Trial Outcomes & Findings for Safety, Tolerability, Pharmacokinetics and Food Effects Study of PBTZ169 (NCT NCT04150224)
NCT ID: NCT04150224
Last Updated: 2020-02-28
Results Overview
Safety and tolerability: number of (S)AEs
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
60 participants
Primary outcome timeframe
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
Results posted on
2020-02-28
Participant Flow
Period 1: Single or double dosing (Cohorts 1-4) Period 2: Multiple dosing (Cohort 5)
Participant milestones
| Measure |
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
|
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
|
Cohort 2 (C2), PBTZ169
Single dose of PBTZ169: 960 mg fasted
PBTZ169 960 mg SD: Once a day fasted
|
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
|
Cohort 4 (C4), PBTZ169
Single dose of PBTZ169: 1280 mg fasted
PBTZ169 1280 mg SD: Once a day fasted
|
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
|
|---|---|---|---|---|---|---|
|
Overall Study
STARTED
|
10
|
10
|
10
|
10
|
10
|
10
|
|
Overall Study
COMPLETED
|
10
|
10
|
10
|
10
|
10
|
10
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Safety, Tolerability, Pharmacokinetics and Food Effects Study of PBTZ169
Baseline characteristics by cohort
| Measure |
Cohort 1 (C1A), PBTZ169
n=10 Participants
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
|
Cohort 1 (C1B), PBTZ169
n=10 Participants
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
|
Cohort 2 (C2), PBTZ169
n=10 Participants
Single dose of PBTZ169: 960 mg fasted
PBTZ169 960 mg SD: Once a day fasted
|
Cohort 3 (C3), PBTZ169
n=10 Participants
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
|
Cohort 4 (C4), PBTZ169
n=10 Participants
Single dose of PBTZ169: 1280 mg fasted
PBTZ169 1280 mg SD: Once a day fasted
|
Cohort 5 (C5), PBTZ169
n=10 Participants
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
|
Total
n=60 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=8 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
10 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
10 Participants
n=5 Participants
|
10 Participants
n=4 Participants
|
10 Participants
n=21 Participants
|
10 Participants
n=8 Participants
|
60 Participants
n=8 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=8 Participants
|
|
Age, Continuous
|
27.2 years
STANDARD_DEVIATION 5.25 • n=5 Participants
|
23.0 years
STANDARD_DEVIATION 2.26 • n=7 Participants
|
23.7 years
STANDARD_DEVIATION 3.95 • n=5 Participants
|
27.1 years
STANDARD_DEVIATION 5.09 • n=4 Participants
|
30.1 years
STANDARD_DEVIATION 9.10 • n=21 Participants
|
26.7 years
STANDARD_DEVIATION 5.01 • n=8 Participants
|
26.3 years
STANDARD_DEVIATION 5.79 • n=8 Participants
|
|
Sex: Female, Male
Female
|
5 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
9 Participants
n=5 Participants
|
5 Participants
n=4 Participants
|
4 Participants
n=21 Participants
|
6 Participants
n=8 Participants
|
32 Participants
n=8 Participants
|
|
Sex: Female, Male
Male
|
5 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
5 Participants
n=4 Participants
|
6 Participants
n=21 Participants
|
4 Participants
n=8 Participants
|
28 Participants
n=8 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=8 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=8 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=8 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=8 Participants
|
|
Race (NIH/OMB)
White
|
10 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
10 Participants
n=5 Participants
|
10 Participants
n=4 Participants
|
10 Participants
n=21 Participants
|
10 Participants
n=8 Participants
|
60 Participants
n=8 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=8 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
00 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=8 Participants
|
PRIMARY outcome
Timeframe: 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 intakePopulation: Safety population
Safety and tolerability: number of (S)AEs
Outcome measures
| Measure |
Cohort 1 (C1A+C1B), PBTZ169
n=20 Participants
Two doses of PBTZ169: 640 mg OD fasted/after meal and 640 mg OD after meal/fasted. Wash-out period ≥6 days.
PBTZ169 640 mg OD: Two administrations once a day with a wash-out period: food effect
|
Cohort 2 (C2), PBTZ169
n=10 Participants
Single dose of PBTZ169: 960 mg fasted
PBTZ169 960 mg SD: Once a day fasted
|
Cohort 3 (C3), PBTZ169
n=10 Participants
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
|
Cohort 4 (C4), PBTZ169
n=10 Participants
Single dose of PBTZ169: 1280 mg fasted
PBTZ169 1280 mg SD: Once a day fasted
|
Cohort 5 (C5), PBTZ169
n=10 Participants
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
|
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
|
|---|---|---|---|---|---|---|
|
Number of Adverse Events
Number of AEs
|
9 AEs
|
4 AEs
|
5 AEs
|
2 AEs
|
9 AEs
|
—
|
|
Number of Adverse Events
Number of SAEs
|
0 AEs
|
0 AEs
|
0 AEs
|
0 AEs
|
0 AEs
|
—
|
|
Number of Adverse Events
Number of drug-related AEs
|
9 AEs
|
4 AEs
|
5 AEs
|
1 AEs
|
6 AEs
|
—
|
|
Number of Adverse Events
Drug-related "Cardiac disorders" AEs
|
3 AEs
|
0 AEs
|
1 AEs
|
0 AEs
|
0 AEs
|
—
|
|
Number of Adverse Events
Drug-related "GastroInt." AEs
|
1 AEs
|
1 AEs
|
1 AEs
|
1 AEs
|
2 AEs
|
—
|
|
Number of Adverse Events
Drug-related "Investigations" AEs
|
4 AEs
|
0 AEs
|
2 AEs
|
0 AEs
|
0 AEs
|
—
|
|
Number of Adverse Events
Drug-related "Nervous syst." AEs
|
1 AEs
|
3 AEs
|
1 AEs
|
0 AEs
|
2 AEs
|
—
|
|
Number of Adverse Events
Drug-related "Metabolic" AEs
|
0 AEs
|
0 AEs
|
0 AEs
|
0 AEs
|
2 AEs
|
—
|
PRIMARY outcome
Timeframe: 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 intakePopulation: Safety population
Safety and tolerability: number of subjects with adverse events
Outcome measures
| Measure |
Cohort 1 (C1A+C1B), PBTZ169
n=20 Participants
Two doses of PBTZ169: 640 mg OD fasted/after meal and 640 mg OD after meal/fasted. Wash-out period ≥6 days.
PBTZ169 640 mg OD: Two administrations once a day with a wash-out period: food effect
|
Cohort 2 (C2), PBTZ169
n=10 Participants
Single dose of PBTZ169: 960 mg fasted
PBTZ169 960 mg SD: Once a day fasted
|
Cohort 3 (C3), PBTZ169
n=10 Participants
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
|
Cohort 4 (C4), PBTZ169
n=10 Participants
Single dose of PBTZ169: 1280 mg fasted
PBTZ169 1280 mg SD: Once a day fasted
|
Cohort 5 (C5), PBTZ169
n=10 Participants
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
|
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
|
|---|---|---|---|---|---|---|
|
Number of Subjects With AEs
Number of sbjs with AEs
|
6 participants
|
3 participants
|
5 participants
|
2 participants
|
6 participants
|
—
|
|
Number of Subjects With AEs
Number of sbjs with drug-related AEs
|
6 participants
|
3 participants
|
5 participants
|
1 participants
|
5 participants
|
—
|
SECONDARY outcome
Timeframe: 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 intakePopulation: Safety population
Safety and tolerability:Clinically significant changes in vital signs (blood pressure, HR, body temperature, RR)
Outcome measures
| Measure |
Cohort 1 (C1A+C1B), PBTZ169
n=10 Participants
Two doses of PBTZ169: 640 mg OD fasted/after meal and 640 mg OD after meal/fasted. Wash-out period ≥6 days.
PBTZ169 640 mg OD: Two administrations once a day with a wash-out period: food effect
|
Cohort 2 (C2), PBTZ169
n=10 Participants
Single dose of PBTZ169: 960 mg fasted
PBTZ169 960 mg SD: Once a day fasted
|
Cohort 3 (C3), PBTZ169
n=10 Participants
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
|
Cohort 4 (C4), PBTZ169
n=10 Participants
Single dose of PBTZ169: 1280 mg fasted
PBTZ169 1280 mg SD: Once a day fasted
|
Cohort 5 (C5), PBTZ169
n=10 Participants
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
|
Cohort 5 (C5), PBTZ169
n=10 Participants
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
|
|---|---|---|---|---|---|---|
|
CS Changes in Vital Signs
CS Changes in blood pressure
|
0 No of cases of CS changes in vital signs
|
0 No of cases of CS changes in vital signs
|
0 No of cases of CS changes in vital signs
|
0 No of cases of CS changes in vital signs
|
0 No of cases of CS changes in vital signs
|
0 No of cases of CS changes in vital signs
|
|
CS Changes in Vital Signs
CS changes in HH: Sinus tachycardia
|
0 No of cases of CS changes in vital signs
|
3 No of cases of CS changes in vital signs
|
0 No of cases of CS changes in vital signs
|
0 No of cases of CS changes in vital signs
|
0 No of cases of CS changes in vital signs
|
0 No of cases of CS changes in vital signs
|
|
CS Changes in Vital Signs
CS Changes in Temperature
|
0 No of cases of CS changes in vital signs
|
0 No of cases of CS changes in vital signs
|
0 No of cases of CS changes in vital signs
|
0 No of cases of CS changes in vital signs
|
0 No of cases of CS changes in vital signs
|
0 No of cases of CS changes in vital signs
|
|
CS Changes in Vital Signs
CS Changes in RR
|
0 No of cases of CS changes in vital signs
|
0 No of cases of CS changes in vital signs
|
0 No of cases of CS changes in vital signs
|
0 No of cases of CS changes in vital signs
|
0 No of cases of CS changes in vital signs
|
0 No of cases of CS changes in vital signs
|
SECONDARY outcome
Timeframe: 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 intakePopulation: Safety population
Clinically significant abnormal deviations in ECG findings
Outcome measures
| Measure |
Cohort 1 (C1A+C1B), PBTZ169
n=10 Participants
Two doses of PBTZ169: 640 mg OD fasted/after meal and 640 mg OD after meal/fasted. Wash-out period ≥6 days.
PBTZ169 640 mg OD: Two administrations once a day with a wash-out period: food effect
|
Cohort 2 (C2), PBTZ169
n=10 Participants
Single dose of PBTZ169: 960 mg fasted
PBTZ169 960 mg SD: Once a day fasted
|
Cohort 3 (C3), PBTZ169
n=10 Participants
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
|
Cohort 4 (C4), PBTZ169
n=10 Participants
Single dose of PBTZ169: 1280 mg fasted
PBTZ169 1280 mg SD: Once a day fasted
|
Cohort 5 (C5), PBTZ169
n=10 Participants
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
|
Cohort 5 (C5), PBTZ169
n=10 Participants
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
|
|---|---|---|---|---|---|---|
|
ECG Results (Safety and Tolerability)
Electrocardiogram repolarisation abnormality
|
1 participants
|
0 participants
|
0 participants
|
1 participants
|
0 participants
|
0 participants
|
|
ECG Results (Safety and Tolerability)
Sinus tachycardia
|
0 participants
|
1 participants
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
|
ECG Results (Safety and Tolerability)
Electrocardiogram abnormal
|
0 participants
|
0 participants
|
0 participants
|
1 participants
|
0 participants
|
0 participants
|
|
ECG Results (Safety and Tolerability)
Defect conduction intraventricular
|
0 participants
|
0 participants
|
0 participants
|
1 participants
|
0 participants
|
0 participants
|
SECONDARY outcome
Timeframe: 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 intakeComplete blood count, biochemical blood test, urine analysis
Outcome measures
| Measure |
Cohort 1 (C1A+C1B), PBTZ169
n=10 Participants
Two doses of PBTZ169: 640 mg OD fasted/after meal and 640 mg OD after meal/fasted. Wash-out period ≥6 days.
PBTZ169 640 mg OD: Two administrations once a day with a wash-out period: food effect
|
Cohort 2 (C2), PBTZ169
n=10 Participants
Single dose of PBTZ169: 960 mg fasted
PBTZ169 960 mg SD: Once a day fasted
|
Cohort 3 (C3), PBTZ169
n=10 Participants
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
|
Cohort 4 (C4), PBTZ169
n=10 Participants
Single dose of PBTZ169: 1280 mg fasted
PBTZ169 1280 mg SD: Once a day fasted
|
Cohort 5 (C5), PBTZ169
n=10 Participants
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
|
Cohort 5 (C5), PBTZ169
n=10 Participants
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
|
|---|---|---|---|---|---|---|
|
Laboratory Examinations Results (Safety and Tolerability)
CS Anaemia
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
1 participants
|
|
Laboratory Examinations Results (Safety and Tolerability)
CS Blood glucose increase
|
1 participants
|
2 participants
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
|
Laboratory Examinations Results (Safety and Tolerability)
CS Hypercreatininaemia
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
2 participants
|
|
Laboratory Examinations Results (Safety and Tolerability)
CS Haemoglobin decreased
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
1 participants
|
|
Laboratory Examinations Results (Safety and Tolerability)
CS Thrombocytosis
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
1 participants
|
SECONDARY outcome
Timeframe: 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 intakePopulation: Safety population
Safety and tolerability: number of physical examinations with CS deviations in results
Outcome measures
| Measure |
Cohort 1 (C1A+C1B), PBTZ169
n=10 Participants
Two doses of PBTZ169: 640 mg OD fasted/after meal and 640 mg OD after meal/fasted. Wash-out period ≥6 days.
PBTZ169 640 mg OD: Two administrations once a day with a wash-out period: food effect
|
Cohort 2 (C2), PBTZ169
n=10 Participants
Single dose of PBTZ169: 960 mg fasted
PBTZ169 960 mg SD: Once a day fasted
|
Cohort 3 (C3), PBTZ169
n=10 Participants
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
|
Cohort 4 (C4), PBTZ169
n=10 Participants
Single dose of PBTZ169: 1280 mg fasted
PBTZ169 1280 mg SD: Once a day fasted
|
Cohort 5 (C5), PBTZ169
n=10 Participants
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
|
Cohort 5 (C5), PBTZ169
n=10 Participants
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
|
|---|---|---|---|---|---|---|
|
Results of Physical Examination: CS Deviations
|
0 CS physical examination deviations
|
0 CS physical examination deviations
|
0 CS physical examination deviations
|
0 CS physical examination deviations
|
0 CS physical examination deviations
|
0 CS physical examination deviations
|
SECONDARY outcome
Timeframe: 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
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
Outcome measures
| Measure |
Cohort 1 (C1A+C1B), PBTZ169
n=20 Participants
Two doses of PBTZ169: 640 mg OD fasted/after meal and 640 mg OD after meal/fasted. Wash-out period ≥6 days.
PBTZ169 640 mg OD: Two administrations once a day with a wash-out period: food effect
|
Cohort 2 (C2), PBTZ169
n=20 Participants
Single dose of PBTZ169: 960 mg fasted
PBTZ169 960 mg SD: Once a day fasted
|
Cohort 3 (C3), PBTZ169
n=10 Participants
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
|
Cohort 4 (C4), PBTZ169
n=10 Participants
Single dose of PBTZ169: 1280 mg fasted
PBTZ169 1280 mg SD: Once a day fasted
|
Cohort 5 (C5), PBTZ169
n=10 Participants
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
|
Cohort 5 (C5), PBTZ169
n=10 Participants
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
|
|---|---|---|---|---|---|---|
|
Peak Plasma Concentration (Сmax)
Before dosing
|
0.250 ng/ml
Geometric Coefficient of Variation 0
|
0.250 ng/ml
Geometric Coefficient of Variation 0
|
0.250 ng/ml
Geometric Coefficient of Variation 0
|
0.250 ng/ml
Geometric Coefficient of Variation 0
|
0.250 ng/ml
Geometric Coefficient of Variation 0
|
0.250 ng/ml
Geometric Coefficient of Variation 0
|
|
Peak Plasma Concentration (Сmax)
0.25 h
|
—
|
—
|
—
|
—
|
—
|
0.250 ng/ml
Geometric Coefficient of Variation 0
|
|
Peak Plasma Concentration (Сmax)
0.5 h
|
10.701 ng/ml
Geometric Coefficient of Variation 236.6
|
0.399 ng/ml
Geometric Coefficient of Variation 199.6
|
19.351 ng/ml
Geometric Coefficient of Variation 228.4
|
26.048 ng/ml
Geometric Coefficient of Variation 131.0
|
24.576 ng/ml
Geometric Coefficient of Variation 76.6
|
1.183 ng/ml
Geometric Coefficient of Variation 864.4
|
|
Peak Plasma Concentration (Сmax)
1 h
|
43.131 ng/ml
Geometric Coefficient of Variation 84.5
|
8.827 ng/ml
Geometric Coefficient of Variation 415.1
|
45.729 ng/ml
Geometric Coefficient of Variation 100.8
|
48.328 ng/ml
Geometric Coefficient of Variation 46.8
|
74.711 ng/ml
Geometric Coefficient of Variation 52.4
|
22.877 ng/ml
Geometric Coefficient of Variation 3056.8
|
|
Peak Plasma Concentration (Сmax)
1.5 h
|
40.998 ng/ml
Geometric Coefficient of Variation 108.3
|
59.226 ng/ml
Geometric Coefficient of Variation 150.6
|
48.390 ng/ml
Geometric Coefficient of Variation 81.1
|
45.679 ng/ml
Geometric Coefficient of Variation 43.9
|
54.949 ng/ml
Geometric Coefficient of Variation 66.3
|
109.319 ng/ml
Geometric Coefficient of Variation 203.7
|
|
Peak Plasma Concentration (Сmax)
2 h
|
33.660 ng/ml
Geometric Coefficient of Variation 118.4
|
95.641 ng/ml
Geometric Coefficient of Variation 113.9
|
43.633 ng/ml
Geometric Coefficient of Variation 145.2
|
23.782 ng/ml
Geometric Coefficient of Variation 46.9
|
39.253 ng/ml
Geometric Coefficient of Variation 73.4
|
162.170 ng/ml
Geometric Coefficient of Variation 141.1
|
|
Peak Plasma Concentration (Сmax)
3 h
|
19.435 ng/ml
Geometric Coefficient of Variation 106.4
|
90.330 ng/ml
Geometric Coefficient of Variation 84.9
|
22.159 ng/ml
Geometric Coefficient of Variation 167.4
|
11.438 ng/ml
Geometric Coefficient of Variation 60.2
|
23.571 ng/ml
Geometric Coefficient of Variation 75.4
|
128.518 ng/ml
Geometric Coefficient of Variation 95.0
|
|
Peak Plasma Concentration (Сmax)
4 h
|
10.775 ng/ml
Geometric Coefficient of Variation 96.4
|
88.719 ng/ml
Geometric Coefficient of Variation 50.2
|
15.773 ng/ml
Geometric Coefficient of Variation 184.0
|
6.593 ng/ml
Geometric Coefficient of Variation 73.8
|
13.897 ng/ml
Geometric Coefficient of Variation 79.0
|
110.614 ng/ml
Geometric Coefficient of Variation 68.7
|
|
Peak Plasma Concentration (Сmax)
6 h
|
4.195 ng/ml
Geometric Coefficient of Variation 75.3
|
31.083 ng/ml
Geometric Coefficient of Variation 46.8
|
5.884 ng/ml
Geometric Coefficient of Variation 171.9
|
3.461 ng/ml
Geometric Coefficient of Variation 51.7
|
5.771 ng/ml
Geometric Coefficient of Variation 73.0
|
68.001 ng/ml
Geometric Coefficient of Variation 127.0
|
|
Peak Plasma Concentration (Сmax)
8 h
|
—
|
—
|
—
|
—
|
—
|
34.331 ng/ml
Geometric Coefficient of Variation 149.2
|
|
Peak Plasma Concentration (Сmax)
9 h
|
1.827 ng/ml
Geometric Coefficient of Variation 77.4
|
10.815 ng/ml
Geometric Coefficient of Variation 71.3
|
2.672 ng/ml
Geometric Coefficient of Variation 166.7
|
1.330 ng/ml
Geometric Coefficient of Variation 39.1
|
2.880 ng/ml
Geometric Coefficient of Variation 87.8
|
—
|
|
Peak Plasma Concentration (Сmax)
10 h
|
—
|
—
|
—
|
—
|
—
|
14.636 ng/ml
Geometric Coefficient of Variation 93.8
|
|
Peak Plasma Concentration (Сmax)
12 h
|
1.144 ng/ml
Geometric Coefficient of Variation 59.1
|
4.621 ng/ml
Geometric Coefficient of Variation 55.6
|
1.944 ng/ml
Geometric Coefficient of Variation 125.3
|
0.859 ng/ml
Geometric Coefficient of Variation 51.7
|
1.440 ng/ml
Geometric Coefficient of Variation 50.7
|
8.917 ng/ml
Geometric Coefficient of Variation 73.8
|
|
Peak Plasma Concentration (Сmax)
12.5 h
|
—
|
—
|
—
|
6.247 ng/ml
Geometric Coefficient of Variation 270.1
|
—
|
—
|
|
Peak Plasma Concentration (Сmax)
13 h
|
—
|
—
|
—
|
26.515 ng/ml
Geometric Coefficient of Variation 152.4
|
—
|
—
|
|
Peak Plasma Concentration (Сmax)
13.5 h
|
—
|
—
|
—
|
54.520 ng/ml
Geometric Coefficient of Variation 65.7
|
—
|
—
|
|
Peak Plasma Concentration (Сmax)
14 h
|
—
|
—
|
—
|
41.996 ng/ml
Geometric Coefficient of Variation 61.7
|
—
|
—
|
|
Peak Plasma Concentration (Сmax)
15 h
|
—
|
—
|
—
|
23.165 ng/ml
Geometric Coefficient of Variation 64.4
|
—
|
—
|
|
Peak Plasma Concentration (Сmax)
16 h
|
—
|
—
|
—
|
13.113 ng/ml
Geometric Coefficient of Variation 88.3
|
—
|
—
|
|
Peak Plasma Concentration (Сmax)
18 h
|
—
|
—
|
—
|
8.351 ng/ml
Geometric Coefficient of Variation 127.2
|
—
|
—
|
|
Peak Plasma Concentration (Сmax)
21 h
|
—
|
—
|
—
|
3.590 ng/ml
Geometric Coefficient of Variation 139.2
|
—
|
—
|
|
Peak Plasma Concentration (Сmax)
24 h
|
0.456 ng/ml
Geometric Coefficient of Variation 106.1
|
1.428 ng/ml
Geometric Coefficient of Variation 42.2
|
0.731 ng/ml
Geometric Coefficient of Variation 85.5
|
1.763 ng/ml
Geometric Coefficient of Variation 75.1
|
0.591 ng/ml
Geometric Coefficient of Variation 55.8
|
4.695 ng/ml
Geometric Coefficient of Variation 128.9
|
|
Peak Plasma Concentration (Сmax)
48 h
|
0.250 ng/ml
Geometric Coefficient of Variation 0
|
0.385 ng/ml
Geometric Coefficient of Variation 62.2
|
0.288 ng/ml
Geometric Coefficient of Variation 47.1
|
0.383 ng/ml
Geometric Coefficient of Variation 65.9
|
0.269 ng/ml
Geometric Coefficient of Variation 23.6
|
—
|
|
Peak Plasma Concentration (Сmax)
72 h
|
0.250 ng/ml
Geometric Coefficient of Variation 0
|
0.260 ng/ml
Geometric Coefficient of Variation 18.3
|
0.250 ng/ml
Geometric Coefficient of Variation 0
|
0.269 ng/ml
Geometric Coefficient of Variation 23.3
|
0.250 ng/ml
Geometric Coefficient of Variation 0
|
—
|
|
Peak Plasma Concentration (Сmax)
Day 7, before dosing
|
—
|
—
|
—
|
—
|
—
|
8.352 ng/ml
Geometric Coefficient of Variation 102.5
|
|
Peak Plasma Concentration (Сmax)
Day 7, 0.25 h
|
—
|
—
|
—
|
—
|
—
|
8.424 ng/ml
Geometric Coefficient of Variation 68.8
|
|
Peak Plasma Concentration (Сmax)
Day 7, 0.5 h
|
—
|
—
|
—
|
—
|
—
|
15.488 ng/ml
Geometric Coefficient of Variation 86.8
|
|
Peak Plasma Concentration (Сmax)
Day 7, 1 h
|
—
|
—
|
—
|
—
|
—
|
102.727 ng/ml
Geometric Coefficient of Variation 146.9
|
|
Peak Plasma Concentration (Сmax)
Day 7, 1.5 h
|
—
|
—
|
—
|
—
|
—
|
196.799 ng/ml
Geometric Coefficient of Variation 124.0
|
|
Peak Plasma Concentration (Сmax)
Day 7, 2 h
|
—
|
—
|
—
|
—
|
—
|
247.253 ng/ml
Geometric Coefficient of Variation 90.7
|
|
Peak Plasma Concentration (Сmax)
Day 7, 3 h
|
—
|
—
|
—
|
—
|
—
|
214.245 ng/ml
Geometric Coefficient of Variation 53.4
|
|
Peak Plasma Concentration (Сmax)
Day 7, 4 h
|
—
|
—
|
—
|
—
|
—
|
163.523 ng/ml
Geometric Coefficient of Variation 36.5
|
|
Peak Plasma Concentration (Сmax)
Day 7, 6 h
|
—
|
—
|
—
|
—
|
—
|
71.494 ng/ml
Geometric Coefficient of Variation 75.1
|
|
Peak Plasma Concentration (Сmax)
Day 7, 8 h
|
—
|
—
|
—
|
—
|
—
|
34.724 ng/ml
Geometric Coefficient of Variation 60.1
|
|
Peak Plasma Concentration (Сmax)
Day 7, 10 h
|
—
|
—
|
—
|
—
|
—
|
21.163 ng/ml
Geometric Coefficient of Variation 62.3
|
|
Peak Plasma Concentration (Сmax)
Day 7, 12 h
|
—
|
—
|
—
|
—
|
—
|
13.464 ng/ml
Geometric Coefficient of Variation 54.6
|
|
Peak Plasma Concentration (Сmax)
Day 7, 24 h
|
—
|
—
|
—
|
—
|
—
|
6.509 ng/ml
Geometric Coefficient of Variation 51.5
|
|
Peak Plasma Concentration (Сmax)
Day 14, befor dosing
|
—
|
—
|
—
|
—
|
—
|
7.657 ng/ml
Geometric Coefficient of Variation 48.2
|
|
Peak Plasma Concentration (Сmax)
Day 14, 0.25 h
|
—
|
—
|
—
|
—
|
—
|
7.625 ng/ml
Geometric Coefficient of Variation 50.6
|
|
Peak Plasma Concentration (Сmax)
Day 14, 0.5 h
|
—
|
—
|
—
|
—
|
—
|
12.027 ng/ml
Geometric Coefficient of Variation 47.3
|
|
Peak Plasma Concentration (Сmax)
Day 14, 1 h
|
—
|
—
|
—
|
—
|
—
|
56.489 ng/ml
Geometric Coefficient of Variation 185.3
|
|
Peak Plasma Concentration (Сmax)
Day 14, 1.5 h
|
—
|
—
|
—
|
—
|
—
|
150.856 ng/ml
Geometric Coefficient of Variation 123.3
|
|
Peak Plasma Concentration (Сmax)
Day 14, 2 h
|
—
|
—
|
—
|
—
|
—
|
208.562 ng/ml
Geometric Coefficient of Variation 56.0
|
|
Peak Plasma Concentration (Сmax)
Day 14, 3 h
|
—
|
—
|
—
|
—
|
—
|
205.471 ng/ml
Geometric Coefficient of Variation 69.6
|
|
Peak Plasma Concentration (Сmax)
Day 14, 4 h
|
—
|
—
|
—
|
—
|
—
|
189.609 ng/ml
Geometric Coefficient of Variation 39.2
|
|
Peak Plasma Concentration (Сmax)
Day 14, 6 h
|
—
|
—
|
—
|
—
|
—
|
81.751 ng/ml
Geometric Coefficient of Variation 55.6
|
|
Peak Plasma Concentration (Сmax)
Day 14, 8 h
|
—
|
—
|
—
|
—
|
—
|
42.315 ng/ml
Geometric Coefficient of Variation 67.0
|
|
Peak Plasma Concentration (Сmax)
Day 14, 10 h
|
—
|
—
|
—
|
—
|
—
|
28.824 ng/ml
Geometric Coefficient of Variation 121.6
|
|
Peak Plasma Concentration (Сmax)
Day 14, 12 h
|
—
|
—
|
—
|
—
|
—
|
14.270 ng/ml
Geometric Coefficient of Variation 48.1
|
|
Peak Plasma Concentration (Сmax)
Day 14, 24 h
|
—
|
—
|
—
|
—
|
—
|
6.040 ng/ml
Geometric Coefficient of Variation 58.1
|
|
Peak Plasma Concentration (Сmax)
Day 14, 48 h
|
—
|
—
|
—
|
—
|
—
|
2.128 ng/ml
Geometric Coefficient of Variation 103.6
|
|
Peak Plasma Concentration (Сmax)
Day 14, 72 h
|
—
|
—
|
—
|
—
|
—
|
0.360 ng/ml
Geometric Coefficient of Variation 90.0
|
SECONDARY outcome
Timeframe: Up to 72 hours after the last drug administrationPBTZ169 concentration before drug intake (Days 2 - 15)
Outcome measures
| Measure |
Cohort 1 (C1A+C1B), PBTZ169
n=10 Participants
Two doses of PBTZ169: 640 mg OD fasted/after meal and 640 mg OD after meal/fasted. Wash-out period ≥6 days.
PBTZ169 640 mg OD: Two administrations once a day with a wash-out period: food effect
|
Cohort 2 (C2), PBTZ169
Single dose of PBTZ169: 960 mg fasted
PBTZ169 960 mg SD: Once a day fasted
|
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
|
Cohort 4 (C4), PBTZ169
Single dose of PBTZ169: 1280 mg fasted
PBTZ169 1280 mg SD: Once a day fasted
|
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
|
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
|
|---|---|---|---|---|---|---|
|
Trough Concentration With Repeated Administration (Ctrough)
Day 2
|
4.695 ng/ml
Geometric Coefficient of Variation 128.9
|
—
|
—
|
—
|
—
|
—
|
|
Trough Concentration With Repeated Administration (Ctrough)
Day 3
|
4.502 ng/ml
Geometric Coefficient of Variation 39.9
|
—
|
—
|
—
|
—
|
—
|
|
Trough Concentration With Repeated Administration (Ctrough)
Day 4
|
6.243 ng/ml
Geometric Coefficient of Variation 42.8
|
—
|
—
|
—
|
—
|
—
|
|
Trough Concentration With Repeated Administration (Ctrough)
Day 5
|
6.874 ng/ml
Geometric Coefficient of Variation 51.7
|
—
|
—
|
—
|
—
|
—
|
|
Trough Concentration With Repeated Administration (Ctrough)
Day 6
|
6.585 ng/ml
Geometric Coefficient of Variation 53.2
|
—
|
—
|
—
|
—
|
—
|
|
Trough Concentration With Repeated Administration (Ctrough)
Day 7
|
8.352 ng/ml
Geometric Coefficient of Variation 102.5
|
—
|
—
|
—
|
—
|
—
|
|
Trough Concentration With Repeated Administration (Ctrough)
Day 8
|
6.509 ng/ml
Geometric Coefficient of Variation 51.5
|
—
|
—
|
—
|
—
|
—
|
|
Trough Concentration With Repeated Administration (Ctrough)
Day 9
|
7.422 ng/ml
Geometric Coefficient of Variation 51.7
|
—
|
—
|
—
|
—
|
—
|
|
Trough Concentration With Repeated Administration (Ctrough)
Day 10
|
6.664 ng/ml
Geometric Coefficient of Variation 58.8
|
—
|
—
|
—
|
—
|
—
|
|
Trough Concentration With Repeated Administration (Ctrough)
Day 11
|
6.433 ng/ml
Geometric Coefficient of Variation 48.7
|
—
|
—
|
—
|
—
|
—
|
|
Trough Concentration With Repeated Administration (Ctrough)
Day 12
|
6.006 ng/ml
Geometric Coefficient of Variation 51.7
|
—
|
—
|
—
|
—
|
—
|
|
Trough Concentration With Repeated Administration (Ctrough)
Day 13
|
5.942 ng/ml
Geometric Coefficient of Variation 44.5
|
—
|
—
|
—
|
—
|
—
|
|
Trough Concentration With Repeated Administration (Ctrough)
Day 14
|
7.657 ng/ml
Geometric Coefficient of Variation 48.2
|
—
|
—
|
—
|
—
|
—
|
|
Trough Concentration With Repeated Administration (Ctrough)
Day 15
|
6.040 ng/ml
Geometric Coefficient of Variation 58.1
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Up to 72 hours after the last drug administrationPopulation: C1-4 - Single or double dose administration, C5 - Multiple administration for 14 days
Cohort 3: Tmax relative to the time of administration in any dosage interval
Outcome measures
| Measure |
Cohort 1 (C1A+C1B), PBTZ169
n=20 Participants
Two doses of PBTZ169: 640 mg OD fasted/after meal and 640 mg OD after meal/fasted. Wash-out period ≥6 days.
PBTZ169 640 mg OD: Two administrations once a day with a wash-out period: food effect
|
Cohort 2 (C2), PBTZ169
n=20 Participants
Single dose of PBTZ169: 960 mg fasted
PBTZ169 960 mg SD: Once a day fasted
|
Cohort 3 (C3), PBTZ169
n=10 Participants
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
|
Cohort 4 (C4), PBTZ169
n=10 Participants
Single dose of PBTZ169: 1280 mg fasted
PBTZ169 1280 mg SD: Once a day fasted
|
Cohort 5 (C5), PBTZ169
n=10 Participants
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
|
Cohort 5 (C5), PBTZ169
n=10 Participants
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
|
|---|---|---|---|---|---|---|
|
Time to Reach Maximum Concentration (Tmax)
Dosing day / Day 1
|
1.73 h
Standard Deviation 0.896
|
2.90 h
Standard Deviation 0.912
|
1.65 h
Standard Deviation 0.709
|
1.35 h
Standard Deviation 0.747
|
1.15 h
Standard Deviation 0.242
|
2.60 h
Standard Deviation 1.410
|
|
Time to Reach Maximum Concentration (Tmax)
Day 7
|
—
|
—
|
—
|
—
|
—
|
2.25 h
Standard Deviation 0.825
|
|
Time to Reach Maximum Concentration (Tmax)
Day 14
|
—
|
—
|
—
|
—
|
—
|
2.40 h
Standard Deviation 1.022
|
SECONDARY outcome
Timeframe: Up to 72 hours after the last drug administrationPopulation: C1-4 - Single or double dose administration, C5 - Multiple administration for 14 days
Outcome measures
| Measure |
Cohort 1 (C1A+C1B), PBTZ169
n=20 Participants
Two doses of PBTZ169: 640 mg OD fasted/after meal and 640 mg OD after meal/fasted. Wash-out period ≥6 days.
PBTZ169 640 mg OD: Two administrations once a day with a wash-out period: food effect
|
Cohort 2 (C2), PBTZ169
n=20 Participants
Single dose of PBTZ169: 960 mg fasted
PBTZ169 960 mg SD: Once a day fasted
|
Cohort 3 (C3), PBTZ169
n=10 Participants
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
|
Cohort 4 (C4), PBTZ169
n=10 Participants
Single dose of PBTZ169: 1280 mg fasted
PBTZ169 1280 mg SD: Once a day fasted
|
Cohort 5 (C5), PBTZ169
n=10 Participants
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
|
Cohort 5 (C5), PBTZ169
n=10 Participants
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
|
|---|---|---|---|---|---|---|
|
Plasma Half-life Time (T1/2)
Dosing day / Day 1
|
5.46 h
Standard Deviation 3.134
|
7.68 h
Standard Deviation 3.063
|
7.68 h
Standard Deviation 2.043
|
6.33 h
Standard Deviation 5.275
|
8.00 h
Standard Deviation 4.258
|
10.07 h
Standard Deviation 4.294
|
|
Plasma Half-life Time (T1/2)
Day 7
|
—
|
—
|
—
|
—
|
—
|
9.98 h
Standard Deviation 3.357
|
|
Plasma Half-life Time (T1/2)
Day 14
|
—
|
—
|
—
|
—
|
—
|
14.81 h
Standard Deviation 4.365
|
SECONDARY outcome
Timeframe: Up to 72 hours after the last drug administrationPopulation: C1-4 - Single or double dose administration, C5 - Multiple administration for 14 days
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
Outcome measures
| Measure |
Cohort 1 (C1A+C1B), PBTZ169
n=20 Participants
Two doses of PBTZ169: 640 mg OD fasted/after meal and 640 mg OD after meal/fasted. Wash-out period ≥6 days.
PBTZ169 640 mg OD: Two administrations once a day with a wash-out period: food effect
|
Cohort 2 (C2), PBTZ169
n=20 Participants
Single dose of PBTZ169: 960 mg fasted
PBTZ169 960 mg SD: Once a day fasted
|
Cohort 3 (C3), PBTZ169
n=10 Participants
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
|
Cohort 4 (C4), PBTZ169
n=10 Participants
Single dose of PBTZ169: 1280 mg fasted
PBTZ169 1280 mg SD: Once a day fasted
|
Cohort 5 (C5), PBTZ169
n=10 Participants
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
|
Cohort 5 (C5), PBTZ169
n=10 Participants
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
|
|---|---|---|---|---|---|---|
|
Area Under the Concentration-time Curve (AUC0 t)
Dosing day / Day 1
|
181.63 ng*h/ml
Standard Deviation 112.236
|
575.19 ng*h/ml
Standard Deviation 221.735
|
258.42 ng*h/ml
Standard Deviation 174.149
|
342.03 ng*h/ml
Standard Deviation 141.061
|
220.77 ng*h/ml
Standard Deviation 124.754
|
—
|
|
Area Under the Concentration-time Curve (AUC0 t)
Day 14
|
—
|
—
|
—
|
—
|
—
|
1479.76 ng*h/ml
Standard Deviation 459.066
|
SECONDARY outcome
Timeframe: Up to 72 hours after the last drug administrationPopulation: C1-4 - Single or double dose administration, C5 - Multiple administration for 14 days
In the time interval from 0 to infinity
Outcome measures
| Measure |
Cohort 1 (C1A+C1B), PBTZ169
n=20 Participants
Two doses of PBTZ169: 640 mg OD fasted/after meal and 640 mg OD after meal/fasted. Wash-out period ≥6 days.
PBTZ169 640 mg OD: Two administrations once a day with a wash-out period: food effect
|
Cohort 2 (C2), PBTZ169
n=20 Participants
Single dose of PBTZ169: 960 mg fasted
PBTZ169 960 mg SD: Once a day fasted
|
Cohort 3 (C3), PBTZ169
n=10 Participants
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
|
Cohort 4 (C4), PBTZ169
n=10 Participants
Single dose of PBTZ169: 1280 mg fasted
PBTZ169 1280 mg SD: Once a day fasted
|
Cohort 5 (C5), PBTZ169
n=10 Participants
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
|
Cohort 5 (C5), PBTZ169
n=10 Participants
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
|
|---|---|---|---|---|---|---|
|
Area Under the Concentration-time Curve (AUC0-∞)
Dosing day / Day 1
|
175.98 ng*h/ml
Standard Deviation 104.828
|
584.06 ng*h/ml
Standard Deviation 221.531
|
267.94 ng*h/ml
Standard Deviation 175.918
|
348.56 ng*h/ml
Standard Deviation 141.198
|
228.93 ng*h/ml
Standard Deviation 124.855
|
1153.89 ng*h/ml
Standard Deviation 482.189
|
|
Area Under the Concentration-time Curve (AUC0-∞)
Day 7
|
—
|
—
|
—
|
—
|
—
|
1479.16 ng*h/ml
Standard Deviation 594.599
|
|
Area Under the Concentration-time Curve (AUC0-∞)
Day 14
|
—
|
—
|
—
|
—
|
—
|
1501.97 ng*h/ml
Standard Deviation 483.483
|
SECONDARY outcome
Timeframe: 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
C5 (multiple administration once a day for 14 days): AUC0-24 was calculated based on measurements within 24 hours after PBTZ169 intake
Outcome measures
| Measure |
Cohort 1 (C1A+C1B), PBTZ169
n=10 Participants
Two doses of PBTZ169: 640 mg OD fasted/after meal and 640 mg OD after meal/fasted. Wash-out period ≥6 days.
PBTZ169 640 mg OD: Two administrations once a day with a wash-out period: food effect
|
Cohort 2 (C2), PBTZ169
Single dose of PBTZ169: 960 mg fasted
PBTZ169 960 mg SD: Once a day fasted
|
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
|
Cohort 4 (C4), PBTZ169
Single dose of PBTZ169: 1280 mg fasted
PBTZ169 1280 mg SD: Once a day fasted
|
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
|
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
|
|---|---|---|---|---|---|---|
|
Area Under the Concentration-time Curve (AUC0-24)
Day 1
|
1111.90 ng/ml*h
Standard Deviation 463.267
|
—
|
—
|
—
|
—
|
—
|
|
Area Under the Concentration-time Curve (AUC0-24)
Day 7
|
1374.48 ng/ml*h
Standard Deviation 575.119
|
—
|
—
|
—
|
—
|
—
|
|
Area Under the Concentration-time Curve (AUC0-24)
Day 14
|
1363.85 ng/ml*h
Standard Deviation 450.006
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Up to 72 hours after the last drug administrationPopulation: C1-4 - Single or double dose administration, C5 - Multiple administration for 14 days
Outcome measures
| Measure |
Cohort 1 (C1A+C1B), PBTZ169
n=20 Participants
Two doses of PBTZ169: 640 mg OD fasted/after meal and 640 mg OD after meal/fasted. Wash-out period ≥6 days.
PBTZ169 640 mg OD: Two administrations once a day with a wash-out period: food effect
|
Cohort 2 (C2), PBTZ169
n=20 Participants
Single dose of PBTZ169: 960 mg fasted
PBTZ169 960 mg SD: Once a day fasted
|
Cohort 3 (C3), PBTZ169
n=10 Participants
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
|
Cohort 4 (C4), PBTZ169
n=10 Participants
Single dose of PBTZ169: 1280 mg fasted
PBTZ169 1280 mg SD: Once a day fasted
|
Cohort 5 (C5), PBTZ169
n=10 Participants
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
|
Cohort 5 (C5), PBTZ169
n=10 Participants
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
|
|---|---|---|---|---|---|---|
|
Total Clearance (Clt/F)
Dosing day / Day 1
|
4910.09 l/h
Standard Deviation 2711.818
|
1260.08 l/h
Standard Deviation 491.974
|
8246.42 l/h
Standard Deviation 12883.377
|
4185.23 l/h
Standard Deviation 1507.230
|
6617.74 l/h
Standard Deviation 2217.282
|
1302.31 l/h
Standard Deviation 548.472
|
|
Total Clearance (Clt/F)
Day 7
|
—
|
—
|
—
|
—
|
—
|
959.89 l/h
Standard Deviation 269.654
|
|
Total Clearance (Clt/F)
Day 14
|
—
|
—
|
—
|
—
|
—
|
924.97 l/h
Standard Deviation 261.681
|
SECONDARY outcome
Timeframe: Up to 72 hours after the last drug administrationPopulation: C1-4 - Single or double dose administration, C5 - Multiple administration for 14 days
Outcome measures
| Measure |
Cohort 1 (C1A+C1B), PBTZ169
n=20 Participants
Two doses of PBTZ169: 640 mg OD fasted/after meal and 640 mg OD after meal/fasted. Wash-out period ≥6 days.
PBTZ169 640 mg OD: Two administrations once a day with a wash-out period: food effect
|
Cohort 2 (C2), PBTZ169
n=20 Participants
Single dose of PBTZ169: 960 mg fasted
PBTZ169 960 mg SD: Once a day fasted
|
Cohort 3 (C3), PBTZ169
n=10 Participants
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
|
Cohort 4 (C4), PBTZ169
n=10 Participants
Single dose of PBTZ169: 1280 mg fasted
PBTZ169 1280 mg SD: Once a day fasted
|
Cohort 5 (C5), PBTZ169
n=10 Participants
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
|
Cohort 5 (C5), PBTZ169
n=10 Participants
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
|
|---|---|---|---|---|---|---|
|
Volume of Distribution (Vd/F)
Dosing day / Day 1
|
33460.07 l
Standard Deviation 19725.828
|
13475.58 l
Standard Deviation 6895.800
|
67278.30 l
Standard Deviation 61222.530
|
34649.86 l
Standard Deviation 29430.057
|
77814.43 l
Standard Deviation 50236.867
|
21126.27 l
Standard Deviation 15900.286
|
|
Volume of Distribution (Vd/F)
Day 7
|
—
|
—
|
—
|
—
|
—
|
13745.97 l
Standard Deviation 5520.697
|
|
Volume of Distribution (Vd/F)
Day 14
|
—
|
—
|
—
|
—
|
—
|
19411.17 l
Standard Deviation 6813.126
|
SECONDARY outcome
Timeframe: Up to 72 hours after the last drug administrationPopulation: C1-4 - Single or double dose administration, C5 - Multiple administration for 14 days
Outcome measures
| Measure |
Cohort 1 (C1A+C1B), PBTZ169
n=20 Participants
Two doses of PBTZ169: 640 mg OD fasted/after meal and 640 mg OD after meal/fasted. Wash-out period ≥6 days.
PBTZ169 640 mg OD: Two administrations once a day with a wash-out period: food effect
|
Cohort 2 (C2), PBTZ169
n=20 Participants
Single dose of PBTZ169: 960 mg fasted
PBTZ169 960 mg SD: Once a day fasted
|
Cohort 3 (C3), PBTZ169
n=10 Participants
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
|
Cohort 4 (C4), PBTZ169
n=10 Participants
Single dose of PBTZ169: 1280 mg fasted
PBTZ169 1280 mg SD: Once a day fasted
|
Cohort 5 (C5), PBTZ169
n=10 Participants
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
|
Cohort 5 (C5), PBTZ169
n=10 Participants
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
|
|---|---|---|---|---|---|---|
|
Elimination Constant Kel
Dosing day / Day 1
|
0.1765 1/h
Standard Deviation 0.1067
|
0.1027 1/h
Standard Deviation 0.0356
|
0.0993 1/h
Standard Deviation 0.0396
|
0.1865 1/h
Standard Deviation 0.1175
|
0.1154 1/h
Standard Deviation 0.0682
|
0.0866 1/h
Standard Deviation 0.0501
|
|
Elimination Constant Kel
Day 7
|
—
|
—
|
—
|
—
|
—
|
0.0765 1/h
Standard Deviation 0.0240
|
|
Elimination Constant Kel
Day 14
|
—
|
—
|
—
|
—
|
—
|
0.0512 1/h
Standard Deviation 0.0180
|
SECONDARY outcome
Timeframe: Up to 72 hours after the last drug administrationf=AUC0-∞(T)/AUC0-∞(R); f'=AUC0-t(T)/AUC0-t(R) Test (T) - PBTZ169 640 mg after meals, reference (R) - PBTZ169 640 mg fasted
Outcome measures
| Measure |
Cohort 1 (C1A+C1B), PBTZ169
n=20 Participants
Two doses of PBTZ169: 640 mg OD fasted/after meal and 640 mg OD after meal/fasted. Wash-out period ≥6 days.
PBTZ169 640 mg OD: Two administrations once a day with a wash-out period: food effect
|
Cohort 2 (C2), PBTZ169
Single dose of PBTZ169: 960 mg fasted
PBTZ169 960 mg SD: Once a day fasted
|
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
|
Cohort 4 (C4), PBTZ169
Single dose of PBTZ169: 1280 mg fasted
PBTZ169 1280 mg SD: Once a day fasted
|
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
|
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
|
|---|---|---|---|---|---|---|
|
Relative Bioavailability
f
|
344.54 % of T/R geometric mean ratio
Interval 293.99 to 403.8
|
—
|
—
|
—
|
—
|
—
|
|
Relative Bioavailability
f'
|
350.20 % of T/R geometric mean ratio
Interval 300.94 to 407.52
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Up to 72 hours after the last drug administrationf"=Cmax(T)/Cmax(R). Test (T) - PBTZ169 640 mg after meals, reference (R) - PBTZ169 640 mg fasted
Outcome measures
| Measure |
Cohort 1 (C1A+C1B), PBTZ169
n=20 Participants
Two doses of PBTZ169: 640 mg OD fasted/after meal and 640 mg OD after meal/fasted. Wash-out period ≥6 days.
PBTZ169 640 mg OD: Two administrations once a day with a wash-out period: food effect
|
Cohort 2 (C2), PBTZ169
Single dose of PBTZ169: 960 mg fasted
PBTZ169 960 mg SD: Once a day fasted
|
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
|
Cohort 4 (C4), PBTZ169
Single dose of PBTZ169: 1280 mg fasted
PBTZ169 1280 mg SD: Once a day fasted
|
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
|
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
|
|---|---|---|---|---|---|---|
|
Relative Degree of Absorption
|
229.03 geometric mean ratio, %
Interval 179.29 to 292.56
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: 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 intakePopulation: Safety population
Safety and tolerability: No. of sbjs with clinically significant changes in vital signs (blood pressure, HR, body temperature, RR)
Outcome measures
| Measure |
Cohort 1 (C1A+C1B), PBTZ169
n=10 Participants
Two doses of PBTZ169: 640 mg OD fasted/after meal and 640 mg OD after meal/fasted. Wash-out period ≥6 days.
PBTZ169 640 mg OD: Two administrations once a day with a wash-out period: food effect
|
Cohort 2 (C2), PBTZ169
n=10 Participants
Single dose of PBTZ169: 960 mg fasted
PBTZ169 960 mg SD: Once a day fasted
|
Cohort 3 (C3), PBTZ169
n=10 Participants
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
|
Cohort 4 (C4), PBTZ169
n=10 Participants
Single dose of PBTZ169: 1280 mg fasted
PBTZ169 1280 mg SD: Once a day fasted
|
Cohort 5 (C5), PBTZ169
n=10 Participants
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
|
Cohort 5 (C5), PBTZ169
n=10 Participants
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
|
|---|---|---|---|---|---|---|
|
Number of Subjects With CS Changes in Vital Signs
CS Blood pressure deviations
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
|
Number of Subjects With CS Changes in Vital Signs
CS Sinus tachycardia
|
0 participants
|
1 participants
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
|
Number of Subjects With CS Changes in Vital Signs
CS Temperature changes
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
|
Number of Subjects With CS Changes in Vital Signs
CS RR changes
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
Adverse Events
Cohort 1 (C1A+C1B), PBTZ169
Serious events: 0 serious events
Other events: 6 other events
Deaths: 0 deaths
Cohort 2 (C2), PBTZ169
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Cohort 3 (C3), PBTZ169
Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths
Cohort 4 (C4), PBTZ169
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Cohort 5 (C5), PBTZ169
Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Cohort 1 (C1A+C1B), PBTZ169
n=20 participants at risk
Two doses of PBTZ169: 640 mg OD fasted/after meal and 640 mg OD after meal/fasted. Wash-out period ≥6 days.
PBTZ169 640 mg OD: Two administrations once a day with a wash-out period: food effect
|
Cohort 2 (C2), PBTZ169
n=10 participants at risk
Single dose of PBTZ169: 960 mg fasted
PBTZ169 960 mg SD: Once a day fasted
|
Cohort 3 (C3), PBTZ169
n=10 participants at risk
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
|
Cohort 4 (C4), PBTZ169
n=10 participants at risk
Single dose of PBTZ169: 1280 mg fasted
PBTZ169 1280 mg SD: Once a day fasted
|
Cohort 5 (C5), PBTZ169
n=10 participants at risk
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
|
|---|---|---|---|---|---|
|
Cardiac disorders
Sinus tachycardia
|
5.0%
1/20 • Number of events 3 • Single and double dosing groups - up to 5 ± 1 days after the last PBTZ169 dose intake (Cohorts 1-4): C1A, C1B - up to Day 12 ± 1 (Day 1 - 1st dosing day) C2, C3, C4 - up to Day 6 ± 1 (Day 1 - dosing day) Multiple dosing group - up to 7 ± 1 days after the last PBTZ169 dose intake (Cohort 5): C5 - up to Day 21±1 (Day 1 - 1st dosing day)
|
0.00%
0/10 • Single and double dosing groups - up to 5 ± 1 days after the last PBTZ169 dose intake (Cohorts 1-4): C1A, C1B - up to Day 12 ± 1 (Day 1 - 1st dosing day) C2, C3, C4 - up to Day 6 ± 1 (Day 1 - dosing day) Multiple dosing group - up to 7 ± 1 days after the last PBTZ169 dose intake (Cohort 5): C5 - up to Day 21±1 (Day 1 - 1st dosing day)
|
0.00%
0/10 • Single and double dosing groups - up to 5 ± 1 days after the last PBTZ169 dose intake (Cohorts 1-4): C1A, C1B - up to Day 12 ± 1 (Day 1 - 1st dosing day) C2, C3, C4 - up to Day 6 ± 1 (Day 1 - dosing day) Multiple dosing group - up to 7 ± 1 days after the last PBTZ169 dose intake (Cohort 5): C5 - up to Day 21±1 (Day 1 - 1st dosing day)
|
0.00%
0/10 • Single and double dosing groups - up to 5 ± 1 days after the last PBTZ169 dose intake (Cohorts 1-4): C1A, C1B - up to Day 12 ± 1 (Day 1 - 1st dosing day) C2, C3, C4 - up to Day 6 ± 1 (Day 1 - dosing day) Multiple dosing group - up to 7 ± 1 days after the last PBTZ169 dose intake (Cohort 5): C5 - up to Day 21±1 (Day 1 - 1st dosing day)
|
0.00%
0/10 • Single and double dosing groups - up to 5 ± 1 days after the last PBTZ169 dose intake (Cohorts 1-4): C1A, C1B - up to Day 12 ± 1 (Day 1 - 1st dosing day) C2, C3, C4 - up to Day 6 ± 1 (Day 1 - dosing day) Multiple dosing group - up to 7 ± 1 days after the last PBTZ169 dose intake (Cohort 5): C5 - up to Day 21±1 (Day 1 - 1st dosing day)
|
|
Cardiac disorders
Defect conduction intraventricular
|
0.00%
0/20 • Single and double dosing groups - up to 5 ± 1 days after the last PBTZ169 dose intake (Cohorts 1-4): C1A, C1B - up to Day 12 ± 1 (Day 1 - 1st dosing day) C2, C3, C4 - up to Day 6 ± 1 (Day 1 - dosing day) Multiple dosing group - up to 7 ± 1 days after the last PBTZ169 dose intake (Cohort 5): C5 - up to Day 21±1 (Day 1 - 1st dosing day)
|
0.00%
0/10 • Single and double dosing groups - up to 5 ± 1 days after the last PBTZ169 dose intake (Cohorts 1-4): C1A, C1B - up to Day 12 ± 1 (Day 1 - 1st dosing day) C2, C3, C4 - up to Day 6 ± 1 (Day 1 - dosing day) Multiple dosing group - up to 7 ± 1 days after the last PBTZ169 dose intake (Cohort 5): C5 - up to Day 21±1 (Day 1 - 1st dosing day)
|
10.0%
1/10 • Number of events 1 • Single and double dosing groups - up to 5 ± 1 days after the last PBTZ169 dose intake (Cohorts 1-4): C1A, C1B - up to Day 12 ± 1 (Day 1 - 1st dosing day) C2, C3, C4 - up to Day 6 ± 1 (Day 1 - dosing day) Multiple dosing group - up to 7 ± 1 days after the last PBTZ169 dose intake (Cohort 5): C5 - up to Day 21±1 (Day 1 - 1st dosing day)
|
0.00%
0/10 • Single and double dosing groups - up to 5 ± 1 days after the last PBTZ169 dose intake (Cohorts 1-4): C1A, C1B - up to Day 12 ± 1 (Day 1 - 1st dosing day) C2, C3, C4 - up to Day 6 ± 1 (Day 1 - dosing day) Multiple dosing group - up to 7 ± 1 days after the last PBTZ169 dose intake (Cohort 5): C5 - up to Day 21±1 (Day 1 - 1st dosing day)
|
0.00%
0/10 • Single and double dosing groups - up to 5 ± 1 days after the last PBTZ169 dose intake (Cohorts 1-4): C1A, C1B - up to Day 12 ± 1 (Day 1 - 1st dosing day) C2, C3, C4 - up to Day 6 ± 1 (Day 1 - dosing day) Multiple dosing group - up to 7 ± 1 days after the last PBTZ169 dose intake (Cohort 5): C5 - up to Day 21±1 (Day 1 - 1st dosing day)
|
|
Gastrointestinal disorders
Diarrhoea
|
5.0%
1/20 • Number of events 1 • Single and double dosing groups - up to 5 ± 1 days after the last PBTZ169 dose intake (Cohorts 1-4): C1A, C1B - up to Day 12 ± 1 (Day 1 - 1st dosing day) C2, C3, C4 - up to Day 6 ± 1 (Day 1 - dosing day) Multiple dosing group - up to 7 ± 1 days after the last PBTZ169 dose intake (Cohort 5): C5 - up to Day 21±1 (Day 1 - 1st dosing day)
|
0.00%
0/10 • Single and double dosing groups - up to 5 ± 1 days after the last PBTZ169 dose intake (Cohorts 1-4): C1A, C1B - up to Day 12 ± 1 (Day 1 - 1st dosing day) C2, C3, C4 - up to Day 6 ± 1 (Day 1 - dosing day) Multiple dosing group - up to 7 ± 1 days after the last PBTZ169 dose intake (Cohort 5): C5 - up to Day 21±1 (Day 1 - 1st dosing day)
|
10.0%
1/10 • Number of events 1 • Single and double dosing groups - up to 5 ± 1 days after the last PBTZ169 dose intake (Cohorts 1-4): C1A, C1B - up to Day 12 ± 1 (Day 1 - 1st dosing day) C2, C3, C4 - up to Day 6 ± 1 (Day 1 - dosing day) Multiple dosing group - up to 7 ± 1 days after the last PBTZ169 dose intake (Cohort 5): C5 - up to Day 21±1 (Day 1 - 1st dosing day)
|
10.0%
1/10 • Number of events 1 • Single and double dosing groups - up to 5 ± 1 days after the last PBTZ169 dose intake (Cohorts 1-4): C1A, C1B - up to Day 12 ± 1 (Day 1 - 1st dosing day) C2, C3, C4 - up to Day 6 ± 1 (Day 1 - dosing day) Multiple dosing group - up to 7 ± 1 days after the last PBTZ169 dose intake (Cohort 5): C5 - up to Day 21±1 (Day 1 - 1st dosing day)
|
10.0%
1/10 • Number of events 1 • Single and double dosing groups - up to 5 ± 1 days after the last PBTZ169 dose intake (Cohorts 1-4): C1A, C1B - up to Day 12 ± 1 (Day 1 - 1st dosing day) C2, C3, C4 - up to Day 6 ± 1 (Day 1 - dosing day) Multiple dosing group - up to 7 ± 1 days after the last PBTZ169 dose intake (Cohort 5): C5 - up to Day 21±1 (Day 1 - 1st dosing day)
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/20 • Single and double dosing groups - up to 5 ± 1 days after the last PBTZ169 dose intake (Cohorts 1-4): C1A, C1B - up to Day 12 ± 1 (Day 1 - 1st dosing day) C2, C3, C4 - up to Day 6 ± 1 (Day 1 - dosing day) Multiple dosing group - up to 7 ± 1 days after the last PBTZ169 dose intake (Cohort 5): C5 - up to Day 21±1 (Day 1 - 1st dosing day)
|
10.0%
1/10 • Number of events 1 • Single and double dosing groups - up to 5 ± 1 days after the last PBTZ169 dose intake (Cohorts 1-4): C1A, C1B - up to Day 12 ± 1 (Day 1 - 1st dosing day) C2, C3, C4 - up to Day 6 ± 1 (Day 1 - dosing day) Multiple dosing group - up to 7 ± 1 days after the last PBTZ169 dose intake (Cohort 5): C5 - up to Day 21±1 (Day 1 - 1st dosing day)
|
0.00%
0/10 • Single and double dosing groups - up to 5 ± 1 days after the last PBTZ169 dose intake (Cohorts 1-4): C1A, C1B - up to Day 12 ± 1 (Day 1 - 1st dosing day) C2, C3, C4 - up to Day 6 ± 1 (Day 1 - dosing day) Multiple dosing group - up to 7 ± 1 days after the last PBTZ169 dose intake (Cohort 5): C5 - up to Day 21±1 (Day 1 - 1st dosing day)
|
0.00%
0/10 • Single and double dosing groups - up to 5 ± 1 days after the last PBTZ169 dose intake (Cohorts 1-4): C1A, C1B - up to Day 12 ± 1 (Day 1 - 1st dosing day) C2, C3, C4 - up to Day 6 ± 1 (Day 1 - dosing day) Multiple dosing group - up to 7 ± 1 days after the last PBTZ169 dose intake (Cohort 5): C5 - up to Day 21±1 (Day 1 - 1st dosing day)
|
0.00%
0/10 • Single and double dosing groups - up to 5 ± 1 days after the last PBTZ169 dose intake (Cohorts 1-4): C1A, C1B - up to Day 12 ± 1 (Day 1 - 1st dosing day) C2, C3, C4 - up to Day 6 ± 1 (Day 1 - dosing day) Multiple dosing group - up to 7 ± 1 days after the last PBTZ169 dose intake (Cohort 5): C5 - up to Day 21±1 (Day 1 - 1st dosing day)
|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/20 • Single and double dosing groups - up to 5 ± 1 days after the last PBTZ169 dose intake (Cohorts 1-4): C1A, C1B - up to Day 12 ± 1 (Day 1 - 1st dosing day) C2, C3, C4 - up to Day 6 ± 1 (Day 1 - dosing day) Multiple dosing group - up to 7 ± 1 days after the last PBTZ169 dose intake (Cohort 5): C5 - up to Day 21±1 (Day 1 - 1st dosing day)
|
0.00%
0/10 • Single and double dosing groups - up to 5 ± 1 days after the last PBTZ169 dose intake (Cohorts 1-4): C1A, C1B - up to Day 12 ± 1 (Day 1 - 1st dosing day) C2, C3, C4 - up to Day 6 ± 1 (Day 1 - dosing day) Multiple dosing group - up to 7 ± 1 days after the last PBTZ169 dose intake (Cohort 5): C5 - up to Day 21±1 (Day 1 - 1st dosing day)
|
0.00%
0/10 • Single and double dosing groups - up to 5 ± 1 days after the last PBTZ169 dose intake (Cohorts 1-4): C1A, C1B - up to Day 12 ± 1 (Day 1 - 1st dosing day) C2, C3, C4 - up to Day 6 ± 1 (Day 1 - dosing day) Multiple dosing group - up to 7 ± 1 days after the last PBTZ169 dose intake (Cohort 5): C5 - up to Day 21±1 (Day 1 - 1st dosing day)
|
0.00%
0/10 • Single and double dosing groups - up to 5 ± 1 days after the last PBTZ169 dose intake (Cohorts 1-4): C1A, C1B - up to Day 12 ± 1 (Day 1 - 1st dosing day) C2, C3, C4 - up to Day 6 ± 1 (Day 1 - dosing day) Multiple dosing group - up to 7 ± 1 days after the last PBTZ169 dose intake (Cohort 5): C5 - up to Day 21±1 (Day 1 - 1st dosing day)
|
10.0%
1/10 • Number of events 1 • Single and double dosing groups - up to 5 ± 1 days after the last PBTZ169 dose intake (Cohorts 1-4): C1A, C1B - up to Day 12 ± 1 (Day 1 - 1st dosing day) C2, C3, C4 - up to Day 6 ± 1 (Day 1 - dosing day) Multiple dosing group - up to 7 ± 1 days after the last PBTZ169 dose intake (Cohort 5): C5 - up to Day 21±1 (Day 1 - 1st dosing day)
|
|
Investigations
Blood glucose increased
|
10.0%
2/20 • Number of events 3 • Single and double dosing groups - up to 5 ± 1 days after the last PBTZ169 dose intake (Cohorts 1-4): C1A, C1B - up to Day 12 ± 1 (Day 1 - 1st dosing day) C2, C3, C4 - up to Day 6 ± 1 (Day 1 - dosing day) Multiple dosing group - up to 7 ± 1 days after the last PBTZ169 dose intake (Cohort 5): C5 - up to Day 21±1 (Day 1 - 1st dosing day)
|
0.00%
0/10 • Single and double dosing groups - up to 5 ± 1 days after the last PBTZ169 dose intake (Cohorts 1-4): C1A, C1B - up to Day 12 ± 1 (Day 1 - 1st dosing day) C2, C3, C4 - up to Day 6 ± 1 (Day 1 - dosing day) Multiple dosing group - up to 7 ± 1 days after the last PBTZ169 dose intake (Cohort 5): C5 - up to Day 21±1 (Day 1 - 1st dosing day)
|
0.00%
0/10 • Single and double dosing groups - up to 5 ± 1 days after the last PBTZ169 dose intake (Cohorts 1-4): C1A, C1B - up to Day 12 ± 1 (Day 1 - 1st dosing day) C2, C3, C4 - up to Day 6 ± 1 (Day 1 - dosing day) Multiple dosing group - up to 7 ± 1 days after the last PBTZ169 dose intake (Cohort 5): C5 - up to Day 21±1 (Day 1 - 1st dosing day)
|
0.00%
0/10 • Single and double dosing groups - up to 5 ± 1 days after the last PBTZ169 dose intake (Cohorts 1-4): C1A, C1B - up to Day 12 ± 1 (Day 1 - 1st dosing day) C2, C3, C4 - up to Day 6 ± 1 (Day 1 - dosing day) Multiple dosing group - up to 7 ± 1 days after the last PBTZ169 dose intake (Cohort 5): C5 - up to Day 21±1 (Day 1 - 1st dosing day)
|
0.00%
0/10 • Single and double dosing groups - up to 5 ± 1 days after the last PBTZ169 dose intake (Cohorts 1-4): C1A, C1B - up to Day 12 ± 1 (Day 1 - 1st dosing day) C2, C3, C4 - up to Day 6 ± 1 (Day 1 - dosing day) Multiple dosing group - up to 7 ± 1 days after the last PBTZ169 dose intake (Cohort 5): C5 - up to Day 21±1 (Day 1 - 1st dosing day)
|
|
Investigations
Electrocardiogram abnormal
|
0.00%
0/20 • Single and double dosing groups - up to 5 ± 1 days after the last PBTZ169 dose intake (Cohorts 1-4): C1A, C1B - up to Day 12 ± 1 (Day 1 - 1st dosing day) C2, C3, C4 - up to Day 6 ± 1 (Day 1 - dosing day) Multiple dosing group - up to 7 ± 1 days after the last PBTZ169 dose intake (Cohort 5): C5 - up to Day 21±1 (Day 1 - 1st dosing day)
|
10.0%
1/10 • Number of events 1 • Single and double dosing groups - up to 5 ± 1 days after the last PBTZ169 dose intake (Cohorts 1-4): C1A, C1B - up to Day 12 ± 1 (Day 1 - 1st dosing day) C2, C3, C4 - up to Day 6 ± 1 (Day 1 - dosing day) Multiple dosing group - up to 7 ± 1 days after the last PBTZ169 dose intake (Cohort 5): C5 - up to Day 21±1 (Day 1 - 1st dosing day)
|
10.0%
1/10 • Number of events 1 • Single and double dosing groups - up to 5 ± 1 days after the last PBTZ169 dose intake (Cohorts 1-4): C1A, C1B - up to Day 12 ± 1 (Day 1 - 1st dosing day) C2, C3, C4 - up to Day 6 ± 1 (Day 1 - dosing day) Multiple dosing group - up to 7 ± 1 days after the last PBTZ169 dose intake (Cohort 5): C5 - up to Day 21±1 (Day 1 - 1st dosing day)
|
0.00%
0/10 • Single and double dosing groups - up to 5 ± 1 days after the last PBTZ169 dose intake (Cohorts 1-4): C1A, C1B - up to Day 12 ± 1 (Day 1 - 1st dosing day) C2, C3, C4 - up to Day 6 ± 1 (Day 1 - dosing day) Multiple dosing group - up to 7 ± 1 days after the last PBTZ169 dose intake (Cohort 5): C5 - up to Day 21±1 (Day 1 - 1st dosing day)
|
0.00%
0/10 • Single and double dosing groups - up to 5 ± 1 days after the last PBTZ169 dose intake (Cohorts 1-4): C1A, C1B - up to Day 12 ± 1 (Day 1 - 1st dosing day) C2, C3, C4 - up to Day 6 ± 1 (Day 1 - dosing day) Multiple dosing group - up to 7 ± 1 days after the last PBTZ169 dose intake (Cohort 5): C5 - up to Day 21±1 (Day 1 - 1st dosing day)
|
|
Investigations
Electrocardiogram repolarisation abnormality
|
5.0%
1/20 • Number of events 1 • Single and double dosing groups - up to 5 ± 1 days after the last PBTZ169 dose intake (Cohorts 1-4): C1A, C1B - up to Day 12 ± 1 (Day 1 - 1st dosing day) C2, C3, C4 - up to Day 6 ± 1 (Day 1 - dosing day) Multiple dosing group - up to 7 ± 1 days after the last PBTZ169 dose intake (Cohort 5): C5 - up to Day 21±1 (Day 1 - 1st dosing day)
|
0.00%
0/10 • Single and double dosing groups - up to 5 ± 1 days after the last PBTZ169 dose intake (Cohorts 1-4): C1A, C1B - up to Day 12 ± 1 (Day 1 - 1st dosing day) C2, C3, C4 - up to Day 6 ± 1 (Day 1 - dosing day) Multiple dosing group - up to 7 ± 1 days after the last PBTZ169 dose intake (Cohort 5): C5 - up to Day 21±1 (Day 1 - 1st dosing day)
|
10.0%
1/10 • Number of events 1 • Single and double dosing groups - up to 5 ± 1 days after the last PBTZ169 dose intake (Cohorts 1-4): C1A, C1B - up to Day 12 ± 1 (Day 1 - 1st dosing day) C2, C3, C4 - up to Day 6 ± 1 (Day 1 - dosing day) Multiple dosing group - up to 7 ± 1 days after the last PBTZ169 dose intake (Cohort 5): C5 - up to Day 21±1 (Day 1 - 1st dosing day)
|
0.00%
0/10 • Single and double dosing groups - up to 5 ± 1 days after the last PBTZ169 dose intake (Cohorts 1-4): C1A, C1B - up to Day 12 ± 1 (Day 1 - 1st dosing day) C2, C3, C4 - up to Day 6 ± 1 (Day 1 - dosing day) Multiple dosing group - up to 7 ± 1 days after the last PBTZ169 dose intake (Cohort 5): C5 - up to Day 21±1 (Day 1 - 1st dosing day)
|
0.00%
0/10 • Single and double dosing groups - up to 5 ± 1 days after the last PBTZ169 dose intake (Cohorts 1-4): C1A, C1B - up to Day 12 ± 1 (Day 1 - 1st dosing day) C2, C3, C4 - up to Day 6 ± 1 (Day 1 - dosing day) Multiple dosing group - up to 7 ± 1 days after the last PBTZ169 dose intake (Cohort 5): C5 - up to Day 21±1 (Day 1 - 1st dosing day)
|
|
Nervous system disorders
Headache
|
5.0%
1/20 • Number of events 1 • Single and double dosing groups - up to 5 ± 1 days after the last PBTZ169 dose intake (Cohorts 1-4): C1A, C1B - up to Day 12 ± 1 (Day 1 - 1st dosing day) C2, C3, C4 - up to Day 6 ± 1 (Day 1 - dosing day) Multiple dosing group - up to 7 ± 1 days after the last PBTZ169 dose intake (Cohort 5): C5 - up to Day 21±1 (Day 1 - 1st dosing day)
|
30.0%
3/10 • Number of events 3 • Single and double dosing groups - up to 5 ± 1 days after the last PBTZ169 dose intake (Cohorts 1-4): C1A, C1B - up to Day 12 ± 1 (Day 1 - 1st dosing day) C2, C3, C4 - up to Day 6 ± 1 (Day 1 - dosing day) Multiple dosing group - up to 7 ± 1 days after the last PBTZ169 dose intake (Cohort 5): C5 - up to Day 21±1 (Day 1 - 1st dosing day)
|
10.0%
1/10 • Number of events 1 • Single and double dosing groups - up to 5 ± 1 days after the last PBTZ169 dose intake (Cohorts 1-4): C1A, C1B - up to Day 12 ± 1 (Day 1 - 1st dosing day) C2, C3, C4 - up to Day 6 ± 1 (Day 1 - dosing day) Multiple dosing group - up to 7 ± 1 days after the last PBTZ169 dose intake (Cohort 5): C5 - up to Day 21±1 (Day 1 - 1st dosing day)
|
0.00%
0/10 • Single and double dosing groups - up to 5 ± 1 days after the last PBTZ169 dose intake (Cohorts 1-4): C1A, C1B - up to Day 12 ± 1 (Day 1 - 1st dosing day) C2, C3, C4 - up to Day 6 ± 1 (Day 1 - dosing day) Multiple dosing group - up to 7 ± 1 days after the last PBTZ169 dose intake (Cohort 5): C5 - up to Day 21±1 (Day 1 - 1st dosing day)
|
10.0%
1/10 • Number of events 2 • Single and double dosing groups - up to 5 ± 1 days after the last PBTZ169 dose intake (Cohorts 1-4): C1A, C1B - up to Day 12 ± 1 (Day 1 - 1st dosing day) C2, C3, C4 - up to Day 6 ± 1 (Day 1 - dosing day) Multiple dosing group - up to 7 ± 1 days after the last PBTZ169 dose intake (Cohort 5): C5 - up to Day 21±1 (Day 1 - 1st dosing day)
|
|
Metabolism and nutrition disorders
Hypercreatininaemia
|
0.00%
0/20 • Single and double dosing groups - up to 5 ± 1 days after the last PBTZ169 dose intake (Cohorts 1-4): C1A, C1B - up to Day 12 ± 1 (Day 1 - 1st dosing day) C2, C3, C4 - up to Day 6 ± 1 (Day 1 - dosing day) Multiple dosing group - up to 7 ± 1 days after the last PBTZ169 dose intake (Cohort 5): C5 - up to Day 21±1 (Day 1 - 1st dosing day)
|
0.00%
0/10 • Single and double dosing groups - up to 5 ± 1 days after the last PBTZ169 dose intake (Cohorts 1-4): C1A, C1B - up to Day 12 ± 1 (Day 1 - 1st dosing day) C2, C3, C4 - up to Day 6 ± 1 (Day 1 - dosing day) Multiple dosing group - up to 7 ± 1 days after the last PBTZ169 dose intake (Cohort 5): C5 - up to Day 21±1 (Day 1 - 1st dosing day)
|
0.00%
0/10 • Single and double dosing groups - up to 5 ± 1 days after the last PBTZ169 dose intake (Cohorts 1-4): C1A, C1B - up to Day 12 ± 1 (Day 1 - 1st dosing day) C2, C3, C4 - up to Day 6 ± 1 (Day 1 - dosing day) Multiple dosing group - up to 7 ± 1 days after the last PBTZ169 dose intake (Cohort 5): C5 - up to Day 21±1 (Day 1 - 1st dosing day)
|
0.00%
0/10 • Single and double dosing groups - up to 5 ± 1 days after the last PBTZ169 dose intake (Cohorts 1-4): C1A, C1B - up to Day 12 ± 1 (Day 1 - 1st dosing day) C2, C3, C4 - up to Day 6 ± 1 (Day 1 - dosing day) Multiple dosing group - up to 7 ± 1 days after the last PBTZ169 dose intake (Cohort 5): C5 - up to Day 21±1 (Day 1 - 1st dosing day)
|
20.0%
2/10 • Number of events 2 • Single and double dosing groups - up to 5 ± 1 days after the last PBTZ169 dose intake (Cohorts 1-4): C1A, C1B - up to Day 12 ± 1 (Day 1 - 1st dosing day) C2, C3, C4 - up to Day 6 ± 1 (Day 1 - dosing day) Multiple dosing group - up to 7 ± 1 days after the last PBTZ169 dose intake (Cohort 5): C5 - up to Day 21±1 (Day 1 - 1st dosing day)
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: OTHER