Healthy
Conditions
Brief summary
This is a Phase 1, first-in-human, randomized, double-blind, placebo-controlled, single ascending dose, sequential group study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of PB2452 with and without ticagrelor pretreatment when administered to healthy male and female subjects. Up to 6 dose levels will be evaluated. This study will have up to 10 cohorts and up to a total of approximately 76 subjects with either 4 or 8 healthy young subjects in Cohorts 1 through 9 or approximately 16 older subjects in Cohort 10. The starting dose of PB2452 will be 100 mg and the planned doses for subsequent cohorts are 300, 1000, 3000, 9000, and 18000 mg.
Interventions
DRUGPB2452 Infusion
30 minute - 12 hour infusion
30 minute - 12 hour infusion
Ticagrelor 180 mg + 90 mg BID for 5 doses prior to MEDI2452 (PB2452) or Placebo
Ticagrelor 180 mg + 90 mg BID for 5 doses prior to MEDI2452 (PB2452) or Placebo and Ticagerlor 180 mg 24 hours following MEDI2452 (PB2452) or Placebo
Sponsors
SFJ Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
Yes
Inclusion criteria
1. The subject is male or female between 18 and 50 years of age, inclusive. 2. The subject has a body mass index between 18 and 35 kg/m2 and a weight of ≥50 kg but ≤120 kg, inclusive, at screening. 3. The subject is considered by the investigator to be in good general health as determined by medical history, clinical laboratory test results, vital sign measurements, 12 lead ECG results, and physical examination findings at screening. Specific inclusionary laboratory values at screening and check-in require the following: * Aspartate transaminase (AST), alanine transaminase (ALT), total serum bilirubin and alkaline phosphatase levels within the normal range as defined by the clinical laboratory * White blood cell (WBC) count, platelet count and hemoglobin level within the normal range as defined by the clinical laboratory * Thyroid stimulating hormone (TSH) level within the normal range as defined by the clinical laboratory at screening * Prothrombin time (PT) and partial thromboplastin time (PTT) level within the normal range as defined by the clinical laboratory 4. Female subjects of childbearing potential must not be pregnant, lactating, or planning to become pregnant before 3 months after the last dose of study drug, and have a negative serum pregnancy test at screening and check-in. Female subjects of childbearing potential must use 2 effective methods of birth control (ie, oral, implantable, patch, or injectable contraceptives in combination with a condom, hormone-containing intrauterine device that has been in place for at least 2 months prior to screening in combination with a condom, double-barrier method \[ie, condoms, sponge, diaphragm, or cervical cap with spermicidal gels or cream\], or vasectomy for male subjects or male partners of female subjects) from 30 days before study drug administration through the end of the study. Women are considered not to be of childbearing potential if they have fulfilled one of the following criteria: documentation of irreversible surgical sterilization (ie, hysterectomy, or bilateral oophorectomy \[not tubal ligation\]), or postmenopausal (defined as amenorrhea for 12 consecutive months following cessation of all exogenous hormonal treatments, and documented plasma follicle-stimulating hormone level \>40 IU/mL or amenorrhea for 24 consecutive months). Male subjects with partners of childbearing potential must agree to use appropriate and effective measures of contraception (eg, condom plus diaphragm with spermicide; condom plus spermicide) during the study and for 30 days after the last dose of study drug, and to refrain from donating sperm for at least 7 days prior to the first dose of study drug until at least 90 days following the last dose of study drug. 5. The subject agrees to comply with all protocol requirements. 6. The subject is able to provide written informed consent.
Exclusion criteria
1. History of any clinically significant acute or chronic disease or medical disorder. 2. History or presence of gastrointestinal, hepatic (with the exception of Gilbert's syndrome), or renal disease or renal insufficiency (ie, estimated glomerular filtration rate \<60 ml/min/1.73m2), or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs. 3. Any clinically significant illness, medical/surgical procedure, or trauma within 4 weeks of the first administration of study drug or any planned surgical procedure that will occur during the study (from screening through the Day 28 follow up visit). 4. Any clinically significant abnormal findings in physical examination, vital signs, laboratory assessments, and ECG parameters identified during screening or check-in. 5. Any history of arterial or venous thrombosis, including any of the following: * History of transient ischemic attack, cardiovascular accident, stroke (ischemic or hemorrhagic), unstable angina, myocardial infarction, or peripheral arterial disease * History of deep venous thrombosis, pulmonary embolus, thrombophlebitis, or cavernous malformations 6. Any increased risk of bleeding, including the following: * Recent history (within 30 days preceding the first dose of study drug) of gastrointestinal bleeding * Any history of severe head trauma, intracranial hemorrhage, intracranial neoplasm, arteriovenous malformation, aneurysm, or proliferative retinopathy * Any history of intracranial, intraocular, retroperitoneal, or spinal bleeding * Any recent (within 30 days preceding the first dose of study drug) major trauma * History of hemorrhagic disorders that may increase the risk of bleeding (eg, hemophilia, von Willebrand's disease) * Receiving chronic treatment with nonsteroidal anti-inflammatory drugs (including aspirin \[greater than 100 mg daily\]), anticoagulants, or other antiplatelet agents that cannot be discontinued (including clopidogrel, prasugrel, ticlopidine, dipyridamole, or cilostazol). * Have taken, within 30 days of screening, any oral or parenteral anticoagulant, including low molecular-weight heparin * Have taken non-steroidal anti-inflammatory medications, including aspirin, within 14 days of screening 7. The subject has a positive test result for hepatitis B surface antigen, hepatitis C virus antibody, or human immunodeficiency virus types 1 or 2 antibodies at screening. 8. Any ongoing or recent (ie, during the screening period) minor medical complaints that may interfere with the interpretation of the study data or are considered unlikely to comply with study procedures, restrictions, and requirements as judged by the investigator. 9. Concomitant oral or IV therapy with strong CYP3A inhibitors, CYP3A substrates with narrow therapeutic indices, or strong CYP3A inducers, which cannot be stopped within at least 5 half-lives, but not shorter than 10 days, before randomization (a list of examples can be found in Section 6.2). 10. Any prescription (excluding hormonal birth control) or over the counter medications (except paracetamol \[up to 2 g per day\]), including herbal or nutritional supplements, within 14 days before the first dose of study drug. 11. The subject has consumed grapefruit or grapefruit juice, Seville orange or Seville orange containing products (eg, marmalade), or alcohol-, or xanthine containing products within 48 hours before dosing with study drug. 12. The subject is participating in any other study or is taking part in a non medication study which, in the opinion of the investigator, would interfere with the outcome of the study. 13. The subject has received another new chemical entity (defined as a compound which has not been approved for marketing) or any marketed or investigational biologic agent within 30 days of the first administration of study drug in this study. The period of exclusion begins 30 days after the final dose or 5 half-lives of the experimental medication has elapsed, whichever is longer. 14. The subject has involvement with any PhaseBio or study site employee or their close relatives (eg, spouse, parents, siblings, or children whether biological or legally adopted). 15. The subject has previously received MEDI2452 (PB2452). 16. The subject is a smoker or has used nicotine or nicotine containing products (eg, snuff, nicotine patch, nicotine chewing gum, mock cigarettes, or inhalers) within 3 months before the first dose of study drug. 17. The subject has a known or suspected history of drug abuse (including alcohol) or has a positive test result for drugs of abuse, alcohol, or cotinine (nicotine level above 300 ng/mL) at screening or check-in. 18. The subject has been involved in strenuous activity or contact sports within 24 hours before the first dose of study drug and while confined in the clinical site. 19. The subject has donated blood or plasma within 1 month of screening or any blood donation/loss more than 500 mL during the 3 months prior to the first dose of study drug. 20. The subject has a history of severe allergy/hypersensitivity or ongoing allergy/hypersensitivity, as judged by the investigator or history of hypersensitivity to drugs with a similar chemical structure or class to ticagrelor, any biologic therapeutic agent, or any significant food allergy that could preclude a standard diet in the clinical site. 21. Concern for the inability of the subject to comply with study procedures and/or follow up, or, in the opinion of the investigator, the subject is not suitable for entry into the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Clinically Significant Cardiac Telemetry Findings | 3 Days - Starting 1 day prior to dosing up to 2 days after dosing | Number of participants per cohort with clinically significant cardiac telemetry findings. |
| Incidence of Clinically Significant 12-Lead Electrocardiogram (ECG) Findings | 60 days - Starting up to 28 days prior to dosing | Number of participants per cohort with clinically significant ECG findings. |
| Number of Participants With Adverse Events (AEs) | Day -3 (Cohorts 4 through 10) or Day -1 (Cohorts 1 through 3) until Day 28 | An AE is defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug-related. |
| Number of Participants With Clinically Significant Laboratory Abnormalities | 30 Day - Starting day of dosing | Number of participants with clinically significant abnormal laboratory findings for hematology, coagulation, serum chemistry, urinalysis and drug tests. |
| Change in Diastolic Blood Pressure | Days 1, 2, 3, 4, 7 and 28 | Diastolic blood pressure measurements were measured at specific time points. |
| Change in Systolic Blood Pressure | Days 1, 2, 3, 4, 7 and 28 | Systolic blood pressure measurements were measured at specific time points. |
| Change In Oral Body Temperature | Days 1, 2, 3, 4, 7 and 28 | Body temperature measurements were measured at specific time points. |
| Change In Respiratory Rate | Days 1, 2, 3, 4, 7 and 28 | Respiratory rate measurements were measured at specific time points. |
| Change In Heart Rate | Days 1, 2, 3, 4, 7 and 28 | Heart rate measurements were measured at specific time points. |
| Participants Experiencing Anti-drug Antibodies (ADAs) | Day -3, Day -1, Day 7, and Day 28 | Incidence of Immunogenicity. |
| Maximal Percent of Baseline Platelet Aggregation (PA(Max)) in Cohorts 4-6 | Before dosing and at 0.5, 1, 2, 3, 6, 12, 24, and 48 hours after PB2452 infusion and 5th ticagrelor dose. | Effectiveness Of Single Ascending Doses Of PB2452. IPA \[maximum (max)\] induced by 20 µM adenosine diphosphate (ADP) at each assessment point. |
| Final Extent Percent of Baseline Platelet Aggregation in Cohorts 4-6 | Before dosing and at 0.5, 1, 2, 3, 6, 12, 24, and 48 hours after PB2452 infusion and 5th ticagrelor dose. | Effectiveness Of Single Ascending Doses Of PB2452. IPA \[final extent\] induced by 20 µM adenosine diphosphate (ADP) at each assessment point. |
| Maximal Actual Platelet Aggregation (APA(Max)) (Cohorts 4-6) | Before dosing and at 0.5, 1, 2, 3, 6, 12, 24, and 48 hours after PB2452 infusion and 5th ticagrelor dose. And at 1, 2, 6, and 12 hours after the Day 2 post-MEDI2452 (PB2452) 6th ticagrelor dose (Cohorts 8 and 9 Only). | Effectiveness Of Single Ascending Doses Of PB2452 - Inhibition of maximal platelet aggregation. |
| Time to Maximum Platelet Aggregation (TPA(Max)) (Cohorts 4-6) | Before dosing and at 0.5, 1, 2, 3, 6, 12, 24, and 48 hours after PB2452 infusion and 5th ticagrelor dose. | Effectiveness Of Single Ascending Doses Of PB2452 - Time to IPAmax. |
| Maximal Percent of Baseline Platelet Aggregation (PA(Max)) (Cohorts 7-10) | Before dosing and at 5 min, 0.25, 0.5, 1, 2, 3, 6, 8, 10, 12, 16, 20, 24, and 48 hours after PB2452 infusion and 5th ticagrelor dose. And at 1, 2, 6, and 12 hours after the Day 2 post-MEDI2452 (PB2452) 6th ticagrelor dose. | Effectiveness Of Single Ascending Doses Of PB2452 - IPA (max) induced by 20 µM ADP at each assessment point. |
| Final Extent Percent of Baseline Platelet Aggregation (Cohorts 7-10) | Before dosing and at 5 min, 0.25, 0.5, 1, 2, 3, 6, 8, 10, 12, 16, 20, 24, and 48 hours after PB2452 infusion and 5th ticagrelor dose. And at 1, 2, 6, and 12 hours after the Day 2 post-MEDI2452 (PB2452) 6th ticagrelor dose. | Effectiveness Of Single Ascending Doses Of PB2452 - IPA (max) induced by 20 µM ADP at each assessment point. |
| Maximal Actual Platelet Aggregation (APA(Max)) (Cohorts 7-10) | Before dosing and at 5 min, 0.25, 0.5, 1, 2, 3, 6, 8, 10, 12, 16, 20, 24, and 48 hours after PB2452 infusion and 5th ticagrelor dose. And at 1, 2, 6, and 12 hours after the Day 2 post-MEDI2452 (PB2452) 6th ticagrelor dose | Effectiveness Of Single Ascending Doses Of PB2452 - Inhibition of maximal platelet aggregation. |
| Time to Maximum Platelet Aggregation (TPA(Max))(Cohorts 7-10) | Before dosing and at 5 min, 0.25, 0.5, 1, 2, 3, 6, 8, 10, 12, 16, 20, 24, and 48 hours after PB2452 infusion and 5th ticagrelor dose. And at 1, 2, 6, and 12 hours after the Day 2 post-MEDI2452 (PB2452) 6th ticagrelor dose. | Effectiveness Of Single Ascending Doses Of PB2452 - Time to IPAmax |
Countries
United States
Participant flow
Pre-assignment details
Healthy participants who met all the inclusion criteria and none of the exclusion criteria were randomly assigned to receive either PB2452 or placebo in a ratio of 3:1 in all treatment cohorts.
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1: 100 mg PB2452 (no Ticagrelor) PB2452 Infusion: single 30-minute IV infusion of 100 mg PB2452 | 3 |
| Cohort 2: 300 mg PB2452 (no Ticagrelor) PB2452 Infusion: single 30-minute IV infusion of 300 mg PB2452 | 3 |
| Cohort 3: 1000 mg PB2452 (no Ticagrelor) PB2452 Infusion: single 30-minute IV infusion of 1000 mg PB2452 | 3 |
| Cohort 1 to 3: Placebo Placebo - Sodium Chloride: single 30-minute IV infusion of placebo | 3 |
| Cohort 4: 1000 mg PB2452 (Ticagrelor Pre-Trx) PB2452 Infusion: single 30-minute IV infusion of 1000 mg PB2452
Ticagrelor Oral Tablet - Pre-Treatment: Ticagrelor 180 mg + 90 mg BID for 5 doses prior to administration of a single IV dose of PB2452 | 6 |
| Cohort 5: 3000 mg PB2452 (Ticagrelor Pre-Trx) PB2452 Infusion: single 30-minute IV infusion of 3000 mg PB2452
Ticagrelor Oral Tablet - Pre-Treatment: Ticagrelor 180 mg + 90 mg BID for 5 doses prior to administration of a single IV dose of PB2452 | 6 |
| Cohort 6: 9000 mg PB2452 (Ticagrelor Pre-Trx) PB2452 Infusion: single 30-minute IV infusion of 9000 mg PB2452
Ticagrelor Oral Tablet - Pre-Treatment: Ticagrelor 180 mg + 90 mg BID for 5 doses prior to administration of a single IV dose of PB2452 | 6 |
| Cohort 4 to 6: Placebo Placebo - Sodium Chloride: single 30-minute IV infusion of placebo | 6 |
| Cohort 7: 18000 mg PB2452 (Ticagrelor Pre-Trx) PB2452 Infusion: single IV infusion of 18000 mg PB2452 for 8 hours
Ticagrelor Oral Tablet - Pre-Treatment: Ticagrelor 180 mg + 90 mg BID for 5 doses prior to administration of a single IV dose of PB2452 | 6 |
| Cohort 8: 18000 mg PB2452 (Ticagrelor Pre-Trx) PB2452 Infusion: single IV infusion of 18000 mg PB2452 for 12 hours
Ticagrelor Oral Tablet - Pre-Treatment: Ticagrelor 180 mg + 90 mg BID for 5 doses prior to administration of a single IV dose of PB2452 | 6 |
| Cohort 9: 18000 mg PB2452 (Ticagrelor Pre-Trx) PB2452 Infusion: single IV infusion of 18000 mg PB2452 for 16 hours and 20 minutes
Ticagrelor Oral Tablet - Pre-Treatment: Ticagrelor 180 mg + 90 mg BID for 5 doses prior to administration of a single IV dose of PB2452 | 3 |
| Cohort 10: 18000 mg PB2452 (Ticagrelor Pre-Trx) PB2452 Infusion: single IV infusion of 18000 mg PB2452 for 16 hours and 12 minutes
Ticagrelor Oral Tablet - Pre-Treatment: Ticagrelor 180 mg + 90 mg BID for 5 doses prior to administration of a single IV dose of PB2452 | 6 |
| Cohort 7 to 10: Placebo Placebo - Sodium Chloride: single 8-hour to 16.5-hour IV infusion of placebo | 7 |
| Total | 64 |
Baseline characteristics
| Characteristic | Cohort 2: 300 mg PB2452 (no Ticagrelor) | Cohort 3: 1000 mg PB2452 (no Ticagrelor) | Cohort 1: 100 mg PB2452 (no Ticagrelor) | Cohort 1 to 3: Placebo | Cohort 4: 1000 mg PB2452 (Ticagrelor Pre-Trx) | Cohort 5: 3000 mg PB2452 (Ticagrelor Pre-Trx) | Cohort 6: 9000 mg PB2452 (Ticagrelor Pre-Trx) | Cohort 4 to 6: Placebo | Cohort 7: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Cohort 8: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Cohort 9: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Cohort 10: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Cohort 7 to 10: Placebo | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 30.0 years STANDARD_DEVIATION 10.58 | 40.0 years STANDARD_DEVIATION 12.49 | 27.7 years STANDARD_DEVIATION 2.89 | 28.0 years STANDARD_DEVIATION 9.17 | 30.7 years STANDARD_DEVIATION 5.99 | 30.2 years STANDARD_DEVIATION 9.95 | 33.8 years STANDARD_DEVIATION 11.96 | 30.7 years STANDARD_DEVIATION 5.79 | 26.7 years STANDARD_DEVIATION 8.87 | 29.7 years STANDARD_DEVIATION 8.04 | 30.7 years STANDARD_DEVIATION 5.86 | 28.7 years STANDARD_DEVIATION 9.03 | 39.4 years STANDARD_DEVIATION 7.16 | 31.4 years STANDARD_DEVIATION 8.71 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Black or African American | 1 Participants | 1 Participants | 2 Participants | 2 Participants | 2 Participants | 2 Participants | 0 Participants | 1 Participants | 3 Participants | 4 Participants | 0 Participants | 3 Participants | 5 Participants | 26 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 1 Participants | 2 Participants | 2 Participants | 1 Participants | 3 Participants | 3 Participants | 4 Participants | 2 Participants | 2 Participants | 2 Participants | 2 Participants | 1 Participants | 3 Participants | 28 Participants |
| Race/Ethnicity, Customized Multiple | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 2 Participants | 1 Participants | 1 Participants | 2 Participants | 3 Participants | 3 Participants | 2 Participants | 4 Participants | 4 Participants | 4 Participants | 1 Participants | 5 Participants | 4 Participants | 36 Participants |
| Race/Ethnicity, Customized White | 2 Participants | 2 Participants | 1 Participants | 1 Participants | 4 Participants | 3 Participants | 5 Participants | 4 Participants | 3 Participants | 1 Participants | 3 Participants | 3 Participants | 2 Participants | 34 Participants |
| Sex: Female, Male Female | 2 Participants | 2 Participants | 1 Participants | 1 Participants | 3 Participants | 3 Participants | 5 Participants | 2 Participants | 2 Participants | 3 Participants | 2 Participants | 2 Participants | 2 Participants | 30 Participants |
| Sex: Female, Male Male | 1 Participants | 1 Participants | 2 Participants | 2 Participants | 3 Participants | 3 Participants | 1 Participants | 4 Participants | 4 Participants | 3 Participants | 1 Participants | 4 Participants | 5 Participants | 34 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 | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk | EG012 affected / at risk | EG013 affected / at risk | EG014 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 0 / 3 | 0 / 3 | 0 / 3 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 3 | 0 / 6 | 0 / 7 | 0 / 48 | 0 / 16 |
| other Total, other adverse events | 0 / 3 | 0 / 3 | 1 / 3 | 1 / 3 | 3 / 6 | 0 / 6 | 6 / 6 | 1 / 6 | 2 / 6 | 2 / 6 | 1 / 3 | 2 / 6 | 0 / 7 | 17 / 48 | 2 / 16 |
| serious Total, serious adverse events | 0 / 3 | 0 / 3 | 0 / 3 | 0 / 3 | 1 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 3 | 0 / 6 | 0 / 7 | 1 / 48 | 0 / 16 |
Outcome results
Primary
Change in Diastolic Blood Pressure
Diastolic blood pressure measurements were measured at specific time points.
Time frame: Days 1, 2, 3, 4, 7 and 28
Population: Safety population: all participants who received any amount of study drug.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: 100 mg PB2452 (no Ticagrelor) | Change in Diastolic Blood Pressure | Change from Baseline - Day 4 | 7.7 mmHg | Standard Deviation 9.45 |
| Cohort 1: 100 mg PB2452 (no Ticagrelor) | Change in Diastolic Blood Pressure | Change from Baseline - Day 1/4 Hour | 1.3 mmHg | Standard Deviation 3.21 |
| Cohort 1: 100 mg PB2452 (no Ticagrelor) | Change in Diastolic Blood Pressure | Change from Baseline - Day 7 | 9.0 mmHg | Standard Deviation 10.58 |
| Cohort 1: 100 mg PB2452 (no Ticagrelor) | Change in Diastolic Blood Pressure | Change from Baseline - Day 2/24 Hour | 3.0 mmHg | Standard Deviation 5.57 |
| Cohort 1: 100 mg PB2452 (no Ticagrelor) | Change in Diastolic Blood Pressure | Change from Baseline - Day 1/8 Hour | 0.3 mmHg | Standard Deviation 7.02 |
| Cohort 1: 100 mg PB2452 (no Ticagrelor) | Change in Diastolic Blood Pressure | Change from Baseline - Day 2/30 Hour | 4.0 mmHg | Standard Deviation 4.36 |
| Cohort 1: 100 mg PB2452 (no Ticagrelor) | Change in Diastolic Blood Pressure | Change from Baseline - Day 1/2 Hour | 12.7 mmHg | Standard Deviation 7.23 |
| Cohort 1: 100 mg PB2452 (no Ticagrelor) | Change in Diastolic Blood Pressure | Change from Baseline - Day 2/36 Hour | 3.3 mmHg | Standard Deviation 5.51 |
| Cohort 1: 100 mg PB2452 (no Ticagrelor) | Change in Diastolic Blood Pressure | Change from Baseline - Day 1/0.75 Hour | 0.7 mmHg | Standard Deviation 10.21 |
| Cohort 1: 100 mg PB2452 (no Ticagrelor) | Change in Diastolic Blood Pressure | Change from Baseline - Day 1/0.5 Hour | 1.7 mmHg | Standard Deviation 6.66 |
| Cohort 1: 100 mg PB2452 (no Ticagrelor) | Change in Diastolic Blood Pressure | Change from Baseline - Day 1/1 Hour | -0.7 mmHg | Standard Deviation 11.37 |
| Cohort 1: 100 mg PB2452 (no Ticagrelor) | Change in Diastolic Blood Pressure | Change from Baseline - Day 28 | 12.0 mmHg | Standard Deviation 7.94 |
| Cohort 1: 100 mg PB2452 (no Ticagrelor) | Change in Diastolic Blood Pressure | Change from Baseline - Day 3/48 Hour | 5.0 mmHg | Standard Deviation 5.29 |
| Cohort 1: 100 mg PB2452 (no Ticagrelor) | Change in Diastolic Blood Pressure | Change from Baseline - Day 3/42 Hour | 1.0 mmHg | Standard Deviation 12.12 |
| Cohort 2: 300 mg PB2452 (no Ticagrelor) | Change in Diastolic Blood Pressure | Change from Baseline - Day 1/1 Hour | 0 mmHg | Standard Deviation 4.58 |
| Cohort 2: 300 mg PB2452 (no Ticagrelor) | Change in Diastolic Blood Pressure | Change from Baseline - Day 7 | -1.3 mmHg | Standard Deviation 6.81 |
| Cohort 2: 300 mg PB2452 (no Ticagrelor) | Change in Diastolic Blood Pressure | Change from Baseline - Day 1/2 Hour | 1.0 mmHg | Standard Deviation 2 |
| Cohort 2: 300 mg PB2452 (no Ticagrelor) | Change in Diastolic Blood Pressure | Change from Baseline - Day 2/36 Hour | -7.7 mmHg | Standard Deviation 5.86 |
| Cohort 2: 300 mg PB2452 (no Ticagrelor) | Change in Diastolic Blood Pressure | Change from Baseline - Day 1/0.5 Hour | -2.3 mmHg | Standard Deviation 7.57 |
| Cohort 2: 300 mg PB2452 (no Ticagrelor) | Change in Diastolic Blood Pressure | Change from Baseline - Day 2/30 Hour | -5.7 mmHg | Standard Deviation 8.02 |
| Cohort 2: 300 mg PB2452 (no Ticagrelor) | Change in Diastolic Blood Pressure | Change from Baseline - Day 3/42 Hour | -9.3 mmHg | Standard Deviation 1.53 |
| Cohort 2: 300 mg PB2452 (no Ticagrelor) | Change in Diastolic Blood Pressure | Change from Baseline - Day 2/24 Hour | -2.7 mmHg | Standard Deviation 4.73 |
| Cohort 2: 300 mg PB2452 (no Ticagrelor) | Change in Diastolic Blood Pressure | Change from Baseline - Day 28 | 5.0 mmHg | Standard Deviation 2.65 |
| Cohort 2: 300 mg PB2452 (no Ticagrelor) | Change in Diastolic Blood Pressure | Change from Baseline - Day 1/0.75 Hour | -1.0 mmHg | Standard Deviation 8.89 |
| Cohort 2: 300 mg PB2452 (no Ticagrelor) | Change in Diastolic Blood Pressure | Change from Baseline - Day 1/8 Hour | -8.7 mmHg | Standard Deviation 4.93 |
| Cohort 2: 300 mg PB2452 (no Ticagrelor) | Change in Diastolic Blood Pressure | Change from Baseline - Day 3/48 Hour | -1.0 mmHg | Standard Deviation 4 |
| Cohort 2: 300 mg PB2452 (no Ticagrelor) | Change in Diastolic Blood Pressure | Change from Baseline - Day 1/4 Hour | -9.0 mmHg | Standard Deviation 2 |
| Cohort 2: 300 mg PB2452 (no Ticagrelor) | Change in Diastolic Blood Pressure | Change from Baseline - Day 4 | 3.7 mmHg | Standard Deviation 4.16 |
| Cohort 3: 1000 mg PB2452 (no Ticagrelor) | Change in Diastolic Blood Pressure | Change from Baseline - Day 3/42 Hour | -6.0 mmHg | Standard Deviation 3.46 |
| Cohort 3: 1000 mg PB2452 (no Ticagrelor) | Change in Diastolic Blood Pressure | Change from Baseline - Day 2/24 Hour | 2.3 mmHg | Standard Deviation 1.15 |
| Cohort 3: 1000 mg PB2452 (no Ticagrelor) | Change in Diastolic Blood Pressure | Change from Baseline - Day 1/0.5 Hour | 5.7 mmHg | Standard Deviation 3.21 |
| Cohort 3: 1000 mg PB2452 (no Ticagrelor) | Change in Diastolic Blood Pressure | Change from Baseline - Day 1/2 Hour | 0.7 mmHg | Standard Deviation 1.53 |
| Cohort 3: 1000 mg PB2452 (no Ticagrelor) | Change in Diastolic Blood Pressure | Change from Baseline - Day 7 | 6.3 mmHg | Standard Deviation 3.06 |
| Cohort 3: 1000 mg PB2452 (no Ticagrelor) | Change in Diastolic Blood Pressure | Change from Baseline - Day 3/48 Hour | -1.7 mmHg | Standard Deviation 6.43 |
| Cohort 3: 1000 mg PB2452 (no Ticagrelor) | Change in Diastolic Blood Pressure | Change from Baseline - Day 2/30 Hour | -4.7 mmHg | Standard Deviation 4.04 |
| Cohort 3: 1000 mg PB2452 (no Ticagrelor) | Change in Diastolic Blood Pressure | Change from Baseline - Day 4 | 2.7 mmHg | Standard Deviation 3.06 |
| Cohort 3: 1000 mg PB2452 (no Ticagrelor) | Change in Diastolic Blood Pressure | Change from Baseline - Day 1/4 Hour | -0.3 mmHg | Standard Deviation 1.53 |
| Cohort 3: 1000 mg PB2452 (no Ticagrelor) | Change in Diastolic Blood Pressure | Change from Baseline - Day 1/1 Hour | 2.7 mmHg | Standard Deviation 6.66 |
| Cohort 3: 1000 mg PB2452 (no Ticagrelor) | Change in Diastolic Blood Pressure | Change from Baseline - Day 1/0.75 Hour | 3.3 mmHg | Standard Deviation 6.43 |
| Cohort 3: 1000 mg PB2452 (no Ticagrelor) | Change in Diastolic Blood Pressure | Change from Baseline - Day 28 | 1.3 mmHg | Standard Deviation 1.53 |
| Cohort 3: 1000 mg PB2452 (no Ticagrelor) | Change in Diastolic Blood Pressure | Change from Baseline - Day 1/8 Hour | -1.3 mmHg | Standard Deviation 4.51 |
| Cohort 3: 1000 mg PB2452 (no Ticagrelor) | Change in Diastolic Blood Pressure | Change from Baseline - Day 2/36 Hour | -0.7 mmHg | Standard Deviation 5.03 |
| Cohort 1 to 3: Placebo | Change in Diastolic Blood Pressure | Change from Baseline - Day 2/24 Hour | -2.7 mmHg | Standard Deviation 4.04 |
| Cohort 1 to 3: Placebo | Change in Diastolic Blood Pressure | Change from Baseline - Day 2/36 Hour | -5.3 mmHg | Standard Deviation 6.81 |
| Cohort 1 to 3: Placebo | Change in Diastolic Blood Pressure | Change from Baseline - Day 1/0.5 Hour | -1.7 mmHg | Standard Deviation 10.02 |
| Cohort 1 to 3: Placebo | Change in Diastolic Blood Pressure | Change from Baseline - Day 28 | 4.0 mmHg | Standard Deviation 4.58 |
| Cohort 1 to 3: Placebo | Change in Diastolic Blood Pressure | Change from Baseline - Day 1/0.75 Hour | -0.3 mmHg | Standard Deviation 9.07 |
| Cohort 1 to 3: Placebo | Change in Diastolic Blood Pressure | Change from Baseline - Day 7 | 6.0 mmHg | Standard Deviation 6.08 |
| Cohort 1 to 3: Placebo | Change in Diastolic Blood Pressure | Change from Baseline - Day 1/1 Hour | 4.0 mmHg | Standard Deviation 6.24 |
| Cohort 1 to 3: Placebo | Change in Diastolic Blood Pressure | Change from Baseline - Day 1/2 Hour | -1.7 mmHg | Standard Deviation 8.14 |
| Cohort 1 to 3: Placebo | Change in Diastolic Blood Pressure | Change from Baseline - Day 3/48 Hour | -3.3 mmHg | Standard Deviation 13.5 |
| Cohort 1 to 3: Placebo | Change in Diastolic Blood Pressure | Change from Baseline - Day 4 | 5.3 mmHg | Standard Deviation 3.79 |
| Cohort 1 to 3: Placebo | Change in Diastolic Blood Pressure | Change from Baseline - Day 1/4 Hour | -3.3 mmHg | Standard Deviation 8.02 |
| Cohort 1 to 3: Placebo | Change in Diastolic Blood Pressure | Change from Baseline - Day 1/8 Hour | 2.7 mmHg | Standard Deviation 4.62 |
| Cohort 1 to 3: Placebo | Change in Diastolic Blood Pressure | Change from Baseline - Day 3/42 Hour | -3.3 mmHg | Standard Deviation 7.02 |
| Cohort 1 to 3: Placebo | Change in Diastolic Blood Pressure | Change from Baseline - Day 2/30 Hour | -6.7 mmHg | Standard Deviation 9.61 |
| Cohort 4: 1000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Diastolic Blood Pressure | Change from Baseline - Day 1/4 Hour | -2.2 mmHg | Standard Deviation 5.53 |
| Cohort 4: 1000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Diastolic Blood Pressure | Change from Baseline - Day 1/0.75 Hour | 0.3 mmHg | Standard Deviation 9.29 |
| Cohort 4: 1000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Diastolic Blood Pressure | Change from Baseline - Day 28 | 8.8 mmHg | Standard Deviation 7.08 |
| Cohort 4: 1000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Diastolic Blood Pressure | Change from Baseline - Day 1/8 Hour | -4.2 mmHg | Standard Deviation 9.91 |
| Cohort 4: 1000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Diastolic Blood Pressure | Change from Baseline - Day 4 | 8.2 mmHg | Standard Deviation 5.42 |
| Cohort 4: 1000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Diastolic Blood Pressure | Change from Baseline - Day 3/42 Hour | -7.2 mmHg | Standard Deviation 7.81 |
| Cohort 4: 1000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Diastolic Blood Pressure | Change from Baseline - Day 1/0.5 Hour | -0.8 mmHg | Standard Deviation 7.76 |
| Cohort 4: 1000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Diastolic Blood Pressure | Change from Baseline - Day 3/48 Hour | 3.8 mmHg | Standard Deviation 7.14 |
| Cohort 4: 1000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Diastolic Blood Pressure | Change from Baseline - Day 1/2 Hour | 1.0 mmHg | Standard Deviation 6.84 |
| Cohort 4: 1000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Diastolic Blood Pressure | Change from Baseline - Day 1/1 Hour | 3.5 mmHg | Standard Deviation 8.78 |
| Cohort 4: 1000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Diastolic Blood Pressure | Change from Baseline - Day 7 | 7.0 mmHg | Standard Deviation 5.44 |
| Cohort 4: 1000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Diastolic Blood Pressure | Change from Baseline - Day 2/36 Hour | 0.2 mmHg | Standard Deviation 9.06 |
| Cohort 4: 1000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Diastolic Blood Pressure | Change from Baseline - Day 2/24 Hour | 1.2 mmHg | Standard Deviation 5.08 |
| Cohort 4: 1000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Diastolic Blood Pressure | Change from Baseline - Day 2/30 Hour | -2.2 mmHg | Standard Deviation 5.6 |
| Cohort 5: 3000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Diastolic Blood Pressure | Change from Baseline - Day 1/4 Hour | -3.3 mmHg | Standard Deviation 4.72 |
| Cohort 5: 3000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Diastolic Blood Pressure | Change from Baseline - Day 2/36 Hour | -2.0 mmHg | Standard Deviation 5.66 |
| Cohort 5: 3000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Diastolic Blood Pressure | Change from Baseline - Day 1/1 Hour | 0.3 mmHg | Standard Deviation 3.33 |
| Cohort 5: 3000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Diastolic Blood Pressure | Change from Baseline - Day 7 | 3.2 mmHg | Standard Deviation 7.08 |
| Cohort 5: 3000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Diastolic Blood Pressure | Change from Baseline - Day 1/0.75 Hour | -1.0 mmHg | Standard Deviation 1.79 |
| Cohort 5: 3000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Diastolic Blood Pressure | Change from Baseline - Day 1/8 Hour | -3.3 mmHg | Standard Deviation 8.02 |
| Cohort 5: 3000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Diastolic Blood Pressure | Change from Baseline - Day 3/48 Hour | -0.2 mmHg | Standard Deviation 4.83 |
| Cohort 5: 3000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Diastolic Blood Pressure | Change from Baseline - Day 3/42 Hour | -3.2 mmHg | Standard Deviation 3.87 |
| Cohort 5: 3000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Diastolic Blood Pressure | Change from Baseline - Day 2/30 Hour | -4.5 mmHg | Standard Deviation 6.22 |
| Cohort 5: 3000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Diastolic Blood Pressure | Change from Baseline - Day 28 | 6.7 mmHg | Standard Deviation 5.61 |
| Cohort 5: 3000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Diastolic Blood Pressure | Change from Baseline - Day 2/24 Hour | -2.3 mmHg | Standard Deviation 4.37 |
| Cohort 5: 3000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Diastolic Blood Pressure | Change from Baseline - Day 1/0.5 Hour | -2.7 mmHg | Standard Deviation 5.39 |
| Cohort 5: 3000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Diastolic Blood Pressure | Change from Baseline - Day 4 | 5.8 mmHg | Standard Deviation 5.71 |
| Cohort 5: 3000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Diastolic Blood Pressure | Change from Baseline - Day 1/2 Hour | -1.5 mmHg | Standard Deviation 3.94 |
| Cohort 6: 9000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Diastolic Blood Pressure | Change from Baseline - Day 1/0.5 Hour | -0.5 mmHg | Standard Deviation 3.39 |
| Cohort 6: 9000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Diastolic Blood Pressure | Change from Baseline - Day 1/0.75 Hour | -1.2 mmHg | Standard Deviation 3.54 |
| Cohort 6: 9000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Diastolic Blood Pressure | Change from Baseline - Day 7 | 4.2 mmHg | Standard Deviation 3.87 |
| Cohort 6: 9000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Diastolic Blood Pressure | Change from Baseline - Day 4 | 4.7 mmHg | Standard Deviation 4.97 |
| Cohort 6: 9000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Diastolic Blood Pressure | Change from Baseline - Day 2/24 Hour | -0.3 mmHg | Standard Deviation 5.28 |
| Cohort 6: 9000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Diastolic Blood Pressure | Change from Baseline - Day 3/48 Hour | 5.8 mmHg | Standard Deviation 10.01 |
| Cohort 6: 9000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Diastolic Blood Pressure | Change from Baseline - Day 1/2 Hour | 0 mmHg | Standard Deviation 3.58 |
| Cohort 6: 9000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Diastolic Blood Pressure | Change from Baseline - Day 3/42 Hour | -1.2 mmHg | Standard Deviation 5.95 |
| Cohort 6: 9000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Diastolic Blood Pressure | Change from Baseline - Day 2/36 Hour | -3.5 mmHg | Standard Deviation 5.13 |
| Cohort 6: 9000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Diastolic Blood Pressure | Change from Baseline - Day 1/8 Hour | -0.2 mmHg | Standard Deviation 5.67 |
| Cohort 6: 9000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Diastolic Blood Pressure | Change from Baseline - Day 1/4 Hour | -0.5 mmHg | Standard Deviation 5.47 |
| Cohort 6: 9000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Diastolic Blood Pressure | Change from Baseline - Day 2/30 Hour | -2.5 mmHg | Standard Deviation 4.93 |
| Cohort 6: 9000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Diastolic Blood Pressure | Change from Baseline - Day 1/1 Hour | 0.3 mmHg | Standard Deviation 3.98 |
| Cohort 6: 9000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Diastolic Blood Pressure | Change from Baseline - Day 28 | 4.7 mmHg | Standard Deviation 5.43 |
| Cohort 4 to 6: Placebo | Change in Diastolic Blood Pressure | Change from Baseline - Day 3/48 Hour | -0.2 mmHg | Standard Deviation 3.97 |
| Cohort 4 to 6: Placebo | Change in Diastolic Blood Pressure | Change from Baseline - Day 1/0.5 Hour | -1.3 mmHg | Standard Deviation 5.13 |
| Cohort 4 to 6: Placebo | Change in Diastolic Blood Pressure | Change from Baseline - Day 1/0.75 Hour | 1.3 mmHg | Standard Deviation 5.54 |
| Cohort 4 to 6: Placebo | Change in Diastolic Blood Pressure | Change from Baseline - Day 1/1 Hour | 2.8 mmHg | Standard Deviation 6.43 |
| Cohort 4 to 6: Placebo | Change in Diastolic Blood Pressure | Change from Baseline - Day 1/2 Hour | -0.3 mmHg | Standard Deviation 3.33 |
| Cohort 4 to 6: Placebo | Change in Diastolic Blood Pressure | Change from Baseline - Day 1/4 Hour | -1.5 mmHg | Standard Deviation 4.04 |
| Cohort 4 to 6: Placebo | Change in Diastolic Blood Pressure | Change from Baseline - Day 1/8 Hour | -0.7 mmHg | Standard Deviation 6.02 |
| Cohort 4 to 6: Placebo | Change in Diastolic Blood Pressure | Change from Baseline - Day 2/24 Hour | 1.7 mmHg | Standard Deviation 6.12 |
| Cohort 4 to 6: Placebo | Change in Diastolic Blood Pressure | Change from Baseline - Day 2/30 Hour | -5.3 mmHg | Standard Deviation 4.68 |
| Cohort 4 to 6: Placebo | Change in Diastolic Blood Pressure | Change from Baseline - Day 2/36 Hour | -4.3 mmHg | Standard Deviation 7.03 |
| Cohort 4 to 6: Placebo | Change in Diastolic Blood Pressure | Change from Baseline - Day 3/42 Hour | -5.5 mmHg | Standard Deviation 3.45 |
| Cohort 4 to 6: Placebo | Change in Diastolic Blood Pressure | Change from Baseline - Day 4 | 2.0 mmHg | Standard Deviation 6.16 |
| Cohort 4 to 6: Placebo | Change in Diastolic Blood Pressure | Change from Baseline - Day 7 | 0.7 mmHg | Standard Deviation 7.34 |
| Cohort 4 to 6: Placebo | Change in Diastolic Blood Pressure | Change from Baseline - Day 28 | 5.7 mmHg | Standard Deviation 4.89 |
| Cohort 7: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Diastolic Blood Pressure | Change from Baseline - Day 28 | 3.5 mmHg | Standard Deviation 3.83 |
| Cohort 7: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Diastolic Blood Pressure | Change from Baseline - Day 1/8 Hour | -3.7 mmHg | Standard Deviation 6.02 |
| Cohort 7: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Diastolic Blood Pressure | Change from Baseline - Day 2/36 Hour | -4.3 mmHg | Standard Deviation 4.13 |
| Cohort 7: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Diastolic Blood Pressure | Change from Baseline - Day 3/42 Hour | -4.0 mmHg | Standard Deviation 4.43 |
| Cohort 7: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Diastolic Blood Pressure | Change from Baseline - Day 2/30 Hour | -6.2 mmHg | Standard Deviation 2.56 |
| Cohort 7: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Diastolic Blood Pressure | Change from Baseline - Day 3/48 Hour | -1.8 mmHg | Standard Deviation 3.97 |
| Cohort 7: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Diastolic Blood Pressure | Change from Baseline - Day 1/0.75 Hour | 1.5 mmHg | Standard Deviation 9.97 |
| Cohort 7: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Diastolic Blood Pressure | Change from Baseline - Day 7 | 0.2 mmHg | Standard Deviation 7.33 |
| Cohort 7: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Diastolic Blood Pressure | Change from Baseline - Day 1/1 Hour | 3.8 mmHg | Standard Deviation 11.18 |
| Cohort 7: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Diastolic Blood Pressure | Change from Baseline - Day 1/0.5 Hour | -2.5 mmHg | Standard Deviation 3.7 |
| Cohort 7: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Diastolic Blood Pressure | Change from Baseline - Day 2/24 Hour | -2.2 mmHg | Standard Deviation 3.31 |
| Cohort 7: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Diastolic Blood Pressure | Change from Baseline - Day 4 | 3.8 mmHg | Standard Deviation 4.4 |
| Cohort 7: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Diastolic Blood Pressure | Change from Baseline - Day 1/2 Hour | 2.7 mmHg | Standard Deviation 9.58 |
| Cohort 7: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Diastolic Blood Pressure | Change from Baseline - Day 1/4 Hour | -3.8 mmHg | Standard Deviation 7.31 |
| Cohort 8: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Diastolic Blood Pressure | Change from Baseline - Day 1/0.5 Hour | 4.5 mmHg | Standard Deviation 3.51 |
| Cohort 8: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Diastolic Blood Pressure | Change from Baseline - Day 2/36 Hour | -7.0 mmHg | Standard Deviation 7.13 |
| Cohort 8: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Diastolic Blood Pressure | Change from Baseline - Day 2/24 Hour | -2.3 mmHg | Standard Deviation 8.14 |
| Cohort 8: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Diastolic Blood Pressure | Change from Baseline - Day 1/8 Hour | -3.2 mmHg | Standard Deviation 5.72 |
| Cohort 8: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Diastolic Blood Pressure | Change from Baseline - Day 28 | 7.8 mmHg | Standard Deviation 5.98 |
| Cohort 8: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Diastolic Blood Pressure | Change from Baseline - Day 3/42 Hour | -6.2 mmHg | Standard Deviation 10.96 |
| Cohort 8: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Diastolic Blood Pressure | Change from Baseline - Day 3/48 Hour | -0.2 mmHg | Standard Deviation 4.71 |
| Cohort 8: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Diastolic Blood Pressure | Change from Baseline - Day 1/4 Hour | -1.5 mmHg | Standard Deviation 6.16 |
| Cohort 8: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Diastolic Blood Pressure | Change from Baseline - Day 1/2 Hour | -1.0 mmHg | Standard Deviation 6.54 |
| Cohort 8: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Diastolic Blood Pressure | Change from Baseline - Day 4 | -4.2 mmHg | Standard Deviation 7.78 |
| Cohort 8: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Diastolic Blood Pressure | Change from Baseline - Day 1/1 Hour | 0.5 mmHg | Standard Deviation 5.54 |
| Cohort 8: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Diastolic Blood Pressure | Change from Baseline - Day 1/0.75 Hour | -0.3 mmHg | Standard Deviation 7.28 |
| Cohort 8: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Diastolic Blood Pressure | Change from Baseline - Day 7 | 6.5 mmHg | Standard Deviation 8.57 |
| Cohort 8: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Diastolic Blood Pressure | Change from Baseline - Day 2/30 Hour | -5.0 mmHg | Standard Deviation 8.58 |
| Cohort 9: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Diastolic Blood Pressure | Change from Baseline - Day 28 | -5.0 mmHg | Standard Deviation 12 |
| Cohort 9: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Diastolic Blood Pressure | Change from Baseline - Day 1/8 Hour | -10.3 mmHg | Standard Deviation 5.03 |
| Cohort 9: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Diastolic Blood Pressure | Change from Baseline - Day 1/2 Hour | -5.3 mmHg | Standard Deviation 1.53 |
| Cohort 9: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Diastolic Blood Pressure | Change from Baseline - Day 3/48 Hour | -7.0 mmHg | Standard Deviation 3.46 |
| Cohort 9: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Diastolic Blood Pressure | Change from Baseline - Day 4 | -10.3 mmHg | Standard Deviation 4.16 |
| Cohort 9: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Diastolic Blood Pressure | Change from Baseline - Day 1/1 Hour | -6.7 mmHg | Standard Deviation 1.53 |
| Cohort 9: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Diastolic Blood Pressure | Change from Baseline - Day 1/0.75 Hour | -2.3 mmHg | Standard Deviation 1.53 |
| Cohort 9: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Diastolic Blood Pressure | Change from Baseline - Day 2/30 Hour | -7.7 mmHg | Standard Deviation 8.74 |
| Cohort 9: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Diastolic Blood Pressure | Change from Baseline - Day 7 | -5.0 mmHg | Standard Deviation 15.62 |
| Cohort 9: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Diastolic Blood Pressure | Change from Baseline - Day 2/36 Hour | -11.7 mmHg | Standard Deviation 8.08 |
| Cohort 9: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Diastolic Blood Pressure | Change from Baseline - Day 1/0.5 Hour | -4.0 mmHg | Standard Deviation 4.58 |
| Cohort 9: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Diastolic Blood Pressure | Change from Baseline - Day 1/4 Hour | -8.7 mmHg | Standard Deviation 5.51 |
| Cohort 9: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Diastolic Blood Pressure | Change from Baseline - Day 3/42 Hour | -12.7 mmHg | Standard Deviation 3.21 |
| Cohort 9: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Diastolic Blood Pressure | Change from Baseline - Day 2/24 Hour | -3.3 mmHg | Standard Deviation 6.66 |
| Cohort 10: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Diastolic Blood Pressure | Change from Baseline - Day 4 | -0.8 mmHg | Standard Deviation 6.4 |
| Cohort 10: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Diastolic Blood Pressure | Change from Baseline - Day 2/30 Hour | -3.0 mmHg | Standard Deviation 4.98 |
| Cohort 10: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Diastolic Blood Pressure | Change from Baseline - Day 1/0.75 Hour | -2.0 mmHg | Standard Deviation 6.48 |
| Cohort 10: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Diastolic Blood Pressure | Change from Baseline - Day 3/42 Hour | -8.0 mmHg | Standard Deviation 10.2 |
| Cohort 10: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Diastolic Blood Pressure | Change from Baseline - Day 28 | 9.2 mmHg | Standard Deviation 6.85 |
| Cohort 10: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Diastolic Blood Pressure | Change from Baseline - Day 2/36 Hour | -5.8 mmHg | Standard Deviation 3.66 |
| Cohort 10: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Diastolic Blood Pressure | Change from Baseline - Day 2/24 Hour | -3.3 mmHg | Standard Deviation 5.57 |
| Cohort 10: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Diastolic Blood Pressure | Change from Baseline - Day 7 | 5.3 mmHg | Standard Deviation 10.63 |
| Cohort 10: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Diastolic Blood Pressure | Change from Baseline - Day 3/48 Hour | -4.5 mmHg | Standard Deviation 6.41 |
| Cohort 10: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Diastolic Blood Pressure | Change from Baseline - Day 1/4 Hour | 1.3 mmHg | Standard Deviation 9.69 |
| Cohort 10: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Diastolic Blood Pressure | Change from Baseline - Day 1/8 Hour | -3.2 mmHg | Standard Deviation 5.6 |
| Cohort 10: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Diastolic Blood Pressure | Change from Baseline - Day 1/1 Hour | -1.7 mmHg | Standard Deviation 6.83 |
| Cohort 10: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Diastolic Blood Pressure | Change from Baseline - Day 1/0.5 Hour | -2.5 mmHg | Standard Deviation 5.96 |
| Cohort 10: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Diastolic Blood Pressure | Change from Baseline - Day 1/2 Hour | -2.6 mmHg | Standard Deviation 4.67 |
| Cohort 7 to 10: Placebo | Change in Diastolic Blood Pressure | Change from Baseline - Day 7 | 7.4 mmHg | Standard Deviation 14.39 |
| Cohort 7 to 10: Placebo | Change in Diastolic Blood Pressure | Change from Baseline - Day 4 | -1.9 mmHg | Standard Deviation 9.62 |
| Cohort 7 to 10: Placebo | Change in Diastolic Blood Pressure | Change from Baseline - Day 2/24 Hour | -1.7 mmHg | Standard Deviation 8.75 |
| Cohort 7 to 10: Placebo | Change in Diastolic Blood Pressure | Change from Baseline - Day 1/1 Hour | 2.1 mmHg | Standard Deviation 9.69 |
| Cohort 7 to 10: Placebo | Change in Diastolic Blood Pressure | Change from Baseline - Day 2/36 Hour | -4.7 mmHg | Standard Deviation 8.2 |
| Cohort 7 to 10: Placebo | Change in Diastolic Blood Pressure | Change from Baseline - Day 1/0.75 Hour | -0.4 mmHg | Standard Deviation 8.92 |
| Cohort 7 to 10: Placebo | Change in Diastolic Blood Pressure | Change from Baseline - Day 3/48 Hour | -2.3 mmHg | Standard Deviation 9.79 |
| Cohort 7 to 10: Placebo | Change in Diastolic Blood Pressure | Change from Baseline - Day 1/2 Hour | 2.9 mmHg | Standard Deviation 9.39 |
| Cohort 7 to 10: Placebo | Change in Diastolic Blood Pressure | Change from Baseline - Day 3/42 Hour | -9.7 mmHg | Standard Deviation 8.9 |
| Cohort 7 to 10: Placebo | Change in Diastolic Blood Pressure | Change from Baseline - Day 1/8 Hour | -3.1 mmHg | Standard Deviation 12.19 |
| Cohort 7 to 10: Placebo | Change in Diastolic Blood Pressure | Change from Baseline - Day 1/0.5 Hour | -1.4 mmHg | Standard Deviation 8.3 |
| Cohort 7 to 10: Placebo | Change in Diastolic Blood Pressure | Change from Baseline - Day 28 | 4.9 mmHg | Standard Deviation 10.17 |
| Cohort 7 to 10: Placebo | Change in Diastolic Blood Pressure | Change from Baseline - Day 1/4 Hour | 0.7 mmHg | Standard Deviation 9.6 |
| Cohort 7 to 10: Placebo | Change in Diastolic Blood Pressure | Change from Baseline - Day 2/30 Hour | -3.1 mmHg | Standard Deviation 13.04 |
Primary
Change In Heart Rate
Heart rate measurements were measured at specific time points.
Time frame: Days 1, 2, 3, 4, 7 and 28
Population: Safety population: all participants who received any amount of study drug.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: 100 mg PB2452 (no Ticagrelor) | Change In Heart Rate | Change from Baseline - Day 1/2 Hour | -3.7 Beats per minute | Standard Deviation 4.62 |
| Cohort 1: 100 mg PB2452 (no Ticagrelor) | Change In Heart Rate | Change from Baseline - Day 1/8 Hour | 1.7 Beats per minute | Standard Deviation 5.03 |
| Cohort 1: 100 mg PB2452 (no Ticagrelor) | Change In Heart Rate | Change from Baseline - Day 4 | 6.0 Beats per minute | Standard Deviation 8.89 |
| Cohort 1: 100 mg PB2452 (no Ticagrelor) | Change In Heart Rate | Change from Baseline - Day 1/4 Hour | -0.3 Beats per minute | Standard Deviation 2.89 |
| Cohort 1: 100 mg PB2452 (no Ticagrelor) | Change In Heart Rate | Change from Baseline - Day 3/48 Hour | -1.0 Beats per minute | Standard Deviation 7 |
| Cohort 1: 100 mg PB2452 (no Ticagrelor) | Change In Heart Rate | Change from Baseline - Day 28 | -7.7 Beats per minute | Standard Deviation 7.77 |
| Cohort 1: 100 mg PB2452 (no Ticagrelor) | Change In Heart Rate | Change from Baseline - Day 2/36 Hour | 2.3 Beats per minute | Standard Deviation 8.5 |
| Cohort 1: 100 mg PB2452 (no Ticagrelor) | Change In Heart Rate | Change from Baseline - Day 7 | -4.3 Beats per minute | Standard Deviation 3.21 |
| Cohort 1: 100 mg PB2452 (no Ticagrelor) | Change In Heart Rate | Change from Baseline - Day 3/42 Hour | 2.0 Beats per minute | Standard Deviation 3 |
| Cohort 1: 100 mg PB2452 (no Ticagrelor) | Change In Heart Rate | Change from Baseline - Day 1/0.5 Hour | -8.3 Beats per minute | Standard Deviation 3.21 |
| Cohort 1: 100 mg PB2452 (no Ticagrelor) | Change In Heart Rate | Change from Baseline - Day 2/24 Hour | -2.0 Beats per minute | Standard Deviation 3 |
| Cohort 1: 100 mg PB2452 (no Ticagrelor) | Change In Heart Rate | Change from Baseline - Day 1/0.75 Hour | -3.0 Beats per minute | Standard Deviation 1.73 |
| Cohort 1: 100 mg PB2452 (no Ticagrelor) | Change In Heart Rate | Change from Baseline - Day 1/1 Hour | -0.3 Beats per minute | Standard Deviation 1.53 |
| Cohort 1: 100 mg PB2452 (no Ticagrelor) | Change In Heart Rate | Change from Baseline - Day 2/30 Hour | 0 Beats per minute | Standard Deviation 6.08 |
| Cohort 2: 300 mg PB2452 (no Ticagrelor) | Change In Heart Rate | Change from Baseline - Day 1/1 Hour | 4.3 Beats per minute | Standard Deviation 1.53 |
| Cohort 2: 300 mg PB2452 (no Ticagrelor) | Change In Heart Rate | Change from Baseline - Day 1/2 Hour | 6.0 Beats per minute | Standard Deviation 1 |
| Cohort 2: 300 mg PB2452 (no Ticagrelor) | Change In Heart Rate | Change from Baseline - Day 3/48 Hour | 10.3 Beats per minute | Standard Deviation 7.02 |
| Cohort 2: 300 mg PB2452 (no Ticagrelor) | Change In Heart Rate | Change from Baseline - Day 2/30 Hour | 11.7 Beats per minute | Standard Deviation 3.21 |
| Cohort 2: 300 mg PB2452 (no Ticagrelor) | Change In Heart Rate | Change from Baseline - Day 1/0.5 Hour | 4.0 Beats per minute | Standard Deviation 3.46 |
| Cohort 2: 300 mg PB2452 (no Ticagrelor) | Change In Heart Rate | Change from Baseline - Day 28 | 4.0 Beats per minute | Standard Deviation 6.56 |
| Cohort 2: 300 mg PB2452 (no Ticagrelor) | Change In Heart Rate | Change from Baseline - Day 2/36 Hour | 12.0 Beats per minute | Standard Deviation 9.64 |
| Cohort 2: 300 mg PB2452 (no Ticagrelor) | Change In Heart Rate | Change from Baseline - Day 1/0.75 Hour | 5.7 Beats per minute | Standard Deviation 1.53 |
| Cohort 2: 300 mg PB2452 (no Ticagrelor) | Change In Heart Rate | Change from Baseline - Day 1/4 Hour | 13.7 Beats per minute | Standard Deviation 4.04 |
| Cohort 2: 300 mg PB2452 (no Ticagrelor) | Change In Heart Rate | Change from Baseline - Day 1/8 Hour | 14.7 Beats per minute | Standard Deviation 0.58 |
| Cohort 2: 300 mg PB2452 (no Ticagrelor) | Change In Heart Rate | Change from Baseline - Day 2/24 Hour | 9.0 Beats per minute | Standard Deviation 8.19 |
| Cohort 2: 300 mg PB2452 (no Ticagrelor) | Change In Heart Rate | Change from Baseline - Day 7 | 8.0 Beats per minute | Standard Deviation 11.36 |
| Cohort 2: 300 mg PB2452 (no Ticagrelor) | Change In Heart Rate | Change from Baseline - Day 3/42 Hour | 8.3 Beats per minute | Standard Deviation 4.04 |
| Cohort 2: 300 mg PB2452 (no Ticagrelor) | Change In Heart Rate | Change from Baseline - Day 4 | 9.0 Beats per minute | Standard Deviation 7.55 |
| Cohort 3: 1000 mg PB2452 (no Ticagrelor) | Change In Heart Rate | Change from Baseline - Day 28 | -8.3 Beats per minute | Standard Deviation 8.08 |
| Cohort 3: 1000 mg PB2452 (no Ticagrelor) | Change In Heart Rate | Change from Baseline - Day 2/24 Hour | -10.7 Beats per minute | Standard Deviation 4.73 |
| Cohort 3: 1000 mg PB2452 (no Ticagrelor) | Change In Heart Rate | Change from Baseline - Day 1/0.75 Hour | -6.7 Beats per minute | Standard Deviation 4.16 |
| Cohort 3: 1000 mg PB2452 (no Ticagrelor) | Change In Heart Rate | Change from Baseline - Day 1/0.5 Hour | -7.0 Beats per minute | Standard Deviation 6.08 |
| Cohort 3: 1000 mg PB2452 (no Ticagrelor) | Change In Heart Rate | Change from Baseline - Day 7 | -10.7 Beats per minute | Standard Deviation 8.74 |
| Cohort 3: 1000 mg PB2452 (no Ticagrelor) | Change In Heart Rate | Change from Baseline - Day 4 | -8.3 Beats per minute | Standard Deviation 7.37 |
| Cohort 3: 1000 mg PB2452 (no Ticagrelor) | Change In Heart Rate | Change from Baseline - Day 1/1 Hour | -7.0 Beats per minute | Standard Deviation 4.58 |
| Cohort 3: 1000 mg PB2452 (no Ticagrelor) | Change In Heart Rate | Change from Baseline - Day 3/48 Hour | -9.3 Beats per minute | Standard Deviation 5.86 |
| Cohort 3: 1000 mg PB2452 (no Ticagrelor) | Change In Heart Rate | Change from Baseline - Day 1/2 Hour | -7.3 Beats per minute | Standard Deviation 6.43 |
| Cohort 3: 1000 mg PB2452 (no Ticagrelor) | Change In Heart Rate | Change from Baseline - Day 3/42 Hour | -3.0 Beats per minute | Standard Deviation 5.57 |
| Cohort 3: 1000 mg PB2452 (no Ticagrelor) | Change In Heart Rate | Change from Baseline - Day 2/36 Hour | -2.0 Beats per minute | Standard Deviation 4 |
| Cohort 3: 1000 mg PB2452 (no Ticagrelor) | Change In Heart Rate | Change from Baseline - Day 1/4 Hour | -3.7 Beats per minute | Standard Deviation 3.21 |
| Cohort 3: 1000 mg PB2452 (no Ticagrelor) | Change In Heart Rate | Change from Baseline - Day 2/30 Hour | 0 Beats per minute | Standard Deviation 3.61 |
| Cohort 3: 1000 mg PB2452 (no Ticagrelor) | Change In Heart Rate | Change from Baseline - Day 1/8 Hour | -5.7 Beats per minute | Standard Deviation 4.73 |
| Cohort 1 to 3: Placebo | Change In Heart Rate | Change from Baseline - Day 3/42 Hour | 2.0 Beats per minute | Standard Deviation 6.08 |
| Cohort 1 to 3: Placebo | Change In Heart Rate | Change from Baseline - Day 2/36 Hour | 5.0 Beats per minute | Standard Deviation 8.54 |
| Cohort 1 to 3: Placebo | Change In Heart Rate | Change from Baseline - Day 7 | 0.3 Beats per minute | Standard Deviation 11.15 |
| Cohort 1 to 3: Placebo | Change In Heart Rate | Change from Baseline - Day 2/24 Hour | -0.3 Beats per minute | Standard Deviation 4.73 |
| Cohort 1 to 3: Placebo | Change In Heart Rate | Change from Baseline - Day 4 | 1.3 Beats per minute | Standard Deviation 12.5 |
| Cohort 1 to 3: Placebo | Change In Heart Rate | Change from Baseline - Day 2/30 Hour | 4.3 Beats per minute | Standard Deviation 4.73 |
| Cohort 1 to 3: Placebo | Change In Heart Rate | Change from Baseline - Day 1/8 Hour | 7.3 Beats per minute | Standard Deviation 14.47 |
| Cohort 1 to 3: Placebo | Change In Heart Rate | Change from Baseline - Day 28 | -9.3 Beats per minute | Standard Deviation 9.07 |
| Cohort 1 to 3: Placebo | Change In Heart Rate | Change from Baseline - Day 3/48 Hour | -3.3 Beats per minute | Standard Deviation 5.69 |
| Cohort 1 to 3: Placebo | Change In Heart Rate | Change from Baseline - Day 1/0.75 Hour | 5.7 Beats per minute | Standard Deviation 7.51 |
| Cohort 1 to 3: Placebo | Change In Heart Rate | Change from Baseline - Day 1/1 Hour | 5.7 Beats per minute | Standard Deviation 9.29 |
| Cohort 1 to 3: Placebo | Change In Heart Rate | Change from Baseline - Day 1/0.5 Hour | 3.0 Beats per minute | Standard Deviation 8 |
| Cohort 1 to 3: Placebo | Change In Heart Rate | Change from Baseline - Day 1/4 Hour | 5.0 Beats per minute | Standard Deviation 8 |
| Cohort 1 to 3: Placebo | Change In Heart Rate | Change from Baseline - Day 1/2 Hour | 1.3 Beats per minute | Standard Deviation 0.58 |
| Cohort 4: 1000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Heart Rate | Change from Baseline - Day 28 | -1.7 Beats per minute | Standard Deviation 5.54 |
| Cohort 4: 1000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Heart Rate | Change from Baseline - Day 1/2 Hour | 3.0 Beats per minute | Standard Deviation 4.1 |
| Cohort 4: 1000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Heart Rate | Change from Baseline - Day 4 | 6.7 Beats per minute | Standard Deviation 9.03 |
| Cohort 4: 1000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Heart Rate | Change from Baseline - Day 2/36 Hour | 9.0 Beats per minute | Standard Deviation 6 |
| Cohort 4: 1000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Heart Rate | Change from Baseline - Day 2/24 Hour | -3.0 Beats per minute | Standard Deviation 5.4 |
| Cohort 4: 1000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Heart Rate | Change from Baseline - Day 1/0.75 Hour | 2.2 Beats per minute | Standard Deviation 9.06 |
| Cohort 4: 1000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Heart Rate | Change from Baseline - Day 1/8 Hour | 8.0 Beats per minute | Standard Deviation 8.32 |
| Cohort 4: 1000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Heart Rate | Change from Baseline - Day 1/4 Hour | 5.7 Beats per minute | Standard Deviation 4.63 |
| Cohort 4: 1000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Heart Rate | Change from Baseline - Day 1/0.5 Hour | 3.5 Beats per minute | Standard Deviation 8.12 |
| Cohort 4: 1000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Heart Rate | Change from Baseline - Day 7 | 4.2 Beats per minute | Standard Deviation 8.61 |
| Cohort 4: 1000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Heart Rate | Change from Baseline - Day 2/30 Hour | 10.0 Beats per minute | Standard Deviation 5.22 |
| Cohort 4: 1000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Heart Rate | Change from Baseline - Day 3/48 Hour | 2.8 Beats per minute | Standard Deviation 3.19 |
| Cohort 4: 1000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Heart Rate | Change from Baseline - Day 3/42 Hour | 5.2 Beats per minute | Standard Deviation 8.89 |
| Cohort 4: 1000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Heart Rate | Change from Baseline - Day 1/1 Hour | 2.3 Beats per minute | Standard Deviation 5.47 |
| Cohort 5: 3000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Heart Rate | Change from Baseline - Day 1/2 Hour | 1.7 Beats per minute | Standard Deviation 5.09 |
| Cohort 5: 3000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Heart Rate | Change from Baseline - Day 1/0.5 Hour | -5.5 Beats per minute | Standard Deviation 3.39 |
| Cohort 5: 3000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Heart Rate | Change from Baseline - Day 1/0.75 Hour | -0.2 Beats per minute | Standard Deviation 5.95 |
| Cohort 5: 3000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Heart Rate | Change from Baseline - Day 1/1 Hour | 0 Beats per minute | Standard Deviation 3.58 |
| Cohort 5: 3000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Heart Rate | Change from Baseline - Day 1/4 Hour | 1.8 Beats per minute | Standard Deviation 3.82 |
| Cohort 5: 3000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Heart Rate | Change from Baseline - Day 1/8 Hour | 5.8 Beats per minute | Standard Deviation 7.76 |
| Cohort 5: 3000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Heart Rate | Change from Baseline - Day 2/24 Hour | 2.0 Beats per minute | Standard Deviation 3.85 |
| Cohort 5: 3000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Heart Rate | Change from Baseline - Day 2/30 Hour | 6.8 Beats per minute | Standard Deviation 7.28 |
| Cohort 5: 3000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Heart Rate | Change from Baseline - Day 2/36 Hour | 7.4 Beats per minute | Standard Deviation 5.86 |
| Cohort 5: 3000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Heart Rate | Change from Baseline - Day 3/42 Hour | -2.5 Beats per minute | Standard Deviation 2.35 |
| Cohort 5: 3000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Heart Rate | Change from Baseline - Day 3/48 Hour | 1.7 Beats per minute | Standard Deviation 5.82 |
| Cohort 5: 3000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Heart Rate | Change from Baseline - Day 4 | 5.2 Beats per minute | Standard Deviation 9.89 |
| Cohort 5: 3000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Heart Rate | Change from Baseline - Day 7 | 5.8 Beats per minute | Standard Deviation 10.57 |
| Cohort 5: 3000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Heart Rate | Change from Baseline - Day 28 | -4.0 Beats per minute | Standard Deviation 3.63 |
| Cohort 6: 9000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Heart Rate | Change from Baseline - Day 2/24 Hour | 0.8 Beats per minute | Standard Deviation 5.15 |
| Cohort 6: 9000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Heart Rate | Change from Baseline - Day 7 | -5.8 Beats per minute | Standard Deviation 5.85 |
| Cohort 6: 9000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Heart Rate | Change from Baseline - Day 1/0.75 Hour | -5.2 Beats per minute | Standard Deviation 2.14 |
| Cohort 6: 9000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Heart Rate | Change from Baseline - Day 28 | -6.5 Beats per minute | Standard Deviation 8.73 |
| Cohort 6: 9000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Heart Rate | Change from Baseline - Day 3/48 Hour | -0.2 Beats per minute | Standard Deviation 5.42 |
| Cohort 6: 9000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Heart Rate | Change from Baseline - Day 2/30 Hour | 3.2 Beats per minute | Standard Deviation 6.43 |
| Cohort 6: 9000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Heart Rate | Change from Baseline - Day 1/0.5 Hour | -0.2 Beats per minute | Standard Deviation 6.21 |
| Cohort 6: 9000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Heart Rate | Change from Baseline - Day 1/4 Hour | 1.5 Beats per minute | Standard Deviation 7.53 |
| Cohort 6: 9000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Heart Rate | Change from Baseline - Day 2/36 Hour | 8.8 Beats per minute | Standard Deviation 6.85 |
| Cohort 6: 9000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Heart Rate | Change from Baseline - Day 1/8 Hour | 3.2 Beats per minute | Standard Deviation 6.15 |
| Cohort 6: 9000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Heart Rate | Change from Baseline - Day 1/1 Hour | -4.7 Beats per minute | Standard Deviation 3.88 |
| Cohort 6: 9000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Heart Rate | Change from Baseline - Day 4 | -3.5 Beats per minute | Standard Deviation 3.73 |
| Cohort 6: 9000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Heart Rate | Change from Baseline - Day 1/2 Hour | -5.0 Beats per minute | Standard Deviation 3.79 |
| Cohort 6: 9000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Heart Rate | Change from Baseline - Day 3/42 Hour | 4.8 Beats per minute | Standard Deviation 11.07 |
| Cohort 4 to 6: Placebo | Change In Heart Rate | Change from Baseline - Day 1/4 Hour | 3.8 Beats per minute | Standard Deviation 9.79 |
| Cohort 4 to 6: Placebo | Change In Heart Rate | Change from Baseline - Day 1/8 Hour | 4.3 Beats per minute | Standard Deviation 15.42 |
| Cohort 4 to 6: Placebo | Change In Heart Rate | Change from Baseline - Day 7 | -4.8 Beats per minute | Standard Deviation 12.67 |
| Cohort 4 to 6: Placebo | Change In Heart Rate | Change from Baseline - Day 1/2 Hour | -2.5 Beats per minute | Standard Deviation 9.79 |
| Cohort 4 to 6: Placebo | Change In Heart Rate | Change from Baseline - Day 1/0.75 Hour | -1.7 Beats per minute | Standard Deviation 11.64 |
| Cohort 4 to 6: Placebo | Change In Heart Rate | Change from Baseline - Day 1/0.5 Hour | -3.0 Beats per minute | Standard Deviation 9.53 |
| Cohort 4 to 6: Placebo | Change In Heart Rate | Change from Baseline - Day 2/24 Hour | 0.3 Beats per minute | Standard Deviation 10.65 |
| Cohort 4 to 6: Placebo | Change In Heart Rate | Change from Baseline - Day 28 | -4.8 Beats per minute | Standard Deviation 6.85 |
| Cohort 4 to 6: Placebo | Change In Heart Rate | Change from Baseline - Day 1/1 Hour | -2.0 Beats per minute | Standard Deviation 10.71 |
| Cohort 4 to 6: Placebo | Change In Heart Rate | Change from Baseline - Day 4 | 2.5 Beats per minute | Standard Deviation 7.74 |
| Cohort 4 to 6: Placebo | Change In Heart Rate | Change from Baseline - Day 3/42 Hour | -1.8 Beats per minute | Standard Deviation 9.47 |
| Cohort 4 to 6: Placebo | Change In Heart Rate | Change from Baseline - Day 3/48 Hour | 2.0 Beats per minute | Standard Deviation 7.77 |
| Cohort 4 to 6: Placebo | Change In Heart Rate | Change from Baseline - Day 2/36 Hour | 3.2 Beats per minute | Standard Deviation 11.89 |
| Cohort 4 to 6: Placebo | Change In Heart Rate | Change from Baseline - Day 2/30 Hour | 3.5 Beats per minute | Standard Deviation 11.15 |
| Cohort 7: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Heart Rate | Change from Baseline - Day 3/42 Hour | 2.0 Beats per minute | Standard Deviation 6.96 |
| Cohort 7: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Heart Rate | Change from Baseline - Day 2/30 Hour | 6.8 Beats per minute | Standard Deviation 6.55 |
| Cohort 7: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Heart Rate | Change from Baseline - Day 4 | 5.0 Beats per minute | Standard Deviation 5.4 |
| Cohort 7: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Heart Rate | Change from Baseline - Day 1/2 Hour | 2.7 Beats per minute | Standard Deviation 11.96 |
| Cohort 7: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Heart Rate | Change from Baseline - Day 1/0.5 Hour | -2.5 Beats per minute | Standard Deviation 5.07 |
| Cohort 7: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Heart Rate | Change from Baseline - Day 2/24 Hour | 0.8 Beats per minute | Standard Deviation 3.87 |
| Cohort 7: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Heart Rate | Change from Baseline - Day 2/36 Hour | 8.0 Beats per minute | Standard Deviation 5.1 |
| Cohort 7: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Heart Rate | Change from Baseline - Day 1/0.75 Hour | 1.5 Beats per minute | Standard Deviation 3.83 |
| Cohort 7: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Heart Rate | Change from Baseline - Day 7 | 0.8 Beats per minute | Standard Deviation 3.96 |
| Cohort 7: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Heart Rate | Change from Baseline - Day 1/8 Hour | 6.5 Beats per minute | Standard Deviation 2.88 |
| Cohort 7: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Heart Rate | Change from Baseline - Day 1/4 Hour | 4.8 Beats per minute | Standard Deviation 2.56 |
| Cohort 7: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Heart Rate | Change from Baseline - Day 1/1 Hour | 0.2 Beats per minute | Standard Deviation 3.43 |
| Cohort 7: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Heart Rate | Change from Baseline - Day 28 | -1.0 Beats per minute | Standard Deviation 3.58 |
| Cohort 7: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Heart Rate | Change from Baseline - Day 3/48 Hour | 2.0 Beats per minute | Standard Deviation 2 |
| Cohort 8: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Heart Rate | Change from Baseline - Day 3/48 Hour | -2.8 Beats per minute | Standard Deviation 6.34 |
| Cohort 8: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Heart Rate | Change from Baseline - Day 4 | 3.5 Beats per minute | Standard Deviation 13.03 |
| Cohort 8: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Heart Rate | Change from Baseline - Day 1/0.75 Hour | -5.3 Beats per minute | Standard Deviation 3.39 |
| Cohort 8: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Heart Rate | Change from Baseline - Day 1/4 Hour | -0.2 Beats per minute | Standard Deviation 6.11 |
| Cohort 8: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Heart Rate | Change from Baseline - Day 2/30 Hour | 6.3 Beats per minute | Standard Deviation 6.65 |
| Cohort 8: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Heart Rate | Change from Baseline - Day 2/24 Hour | -4.5 Beats per minute | Standard Deviation 4.76 |
| Cohort 8: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Heart Rate | Change from Baseline - Day 1/0.5 Hour | -5.5 Beats per minute | Standard Deviation 5.8 |
| Cohort 8: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Heart Rate | Change from Baseline - Day 2/36 Hour | 10.0 Beats per minute | Standard Deviation 8.88 |
| Cohort 8: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Heart Rate | Change from Baseline - Day 7 | -4.5 Beats per minute | Standard Deviation 8.48 |
| Cohort 8: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Heart Rate | Change from Baseline - Day 1/2 Hour | -5.8 Beats per minute | Standard Deviation 6.62 |
| Cohort 8: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Heart Rate | Change from Baseline - Day 3/42 Hour | -1.5 Beats per minute | Standard Deviation 6.66 |
| Cohort 8: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Heart Rate | Change from Baseline - Day 1/1 Hour | -5.7 Beats per minute | Standard Deviation 5.13 |
| Cohort 8: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Heart Rate | Change from Baseline - Day 28 | 0.2 Beats per minute | Standard Deviation 11.36 |
| Cohort 8: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Heart Rate | Change from Baseline - Day 1/8 Hour | 4.0 Beats per minute | Standard Deviation 10.65 |
| Cohort 9: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Heart Rate | Change from Baseline - Day 1/0.5 Hour | -4.0 Beats per minute | Standard Deviation 9.54 |
| Cohort 9: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Heart Rate | Change from Baseline - Day 2/24 Hour | -2.0 Beats per minute | Standard Deviation 3 |
| Cohort 9: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Heart Rate | Change from Baseline - Day 1/4 Hour | -0.3 Beats per minute | Standard Deviation 3.06 |
| Cohort 9: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Heart Rate | Change from Baseline - Day 2/30 Hour | 0 Beats per minute | Standard Deviation 4.36 |
| Cohort 9: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Heart Rate | Change from Baseline - Day 1/2 Hour | -3.7 Beats per minute | Standard Deviation 9.71 |
| Cohort 9: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Heart Rate | Change from Baseline - Day 2/36 Hour | 3.3 Beats per minute | Standard Deviation 3.21 |
| Cohort 9: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Heart Rate | Change from Baseline - Day 3/42 Hour | 0.7 Beats per minute | Standard Deviation 5.51 |
| Cohort 9: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Heart Rate | Change from Baseline - Day 1/1 Hour | -7.3 Beats per minute | Standard Deviation 7.51 |
| Cohort 9: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Heart Rate | Change from Baseline - Day 3/48 Hour | 1.7 Beats per minute | Standard Deviation 1.15 |
| Cohort 9: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Heart Rate | Change from Baseline - Day 1/0.75 Hour | -5.3 Beats per minute | Standard Deviation 6.66 |
| Cohort 9: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Heart Rate | Change from Baseline - Day 28 | -12.0 Beats per minute | Standard Deviation 16 |
| Cohort 9: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Heart Rate | Change from Baseline - Day 4 | 7.7 Beats per minute | Standard Deviation 7.77 |
| Cohort 9: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Heart Rate | Change from Baseline - Day 7 | -12.0 Beats per minute | Standard Deviation 10.39 |
| Cohort 9: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Heart Rate | Change from Baseline - Day 1/8 Hour | 2.7 Beats per minute | Standard Deviation 1.53 |
| Cohort 10: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Heart Rate | Change from Baseline - Day 28 | -4.7 Beats per minute | Standard Deviation 1.75 |
| Cohort 10: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Heart Rate | Change from Baseline - Day 2/36 Hour | 12.7 Beats per minute | Standard Deviation 8.73 |
| Cohort 10: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Heart Rate | Change from Baseline - Day 1/2 Hour | -3.2 Beats per minute | Standard Deviation 0.84 |
| Cohort 10: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Heart Rate | Change from Baseline - Day 1/1 Hour | 1.0 Beats per minute | Standard Deviation 2.37 |
| Cohort 10: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Heart Rate | Change from Baseline - Day 3/42 Hour | 1.5 Beats per minute | Standard Deviation 5.68 |
| Cohort 10: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Heart Rate | Change from Baseline - Day 2/30 Hour | 8.2 Beats per minute | Standard Deviation 5.88 |
| Cohort 10: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Heart Rate | Change from Baseline - Day 1/8 Hour | 8.5 Beats per minute | Standard Deviation 6.16 |
| Cohort 10: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Heart Rate | Change from Baseline - Day 3/48 Hour | 3.8 Beats per minute | Standard Deviation 4.79 |
| Cohort 10: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Heart Rate | Change from Baseline - Day 1/0.5 Hour | -1.0 Beats per minute | Standard Deviation 3.35 |
| Cohort 10: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Heart Rate | Change from Baseline - Day 1/4 Hour | 6.0 Beats per minute | Standard Deviation 3.58 |
| Cohort 10: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Heart Rate | Change from Baseline - Day 2/24 Hour | 1.3 Beats per minute | Standard Deviation 6.41 |
| Cohort 10: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Heart Rate | Change from Baseline - Day 1/0.75 Hour | 1.3 Beats per minute | Standard Deviation 5.54 |
| Cohort 10: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Heart Rate | Change from Baseline - Day 7 | 2.3 Beats per minute | Standard Deviation 7.31 |
| Cohort 10: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Heart Rate | Change from Baseline - Day 4 | 3.5 Beats per minute | Standard Deviation 8.38 |
| Cohort 7 to 10: Placebo | Change In Heart Rate | Change from Baseline - Day 2/24 Hour | -2.4 Beats per minute | Standard Deviation 5.09 |
| Cohort 7 to 10: Placebo | Change In Heart Rate | Change from Baseline - Day 4 | 1.4 Beats per minute | Standard Deviation 7.96 |
| Cohort 7 to 10: Placebo | Change In Heart Rate | Change from Baseline - Day 3/48 Hour | -1.1 Beats per minute | Standard Deviation 5.21 |
| Cohort 7 to 10: Placebo | Change In Heart Rate | Change from Baseline - Day 1/0.5 Hour | -4.6 Beats per minute | Standard Deviation 7.23 |
| Cohort 7 to 10: Placebo | Change In Heart Rate | Change from Baseline - Day 3/42 Hour | -0.1 Beats per minute | Standard Deviation 9.15 |
| Cohort 7 to 10: Placebo | Change In Heart Rate | Change from Baseline - Day 1/1 Hour | -2.7 Beats per minute | Standard Deviation 3.59 |
| Cohort 7 to 10: Placebo | Change In Heart Rate | Change from Baseline - Day 2/36 Hour | 2.3 Beats per minute | Standard Deviation 7.74 |
| Cohort 7 to 10: Placebo | Change In Heart Rate | Change from Baseline - Day 7 | 1.7 Beats per minute | Standard Deviation 7.34 |
| Cohort 7 to 10: Placebo | Change In Heart Rate | Change from Baseline - Day 1/2 Hour | -2.9 Beats per minute | Standard Deviation 6.36 |
| Cohort 7 to 10: Placebo | Change In Heart Rate | Change from Baseline - Day 2/30 Hour | 3.4 Beats per minute | Standard Deviation 5.5 |
| Cohort 7 to 10: Placebo | Change In Heart Rate | Change from Baseline - Day 1/8 Hour | 5.9 Beats per minute | Standard Deviation 7.47 |
| Cohort 7 to 10: Placebo | Change In Heart Rate | Change from Baseline - Day 28 | -0.1 Beats per minute | Standard Deviation 12.06 |
| Cohort 7 to 10: Placebo | Change In Heart Rate | Change from Baseline - Day 1/4 Hour | 1.6 Beats per minute | Standard Deviation 7.81 |
| Cohort 7 to 10: Placebo | Change In Heart Rate | Change from Baseline - Day 1/0.75 Hour | -2.6 Beats per minute | Standard Deviation 5.38 |
Primary
Change In Oral Body Temperature
Body temperature measurements were measured at specific time points.
Time frame: Days 1, 2, 3, 4, 7 and 28
Population: Safety population: all participants who received any amount of study drug.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: 100 mg PB2452 (no Ticagrelor) | Change In Oral Body Temperature | Change from Baseline - Day 4 | 0 Degrees Celsius | Standard Deviation 0.3 |
| Cohort 1: 100 mg PB2452 (no Ticagrelor) | Change In Oral Body Temperature | Change from Baseline - Day 1/4 Hour | 0.17 Degrees Celsius | Standard Deviation 0.289 |
| Cohort 1: 100 mg PB2452 (no Ticagrelor) | Change In Oral Body Temperature | Change from Baseline - Day 3/48 Hour | -0.20 Degrees Celsius | Standard Deviation 0.529 |
| Cohort 1: 100 mg PB2452 (no Ticagrelor) | Change In Oral Body Temperature | Change from Baseline - Day 7 | -0.03 Degrees Celsius | Standard Deviation 0.551 |
| Cohort 1: 100 mg PB2452 (no Ticagrelor) | Change In Oral Body Temperature | Change from Baseline - Day 2/24 Hour | -0.13 Degrees Celsius | Standard Deviation 0.306 |
| Cohort 1: 100 mg PB2452 (no Ticagrelor) | Change In Oral Body Temperature | Change from Baseline - Day 2/36 Hour | 0.17 Degrees Celsius | Standard Deviation 0.666 |
| Cohort 1: 100 mg PB2452 (no Ticagrelor) | Change In Oral Body Temperature | Change from Baseline - Day 1/2 Hour | -0.03 Degrees Celsius | Standard Deviation 0.379 |
| Cohort 1: 100 mg PB2452 (no Ticagrelor) | Change In Oral Body Temperature | Change from Baseline - Day 28 | -0.20 Degrees Celsius | Standard Deviation 0.624 |
| Cohort 1: 100 mg PB2452 (no Ticagrelor) | Change In Oral Body Temperature | Change from Baseline - Day 1/8 Hour | 0.30 Degrees Celsius | Standard Deviation 0.436 |
| Cohort 1: 100 mg PB2452 (no Ticagrelor) | Change In Oral Body Temperature | Change from Baseline - Day 3/42 Hour | -0.10 Degrees Celsius | Standard Deviation 0.4 |
| Cohort 1: 100 mg PB2452 (no Ticagrelor) | Change In Oral Body Temperature | Change from Baseline - Day 1/0.75 Hour | 0.03 Degrees Celsius | Standard Deviation 0.231 |
| Cohort 1: 100 mg PB2452 (no Ticagrelor) | Change In Oral Body Temperature | Change from Baseline - Day 1/1 Hour | -0.13 Degrees Celsius | Standard Deviation 0.306 |
| Cohort 1: 100 mg PB2452 (no Ticagrelor) | Change In Oral Body Temperature | Change from Baseline - Day 2/30 Hour | 0.30 Degrees Celsius | Standard Deviation 0.608 |
| Cohort 2: 300 mg PB2452 (no Ticagrelor) | Change In Oral Body Temperature | Change from Baseline - Day 1/1 Hour | -0.17 Degrees Celsius | Standard Deviation 0.208 |
| Cohort 2: 300 mg PB2452 (no Ticagrelor) | Change In Oral Body Temperature | Change from Baseline - Day 2/30 Hour | -0.30 Degrees Celsius | Standard Deviation 0.1 |
| Cohort 2: 300 mg PB2452 (no Ticagrelor) | Change In Oral Body Temperature | Change from Baseline - Day 7 | -0.53 Degrees Celsius | Standard Deviation 0.404 |
| Cohort 2: 300 mg PB2452 (no Ticagrelor) | Change In Oral Body Temperature | Change from Baseline - Day 1/4 Hour | -0.20 Degrees Celsius | Standard Deviation 0.2 |
| Cohort 2: 300 mg PB2452 (no Ticagrelor) | Change In Oral Body Temperature | Change from Baseline - Day 2/24 Hour | -0.43 Degrees Celsius | Standard Deviation 0.058 |
| Cohort 2: 300 mg PB2452 (no Ticagrelor) | Change In Oral Body Temperature | Change from Baseline - Day 1/0.75 Hour | -0.20 Degrees Celsius | Standard Deviation 0.361 |
| Cohort 2: 300 mg PB2452 (no Ticagrelor) | Change In Oral Body Temperature | Change from Baseline - Day 4 | -0.27 Degrees Celsius | Standard Deviation 0.153 |
| Cohort 2: 300 mg PB2452 (no Ticagrelor) | Change In Oral Body Temperature | Change from Baseline - Day 2/36 Hour | -0.47 Degrees Celsius | Standard Deviation 0.351 |
| Cohort 2: 300 mg PB2452 (no Ticagrelor) | Change In Oral Body Temperature | Change from Baseline - Day 3/42 Hour | -0.83 Degrees Celsius | Standard Deviation 0.231 |
| Cohort 2: 300 mg PB2452 (no Ticagrelor) | Change In Oral Body Temperature | Change from Baseline - Day 28 | -0.43 Degrees Celsius | Standard Deviation 0.058 |
| Cohort 2: 300 mg PB2452 (no Ticagrelor) | Change In Oral Body Temperature | Change from Baseline - Day 1/8 Hour | 0.07 Degrees Celsius | Standard Deviation 0.153 |
| Cohort 2: 300 mg PB2452 (no Ticagrelor) | Change In Oral Body Temperature | Change from Baseline - Day 1/2 Hour | -0.03 Degrees Celsius | Standard Deviation 0.115 |
| Cohort 2: 300 mg PB2452 (no Ticagrelor) | Change In Oral Body Temperature | Change from Baseline - Day 3/48 Hour | -0.27 Degrees Celsius | Standard Deviation 0.058 |
| Cohort 3: 1000 mg PB2452 (no Ticagrelor) | Change In Oral Body Temperature | Change from Baseline - Day 1/0.5 Hour | -0.23 Degrees Celsius | Standard Deviation 0.321 |
| Cohort 3: 1000 mg PB2452 (no Ticagrelor) | Change In Oral Body Temperature | Change from Baseline - Day 3/48 Hour | -0.13 Degrees Celsius | Standard Deviation 0.208 |
| Cohort 3: 1000 mg PB2452 (no Ticagrelor) | Change In Oral Body Temperature | Change from Baseline - Day 2/24 Hour | -0.13 Degrees Celsius | Standard Deviation 0.306 |
| Cohort 3: 1000 mg PB2452 (no Ticagrelor) | Change In Oral Body Temperature | Change from Baseline - Day 1/0.75 Hour | 0.13 Degrees Celsius | Standard Deviation 0.115 |
| Cohort 3: 1000 mg PB2452 (no Ticagrelor) | Change In Oral Body Temperature | Change from Baseline - Day 2/30 Hour | -0.17 Degrees Celsius | Standard Deviation 0.058 |
| Cohort 3: 1000 mg PB2452 (no Ticagrelor) | Change In Oral Body Temperature | Change from Baseline - Day 1/1 Hour | 0.07 Degrees Celsius | Standard Deviation 0.231 |
| Cohort 3: 1000 mg PB2452 (no Ticagrelor) | Change In Oral Body Temperature | Change from Baseline - Day 7 | 0 Degrees Celsius | Standard Deviation 0.265 |
| Cohort 3: 1000 mg PB2452 (no Ticagrelor) | Change In Oral Body Temperature | Change from Baseline - Day 1/2 Hour | 0.17 Degrees Celsius | Standard Deviation 0.351 |
| Cohort 3: 1000 mg PB2452 (no Ticagrelor) | Change In Oral Body Temperature | Change from Baseline - Day 3/42 Hour | -0.30 Degrees Celsius | Standard Deviation 0.2 |
| Cohort 3: 1000 mg PB2452 (no Ticagrelor) | Change In Oral Body Temperature | Change from Baseline - Day 4 | 0.07 Degrees Celsius | Standard Deviation 0.404 |
| Cohort 3: 1000 mg PB2452 (no Ticagrelor) | Change In Oral Body Temperature | Change from Baseline - Day 1/4 Hour | 0.07 Degrees Celsius | Standard Deviation 0.058 |
| Cohort 3: 1000 mg PB2452 (no Ticagrelor) | Change In Oral Body Temperature | Change from Baseline - Day 2/36 Hour | 0.30 Degrees Celsius | Standard Deviation 0.361 |
| Cohort 3: 1000 mg PB2452 (no Ticagrelor) | Change In Oral Body Temperature | Change from Baseline - Day 28 | -0.10 Degrees Celsius | Standard Deviation 0.2 |
| Cohort 3: 1000 mg PB2452 (no Ticagrelor) | Change In Oral Body Temperature | Change from Baseline - Day 1/8 Hour | 0.03 Degrees Celsius | Standard Deviation 0.153 |
| Cohort 1 to 3: Placebo | Change In Oral Body Temperature | Change from Baseline - Day 1/2 Hour | 0.10 Degrees Celsius | Standard Deviation 0 |
| Cohort 1 to 3: Placebo | Change In Oral Body Temperature | Change from Baseline - Day 2/30 Hour | 0.27 Degrees Celsius | Standard Deviation 0.153 |
| Cohort 1 to 3: Placebo | Change In Oral Body Temperature | Change from Baseline - Day 4 | -0.27 Degrees Celsius | Standard Deviation 0.651 |
| Cohort 1 to 3: Placebo | Change In Oral Body Temperature | Change from Baseline - Day 1/0.75 Hour | 0 Degrees Celsius | Standard Deviation 0.265 |
| Cohort 1 to 3: Placebo | Change In Oral Body Temperature | Change from Baseline - Day 2/24 Hour | -0.17 Degrees Celsius | Standard Deviation 0.404 |
| Cohort 1 to 3: Placebo | Change In Oral Body Temperature | Change from Baseline - Day 1/4 Hour | 0.17 Degrees Celsius | Standard Deviation 0.153 |
| Cohort 1 to 3: Placebo | Change In Oral Body Temperature | Change from Baseline - Day 3/42 Hour | -0.33 Degrees Celsius | Standard Deviation 0.603 |
| Cohort 1 to 3: Placebo | Change In Oral Body Temperature | Change from Baseline - Day 1/0.5 Hour | 0.30 Degrees Celsius | — |
| Cohort 1 to 3: Placebo | Change In Oral Body Temperature | Change from Baseline - Day 3/48 Hour | -0.20 Degrees Celsius | Standard Deviation 0.2 |
| Cohort 1 to 3: Placebo | Change In Oral Body Temperature | Change from Baseline - Day 1/8 Hour | 0.60 Degrees Celsius | Standard Deviation 0.624 |
| Cohort 1 to 3: Placebo | Change In Oral Body Temperature | Change from Baseline - Day 7 | -0.50 Degrees Celsius | Standard Deviation 0.7 |
| Cohort 1 to 3: Placebo | Change In Oral Body Temperature | Change from Baseline - Day 2/36 Hour | 0.23 Degrees Celsius | Standard Deviation 0.306 |
| Cohort 1 to 3: Placebo | Change In Oral Body Temperature | Change from Baseline - Day 1/1 Hour | -0.57 Degrees Celsius | Standard Deviation 1.002 |
| Cohort 1 to 3: Placebo | Change In Oral Body Temperature | Change from Baseline - Day 28 | -0.37 Degrees Celsius | Standard Deviation 0.569 |
| Cohort 4: 1000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Oral Body Temperature | Change from Baseline - Day 1/4 Hour | 0.10 Degrees Celsius | Standard Deviation 0.155 |
| Cohort 4: 1000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Oral Body Temperature | Change from Baseline - Day 1/2 Hour | 0.05 Degrees Celsius | Standard Deviation 0.187 |
| Cohort 4: 1000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Oral Body Temperature | Change from Baseline - Day 1/0.5 Hour | 0.12 Degrees Celsius | Standard Deviation 0.183 |
| Cohort 4: 1000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Oral Body Temperature | Change from Baseline - Day 1/8 Hour | 0.18 Degrees Celsius | Standard Deviation 0.248 |
| Cohort 4: 1000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Oral Body Temperature | Change from Baseline - Day 3/48 Hour | 0.18 Degrees Celsius | Standard Deviation 0.172 |
| Cohort 4: 1000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Oral Body Temperature | Change from Baseline - Day 2/30 Hour | 0.30 Degrees Celsius | Standard Deviation 0.303 |
| Cohort 4: 1000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Oral Body Temperature | Change from Baseline - Day 4 | 0.10 Degrees Celsius | Standard Deviation 0.438 |
| Cohort 4: 1000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Oral Body Temperature | Change from Baseline - Day 1/1 Hour | 0.07 Degrees Celsius | Standard Deviation 0.186 |
| Cohort 4: 1000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Oral Body Temperature | Change from Baseline - Day 2/24 Hour | 0.20 Degrees Celsius | Standard Deviation 0.297 |
| Cohort 4: 1000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Oral Body Temperature | Change from Baseline - Day 1/0.75 Hour | 0.12 Degrees Celsius | Standard Deviation 0.248 |
| Cohort 4: 1000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Oral Body Temperature | Change from Baseline - Day 3/42 Hour | -0.37 Degrees Celsius | Standard Deviation 0.314 |
| Cohort 4: 1000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Oral Body Temperature | Change from Baseline - Day 7 | -0.13 Degrees Celsius | Standard Deviation 0.333 |
| Cohort 4: 1000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Oral Body Temperature | Change from Baseline - Day 28 | -0.20 Degrees Celsius | Standard Deviation 0.303 |
| Cohort 4: 1000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Oral Body Temperature | Change from Baseline - Day 2/36 Hour | 0.18 Degrees Celsius | Standard Deviation 0.232 |
| Cohort 5: 3000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Oral Body Temperature | Change from Baseline - Day 28 | 0.03 Degrees Celsius | Standard Deviation 0.408 |
| Cohort 5: 3000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Oral Body Temperature | Change from Baseline - Day 2/36 Hour | 0.03 Degrees Celsius | Standard Deviation 0.28 |
| Cohort 5: 3000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Oral Body Temperature | Change from Baseline - Day 1/0.75 Hour | 0.07 Degrees Celsius | Standard Deviation 0.234 |
| Cohort 5: 3000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Oral Body Temperature | Change from Baseline - Day 7 | 0.50 Degrees Celsius | Standard Deviation 0.363 |
| Cohort 5: 3000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Oral Body Temperature | Change from Baseline - Day 1/1 Hour | -0.05 Degrees Celsius | Standard Deviation 0.308 |
| Cohort 5: 3000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Oral Body Temperature | Change from Baseline - Day 1/0.5 Hour | -0.05 Degrees Celsius | Standard Deviation 0.217 |
| Cohort 5: 3000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Oral Body Temperature | Change from Baseline - Day 1/2 Hour | -0.02 Degrees Celsius | Standard Deviation 0.248 |
| Cohort 5: 3000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Oral Body Temperature | Change from Baseline - Day 4 | 0.08 Degrees Celsius | Standard Deviation 0.417 |
| Cohort 5: 3000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Oral Body Temperature | Change from Baseline - Day 1/4 Hour | 0.18 Degrees Celsius | Standard Deviation 0.271 |
| Cohort 5: 3000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Oral Body Temperature | Change from Baseline - Day 3/48 Hour | -0.20 Degrees Celsius | Standard Deviation 0.261 |
| Cohort 5: 3000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Oral Body Temperature | Change from Baseline - Day 1/8 Hour | 0.33 Degrees Celsius | Standard Deviation 0.585 |
| Cohort 5: 3000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Oral Body Temperature | Change from Baseline - Day 2/24 Hour | -0.08 Degrees Celsius | Standard Deviation 0.264 |
| Cohort 5: 3000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Oral Body Temperature | Change from Baseline - Day 3/42 Hour | -0.23 Degrees Celsius | Standard Deviation 0.333 |
| Cohort 5: 3000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Oral Body Temperature | Change from Baseline - Day 2/30 Hour | 0.20 Degrees Celsius | Standard Deviation 0.316 |
| Cohort 6: 9000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Oral Body Temperature | Change from Baseline - Day 2/24 Hour | -0.18 Degrees Celsius | Standard Deviation 0.325 |
| Cohort 6: 9000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Oral Body Temperature | Change from Baseline - Day 1/8 Hour | -0.07 Degrees Celsius | Standard Deviation 0.383 |
| Cohort 6: 9000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Oral Body Temperature | Change from Baseline - Day 2/30 Hour | -0.17 Degrees Celsius | Standard Deviation 0.592 |
| Cohort 6: 9000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Oral Body Temperature | Change from Baseline - Day 3/48 Hour | -0.37 Degrees Celsius | Standard Deviation 0.497 |
| Cohort 6: 9000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Oral Body Temperature | Change from Baseline - Day 1/4 Hour | 0.07 Degrees Celsius | Standard Deviation 0.294 |
| Cohort 6: 9000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Oral Body Temperature | Change from Baseline - Day 1/0.5 Hour | -0.15 Degrees Celsius | Standard Deviation 0.207 |
| Cohort 6: 9000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Oral Body Temperature | Change from Baseline - Day 1/2 Hour | -0.03 Degrees Celsius | Standard Deviation 0.207 |
| Cohort 6: 9000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Oral Body Temperature | Change from Baseline - Day 4 | -0.15 Degrees Celsius | Standard Deviation 0.327 |
| Cohort 6: 9000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Oral Body Temperature | Change from Baseline - Day 1/1 Hour | -0.13 Degrees Celsius | Standard Deviation 0.121 |
| Cohort 6: 9000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Oral Body Temperature | Change from Baseline - Day 7 | -0.32 Degrees Celsius | Standard Deviation 0.293 |
| Cohort 6: 9000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Oral Body Temperature | Change from Baseline - Day 1/0.75 Hour | -0.03 Degrees Celsius | Standard Deviation 0.301 |
| Cohort 6: 9000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Oral Body Temperature | Change from Baseline - Day 3/42 Hour | -0.43 Degrees Celsius | Standard Deviation 0.403 |
| Cohort 6: 9000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Oral Body Temperature | Change from Baseline - Day 28 | -0.03 Degrees Celsius | Standard Deviation 0.383 |
| Cohort 6: 9000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Oral Body Temperature | Change from Baseline - Day 2/36 Hour | -0.10 Degrees Celsius | Standard Deviation 0.253 |
| Cohort 4 to 6: Placebo | Change In Oral Body Temperature | Change from Baseline - Day 3/48 Hour | -0.10 Degrees Celsius | Standard Deviation 0.374 |
| Cohort 4 to 6: Placebo | Change In Oral Body Temperature | Change from Baseline - Day 1/0.5 Hour | -0.02 Degrees Celsius | Standard Deviation 0.313 |
| Cohort 4 to 6: Placebo | Change In Oral Body Temperature | Change from Baseline - Day 1/0.75 Hour | 0.03 Degrees Celsius | Standard Deviation 0.273 |
| Cohort 4 to 6: Placebo | Change In Oral Body Temperature | Change from Baseline - Day 1/1 Hour | 0 Degrees Celsius | Standard Deviation 0.434 |
| Cohort 4 to 6: Placebo | Change In Oral Body Temperature | Change from Baseline - Day 1/2 Hour | 0.10 Degrees Celsius | Standard Deviation 0.341 |
| Cohort 4 to 6: Placebo | Change In Oral Body Temperature | Change from Baseline - Day 1/4 Hour | 0.20 Degrees Celsius | Standard Deviation 0.253 |
| Cohort 4 to 6: Placebo | Change In Oral Body Temperature | Change from Baseline - Day 1/8 Hour | -0.07 Degrees Celsius | Standard Deviation 0.225 |
| Cohort 4 to 6: Placebo | Change In Oral Body Temperature | Change from Baseline - Day 2/24 Hour | -0.15 Degrees Celsius | Standard Deviation 0.226 |
| Cohort 4 to 6: Placebo | Change In Oral Body Temperature | Change from Baseline - Day 2/30 Hour | -0.03 Degrees Celsius | Standard Deviation 0.361 |
| Cohort 4 to 6: Placebo | Change In Oral Body Temperature | Change from Baseline - Day 2/36 Hour | 0.07 Degrees Celsius | Standard Deviation 0.273 |
| Cohort 4 to 6: Placebo | Change In Oral Body Temperature | Change from Baseline - Day 3/42 Hour | -0.38 Degrees Celsius | Standard Deviation 0.343 |
| Cohort 4 to 6: Placebo | Change In Oral Body Temperature | Change from Baseline - Day 4 | -0.12 Degrees Celsius | Standard Deviation 0.488 |
| Cohort 4 to 6: Placebo | Change In Oral Body Temperature | Change from Baseline - Day 7 | -0.08 Degrees Celsius | Standard Deviation 0.147 |
| Cohort 4 to 6: Placebo | Change In Oral Body Temperature | Change from Baseline - Day 28 | -0.18 Degrees Celsius | Standard Deviation 0.293 |
| Cohort 7: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Oral Body Temperature | Change from Baseline - Day 1/0.75 Hour | 0.07 Degrees Celsius | Standard Deviation 0.186 |
| Cohort 7: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Oral Body Temperature | Change from Baseline - Day 1/2 Hour | 0.07 Degrees Celsius | Standard Deviation 0.339 |
| Cohort 7: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Oral Body Temperature | Change from Baseline - Day 1/4 Hour | 0.07 Degrees Celsius | Standard Deviation 0.403 |
| Cohort 7: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Oral Body Temperature | Change from Baseline - Day 3/48 Hour | 0.03 Degrees Celsius | Standard Deviation 0.333 |
| Cohort 7: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Oral Body Temperature | Change from Baseline - Day 1/8 Hour | 0.17 Degrees Celsius | Standard Deviation 0.273 |
| Cohort 7: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Oral Body Temperature | Change from Baseline - Day 2/30 Hour | 0.02 Degrees Celsius | Standard Deviation 0.343 |
| Cohort 7: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Oral Body Temperature | Change from Baseline - Day 2/36 Hour | -0.10 Degrees Celsius | Standard Deviation 0.283 |
| Cohort 7: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Oral Body Temperature | Change from Baseline - Day 7 | -0.04 Degrees Celsius | Standard Deviation 0.241 |
| Cohort 7: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Oral Body Temperature | Change from Baseline - Day 1/1 Hour | 0 Degrees Celsius | Standard Deviation 0.228 |
| Cohort 7: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Oral Body Temperature | Change from Baseline - Day 28 | -0.08 Degrees Celsius | Standard Deviation 0.458 |
| Cohort 7: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Oral Body Temperature | Change from Baseline - Day 2/24 Hour | -0.32 Degrees Celsius | Standard Deviation 0.397 |
| Cohort 7: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Oral Body Temperature | Change from Baseline - Day 4 | -0.33 Degrees Celsius | Standard Deviation 0.294 |
| Cohort 7: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Oral Body Temperature | Change from Baseline - Day 1/0.5 Hour | 0.05 Degrees Celsius | Standard Deviation 0.265 |
| Cohort 7: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Oral Body Temperature | Change from Baseline - Day 3/42 Hour | -0.57 Degrees Celsius | Standard Deviation 0.163 |
| Cohort 8: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Oral Body Temperature | Change from Baseline - Day 7 | -0.33 Degrees Celsius | Standard Deviation 0.367 |
| Cohort 8: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Oral Body Temperature | Change from Baseline - Day 2/36 Hour | -0.27 Degrees Celsius | Standard Deviation 0.25 |
| Cohort 8: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Oral Body Temperature | Change from Baseline - Day 2/24 Hour | -0.15 Degrees Celsius | Standard Deviation 0.356 |
| Cohort 8: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Oral Body Temperature | Change from Baseline - Day 28 | -0.45 Degrees Celsius | Standard Deviation 0.302 |
| Cohort 8: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Oral Body Temperature | Change from Baseline - Day 3/42 Hour | -0.28 Degrees Celsius | Standard Deviation 0.454 |
| Cohort 8: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Oral Body Temperature | Change from Baseline - Day 1/8 Hour | 0.04 Degrees Celsius | Standard Deviation 0.288 |
| Cohort 8: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Oral Body Temperature | Change from Baseline - Day 1/4 Hour | 0.22 Degrees Celsius | Standard Deviation 0.479 |
| Cohort 8: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Oral Body Temperature | Change from Baseline - Day 3/48 Hour | -0.20 Degrees Celsius | Standard Deviation 0.276 |
| Cohort 8: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Oral Body Temperature | Change from Baseline - Day 1/2 Hour | -0.08 Degrees Celsius | Standard Deviation 0.194 |
| Cohort 8: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Oral Body Temperature | Change from Baseline - Day 4 | -0.08 Degrees Celsius | Standard Deviation 0.293 |
| Cohort 8: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Oral Body Temperature | Change from Baseline - Day 1/1 Hour | -0.07 Degrees Celsius | Standard Deviation 0.197 |
| Cohort 8: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Oral Body Temperature | Change from Baseline - Day 1/0.75 Hour | 0.03 Degrees Celsius | Standard Deviation 0.242 |
| Cohort 8: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Oral Body Temperature | Change from Baseline - Day 1/0.5 Hour | -0.03 Degrees Celsius | Standard Deviation 0.465 |
| Cohort 8: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Oral Body Temperature | Change from Baseline - Day 2/30 Hour | 0 Degrees Celsius | Standard Deviation 0.59 |
| Cohort 9: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Oral Body Temperature | Change from Baseline - Day 1/4 Hour | 0.20 Degrees Celsius | Standard Deviation 0.361 |
| Cohort 9: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Oral Body Temperature | Change from Baseline - Day 1/0.75 Hour | 0.10 Degrees Celsius | Standard Deviation 0.173 |
| Cohort 9: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Oral Body Temperature | Change from Baseline - Day 2/36 Hour | 0.13 Degrees Celsius | Standard Deviation 0.416 |
| Cohort 9: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Oral Body Temperature | Change from Baseline - Day 1/1 Hour | 0.10 Degrees Celsius | Standard Deviation 0.265 |
| Cohort 9: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Oral Body Temperature | Change from Baseline - Day 1/2 Hour | 0.10 Degrees Celsius | Standard Deviation 0.2 |
| Cohort 9: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Oral Body Temperature | Change from Baseline - Day 2/24 Hour | -0.10 Degrees Celsius | Standard Deviation 0.1 |
| Cohort 9: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Oral Body Temperature | Change from Baseline - Day 3/48 Hour | 0.10 Degrees Celsius | Standard Deviation 0.1 |
| Cohort 9: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Oral Body Temperature | Change from Baseline - Day 1/0.5 Hour | -0.17 Degrees Celsius | Standard Deviation 0.473 |
| Cohort 9: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Oral Body Temperature | Change from Baseline - Day 3/42 Hour | -0.37 Degrees Celsius | Standard Deviation 0.208 |
| Cohort 9: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Oral Body Temperature | Change from Baseline - Day 1/8 Hour | 0.27 Degrees Celsius | Standard Deviation 0.058 |
| Cohort 9: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Oral Body Temperature | Change from Baseline - Day 28 | -0.07 Degrees Celsius | Standard Deviation 0.651 |
| Cohort 9: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Oral Body Temperature | Change from Baseline - Day 2/30 Hour | -0.17 Degrees Celsius | Standard Deviation 0.404 |
| Cohort 9: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Oral Body Temperature | Change from Baseline - Day 7 | 0.37 Degrees Celsius | Standard Deviation 0.231 |
| Cohort 9: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Oral Body Temperature | Change from Baseline - Day 4 | 0.33 Degrees Celsius | Standard Deviation 0.306 |
| Cohort 10: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Oral Body Temperature | Change from Baseline - Day 1/0.75 Hour | 0.03 Degrees Celsius | Standard Deviation 0.186 |
| Cohort 10: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Oral Body Temperature | Change from Baseline - Day 3/48 Hour | -0.23 Degrees Celsius | Standard Deviation 0.372 |
| Cohort 10: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Oral Body Temperature | Change from Baseline - Day 3/42 Hour | -0.52 Degrees Celsius | Standard Deviation 0.232 |
| Cohort 10: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Oral Body Temperature | Change from Baseline - Day 1/2 Hour | -0.20 Degrees Celsius | Standard Deviation 0.274 |
| Cohort 10: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Oral Body Temperature | Change from Baseline - Day 4 | -0.20 Degrees Celsius | Standard Deviation 0.283 |
| Cohort 10: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Oral Body Temperature | Change from Baseline - Day 1/1 Hour | -0.05 Degrees Celsius | Standard Deviation 0.207 |
| Cohort 10: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Oral Body Temperature | Change from Baseline - Day 2/30 Hour | -0.15 Degrees Celsius | Standard Deviation 0.251 |
| Cohort 10: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Oral Body Temperature | Change from Baseline - Day 28 | -0.35 Degrees Celsius | Standard Deviation 0.509 |
| Cohort 10: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Oral Body Temperature | Change from Baseline - Day 2/24 Hour | -0.18 Degrees Celsius | Standard Deviation 0.454 |
| Cohort 10: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Oral Body Temperature | Change from Baseline - Day 7 | -0.43 Degrees Celsius | Standard Deviation 0.468 |
| Cohort 10: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Oral Body Temperature | Change from Baseline - Day 1/0.5 Hour | -0.10 Degrees Celsius | Standard Deviation 0.141 |
| Cohort 10: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Oral Body Temperature | Change from Baseline - Day 1/8 Hour | 0.03 Degrees Celsius | Standard Deviation 0.288 |
| Cohort 10: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Oral Body Temperature | Change from Baseline - Day 1/4 Hour | 0.13 Degrees Celsius | Standard Deviation 0.361 |
| Cohort 10: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Oral Body Temperature | Change from Baseline - Day 2/36 Hour | -0.03 Degrees Celsius | Standard Deviation 0.423 |
| Cohort 7 to 10: Placebo | Change In Oral Body Temperature | Change from Baseline - Day 7 | -0.14 Degrees Celsius | Standard Deviation 0.294 |
| Cohort 7 to 10: Placebo | Change In Oral Body Temperature | Change from Baseline - Day 1/8 Hour | 0.10 Degrees Celsius | Standard Deviation 0.346 |
| Cohort 7 to 10: Placebo | Change In Oral Body Temperature | Change from Baseline - Day 2/36 Hour | -0.11 Degrees Celsius | Standard Deviation 0.463 |
| Cohort 7 to 10: Placebo | Change In Oral Body Temperature | Change from Baseline - Day 1/0.5 Hour | -0.41 Degrees Celsius | Standard Deviation 1.512 |
| Cohort 7 to 10: Placebo | Change In Oral Body Temperature | Change from Baseline - Day 1/2 Hour | 0 Degrees Celsius | Standard Deviation 0.277 |
| Cohort 7 to 10: Placebo | Change In Oral Body Temperature | Change from Baseline - Day 1/1 Hour | 0.01 Degrees Celsius | Standard Deviation 0.402 |
| Cohort 7 to 10: Placebo | Change In Oral Body Temperature | Change from Baseline - Day 28 | -0.13 Degrees Celsius | Standard Deviation 0.39 |
| Cohort 7 to 10: Placebo | Change In Oral Body Temperature | Change from Baseline - Day 1/0.75 Hour | 0.03 Degrees Celsius | Standard Deviation 0.304 |
| Cohort 7 to 10: Placebo | Change In Oral Body Temperature | Change from Baseline - Day 4 | 0.03 Degrees Celsius | Standard Deviation 0.293 |
| Cohort 7 to 10: Placebo | Change In Oral Body Temperature | Change from Baseline - Day 3/48 Hour | -0.01 Degrees Celsius | Standard Deviation 0.344 |
| Cohort 7 to 10: Placebo | Change In Oral Body Temperature | Change from Baseline - Day 1/4 Hour | 0.13 Degrees Celsius | Standard Deviation 0.35 |
| Cohort 7 to 10: Placebo | Change In Oral Body Temperature | Change from Baseline - Day 2/24 Hour | -0.30 Degrees Celsius | Standard Deviation 0.416 |
| Cohort 7 to 10: Placebo | Change In Oral Body Temperature | Change from Baseline - Day 2/30 Hour | -0.07 Degrees Celsius | Standard Deviation 0.419 |
| Cohort 7 to 10: Placebo | Change In Oral Body Temperature | Change from Baseline - Day 3/42 Hour | -0.29 Degrees Celsius | Standard Deviation 0.353 |
Primary
Change In Respiratory Rate
Respiratory rate measurements were measured at specific time points.
Time frame: Days 1, 2, 3, 4, 7 and 28
Population: Safety population: all participants who received any amount of study drug.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: 100 mg PB2452 (no Ticagrelor) | Change In Respiratory Rate | Change from Baseline - Day 1/0.75 Hour | -0.7 Breaths per minute | Standard Deviation 2.31 |
| Cohort 1: 100 mg PB2452 (no Ticagrelor) | Change In Respiratory Rate | Change from Baseline - Day 3/48 Hour | -2.7 Breaths per minute | Standard Deviation 1.15 |
| Cohort 1: 100 mg PB2452 (no Ticagrelor) | Change In Respiratory Rate | Change from Baseline - Day 1/1 Hour | -3.3 Breaths per minute | Standard Deviation 2.31 |
| Cohort 1: 100 mg PB2452 (no Ticagrelor) | Change In Respiratory Rate | Change from Baseline - Day 3/42 Hour | -0.7 Breaths per minute | Standard Deviation 3.06 |
| Cohort 1: 100 mg PB2452 (no Ticagrelor) | Change In Respiratory Rate | Change from Baseline - Day 7 | 1.3 Breaths per minute | Standard Deviation 4.16 |
| Cohort 1: 100 mg PB2452 (no Ticagrelor) | Change In Respiratory Rate | Change from Baseline - Day 1/4 Hour | -0.7 Breaths per minute | Standard Deviation 1.15 |
| Cohort 1: 100 mg PB2452 (no Ticagrelor) | Change In Respiratory Rate | Change from Baseline - Day 2/24 Hour | -2.0 Breaths per minute | Standard Deviation 0 |
| Cohort 1: 100 mg PB2452 (no Ticagrelor) | Change In Respiratory Rate | Change from Baseline - Day 1/8 Hour | 1.3 Breaths per minute | Standard Deviation 3.06 |
| Cohort 1: 100 mg PB2452 (no Ticagrelor) | Change In Respiratory Rate | Change from Baseline - Day 1/2 Hour | -1.3 Breaths per minute | Standard Deviation 1.15 |
| Cohort 1: 100 mg PB2452 (no Ticagrelor) | Change In Respiratory Rate | Change from Baseline - Day 2/36 Hour | 2.0 Breaths per minute | Standard Deviation 4 |
| Cohort 1: 100 mg PB2452 (no Ticagrelor) | Change In Respiratory Rate | Change from Baseline - Day 2/30 Hour | 2.7 Breaths per minute | Standard Deviation 3.06 |
| Cohort 1: 100 mg PB2452 (no Ticagrelor) | Change In Respiratory Rate | Change from Baseline - Day 4 | -0.7 Breaths per minute | Standard Deviation 6.11 |
| Cohort 1: 100 mg PB2452 (no Ticagrelor) | Change In Respiratory Rate | Change from Baseline - Day 28 | 0.7 Breaths per minute | Standard Deviation 1.15 |
| Cohort 1: 100 mg PB2452 (no Ticagrelor) | Change In Respiratory Rate | Change from Baseline - Day 1/0.5 Hour | 0 Breaths per minute | Standard Deviation 0 |
| Cohort 2: 300 mg PB2452 (no Ticagrelor) | Change In Respiratory Rate | Change from Baseline - Day 3/42 Hour | 3.3 Breaths per minute | Standard Deviation 2.31 |
| Cohort 2: 300 mg PB2452 (no Ticagrelor) | Change In Respiratory Rate | Change from Baseline - Day 2/30 Hour | 3.3 Breaths per minute | Standard Deviation 2.31 |
| Cohort 2: 300 mg PB2452 (no Ticagrelor) | Change In Respiratory Rate | Change from Baseline - Day 1/4 Hour | 0 Breaths per minute | Standard Deviation 2 |
| Cohort 2: 300 mg PB2452 (no Ticagrelor) | Change In Respiratory Rate | Change from Baseline - Day 3/48 Hour | 1.3 Breaths per minute | Standard Deviation 2.31 |
| Cohort 2: 300 mg PB2452 (no Ticagrelor) | Change In Respiratory Rate | Change from Baseline - Day 2/36 Hour | 6.0 Breaths per minute | Standard Deviation 0 |
| Cohort 2: 300 mg PB2452 (no Ticagrelor) | Change In Respiratory Rate | Change from Baseline - Day 1/0.75 Hour | 3.3 Breaths per minute | Standard Deviation 1.15 |
| Cohort 2: 300 mg PB2452 (no Ticagrelor) | Change In Respiratory Rate | Change from Baseline - Day 1/8 Hour | 5.3 Breaths per minute | Standard Deviation 1.15 |
| Cohort 2: 300 mg PB2452 (no Ticagrelor) | Change In Respiratory Rate | Change from Baseline - Day 1/0.5 Hour | 0 Breaths per minute | Standard Deviation 0 |
| Cohort 2: 300 mg PB2452 (no Ticagrelor) | Change In Respiratory Rate | Change from Baseline - Day 2/24 Hour | 1.3 Breaths per minute | Standard Deviation 3.06 |
| Cohort 2: 300 mg PB2452 (no Ticagrelor) | Change In Respiratory Rate | Change from Baseline - Day 7 | 2.0 Breaths per minute | Standard Deviation 0 |
| Cohort 2: 300 mg PB2452 (no Ticagrelor) | Change In Respiratory Rate | Change from Baseline - Day 1/1 Hour | 2.7 Breaths per minute | Standard Deviation 2.31 |
| Cohort 2: 300 mg PB2452 (no Ticagrelor) | Change In Respiratory Rate | Change from Baseline - Day 4 | 4.7 Breaths per minute | Standard Deviation 3.06 |
| Cohort 2: 300 mg PB2452 (no Ticagrelor) | Change In Respiratory Rate | Change from Baseline - Day 28 | 4.0 Breaths per minute | Standard Deviation 0 |
| Cohort 2: 300 mg PB2452 (no Ticagrelor) | Change In Respiratory Rate | Change from Baseline - Day 1/2 Hour | 0 Breaths per minute | Standard Deviation 2 |
| Cohort 3: 1000 mg PB2452 (no Ticagrelor) | Change In Respiratory Rate | Change from Baseline - Day 28 | -1.3 Breaths per minute | Standard Deviation 1.15 |
| Cohort 3: 1000 mg PB2452 (no Ticagrelor) | Change In Respiratory Rate | Change from Baseline - Day 1/1 Hour | 0.7 Breaths per minute | Standard Deviation 3.06 |
| Cohort 3: 1000 mg PB2452 (no Ticagrelor) | Change In Respiratory Rate | Change from Baseline - Day 2/36 Hour | -1.3 Breaths per minute | Standard Deviation 3.06 |
| Cohort 3: 1000 mg PB2452 (no Ticagrelor) | Change In Respiratory Rate | Change from Baseline - Day 1/2 Hour | 0.7 Breaths per minute | Standard Deviation 2.31 |
| Cohort 3: 1000 mg PB2452 (no Ticagrelor) | Change In Respiratory Rate | Change from Baseline - Day 3/42 Hour | -4.7 Breaths per minute | Standard Deviation 2.31 |
| Cohort 3: 1000 mg PB2452 (no Ticagrelor) | Change In Respiratory Rate | Change from Baseline - Day 1/0.5 Hour | -2.0 Breaths per minute | Standard Deviation 0 |
| Cohort 3: 1000 mg PB2452 (no Ticagrelor) | Change In Respiratory Rate | Change from Baseline - Day 1/4 Hour | -2.0 Breaths per minute | Standard Deviation 2 |
| Cohort 3: 1000 mg PB2452 (no Ticagrelor) | Change In Respiratory Rate | Change from Baseline - Day 2/30 Hour | 0.7 Breaths per minute | Standard Deviation 1.15 |
| Cohort 3: 1000 mg PB2452 (no Ticagrelor) | Change In Respiratory Rate | Change from Baseline - Day 4 | -2.0 Breaths per minute | Standard Deviation 2 |
| Cohort 3: 1000 mg PB2452 (no Ticagrelor) | Change In Respiratory Rate | Change from Baseline - Day 7 | -1.3 Breaths per minute | Standard Deviation 1.15 |
| Cohort 3: 1000 mg PB2452 (no Ticagrelor) | Change In Respiratory Rate | Change from Baseline - Day 3/48 Hour | -0.7 Breaths per minute | Standard Deviation 1.15 |
| Cohort 3: 1000 mg PB2452 (no Ticagrelor) | Change In Respiratory Rate | Change from Baseline - Day 1/8 Hour | -2.0 Breaths per minute | Standard Deviation 4 |
| Cohort 3: 1000 mg PB2452 (no Ticagrelor) | Change In Respiratory Rate | Change from Baseline - Day 2/24 Hour | -0.7 Breaths per minute | Standard Deviation 2.31 |
| Cohort 3: 1000 mg PB2452 (no Ticagrelor) | Change In Respiratory Rate | Change from Baseline - Day 1/0.75 Hour | -1.3 Breaths per minute | Standard Deviation 3.06 |
| Cohort 1 to 3: Placebo | Change In Respiratory Rate | Change from Baseline - Day 28 | 1.3 Breaths per minute | Standard Deviation 3.06 |
| Cohort 1 to 3: Placebo | Change In Respiratory Rate | Change from Baseline - Day 2/30 Hour | 1.3 Breaths per minute | Standard Deviation 5.03 |
| Cohort 1 to 3: Placebo | Change In Respiratory Rate | Change from Baseline - Day 1/0.75 Hour | -1.3 Breaths per minute | Standard Deviation 4.16 |
| Cohort 1 to 3: Placebo | Change In Respiratory Rate | Change from Baseline - Day 7 | 1.3 Breaths per minute | Standard Deviation 5.03 |
| Cohort 1 to 3: Placebo | Change In Respiratory Rate | Change from Baseline - Day 1/1 Hour | -1.3 Breaths per minute | Standard Deviation 4.16 |
| Cohort 1 to 3: Placebo | Change In Respiratory Rate | Change from Baseline - Day 4 | 0.7 Breaths per minute | Standard Deviation 3.06 |
| Cohort 1 to 3: Placebo | Change In Respiratory Rate | Change from Baseline - Day 1/2 Hour | 0 Breaths per minute | Standard Deviation 2 |
| Cohort 1 to 3: Placebo | Change In Respiratory Rate | Change from Baseline - Day 1/0.5 Hour | -2.0 Breaths per minute | — |
| Cohort 1 to 3: Placebo | Change In Respiratory Rate | Change from Baseline - Day 3/48 Hour | 1.3 Breaths per minute | Standard Deviation 3.06 |
| Cohort 1 to 3: Placebo | Change In Respiratory Rate | Change from Baseline - Day 1/4 Hour | -0.7 Breaths per minute | Standard Deviation 3.06 |
| Cohort 1 to 3: Placebo | Change In Respiratory Rate | Change from Baseline - Day 3/42 Hour | 0.7 Breaths per minute | Standard Deviation 6.11 |
| Cohort 1 to 3: Placebo | Change In Respiratory Rate | Change from Baseline - Day 1/8 Hour | 1.3 Breaths per minute | Standard Deviation 7.02 |
| Cohort 1 to 3: Placebo | Change In Respiratory Rate | Change from Baseline - Day 2/36 Hour | -0.7 Breaths per minute | Standard Deviation 6.43 |
| Cohort 1 to 3: Placebo | Change In Respiratory Rate | Change from Baseline - Day 2/24 Hour | 0.7 Breaths per minute | Standard Deviation 2.31 |
| Cohort 4: 1000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Respiratory Rate | Change from Baseline - Day 4 | -1.0 Breaths per minute | Standard Deviation 2.1 |
| Cohort 4: 1000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Respiratory Rate | Change from Baseline - Day 1/4 Hour | -2.3 Breaths per minute | Standard Deviation 4.63 |
| Cohort 4: 1000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Respiratory Rate | Change from Baseline - Day 1/0.5 Hour | -1.3 Breaths per minute | Standard Deviation 3.27 |
| Cohort 4: 1000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Respiratory Rate | Change from Baseline - Day 3/42 Hour | -0.7 Breaths per minute | Standard Deviation 2.42 |
| Cohort 4: 1000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Respiratory Rate | Change from Baseline - Day 2/30 Hour | 0.7 Breaths per minute | Standard Deviation 4.84 |
| Cohort 4: 1000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Respiratory Rate | Change from Baseline - Day 1/1 Hour | -1.0 Breaths per minute | Standard Deviation 3.95 |
| Cohort 4: 1000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Respiratory Rate | Change from Baseline - Day 7 | -2.7 Breaths per minute | Standard Deviation 3.5 |
| Cohort 4: 1000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Respiratory Rate | Change from Baseline - Day 1/0.75 Hour | -1.3 Breaths per minute | Standard Deviation 4.32 |
| Cohort 4: 1000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Respiratory Rate | Change from Baseline - Day 1/8 Hour | -0.3 Breaths per minute | Standard Deviation 2.94 |
| Cohort 4: 1000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Respiratory Rate | Change from Baseline - Day 2/36 Hour | -1.0 Breaths per minute | Standard Deviation 3.74 |
| Cohort 4: 1000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Respiratory Rate | Change from Baseline - Day 2/24 Hour | -3.0 Breaths per minute | Standard Deviation 3.03 |
| Cohort 4: 1000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Respiratory Rate | Change from Baseline - Day 28 | -2.0 Breaths per minute | Standard Deviation 2.19 |
| Cohort 4: 1000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Respiratory Rate | Change from Baseline - Day 3/48 Hour | -1.7 Breaths per minute | Standard Deviation 4.27 |
| Cohort 4: 1000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Respiratory Rate | Change from Baseline - Day 1/2 Hour | -1.3 Breaths per minute | Standard Deviation 3.01 |
| Cohort 5: 3000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Respiratory Rate | Change from Baseline - Day 1/2 Hour | 1.3 Breaths per minute | Standard Deviation 3.27 |
| Cohort 5: 3000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Respiratory Rate | Change from Baseline - Day 1/8 Hour | 3.0 Breaths per minute | Standard Deviation 2.76 |
| Cohort 5: 3000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Respiratory Rate | Change from Baseline - Day 1/4 Hour | 1.0 Breaths per minute | Standard Deviation 2.1 |
| Cohort 5: 3000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Respiratory Rate | Change from Baseline - Day 1/0.5 Hour | 0.3 Breaths per minute | Standard Deviation 2.94 |
| Cohort 5: 3000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Respiratory Rate | Change from Baseline - Day 3/42 Hour | 0.3 Breaths per minute | Standard Deviation 3.44 |
| Cohort 5: 3000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Respiratory Rate | Change from Baseline - Day 2/36 Hour | 0.7 Breaths per minute | Standard Deviation 2.07 |
| Cohort 5: 3000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Respiratory Rate | Change from Baseline - Day 28 | -2.0 Breaths per minute | Standard Deviation 1.26 |
| Cohort 5: 3000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Respiratory Rate | Change from Baseline - Day 1/1 Hour | 0.3 Breaths per minute | Standard Deviation 2.34 |
| Cohort 5: 3000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Respiratory Rate | Change from Baseline - Day 3/48 Hour | -0.3 Breaths per minute | Standard Deviation 2.34 |
| Cohort 5: 3000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Respiratory Rate | Change from Baseline - Day 4 | -0.3 Breaths per minute | Standard Deviation 2.34 |
| Cohort 5: 3000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Respiratory Rate | Change from Baseline - Day 7 | 0.7 Breaths per minute | Standard Deviation 3.01 |
| Cohort 5: 3000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Respiratory Rate | Change from Baseline - Day 1/0.75 Hour | 0 Breaths per minute | Standard Deviation 2.19 |
| Cohort 5: 3000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Respiratory Rate | Change from Baseline - Day 2/24 Hour | -1.0 Breaths per minute | Standard Deviation 2.1 |
| Cohort 5: 3000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Respiratory Rate | Change from Baseline - Day 2/30 Hour | 1.0 Breaths per minute | Standard Deviation 2.1 |
| Cohort 6: 9000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Respiratory Rate | Change from Baseline - Day 3/48 Hour | 0.7 Breaths per minute | Standard Deviation 2.07 |
| Cohort 6: 9000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Respiratory Rate | Change from Baseline - Day 1/0.5 Hour | 0 Breaths per minute | Standard Deviation 0 |
| Cohort 6: 9000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Respiratory Rate | Change from Baseline - Day 1/0.75 Hour | 0.7 Breaths per minute | Standard Deviation 1.63 |
| Cohort 6: 9000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Respiratory Rate | Change from Baseline - Day 1/1 Hour | 1.3 Breaths per minute | Standard Deviation 1.03 |
| Cohort 6: 9000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Respiratory Rate | Change from Baseline - Day 1/2 Hour | 3.3 Breaths per minute | Standard Deviation 1.63 |
| Cohort 6: 9000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Respiratory Rate | Change from Baseline - Day 1/4 Hour | 1.7 Breaths per minute | Standard Deviation 2.34 |
| Cohort 6: 9000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Respiratory Rate | Change from Baseline - Day 1/8 Hour | -1.0 Breaths per minute | Standard Deviation 2.76 |
| Cohort 6: 9000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Respiratory Rate | Change from Baseline - Day 2/24 Hour | 2.3 Breaths per minute | Standard Deviation 2.66 |
| Cohort 6: 9000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Respiratory Rate | Change from Baseline - Day 2/30 Hour | 2.7 Breaths per minute | Standard Deviation 2.42 |
| Cohort 6: 9000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Respiratory Rate | Change from Baseline - Day 2/36 Hour | -0.7 Breaths per minute | Standard Deviation 2.07 |
| Cohort 6: 9000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Respiratory Rate | Change from Baseline - Day 3/42 Hour | 2.7 Breaths per minute | Standard Deviation 3.5 |
| Cohort 6: 9000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Respiratory Rate | Change from Baseline - Day 4 | 4.0 Breaths per minute | Standard Deviation 1.79 |
| Cohort 6: 9000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Respiratory Rate | Change from Baseline - Day 7 | 2.7 Breaths per minute | Standard Deviation 3.01 |
| Cohort 6: 9000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Respiratory Rate | Change from Baseline - Day 28 | 0 Breaths per minute | Standard Deviation 2.19 |
| Cohort 4 to 6: Placebo | Change In Respiratory Rate | Change from Baseline - Day 3/42 Hour | -1.0 Breaths per minute | Standard Deviation 2.1 |
| Cohort 4 to 6: Placebo | Change In Respiratory Rate | Change from Baseline - Day 3/48 Hour | 0.3 Breaths per minute | Standard Deviation 2.34 |
| Cohort 4 to 6: Placebo | Change In Respiratory Rate | Change from Baseline - Day 1/2 Hour | 0 Breaths per minute | Standard Deviation 3.35 |
| Cohort 4 to 6: Placebo | Change In Respiratory Rate | Change from Baseline - Day 1/0.5 Hour | -1.0 Breaths per minute | Standard Deviation 2.1 |
| Cohort 4 to 6: Placebo | Change In Respiratory Rate | Change from Baseline - Day 7 | -1.3 Breaths per minute | Standard Deviation 1.63 |
| Cohort 4 to 6: Placebo | Change In Respiratory Rate | Change from Baseline - Day 28 | -0.7 Breaths per minute | Standard Deviation 2.42 |
| Cohort 4 to 6: Placebo | Change In Respiratory Rate | Change from Baseline - Day 1/8 Hour | 0.3 Breaths per minute | Standard Deviation 3.2 |
| Cohort 4 to 6: Placebo | Change In Respiratory Rate | Change from Baseline - Day 2/36 Hour | -2.0 Breaths per minute | Standard Deviation 3.58 |
| Cohort 4 to 6: Placebo | Change In Respiratory Rate | Change from Baseline - Day 1/0.75 Hour | -1.7 Breaths per minute | Standard Deviation 2.94 |
| Cohort 4 to 6: Placebo | Change In Respiratory Rate | Change from Baseline - Day 4 | 1.0 Breaths per minute | Standard Deviation 2.76 |
| Cohort 4 to 6: Placebo | Change In Respiratory Rate | Change from Baseline - Day 1/1 Hour | -0.3 Breaths per minute | Standard Deviation 2.94 |
| Cohort 4 to 6: Placebo | Change In Respiratory Rate | Change from Baseline - Day 2/30 Hour | 0 Breaths per minute | Standard Deviation 5.51 |
| Cohort 4 to 6: Placebo | Change In Respiratory Rate | Change from Baseline - Day 1/4 Hour | 0 Breaths per minute | Standard Deviation 1.26 |
| Cohort 4 to 6: Placebo | Change In Respiratory Rate | Change from Baseline - Day 2/24 Hour | -1.0 Breaths per minute | Standard Deviation 2.1 |
| Cohort 7: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Respiratory Rate | Change from Baseline - Day 1/4 Hour | 0.3 Breaths per minute | Standard Deviation 4.27 |
| Cohort 7: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Respiratory Rate | Change from Baseline - Day 2/24 Hour | -1.0 Breaths per minute | Standard Deviation 2.1 |
| Cohort 7: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Respiratory Rate | Change from Baseline - Day 3/48 Hour | -0.7 Breaths per minute | Standard Deviation 2.42 |
| Cohort 7: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Respiratory Rate | Change from Baseline - Day 2/36 Hour | 0.3 Breaths per minute | Standard Deviation 2.66 |
| Cohort 7: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Respiratory Rate | Change from Baseline - Day 2/30 Hour | -2.7 Breaths per minute | Standard Deviation 2.73 |
| Cohort 7: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Respiratory Rate | Change from Baseline - Day 1/2 Hour | 0.7 Breaths per minute | Standard Deviation 3.01 |
| Cohort 7: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Respiratory Rate | Change from Baseline - Day 1/1 Hour | -0.7 Breaths per minute | Standard Deviation 2.07 |
| Cohort 7: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Respiratory Rate | Change from Baseline - Day 1/0.5 Hour | 0.5 Breaths per minute | Standard Deviation 1.91 |
| Cohort 7: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Respiratory Rate | Change from Baseline - Day 7 | 0.4 Breaths per minute | Standard Deviation 2.61 |
| Cohort 7: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Respiratory Rate | Change from Baseline - Day 1/0.75 Hour | -0.7 Breaths per minute | Standard Deviation 3.5 |
| Cohort 7: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Respiratory Rate | Change from Baseline - Day 4 | 1.0 Breaths per minute | Standard Deviation 2.76 |
| Cohort 7: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Respiratory Rate | Change from Baseline - Day 1/8 Hour | 2.0 Breaths per minute | Standard Deviation 2.53 |
| Cohort 7: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Respiratory Rate | Change from Baseline - Day 3/42 Hour | -1.0 Breaths per minute | Standard Deviation 3.29 |
| Cohort 7: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Respiratory Rate | Change from Baseline - Day 28 | -0.7 Breaths per minute | Standard Deviation 4.84 |
| Cohort 8: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Respiratory Rate | Change from Baseline - Day 1/8 Hour | -2.0 Breaths per minute | Standard Deviation 5.83 |
| Cohort 8: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Respiratory Rate | Change from Baseline - Day 2/30 Hour | 1.7 Breaths per minute | Standard Deviation 2.34 |
| Cohort 8: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Respiratory Rate | Change from Baseline - Day 2/36 Hour | 0.7 Breaths per minute | Standard Deviation 2.42 |
| Cohort 8: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Respiratory Rate | Change from Baseline - Day 1/4 Hour | 0.3 Breaths per minute | Standard Deviation 0.82 |
| Cohort 8: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Respiratory Rate | Change from Baseline - Day 28 | 0.7 Breaths per minute | Standard Deviation 3.27 |
| Cohort 8: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Respiratory Rate | Change from Baseline - Day 3/42 Hour | 2.0 Breaths per minute | Standard Deviation 1.79 |
| Cohort 8: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Respiratory Rate | Change from Baseline - Day 1/2 Hour | 0.3 Breaths per minute | Standard Deviation 2.66 |
| Cohort 8: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Respiratory Rate | Change from Baseline - Day 3/48 Hour | -0.7 Breaths per minute | Standard Deviation 1.63 |
| Cohort 8: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Respiratory Rate | Change from Baseline - Day 1/1 Hour | 0 Breaths per minute | Standard Deviation 2.83 |
| Cohort 8: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Respiratory Rate | Change from Baseline - Day 4 | 2.3 Breaths per minute | Standard Deviation 3.67 |
| Cohort 8: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Respiratory Rate | Change from Baseline - Day 1/0.75 Hour | -1.0 Breaths per minute | Standard Deviation 2.45 |
| Cohort 8: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Respiratory Rate | Change from Baseline - Day 7 | 3.7 Breaths per minute | Standard Deviation 1.51 |
| Cohort 8: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Respiratory Rate | Change from Baseline - Day 1/0.5 Hour | -1.0 Breaths per minute | Standard Deviation 1.15 |
| Cohort 8: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Respiratory Rate | Change from Baseline - Day 2/24 Hour | -1.0 Breaths per minute | Standard Deviation 3.03 |
| Cohort 9: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Respiratory Rate | Change from Baseline - Day 1/0.5 Hour | -0.7 Breaths per minute | Standard Deviation 3.06 |
| Cohort 9: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Respiratory Rate | Change from Baseline - Day 3/48 Hour | -1.3 Breaths per minute | Standard Deviation 3.06 |
| Cohort 9: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Respiratory Rate | Change from Baseline - Day 1/1 Hour | -2.7 Breaths per minute | Standard Deviation 3.06 |
| Cohort 9: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Respiratory Rate | Change from Baseline - Day 1/4 Hour | 2.0 Breaths per minute | Standard Deviation 4 |
| Cohort 9: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Respiratory Rate | Change from Baseline - Day 28 | 0.7 Breaths per minute | Standard Deviation 4.16 |
| Cohort 9: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Respiratory Rate | Change from Baseline - Day 4 | 0 Breaths per minute | Standard Deviation 5.29 |
| Cohort 9: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Respiratory Rate | Change from Baseline - Day 1/0.75 Hour | -2.0 Breaths per minute | Standard Deviation 4 |
| Cohort 9: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Respiratory Rate | Change from Baseline - Day 2/24 Hour | -3.3 Breaths per minute | Standard Deviation 1.15 |
| Cohort 9: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Respiratory Rate | Change from Baseline - Day 2/36 Hour | 1.3 Breaths per minute | Standard Deviation 3.06 |
| Cohort 9: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Respiratory Rate | Change from Baseline - Day 1/8 Hour | -2.0 Breaths per minute | Standard Deviation 5.29 |
| Cohort 9: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Respiratory Rate | Change from Baseline - Day 2/30 Hour | -0.7 Breaths per minute | Standard Deviation 4.62 |
| Cohort 9: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Respiratory Rate | Change from Baseline - Day 7 | -0.7 Breaths per minute | Standard Deviation 4.62 |
| Cohort 9: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Respiratory Rate | Change from Baseline - Day 1/2 Hour | -0.7 Breaths per minute | Standard Deviation 5.03 |
| Cohort 9: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Respiratory Rate | Change from Baseline - Day 3/42 Hour | 1.3 Breaths per minute | Standard Deviation 4.16 |
| Cohort 10: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Respiratory Rate | Change from Baseline - Day 2/24 Hour | -1.3 Breaths per minute | Standard Deviation 4.32 |
| Cohort 10: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Respiratory Rate | Change from Baseline - Day 4 | -0.3 Breaths per minute | Standard Deviation 1.97 |
| Cohort 10: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Respiratory Rate | Change from Baseline - Day 1/0.75 Hour | -0.3 Breaths per minute | Standard Deviation 3.2 |
| Cohort 10: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Respiratory Rate | Change from Baseline - Day 1/2 Hour | -0.8 Breaths per minute | Standard Deviation 3.03 |
| Cohort 10: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Respiratory Rate | Change from Baseline - Day 3/42 Hour | 0.3 Breaths per minute | Standard Deviation 1.97 |
| Cohort 10: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Respiratory Rate | Change from Baseline - Day 2/36 Hour | 0 Breaths per minute | Standard Deviation 2.53 |
| Cohort 10: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Respiratory Rate | Change from Baseline - Day 28 | -0.3 Breaths per minute | Standard Deviation 3.88 |
| Cohort 10: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Respiratory Rate | Change from Baseline - Day 1/8 Hour | -0.3 Breaths per minute | Standard Deviation 0.82 |
| Cohort 10: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Respiratory Rate | Change from Baseline - Day 7 | -1.0 Breaths per minute | Standard Deviation 2.1 |
| Cohort 10: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Respiratory Rate | Change from Baseline - Day 3/48 Hour | -0.7 Breaths per minute | Standard Deviation 2.73 |
| Cohort 10: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Respiratory Rate | Change from Baseline - Day 1/1 Hour | -1.0 Breaths per minute | Standard Deviation 3.29 |
| Cohort 10: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Respiratory Rate | Change from Baseline - Day 1/0.5 Hour | -0.7 Breaths per minute | Standard Deviation 3.01 |
| Cohort 10: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Respiratory Rate | Change from Baseline - Day 1/4 Hour | -2.3 Breaths per minute | Standard Deviation 2.34 |
| Cohort 10: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change In Respiratory Rate | Change from Baseline - Day 2/30 Hour | 0 Breaths per minute | Standard Deviation 1.79 |
| Cohort 7 to 10: Placebo | Change In Respiratory Rate | Change from Baseline - Day 2/36 Hour | 0.9 Breaths per minute | Standard Deviation 3.63 |
| Cohort 7 to 10: Placebo | Change In Respiratory Rate | Change from Baseline - Day 7 | 1.7 Breaths per minute | Standard Deviation 2.93 |
| Cohort 7 to 10: Placebo | Change In Respiratory Rate | Change from Baseline - Day 4 | 0.3 Breaths per minute | Standard Deviation 3.15 |
| Cohort 7 to 10: Placebo | Change In Respiratory Rate | Change from Baseline - Day 1/0.75 Hour | -0.9 Breaths per minute | Standard Deviation 2.27 |
| Cohort 7 to 10: Placebo | Change In Respiratory Rate | Change from Baseline - Day 3/48 Hour | 0.6 Breaths per minute | Standard Deviation 3.95 |
| Cohort 7 to 10: Placebo | Change In Respiratory Rate | Change from Baseline - Day 1/8 Hour | 0.6 Breaths per minute | Standard Deviation 4.58 |
| Cohort 7 to 10: Placebo | Change In Respiratory Rate | Change from Baseline - Day 1/4 Hour | -0.3 Breaths per minute | Standard Deviation 3.73 |
| Cohort 7 to 10: Placebo | Change In Respiratory Rate | Change from Baseline - Day 2/30 Hour | -0.3 Breaths per minute | Standard Deviation 4.07 |
| Cohort 7 to 10: Placebo | Change In Respiratory Rate | Change from Baseline - Day 1/0.5 Hour | -0.6 Breaths per minute | Standard Deviation 3.6 |
| Cohort 7 to 10: Placebo | Change In Respiratory Rate | Change from Baseline - Day 2/24 Hour | -1.4 Breaths per minute | Standard Deviation 2.51 |
| Cohort 7 to 10: Placebo | Change In Respiratory Rate | Change from Baseline - Day 1/2 Hour | 1.4 Breaths per minute | Standard Deviation 3.6 |
| Cohort 7 to 10: Placebo | Change In Respiratory Rate | Change from Baseline - Day 28 | 0.3 Breaths per minute | Standard Deviation 2.69 |
| Cohort 7 to 10: Placebo | Change In Respiratory Rate | Change from Baseline - Day 3/42 Hour | 2.9 Breaths per minute | Standard Deviation 2.79 |
| Cohort 7 to 10: Placebo | Change In Respiratory Rate | Change from Baseline - Day 1/1 Hour | 0.3 Breaths per minute | Standard Deviation 3.9 |
Primary
Change in Systolic Blood Pressure
Systolic blood pressure measurements were measured at specific time points.
Time frame: Days 1, 2, 3, 4, 7 and 28
Population: Safety population: all participants who received any amount of study drug.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: 100 mg PB2452 (no Ticagrelor) | Change in Systolic Blood Pressure | Change from Baseline - Day 28 | 12.0 mmHg | Standard Deviation 7.21 |
| Cohort 1: 100 mg PB2452 (no Ticagrelor) | Change in Systolic Blood Pressure | Change from Baseline - Day 2/24 Hour | 4.7 mmHg | Standard Deviation 5.13 |
| Cohort 1: 100 mg PB2452 (no Ticagrelor) | Change in Systolic Blood Pressure | Change from Baseline - Day 3/48 Hour | 2.0 mmHg | Standard Deviation 8.72 |
| Cohort 1: 100 mg PB2452 (no Ticagrelor) | Change in Systolic Blood Pressure | Change from Baseline - Day 2/30 Hour | 4.0 mmHg | Standard Deviation 12.12 |
| Cohort 1: 100 mg PB2452 (no Ticagrelor) | Change in Systolic Blood Pressure | Change from Baseline - Day 1/0.5 Hour | 3.0 mmHg | Standard Deviation 15.1 |
| Cohort 1: 100 mg PB2452 (no Ticagrelor) | Change in Systolic Blood Pressure | Change from Baseline - Day 7 | 11.7 mmHg | Standard Deviation 5.51 |
| Cohort 1: 100 mg PB2452 (no Ticagrelor) | Change in Systolic Blood Pressure | Change from Baseline - Day 3/42 Hour | 2.3 mmHg | Standard Deviation 9.07 |
| Cohort 1: 100 mg PB2452 (no Ticagrelor) | Change in Systolic Blood Pressure | Change from Baseline - Day 2/36 Hour | 1.0 mmHg | Standard Deviation 6.08 |
| Cohort 1: 100 mg PB2452 (no Ticagrelor) | Change in Systolic Blood Pressure | Change from Baseline - Day 1/8 Hour | 0.7 mmHg | Standard Deviation 11.02 |
| Cohort 1: 100 mg PB2452 (no Ticagrelor) | Change in Systolic Blood Pressure | Change from Baseline - Day 4 | 15.0 mmHg | Standard Deviation 2.65 |
| Cohort 1: 100 mg PB2452 (no Ticagrelor) | Change in Systolic Blood Pressure | Change from Baseline - Day 1/4 Hour | 5.7 mmHg | Standard Deviation 9.87 |
| Cohort 1: 100 mg PB2452 (no Ticagrelor) | Change in Systolic Blood Pressure | Change from Baseline - Day 1/2 Hour | 5.7 mmHg | Standard Deviation 10.21 |
| Cohort 1: 100 mg PB2452 (no Ticagrelor) | Change in Systolic Blood Pressure | Change from Baseline - Day 1/1 Hour | 7.7 mmHg | Standard Deviation 5.13 |
| Cohort 1: 100 mg PB2452 (no Ticagrelor) | Change in Systolic Blood Pressure | Change from Baseline - Day 1/0.75 Hour | 4.0 mmHg | Standard Deviation 5 |
| Cohort 2: 300 mg PB2452 (no Ticagrelor) | Change in Systolic Blood Pressure | Change from Baseline - Day 3/42 Hour | -9.7 mmHg | Standard Deviation 2.52 |
| Cohort 2: 300 mg PB2452 (no Ticagrelor) | Change in Systolic Blood Pressure | Change from Baseline - Day 28 | 6.3 mmHg | Standard Deviation 6.51 |
| Cohort 2: 300 mg PB2452 (no Ticagrelor) | Change in Systolic Blood Pressure | Change from Baseline - Day 1/4 Hour | -4.0 mmHg | Standard Deviation 3.61 |
| Cohort 2: 300 mg PB2452 (no Ticagrelor) | Change in Systolic Blood Pressure | Change from Baseline - Day 1/0.75 Hour | 2.0 mmHg | Standard Deviation 4.36 |
| Cohort 2: 300 mg PB2452 (no Ticagrelor) | Change in Systolic Blood Pressure | Change from Baseline - Day 2/24 Hour | -3.7 mmHg | Standard Deviation 11.59 |
| Cohort 2: 300 mg PB2452 (no Ticagrelor) | Change in Systolic Blood Pressure | Change from Baseline - Day 2/30 Hour | 1.0 mmHg | Standard Deviation 10.15 |
| Cohort 2: 300 mg PB2452 (no Ticagrelor) | Change in Systolic Blood Pressure | Change from Baseline - Day 7 | 5.7 mmHg | Standard Deviation 15.5 |
| Cohort 2: 300 mg PB2452 (no Ticagrelor) | Change in Systolic Blood Pressure | Change from Baseline - Day 4 | 1.0 mmHg | Standard Deviation 5.57 |
| Cohort 2: 300 mg PB2452 (no Ticagrelor) | Change in Systolic Blood Pressure | Change from Baseline - Day 1/1 Hour | 2.7 mmHg | Standard Deviation 3.06 |
| Cohort 2: 300 mg PB2452 (no Ticagrelor) | Change in Systolic Blood Pressure | Change from Baseline - Day 1/0.5 Hour | -0.7 mmHg | Standard Deviation 8.33 |
| Cohort 2: 300 mg PB2452 (no Ticagrelor) | Change in Systolic Blood Pressure | Change from Baseline - Day 1/8 Hour | -1.0 mmHg | Standard Deviation 4.36 |
| Cohort 2: 300 mg PB2452 (no Ticagrelor) | Change in Systolic Blood Pressure | Change from Baseline - Day 3/48 Hour | 5.3 mmHg | Standard Deviation 7.57 |
| Cohort 2: 300 mg PB2452 (no Ticagrelor) | Change in Systolic Blood Pressure | Change from Baseline - Day 2/36 Hour | -0.7 mmHg | Standard Deviation 7.77 |
| Cohort 2: 300 mg PB2452 (no Ticagrelor) | Change in Systolic Blood Pressure | Change from Baseline - Day 1/2 Hour | -1.3 mmHg | Standard Deviation 4.93 |
| Cohort 3: 1000 mg PB2452 (no Ticagrelor) | Change in Systolic Blood Pressure | Change from Baseline - Day 1/1 Hour | 3.0 mmHg | Standard Deviation 4.58 |
| Cohort 3: 1000 mg PB2452 (no Ticagrelor) | Change in Systolic Blood Pressure | Change from Baseline - Day 1/0.5 Hour | 6.7 mmHg | Standard Deviation 6.51 |
| Cohort 3: 1000 mg PB2452 (no Ticagrelor) | Change in Systolic Blood Pressure | Change from Baseline - Day 3/42 Hour | 3.0 mmHg | Standard Deviation 12.12 |
| Cohort 3: 1000 mg PB2452 (no Ticagrelor) | Change in Systolic Blood Pressure | Change from Baseline - Day 1/8 Hour | -2.0 mmHg | Standard Deviation 1.73 |
| Cohort 3: 1000 mg PB2452 (no Ticagrelor) | Change in Systolic Blood Pressure | Change from Baseline - Day 2/36 Hour | 5.0 mmHg | Standard Deviation 6 |
| Cohort 3: 1000 mg PB2452 (no Ticagrelor) | Change in Systolic Blood Pressure | Change from Baseline - Day 1/4 Hour | 1.3 mmHg | Standard Deviation 3.21 |
| Cohort 3: 1000 mg PB2452 (no Ticagrelor) | Change in Systolic Blood Pressure | Change from Baseline - Day 1/2 Hour | 1.7 mmHg | Standard Deviation 9.07 |
| Cohort 3: 1000 mg PB2452 (no Ticagrelor) | Change in Systolic Blood Pressure | Change from Baseline - Day 7 | 6.3 mmHg | Standard Deviation 13.5 |
| Cohort 3: 1000 mg PB2452 (no Ticagrelor) | Change in Systolic Blood Pressure | Change from Baseline - Day 2/30 Hour | 0.7 mmHg | Standard Deviation 4.51 |
| Cohort 3: 1000 mg PB2452 (no Ticagrelor) | Change in Systolic Blood Pressure | Change from Baseline - Day 1/0.75 Hour | 2.3 mmHg | Standard Deviation 6.03 |
| Cohort 3: 1000 mg PB2452 (no Ticagrelor) | Change in Systolic Blood Pressure | Change from Baseline - Day 4 | 2.3 mmHg | Standard Deviation 9.07 |
| Cohort 3: 1000 mg PB2452 (no Ticagrelor) | Change in Systolic Blood Pressure | Change from Baseline - Day 3/48 Hour | 0.3 mmHg | Standard Deviation 7.77 |
| Cohort 3: 1000 mg PB2452 (no Ticagrelor) | Change in Systolic Blood Pressure | Change from Baseline - Day 2/24 Hour | 5.7 mmHg | Standard Deviation 7.77 |
| Cohort 3: 1000 mg PB2452 (no Ticagrelor) | Change in Systolic Blood Pressure | Change from Baseline - Day 28 | 1.0 mmHg | Standard Deviation 8.19 |
| Cohort 1 to 3: Placebo | Change in Systolic Blood Pressure | Change from Baseline - Day 2/30 Hour | 4.3 mmHg | Standard Deviation 12.1 |
| Cohort 1 to 3: Placebo | Change in Systolic Blood Pressure | Change from Baseline - Day 2/24 Hour | 3.7 mmHg | Standard Deviation 9.61 |
| Cohort 1 to 3: Placebo | Change in Systolic Blood Pressure | Change from Baseline - Day 1/0.5 Hour | 0.3 mmHg | Standard Deviation 12.86 |
| Cohort 1 to 3: Placebo | Change in Systolic Blood Pressure | Change from Baseline - Day 7 | 7.7 mmHg | Standard Deviation 7.51 |
| Cohort 1 to 3: Placebo | Change in Systolic Blood Pressure | Change from Baseline - Day 1/0.75 Hour | 1.0 mmHg | Standard Deviation 13.23 |
| Cohort 1 to 3: Placebo | Change in Systolic Blood Pressure | Change from Baseline - Day 4 | 6.3 mmHg | Standard Deviation 3.79 |
| Cohort 1 to 3: Placebo | Change in Systolic Blood Pressure | Change from Baseline - Day 1/1 Hour | 2.0 mmHg | Standard Deviation 4.36 |
| Cohort 1 to 3: Placebo | Change in Systolic Blood Pressure | Change from Baseline - Day 28 | 0.7 mmHg | Standard Deviation 8.74 |
| Cohort 1 to 3: Placebo | Change in Systolic Blood Pressure | Change from Baseline - Day 3/48 Hour | 0.3 mmHg | Standard Deviation 3.21 |
| Cohort 1 to 3: Placebo | Change in Systolic Blood Pressure | Change from Baseline - Day 1/2 Hour | -0.3 mmHg | Standard Deviation 5.86 |
| Cohort 1 to 3: Placebo | Change in Systolic Blood Pressure | Change from Baseline - Day 3/42 Hour | -6.0 mmHg | Standard Deviation 4.58 |
| Cohort 1 to 3: Placebo | Change in Systolic Blood Pressure | Change from Baseline - Day 2/36 Hour | -2.7 mmHg | Standard Deviation 5.86 |
| Cohort 1 to 3: Placebo | Change in Systolic Blood Pressure | Change from Baseline - Day 1/4 Hour | -1.3 mmHg | Standard Deviation 8.14 |
| Cohort 1 to 3: Placebo | Change in Systolic Blood Pressure | Change from Baseline - Day 1/8 Hour | -1.3 mmHg | Standard Deviation 18.77 |
| Cohort 4: 1000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Systolic Blood Pressure | Change from Baseline - Day 1/4 Hour | -2.3 mmHg | Standard Deviation 3.5 |
| Cohort 4: 1000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Systolic Blood Pressure | Change from Baseline - Day 1/2 Hour | -2.5 mmHg | Standard Deviation 10.19 |
| Cohort 4: 1000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Systolic Blood Pressure | Change from Baseline - Day 3/42 Hour | -8.2 mmHg | Standard Deviation 8.77 |
| Cohort 4: 1000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Systolic Blood Pressure | Change from Baseline - Day 3/48 Hour | 3.8 mmHg | Standard Deviation 7.78 |
| Cohort 4: 1000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Systolic Blood Pressure | Change from Baseline - Day 2/30 Hour | -3.3 mmHg | Standard Deviation 6.86 |
| Cohort 4: 1000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Systolic Blood Pressure | Change from Baseline - Day 1/1 Hour | 2.7 mmHg | Standard Deviation 5.2 |
| Cohort 4: 1000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Systolic Blood Pressure | Change from Baseline - Day 4 | 1.0 mmHg | Standard Deviation 3.95 |
| Cohort 4: 1000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Systolic Blood Pressure | Change from Baseline - Day 28 | 10.0 mmHg | Standard Deviation 10.55 |
| Cohort 4: 1000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Systolic Blood Pressure | Change from Baseline - Day 1/0.75 Hour | -1.2 mmHg | Standard Deviation 6.24 |
| Cohort 4: 1000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Systolic Blood Pressure | Change from Baseline - Day 7 | 4.8 mmHg | Standard Deviation 5.91 |
| Cohort 4: 1000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Systolic Blood Pressure | Change from Baseline - Day 1/0.5 Hour | -4.8 mmHg | Standard Deviation 4.75 |
| Cohort 4: 1000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Systolic Blood Pressure | Change from Baseline - Day 2/24 Hour | -2.8 mmHg | Standard Deviation 3.71 |
| Cohort 4: 1000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Systolic Blood Pressure | Change from Baseline - Day 2/36 Hour | 3.8 mmHg | Standard Deviation 10.4 |
| Cohort 4: 1000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Systolic Blood Pressure | Change from Baseline - Day 1/8 Hour | -2.2 mmHg | Standard Deviation 11.05 |
| Cohort 5: 3000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Systolic Blood Pressure | Change from Baseline - Day 1/0.5 Hour | -0.3 mmHg | Standard Deviation 2.42 |
| Cohort 5: 3000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Systolic Blood Pressure | Change from Baseline - Day 1/0.75 Hour | 0.2 mmHg | Standard Deviation 3.43 |
| Cohort 5: 3000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Systolic Blood Pressure | Change from Baseline - Day 1/1 Hour | 1.7 mmHg | Standard Deviation 5.61 |
| Cohort 5: 3000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Systolic Blood Pressure | Change from Baseline - Day 1/2 Hour | -1.2 mmHg | Standard Deviation 4.45 |
| Cohort 5: 3000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Systolic Blood Pressure | Change from Baseline - Day 1/4 Hour | -1.5 mmHg | Standard Deviation 4.32 |
| Cohort 5: 3000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Systolic Blood Pressure | Change from Baseline - Day 1/8 Hour | -2.3 mmHg | Standard Deviation 3.67 |
| Cohort 5: 3000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Systolic Blood Pressure | Change from Baseline - Day 2/24 Hour | -1.7 mmHg | Standard Deviation 5.96 |
| Cohort 5: 3000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Systolic Blood Pressure | Change from Baseline - Day 2/30 Hour | -4.2 mmHg | Standard Deviation 11.27 |
| Cohort 5: 3000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Systolic Blood Pressure | Change from Baseline - Day 2/36 Hour | 2.2 mmHg | Standard Deviation 5.23 |
| Cohort 5: 3000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Systolic Blood Pressure | Change from Baseline - Day 3/42 Hour | -3.3 mmHg | Standard Deviation 8.31 |
| Cohort 5: 3000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Systolic Blood Pressure | Change from Baseline - Day 3/48 Hour | 3.7 mmHg | Standard Deviation 7.97 |
| Cohort 5: 3000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Systolic Blood Pressure | Change from Baseline - Day 4 | 2.3 mmHg | Standard Deviation 5.16 |
| Cohort 5: 3000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Systolic Blood Pressure | Change from Baseline - Day 7 | 5.2 mmHg | Standard Deviation 6.68 |
| Cohort 5: 3000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Systolic Blood Pressure | Change from Baseline - Day 28 | 3.5 mmHg | Standard Deviation 9.83 |
| Cohort 6: 9000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Systolic Blood Pressure | Change from Baseline - Day 2/24 Hour | 3.5 mmHg | Standard Deviation 8.46 |
| Cohort 6: 9000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Systolic Blood Pressure | Change from Baseline - Day 7 | 0.2 mmHg | Standard Deviation 4.58 |
| Cohort 6: 9000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Systolic Blood Pressure | Change from Baseline - Day 1/0.75 Hour | 2.8 mmHg | Standard Deviation 2.93 |
| Cohort 6: 9000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Systolic Blood Pressure | Change from Baseline - Day 28 | 6.0 mmHg | Standard Deviation 7.46 |
| Cohort 6: 9000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Systolic Blood Pressure | Change from Baseline - Day 3/48 Hour | 4.3 mmHg | Standard Deviation 8.98 |
| Cohort 6: 9000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Systolic Blood Pressure | Change from Baseline - Day 2/30 Hour | -0.7 mmHg | Standard Deviation 6.22 |
| Cohort 6: 9000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Systolic Blood Pressure | Change from Baseline - Day 1/0.5 Hour | 1.3 mmHg | Standard Deviation 2.73 |
| Cohort 6: 9000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Systolic Blood Pressure | Change from Baseline - Day 1/4 Hour | -1.3 mmHg | Standard Deviation 5.13 |
| Cohort 6: 9000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Systolic Blood Pressure | Change from Baseline - Day 2/36 Hour | -2.8 mmHg | Standard Deviation 8.52 |
| Cohort 6: 9000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Systolic Blood Pressure | Change from Baseline - Day 1/8 Hour | 1.8 mmHg | Standard Deviation 10.3 |
| Cohort 6: 9000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Systolic Blood Pressure | Change from Baseline - Day 1/1 Hour | 1.2 mmHg | Standard Deviation 1.72 |
| Cohort 6: 9000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Systolic Blood Pressure | Change from Baseline - Day 4 | -2.3 mmHg | Standard Deviation 6.98 |
| Cohort 6: 9000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Systolic Blood Pressure | Change from Baseline - Day 1/2 Hour | 0.3 mmHg | Standard Deviation 5.79 |
| Cohort 6: 9000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Systolic Blood Pressure | Change from Baseline - Day 3/42 Hour | -3.0 mmHg | Standard Deviation 6.69 |
| Cohort 4 to 6: Placebo | Change in Systolic Blood Pressure | Change from Baseline - Day 1/4 Hour | -0.8 mmHg | Standard Deviation 7.78 |
| Cohort 4 to 6: Placebo | Change in Systolic Blood Pressure | Change from Baseline - Day 1/8 Hour | 0 mmHg | Standard Deviation 6.32 |
| Cohort 4 to 6: Placebo | Change in Systolic Blood Pressure | Change from Baseline - Day 7 | 1.7 mmHg | Standard Deviation 10.97 |
| Cohort 4 to 6: Placebo | Change in Systolic Blood Pressure | Change from Baseline - Day 1/2 Hour | -1.7 mmHg | Standard Deviation 5.61 |
| Cohort 4 to 6: Placebo | Change in Systolic Blood Pressure | Change from Baseline - Day 1/0.75 Hour | 1.3 mmHg | Standard Deviation 8.12 |
| Cohort 4 to 6: Placebo | Change in Systolic Blood Pressure | Change from Baseline - Day 1/0.5 Hour | -3.0 mmHg | Standard Deviation 6.87 |
| Cohort 4 to 6: Placebo | Change in Systolic Blood Pressure | Change from Baseline - Day 2/24 Hour | 1.8 mmHg | Standard Deviation 8.35 |
| Cohort 4 to 6: Placebo | Change in Systolic Blood Pressure | Change from Baseline - Day 28 | 0.8 mmHg | Standard Deviation 8.38 |
| Cohort 4 to 6: Placebo | Change in Systolic Blood Pressure | Change from Baseline - Day 1/1 Hour | -0.5 mmHg | Standard Deviation 6.44 |
| Cohort 4 to 6: Placebo | Change in Systolic Blood Pressure | Change from Baseline - Day 4 | 6.7 mmHg | Standard Deviation 11.34 |
| Cohort 4 to 6: Placebo | Change in Systolic Blood Pressure | Change from Baseline - Day 3/42 Hour | -3.8 mmHg | Standard Deviation 10.46 |
| Cohort 4 to 6: Placebo | Change in Systolic Blood Pressure | Change from Baseline - Day 3/48 Hour | 1.5 mmHg | Standard Deviation 6.25 |
| Cohort 4 to 6: Placebo | Change in Systolic Blood Pressure | Change from Baseline - Day 2/36 Hour | -0.2 mmHg | Standard Deviation 11.62 |
| Cohort 4 to 6: Placebo | Change in Systolic Blood Pressure | Change from Baseline - Day 2/30 Hour | -4.0 mmHg | Standard Deviation 8.79 |
| Cohort 7: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Systolic Blood Pressure | Change from Baseline - Day 3/42 Hour | -7.7 mmHg | Standard Deviation 7.63 |
| Cohort 7: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Systolic Blood Pressure | Change from Baseline - Day 2/30 Hour | -1.5 mmHg | Standard Deviation 2.26 |
| Cohort 7: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Systolic Blood Pressure | Change from Baseline - Day 4 | 2.7 mmHg | Standard Deviation 10.58 |
| Cohort 7: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Systolic Blood Pressure | Change from Baseline - Day 1/2 Hour | 7.8 mmHg | Standard Deviation 7.44 |
| Cohort 7: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Systolic Blood Pressure | Change from Baseline - Day 1/0.5 Hour | 1.5 mmHg | Standard Deviation 6.61 |
| Cohort 7: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Systolic Blood Pressure | Change from Baseline - Day 2/24 Hour | 1.3 mmHg | Standard Deviation 6.09 |
| Cohort 7: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Systolic Blood Pressure | Change from Baseline - Day 2/36 Hour | 1.0 mmHg | Standard Deviation 4.1 |
| Cohort 7: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Systolic Blood Pressure | Change from Baseline - Day 1/0.75 Hour | 11.5 mmHg | Standard Deviation 12.93 |
| Cohort 7: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Systolic Blood Pressure | Change from Baseline - Day 7 | 1.6 mmHg | Standard Deviation 10.21 |
| Cohort 7: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Systolic Blood Pressure | Change from Baseline - Day 1/8 Hour | -0.8 mmHg | Standard Deviation 6.18 |
| Cohort 7: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Systolic Blood Pressure | Change from Baseline - Day 1/4 Hour | 0.3 mmHg | Standard Deviation 3.14 |
| Cohort 7: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Systolic Blood Pressure | Change from Baseline - Day 1/1 Hour | 8.0 mmHg | Standard Deviation 12.21 |
| Cohort 7: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Systolic Blood Pressure | Change from Baseline - Day 28 | 8.7 mmHg | Standard Deviation 4.93 |
| Cohort 7: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Systolic Blood Pressure | Change from Baseline - Day 3/48 Hour | 1.0 mmHg | Standard Deviation 5.9 |
| Cohort 8: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Systolic Blood Pressure | Change from Baseline - Day 3/48 Hour | -0.5 mmHg | Standard Deviation 11.26 |
| Cohort 8: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Systolic Blood Pressure | Change from Baseline - Day 4 | -5.3 mmHg | Standard Deviation 11.22 |
| Cohort 8: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Systolic Blood Pressure | Change from Baseline - Day 1/0.75 Hour | -1.2 mmHg | Standard Deviation 11.13 |
| Cohort 8: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Systolic Blood Pressure | Change from Baseline - Day 1/4 Hour | -1.7 mmHg | Standard Deviation 13.29 |
| Cohort 8: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Systolic Blood Pressure | Change from Baseline - Day 2/30 Hour | -3.7 mmHg | Standard Deviation 13.91 |
| Cohort 8: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Systolic Blood Pressure | Change from Baseline - Day 2/24 Hour | -7.0 mmHg | Standard Deviation 16.46 |
| Cohort 8: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Systolic Blood Pressure | Change from Baseline - Day 1/0.5 Hour | -0.3 mmHg | Standard Deviation 8.3 |
| Cohort 8: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Systolic Blood Pressure | Change from Baseline - Day 2/36 Hour | -3.0 mmHg | Standard Deviation 11.26 |
| Cohort 8: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Systolic Blood Pressure | Change from Baseline - Day 7 | 3.5 mmHg | Standard Deviation 12.82 |
| Cohort 8: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Systolic Blood Pressure | Change from Baseline - Day 1/2 Hour | -3.2 mmHg | Standard Deviation 10.15 |
| Cohort 8: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Systolic Blood Pressure | Change from Baseline - Day 3/42 Hour | -10.0 mmHg | Standard Deviation 12.96 |
| Cohort 8: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Systolic Blood Pressure | Change from Baseline - Day 1/1 Hour | 0.2 mmHg | Standard Deviation 6.85 |
| Cohort 8: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Systolic Blood Pressure | Change from Baseline - Day 28 | 3.8 mmHg | Standard Deviation 10.19 |
| Cohort 8: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Systolic Blood Pressure | Change from Baseline - Day 1/8 Hour | -4.8 mmHg | Standard Deviation 10.28 |
| Cohort 9: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Systolic Blood Pressure | Change from Baseline - Day 1/0.5 Hour | 4.7 mmHg | Standard Deviation 7.37 |
| Cohort 9: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Systolic Blood Pressure | Change from Baseline - Day 2/24 Hour | 1.7 mmHg | Standard Deviation 12.86 |
| Cohort 9: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Systolic Blood Pressure | Change from Baseline - Day 1/4 Hour | -7.0 mmHg | Standard Deviation 16.52 |
| Cohort 9: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Systolic Blood Pressure | Change from Baseline - Day 2/30 Hour | -0.7 mmHg | Standard Deviation 15.95 |
| Cohort 9: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Systolic Blood Pressure | Change from Baseline - Day 1/2 Hour | -4.7 mmHg | Standard Deviation 2.52 |
| Cohort 9: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Systolic Blood Pressure | Change from Baseline - Day 2/36 Hour | -0.7 mmHg | Standard Deviation 15.14 |
| Cohort 9: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Systolic Blood Pressure | Change from Baseline - Day 3/42 Hour | -2.7 mmHg | Standard Deviation 14.15 |
| Cohort 9: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Systolic Blood Pressure | Change from Baseline - Day 1/1 Hour | 4.7 mmHg | Standard Deviation 7.57 |
| Cohort 9: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Systolic Blood Pressure | Change from Baseline - Day 3/48 Hour | 3.0 mmHg | Standard Deviation 11.53 |
| Cohort 9: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Systolic Blood Pressure | Change from Baseline - Day 1/0.75 Hour | -6.0 mmHg | Standard Deviation 5.29 |
| Cohort 9: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Systolic Blood Pressure | Change from Baseline - Day 28 | -0.3 mmHg | Standard Deviation 17.01 |
| Cohort 9: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Systolic Blood Pressure | Change from Baseline - Day 4 | -4.3 mmHg | Standard Deviation 14.47 |
| Cohort 9: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Systolic Blood Pressure | Change from Baseline - Day 7 | 3.3 mmHg | Standard Deviation 16.62 |
| Cohort 9: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Systolic Blood Pressure | Change from Baseline - Day 1/8 Hour | -11.7 mmHg | Standard Deviation 8.62 |
| Cohort 10: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Systolic Blood Pressure | Change from Baseline - Day 28 | 8.7 mmHg | Standard Deviation 11.04 |
| Cohort 10: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Systolic Blood Pressure | Change from Baseline - Day 2/36 Hour | 1.5 mmHg | Standard Deviation 9.97 |
| Cohort 10: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Systolic Blood Pressure | Change from Baseline - Day 1/2 Hour | 1.0 mmHg | Standard Deviation 2.12 |
| Cohort 10: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Systolic Blood Pressure | Change from Baseline - Day 1/1 Hour | -1.7 mmHg | Standard Deviation 6.65 |
| Cohort 10: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Systolic Blood Pressure | Change from Baseline - Day 3/42 Hour | -7.3 mmHg | Standard Deviation 14.79 |
| Cohort 10: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Systolic Blood Pressure | Change from Baseline - Day 2/30 Hour | -4.0 mmHg | Standard Deviation 6.13 |
| Cohort 10: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Systolic Blood Pressure | Change from Baseline - Day 1/8 Hour | 0.8 mmHg | Standard Deviation 6.62 |
| Cohort 10: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Systolic Blood Pressure | Change from Baseline - Day 3/48 Hour | -2.3 mmHg | Standard Deviation 12.42 |
| Cohort 10: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Systolic Blood Pressure | Change from Baseline - Day 1/0.5 Hour | -1.7 mmHg | Standard Deviation 4.63 |
| Cohort 10: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Systolic Blood Pressure | Change from Baseline - Day 1/4 Hour | 1.2 mmHg | Standard Deviation 6.49 |
| Cohort 10: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Systolic Blood Pressure | Change from Baseline - Day 2/24 Hour | -0.5 mmHg | Standard Deviation 8.6 |
| Cohort 10: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Systolic Blood Pressure | Change from Baseline - Day 1/0.75 Hour | -3.3 mmHg | Standard Deviation 4.8 |
| Cohort 10: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Systolic Blood Pressure | Change from Baseline - Day 7 | 4.5 mmHg | Standard Deviation 8.69 |
| Cohort 10: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Change in Systolic Blood Pressure | Change from Baseline - Day 4 | 1.3 mmHg | Standard Deviation 7.87 |
| Cohort 7 to 10: Placebo | Change in Systolic Blood Pressure | Change from Baseline - Day 2/24 Hour | 1.9 mmHg | Standard Deviation 7.95 |
| Cohort 7 to 10: Placebo | Change in Systolic Blood Pressure | Change from Baseline - Day 4 | -4.4 mmHg | Standard Deviation 12.95 |
| Cohort 7 to 10: Placebo | Change in Systolic Blood Pressure | Change from Baseline - Day 3/48 Hour | -1.1 mmHg | Standard Deviation 12.39 |
| Cohort 7 to 10: Placebo | Change in Systolic Blood Pressure | Change from Baseline - Day 1/0.5 Hour | -0.7 mmHg | Standard Deviation 4.68 |
| Cohort 7 to 10: Placebo | Change in Systolic Blood Pressure | Change from Baseline - Day 3/42 Hour | -7.7 mmHg | Standard Deviation 17.97 |
| Cohort 7 to 10: Placebo | Change in Systolic Blood Pressure | Change from Baseline - Day 1/1 Hour | 1.0 mmHg | Standard Deviation 9.04 |
| Cohort 7 to 10: Placebo | Change in Systolic Blood Pressure | Change from Baseline - Day 2/36 Hour | 1.9 mmHg | Standard Deviation 13.12 |
| Cohort 7 to 10: Placebo | Change in Systolic Blood Pressure | Change from Baseline - Day 7 | 10.1 mmHg | Standard Deviation 13.8 |
| Cohort 7 to 10: Placebo | Change in Systolic Blood Pressure | Change from Baseline - Day 1/2 Hour | 1.0 mmHg | Standard Deviation 6.22 |
| Cohort 7 to 10: Placebo | Change in Systolic Blood Pressure | Change from Baseline - Day 2/30 Hour | -3.3 mmHg | Standard Deviation 14.07 |
| Cohort 7 to 10: Placebo | Change in Systolic Blood Pressure | Change from Baseline - Day 1/8 Hour | -0.7 mmHg | Standard Deviation 11.43 |
| Cohort 7 to 10: Placebo | Change in Systolic Blood Pressure | Change from Baseline - Day 28 | 10.6 mmHg | Standard Deviation 12.91 |
| Cohort 7 to 10: Placebo | Change in Systolic Blood Pressure | Change from Baseline - Day 1/4 Hour | 0.1 mmHg | Standard Deviation 11.35 |
| Cohort 7 to 10: Placebo | Change in Systolic Blood Pressure | Change from Baseline - Day 1/0.75 Hour | -1.4 mmHg | Standard Deviation 7.28 |
Primary
Final Extent Percent of Baseline Platelet Aggregation (Cohorts 7-10)
Effectiveness Of Single Ascending Doses Of PB2452 - IPA (max) induced by 20 µM ADP at each assessment point.
Time frame: Before dosing and at 5 min, 0.25, 0.5, 1, 2, 3, 6, 8, 10, 12, 16, 20, 24, and 48 hours after PB2452 infusion and 5th ticagrelor dose. And at 1, 2, 6, and 12 hours after the Day 2 post-MEDI2452 (PB2452) 6th ticagrelor dose.
Population: PD Population: all participants who received at least 1 dose of ticagrelor and had at least 1 measurable post dose LTA value.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1: 100 mg PB2452 (no Ticagrelor) | Final Extent Percent of Baseline Platelet Aggregation (Cohorts 7-10) | 51.5 percentage | Standard Deviation 26.4 |
| Cohort 2: 300 mg PB2452 (no Ticagrelor) | Final Extent Percent of Baseline Platelet Aggregation (Cohorts 7-10) | 96.1 percentage | Standard Deviation 9.6 |
| Cohort 3: 1000 mg PB2452 (no Ticagrelor) | Final Extent Percent of Baseline Platelet Aggregation (Cohorts 7-10) | 98.2 percentage | Standard Deviation 3.4 |
| Cohort 1 to 3: Placebo | Final Extent Percent of Baseline Platelet Aggregation (Cohorts 7-10) | 100.0 percentage | Standard Deviation 0 |
| Cohort 4: 1000 mg PB2452 (Ticagrelor Pre-Trx) | Final Extent Percent of Baseline Platelet Aggregation (Cohorts 7-10) | 97.3 percentage | Standard Deviation 4.7 |
Primary
Final Extent Percent of Baseline Platelet Aggregation in Cohorts 4-6
Effectiveness Of Single Ascending Doses Of PB2452. IPA \[final extent\] induced by 20 µM adenosine diphosphate (ADP) at each assessment point.
Time frame: Before dosing and at 0.5, 1, 2, 3, 6, 12, 24, and 48 hours after PB2452 infusion and 5th ticagrelor dose.
Population: Pharmacodynamic (PD) Population: all participants who received at least 1 dose of ticagrelor and had at least 1 measurable post dose light transmission aggregometry (LTA) value.~PD samples were not collected for participants in Cohorts 1 to 3; therefore, they were not included in the PD Population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1: 100 mg PB2452 (no Ticagrelor) | Final Extent Percent of Baseline Platelet Aggregation in Cohorts 4-6 | 66.5 percentage | Standard Deviation 30.3 |
| Cohort 2: 300 mg PB2452 (no Ticagrelor) | Final Extent Percent of Baseline Platelet Aggregation in Cohorts 4-6 | 58.4 percentage | Standard Deviation 27 |
| Cohort 3: 1000 mg PB2452 (no Ticagrelor) | Final Extent Percent of Baseline Platelet Aggregation in Cohorts 4-6 | 90.6 percentage | Standard Deviation 9.7 |
| Cohort 1 to 3: Placebo | Final Extent Percent of Baseline Platelet Aggregation in Cohorts 4-6 | 94.6 percentage | Standard Deviation 9.3 |
Primary
Incidence of Clinically Significant 12-Lead Electrocardiogram (ECG) Findings
Number of participants per cohort with clinically significant ECG findings.
Time frame: 60 days - Starting up to 28 days prior to dosing
Population: Safety population: all participants who received any amount of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1: 100 mg PB2452 (no Ticagrelor) | Incidence of Clinically Significant 12-Lead Electrocardiogram (ECG) Findings | 0 Participants |
| Cohort 2: 300 mg PB2452 (no Ticagrelor) | Incidence of Clinically Significant 12-Lead Electrocardiogram (ECG) Findings | 0 Participants |
| Cohort 3: 1000 mg PB2452 (no Ticagrelor) | Incidence of Clinically Significant 12-Lead Electrocardiogram (ECG) Findings | 0 Participants |
| Cohort 1 to 3: Placebo | Incidence of Clinically Significant 12-Lead Electrocardiogram (ECG) Findings | 0 Participants |
| Cohort 4: 1000 mg PB2452 (Ticagrelor Pre-Trx) | Incidence of Clinically Significant 12-Lead Electrocardiogram (ECG) Findings | 0 Participants |
| Cohort 5: 3000 mg PB2452 (Ticagrelor Pre-Trx) | Incidence of Clinically Significant 12-Lead Electrocardiogram (ECG) Findings | 0 Participants |
| Cohort 6: 9000 mg PB2452 (Ticagrelor Pre-Trx) | Incidence of Clinically Significant 12-Lead Electrocardiogram (ECG) Findings | 0 Participants |
| Cohort 4 to 6: Placebo | Incidence of Clinically Significant 12-Lead Electrocardiogram (ECG) Findings | 0 Participants |
| Cohort 7: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Incidence of Clinically Significant 12-Lead Electrocardiogram (ECG) Findings | 0 Participants |
| Cohort 8: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Incidence of Clinically Significant 12-Lead Electrocardiogram (ECG) Findings | 0 Participants |
| Cohort 9: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Incidence of Clinically Significant 12-Lead Electrocardiogram (ECG) Findings | 0 Participants |
| Cohort 10: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Incidence of Clinically Significant 12-Lead Electrocardiogram (ECG) Findings | 0 Participants |
| Cohort 7 to 10: Placebo | Incidence of Clinically Significant 12-Lead Electrocardiogram (ECG) Findings | 0 Participants |
Primary
Incidence of Clinically Significant Cardiac Telemetry Findings
Number of participants per cohort with clinically significant cardiac telemetry findings.
Time frame: 3 Days - Starting 1 day prior to dosing up to 2 days after dosing
Population: Safety population: all participants who received any amount of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1: 100 mg PB2452 (no Ticagrelor) | Incidence of Clinically Significant Cardiac Telemetry Findings | 0 Participants |
| Cohort 2: 300 mg PB2452 (no Ticagrelor) | Incidence of Clinically Significant Cardiac Telemetry Findings | 0 Participants |
| Cohort 3: 1000 mg PB2452 (no Ticagrelor) | Incidence of Clinically Significant Cardiac Telemetry Findings | 0 Participants |
| Cohort 1 to 3: Placebo | Incidence of Clinically Significant Cardiac Telemetry Findings | 0 Participants |
| Cohort 4: 1000 mg PB2452 (Ticagrelor Pre-Trx) | Incidence of Clinically Significant Cardiac Telemetry Findings | 0 Participants |
| Cohort 5: 3000 mg PB2452 (Ticagrelor Pre-Trx) | Incidence of Clinically Significant Cardiac Telemetry Findings | 0 Participants |
| Cohort 6: 9000 mg PB2452 (Ticagrelor Pre-Trx) | Incidence of Clinically Significant Cardiac Telemetry Findings | 0 Participants |
| Cohort 4 to 6: Placebo | Incidence of Clinically Significant Cardiac Telemetry Findings | 0 Participants |
| Cohort 7: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Incidence of Clinically Significant Cardiac Telemetry Findings | 0 Participants |
| Cohort 8: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Incidence of Clinically Significant Cardiac Telemetry Findings | 0 Participants |
| Cohort 9: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Incidence of Clinically Significant Cardiac Telemetry Findings | 0 Participants |
| Cohort 10: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Incidence of Clinically Significant Cardiac Telemetry Findings | 0 Participants |
| Cohort 7 to 10: Placebo | Incidence of Clinically Significant Cardiac Telemetry Findings | 0 Participants |
Primary
Maximal Actual Platelet Aggregation (APA(Max)) (Cohorts 4-6)
Effectiveness Of Single Ascending Doses Of PB2452 - Inhibition of maximal platelet aggregation.
Time frame: Before dosing and at 0.5, 1, 2, 3, 6, 12, 24, and 48 hours after PB2452 infusion and 5th ticagrelor dose. And at 1, 2, 6, and 12 hours after the Day 2 post-MEDI2452 (PB2452) 6th ticagrelor dose (Cohorts 8 and 9 Only).
Population: PD Population: all participants who received at least 1 dose of ticagrelor and had at least 1 measurable post dose LTA value.~PD samples were not collected for participants in Cohorts 1 to 3, therefore, they were not included in the PD Population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1: 100 mg PB2452 (no Ticagrelor) | Maximal Actual Platelet Aggregation (APA(Max)) (Cohorts 4-6) | 61.7 percentage | Standard Deviation 13.3 |
| Cohort 2: 300 mg PB2452 (no Ticagrelor) | Maximal Actual Platelet Aggregation (APA(Max)) (Cohorts 4-6) | 59.5 percentage | Standard Deviation 15.1 |
| Cohort 3: 1000 mg PB2452 (no Ticagrelor) | Maximal Actual Platelet Aggregation (APA(Max)) (Cohorts 4-6) | 77.5 percentage | Standard Deviation 8.4 |
| Cohort 1 to 3: Placebo | Maximal Actual Platelet Aggregation (APA(Max)) (Cohorts 4-6) | 83.7 percentage | Standard Deviation 13.8 |
Primary
Maximal Actual Platelet Aggregation (APA(Max)) (Cohorts 7-10)
Effectiveness Of Single Ascending Doses Of PB2452 - Inhibition of maximal platelet aggregation.
Time frame: Before dosing and at 5 min, 0.25, 0.5, 1, 2, 3, 6, 8, 10, 12, 16, 20, 24, and 48 hours after PB2452 infusion and 5th ticagrelor dose. And at 1, 2, 6, and 12 hours after the Day 2 post-MEDI2452 (PB2452) 6th ticagrelor dose
Population: PD Population: all participants who received at least 1 dose of ticagrelor and had at least 1 measurable post dose LTA value.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1: 100 mg PB2452 (no Ticagrelor) | Maximal Actual Platelet Aggregation (APA(Max)) (Cohorts 7-10) | 51.9 percentage | Standard Deviation 17.8 |
| Cohort 2: 300 mg PB2452 (no Ticagrelor) | Maximal Actual Platelet Aggregation (APA(Max)) (Cohorts 7-10) | 84.8 percentage | Standard Deviation 9.3 |
| Cohort 3: 1000 mg PB2452 (no Ticagrelor) | Maximal Actual Platelet Aggregation (APA(Max)) (Cohorts 7-10) | 86.0 percentage | Standard Deviation 5.7 |
| Cohort 1 to 3: Placebo | Maximal Actual Platelet Aggregation (APA(Max)) (Cohorts 7-10) | 94.7 percentage | Standard Deviation 1.2 |
| Cohort 4: 1000 mg PB2452 (Ticagrelor Pre-Trx) | Maximal Actual Platelet Aggregation (APA(Max)) (Cohorts 7-10) | 86.0 percentage | Standard Deviation 2.8 |
Primary
Maximal Percent of Baseline Platelet Aggregation (PA(Max)) (Cohorts 7-10)
Effectiveness Of Single Ascending Doses Of PB2452 - IPA (max) induced by 20 µM ADP at each assessment point.
Time frame: Before dosing and at 5 min, 0.25, 0.5, 1, 2, 3, 6, 8, 10, 12, 16, 20, 24, and 48 hours after PB2452 infusion and 5th ticagrelor dose. And at 1, 2, 6, and 12 hours after the Day 2 post-MEDI2452 (PB2452) 6th ticagrelor dose.
Population: PD Population: all participants who received at least 1 dose of ticagrelor and had at least 1 measurable post dose LTA value.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1: 100 mg PB2452 (no Ticagrelor) | Maximal Percent of Baseline Platelet Aggregation (PA(Max)) (Cohorts 7-10) | 62.2 percentage | Standard Deviation 20.1 |
| Cohort 2: 300 mg PB2452 (no Ticagrelor) | Maximal Percent of Baseline Platelet Aggregation (PA(Max)) (Cohorts 7-10) | 98.9 percentage | Standard Deviation 2.8 |
| Cohort 3: 1000 mg PB2452 (no Ticagrelor) | Maximal Percent of Baseline Platelet Aggregation (PA(Max)) (Cohorts 7-10) | 98.6 percentage | Standard Deviation 3 |
| Cohort 1 to 3: Placebo | Maximal Percent of Baseline Platelet Aggregation (PA(Max)) (Cohorts 7-10) | 100.0 percentage | Standard Deviation 0 |
| Cohort 4: 1000 mg PB2452 (Ticagrelor Pre-Trx) | Maximal Percent of Baseline Platelet Aggregation (PA(Max)) (Cohorts 7-10) | 98.7 percentage | Standard Deviation 2.1 |
Primary
Maximal Percent of Baseline Platelet Aggregation (PA(Max)) in Cohorts 4-6
Effectiveness Of Single Ascending Doses Of PB2452. IPA \[maximum (max)\] induced by 20 µM adenosine diphosphate (ADP) at each assessment point.
Time frame: Before dosing and at 0.5, 1, 2, 3, 6, 12, 24, and 48 hours after PB2452 infusion and 5th ticagrelor dose.
Population: Pharmacodynamic (PD) Population: all participants who received at least 1 dose of ticagrelor and had at least 1 measurable post dose light transmission aggregometry (LTA) value.~PD samples were not collected for participants in Cohorts 1 to 3; therefore, they were not included in the PD Population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1: 100 mg PB2452 (no Ticagrelor) | Maximal Percent of Baseline Platelet Aggregation (PA(Max)) in Cohorts 4-6 | 77.1 percentage | Standard Deviation 14.5 |
| Cohort 2: 300 mg PB2452 (no Ticagrelor) | Maximal Percent of Baseline Platelet Aggregation (PA(Max)) in Cohorts 4-6 | 67.9 percentage | Standard Deviation 18.3 |
| Cohort 3: 1000 mg PB2452 (no Ticagrelor) | Maximal Percent of Baseline Platelet Aggregation (PA(Max)) in Cohorts 4-6 | 92.6 percentage | Standard Deviation 9.2 |
| Cohort 1 to 3: Placebo | Maximal Percent of Baseline Platelet Aggregation (PA(Max)) in Cohorts 4-6 | 97.3 percentage | Standard Deviation 3.9 |
Primary
Number of Participants With Adverse Events (AEs)
An AE is defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug-related.
Time frame: Day -3 (Cohorts 4 through 10) or Day -1 (Cohorts 1 through 3) until Day 28
Population: Safety population: all participants who received any amount of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1: 100 mg PB2452 (no Ticagrelor) | Number of Participants With Adverse Events (AEs) | Any dose limiting toxicity | 0 Participants |
| Cohort 1: 100 mg PB2452 (no Ticagrelor) | Number of Participants With Adverse Events (AEs) | Any SAE | 0 Participants |
| Cohort 1: 100 mg PB2452 (no Ticagrelor) | Number of Participants With Adverse Events (AEs) | Any severe TEAE | 0 Participants |
| Cohort 1: 100 mg PB2452 (no Ticagrelor) | Number of Participants With Adverse Events (AEs) | Any AE leading to early study discontinuation | 0 Participants |
| Cohort 1: 100 mg PB2452 (no Ticagrelor) | Number of Participants With Adverse Events (AEs) | Any death | 0 Participants |
| Cohort 1: 100 mg PB2452 (no Ticagrelor) | Number of Participants With Adverse Events (AEs) | Any Treatment-Emergent AE | 0 Participants |
| Cohort 1: 100 mg PB2452 (no Ticagrelor) | Number of Participants With Adverse Events (AEs) | Any study-drug-related TEAE | 0 Participants |
| Cohort 2: 300 mg PB2452 (no Ticagrelor) | Number of Participants With Adverse Events (AEs) | Any Treatment-Emergent AE | 0 Participants |
| Cohort 2: 300 mg PB2452 (no Ticagrelor) | Number of Participants With Adverse Events (AEs) | Any severe TEAE | 0 Participants |
| Cohort 2: 300 mg PB2452 (no Ticagrelor) | Number of Participants With Adverse Events (AEs) | Any SAE | 0 Participants |
| Cohort 2: 300 mg PB2452 (no Ticagrelor) | Number of Participants With Adverse Events (AEs) | Any death | 0 Participants |
| Cohort 2: 300 mg PB2452 (no Ticagrelor) | Number of Participants With Adverse Events (AEs) | Any dose limiting toxicity | 0 Participants |
| Cohort 2: 300 mg PB2452 (no Ticagrelor) | Number of Participants With Adverse Events (AEs) | Any study-drug-related TEAE | 0 Participants |
| Cohort 2: 300 mg PB2452 (no Ticagrelor) | Number of Participants With Adverse Events (AEs) | Any AE leading to early study discontinuation | 0 Participants |
| Cohort 3: 1000 mg PB2452 (no Ticagrelor) | Number of Participants With Adverse Events (AEs) | Any Treatment-Emergent AE | 1 Participants |
| Cohort 3: 1000 mg PB2452 (no Ticagrelor) | Number of Participants With Adverse Events (AEs) | Any death | 0 Participants |
| Cohort 3: 1000 mg PB2452 (no Ticagrelor) | Number of Participants With Adverse Events (AEs) | Any SAE | 0 Participants |
| Cohort 3: 1000 mg PB2452 (no Ticagrelor) | Number of Participants With Adverse Events (AEs) | Any severe TEAE | 0 Participants |
| Cohort 3: 1000 mg PB2452 (no Ticagrelor) | Number of Participants With Adverse Events (AEs) | Any AE leading to early study discontinuation | 0 Participants |
| Cohort 3: 1000 mg PB2452 (no Ticagrelor) | Number of Participants With Adverse Events (AEs) | Any study-drug-related TEAE | 0 Participants |
| Cohort 3: 1000 mg PB2452 (no Ticagrelor) | Number of Participants With Adverse Events (AEs) | Any dose limiting toxicity | 0 Participants |
| Cohort 1 to 3: Placebo | Number of Participants With Adverse Events (AEs) | Any dose limiting toxicity | 0 Participants |
| Cohort 1 to 3: Placebo | Number of Participants With Adverse Events (AEs) | Any SAE | 0 Participants |
| Cohort 1 to 3: Placebo | Number of Participants With Adverse Events (AEs) | Any study-drug-related TEAE | 0 Participants |
| Cohort 1 to 3: Placebo | Number of Participants With Adverse Events (AEs) | Any death | 0 Participants |
| Cohort 1 to 3: Placebo | Number of Participants With Adverse Events (AEs) | Any severe TEAE | 0 Participants |
| Cohort 1 to 3: Placebo | Number of Participants With Adverse Events (AEs) | Any AE leading to early study discontinuation | 0 Participants |
| Cohort 1 to 3: Placebo | Number of Participants With Adverse Events (AEs) | Any Treatment-Emergent AE | 1 Participants |
| Cohort 4: 1000 mg PB2452 (Ticagrelor Pre-Trx) | Number of Participants With Adverse Events (AEs) | Any severe TEAE | 1 Participants |
| Cohort 4: 1000 mg PB2452 (Ticagrelor Pre-Trx) | Number of Participants With Adverse Events (AEs) | Any Treatment-Emergent AE | 3 Participants |
| Cohort 4: 1000 mg PB2452 (Ticagrelor Pre-Trx) | Number of Participants With Adverse Events (AEs) | Any death | 0 Participants |
| Cohort 4: 1000 mg PB2452 (Ticagrelor Pre-Trx) | Number of Participants With Adverse Events (AEs) | Any dose limiting toxicity | 0 Participants |
| Cohort 4: 1000 mg PB2452 (Ticagrelor Pre-Trx) | Number of Participants With Adverse Events (AEs) | Any AE leading to early study discontinuation | 0 Participants |
| Cohort 4: 1000 mg PB2452 (Ticagrelor Pre-Trx) | Number of Participants With Adverse Events (AEs) | Any study-drug-related TEAE | 0 Participants |
| Cohort 4: 1000 mg PB2452 (Ticagrelor Pre-Trx) | Number of Participants With Adverse Events (AEs) | Any SAE | 1 Participants |
| Cohort 5: 3000 mg PB2452 (Ticagrelor Pre-Trx) | Number of Participants With Adverse Events (AEs) | Any study-drug-related TEAE | 0 Participants |
| Cohort 5: 3000 mg PB2452 (Ticagrelor Pre-Trx) | Number of Participants With Adverse Events (AEs) | Any death | 0 Participants |
| Cohort 5: 3000 mg PB2452 (Ticagrelor Pre-Trx) | Number of Participants With Adverse Events (AEs) | Any Treatment-Emergent AE | 0 Participants |
| Cohort 5: 3000 mg PB2452 (Ticagrelor Pre-Trx) | Number of Participants With Adverse Events (AEs) | Any severe TEAE | 0 Participants |
| Cohort 5: 3000 mg PB2452 (Ticagrelor Pre-Trx) | Number of Participants With Adverse Events (AEs) | Any SAE | 0 Participants |
| Cohort 5: 3000 mg PB2452 (Ticagrelor Pre-Trx) | Number of Participants With Adverse Events (AEs) | Any AE leading to early study discontinuation | 0 Participants |
| Cohort 5: 3000 mg PB2452 (Ticagrelor Pre-Trx) | Number of Participants With Adverse Events (AEs) | Any dose limiting toxicity | 0 Participants |
| Cohort 6: 9000 mg PB2452 (Ticagrelor Pre-Trx) | Number of Participants With Adverse Events (AEs) | Any AE leading to early study discontinuation | 0 Participants |
| Cohort 6: 9000 mg PB2452 (Ticagrelor Pre-Trx) | Number of Participants With Adverse Events (AEs) | Any study-drug-related TEAE | 0 Participants |
| Cohort 6: 9000 mg PB2452 (Ticagrelor Pre-Trx) | Number of Participants With Adverse Events (AEs) | Any severe TEAE | 0 Participants |
| Cohort 6: 9000 mg PB2452 (Ticagrelor Pre-Trx) | Number of Participants With Adverse Events (AEs) | Any death | 0 Participants |
| Cohort 6: 9000 mg PB2452 (Ticagrelor Pre-Trx) | Number of Participants With Adverse Events (AEs) | Any Treatment-Emergent AE | 6 Participants |
| Cohort 6: 9000 mg PB2452 (Ticagrelor Pre-Trx) | Number of Participants With Adverse Events (AEs) | Any SAE | 0 Participants |
| Cohort 6: 9000 mg PB2452 (Ticagrelor Pre-Trx) | Number of Participants With Adverse Events (AEs) | Any dose limiting toxicity | 0 Participants |
| Cohort 4 to 6: Placebo | Number of Participants With Adverse Events (AEs) | Any Treatment-Emergent AE | 1 Participants |
| Cohort 4 to 6: Placebo | Number of Participants With Adverse Events (AEs) | Any SAE | 0 Participants |
| Cohort 4 to 6: Placebo | Number of Participants With Adverse Events (AEs) | Any study-drug-related TEAE | 0 Participants |
| Cohort 4 to 6: Placebo | Number of Participants With Adverse Events (AEs) | Any severe TEAE | 0 Participants |
| Cohort 4 to 6: Placebo | Number of Participants With Adverse Events (AEs) | Any death | 0 Participants |
| Cohort 4 to 6: Placebo | Number of Participants With Adverse Events (AEs) | Any dose limiting toxicity | 0 Participants |
| Cohort 4 to 6: Placebo | Number of Participants With Adverse Events (AEs) | Any AE leading to early study discontinuation | 0 Participants |
| Cohort 7: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Number of Participants With Adverse Events (AEs) | Any study-drug-related TEAE | 0 Participants |
| Cohort 7: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Number of Participants With Adverse Events (AEs) | Any severe TEAE | 0 Participants |
| Cohort 7: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Number of Participants With Adverse Events (AEs) | Any SAE | 0 Participants |
| Cohort 7: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Number of Participants With Adverse Events (AEs) | Any AE leading to early study discontinuation | 0 Participants |
| Cohort 7: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Number of Participants With Adverse Events (AEs) | Any Treatment-Emergent AE | 2 Participants |
| Cohort 7: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Number of Participants With Adverse Events (AEs) | Any dose limiting toxicity | 0 Participants |
| Cohort 7: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Number of Participants With Adverse Events (AEs) | Any death | 0 Participants |
| Cohort 8: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Number of Participants With Adverse Events (AEs) | Any severe TEAE | 0 Participants |
| Cohort 8: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Number of Participants With Adverse Events (AEs) | Any dose limiting toxicity | 0 Participants |
| Cohort 8: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Number of Participants With Adverse Events (AEs) | Any Treatment-Emergent AE | 2 Participants |
| Cohort 8: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Number of Participants With Adverse Events (AEs) | Any AE leading to early study discontinuation | 0 Participants |
| Cohort 8: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Number of Participants With Adverse Events (AEs) | Any death | 0 Participants |
| Cohort 8: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Number of Participants With Adverse Events (AEs) | Any SAE | 0 Participants |
| Cohort 8: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Number of Participants With Adverse Events (AEs) | Any study-drug-related TEAE | 0 Participants |
| Cohort 9: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Number of Participants With Adverse Events (AEs) | Any death | 0 Participants |
| Cohort 9: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Number of Participants With Adverse Events (AEs) | Any AE leading to early study discontinuation | 0 Participants |
| Cohort 9: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Number of Participants With Adverse Events (AEs) | Any study-drug-related TEAE | 0 Participants |
| Cohort 9: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Number of Participants With Adverse Events (AEs) | Any Treatment-Emergent AE | 1 Participants |
| Cohort 9: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Number of Participants With Adverse Events (AEs) | Any SAE | 0 Participants |
| Cohort 9: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Number of Participants With Adverse Events (AEs) | Any severe TEAE | 0 Participants |
| Cohort 9: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Number of Participants With Adverse Events (AEs) | Any dose limiting toxicity | 0 Participants |
| Cohort 10: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Number of Participants With Adverse Events (AEs) | Any death | 0 Participants |
| Cohort 10: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Number of Participants With Adverse Events (AEs) | Any severe TEAE | 0 Participants |
| Cohort 10: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Number of Participants With Adverse Events (AEs) | Any dose limiting toxicity | 0 Participants |
| Cohort 10: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Number of Participants With Adverse Events (AEs) | Any study-drug-related TEAE | 0 Participants |
| Cohort 10: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Number of Participants With Adverse Events (AEs) | Any Treatment-Emergent AE | 2 Participants |
| Cohort 10: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Number of Participants With Adverse Events (AEs) | Any AE leading to early study discontinuation | 0 Participants |
| Cohort 10: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Number of Participants With Adverse Events (AEs) | Any SAE | 0 Participants |
| Cohort 7 to 10: Placebo | Number of Participants With Adverse Events (AEs) | Any death | 0 Participants |
| Cohort 7 to 10: Placebo | Number of Participants With Adverse Events (AEs) | Any SAE | 0 Participants |
| Cohort 7 to 10: Placebo | Number of Participants With Adverse Events (AEs) | Any AE leading to early study discontinuation | 0 Participants |
| Cohort 7 to 10: Placebo | Number of Participants With Adverse Events (AEs) | Any Treatment-Emergent AE | 0 Participants |
| Cohort 7 to 10: Placebo | Number of Participants With Adverse Events (AEs) | Any study-drug-related TEAE | 0 Participants |
| Cohort 7 to 10: Placebo | Number of Participants With Adverse Events (AEs) | Any dose limiting toxicity | 0 Participants |
| Cohort 7 to 10: Placebo | Number of Participants With Adverse Events (AEs) | Any severe TEAE | 0 Participants |
Primary
Number of Participants With Clinically Significant Laboratory Abnormalities
Number of participants with clinically significant abnormal laboratory findings for hematology, coagulation, serum chemistry, urinalysis and drug tests.
Time frame: 30 Day - Starting day of dosing
Population: Safety population: all participants who received any amount of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1: 100 mg PB2452 (no Ticagrelor) | Number of Participants With Clinically Significant Laboratory Abnormalities | 0 Participants |
| Cohort 2: 300 mg PB2452 (no Ticagrelor) | Number of Participants With Clinically Significant Laboratory Abnormalities | 0 Participants |
| Cohort 3: 1000 mg PB2452 (no Ticagrelor) | Number of Participants With Clinically Significant Laboratory Abnormalities | 0 Participants |
| Cohort 1 to 3: Placebo | Number of Participants With Clinically Significant Laboratory Abnormalities | 0 Participants |
| Cohort 4: 1000 mg PB2452 (Ticagrelor Pre-Trx) | Number of Participants With Clinically Significant Laboratory Abnormalities | 0 Participants |
| Cohort 5: 3000 mg PB2452 (Ticagrelor Pre-Trx) | Number of Participants With Clinically Significant Laboratory Abnormalities | 0 Participants |
| Cohort 6: 9000 mg PB2452 (Ticagrelor Pre-Trx) | Number of Participants With Clinically Significant Laboratory Abnormalities | 0 Participants |
| Cohort 4 to 6: Placebo | Number of Participants With Clinically Significant Laboratory Abnormalities | 0 Participants |
| Cohort 7: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Number of Participants With Clinically Significant Laboratory Abnormalities | 0 Participants |
| Cohort 8: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Number of Participants With Clinically Significant Laboratory Abnormalities | 0 Participants |
| Cohort 9: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Number of Participants With Clinically Significant Laboratory Abnormalities | 0 Participants |
| Cohort 10: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Number of Participants With Clinically Significant Laboratory Abnormalities | 0 Participants |
| Cohort 7 to 10: Placebo | Number of Participants With Clinically Significant Laboratory Abnormalities | 0 Participants |
Primary
Participants Experiencing Anti-drug Antibodies (ADAs)
Incidence of Immunogenicity.
Time frame: Day -3, Day -1, Day 7, and Day 28
Population: Safety population: all participants who received any amount of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1: 100 mg PB2452 (no Ticagrelor) | Participants Experiencing Anti-drug Antibodies (ADAs) | Day 7 | 1 Participants |
| Cohort 1: 100 mg PB2452 (no Ticagrelor) | Participants Experiencing Anti-drug Antibodies (ADAs) | Day -1 | 1 Participants |
| Cohort 1: 100 mg PB2452 (no Ticagrelor) | Participants Experiencing Anti-drug Antibodies (ADAs) | Day 28 | 1 Participants |
| Cohort 1: 100 mg PB2452 (no Ticagrelor) | Participants Experiencing Anti-drug Antibodies (ADAs) | Day -3 | NA Participants |
| Cohort 2: 300 mg PB2452 (no Ticagrelor) | Participants Experiencing Anti-drug Antibodies (ADAs) | Day -3 | NA Participants |
| Cohort 2: 300 mg PB2452 (no Ticagrelor) | Participants Experiencing Anti-drug Antibodies (ADAs) | Day 7 | 0 Participants |
| Cohort 2: 300 mg PB2452 (no Ticagrelor) | Participants Experiencing Anti-drug Antibodies (ADAs) | Day -1 | 0 Participants |
| Cohort 2: 300 mg PB2452 (no Ticagrelor) | Participants Experiencing Anti-drug Antibodies (ADAs) | Day 28 | 0 Participants |
| Cohort 3: 1000 mg PB2452 (no Ticagrelor) | Participants Experiencing Anti-drug Antibodies (ADAs) | Day 7 | 0 Participants |
| Cohort 3: 1000 mg PB2452 (no Ticagrelor) | Participants Experiencing Anti-drug Antibodies (ADAs) | Day 28 | 1 Participants |
| Cohort 3: 1000 mg PB2452 (no Ticagrelor) | Participants Experiencing Anti-drug Antibodies (ADAs) | Day -1 | 0 Participants |
| Cohort 3: 1000 mg PB2452 (no Ticagrelor) | Participants Experiencing Anti-drug Antibodies (ADAs) | Day -3 | NA Participants |
| Cohort 1 to 3: Placebo | Participants Experiencing Anti-drug Antibodies (ADAs) | Day 28 | 0 Participants |
| Cohort 1 to 3: Placebo | Participants Experiencing Anti-drug Antibodies (ADAs) | Day -3 | NA Participants |
| Cohort 1 to 3: Placebo | Participants Experiencing Anti-drug Antibodies (ADAs) | Day -1 | 1 Participants |
| Cohort 1 to 3: Placebo | Participants Experiencing Anti-drug Antibodies (ADAs) | Day 7 | 1 Participants |
| Cohort 4: 1000 mg PB2452 (Ticagrelor Pre-Trx) | Participants Experiencing Anti-drug Antibodies (ADAs) | Day 28 | 2 Participants |
| Cohort 4: 1000 mg PB2452 (Ticagrelor Pre-Trx) | Participants Experiencing Anti-drug Antibodies (ADAs) | Day -3 | 1 Participants |
| Cohort 4: 1000 mg PB2452 (Ticagrelor Pre-Trx) | Participants Experiencing Anti-drug Antibodies (ADAs) | Day 7 | 1 Participants |
| Cohort 4: 1000 mg PB2452 (Ticagrelor Pre-Trx) | Participants Experiencing Anti-drug Antibodies (ADAs) | Day -1 | NA Participants |
| Cohort 5: 3000 mg PB2452 (Ticagrelor Pre-Trx) | Participants Experiencing Anti-drug Antibodies (ADAs) | Day -1 | NA Participants |
| Cohort 5: 3000 mg PB2452 (Ticagrelor Pre-Trx) | Participants Experiencing Anti-drug Antibodies (ADAs) | Day -3 | 2 Participants |
| Cohort 5: 3000 mg PB2452 (Ticagrelor Pre-Trx) | Participants Experiencing Anti-drug Antibodies (ADAs) | Day 28 | 2 Participants |
| Cohort 5: 3000 mg PB2452 (Ticagrelor Pre-Trx) | Participants Experiencing Anti-drug Antibodies (ADAs) | Day 7 | 1 Participants |
| Cohort 6: 9000 mg PB2452 (Ticagrelor Pre-Trx) | Participants Experiencing Anti-drug Antibodies (ADAs) | Day 7 | 1 Participants |
| Cohort 6: 9000 mg PB2452 (Ticagrelor Pre-Trx) | Participants Experiencing Anti-drug Antibodies (ADAs) | Day -1 | NA Participants |
| Cohort 6: 9000 mg PB2452 (Ticagrelor Pre-Trx) | Participants Experiencing Anti-drug Antibodies (ADAs) | Day 28 | 1 Participants |
| Cohort 6: 9000 mg PB2452 (Ticagrelor Pre-Trx) | Participants Experiencing Anti-drug Antibodies (ADAs) | Day -3 | 0 Participants |
| Cohort 4 to 6: Placebo | Participants Experiencing Anti-drug Antibodies (ADAs) | Day 28 | 1 Participants |
| Cohort 4 to 6: Placebo | Participants Experiencing Anti-drug Antibodies (ADAs) | Day -3 | 1 Participants |
| Cohort 4 to 6: Placebo | Participants Experiencing Anti-drug Antibodies (ADAs) | Day -1 | NA Participants |
| Cohort 4 to 6: Placebo | Participants Experiencing Anti-drug Antibodies (ADAs) | Day 7 | 2 Participants |
| Cohort 7: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Participants Experiencing Anti-drug Antibodies (ADAs) | Day -1 | NA Participants |
| Cohort 7: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Participants Experiencing Anti-drug Antibodies (ADAs) | Day -3 | 2 Participants |
| Cohort 7: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Participants Experiencing Anti-drug Antibodies (ADAs) | Day 7 | 1 Participants |
| Cohort 7: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Participants Experiencing Anti-drug Antibodies (ADAs) | Day 28 | 5 Participants |
| Cohort 8: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Participants Experiencing Anti-drug Antibodies (ADAs) | Day 28 | 4 Participants |
| Cohort 8: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Participants Experiencing Anti-drug Antibodies (ADAs) | Day -1 | NA Participants |
| Cohort 8: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Participants Experiencing Anti-drug Antibodies (ADAs) | Day 7 | 4 Participants |
| Cohort 8: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Participants Experiencing Anti-drug Antibodies (ADAs) | Day -3 | 4 Participants |
| Cohort 9: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Participants Experiencing Anti-drug Antibodies (ADAs) | Day 7 | 0 Participants |
| Cohort 9: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Participants Experiencing Anti-drug Antibodies (ADAs) | Day 28 | 0 Participants |
| Cohort 9: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Participants Experiencing Anti-drug Antibodies (ADAs) | Day -1 | NA Participants |
| Cohort 9: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Participants Experiencing Anti-drug Antibodies (ADAs) | Day -3 | 0 Participants |
| Cohort 10: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Participants Experiencing Anti-drug Antibodies (ADAs) | Day -1 | NA Participants |
| Cohort 10: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Participants Experiencing Anti-drug Antibodies (ADAs) | Day 7 | 2 Participants |
| Cohort 10: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Participants Experiencing Anti-drug Antibodies (ADAs) | Day 28 | 5 Participants |
| Cohort 10: 18000 mg PB2452 (Ticagrelor Pre-Trx) | Participants Experiencing Anti-drug Antibodies (ADAs) | Day -3 | 5 Participants |
| Cohort 7 to 10: Placebo | Participants Experiencing Anti-drug Antibodies (ADAs) | Day -3 | 0 Participants |
| Cohort 7 to 10: Placebo | Participants Experiencing Anti-drug Antibodies (ADAs) | Day 28 | 0 Participants |
| Cohort 7 to 10: Placebo | Participants Experiencing Anti-drug Antibodies (ADAs) | Day 7 | 0 Participants |
| Cohort 7 to 10: Placebo | Participants Experiencing Anti-drug Antibodies (ADAs) | Day -1 | NA Participants |
| All PB2452 | Participants Experiencing Anti-drug Antibodies (ADAs) | Day -3 | 14 Participants |
| All PB2452 | Participants Experiencing Anti-drug Antibodies (ADAs) | Day -1 | 1 Participants |
| All PB2452 | Participants Experiencing Anti-drug Antibodies (ADAs) | Day 7 | 11 Participants |
| All PB2452 | Participants Experiencing Anti-drug Antibodies (ADAs) | Day 28 | 21 Participants |
| All Placebo | Participants Experiencing Anti-drug Antibodies (ADAs) | Day -1 | 1 Participants |
| All Placebo | Participants Experiencing Anti-drug Antibodies (ADAs) | Day 28 | 1 Participants |
| All Placebo | Participants Experiencing Anti-drug Antibodies (ADAs) | Day 7 | 3 Participants |
| All Placebo | Participants Experiencing Anti-drug Antibodies (ADAs) | Day -3 | 1 Participants |
Primary
Time to Maximum Platelet Aggregation (TPA(Max)) (Cohorts 4-6)
Effectiveness Of Single Ascending Doses Of PB2452 - Time to IPAmax.
Time frame: Before dosing and at 0.5, 1, 2, 3, 6, 12, 24, and 48 hours after PB2452 infusion and 5th ticagrelor dose.
Population: PD Population: all participants who received at least 1 dose of ticagrelor and had at least 1 measurable post dose LTA value.~PD samples were not collected for participants in Cohorts 1 to 3, therefore, they were not included in the PD Population.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1: 100 mg PB2452 (no Ticagrelor) | Time to Maximum Platelet Aggregation (TPA(Max)) (Cohorts 4-6) | 48.00 hours |
| Cohort 2: 300 mg PB2452 (no Ticagrelor) | Time to Maximum Platelet Aggregation (TPA(Max)) (Cohorts 4-6) | 48.00 hours |
| Cohort 3: 1000 mg PB2452 (no Ticagrelor) | Time to Maximum Platelet Aggregation (TPA(Max)) (Cohorts 4-6) | 0.51 hours |
| Cohort 1 to 3: Placebo | Time to Maximum Platelet Aggregation (TPA(Max)) (Cohorts 4-6) | 0.82 hours |
Primary
Time to Maximum Platelet Aggregation (TPA(Max))(Cohorts 7-10)
Effectiveness Of Single Ascending Doses Of PB2452 - Time to IPAmax
Time frame: Before dosing and at 5 min, 0.25, 0.5, 1, 2, 3, 6, 8, 10, 12, 16, 20, 24, and 48 hours after PB2452 infusion and 5th ticagrelor dose. And at 1, 2, 6, and 12 hours after the Day 2 post-MEDI2452 (PB2452) 6th ticagrelor dose.
Population: PD Population: all participants who received at least 1 dose of ticagrelor and had at least 1 measurable post dose LTA value.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1: 100 mg PB2452 (no Ticagrelor) | Time to Maximum Platelet Aggregation (TPA(Max))(Cohorts 7-10) | 48.00 hours |
| Cohort 2: 300 mg PB2452 (no Ticagrelor) | Time to Maximum Platelet Aggregation (TPA(Max))(Cohorts 7-10) | 6.00 hours |
| Cohort 3: 1000 mg PB2452 (no Ticagrelor) | Time to Maximum Platelet Aggregation (TPA(Max))(Cohorts 7-10) | 5.50 hours |
| Cohort 1 to 3: Placebo | Time to Maximum Platelet Aggregation (TPA(Max))(Cohorts 7-10) | 6.00 hours |
| Cohort 4: 1000 mg PB2452 (Ticagrelor Pre-Trx) | Time to Maximum Platelet Aggregation (TPA(Max))(Cohorts 7-10) | 1.25 hours |