrombocytes number in the blood
The influence of the study drug on the number and morphology of thrombocytes will be assessed. Normal range for the study: 180-400 х10^9 per liter.
Change in hematocrit
It is the percentage of red blood cells (RBC's) in the blood. The hematocrit test indicates the percentage of blood by volume that is composed of red blood cells. A hematocrit is measured in L/L (litre of cells per litre of blood). Normal range for the study: 36-55% .
Change in Erythrocyte Sedimentation Rate (ESR))
ESR indirectly measures the degree of inflammation present in the body. The test actually measures the rate sedimentation of erythrocytes in a sample of blood that has been placed into a tall, thin, vertical tube. Results are reported as the millimeters of plasma that are present at the top portion of the tube after one hour. The ESR is non-specific test that provides general information about the presence or absence of an inflammatory condition. Normal range for the study: 2-10 mm/hour.
Change in prothrombin index
Measured in percents. Normal range for the study: 70-130 %
Change in activated partial thromboplastin time (aPTT)
Measured in seconds. Normal range for the study: 23-38 seconds
Change in prothrombin ratio
The ratio of a patient's prothrombin time to a normal (control) sample, raised to the power of the ISI value for the analytical system being used. Measured as a ratio. Normal range for the study:0,9-1,2
Change in thrombin time
Thrombin clotting time measures the time it takes for a clot to form in the plasma of a blood sample containing anticoagulant, after an excess of thrombin has been added.Measured in seconds. Normal range for the study:15-21 seconds
Change of protein level in urine
Proteinuria caused by study drug will be assessed. It may be due to kidney damage, heart failure, loss of body fluids (dehydration), high blood pressure. Protein level in urine is measured in mg/L.
Change in Urinary glucose
Glycosuria caused by study drug will be assessed. Measured in mmol/L Normal range for the study: 0 to 0.8 mmol/L.
Hematuria
Hematuria caused by study drug will be assessed.It is measured in the number of red blood cells per high-power field in microscopic investigation of urine sediment.
Leucocyturia
Leucocytes in urine after study drug intake will be assessed. Leucocyturia may be due to inflammation of the urinary track or adjacent tissue. It is measured in the number of white blood cells per high-power field in microscopic investigation of urine sediment.
Ketonuria
Ketone bodies present in the urine after study drug intake will be assessed. It may be due to excess ketones production as an indication that the body is using an alternative source of energy. It is measured in mg/dL. A negative test result is normal.
An abnormal result: small ketonuria: <20 mg/dL; moderate ketonuria: 30 to 40 mg/dL; large ketonuria: >80 mg/dL
Change in urine pH
The influence of study drug on to urine pH will be evaluated. The normal values range from pH 4.6 to 8.0
Change in immunoglobulin A (IgA) level in blood
The influence of study drug onto IgA level in blood will be evaluated. It is measured in g/L. Normal range for the study: 0,7-4,0 g/L.
Change in immunoglobulin M (IgM) level in blood
The influence of study drug onto IgM level in blood will be evaluated. It is measured in g/L. Normal range for the study: 0,4-2,3 g/L.
Change in immunoglobulin G (IgG) level in blood
The influence of study drug onto IgG level in blood will be evaluated. It is measured in g/L. Normal range for the study: 7-16 g/L.
Change in immunoglobulin E (IgE) level in blood
The influence of study drug onto IgE level in blood will be evaluated. It is measured in IU/ml . Normal range for the study: 0,100-200,0 IU/ml.
Change in Rheumatoid factor
The influence of study drug onto Rheumatoid factor in blood will be evaluated. It is measured in IU/ml . Normal range for the study: 0-25 IU/ml.
Change in C-Reactive Protein
The influence of study drug onto C-Reactive Protein in blood will be evaluated. It is measured in mg/l . Normal range for the study: 0-5 mg/l
Change in Antimitochondrial Antibody
The influence of study drug on Antimitochondrial Antibody in blood will be evaluated. It is measured in IU/ml. Normal range for the study: 0-10 IU/ml
Change in antinuclear antibody
The influence of study drug on antinuclear antibody in blood will be evaluated. It is measured in IU/ml. Normal range for the study: 0-40 IU/ml
Change from baseline in CD3+tcells
The influence of study drug on CD3+ tcells percent in blood will be evaluated. Normal range for the study: 52-76 %
Change from baseline in CD4+tcells
The influence of study drug on CD4+ tcells percent in blood will be evaluated. Normal range for the study: 31-46 %
Change from baseline in CD8+tcells
The influence of study drug on CD8+ tcells percent in blood will be evaluated. Normal range for the study: 23-40 %
Change from baseline in Ratio CD4/CD8
The influence of study drug on Ratio CD4/CD8 in blood will be evaluated. Normal range for the study: 1.2-2.0 %
Full Information
NCT ID
NCT04174937
First Posted
December 7, 2017
Last Updated
November 20, 2019
Sponsor
Scientific Center for Anti-infectious Drugs, Kazakhstan
Collaborators
Institute Of Cardiology & Internal Diseases, Kazakhstan, Al-Farabi Kazakh National University (KazNU)
1. Study Identification
Unique Protocol Identification Number
NCT04174937
Brief Title
PA Tolerability, Safety and Pharmacokinetics in Healthy Volunteers
Acronym
PA
Official Title
A Randomized, Placebo-controlled Study of the Tolerability, Safety and Pharmacokinetics of PA in Healthy Volunteers
Study Type
Interventional
2. Study Status
Record Verification Date
November 2019
Overall Recruitment Status
Completed
Study Start Date
June 17, 2016 (Actual)
Primary Completion Date
May 15, 2019 (Actual)
Study Completion Date
September 15, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Scientific Center for Anti-infectious Drugs, Kazakhstan
Collaborators
Institute Of Cardiology & Internal Diseases, Kazakhstan, Al-Farabi Kazakh National University (KazNU)
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This is a first-in-human (FIH) study to explore the safety, tolerability and pharmacokinetics of PA after oral ascending dose administration to healthy male volunteers.
Detailed Description
The first-in-human dose (FHD) trial is a randomized, double-blind, placebo-controlled, dose-escalation trial assessing safety, tolerability and pharmacokinetics (PK) of single and multiple oral doses of PA in healthy male subjects.
The study consists of two stages: single dose administration and multiple dose administration.
The single dose administration stage includes 5 cohorts, multiple dose administration stage includes at least 4 cohorts (groups). Each cohort includes 8 subjects (6 active drugs and 2 placebos). Cohorts intake ascending doses of study drug. The dose of 1st cohort is 1,0 mg/ml, the doses for the following cohorts will be estimated by the Data Monitoring Committee based on pharmacokinetics and safety results of previous group.
For each subject study includes screening period, one baseline period on Day -1, a treatment period (1 day - at single dose stage; 14 days - at multiple dose stage), followed by safety, PK, assessments up to 72-96 hours post dose. Follow-up visits will take place on Day 7 ; 30; 60 (single dose stage) and 30; 60; 90 (multiple dose stage).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Infections, Respiratory
Keywords
Safety, Iodine complex, Pharmacokinetics, Antibiotic potentiator
7. Study Design
Primary Purpose
Other
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
72 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Potentiator of antibiotics (PA)
Arm Type
Experimental
Arm Description
Potenciator of antibiotics (PA) , albumin complex of tetraiodid was given per os, single and multiple doses for the different periods (but not exceeding 14 days)
Arm Title
Patients taking placebo PA
Arm Type
Placebo Comparator
Arm Description
Placebo without any active pharmaceutical ingredients was given per os dosed for the patients in same periods of time as per experimental group, single and multiple doses for the different periods (but not exceeding 14 days)
Intervention Type
Drug
Intervention Name(s)
Potentiator of antibiotics (PA)
Other Intervention Name(s)
Albumin complex of tetraiodide
Intervention Description
Intervention is administered to patients in this Arm
Intervention Type
Other
Intervention Name(s)
Placebo PA
Intervention Description
Intervention is administered to patients in this Arm
Primary Outcome Measure Information:
Title
Adverse Events (AE)
Description
The safety of ascending single and multiple doses of Study Drug in healthy male subjects will be assessed by adverse event and serious adverse event monitoring.
Time Frame
Adverse event reporting will be performed throughout the trial from the Screening visit until the Final visit (up to 90 days)
Secondary Outcome Measure Information:
Title
Area under plasma concentration time curve (AUC∞)
Description
AUC∞ characterizes the total concentration of a drug in serum during the entire observation time. AUC0-∞ is area under the сurve concentration of a drug in blood versus time during the entire observation time. It is calculated on the basis of experimental data. It is measured in μg*hours/liter.
Time Frame
Blood collections at the following time points: before drug intake (two points - 1 day and 10 min), and 5 min, 15 min, 30 min, and 1, 1.5; 2; 3; 6; 9; 12; 15; 24; 48 and 72 hours after study drug administration
Title
Maximum concentration of drug in the blood (Cmax)
Description
Maximum concentration of drug in the blood after its intake. It is measured in μg /liter.
Time Frame
Blood collections at the following time points: before drug intake (two points - 1 day and 10 min), and 5 min, 15 min, 30 min, and 1, 1.5; 2; 3; 6; 9; 12; 15; 24; 48 and 72 hours after study drug administration
Title
Time to reach maximum drug concentration (Tmax)
Description
The time required to reach maximum concentration of the drug in blood. Determined by measurements. It is measured in hours.
Time Frame
Blood collections at the following time points: before drug intake (two points - 1 day and 10 min), and 5 min, 15 min, 30 min, and 1, 1.5; 2; 3; 6; 9; 12; 15; 24; 48 and 72 hours after study drug administration
Title
Half-life time (T1/2)
Description
The interval of time required to eliminate the half of drug dose from blood. It is calculated on the basis of experimental data. It is measured in hours.
Time Frame
Blood collections at the following time points: 5 min, 15 min, 30 min, and 1, 1.5; 2; 3; 6; 9; 12; 15; 24; 48 and 72 hours after study drug administration
Title
Total clearance (СL)
Description
The total clearance is the volume of plasma from which a substance is completely removed per the unit of time. It is calculated on the basis of experimental data. Clearance is measured in liters / hour * kg of body weight.
Time Frame
Blood collections at the following time points: before drug intake (two points - 1 day and 10 min), and 5 min, 15 min, 30 min, and 1, 1.5; 2; 3; 6; 9; 12; 15; 24; 48 and 72 hours after study drug administration
Title
Mean residence time of drug (MRT)
Description
MRT is the average time of the drug molecules stays in the body. It is calculated on the basis of experimental data. It is measured in hours.
Time Frame
Blood collections at the following time points: before drug intake (two points - 1 day and 10 min), and 5 min, 15 min, 30 min, and 1, 1.5; 2; 3; 6; 9; 12; 15; 24; 48 and 72 hours after study drug administration
Title
Drug excretion (%)
Description
Drug excretion with urine over specified periods of time. It is calculated on the basis of experimental data. It is defined as a percentage (%) of single dose or of the total drug amount during its multiple use.It is measured in percents (%).
Time Frame
Urine samples taken during 0-96 h after drug intake
Title
Volume of distribution (Vλz)
Description
Volume of distribution is the theoretical volume that would be necessary to contain the total amount of an administered drug at the same concentration that it is observed in the blood plasma. Volume of distribution of the drug in blood is calculated base on terminal phase of drug pharmacokinetic curve. Volume of distribution is an apparent volume that would be necessary to contain the total amount of an administered drug at the same concentration that it is observed in the blood plasma. It is evaluated on the basis of experimental data. It is measured in liters / kg.
Time Frame
Blood collections at the following time points: 5 min, 15 min, 30 min, and 1, 1.5; 2; 3; 6; 9; 12; 15; 24; 48 and 72 hours after study drug administration
Title
Drug elimination rate constant (Lambda-z (λz))
Description
Drug elimination rate constant in the terminal phase of the pharmacokinetic curve. Elimination rate constant characterizes absorption and excretion. It is measured in 1/hours.
Time Frame
0-72 hours
Title
Accumulation index (Rac)
Description
The degree of accumulation of the drug in the blood at multiple-dose administration. It is evaluated on basis experimental data.
Time Frame
Blood sampling at multiple dosing: Day 1-17
Title
Change in thyroid stimulating hormone (TSH)
Description
TSH stimulates the thyroid gland to synthesize and secrete thyroid hormone. TSH serum measurements are used to detect primary hypo- and hyperthyroidism. The capability of a TSH assay to distinguish between normal and subnormal concentrations is essential for thyroid testing strategy. It is measured in milli international units per liter (mlU/L). Normal range for the study: 0.5-4.8 mlU/L.
Time Frame
Screening visit; Single dose intake: Day 1 - before and 12 hours after dose; Day 2; Day 3; Day 60. Multiple dose intake: Day 1 - before and 12 hours after dosing; Days 2;3;5;9;14;17;30;60;90
Title
Change in total triiodothyronine (TT3)
Description
Total triiodothyronine measured in serum and used to diagnose thyroid diseases such as hyperthyroidism and T3-thyrotoxicosis. It is measured in nmol/L. Normal range for the study: 0.85-2.62 nmol/L.
Time Frame
Screening visit; Single dose intake: Day 1 - before and 12 hours after dose; Day 2; Day 3; Day 60. Multiple dose intake: Day 1 - before and 12 hours after dosing; Days 2;3;5;9;14;17;30;60;90
Title
Change in free triiodothyronine (FT3)
Description
The FT3 is not bound to transport proteins in the circulating blood (unbound T3). It is metabolically active. T3 plays an important role in regulating metabolism. The Free T3 test helps determine whether the thyroid is functioning properly. It is to help diagnose hyperthyroidism and monitor the progress of a patient with a thyroid disorder. It is measured in pmol/L. Normal range for the study: 3.5-6.5 pmol/L.
Time Frame
Screening visit; Single dose intake: Day 1 - before and 12 hours after dose; Day 2; Day 3; Day 60. Multiple dose intake: Day 1 - before and 12 hours after dosing; Days 2;3;5;9;14;17;30;60;90
Title
Change in total thyroxine (TT4)
Description
Total thyroxine is a hormone used to help diagnose hyper- and hypothyroidism. The TT4 test is usually used with a TSH test to help determine whether the thyroid hormone feedback system is functioning properly, and the results help to distinguish between causes of hyper- and hypothyroidism. It is measured in nmol/L. Normal range for the study: 54 -167 nmol/L.
Time Frame
Screening visit; Single dose intake: Day 1 - before and 12 hours after dose; Day 2; Day 3; Day 60. Multiple dose intake: Day 1 - before and 12 hours after dosing; Days 2;3;5;9;14;17;30;60;90
Title
Change in free thyroxine (FT4)
Description
The FT4 is an unbound fraction of thyroxine. It is not bound to transport proteins, free in the circulation. The free T4 is metabolically active. It is used in combination with TSH for the diagnosis of thyroid disorders and follow-up of patients with thyroid disorders. It is measured in pmol/L. Normal range for the study: 10-22 pmol/L.
Time Frame
Screening visit; Single dose intake: Day 1 - before and 12 hours after dose; Day 2; Day 3; Day 60. Multiple dose intake: Day 1 - before and 12 hours after dosing; Days 2;3;5;9;14;17;30;60;90
Title
Change in anti-thyroglobulin antibody
Description
Thyroglobulin (Tg) is a glycoprotein found in thyroid follicular cells that plays a critical role in the biosynthesis of key thyroid hormones. The measurement of anti-TG antibody has been shown to be an aid in the diagnosis of thyroid disorders. It is measured in kilo international units per liter (klU/L). Normal range for the study: up to 40 klU/L.
Time Frame
Screening visit; Single dose intake: Day 1 - before and 12 hours after dose; Day 2; Day 3; Day 60. Multiple dose intake: Day 1 - before and 12 hours after dosing; Days 2;3;5;9;14;17;30;60;90
Title
Change in anti-thyroid peroxidase antibody
Description
Anti-thyroid peroxidase antibody is a protein found in thyroid follicular cells, is a catalyst in the synthesis of key thyroid hormones. Elevated levels of anti-TPO antibody are a risk factor for autoimmune thyroid diseases. It is measured in klU/L. Normal range for the study: up to 35 klU/L.
Time Frame
Screening visit; Single dose intake: Day 1 - before and 12 hours after dose; Day 2; Day 3; Day 60. Multiple dose intake: Day 1 - before and 12 hours after dosing; Days 2;3;5;9;14;17;30;60;90
Title
Change from baseline in thyroid ultrasound
Description
Thyroid Ultrasound is used to assess the size of the Thyroid gland and to find out if there are nodules or lesions within the gland. Also the test is used to suspect thyroid disease at screening visit to not include volunteer into the trial.
Time Frame
Screening visit; Final visit (Day 60 - at Single dose intake; Day 90 - at Multiple dose intake)
Title
Change from baseline in electrocardiogram (ECG)
Description
A 12-lead resting ECG with a 10 second rhythm strip to be recorded, which includes PR, QT, and QTc intervals as well as QRS interval duration. ECG will be interpreted as "normal", "abnormal, not clinically significant", or "abnormal, clinically significant". Findings classified as "abnormal, clinically significant" will be registered as adverse events if evaluated after dosing.
Time Frame
Screening visit; before dose (Day -1); Day 1 - after dose (4 hours); Final visit (Day 60). Multiple dose intake: before dose (Day -1); Day 1 and 15 - 4 hours after dose; Final visit (Day 90).
Title
Change in Respiratory Rate
Description
Respiratory rate is an essential vital sign and a fundamental element of patient assessment. It is assessed in combination with heart rate, blood pressure, body temperature. It is measured by counting the breaths (number of times the chest moves up and down) for a full minute in relaxed condition. Normal range for the study is 12-20 breaths per minute.
Time Frame
every visit up to 90 days
Title
Change in Heart Rate
Description
The heart rate is one of the vital signs. It measures the number of times the heart beats per minute. It is measured in relaxed condition by checking the pulse. To calculate the beats per minute, the patient's pulse is counted for 15 seconds and multiplied by four. Normal range for the study is 60-90 beats per minute.
Time Frame
every visit up to 90 days
Title
Change in Blood Pressure
Description
Blood Pressure is measured with a sphygmomanometer in a resting condition in three hours after study drug intake, before blood sampling. Subjects should abstain from eating, drinking, smoking one hour before measurement. The bladder should have been emptied. Subject should have been sitting quietly for about 5 minutes before the measurement. Tight clothes should have been removed. Measurements should be taken in sitting position so that the arm and back are supported. Blood Pressure is measured in millimeters of mercury (mm Hg). The systolic and diastolic blood pressure is recorded.
Time Frame
every visit up to 90 days
Title
Change in Body Temperature
Description
Body Temperature is measured with a mercury thermometer in the armpit in a resting condition three hours after study drug intake, before blood sampling.
Time Frame
every visit up to 90 days
Title
Symptoms of musculoskeletal system
Description
The symptoms are recorded as a score on a scale. If there are no symptoms the result is reported as "Normal" (score=0). If there are any musculoskeletal symptoms the result is reported as "Abnormal". Each symptom will be estimated as "Clinically non-significant" (score=1) or "Clinically significant"(score=2) and described. The relationship of symptoms with the study drug is assessed as:"Definitely related"(score=3); "Probably related"(score=2); "Possibly related"(score=1); "Not related"(score=0). The scores of clinical significance are summarized with the score of the drug relation. The higher scores mean a worse outcome.
Time Frame
From baseline till the last visit (daily during hospital stay, every visit in follow-up period - up to 90 days)
Title
Symptoms of cardiovascular system
Description
The symptoms are recorded as a score on a scale. If there are no symptoms the result is reported as "Normal" (score=0). If there are any cardiovascular symptoms the result is reported as "Abnormal". Each symptom will be estimated as "Clinically non-significant" (score=1) or "Clinically significant"(score=2) and described. The relationship of symptoms with the study drug is assessed as:"Definitely related"(score=3); "Probably related"(score=2); "Possibly related"(score=1); "Not related"(score=0). The scores of clinical significance are summarized with the score of the drug relation. The higher scores mean a worse outcome.
Time Frame
From baseline till the last visit (daily during hospital stay, every visit in follow-up period - up to 90 days)
Title
Symptoms of lymphatic system
Description
The symptoms are recorded as a score on a scale. If there are no symptoms the result is reported as "Normal" (score=0). If there are any lymphatic symptoms the result is reported as "Abnormal". Each symptom will be estimated as "Clinically non-significant" (score=1) or "Clinically significant"(score=2) and described. The relationship of symptoms with the study drug is assessed as:"Definitely related"(score=3); "Probably related"(score=2); "Possibly related"(score=1); "Not related"(score=0). The scores of clinical significance are summarized with the score of the drug relation. The higher scores mean a worse outcome.
Time Frame
From baseline till the last visit (daily during hospital stay, every visit in follow-up period - up to 90 days)
Title
Symptoms of nervous system
Description
The symptoms are recorded as a score on a scale. If there are no symptoms the result is reported as "Normal" (score=0). If there are any nervous symptoms the result is reported as "Abnormal". Each symptom will be estimated as "Clinically non-significant" (score=1) or "Clinically significant"(score=2) and described. The relationship of symptoms with the study drug is assessed as:"Definitely related"(score=3); "Probably related"(score=2); "Possibly related"(score=1); "Not related"(score=0). The scores of clinical significance are summarized with the score of the drug relation. The higher scores mean a worse outcome.
Time Frame
From baseline till the last visit (daily during hospital stay, every visit in follow-up period - up to 90 days)
Title
Symptoms of Respiratory system
Description
The symptoms are recorded as a score on a scale. If there are no symptoms the result is reported as "Normal" (score=0). If there are any Respiratory symptoms the result is reported as "Abnormal". Each symptom will be estimated as "Clinically non-significant" (score=1) or "Clinically significant"(score=2) and described. The relationship of symptoms with the study drug is assessed as:"Definitely related"(score=3); "Probably related"(score=2); "Possibly related"(score=1); "Not related"(score=0). The scores of clinical significance are summarized with the score of the drug relation. The higher scores mean a worse outcome.
Time Frame
From baseline till the last visit (daily during hospital stay, every visit in follow-up period - up to 90 days)
Title
Symptoms of Gastrointestinal system
Description
The symptoms are recorded as a score on a scale. If there are no symptoms the result is reported as "Normal" (score=0). If there are any gastrointestinal symptoms the result is reported as "Abnormal". Each symptom will be estimated as "Clinically non-significant" (score=1) or "Clinically significant"(score=2) and described. The relationship of symptoms with the study drug is assessed as:"Definitely related"(score=3); "Probably related"(score=2); "Possibly related"(score=1); "Not related"(score=0). The scores of clinical significance are summarized with the score of the drug relation. The higher scores mean a worse outcome.
Time Frame
From baseline till the last visit (daily during hospital stay, every visit in follow-up period - up to 90 days)
Title
Symptoms of urinary system
Description
The symptoms are recorded as a score on a scale. If there are no symptoms the result is reported as "Normal" (score=0). If there are any urinary symptoms the result is reported as "Abnormal". Each symptom will be estimated as "Clinically non-significant" (score=1) or "Clinically significant"(score=2) and described. The relationship of symptoms with the study drug is assessed as:"Definitely related"(score=3); "Probably related"(score=2); "Possibly related"(score=1); "Not related"(score=0). The scores of clinical significance are summarized with the score of the drug relation. The higher scores mean a worse outcome.
Time Frame
From baseline till the last visit (daily during hospital stay, every visit in follow-up period - up to 90 days)
Title
Symptoms of Endocrine system
Description
The symptoms are recorded as a score on a scale. If there are no symptoms the result is reported as "Normal" (score=0). If there are any endocrine system symptoms the result is reported as "Abnormal". Each symptom will be estimated as "Clinically non-significant" (score=1) or "Clinically significant"(score=2) and described. The relationship of symptoms with the study drug is assessed as:"Definitely related"(score=3); "Probably related"(score=2); "Possibly related"(score=1); "Not related"(score=0). The scores of clinical significance are summarized with the score of the drug relation. The higher scores mean a worse outcome.
Time Frame
From baseline till the last visit (daily during hospital stay, every visit in follow-up period - up to 90 days)
Title
Symptoms of Skin and subcutaneous tissue
Description
The symptoms are recorded as a score on a scale. If there are no symptoms the result is reported as "Normal" (score=0). If there are any skin and subcutaneous tissue symptoms the result is reported as "Abnormal". Each symptom will be estimated as "Clinically non-significant" (score=1) or "Clinically significant"(score=2) and described. The relationship of symptoms with the study drug is assessed as:"Definitely related"(score=3); "Probably related"(score=2); "Possibly related"(score=1); "Not related"(score=0). The scores of clinical significance are summarized with the score of the drug relation. The higher scores mean a worse outcome.
Time Frame
From baseline till the last visit (daily during hospital stay, every visit in follow-up period - up to 90 days)
Title
Change in Alanine transaminase (ALT)
Description
The ALT test measures the amount of ALT in the blood. High levels of ALT in the blood can indicate a liver problem, even before clinical signs of liver disease. It is measured in IU/L. Normal range for the study: ≤ 45 IU/L.
Time Frame
Single dose intake: Screening visit; before dose (Day -1); Day 1 - after dose (3 hours); Days 2;7;30;60. Multiple dose intake: Screening visit; before dose (Day -1); Days 1; 3;10;14-after dose (3 hours); Days 17;30;60;90
Title
Change in Aspartate aminotransferase (AST)
Description
The AST blood test measures the amount of AST in the blood. AST is an enzyme that is found mostly in the liver. AST releases into bloodstream when liver is damaged. The test can help to diagnose liver damage or disease. It is measured in IU/L. Normal range for the study: ≤ 41 IU/L.
Time Frame
Single dose intake: Screening visit; before dose (Day -1); Day 1 - after dose (3 hours); Days 2;7;30;60. Multiple dose intake: Screening visit; before dose (Day -1); Days 1; 3;10;14-after dose (3 hours); Days 17;30;60;90
Title
Change in Bilirubin / bilirubin fractions
Description
The level of bilirubin is measured in the blood by the bilirubin blood test. Direct bilirubin is water-soluble form of bilirubin. Indirect bilirubin is fat-soluble form of bilirubin.
Direct and indirect are measured solely. Total and direct bilirubin levels can be measured from the blood, but indirect bilirubin is calculated from the total and direct bilirubin. It is measured in μmol/L. Normal range for the study: 8,6-20,5 μmol/L.
Time Frame
Single dose intake: Screening visit; before dose (Day -1); Day 1 - after dose (3 hours); Days 2;7;30;60. Multiple dose intake: Screening visit; before dose (Day -1); Days 1; 3;10;14-after dose (3 hours); Days 17;30;60;90
Title
Change in Creatinine
Description
Serum creatinine is measured in the blood. Creatinine measurements are used in the trial as the indicator of kidney function. Elevated creatinine level signifies impaired kidney function or kidney disease. As the kidneys become impaired for any reason, the creatinine level in the blood will rise due to poor clearance of creatinine by the kidneys. Abnormally high levels of creatinine thus warn of possible malfunction or failure of the kidneys. It is measured in μmol/L. Normal range for the study: ≤133 μmol/L.
Time Frame
Single dose intake: Screening visit; before dose (Day -1); Day 1 - after dose (3 hours); Days 2;7;30;60. Multiple dose intake: Screening visit; before dose (Day -1); Days 1; 3;10;14-after dose (3 hours); Days 17;30;60;90
Title
Change in Alkaline phosphatase
Description
The alkaline phosphatase is measured in the blood. High levels of alkaline phosphatase may indicate the liver damage. It is measured in IU/L. Normal range for the study: 40-129 IU/L.
Time Frame
Single dose intake: Screening visit; before dose (Day -1); Day 1 - after dose (3 hours); Days 2;7;30;60. Multiple dose intake: Screening visit; before dose (Day -1); Days 1; 3;10;14-after dose (3 hours); Days 17;30;60;90
Title
Change in Blood Urea Nitrogen
Description
The amount of urea nitrogen is measured in the blood. The urea is produced by liver in the urea cycle as a waste product of the digestion of proteins. The elevated levels of Blood Urea Nitrogen may be a sign that that kidneys aren't working efficiently. The accumulation of urea and other nitrogen-containing compounds in the blood due to renal failure leads to uremia. The main causes of an increase in Blood Urea Nitrogen are: high protein diet, decrease in glomerular filtration rate (suggestive of renal failure), decrease in blood volume (hypovolemia), congestive heart failure, gastrointestinal hemorrhage,[4] fever, and increased catabolism. Hypothyroidism can cause both decreased glomerular filtration rate and hypovolemia, but Blood Urea Nitrogen -to-creatinine ratio has been found to be lowered in hypothyroidism and raised in hyperthyroidism. It is measured in mmol/L. Normal range for the study: ≤8.3 mmol/L.
Time Frame
Single dose intake: Screening visit; before dose (Day -1); Day 1 - after dose (3 hours); Days 2;7;30;60. Multiple dose intake: Screening visit; before dose (Day -1); Days 1; 3;10;14-after dose (3 hours); Days 17;30;60;90
Title
Change in Uric acid
Description
Uric acid is a product of the metabolic breakdown of purine nucleotides, and it is a normal component of urine. High blood concentrations of uric acid may be caused by study drug, hypothyroidism, kidney damage and called hyperuricemia. It can lead to gout and are associated with other medical conditions, including diabetes and the formation of ammonium acid urate kidney stones.
Uric acid in blood is measured in mmol/L. Normal range for the study: ≤480 mmol/L.
Time Frame
Single dose intake: Screening visit; before dose (Day -1); Day 1 - after dose (3 hours); Days 2;7;30;60. Multiple dose intake: Screening visit; before dose (Day -1); Days 1; 3;10;14-after dose (3 hours); Days 17;30;60;90
Title
Change in Alpha-amylase (α-amylase)
Description
α-amylase is an enzyme that catalyze the hydrolysis of starch into smaller carbohydrate molecules.
The alpha-amylase is produced by the salivary glands, whereas pancreatic amylase is secreted by the pancreas into the small intestine. Both the salivary and pancreatic amylases are α-amylases.
Blood serum amylase may be increased in case of the pancreas damage by the study drug. α-amylase in blood is measured in mmol/L. Normal range for the study: 28-100 U/L
Time Frame
Single dose intake: Screening visit; before dose (Day -1); Day 1 - after dose (3 hours); Days 2;7;30;60. Multiple dose intake: Screening visit; before dose (Day -1); Days 1; 3;10;14-after dose (3 hours); Days 17;30;60;90
Title
Change in Serum total protein
Description
Protein in the serum consists of albumin and globulin. Protein fractions are determined using electrophoresis. Total protein levels in the blood give a general indication of the state of hydration, nutrition or proper functioning of certain major organs such as the liver, kidneys or bone marrow. Total protein in blood is measured in g/L. Normal range for the study: 64-83 g/L. Concentrations below the reference range may be a sign of low albumin concentration, liver damage, acute inflammation, or a problem of malnutrition or malabsorption of amino acids necessary for protein formation. It may be also a sign of immunodeficiency. Too much protein loss from the kidneys or too much water in the blood can also cause hypoproteinemia. Concentrations above the reference range (hyperproteinemia) may indicate dehydration or an increase in the gammaglobulin fraction, as found in chronic inflammatory diseases, certain viral infections or bone marrow disorders.
Time Frame
Single dose intake: Screening visit; before dose (Day -1); Day 1 - after dose (3 hours); Days 2;7;30;60. Multiple dose intake: Screening visit; before dose (Day -1); Days 1; 3;10;14-after dose (3 hours); Days 17;30;60;90
Title
Change in Albumin level in blood
Description
Albumin is a protein made by the liver. Albumin is measured in the blood. Albumin carries substances such as hormones, medicines, and enzymes throughout the body. Low albumin levels can indicate a problem with the liver or kidneys. Albumin in blood is measured in g/L. Normal range for the study: 35-55 g/L.
Time Frame
Single dose intake: Screening visit; before dose (Day -1); Day 1 - after dose (3 hours); Days 2;7;30;60. Multiple dose intake: Screening visit; before dose (Day -1); Days 1; 3;10;14-after dose (3 hours); Days 17;30;60;90
Title
Change in Glucose level in blood
Description
Measuring blood glucose levels is primarily used to monitor blood sugar levels to diagnose hyperglycemia or hypoglycemia caused by study drug. It is measured in fasting condition. Glucose in blood is measured in mmol/L. Normal range for the study: 4,11-5,89 mmol/L.
Time Frame
Single dose study:Screening visit; before dose (Day -1); Day 1 - after dose (3 hours); Days 2;7;30;60. Multiple dose study: Screening visit; before dose (Day -1); Days 1; 3;10;14-after dose (3 hours); Days 17;30;60;90
Title
Change in Total cholesterol
Description
It is measured in the blood. It includes all the cholesterol in all the lipoprotein particles: high-density lipoprotein cholesterol (HDL) and low-density lipoprotein cholesterol (LDL).
Total cholesterol in blood is measured in mmol/L. Normal range for the study: ≤5.2 mmol/L. It is used to diagnose the metabolism of lipids and the liver function.
Time Frame
Single dose intake: Screening visit; before dose (Day -1); Day 1 - after dose (3 hours); Days 2;7;30;60. Multiple dose intake: Screening visit; before dose (Day -1); Days 1; 3;10;14-after dose (3 hours); Days 17;30;60;90
Title
Change in Potassium in blood
Description
Measurement of the amount of potassium in the blood helps to diagnose an electrolyte imbalance caused by study drug. Changed potassium level (hypokaliemia, hyperkaliemia) may cause such problems as muscle weakness or contractions, nerve signals transmission, cardiac arrhythmia, hypertension, may affect the kidney function and hormone release. Potassium in the blood is measured in mmol/L. Normal range for the study: 3.5 - 5.3 mmol/L
Time Frame
Single dose study:Screening visit; before dose (Day -1); Day 1 - after dose (3 hours); Days 2;7;30;60. Multiple dose study: Screening visit; before dose (Day -1); Days 1; 3;10;14-after dose (3 hours); Days 17;30;60;90
Title
Change in Serum calcium
Description
Measurement of the amount of calcium in the blood helps to diagnose an electrolyte imbalance caused by study drug. Changed calcium level (hypocalcaemia, hypercalcaemia) may influence the proper functioning of muscles, nerves, and the heart, coagulation, maintenance of bones and teeth.Calcium in the blood is measured in mmol/L. Normal range for the study: 2,15-2,55 mmol/L.
Time Frame
Single dose intake: Screening visit; before dose (Day -1); Day 1 - after dose (3 hours); Days 2;7;30;60. Multiple dose intake: Screening visit; before dose (Day -1); Days 1; 3;10;14-after dose (3 hours); Days 17;30;60;90
Title
Change in Serum magnesium
Description
Measurement of the amount of magnesium in the blood helps to diagnose an electrolyte imbalance caused by study drug. Abnormal levels of magnesium may influence the proper functioning of muscles, nerves, and the heart, helps control blood pressure and blood sugar. Low level of magnesium in the body may cause numerous symptoms: poor coordination, muscle spasms, loss of appetite, personality changes, and nystagmus. Magnesium in the blood is measured in mmol/L. Normal range for the study: 0,65- 1,5 mmol/L.
Time Frame
Single dose intake: Screening visit; before dose (Day -1); Day 1 - after dose (3 hours); Days 2;7;30;60. Multiple dose intake: Screening visit; before dose (Day -1); Days 1; 3;10;14-after dose (3 hours); Days 17;30;60;90
Title
Change in erythrocytes number in blood
Description
The influence of the study drug on the number and morphology of erythrocytes will be assessed. Normal range for the study: 3,9-5,5 х10^12 per liter.
Time Frame
Single dose intake: Screening visit; before dose (Day -1); Day 1 - after dose (3 hours); Days 2;7;30;60. Multiple dose intake: Screening visit; before dose (Day -1); Days 1; 3;10;14-after dose (3 hours); Days 17;30;60;90
Title
Change in hemoglobin
Description
The influence of the study drug on to the amount of hemoglobin will be assessed. Normal range for the study: 130-180 g/L.
Time Frame
Single dose intake: Screening visit; before dose (Day -1); Day 1 - after dose (3 hours); Days 2;7;30;60. Multiple dose intake: Screening visit; before dose (Day -1); Days 1; 3;10;14-after dose (3 hours); Days 17;30;60;90
Title
Change in leucocytes number in the blood
Description
The influence of the study drug on the number and morphology of leucocytes will be assessed. Normal range for the study: 4,0-9,0 х10^9 per liter.
Time Frame
Single dose intake: Screening visit; before dose (Day -1); Day 1 - after dose (3 hours); Days 2;7;30;60. Multiple dose intake: Screening visit; before dose (Day -1); Days 1; 3;10;14-after dose (3 hours); Days 17;30;60;90
Title
Change in thrombocytes number in the blood
Description
The influence of the study drug on the number and morphology of thrombocytes will be assessed. Normal range for the study: 180-400 х10^9 per liter.
Time Frame
Single dose intake: Screening visit; before dose (Day -1); Day 1 - after dose (3 hours); Days 2;7;30;60. Multiple dose intake: Screening visit; before dose (Day -1); Days 1; 3;10;14-after dose (3 hours); Days 17;30;60;90
Title
Change in hematocrit
Description
It is the percentage of red blood cells (RBC's) in the blood. The hematocrit test indicates the percentage of blood by volume that is composed of red blood cells. A hematocrit is measured in L/L (litre of cells per litre of blood). Normal range for the study: 36-55% .
Time Frame
Single dose intake: Screening visit; before dose (Day -1); Day 1 - after dose (3 hours); Days 2;7;30;60. Multiple dose intake: Screening visit; before dose (Day -1); Days 1; 3;10;14-after dose (3 hours); Days 17;30;60;90
Title
Change in Erythrocyte Sedimentation Rate (ESR))
Description
ESR indirectly measures the degree of inflammation present in the body. The test actually measures the rate sedimentation of erythrocytes in a sample of blood that has been placed into a tall, thin, vertical tube. Results are reported as the millimeters of plasma that are present at the top portion of the tube after one hour. The ESR is non-specific test that provides general information about the presence or absence of an inflammatory condition. Normal range for the study: 2-10 mm/hour.
Time Frame
Single dose intake: Screening visit; before dose (Day -1); Day 1 - after dose (3 hours); Days 2;7;30;60. Multiple dose intake: Screening visit; before dose (Day -1); Days 1; 3;10;14-after dose (3 hours); Days 17;30;60;90
Title
Change in prothrombin index
Description
Measured in percents. Normal range for the study: 70-130 %
Time Frame
Single dose intake: Screening visit; before dose (Day -1); Day 1 - after dose (3 hours); Days 2;7;30;60. Multiple dose intake: Screening visit; before dose (Day -1); Days 1; 3;10;14-after dose (3 hours); Days 15;16;17;30;60;90
Title
Change in activated partial thromboplastin time (aPTT)
Description
Measured in seconds. Normal range for the study: 23-38 seconds
Time Frame
Single dose intake: Screening visit; before dose (Day -1); Day 1 - after dose (3 hours); Days 2;7;30;60. Multiple dose intake: Screening visit; before dose (Day -1); Days 1; 3;10;14-after dose (3 hours); Days 15;16;17;30;60;90
Title
Change in prothrombin ratio
Description
The ratio of a patient's prothrombin time to a normal (control) sample, raised to the power of the ISI value for the analytical system being used. Measured as a ratio. Normal range for the study:0,9-1,2
Time Frame
Single dose intake: Screening visit; before dose (Day -1); Day 1 - after dose (3 hours); Days 2;7;30;60. Multiple dose intake: Screening visit; before dose (Day -1); Days 1; 3;10;14-after dose (3 hours); Days 15;16;17;30;60;90
Title
Change in thrombin time
Description
Thrombin clotting time measures the time it takes for a clot to form in the plasma of a blood sample containing anticoagulant, after an excess of thrombin has been added.Measured in seconds. Normal range for the study:15-21 seconds
Time Frame
Single dose intake: Screening visit; before dose (Day -1); Day 1 - after dose (3 hours); Days 2;7;30;60. Multiple dose intake: Screening visit; before dose (Day -1); Days 1; 3;10;14-after dose (3 hours); Days 15;16;17;30;60;90
Title
Change of protein level in urine
Description
Proteinuria caused by study drug will be assessed. It may be due to kidney damage, heart failure, loss of body fluids (dehydration), high blood pressure. Protein level in urine is measured in mg/L.
Time Frame
Single dose intake: Screening visit; before dose (Day -1); Day 1 - after dose (3 hours); Days 2;7;30;60. Multiple dose intake: Screening visit; before dose (Day -1); Days 1; 3;10;14-after dose (3 hours); Days 17;30;60;90
Title
Change in Urinary glucose
Description
Glycosuria caused by study drug will be assessed. Measured in mmol/L Normal range for the study: 0 to 0.8 mmol/L.
Time Frame
Single dose intake: Screening visit; before dose (Day -1); Day 1 - after dose (3 hours); Days 2;7;30;60. Multiple dose intake: Screening visit; before dose (Day -1); Days 1; 3;10;14-after dose (3 hours); Days 17;30;60;90
Title
Hematuria
Description
Hematuria caused by study drug will be assessed.It is measured in the number of red blood cells per high-power field in microscopic investigation of urine sediment.
Time Frame
Single dose intake: Screening visit; before dose (Day -1); Day 1 - after dose (3 hours); Days 2;7;30;60. Multiple dose intake: Screening visit; before dose (Day -1); Days 1; 3;10;14-after dose (3 hours); Days 17;30;60;90
Title
Leucocyturia
Description
Leucocytes in urine after study drug intake will be assessed. Leucocyturia may be due to inflammation of the urinary track or adjacent tissue. It is measured in the number of white blood cells per high-power field in microscopic investigation of urine sediment.
Time Frame
Single dose intake: Screening visit; before dose (Day -1); Day 1 - after dose (3 hours); Days 2;7;30;60. Multiple dose intake: Screening visit; before dose (Day -1); Days 1; 3;10;14-after dose (3 hours); Days 17;30;60;90
Title
Ketonuria
Description
Ketone bodies present in the urine after study drug intake will be assessed. It may be due to excess ketones production as an indication that the body is using an alternative source of energy. It is measured in mg/dL. A negative test result is normal.
An abnormal result: small ketonuria: <20 mg/dL; moderate ketonuria: 30 to 40 mg/dL; large ketonuria: >80 mg/dL
Time Frame
Single dose intake: Screening visit; before dose (Day -1); Day 1 - after dose (3 hours); Days 2;7;30;60. Multiple dose intake: Screening visit; before dose (Day -1); Days 1; 3;10;14-after dose (3 hours); Days 17;30;60;90
Title
Change in urine pH
Description
The influence of study drug on to urine pH will be evaluated. The normal values range from pH 4.6 to 8.0
Time Frame
Single dose intake: Screening visit; before dose (Day -1); Day 1 - after dose (3 hours); Days 2;7;30;60. Multiple dose intake: Screening visit; before dose (Day -1); Days 1; 3;10;14-after dose (3 hours); Days 17;30;60;90
Title
Change in immunoglobulin A (IgA) level in blood
Description
The influence of study drug onto IgA level in blood will be evaluated. It is measured in g/L. Normal range for the study: 0,7-4,0 g/L.
Time Frame
Single dose study: before dose (Day -1); Day 1 - after dose (3 hours); Day 2. Multiple dose study: before dose (Day -1) Days 14; 17; 30;60; 90
Title
Change in immunoglobulin M (IgM) level in blood
Description
The influence of study drug onto IgM level in blood will be evaluated. It is measured in g/L. Normal range for the study: 0,4-2,3 g/L.
Time Frame
Single dose intake: before dose (Day -1); Day 1 - after dose (3 hours); Day 2. Multiple dose intake: before dose (Day -1) Days 14; 17; 30;60; 90
Title
Change in immunoglobulin G (IgG) level in blood
Description
The influence of study drug onto IgG level in blood will be evaluated. It is measured in g/L. Normal range for the study: 7-16 g/L.
Time Frame
Single dose intake: before dose (Day -1); Day 1 - after dose (3 hours); Day 2. Multiple dose intake: before dose (Day -1) Days 14; 17; 30;60; 90
Title
Change in immunoglobulin E (IgE) level in blood
Description
The influence of study drug onto IgE level in blood will be evaluated. It is measured in IU/ml . Normal range for the study: 0,100-200,0 IU/ml.
Time Frame
Single dose intake: Screening visit; Day 1 - after dose (3 hours); Day 2. Multiple dose intake: Screening visit; Days 14; 17; 30;60; 90
Title
Change in Rheumatoid factor
Description
The influence of study drug onto Rheumatoid factor in blood will be evaluated. It is measured in IU/ml . Normal range for the study: 0-25 IU/ml.
Time Frame
Single dose intake: Screening visit; Day 1 - after dose (3 hours); Day 2. Multiple dose intake: Screening visit; Days 14; 17; 30;60; 90
Title
Change in C-Reactive Protein
Description
The influence of study drug onto C-Reactive Protein in blood will be evaluated. It is measured in mg/l . Normal range for the study: 0-5 mg/l
Time Frame
Single dose intake: Screening visit; Day 1 - after dose (3 hours); Day 2. Multiple dose intake: Screening visit; Days 14; 17; 30;60; 90
Title
Change in Antimitochondrial Antibody
Description
The influence of study drug on Antimitochondrial Antibody in blood will be evaluated. It is measured in IU/ml. Normal range for the study: 0-10 IU/ml
Time Frame
Single dose intake: before dose (Day -1); Day 30; Day 60. Multiple dose intake: before dose (Day -1); Day 60; Day90
Title
Change in antinuclear antibody
Description
The influence of study drug on antinuclear antibody in blood will be evaluated. It is measured in IU/ml. Normal range for the study: 0-40 IU/ml
Time Frame
Single dose intake: before dose (Day -1); Day 30; Day 60. Multiple dose intake: before dose (Day -1); Day 60; Day90
Title
Change from baseline in CD3+tcells
Description
The influence of study drug on CD3+ tcells percent in blood will be evaluated. Normal range for the study: 52-76 %
Time Frame
Single dose intake: before dose (Day -1); Day 1 - after dose (3 hours); Days 2; 17; 30; 60. Multiple dose intake: before dose (Day -1); Day 1; 14 - after dose (3 hours); Days 17;30;60;90
Title
Change from baseline in CD4+tcells
Description
The influence of study drug on CD4+ tcells percent in blood will be evaluated. Normal range for the study: 31-46 %
Time Frame
Single dose intake: before dose (Day -1); Day 1 - after dose (3 hours); Days 2; 17; 30; 60. Multiple dose intake: before dose (Day -1); Day 1; 14 - after dose (3 hours); Days 17;30;60;90
Title
Change from baseline in CD8+tcells
Description
The influence of study drug on CD8+ tcells percent in blood will be evaluated. Normal range for the study: 23-40 %
Time Frame
Single dose intake: before dose (Day -1); Day 1 - after dose (3 hours); Days 2; 17; 30; 60. Multiple dose intake: before dose (Day -1); Day 1; 14 - after dose (3 hours); Days 17;30;60;90
Title
Change from baseline in Ratio CD4/CD8
Description
The influence of study drug on Ratio CD4/CD8 in blood will be evaluated. Normal range for the study: 1.2-2.0 %
Time Frame
Single dose intake: before dose (Day -1); Day 1 - after dose (3 hours); Days 2; 17; 30; 60. Multiple dose intake: before dose (Day -1); Day 1; 14 - after dose (3 hours); Days 17;30;60;90
10. Eligibility
Sex
Male
Gender Based
Yes
Gender Eligibility Description
males
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Age 18 to 55 years
Body mass index 16 to 30
Subjects should be in good physical and mental health based on medical history, clinical examination and laboratory investigations
Subjects should have signed informed consent prior to screening and the clinical study after they have read and understood the objective, conduct, risks related to the study, and their rights as study participants
Subjects should have signed informed consent for being tested for HIV
Subjects should have signed informed consent to be tested for alcoholemia, use of cannabinoids, cocaine, morphine, benzodiazepines, barbiturates and amphetamine
Exclusion Criteria:
Subjects should not have evidence of any physical and/or mental health issues at screening and/or results of any clinical, laboratory and/or technical procedures at screening outside of the normal range
Subjects should not be taking any concomitant medication
Subjects should not have a history of allergies, hypersensitivity or intolerance to iodine or iodide or to medicines containing iodine such as contrast media used for radiologic examinations
Subjects should not have a history of addiction or abuse of drugs or alcohol
Subjects should not be in a position of subordination or other dependence on persons involved in the study such as sponsor, investigators, or any other person or institution interested in its results
Subjects should not be members of the armed forces or prison inmates
Subjects should not have positive serology for Hepatitis B, Hepatitis C or HIV
Subjects should not have any apparent functional and/or physical defects which may or interfere with the study or distort results
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Amirkan A Azembayev, PhD
Organizational Affiliation
JSC "Scientific Center for Anti-infectious Drugs"
Official's Role
Study Director
Facility Information:
Facility Name
Institute Of Cardiology & Internal Diseases
City
Almaty
State/Province
Almatinskaya
ZIP/Postal Code
A05B0H6
Country
Kazakhstan
12. IPD Sharing Statement
Plan to Share IPD
No
Links:
URL
http://scaid.kz
Description
Information about the organization developed and produced new drug
URL
https://www.ncbi.nlm.nih.gov/pubmed/22332742
Description
Structure and possible mechanism of action of new drug
URL
https://link.springer.com/chapter/10.1007%2F978-1-4899-7699-4_10
Description
Interaction of iodine complexes with viral DNA
URL
https://www.rjpbcs.com/pdf/2016_7(6)
Description
Quantitative Determination of Iodide Ions in Substances and Tablets Containing Iodine Adducts
Learn more about this trial
PA Tolerability, Safety and Pharmacokinetics in Healthy Volunteers
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