Healthy Subjects
Conditions
Keywords
PBTZ169, Macozinone, Antimycobacterial, Tuberculosis, Drug Resistant Tubercolosis, MDR-TB, XDR-TB
Brief summary
Open-label prospective non-comparative ascending dose randomized cohort study of single and multiple oral administration of PBTZ169 (capsules 80 mg) in healthy volunteers
Detailed description
Open-label prospective non-comparativerandomized cohort study of safety, tolerability, pharmacokinetics and the effect of food of PBTZ169 in adult healthy volunteers after single and multiple oral administration. Study was conducted in one study center in the Russian Federation. The study included two stages: Stage 1 - single or double oral administration with dose escalation (fasted/after meal) in 5 cohorts 10 healthy volunteers each plus 5 back-up volunteers; Stage 2 - multiple oral administration once a day after meal for 14 days in 1 cohort of 10 healthy volunteers.
Interventions
DRUGPBTZ169 640 mg OD
Two administrations once a day with a wash-out period: food effect
DRUGPBTZ169 640 mg BiD
Twice a day fasted; 1 day of administration
DRUGPBTZ169 960 mg SD
Once a day fasted
DRUGPBTZ169 1280 mg SD
Once a day fasted
DRUGPBTZ169 1280 mg MD
Once a day after meal, 14 doses
Sponsors
Nearmedic Plus LLC
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
1. Written informed consent from the volunteer. 2. Men and women aged 18-45 years, inclusive. 3. Body mass index of 18.5-30 kg/m2. 4. Verified healthy diagnosis based on physical examination, vital signs, standard laboratory tests (complete blood count and biochemical blood test, urine analysis) and instrumental tests (ECG, fluorography examination or X-ray examination). 5. Negative results of tests for human immunodeficiency virus (HIV), syphilis, hepatitis B (Hbs Ag) and hepatitis C (antibodies to HCV). 6. Ability to comply with all the requirements of the protocol in the opinion of the investigator. 7. Consent of the participant and his/her partner to use reliable contraceptive methods during the study and within 90 days after the end of their participation. A reliable method of contraception is a combination of a male condom with at least one of the following methods: * hormonal contraceptives used by the male's partner (only if she does not participate in this clinical study); * use of aerosols, creams, suppositories and other agents containing spermicides; * use of intrauterine device by female partner.
Exclusion criteria
1. History of allergies, including at least one episode of allergy to medications. 2. Chronic diseases of the cardiovascular, bronchopulmonary, neuroendocrine systems, ENT, as well as diseases of the gastrointestinal tract, liver, kidneys, blood, skin. 3. Hypolactasia (lactose intolerance, lactase deficiency) or glucose-galatose malabsorption in medical history. 4. Chronic eye diseases except for myopia, hypermetropia and astigmatism of mild and moderate severity. 5. Surgeries on the gastrointestinal tract (except for appendectomy done more than 1 year before screening). 6. Regular administration or use (including externally) of hormonal agent for more than 1 week less than 45 days before screening 7. Regular administration of medicinal products less than 4 weeks before screening. 8. Use of medicinal products that have a pronounced effect on liver function or hemodynamics (barbiturates, omeprazole, cimetidine, etc.) less than 30 days before screening. 9. Positive test for narcotics and psychotropic products. 10. Blood pressure after resting in supine position for at least 5 minutes above 130 mm Hg (systolic blood pressure) and 90 mm Hg (diastolic blood pressure) or below 110 mm Hg (systolic blood pressure) and 60 mm Hg (diastolic blood pressure). 11. Heart rate (according to ECG) after resting in supine position for at least 5 minutes above 90 bpm or below 60 bpm. 12. Blood donation (450 mL of blood or plasma and more) less than 3 months before the screening. 13. Acute infectious diseases less than 4 weeks before screening. 14. Administration of more than 10 units of alcohol per week (1 unit of alcohol is equivalent to 500 mL of beer, 200 mL of wine or 50 mL of a spirit) or history of alcoholism, drug abuse, substance abuse. 15. Mental diseases. 16. Smoking for three months before screening. 17. Participation in any clinical study less than 3 months before screening. 18. Planned conception or sperm donation during the study after the administration of the investigational product or within 3 months after the last administration of the product. 19. Positive pregnancy test for women. 20. Breastfeeding period.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Adverse Events | Up to last visit time point: C2, C3, C4 up to Day 7; C1 up to Day 13; C5 up to Day 21 after first drug intake | Safety and tolerability: number of (S)AEs |
| Number of Subjects With AEs | Up to last visit time point: C2, C3, C4 up to Day 7; C1 up to Day 13; C5 up to Day 21 after first drug intake | Safety and tolerability: number of subjects with adverse events |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Laboratory Examinations Results (Safety and Tolerability) | Up to last visit time point: C2, C3, C4 up to Day 7; C1 up to Day 13; C5 up to Day 21 after first drug intake | Complete blood count, biochemical blood test, urine analysis |
| Results of Physical Examination: CS Deviations | Up to last visit time point: C2, C3, C4 up to Day 7; C1 up to Day 13; C5 up to Day 21 after first drug intake | Safety and tolerability: number of physical examinations with CS deviations in results |
| Peak Plasma Concentration (Сmax) | In the dosing interval (up to 72 hours after the last drug administration) | Сmax of PBTZ169 at the timepoints: C1A, C1B, C2 and C4: point 0 (-5 min to -1 min), 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 9:00, 12:00, 24:00, 48:00 and 72:00 (h:min). C3 (two administrations): point 0 (-5 min to -1 min), 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 9:00, 12:00 (the point before the second administration from -5 min to -1 min), 12:30, 13:00, 13:30, 14:00, 15:00, 16:00, 18:00, 21:00, 24:00, 48:00 , 72:00 (h:min) after the first administration of the medicinal product. C5 (14 days of intake): 5 minutes before the administration (only until the first dose), 0 min and within 24 h after the administration of the 1st, 7th and last (14th) dose: 0:15, 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00, 24:00 (h:min after the administration of a dose of the medicinal product); at 48 h and 72 h points after the last (14th) dose of PBTZ169 |
| Trough Concentration With Repeated Administration (Ctrough) | Up to 72 hours after the last drug administration | PBTZ169 concentration before drug intake (Days 2 - 15) |
| Time to Reach Maximum Concentration (Tmax) | Up to 72 hours after the last drug administration | Cohort 3: Tmax relative to the time of administration in any dosage interval |
| Plasma Half-life Time (T1/2) | Up to 72 hours after the last drug administration | — |
| Area Under the Concentration-time Curve (AUC0 t) | Up to 72 hours after the last drug administration | In the time interval from 0 to time (t) when the last blood sample is collected with a concentration above the limit of quantification. C5: for the data of Day 14 based on measurements within 72 hours after the last dose administration |
| CS Changes in Vital Signs | Up to last visit time point: C2, C3, C4 up to Day 7; C1 up to Day 13; C5 up to Day 21 after first drug intake | Safety and tolerability:Clinically significant changes in vital signs (blood pressure, HR, body temperature, RR) |
| Area Under the Concentration-time Curve (AUC0-24) | In the dosing interval (up to 24 hours after drug administration) | C5 (multiple administration once a day for 14 days): AUC0-24 was calculated based on measurements within 24 hours after PBTZ169 intake |
| Total Clearance (Clt/F) | Up to 72 hours after the last drug administration | — |
| Volume of Distribution (Vd/F) | Up to 72 hours after the last drug administration | — |
| Elimination Constant Kel | Up to 72 hours after the last drug administration | — |
| Relative Bioavailability | Up to 72 hours after the last drug administration | f=AUC0-∞(T)/AUC0-∞(R); f'=AUC0-t(T)/AUC0-t(R) Test (T) - PBTZ169 640 mg after meals, reference (R) - PBTZ169 640 mg fasted |
| Relative Degree of Absorption | Up to 72 hours after the last drug administration | f=Cmax(T)/Cmax(R). Test (T) - PBTZ169 640 mg after meals, reference (R) - PBTZ169 640 mg fasted |
| Number of Subjects With CS Changes in Vital Signs | Up to last visit time point: C2, C3, C4 up to Day 7; C1 up to Day 13; C5 up to Day 21 after first drug intake | Safety and tolerability: No. of sbjs with clinically significant changes in vital signs (blood pressure, HR, body temperature, RR) |
| Area Under the Concentration-time Curve (AUC0-∞) | Up to 72 hours after the last drug administration | In the time interval from 0 to infinity |
| ECG Results (Safety and Tolerability) | Up to last visit time point: C2, C3, C4 up to Day 7; C1 up to Day 13; C5 up to Day 21 after first drug intake | Clinically significant abnormal deviations in ECG findings |
Countries
Russia
Participant flow
Recruitment details
Period 1: Single or double dosing (Cohorts 1-4) Period 2: Multiple dosing (Cohort 5)
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1 (C1A), PBTZ169 Two doses of PBTZ169: 640 mg OD fasted and 640 mg OD after meal. Wash-out period ≥6 days.
PBTZ169 640 mg OD: Two administrations once a day with a wash-out period: food effect | 10 |
| Cohort 1 (C1B), PBTZ169 Two doses of PBTZ169: 640 mg OD after meal and 640 OD mg fasted. Wash-out period ≥6 days.
PBTZ169 640 mg OD: Two administrations once a day with a wash-out period: food effect | 10 |
| Cohort 2 (C2), PBTZ169 Single dose of PBTZ169: 960 mg fasted
PBTZ169 960 mg SD: Once a day fasted | 10 |
| Cohort 3 (C3), PBTZ169 Two doses of PBTZ169: 640 mg twice a day (fasted) with a 12-hour interval; total daily dose - 1280 mg
PBTZ169 640 mg BiD: Twice a day fasted; 1 day of administration | 10 |
| Cohort 4 (C4), PBTZ169 Single dose of PBTZ169: 1280 mg fasted
PBTZ169 1280 mg SD: Once a day fasted | 10 |
| Cohort 5 (C5), PBTZ169 Multiple administration of PBTZ169: 1280 mg once a day after meal for 14 days
PBTZ169 1280 mg MD: Once a day after meal, 14 doses | 10 |
| Total | 60 |
Baseline characteristics
| Characteristic | Cohort 1 (C1B), PBTZ169 | Cohort 2 (C2), PBTZ169 | Cohort 3 (C3), PBTZ169 | Cohort 1 (C1A), PBTZ169 | Cohort 4 (C4), PBTZ169 | Cohort 5 (C5), PBTZ169 | Total |
|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 10 Participants | 10 Participants | 10 Participants | 10 Participants | 10 Participants | 10 Participants | 60 Participants |
| Age, Continuous | 23.0 years STANDARD_DEVIATION 2.26 | 23.7 years STANDARD_DEVIATION 3.95 | 27.1 years STANDARD_DEVIATION 5.09 | 27.2 years STANDARD_DEVIATION 5.25 | 30.1 years STANDARD_DEVIATION 9.1 | 26.7 years STANDARD_DEVIATION 5.01 | 26.3 years STANDARD_DEVIATION 5.79 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 00 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 10 Participants | 10 Participants | 10 Participants | 10 Participants | 10 Participants | 10 Participants | 60 Participants |
| Sex: Female, Male Female | 3 Participants | 9 Participants | 5 Participants | 5 Participants | 4 Participants | 6 Participants | 32 Participants |
| Sex: Female, Male Male | 7 Participants | 1 Participants | 5 Participants | 5 Participants | 6 Participants | 4 Participants | 28 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 20 | 0 / 10 | 0 / 10 | 0 / 10 | 0 / 10 |
| other Total, other adverse events | 6 / 20 | 3 / 10 | 5 / 10 | 1 / 10 | 5 / 10 |
| serious Total, serious adverse events | 0 / 20 | 0 / 10 | 0 / 10 | 0 / 10 | 0 / 10 |
Outcome results
Primary
Number of Adverse Events
Safety and tolerability: number of (S)AEs
Time frame: Up to last visit time point: C2, C3, C4 up to Day 7; C1 up to Day 13; C5 up to Day 21 after first drug intake
Population: Safety population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1 (C1A+C1B), PBTZ169 | Number of Adverse Events | Drug-related Investigations AEs | 4 AEs |
| Cohort 1 (C1A+C1B), PBTZ169 | Number of Adverse Events | Number of SAEs | 0 AEs |
| Cohort 1 (C1A+C1B), PBTZ169 | Number of Adverse Events | Drug-related GastroInt. AEs | 1 AEs |
| Cohort 1 (C1A+C1B), PBTZ169 | Number of Adverse Events | Drug-related Metabolic AEs | 0 AEs |
| Cohort 1 (C1A+C1B), PBTZ169 | Number of Adverse Events | Drug-related Nervous syst. AEs | 1 AEs |
| Cohort 1 (C1A+C1B), PBTZ169 | Number of Adverse Events | Number of drug-related AEs | 9 AEs |
| Cohort 1 (C1A+C1B), PBTZ169 | Number of Adverse Events | Number of AEs | 9 AEs |
| Cohort 1 (C1A+C1B), PBTZ169 | Number of Adverse Events | Drug-related Cardiac disorders AEs | 3 AEs |
| Cohort 2 (C2), PBTZ169 | Number of Adverse Events | Drug-related GastroInt. AEs | 1 AEs |
| Cohort 2 (C2), PBTZ169 | Number of Adverse Events | Drug-related Investigations AEs | 0 AEs |
| Cohort 2 (C2), PBTZ169 | Number of Adverse Events | Number of SAEs | 0 AEs |
| Cohort 2 (C2), PBTZ169 | Number of Adverse Events | Number of AEs | 4 AEs |
| Cohort 2 (C2), PBTZ169 | Number of Adverse Events | Drug-related Cardiac disorders AEs | 0 AEs |
| Cohort 2 (C2), PBTZ169 | Number of Adverse Events | Drug-related Metabolic AEs | 0 AEs |
| Cohort 2 (C2), PBTZ169 | Number of Adverse Events | Drug-related Nervous syst. AEs | 3 AEs |
| Cohort 2 (C2), PBTZ169 | Number of Adverse Events | Number of drug-related AEs | 4 AEs |
| Cohort 3 (C3), PBTZ169 | Number of Adverse Events | Number of drug-related AEs | 5 AEs |
| Cohort 3 (C3), PBTZ169 | Number of Adverse Events | Drug-related Cardiac disorders AEs | 1 AEs |
| Cohort 3 (C3), PBTZ169 | Number of Adverse Events | Number of SAEs | 0 AEs |
| Cohort 3 (C3), PBTZ169 | Number of Adverse Events | Number of AEs | 5 AEs |
| Cohort 3 (C3), PBTZ169 | Number of Adverse Events | Drug-related GastroInt. AEs | 1 AEs |
| Cohort 3 (C3), PBTZ169 | Number of Adverse Events | Drug-related Investigations AEs | 2 AEs |
| Cohort 3 (C3), PBTZ169 | Number of Adverse Events | Drug-related Nervous syst. AEs | 1 AEs |
| Cohort 3 (C3), PBTZ169 | Number of Adverse Events | Drug-related Metabolic AEs | 0 AEs |
| Cohort 4 (C4), PBTZ169 | Number of Adverse Events | Drug-related GastroInt. AEs | 1 AEs |
| Cohort 4 (C4), PBTZ169 | Number of Adverse Events | Number of AEs | 2 AEs |
| Cohort 4 (C4), PBTZ169 | Number of Adverse Events | Drug-related Investigations AEs | 0 AEs |
| Cohort 4 (C4), PBTZ169 | Number of Adverse Events | Number of SAEs | 0 AEs |
| Cohort 4 (C4), PBTZ169 | Number of Adverse Events | Drug-related Cardiac disorders AEs | 0 AEs |
| Cohort 4 (C4), PBTZ169 | Number of Adverse Events | Drug-related Metabolic AEs | 0 AEs |
| Cohort 4 (C4), PBTZ169 | Number of Adverse Events | Drug-related Nervous syst. AEs | 0 AEs |
| Cohort 4 (C4), PBTZ169 | Number of Adverse Events | Number of drug-related AEs | 1 AEs |
| Cohort 5 (C5), PBTZ169 | Number of Adverse Events | Number of AEs | 9 AEs |
| Cohort 5 (C5), PBTZ169 | Number of Adverse Events | Drug-related GastroInt. AEs | 2 AEs |
| Cohort 5 (C5), PBTZ169 | Number of Adverse Events | Number of SAEs | 0 AEs |
| Cohort 5 (C5), PBTZ169 | Number of Adverse Events | Drug-related Metabolic AEs | 2 AEs |
| Cohort 5 (C5), PBTZ169 | Number of Adverse Events | Drug-related Nervous syst. AEs | 2 AEs |
| Cohort 5 (C5), PBTZ169 | Number of Adverse Events | Drug-related Investigations AEs | 0 AEs |
| Cohort 5 (C5), PBTZ169 | Number of Adverse Events | Number of drug-related AEs | 6 AEs |
| Cohort 5 (C5), PBTZ169 | Number of Adverse Events | Drug-related Cardiac disorders AEs | 0 AEs |
Primary
Number of Subjects With AEs
Safety and tolerability: number of subjects with adverse events
Time frame: Up to last visit time point: C2, C3, C4 up to Day 7; C1 up to Day 13; C5 up to Day 21 after first drug intake
Population: Safety population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1 (C1A+C1B), PBTZ169 | Number of Subjects With AEs | Number of sbjs with AEs | 6 participants |
| Cohort 1 (C1A+C1B), PBTZ169 | Number of Subjects With AEs | Number of sbjs with drug-related AEs | 6 participants |
| Cohort 2 (C2), PBTZ169 | Number of Subjects With AEs | Number of sbjs with AEs | 3 participants |
| Cohort 2 (C2), PBTZ169 | Number of Subjects With AEs | Number of sbjs with drug-related AEs | 3 participants |
| Cohort 3 (C3), PBTZ169 | Number of Subjects With AEs | Number of sbjs with AEs | 5 participants |
| Cohort 3 (C3), PBTZ169 | Number of Subjects With AEs | Number of sbjs with drug-related AEs | 5 participants |
| Cohort 4 (C4), PBTZ169 | Number of Subjects With AEs | Number of sbjs with drug-related AEs | 1 participants |
| Cohort 4 (C4), PBTZ169 | Number of Subjects With AEs | Number of sbjs with AEs | 2 participants |
| Cohort 5 (C5), PBTZ169 | Number of Subjects With AEs | Number of sbjs with AEs | 6 participants |
| Cohort 5 (C5), PBTZ169 | Number of Subjects With AEs | Number of sbjs with drug-related AEs | 5 participants |
Secondary
Area Under the Concentration-time Curve (AUC0-∞)
In the time interval from 0 to infinity
Time frame: Up to 72 hours after the last drug administration
Population: C1-4 - Single or double dose administration, C5 - Multiple administration for 14 days
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 (C1A+C1B), PBTZ169 | Area Under the Concentration-time Curve (AUC0-∞) | Dosing day / Day 1 | 175.98 ng*h/ml | Standard Deviation 104.828 |
| Cohort 2 (C2), PBTZ169 | Area Under the Concentration-time Curve (AUC0-∞) | Dosing day / Day 1 | 584.06 ng*h/ml | Standard Deviation 221.531 |
| Cohort 3 (C3), PBTZ169 | Area Under the Concentration-time Curve (AUC0-∞) | Dosing day / Day 1 | 267.94 ng*h/ml | Standard Deviation 175.918 |
| Cohort 4 (C4), PBTZ169 | Area Under the Concentration-time Curve (AUC0-∞) | Dosing day / Day 1 | 348.56 ng*h/ml | Standard Deviation 141.198 |
| Cohort 5 (C5), PBTZ169 | Area Under the Concentration-time Curve (AUC0-∞) | Dosing day / Day 1 | 228.93 ng*h/ml | Standard Deviation 124.855 |
| Cohort 5 (C5), PBTZ169 | Area Under the Concentration-time Curve (AUC0-∞) | Dosing day / Day 1 | 1153.89 ng*h/ml | Standard Deviation 482.189 |
| Cohort 5 (C5), PBTZ169 | Area Under the Concentration-time Curve (AUC0-∞) | Day 14 | 1501.97 ng*h/ml | Standard Deviation 483.483 |
| Cohort 5 (C5), PBTZ169 | Area Under the Concentration-time Curve (AUC0-∞) | Day 7 | 1479.16 ng*h/ml | Standard Deviation 594.599 |
Secondary
Area Under the Concentration-time Curve (AUC0-24)
C5 (multiple administration once a day for 14 days): AUC0-24 was calculated based on measurements within 24 hours after PBTZ169 intake
Time frame: In the dosing interval (up to 24 hours after drug administration)
Population: C5 (multiple administration for 14 days) - AUC0-τ within 72 hours after the last (14th) dose administration
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 (C1A+C1B), PBTZ169 | Area Under the Concentration-time Curve (AUC0-24) | Day 1 | 1111.90 ng/ml*h | Standard Deviation 463.267 |
| Cohort 1 (C1A+C1B), PBTZ169 | Area Under the Concentration-time Curve (AUC0-24) | Day 7 | 1374.48 ng/ml*h | Standard Deviation 575.119 |
| Cohort 1 (C1A+C1B), PBTZ169 | Area Under the Concentration-time Curve (AUC0-24) | Day 14 | 1363.85 ng/ml*h | Standard Deviation 450.006 |
Secondary
Area Under the Concentration-time Curve (AUC0 t)
In the time interval from 0 to time (t) when the last blood sample is collected with a concentration above the limit of quantification. C5: for the data of Day 14 based on measurements within 72 hours after the last dose administration
Time frame: Up to 72 hours after the last drug administration
Population: C1-4 - Single or double dose administration, C5 - Multiple administration for 14 days
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 (C1A+C1B), PBTZ169 | Area Under the Concentration-time Curve (AUC0 t) | Dosing day / Day 1 | 181.63 ng*h/ml | Standard Deviation 112.236 |
| Cohort 2 (C2), PBTZ169 | Area Under the Concentration-time Curve (AUC0 t) | Dosing day / Day 1 | 575.19 ng*h/ml | Standard Deviation 221.735 |
| Cohort 3 (C3), PBTZ169 | Area Under the Concentration-time Curve (AUC0 t) | Dosing day / Day 1 | 258.42 ng*h/ml | Standard Deviation 174.149 |
| Cohort 4 (C4), PBTZ169 | Area Under the Concentration-time Curve (AUC0 t) | Dosing day / Day 1 | 342.03 ng*h/ml | Standard Deviation 141.061 |
| Cohort 5 (C5), PBTZ169 | Area Under the Concentration-time Curve (AUC0 t) | Dosing day / Day 1 | 220.77 ng*h/ml | Standard Deviation 124.754 |
| Cohort 5 (C5), PBTZ169 | Area Under the Concentration-time Curve (AUC0 t) | Day 14 | 1479.76 ng*h/ml | Standard Deviation 459.066 |
Secondary
CS Changes in Vital Signs
Safety and tolerability:Clinically significant changes in vital signs (blood pressure, HR, body temperature, RR)
Time frame: Up to last visit time point: C2, C3, C4 up to Day 7; C1 up to Day 13; C5 up to Day 21 after first drug intake
Population: Safety population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1 (C1A+C1B), PBTZ169 | CS Changes in Vital Signs | CS Changes in blood pressure | 0 No of cases of CS changes in vital signs |
| Cohort 1 (C1A+C1B), PBTZ169 | CS Changes in Vital Signs | CS changes in HH: Sinus tachycardia | 0 No of cases of CS changes in vital signs |
| Cohort 1 (C1A+C1B), PBTZ169 | CS Changes in Vital Signs | CS Changes in Temperature | 0 No of cases of CS changes in vital signs |
| Cohort 1 (C1A+C1B), PBTZ169 | CS Changes in Vital Signs | CS Changes in RR | 0 No of cases of CS changes in vital signs |
| Cohort 2 (C2), PBTZ169 | CS Changes in Vital Signs | CS Changes in Temperature | 0 No of cases of CS changes in vital signs |
| Cohort 2 (C2), PBTZ169 | CS Changes in Vital Signs | CS changes in HH: Sinus tachycardia | 3 No of cases of CS changes in vital signs |
| Cohort 2 (C2), PBTZ169 | CS Changes in Vital Signs | CS Changes in blood pressure | 0 No of cases of CS changes in vital signs |
| Cohort 2 (C2), PBTZ169 | CS Changes in Vital Signs | CS Changes in RR | 0 No of cases of CS changes in vital signs |
| Cohort 3 (C3), PBTZ169 | CS Changes in Vital Signs | CS Changes in RR | 0 No of cases of CS changes in vital signs |
| Cohort 3 (C3), PBTZ169 | CS Changes in Vital Signs | CS Changes in Temperature | 0 No of cases of CS changes in vital signs |
| Cohort 3 (C3), PBTZ169 | CS Changes in Vital Signs | CS changes in HH: Sinus tachycardia | 0 No of cases of CS changes in vital signs |
| Cohort 3 (C3), PBTZ169 | CS Changes in Vital Signs | CS Changes in blood pressure | 0 No of cases of CS changes in vital signs |
| Cohort 4 (C4), PBTZ169 | CS Changes in Vital Signs | CS Changes in blood pressure | 0 No of cases of CS changes in vital signs |
| Cohort 4 (C4), PBTZ169 | CS Changes in Vital Signs | CS Changes in RR | 0 No of cases of CS changes in vital signs |
| Cohort 4 (C4), PBTZ169 | CS Changes in Vital Signs | CS changes in HH: Sinus tachycardia | 0 No of cases of CS changes in vital signs |
| Cohort 4 (C4), PBTZ169 | CS Changes in Vital Signs | CS Changes in Temperature | 0 No of cases of CS changes in vital signs |
| Cohort 5 (C5), PBTZ169 | CS Changes in Vital Signs | CS Changes in Temperature | 0 No of cases of CS changes in vital signs |
| Cohort 5 (C5), PBTZ169 | CS Changes in Vital Signs | CS Changes in RR | 0 No of cases of CS changes in vital signs |
| Cohort 5 (C5), PBTZ169 | CS Changes in Vital Signs | CS changes in HH: Sinus tachycardia | 0 No of cases of CS changes in vital signs |
| Cohort 5 (C5), PBTZ169 | CS Changes in Vital Signs | CS Changes in blood pressure | 0 No of cases of CS changes in vital signs |
| Cohort 5 (C5), PBTZ169 | CS Changes in Vital Signs | CS changes in HH: Sinus tachycardia | 0 No of cases of CS changes in vital signs |
| Cohort 5 (C5), PBTZ169 | CS Changes in Vital Signs | CS Changes in Temperature | 0 No of cases of CS changes in vital signs |
| Cohort 5 (C5), PBTZ169 | CS Changes in Vital Signs | CS Changes in RR | 0 No of cases of CS changes in vital signs |
| Cohort 5 (C5), PBTZ169 | CS Changes in Vital Signs | CS Changes in blood pressure | 0 No of cases of CS changes in vital signs |
Secondary
ECG Results (Safety and Tolerability)
Clinically significant abnormal deviations in ECG findings
Time frame: Up to last visit time point: C2, C3, C4 up to Day 7; C1 up to Day 13; C5 up to Day 21 after first drug intake
Population: Safety population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1 (C1A+C1B), PBTZ169 | ECG Results (Safety and Tolerability) | Electrocardiogram repolarisation abnormality | 1 participants |
| Cohort 1 (C1A+C1B), PBTZ169 | ECG Results (Safety and Tolerability) | Sinus tachycardia | 0 participants |
| Cohort 1 (C1A+C1B), PBTZ169 | ECG Results (Safety and Tolerability) | Electrocardiogram abnormal | 0 participants |
| Cohort 1 (C1A+C1B), PBTZ169 | ECG Results (Safety and Tolerability) | Defect conduction intraventricular | 0 participants |
| Cohort 2 (C2), PBTZ169 | ECG Results (Safety and Tolerability) | Electrocardiogram abnormal | 0 participants |
| Cohort 2 (C2), PBTZ169 | ECG Results (Safety and Tolerability) | Sinus tachycardia | 1 participants |
| Cohort 2 (C2), PBTZ169 | ECG Results (Safety and Tolerability) | Electrocardiogram repolarisation abnormality | 0 participants |
| Cohort 2 (C2), PBTZ169 | ECG Results (Safety and Tolerability) | Defect conduction intraventricular | 0 participants |
| Cohort 3 (C3), PBTZ169 | ECG Results (Safety and Tolerability) | Defect conduction intraventricular | 0 participants |
| Cohort 3 (C3), PBTZ169 | ECG Results (Safety and Tolerability) | Electrocardiogram abnormal | 0 participants |
| Cohort 3 (C3), PBTZ169 | ECG Results (Safety and Tolerability) | Sinus tachycardia | 0 participants |
| Cohort 3 (C3), PBTZ169 | ECG Results (Safety and Tolerability) | Electrocardiogram repolarisation abnormality | 0 participants |
| Cohort 4 (C4), PBTZ169 | ECG Results (Safety and Tolerability) | Electrocardiogram repolarisation abnormality | 1 participants |
| Cohort 4 (C4), PBTZ169 | ECG Results (Safety and Tolerability) | Defect conduction intraventricular | 1 participants |
| Cohort 4 (C4), PBTZ169 | ECG Results (Safety and Tolerability) | Sinus tachycardia | 0 participants |
| Cohort 4 (C4), PBTZ169 | ECG Results (Safety and Tolerability) | Electrocardiogram abnormal | 1 participants |
| Cohort 5 (C5), PBTZ169 | ECG Results (Safety and Tolerability) | Electrocardiogram abnormal | 0 participants |
| Cohort 5 (C5), PBTZ169 | ECG Results (Safety and Tolerability) | Defect conduction intraventricular | 0 participants |
| Cohort 5 (C5), PBTZ169 | ECG Results (Safety and Tolerability) | Sinus tachycardia | 0 participants |
| Cohort 5 (C5), PBTZ169 | ECG Results (Safety and Tolerability) | Electrocardiogram repolarisation abnormality | 0 participants |
| Cohort 5 (C5), PBTZ169 | ECG Results (Safety and Tolerability) | Sinus tachycardia | 0 participants |
| Cohort 5 (C5), PBTZ169 | ECG Results (Safety and Tolerability) | Electrocardiogram abnormal | 0 participants |
| Cohort 5 (C5), PBTZ169 | ECG Results (Safety and Tolerability) | Defect conduction intraventricular | 0 participants |
| Cohort 5 (C5), PBTZ169 | ECG Results (Safety and Tolerability) | Electrocardiogram repolarisation abnormality | 0 participants |
Secondary
Elimination Constant Kel
Time frame: Up to 72 hours after the last drug administration
Population: C1-4 - Single or double dose administration, C5 - Multiple administration for 14 days
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 (C1A+C1B), PBTZ169 | Elimination Constant Kel | Dosing day / Day 1 | 0.1765 1/h | Standard Deviation 0.1067 |
| Cohort 2 (C2), PBTZ169 | Elimination Constant Kel | Dosing day / Day 1 | 0.1027 1/h | Standard Deviation 0.0356 |
| Cohort 3 (C3), PBTZ169 | Elimination Constant Kel | Dosing day / Day 1 | 0.0993 1/h | Standard Deviation 0.0396 |
| Cohort 4 (C4), PBTZ169 | Elimination Constant Kel | Dosing day / Day 1 | 0.1865 1/h | Standard Deviation 0.1175 |
| Cohort 5 (C5), PBTZ169 | Elimination Constant Kel | Dosing day / Day 1 | 0.1154 1/h | Standard Deviation 0.0682 |
| Cohort 5 (C5), PBTZ169 | Elimination Constant Kel | Dosing day / Day 1 | 0.0866 1/h | Standard Deviation 0.0501 |
| Cohort 5 (C5), PBTZ169 | Elimination Constant Kel | Day 7 | 0.0765 1/h | Standard Deviation 0.024 |
| Cohort 5 (C5), PBTZ169 | Elimination Constant Kel | Day 14 | 0.0512 1/h | Standard Deviation 0.018 |
Secondary
Laboratory Examinations Results (Safety and Tolerability)
Complete blood count, biochemical blood test, urine analysis
Time frame: Up to last visit time point: C2, C3, C4 up to Day 7; C1 up to Day 13; C5 up to Day 21 after first drug intake
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1 (C1A+C1B), PBTZ169 | Laboratory Examinations Results (Safety and Tolerability) | CS Haemoglobin decreased | 0 participants |
| Cohort 1 (C1A+C1B), PBTZ169 | Laboratory Examinations Results (Safety and Tolerability) | CS Hypercreatininaemia | 0 participants |
| Cohort 1 (C1A+C1B), PBTZ169 | Laboratory Examinations Results (Safety and Tolerability) | CS Blood glucose increase | 1 participants |
| Cohort 1 (C1A+C1B), PBTZ169 | Laboratory Examinations Results (Safety and Tolerability) | CS Thrombocytosis | 0 participants |
| Cohort 1 (C1A+C1B), PBTZ169 | Laboratory Examinations Results (Safety and Tolerability) | CS Anaemia | 0 participants |
| Cohort 2 (C2), PBTZ169 | Laboratory Examinations Results (Safety and Tolerability) | CS Hypercreatininaemia | 0 participants |
| Cohort 2 (C2), PBTZ169 | Laboratory Examinations Results (Safety and Tolerability) | CS Haemoglobin decreased | 0 participants |
| Cohort 2 (C2), PBTZ169 | Laboratory Examinations Results (Safety and Tolerability) | CS Blood glucose increase | 2 participants |
| Cohort 2 (C2), PBTZ169 | Laboratory Examinations Results (Safety and Tolerability) | CS Thrombocytosis | 0 participants |
| Cohort 2 (C2), PBTZ169 | Laboratory Examinations Results (Safety and Tolerability) | CS Anaemia | 0 participants |
| Cohort 3 (C3), PBTZ169 | Laboratory Examinations Results (Safety and Tolerability) | CS Hypercreatininaemia | 0 participants |
| Cohort 3 (C3), PBTZ169 | Laboratory Examinations Results (Safety and Tolerability) | CS Haemoglobin decreased | 0 participants |
| Cohort 3 (C3), PBTZ169 | Laboratory Examinations Results (Safety and Tolerability) | CS Thrombocytosis | 0 participants |
| Cohort 3 (C3), PBTZ169 | Laboratory Examinations Results (Safety and Tolerability) | CS Anaemia | 0 participants |
| Cohort 3 (C3), PBTZ169 | Laboratory Examinations Results (Safety and Tolerability) | CS Blood glucose increase | 0 participants |
| Cohort 4 (C4), PBTZ169 | Laboratory Examinations Results (Safety and Tolerability) | CS Anaemia | 0 participants |
| Cohort 4 (C4), PBTZ169 | Laboratory Examinations Results (Safety and Tolerability) | CS Blood glucose increase | 0 participants |
| Cohort 4 (C4), PBTZ169 | Laboratory Examinations Results (Safety and Tolerability) | CS Hypercreatininaemia | 0 participants |
| Cohort 4 (C4), PBTZ169 | Laboratory Examinations Results (Safety and Tolerability) | CS Haemoglobin decreased | 0 participants |
| Cohort 4 (C4), PBTZ169 | Laboratory Examinations Results (Safety and Tolerability) | CS Thrombocytosis | 0 participants |
| Cohort 5 (C5), PBTZ169 | Laboratory Examinations Results (Safety and Tolerability) | CS Haemoglobin decreased | 0 participants |
| Cohort 5 (C5), PBTZ169 | Laboratory Examinations Results (Safety and Tolerability) | CS Blood glucose increase | 0 participants |
| Cohort 5 (C5), PBTZ169 | Laboratory Examinations Results (Safety and Tolerability) | CS Thrombocytosis | 0 participants |
| Cohort 5 (C5), PBTZ169 | Laboratory Examinations Results (Safety and Tolerability) | CS Hypercreatininaemia | 0 participants |
| Cohort 5 (C5), PBTZ169 | Laboratory Examinations Results (Safety and Tolerability) | CS Anaemia | 0 participants |
| Cohort 5 (C5), PBTZ169 | Laboratory Examinations Results (Safety and Tolerability) | CS Blood glucose increase | 0 participants |
| Cohort 5 (C5), PBTZ169 | Laboratory Examinations Results (Safety and Tolerability) | CS Haemoglobin decreased | 1 participants |
| Cohort 5 (C5), PBTZ169 | Laboratory Examinations Results (Safety and Tolerability) | CS Hypercreatininaemia | 2 participants |
| Cohort 5 (C5), PBTZ169 | Laboratory Examinations Results (Safety and Tolerability) | CS Thrombocytosis | 1 participants |
| Cohort 5 (C5), PBTZ169 | Laboratory Examinations Results (Safety and Tolerability) | CS Anaemia | 1 participants |
Secondary
Number of Subjects With CS Changes in Vital Signs
Safety and tolerability: No. of sbjs with clinically significant changes in vital signs (blood pressure, HR, body temperature, RR)
Time frame: Up to last visit time point: C2, C3, C4 up to Day 7; C1 up to Day 13; C5 up to Day 21 after first drug intake
Population: Safety population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1 (C1A+C1B), PBTZ169 | Number of Subjects With CS Changes in Vital Signs | CS Sinus tachycardia | 0 participants |
| Cohort 1 (C1A+C1B), PBTZ169 | Number of Subjects With CS Changes in Vital Signs | CS RR changes | 0 participants |
| Cohort 1 (C1A+C1B), PBTZ169 | Number of Subjects With CS Changes in Vital Signs | CS Temperature changes | 0 participants |
| Cohort 1 (C1A+C1B), PBTZ169 | Number of Subjects With CS Changes in Vital Signs | CS Blood pressure deviations | 0 participants |
| Cohort 2 (C2), PBTZ169 | Number of Subjects With CS Changes in Vital Signs | CS Sinus tachycardia | 1 participants |
| Cohort 2 (C2), PBTZ169 | Number of Subjects With CS Changes in Vital Signs | CS RR changes | 0 participants |
| Cohort 2 (C2), PBTZ169 | Number of Subjects With CS Changes in Vital Signs | CS Blood pressure deviations | 0 participants |
| Cohort 2 (C2), PBTZ169 | Number of Subjects With CS Changes in Vital Signs | CS Temperature changes | 0 participants |
| Cohort 3 (C3), PBTZ169 | Number of Subjects With CS Changes in Vital Signs | CS RR changes | 0 participants |
| Cohort 3 (C3), PBTZ169 | Number of Subjects With CS Changes in Vital Signs | CS Sinus tachycardia | 0 participants |
| Cohort 3 (C3), PBTZ169 | Number of Subjects With CS Changes in Vital Signs | CS Temperature changes | 0 participants |
| Cohort 3 (C3), PBTZ169 | Number of Subjects With CS Changes in Vital Signs | CS Blood pressure deviations | 0 participants |
| Cohort 4 (C4), PBTZ169 | Number of Subjects With CS Changes in Vital Signs | CS Temperature changes | 0 participants |
| Cohort 4 (C4), PBTZ169 | Number of Subjects With CS Changes in Vital Signs | CS RR changes | 0 participants |
| Cohort 4 (C4), PBTZ169 | Number of Subjects With CS Changes in Vital Signs | CS Sinus tachycardia | 0 participants |
| Cohort 4 (C4), PBTZ169 | Number of Subjects With CS Changes in Vital Signs | CS Blood pressure deviations | 0 participants |
| Cohort 5 (C5), PBTZ169 | Number of Subjects With CS Changes in Vital Signs | CS Sinus tachycardia | 0 participants |
| Cohort 5 (C5), PBTZ169 | Number of Subjects With CS Changes in Vital Signs | CS Temperature changes | 0 participants |
| Cohort 5 (C5), PBTZ169 | Number of Subjects With CS Changes in Vital Signs | CS RR changes | 0 participants |
| Cohort 5 (C5), PBTZ169 | Number of Subjects With CS Changes in Vital Signs | CS Blood pressure deviations | 0 participants |
| Cohort 5 (C5), PBTZ169 | Number of Subjects With CS Changes in Vital Signs | CS RR changes | 0 participants |
| Cohort 5 (C5), PBTZ169 | Number of Subjects With CS Changes in Vital Signs | CS Blood pressure deviations | 0 participants |
| Cohort 5 (C5), PBTZ169 | Number of Subjects With CS Changes in Vital Signs | CS Sinus tachycardia | 0 participants |
| Cohort 5 (C5), PBTZ169 | Number of Subjects With CS Changes in Vital Signs | CS Temperature changes | 0 participants |
Secondary
Peak Plasma Concentration (Сmax)
Сmax of PBTZ169 at the timepoints: C1A, C1B, C2 and C4: point 0 (-5 min to -1 min), 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 9:00, 12:00, 24:00, 48:00 and 72:00 (h:min). C3 (two administrations): point 0 (-5 min to -1 min), 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 9:00, 12:00 (the point before the second administration from -5 min to -1 min), 12:30, 13:00, 13:30, 14:00, 15:00, 16:00, 18:00, 21:00, 24:00, 48:00 , 72:00 (h:min) after the first administration of the medicinal product. C5 (14 days of intake): 5 minutes before the administration (only until the first dose), 0 min and within 24 h after the administration of the 1st, 7th and last (14th) dose: 0:15, 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00, 24:00 (h:min after the administration of a dose of the medicinal product); at 48 h and 72 h points after the last (14th) dose of PBTZ169
Time frame: In the dosing interval (up to 72 hours after the last drug administration)
Population: C1-4 - Single or double dose administration, C5 - Multiple administration for 14 days
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 (C1A+C1B), PBTZ169 | Peak Plasma Concentration (Сmax) | 12 h | 1.144 ng/ml | Geometric Coefficient of Variation 59.1 |
| Cohort 1 (C1A+C1B), PBTZ169 | Peak Plasma Concentration (Сmax) | 72 h | 0.250 ng/ml | Geometric Coefficient of Variation 0 |
| Cohort 1 (C1A+C1B), PBTZ169 | Peak Plasma Concentration (Сmax) | 2 h | 33.660 ng/ml | Geometric Coefficient of Variation 118.4 |
| Cohort 1 (C1A+C1B), PBTZ169 | Peak Plasma Concentration (Сmax) | 4 h | 10.775 ng/ml | Geometric Coefficient of Variation 96.4 |
| Cohort 1 (C1A+C1B), PBTZ169 | Peak Plasma Concentration (Сmax) | 24 h | 0.456 ng/ml | Geometric Coefficient of Variation 106.1 |
| Cohort 1 (C1A+C1B), PBTZ169 | Peak Plasma Concentration (Сmax) | Before dosing | 0.250 ng/ml | Geometric Coefficient of Variation 0 |
| Cohort 1 (C1A+C1B), PBTZ169 | Peak Plasma Concentration (Сmax) | 9 h | 1.827 ng/ml | Geometric Coefficient of Variation 77.4 |
| Cohort 1 (C1A+C1B), PBTZ169 | Peak Plasma Concentration (Сmax) | 6 h | 4.195 ng/ml | Geometric Coefficient of Variation 75.3 |
| Cohort 1 (C1A+C1B), PBTZ169 | Peak Plasma Concentration (Сmax) | 1.5 h | 40.998 ng/ml | Geometric Coefficient of Variation 108.3 |
| Cohort 1 (C1A+C1B), PBTZ169 | Peak Plasma Concentration (Сmax) | 1 h | 43.131 ng/ml | Geometric Coefficient of Variation 84.5 |
| Cohort 1 (C1A+C1B), PBTZ169 | Peak Plasma Concentration (Сmax) | 48 h | 0.250 ng/ml | Geometric Coefficient of Variation 0 |
| Cohort 1 (C1A+C1B), PBTZ169 | Peak Plasma Concentration (Сmax) | 0.5 h | 10.701 ng/ml | Geometric Coefficient of Variation 236.6 |
| Cohort 1 (C1A+C1B), PBTZ169 | Peak Plasma Concentration (Сmax) | 3 h | 19.435 ng/ml | Geometric Coefficient of Variation 106.4 |
| Cohort 2 (C2), PBTZ169 | Peak Plasma Concentration (Сmax) | 1 h | 8.827 ng/ml | Geometric Coefficient of Variation 415.1 |
| Cohort 2 (C2), PBTZ169 | Peak Plasma Concentration (Сmax) | 4 h | 88.719 ng/ml | Geometric Coefficient of Variation 50.2 |
| Cohort 2 (C2), PBTZ169 | Peak Plasma Concentration (Сmax) | 6 h | 31.083 ng/ml | Geometric Coefficient of Variation 46.8 |
| Cohort 2 (C2), PBTZ169 | Peak Plasma Concentration (Сmax) | 3 h | 90.330 ng/ml | Geometric Coefficient of Variation 84.9 |
| Cohort 2 (C2), PBTZ169 | Peak Plasma Concentration (Сmax) | 9 h | 10.815 ng/ml | Geometric Coefficient of Variation 71.3 |
| Cohort 2 (C2), PBTZ169 | Peak Plasma Concentration (Сmax) | 1.5 h | 59.226 ng/ml | Geometric Coefficient of Variation 150.6 |
| Cohort 2 (C2), PBTZ169 | Peak Plasma Concentration (Сmax) | 0.5 h | 0.399 ng/ml | Geometric Coefficient of Variation 199.6 |
| Cohort 2 (C2), PBTZ169 | Peak Plasma Concentration (Сmax) | 48 h | 0.385 ng/ml | Geometric Coefficient of Variation 62.2 |
| Cohort 2 (C2), PBTZ169 | Peak Plasma Concentration (Сmax) | 24 h | 1.428 ng/ml | Geometric Coefficient of Variation 42.2 |
| Cohort 2 (C2), PBTZ169 | Peak Plasma Concentration (Сmax) | Before dosing | 0.250 ng/ml | Geometric Coefficient of Variation 0 |
| Cohort 2 (C2), PBTZ169 | Peak Plasma Concentration (Сmax) | 2 h | 95.641 ng/ml | Geometric Coefficient of Variation 113.9 |
| Cohort 2 (C2), PBTZ169 | Peak Plasma Concentration (Сmax) | 72 h | 0.260 ng/ml | Geometric Coefficient of Variation 18.3 |
| Cohort 2 (C2), PBTZ169 | Peak Plasma Concentration (Сmax) | 12 h | 4.621 ng/ml | Geometric Coefficient of Variation 55.6 |
| Cohort 3 (C3), PBTZ169 | Peak Plasma Concentration (Сmax) | 1.5 h | 48.390 ng/ml | Geometric Coefficient of Variation 81.1 |
| Cohort 3 (C3), PBTZ169 | Peak Plasma Concentration (Сmax) | 2 h | 43.633 ng/ml | Geometric Coefficient of Variation 145.2 |
| Cohort 3 (C3), PBTZ169 | Peak Plasma Concentration (Сmax) | 72 h | 0.250 ng/ml | Geometric Coefficient of Variation 0 |
| Cohort 3 (C3), PBTZ169 | Peak Plasma Concentration (Сmax) | 3 h | 22.159 ng/ml | Geometric Coefficient of Variation 167.4 |
| Cohort 3 (C3), PBTZ169 | Peak Plasma Concentration (Сmax) | 48 h | 0.288 ng/ml | Geometric Coefficient of Variation 47.1 |
| Cohort 3 (C3), PBTZ169 | Peak Plasma Concentration (Сmax) | 24 h | 0.731 ng/ml | Geometric Coefficient of Variation 85.5 |
| Cohort 3 (C3), PBTZ169 | Peak Plasma Concentration (Сmax) | Before dosing | 0.250 ng/ml | Geometric Coefficient of Variation 0 |
| Cohort 3 (C3), PBTZ169 | Peak Plasma Concentration (Сmax) | 1 h | 45.729 ng/ml | Geometric Coefficient of Variation 100.8 |
| Cohort 3 (C3), PBTZ169 | Peak Plasma Concentration (Сmax) | 12 h | 1.944 ng/ml | Geometric Coefficient of Variation 125.3 |
| Cohort 3 (C3), PBTZ169 | Peak Plasma Concentration (Сmax) | 0.5 h | 19.351 ng/ml | Geometric Coefficient of Variation 228.4 |
| Cohort 3 (C3), PBTZ169 | Peak Plasma Concentration (Сmax) | 9 h | 2.672 ng/ml | Geometric Coefficient of Variation 166.7 |
| Cohort 3 (C3), PBTZ169 | Peak Plasma Concentration (Сmax) | 4 h | 15.773 ng/ml | Geometric Coefficient of Variation 184 |
| Cohort 3 (C3), PBTZ169 | Peak Plasma Concentration (Сmax) | 6 h | 5.884 ng/ml | Geometric Coefficient of Variation 171.9 |
| Cohort 4 (C4), PBTZ169 | Peak Plasma Concentration (Сmax) | 0.5 h | 26.048 ng/ml | Geometric Coefficient of Variation 131 |
| Cohort 4 (C4), PBTZ169 | Peak Plasma Concentration (Сmax) | 3 h | 11.438 ng/ml | Geometric Coefficient of Variation 60.2 |
| Cohort 4 (C4), PBTZ169 | Peak Plasma Concentration (Сmax) | 4 h | 6.593 ng/ml | Geometric Coefficient of Variation 73.8 |
| Cohort 4 (C4), PBTZ169 | Peak Plasma Concentration (Сmax) | 13 h | 26.515 ng/ml | Geometric Coefficient of Variation 152.4 |
| Cohort 4 (C4), PBTZ169 | Peak Plasma Concentration (Сmax) | Before dosing | 0.250 ng/ml | Geometric Coefficient of Variation 0 |
| Cohort 4 (C4), PBTZ169 | Peak Plasma Concentration (Сmax) | 1.5 h | 45.679 ng/ml | Geometric Coefficient of Variation 43.9 |
| Cohort 4 (C4), PBTZ169 | Peak Plasma Concentration (Сmax) | 1 h | 48.328 ng/ml | Geometric Coefficient of Variation 46.8 |
| Cohort 4 (C4), PBTZ169 | Peak Plasma Concentration (Сmax) | 2 h | 23.782 ng/ml | Geometric Coefficient of Variation 46.9 |
| Cohort 4 (C4), PBTZ169 | Peak Plasma Concentration (Сmax) | 6 h | 3.461 ng/ml | Geometric Coefficient of Variation 51.7 |
| Cohort 4 (C4), PBTZ169 | Peak Plasma Concentration (Сmax) | 9 h | 1.330 ng/ml | Geometric Coefficient of Variation 39.1 |
| Cohort 4 (C4), PBTZ169 | Peak Plasma Concentration (Сmax) | 12 h | 0.859 ng/ml | Geometric Coefficient of Variation 51.7 |
| Cohort 4 (C4), PBTZ169 | Peak Plasma Concentration (Сmax) | 12.5 h | 6.247 ng/ml | Geometric Coefficient of Variation 270.1 |
| Cohort 4 (C4), PBTZ169 | Peak Plasma Concentration (Сmax) | 13.5 h | 54.520 ng/ml | Geometric Coefficient of Variation 65.7 |
| Cohort 4 (C4), PBTZ169 | Peak Plasma Concentration (Сmax) | 14 h | 41.996 ng/ml | Geometric Coefficient of Variation 61.7 |
| Cohort 4 (C4), PBTZ169 | Peak Plasma Concentration (Сmax) | 15 h | 23.165 ng/ml | Geometric Coefficient of Variation 64.4 |
| Cohort 4 (C4), PBTZ169 | Peak Plasma Concentration (Сmax) | 16 h | 13.113 ng/ml | Geometric Coefficient of Variation 88.3 |
| Cohort 4 (C4), PBTZ169 | Peak Plasma Concentration (Сmax) | 18 h | 8.351 ng/ml | Geometric Coefficient of Variation 127.2 |
| Cohort 4 (C4), PBTZ169 | Peak Plasma Concentration (Сmax) | 21 h | 3.590 ng/ml | Geometric Coefficient of Variation 139.2 |
| Cohort 4 (C4), PBTZ169 | Peak Plasma Concentration (Сmax) | 24 h | 1.763 ng/ml | Geometric Coefficient of Variation 75.1 |
| Cohort 4 (C4), PBTZ169 | Peak Plasma Concentration (Сmax) | 48 h | 0.383 ng/ml | Geometric Coefficient of Variation 65.9 |
| Cohort 4 (C4), PBTZ169 | Peak Plasma Concentration (Сmax) | 72 h | 0.269 ng/ml | Geometric Coefficient of Variation 23.3 |
| Cohort 5 (C5), PBTZ169 | Peak Plasma Concentration (Сmax) | 48 h | 0.269 ng/ml | Geometric Coefficient of Variation 23.6 |
| Cohort 5 (C5), PBTZ169 | Peak Plasma Concentration (Сmax) | 72 h | 0.250 ng/ml | Geometric Coefficient of Variation 0 |
| Cohort 5 (C5), PBTZ169 | Peak Plasma Concentration (Сmax) | 3 h | 23.571 ng/ml | Geometric Coefficient of Variation 75.4 |
| Cohort 5 (C5), PBTZ169 | Peak Plasma Concentration (Сmax) | 2 h | 39.253 ng/ml | Geometric Coefficient of Variation 73.4 |
| Cohort 5 (C5), PBTZ169 | Peak Plasma Concentration (Сmax) | 6 h | 5.771 ng/ml | Geometric Coefficient of Variation 73 |
| Cohort 5 (C5), PBTZ169 | Peak Plasma Concentration (Сmax) | 1.5 h | 54.949 ng/ml | Geometric Coefficient of Variation 66.3 |
| Cohort 5 (C5), PBTZ169 | Peak Plasma Concentration (Сmax) | 12 h | 1.440 ng/ml | Geometric Coefficient of Variation 50.7 |
| Cohort 5 (C5), PBTZ169 | Peak Plasma Concentration (Сmax) | 4 h | 13.897 ng/ml | Geometric Coefficient of Variation 79 |
| Cohort 5 (C5), PBTZ169 | Peak Plasma Concentration (Сmax) | 24 h | 0.591 ng/ml | Geometric Coefficient of Variation 55.8 |
| Cohort 5 (C5), PBTZ169 | Peak Plasma Concentration (Сmax) | 1 h | 74.711 ng/ml | Geometric Coefficient of Variation 52.4 |
| Cohort 5 (C5), PBTZ169 | Peak Plasma Concentration (Сmax) | 0.5 h | 24.576 ng/ml | Geometric Coefficient of Variation 76.6 |
| Cohort 5 (C5), PBTZ169 | Peak Plasma Concentration (Сmax) | Before dosing | 0.250 ng/ml | Geometric Coefficient of Variation 0 |
| Cohort 5 (C5), PBTZ169 | Peak Plasma Concentration (Сmax) | 9 h | 2.880 ng/ml | Geometric Coefficient of Variation 87.8 |
| Cohort 5 (C5), PBTZ169 | Peak Plasma Concentration (Сmax) | Day 14, 72 h | 0.360 ng/ml | Geometric Coefficient of Variation 90 |
| Cohort 5 (C5), PBTZ169 | Peak Plasma Concentration (Сmax) | Day 14, 8 h | 42.315 ng/ml | Geometric Coefficient of Variation 67 |
| Cohort 5 (C5), PBTZ169 | Peak Plasma Concentration (Сmax) | Day 14, 12 h | 14.270 ng/ml | Geometric Coefficient of Variation 48.1 |
| Cohort 5 (C5), PBTZ169 | Peak Plasma Concentration (Сmax) | 24 h | 4.695 ng/ml | Geometric Coefficient of Variation 128.9 |
| Cohort 5 (C5), PBTZ169 | Peak Plasma Concentration (Сmax) | 8 h | 34.331 ng/ml | Geometric Coefficient of Variation 149.2 |
| Cohort 5 (C5), PBTZ169 | Peak Plasma Concentration (Сmax) | Day 14, 24 h | 6.040 ng/ml | Geometric Coefficient of Variation 58.1 |
| Cohort 5 (C5), PBTZ169 | Peak Plasma Concentration (Сmax) | 3 h | 128.518 ng/ml | Geometric Coefficient of Variation 95 |
| Cohort 5 (C5), PBTZ169 | Peak Plasma Concentration (Сmax) | 0.5 h | 1.183 ng/ml | Geometric Coefficient of Variation 864.4 |
| Cohort 5 (C5), PBTZ169 | Peak Plasma Concentration (Сmax) | Day 14, 48 h | 2.128 ng/ml | Geometric Coefficient of Variation 103.6 |
| Cohort 5 (C5), PBTZ169 | Peak Plasma Concentration (Сmax) | Day 7, before dosing | 8.352 ng/ml | Geometric Coefficient of Variation 102.5 |
| Cohort 5 (C5), PBTZ169 | Peak Plasma Concentration (Сmax) | Day 7, 0.25 h | 8.424 ng/ml | Geometric Coefficient of Variation 68.8 |
| Cohort 5 (C5), PBTZ169 | Peak Plasma Concentration (Сmax) | Day 7, 1 h | 102.727 ng/ml | Geometric Coefficient of Variation 146.9 |
| Cohort 5 (C5), PBTZ169 | Peak Plasma Concentration (Сmax) | Day 7, 1.5 h | 196.799 ng/ml | Geometric Coefficient of Variation 124 |
| Cohort 5 (C5), PBTZ169 | Peak Plasma Concentration (Сmax) | Day 7, 2 h | 247.253 ng/ml | Geometric Coefficient of Variation 90.7 |
| Cohort 5 (C5), PBTZ169 | Peak Plasma Concentration (Сmax) | Day 7, 3 h | 214.245 ng/ml | Geometric Coefficient of Variation 53.4 |
| Cohort 5 (C5), PBTZ169 | Peak Plasma Concentration (Сmax) | Day 7, 4 h | 163.523 ng/ml | Geometric Coefficient of Variation 36.5 |
| Cohort 5 (C5), PBTZ169 | Peak Plasma Concentration (Сmax) | Day 7, 6 h | 71.494 ng/ml | Geometric Coefficient of Variation 75.1 |
| Cohort 5 (C5), PBTZ169 | Peak Plasma Concentration (Сmax) | Day 7, 8 h | 34.724 ng/ml | Geometric Coefficient of Variation 60.1 |
| Cohort 5 (C5), PBTZ169 | Peak Plasma Concentration (Сmax) | Day 7, 10 h | 21.163 ng/ml | Geometric Coefficient of Variation 62.3 |
| Cohort 5 (C5), PBTZ169 | Peak Plasma Concentration (Сmax) | Day 7, 12 h | 13.464 ng/ml | Geometric Coefficient of Variation 54.6 |
| Cohort 5 (C5), PBTZ169 | Peak Plasma Concentration (Сmax) | Day 7, 24 h | 6.509 ng/ml | Geometric Coefficient of Variation 51.5 |
| Cohort 5 (C5), PBTZ169 | Peak Plasma Concentration (Сmax) | 2 h | 162.170 ng/ml | Geometric Coefficient of Variation 141.1 |
| Cohort 5 (C5), PBTZ169 | Peak Plasma Concentration (Сmax) | 4 h | 110.614 ng/ml | Geometric Coefficient of Variation 68.7 |
| Cohort 5 (C5), PBTZ169 | Peak Plasma Concentration (Сmax) | 1.5 h | 109.319 ng/ml | Geometric Coefficient of Variation 203.7 |
| Cohort 5 (C5), PBTZ169 | Peak Plasma Concentration (Сmax) | 10 h | 14.636 ng/ml | Geometric Coefficient of Variation 93.8 |
| Cohort 5 (C5), PBTZ169 | Peak Plasma Concentration (Сmax) | 6 h | 68.001 ng/ml | Geometric Coefficient of Variation 127 |
| Cohort 5 (C5), PBTZ169 | Peak Plasma Concentration (Сmax) | 1 h | 22.877 ng/ml | Geometric Coefficient of Variation 3056.8 |
| Cohort 5 (C5), PBTZ169 | Peak Plasma Concentration (Сmax) | Day 14, 0.25 h | 7.625 ng/ml | Geometric Coefficient of Variation 50.6 |
| Cohort 5 (C5), PBTZ169 | Peak Plasma Concentration (Сmax) | Day 14, befor dosing | 7.657 ng/ml | Geometric Coefficient of Variation 48.2 |
| Cohort 5 (C5), PBTZ169 | Peak Plasma Concentration (Сmax) | 0.25 h | 0.250 ng/ml | Geometric Coefficient of Variation 0 |
| Cohort 5 (C5), PBTZ169 | Peak Plasma Concentration (Сmax) | Before dosing | 0.250 ng/ml | Geometric Coefficient of Variation 0 |
| Cohort 5 (C5), PBTZ169 | Peak Plasma Concentration (Сmax) | Day 14, 0.5 h | 12.027 ng/ml | Geometric Coefficient of Variation 47.3 |
| Cohort 5 (C5), PBTZ169 | Peak Plasma Concentration (Сmax) | Day 7, 0.5 h | 15.488 ng/ml | Geometric Coefficient of Variation 86.8 |
| Cohort 5 (C5), PBTZ169 | Peak Plasma Concentration (Сmax) | 12 h | 8.917 ng/ml | Geometric Coefficient of Variation 73.8 |
| Cohort 5 (C5), PBTZ169 | Peak Plasma Concentration (Сmax) | Day 14, 1 h | 56.489 ng/ml | Geometric Coefficient of Variation 185.3 |
| Cohort 5 (C5), PBTZ169 | Peak Plasma Concentration (Сmax) | Day 14, 1.5 h | 150.856 ng/ml | Geometric Coefficient of Variation 123.3 |
| Cohort 5 (C5), PBTZ169 | Peak Plasma Concentration (Сmax) | Day 14, 2 h | 208.562 ng/ml | Geometric Coefficient of Variation 56 |
| Cohort 5 (C5), PBTZ169 | Peak Plasma Concentration (Сmax) | Day 14, 3 h | 205.471 ng/ml | Geometric Coefficient of Variation 69.6 |
| Cohort 5 (C5), PBTZ169 | Peak Plasma Concentration (Сmax) | Day 14, 4 h | 189.609 ng/ml | Geometric Coefficient of Variation 39.2 |
| Cohort 5 (C5), PBTZ169 | Peak Plasma Concentration (Сmax) | Day 14, 6 h | 81.751 ng/ml | Geometric Coefficient of Variation 55.6 |
| Cohort 5 (C5), PBTZ169 | Peak Plasma Concentration (Сmax) | Day 14, 10 h | 28.824 ng/ml | Geometric Coefficient of Variation 121.6 |
Secondary
Plasma Half-life Time (T1/2)
Time frame: Up to 72 hours after the last drug administration
Population: C1-4 - Single or double dose administration, C5 - Multiple administration for 14 days
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 (C1A+C1B), PBTZ169 | Plasma Half-life Time (T1/2) | Dosing day / Day 1 | 5.46 h | Standard Deviation 3.134 |
| Cohort 2 (C2), PBTZ169 | Plasma Half-life Time (T1/2) | Dosing day / Day 1 | 7.68 h | Standard Deviation 3.063 |
| Cohort 3 (C3), PBTZ169 | Plasma Half-life Time (T1/2) | Dosing day / Day 1 | 7.68 h | Standard Deviation 2.043 |
| Cohort 4 (C4), PBTZ169 | Plasma Half-life Time (T1/2) | Dosing day / Day 1 | 6.33 h | Standard Deviation 5.275 |
| Cohort 5 (C5), PBTZ169 | Plasma Half-life Time (T1/2) | Dosing day / Day 1 | 8.00 h | Standard Deviation 4.258 |
| Cohort 5 (C5), PBTZ169 | Plasma Half-life Time (T1/2) | Day 7 | 9.98 h | Standard Deviation 3.357 |
| Cohort 5 (C5), PBTZ169 | Plasma Half-life Time (T1/2) | Dosing day / Day 1 | 10.07 h | Standard Deviation 4.294 |
| Cohort 5 (C5), PBTZ169 | Plasma Half-life Time (T1/2) | Day 14 | 14.81 h | Standard Deviation 4.365 |
Secondary
Relative Bioavailability
f=AUC0-∞(T)/AUC0-∞(R); f'=AUC0-t(T)/AUC0-t(R) Test (T) - PBTZ169 640 mg after meals, reference (R) - PBTZ169 640 mg fasted
Time frame: Up to 72 hours after the last drug administration
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Cohort 1 (C1A+C1B), PBTZ169 | Relative Bioavailability | f | 344.54 % of T/R geometric mean ratio |
| Cohort 1 (C1A+C1B), PBTZ169 | Relative Bioavailability | f' | 350.20 % of T/R geometric mean ratio |
Secondary
Relative Degree of Absorption
f=Cmax(T)/Cmax(R). Test (T) - PBTZ169 640 mg after meals, reference (R) - PBTZ169 640 mg fasted
Time frame: Up to 72 hours after the last drug administration
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Cohort 1 (C1A+C1B), PBTZ169 | Relative Degree of Absorption | 229.03 geometric mean ratio, % |
Secondary
Results of Physical Examination: CS Deviations
Safety and tolerability: number of physical examinations with CS deviations in results
Time frame: Up to last visit time point: C2, C3, C4 up to Day 7; C1 up to Day 13; C5 up to Day 21 after first drug intake
Population: Safety population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1 (C1A+C1B), PBTZ169 | Results of Physical Examination: CS Deviations | 0 CS physical examination deviations |
| Cohort 2 (C2), PBTZ169 | Results of Physical Examination: CS Deviations | 0 CS physical examination deviations |
| Cohort 3 (C3), PBTZ169 | Results of Physical Examination: CS Deviations | 0 CS physical examination deviations |
| Cohort 4 (C4), PBTZ169 | Results of Physical Examination: CS Deviations | 0 CS physical examination deviations |
| Cohort 5 (C5), PBTZ169 | Results of Physical Examination: CS Deviations | 0 CS physical examination deviations |
| Cohort 5 (C5), PBTZ169 | Results of Physical Examination: CS Deviations | 0 CS physical examination deviations |
Secondary
Time to Reach Maximum Concentration (Tmax)
Cohort 3: Tmax relative to the time of administration in any dosage interval
Time frame: Up to 72 hours after the last drug administration
Population: C1-4 - Single or double dose administration, C5 - Multiple administration for 14 days
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 (C1A+C1B), PBTZ169 | Time to Reach Maximum Concentration (Tmax) | Dosing day / Day 1 | 1.73 h | Standard Deviation 0.896 |
| Cohort 2 (C2), PBTZ169 | Time to Reach Maximum Concentration (Tmax) | Dosing day / Day 1 | 2.90 h | Standard Deviation 0.912 |
| Cohort 3 (C3), PBTZ169 | Time to Reach Maximum Concentration (Tmax) | Dosing day / Day 1 | 1.65 h | Standard Deviation 0.709 |
| Cohort 4 (C4), PBTZ169 | Time to Reach Maximum Concentration (Tmax) | Dosing day / Day 1 | 1.35 h | Standard Deviation 0.747 |
| Cohort 5 (C5), PBTZ169 | Time to Reach Maximum Concentration (Tmax) | Dosing day / Day 1 | 1.15 h | Standard Deviation 0.242 |
| Cohort 5 (C5), PBTZ169 | Time to Reach Maximum Concentration (Tmax) | Dosing day / Day 1 | 2.60 h | Standard Deviation 1.41 |
| Cohort 5 (C5), PBTZ169 | Time to Reach Maximum Concentration (Tmax) | Day 7 | 2.25 h | Standard Deviation 0.825 |
| Cohort 5 (C5), PBTZ169 | Time to Reach Maximum Concentration (Tmax) | Day 14 | 2.40 h | Standard Deviation 1.022 |
Secondary
Total Clearance (Clt/F)
Time frame: Up to 72 hours after the last drug administration
Population: C1-4 - Single or double dose administration, C5 - Multiple administration for 14 days
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 (C1A+C1B), PBTZ169 | Total Clearance (Clt/F) | Dosing day / Day 1 | 4910.09 l/h | Standard Deviation 2711.818 |
| Cohort 2 (C2), PBTZ169 | Total Clearance (Clt/F) | Dosing day / Day 1 | 1260.08 l/h | Standard Deviation 491.974 |
| Cohort 3 (C3), PBTZ169 | Total Clearance (Clt/F) | Dosing day / Day 1 | 8246.42 l/h | Standard Deviation 12883.377 |
| Cohort 4 (C4), PBTZ169 | Total Clearance (Clt/F) | Dosing day / Day 1 | 4185.23 l/h | Standard Deviation 1507.23 |
| Cohort 5 (C5), PBTZ169 | Total Clearance (Clt/F) | Dosing day / Day 1 | 6617.74 l/h | Standard Deviation 2217.282 |
| Cohort 5 (C5), PBTZ169 | Total Clearance (Clt/F) | Dosing day / Day 1 | 1302.31 l/h | Standard Deviation 548.472 |
| Cohort 5 (C5), PBTZ169 | Total Clearance (Clt/F) | Day 7 | 959.89 l/h | Standard Deviation 269.654 |
| Cohort 5 (C5), PBTZ169 | Total Clearance (Clt/F) | Day 14 | 924.97 l/h | Standard Deviation 261.681 |
Secondary
Trough Concentration With Repeated Administration (Ctrough)
PBTZ169 concentration before drug intake (Days 2 - 15)
Time frame: Up to 72 hours after the last drug administration
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 (C1A+C1B), PBTZ169 | Trough Concentration With Repeated Administration (Ctrough) | Day 7 | 8.352 ng/ml | Geometric Coefficient of Variation 102.5 |
| Cohort 1 (C1A+C1B), PBTZ169 | Trough Concentration With Repeated Administration (Ctrough) | Day 8 | 6.509 ng/ml | Geometric Coefficient of Variation 51.5 |
| Cohort 1 (C1A+C1B), PBTZ169 | Trough Concentration With Repeated Administration (Ctrough) | Day 2 | 4.695 ng/ml | Geometric Coefficient of Variation 128.9 |
| Cohort 1 (C1A+C1B), PBTZ169 | Trough Concentration With Repeated Administration (Ctrough) | Day 3 | 4.502 ng/ml | Geometric Coefficient of Variation 39.9 |
| Cohort 1 (C1A+C1B), PBTZ169 | Trough Concentration With Repeated Administration (Ctrough) | Day 4 | 6.243 ng/ml | Geometric Coefficient of Variation 42.8 |
| Cohort 1 (C1A+C1B), PBTZ169 | Trough Concentration With Repeated Administration (Ctrough) | Day 5 | 6.874 ng/ml | Geometric Coefficient of Variation 51.7 |
| Cohort 1 (C1A+C1B), PBTZ169 | Trough Concentration With Repeated Administration (Ctrough) | Day 6 | 6.585 ng/ml | Geometric Coefficient of Variation 53.2 |
| Cohort 1 (C1A+C1B), PBTZ169 | Trough Concentration With Repeated Administration (Ctrough) | Day 9 | 7.422 ng/ml | Geometric Coefficient of Variation 51.7 |
| Cohort 1 (C1A+C1B), PBTZ169 | Trough Concentration With Repeated Administration (Ctrough) | Day 10 | 6.664 ng/ml | Geometric Coefficient of Variation 58.8 |
| Cohort 1 (C1A+C1B), PBTZ169 | Trough Concentration With Repeated Administration (Ctrough) | Day 11 | 6.433 ng/ml | Geometric Coefficient of Variation 48.7 |
| Cohort 1 (C1A+C1B), PBTZ169 | Trough Concentration With Repeated Administration (Ctrough) | Day 12 | 6.006 ng/ml | Geometric Coefficient of Variation 51.7 |
| Cohort 1 (C1A+C1B), PBTZ169 | Trough Concentration With Repeated Administration (Ctrough) | Day 13 | 5.942 ng/ml | Geometric Coefficient of Variation 44.5 |
| Cohort 1 (C1A+C1B), PBTZ169 | Trough Concentration With Repeated Administration (Ctrough) | Day 14 | 7.657 ng/ml | Geometric Coefficient of Variation 48.2 |
| Cohort 1 (C1A+C1B), PBTZ169 | Trough Concentration With Repeated Administration (Ctrough) | Day 15 | 6.040 ng/ml | Geometric Coefficient of Variation 58.1 |
Secondary
Volume of Distribution (Vd/F)
Time frame: Up to 72 hours after the last drug administration
Population: C1-4 - Single or double dose administration, C5 - Multiple administration for 14 days
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 (C1A+C1B), PBTZ169 | Volume of Distribution (Vd/F) | Dosing day / Day 1 | 33460.07 l | Standard Deviation 19725.828 |
| Cohort 2 (C2), PBTZ169 | Volume of Distribution (Vd/F) | Dosing day / Day 1 | 13475.58 l | Standard Deviation 6895.8 |
| Cohort 3 (C3), PBTZ169 | Volume of Distribution (Vd/F) | Dosing day / Day 1 | 67278.30 l | Standard Deviation 61222.53 |
| Cohort 4 (C4), PBTZ169 | Volume of Distribution (Vd/F) | Dosing day / Day 1 | 34649.86 l | Standard Deviation 29430.057 |
| Cohort 5 (C5), PBTZ169 | Volume of Distribution (Vd/F) | Dosing day / Day 1 | 77814.43 l | Standard Deviation 50236.867 |
| Cohort 5 (C5), PBTZ169 | Volume of Distribution (Vd/F) | Dosing day / Day 1 | 21126.27 l | Standard Deviation 15900.286 |
| Cohort 5 (C5), PBTZ169 | Volume of Distribution (Vd/F) | Day 7 | 13745.97 l | Standard Deviation 5520.697 |
| Cohort 5 (C5), PBTZ169 | Volume of Distribution (Vd/F) | Day 14 | 19411.17 l | Standard Deviation 6813.126 |