This is a Phase 2A, randomized, double-blind, placebo-controlled, single dose, sequential group study to evaluate the safety, tolerability, PK, and PD of PB2452 vs matching placebo with ticagrelor (with or without acetylsalicylic acid (ASA)) pretreatment when various dose levels and administration regimens are administered to healthy younger (ages 18 to 50), older (ages 50 to 64 years) and elderly (ages 65 to 80 years) male and female subjects. Up to 5 dose levels and/or administration regimens will be evaluated in up to 5 cohorts. Each cohort will include approximately 8 to 12 subjects randomized in a 3:1 ratio (PB2452:placebo).
The study will consist of a Screening period, a Check-in day and Pretreatment Period, an on-site Randomization/Treatment day, 3 days on-site for treatment and safety monitoring, a Follow-up Visit (Day 7), and a Final Follow-up visit (Day 28). Seven days prior to Randomization, subjects in Cohorts 1 and 2 will be administered acetylsalicylic acid (ASA) 81 mg orally once daily (QD) until the final dose on the morning of Day 1 before receiving study drug. A ticagrelor 180 mg oral dose will be administered on the morning of Day -2 followed by either 90 mg or 180 mg every 12 hours (BID) until the 5th dose has been administered on the morning of Day 1. On Day 1, subjects who meet all the inclusion criteria and none of the exclusion criteria will be randomized in a ratio 3:1 (PB2452:placebo), to receive an IV dose of PB2452 or placebo 2 hours following the 5th ticagrelor dose. Subjects may be discharged from the clinical site between Days 3 and 7 inclusive and will return for a Follow-up visit on Day 7, if already discharged, and on Day 28 (±2 days).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
23
30 minute - 24 hour infusion
30 minute - 24 hour infusion
Ticagrelor 180 mg + 90 mg BID for 5 doses prior to PB2452 or Placebo
Ticagrelor 180 mg + 90 mg BID for 5 doses prior to PB2452 or Placebo and Ticagrelor 180 mg 24 hours following PB2452 or Placebo
Ticagrelor 180 mg BID for 5 doses prior to PB2452 or Placebo
30 minute - 16 hour infusion
Placebo - Sodium Chloride
PPD
Austin, Texas, United States
Number Of Participants With Treatment-emergent Adverse Events (TEAEs) And Serious Adverse Events (SAEs)
An adverse event (AE) is defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not it is considered drug-related. A TEAE is defined as any AE not present before exposure to study drug or any AE already present that worsens in intensity or frequency after exposure to study drug. An SAE/suspected unexpected serious adverse reaction if, in the view of either the investigator or Sponsor, it results in any of the following outcomes: death, life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, or congenital anomaly or birth defect. A summary of serious and all other non-serious adverse events, regardless of causality, is located in the Reported Adverse Events module.
Time frame: Day -3 up to Day 28
Number of Participants With Clinical Laboratory Abnormalities
Number of participants with clinically significant abnormal laboratory findings for hematology, coagulation, serum chemistry, and urinalysis.
Time frame: Day -45 up to Day 28
Mean Diastolic Blood Pressure at Baseline
Time frame: Baseline
Percent Change In Diastolic Blood Pressure From Baseline To Day 28
Diastolic blood pressure measurements were measured at specific time points.
Time frame: Day 1 (10, 20, 30, 45, and 60 minutes post-dose), Day 2, Day 3, Day 7, and Day 28
Mean Systolic Blood Pressure at Baseline
Time frame: Baseline
Percent Change In Systolic Blood Pressure From Baseline To Day 28
Systolic blood pressure measurements were measured at specific time points.
Time frame: Day 1 (10, 20, 30, 45, and 60 minutes post-dose), Day 2, Day 3, Day 7, and Day 28
Mean Oral Body Temperature at Baseline
Time frame: Baseline
Percent Change In Oral Body Temperature From Baseline To Day 28
Body temperature measurements were measured at specific time points.
Time frame: Day 1 (45 and 60 minutes post-dose), Day 2, Day 3, Day 7, and Day 28
Mean Respiratory Rate at Baseline
Time frame: Baseline
Percent Change In Respiratory Rate From Baseline To Day 28
Respiratory rate measurements were measured at specific time points.
Time frame: Day 1 (45 and 60 minutes post-dose), Day 2, Day 3, Day 7, and Day 28
Mean Heart Rate at Baseline
Time frame: Baseline
Percent Change In Heart Rate From Baseline To Day 28
Heart rate measurements were measured at specific time points.
Time frame: Baseline, Day 1 (10, 20, 30, 45, and 60 minutes post-dose), Day 2, Day 3, Day 7, and Day 28
Incidence Of Clinically Significant 12-Lead Electrocardiogram (ECG) Findings
Number of participants per cohort with clinically significant ECG findings.
Time frame: Up to Day 28
Participants Experiencing Anti-drug Antibodies (ADAs)
Number of participants who developed ADAs to PB2452.
Time frame: Day -3, Day 1, Day 7, and Day 28
Number of Participants With Adverse Events During Physical Examination
Participants with adverse events noted during physical exam between baseline and end of study.
Time frame: Baseline through Day 28
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