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Clinical trial information and results are updated daily from ClinicalTrials.gov. The latest data update was conducted on 01/20/2021.

Study to Evaluate the Safety, Tolerability, PK and PD of PB2452 in Healthy Younger, Older and Elderly Subjects

Clinicaltrials.gov identifier NCT03928353

Recruitment Status Completed

First Posted April 26, 2019

Last update posted February 17, 2020

Study Description

Brief summary:

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).

  • Condition or Disease:Healthy
  • Intervention/Treatment: Drug: PB2452 Infusion
    Drug: Placebo - Sodium Chloride
    Drug: Ticagrelor Oral Tablet - Pre-Treatment
    Drug: Ticagrelor Oral Tablet - Pre-Treatment and Post-Treatment
    Drug: Ticagrelor Oral Tablet - Pre-Treatment
    Drug: PB2452 Infusion
    Drug: Placebo - Sodium Chloride
  • Phase: Phase 2
Detailed Description

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 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 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 Design
  • Study Type: Interventional
  • Actual Enrollment: 23 participants
  • Allocation: Randomized
  • Intervention Model: Sequential Assignment
  • Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
  • Primary Purpose: Treatment
  • Official Title: A Phase 2A, Randomized, Double-blind, Placebo-controlled, Single Dose, Sequential Group Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of PB2452 With Ticagrelor Pretreatment in Older and Elderly Subjects and With High-Dose Ticagrelor Pretreatment in Healthy Younger Subjects
  • Actual Study Start Date: April 2019
  • Actual Primary Completion Date: October 2019
  • Actual Study Completion Date: October 2019
Arms and interventions
Arm Intervention/treatment
Experimental: 3: 18 g or greater PB2452 or Placebo (Ticagrelor Pre-Trx)
PB2452 Infusion or Placebo - Sodium Chloride with Ticagrelor Oral Tablet: 180 mg BID for a total of 5 doses
Drug: PB2452 Infusion
30 minute - 24 hour infusion

Drug: Placebo - Sodium Chloride
30 minute - 24 hour infusion

Drug: Ticagrelor Oral Tablet - Pre-Treatment
Ticagrelor 180 mg BID for 5 doses prior to PB2452 or Placebo
Experimental: 4: 18 g or greater PB2452 or Placebo (Ticagrelor Pre-Trx)
PB2452 Infusion or Placebo - Sodium Chloride With Ticagrelor Oral Tablet: 180 mg BID for a total of 5 doses
Drug: PB2452 Infusion
30 minute - 24 hour infusion

Drug: Placebo - Sodium Chloride
30 minute - 24 hour infusion

Drug: Ticagrelor Oral Tablet - Pre-Treatment
Ticagrelor 180 mg BID for 5 doses prior to PB2452 or Placebo
Experimental: 5: 18 g or greater PB2452 or Placebo (Ticagrelor Pre-Trx)
PB2452 Infusion or Placebo - Sodium Chloride with Ticagrelor Oral Tablet: 180 mg BID for a total of 5 doses
Drug: PB2452 Infusion
30 minute - 24 hour infusion

Drug: Placebo - Sodium Chloride
30 minute - 24 hour infusion

Drug: Ticagrelor Oral Tablet - Pre-Treatment
Ticagrelor 180 mg + 90 mg BID for 5 doses prior to PB2452 or Placebo

Drug: Ticagrelor Oral Tablet - Pre-Treatment and Post-Treatment
Ticagrelor 180 mg + 90 mg BID for 5 doses prior to PB2452 or Placebo and Ticagerlor 180 mg 24 hours following PB2452 or Placebo

Drug: Ticagrelor Oral Tablet - Pre-Treatment
Ticagrelor 180 mg BID for 5 doses prior to PB2452 or Placebo
Experimental: 1: 18 g PB2452 or Placebo (Ticagrelor Pre-Trx)
PB2452 Infusion or Placebo - Sodium Chloride with Ticagrelor Oral Tablet: 180 mg+90 mg BID for a total of 5 doses
Drug: Ticagrelor Oral Tablet - Pre-Treatment
Ticagrelor 180 mg + 90 mg BID for 5 doses prior to PB2452 or Placebo

Drug: PB2452 Infusion
30 minute - 16 hour infusion

Drug: Placebo - Sodium Chloride
Placebo - Sodium Chloride
Experimental: 2: 18 g or greater PB2452 or Placebo (Ticagrelor Pre-Trx)
PB2452 Infusion or Placebo - Sodium Chloride with Ticagrelor Oral Tablet: 180 mg+90 mg BID for a total of 5 doses
Drug: Ticagrelor Oral Tablet - Pre-Treatment
Ticagrelor 180 mg + 90 mg BID for 5 doses prior to PB2452 or Placebo

Drug: PB2452 Infusion
30 minute - 16 hour infusion

Drug: Placebo - Sodium Chloride
Placebo - Sodium Chloride
Outcome Measures
  • Primary Outcome Measures: 1. 12-Lead ECG - Incidence of clinically significant findings [ Time Frame: 73 days - Starting up to 45 days prior to dosing ]
  • 2. Vital Sign Measurements - Changes in Heart Rate [ Time Frame: 73 days - Starting up to 45 days prior to dosing ]
  • 3. Anti-Drug Antibodies [ Time Frame: 31 days - Starting 3 days prior to dosing and collected post-dose at Day 1, 7 and 28. May be extended in the event that result does not return to baseline in time allotted. ]
    Development of anti-drug antibodies
  • 4. Incidence and severity of AEs [ Time Frame: 73 days - Starting up to 45 days prior to dosing ]
  • 5. Incidence of Clinical Laboratory Abnormalities [ Time Frame: 28 days - Starting day of dosing ]
  • 6. Vital Sign Measurements - Changes in Diastolic Blood Pressure [ Time Frame: 73 days - Starting up to 45 days prior to dosing ]
  • 7. Vital Sign Measurements - Changes in Systolic Blood Pressure [ Time Frame: 73 days - Starting up to 45 days prior to dosing ]
  • 8. Vital Sign Measurements - Changes in Oral Body Temperature [ Time Frame: 73 days - Starting up to 45 days prior to dosing ]
  • 9. Vital Sign Measurements - Changes in Respiratory Rate [ Time Frame: 73 days - Starting up to 45 days prior to dosing ]
  • 10. Adverse events based on physical examination [ Time Frame: 73 days - Starting up to 45 days prior to dosing and collected pre-dose and Days 3, 7, and 28. ]
    Incidence of adverse events noted during physical exam between baseline and end of study
  • Secondary Outcome Measures: 1. PB2452 Pharmacokinetic profile - (AUC) [ Time Frame: Before dosing and at 5, 15 and 30 minutes, 1, 2, 4, 8, 12, 20, 24, 36, 48 hours, 7 and 28 days after the start of infusion (exact sample times may be adjusted) ]
    Area under the plasma concentration versus time curve from time 0 to the time of the last quantifiable concentration (AUC0-t)
  • 2. PB2452 Pharmacokinetic profile - Cmax [ Time Frame: Before dosing and at 5, 15 and 30 minutes, 1, 2, 4, 8, 12, 20, 24, 36, 48 hours, 7 and 28 days after the start of infusion (exact sample times may be adjusted) ]
    Observed maximum plasma concentration
  • 3. PB2452 Pharmacokinetic profile - Tmax [ Time Frame: Before dosing and at 5, 15 and 30 minutes, 1, 2, 4, 8, 12, 20, 24, 36, 48 hours, 7 and 28 days after the start of infusion (exact sample times may be adjusted) ]
    Time to reach the observed maximum plasma concentration
  • 4. PB2452 Pharmacokinetic profile - AUC0-24 [ Time Frame: Before dosing and at 5, 15 and 30 minutes, 1, 2, 4, 8, 12, 20, 24 hours after the start of infusion (exact sample times may be adjusted) ]
    AUC from time 0 to 24 hours post dose
  • 5. PB2452 Pharmacokinetic profile - AUC0-48 [ Time Frame: Before dosing and at 5, 15 and 30 minutes, 1, 2, 4, 8, 12, 20, 24, 36 and 48 hours after the start of infusion (exact sample times may be adjusted) ]
    AUC from time 0 to 48 hours post dose
  • 6. PB2452 Pharmacokinetic profile - AUC0-inf [ Time Frame: Before dosing and at 5, 15 and 30 minutes, 1, 2, 4, 8, 12, 20, 24, 36, 48 hours, 7 and 28 days after the start of infusion (exact sample times may be adjusted) ]
    AUC from time 0 extrapolated to infinity if data permit)
  • 7. PB2452 Pharmacokinetic profile - t½ [ Time Frame: Before dosing and at 5, 15 and 30 minutes, 1, 2, 4, 8, 12, 20, 24, 36, 48 hours, 7 and 28 days after the start of infusion (exact sample times may be adjusted) ]
    Terminal elimination half-life (if data permit)
  • 8. PB2452 Pharmacokinetic profile - CL [ Time Frame: Before dosing and at 5, 15 and 30 minutes, 1, 2, 4, 8, 12, 20, 24, 36, 48 hours, 7 and 28 days after the start of infusion (exact sample times may be adjusted) ]
    Apparent clearance (if data permit)
  • 9. Ticagrelor and Ticagrelor Active Metabolite (TAM) Pharmacokinetic profile - Cmax [ Time Frame: Before dosing and at 5, 15 and 30 minutes, 1, 2, 4, 8, 12, 20, 24, 36, 48 hours, 7 and 28 days after the start of infusion (exact sample times may be adjusted) ]
    Observed maximum plasma concentration
  • 10. Ticagrelor and Ticagrelor Active Metabolite (TAM) Pharmacokinetic profile - Tmax [ Time Frame: Before dosing and at 5, 15 and 30 minutes, 1, 2, 4, 8, 12, 20, 24, 36, 48 hours, 7 and 28 days after the start of infusion (exact sample times may be adjusted) ]
    Time to reach the observed maximum plasma concentration
  • 11. Ticagrelor and Ticagrelor Active Metabolite (TAM) Pharmacokinetic profile - AUC(0-t) [ Time Frame: Before dosing and at 5, 15 and 30 minutes, 1, 2, 4, 8, 12, 20, 24, 36, 48 hours, 7 and 28 days after the start of infusion (exact sample times may be adjusted) ]
    AUC from time 0 to time after last quantifiable concentration
  • 12. Ticagrelor and Ticagrelor Active Metabolite (TAM) Pharmacokinetic profile - AUC(0-12) [ Time Frame: Before dosing and at 5, 15 and 30 minutes, 1, 2, 4, 8, and 12 hours after the start of infusion (exact sample times may be adjusted) ]
    AUC from time 0 to 12 hours after dosing
  • 13. Ticagrelor and Ticagrelor Active Metabolite (TAM) Pharmacokinetic profile - AUC(0-24) [ Time Frame: Before dosing and at 5, 15 and 30 minutes, 1, 2, 4, 8, 12, 20, and 24 hours after the start of infusion (exact sample times may be adjusted) ]
    AUC from time 0 to 24 hours after dosing
  • 14. Ticagrelor and Ticagrelor Active Metabolite (TAM) Pharmacokinetic profile - AUC(0-48) [ Time Frame: Before dosing and at 5, 15 and 30 minutes, 1, 2, 4, 8, 12, 20, 24, 36 and 48 hours after the start of infusion (exact sample times may be adjusted) ]
    AUC from time 0 to 48 hours after dosing
  • 15. Ticagrelor and Ticagrelor Active Metabolite (TAM) Pharmacokinetic profile - AUC0-inf [ Time Frame: Before dosing and at 5, 15 and 30 minutes, 1, 2, 4, 8, 12, 20, 24, 36, 48 hours, 7 and 28 days after the start of infusion (exact sample times may be adjusted) ]
    AUC from time 0 extrapolated to infinity if data permit)
  • 16. Ticagrelor and Ticagrelor Active Metabolite (TAM) Pharmacokinetic profile - t½ [ Time Frame: Before dosing and at 5, 15 and 30 minutes, 1, 2, 4, 8, 12, 20, 24, 36, 48 hours, 7 and 28 days after the start of infusion (exact sample times may be adjusted) ]
    Terminal elimination half-life (if data permit)
  • 17. Ticagrelor and Ticagrelor Active Metabolite (TAM) Urine Pharmacokinetic profile - Ae24 [ Time Frame: Before dosing and 0 to 6, 6 to 12, and 12 to 24 hours after the initiation of the PB2452 infusion. ]
    Total amount of drug excreted in urine at 24 hours after dosing
  • 18. Ticagrelor and Ticagrelor Active Metabolite (TAM) Urine Pharmacokinetic profile - Ae48 [ Time Frame: Before dosing and 0 to 6, 6 to 12, 12 to 24 and 24 to 48 hours after the initiation of the PB2452 infusion. ]
    Total amount of drug excreted in urine at 48 hours after dosing
  • 19. Ticagrelor and Ticagrelor Active Metabolite (TAM) Urine Pharmacokinetic profile - Aet1-t2 [ Time Frame: Before dosing and 0 to 6, 6 to 12, 12 to 24 and 24 to 48 hours after the initiation of the PB2452 infusion. ]
    Ae from time t1 to t2 hours where the values of t1 to t2 are 0 to 6, 6 to 12, and 12 to 24 and 24 to 48
  • 20. Ticagrelor and Ticagrelor Active Metabolite (TAM) Urine Pharmacokinetic profile - Fe24 [ Time Frame: Before dosing and 0 to 6, 6 to 12, and 12 to 24 hours after the initiation of the PB2452 infusion and 5th ticagrelor dose. ]
    Fraction excreted in urine from 1 to 24 hours after dosing
  • 21. Ticagrelor and Ticagrelor Active Metabolite (TAM) Urine Pharmacokinetic profile - Fe48 [ Time Frame: Before dosing and 0 to 6, 6 to 12, 12 to 24 and 24 to 48 hours after the initiation of the PB2452 infusion and 5th ticagrelor dose. ]
    Fraction excreted in urine from 1 to 48 hours after dosing
  • 22. Ticagrelor and Ticagrelor Active Metabolite (TAM) Urine Pharmacokinetic profile - CLr [ Time Frame: Before dosing and 0 to 6, 6 to 12, and 12 to 24 hours after the initiation of the PB2452 infusion and 5th ticagrelor dose. ]
    Renal clearance for 24 hours after dosing
  • 23. Effectiveness of single ascending doses of PB2452 - PRU at each assessment point [ Time Frame: Before dosing and at 5, 15 and 30 minutes, 1, 2, 4, 8, 12, 20, 24, 36 and 48 hours after the start of infusion (exact sample times may be adjusted) ]
    P2Y12 Reaction Units with VerifyNow P2Y12 Assay
  • 24. Effectiveness of single ascending doses of PB2452 - % Reversal by PRU [ Time Frame: Before dosing and at 5, 15 and 30 minutes, 1, 2, 4, 8, 12, 20, 24, 36 and 48 hours after the start of infusion (exact sample times may be adjusted) ]
    Percent of reversal in ticagrelor antiplatelet activity by PRU at each assessment point
  • 25. Effectiveness of single ascending doses of PB2452 - Maximum PRU [ Time Frame: Before dosing and at 5, 15 and 30 minutes, 1, 2, 4, 8, 12, 20, 24, 36 and 48 hours after the start of infusion (exact sample times may be adjusted) ]
    Maximum PRU at each assessment point
  • 26. Effectiveness of single ascending doses of PB2452 - Time to Maximum PRU [ Time Frame: Before dosing and at 5, 15 and 30 minutes, 1, 2, 4, 8, 12, 20, 24, 36 and 48 hours after the start of infusion (exact sample times may be adjusted) ]
    Time to Maximum PRU at each assessment point
  • 27. Effectiveness of single ascending doses of PB2452 - Maximum PRU within 4 hours [ Time Frame: Before dosing and at 5, 15 and 30 minutes, 1, 2, and 4 hours after the start of infusion (exact sample times may be adjusted) ]
    Maximum PRU within 4 hours
  • 28. Effectiveness of single ascending doses of PB2452 - Time to ≥ 180 PRU [ Time Frame: Before dosing and at 5, 15 and 30 minutes, 1, 2, 4, 8, 12, 20, 24, 36 and 48 hours after the start of infusion (exact sample times may be adjusted) ]
    Time to ≥ 180 PRU
  • 29. Effectiveness of single ascending doses of PB2452 - Time to ≥ 200 PRU [ Time Frame: Before dosing and at 5, 15 and 30 minutes, 1, 2, 4, 8, 12, 20, 24, 36 and 48 hours after the start of infusion (exact sample times may be adjusted) ]
    Time to ≥ 200 PRU
  • 30. Effectiveness of single ascending doses of PB2452 - Time to ≥ 220 PRU [ Time Frame: Before dosing and at 5, 15 and 30 minutes, 1, 2, 4, 8, 12, 20, 24, 36 and 48 hours after the start of infusion (exact sample times may be adjusted) ]
    Time to ≥ 220 PRU
  • 31. Effectiveness of single ascending doses of PB2452 - Time to 60% of reversal in PRU [ Time Frame: Before dosing and at 5, 15 and 30 minutes, 1, 2, 4, 8, 12, 20, 24, 36 and 48 hours after the start of infusion (exact sample times may be adjusted) ]
    Time to 60% of reversal in PRU
  • 32. Effectiveness of single ascending doses of PB2452 - Time to 80% of reversal in PRU [ Time Frame: Before dosing and at 5, 15 and 30 minutes, 1, 2, 4, 8, 12, 20, 24, 36 and 48 hours after the start of infusion (exact sample times may be adjusted) ]
    Time to 80% of reversal in PRU
  • 33. Effectiveness of single ascending doses of PB2452 - Time to 90% of reversal in PRU [ Time Frame: Before dosing and at 5, 15 and 30 minutes, 1, 2, 4, 8, 12, 20, 24, 36 and 48 hours after the start of infusion (exact sample times may be adjusted) ]
    Time to 90% of reversal in PRU
  • 34. Effectiveness of single ascending doses of PB2452 - LTA at each assessment point [ Time Frame: Before dosing and at 5, 15 and 30 minutes, 1, 2, 4, 8, 12, 20, 24, 36 and 48 hours after the start of infusion (exact sample times may be adjusted) ]
    Maximum and final extent of aggregation for up to 4 platelet agonists at each assessment point
  • 35. Effectiveness of single ascending doses of PB2452 - % Reversal by LTA [ Time Frame: Before dosing and at 5, 15 and 30 minutes, 1, 2, 4, 8, 12, 20, 24, 36 and 48 hours after the start of infusion (exact sample times may be adjusted) ]
    Percent of reversal in ticagrelor antiplatelet activity by LTA at each assessment point
  • 36. Effectiveness of single ascending doses of PB2452 - Maximum platelet aggregation by LTA [ Time Frame: Before dosing and at 5, 15 and 30 minutes, 1, 2, 4, 8, 12, 20, 24, 36 and 48 hours after the start of infusion (exact sample times may be adjusted) ]
    Maximum platelet aggregation by LTA at each assessment point
  • 37. Effectiveness of single ascending doses of PB2452 - Time to maximum platelet aggregation by LTA [ Time Frame: Before dosing and at 5, 15 and 30 minutes, 1, 2, 4, 8, 12, 20, 24, 36 and 48 hours after the start of infusion (exact sample times may be adjusted) ]
    Time to maximum platelet aggregation by LTA at each assessment point
  • 38. Effectiveness of single ascending doses of PB2452 - Maximum platelet aggregation within 4 hours by LTA [ Time Frame: Before dosing and at 5, 15 and 30 minutes, 1, 2, and 4 hours after the start of infusion (exact sample times may be adjusted) ]
    Maximum platelet aggregation within 4 hours by LTA
  • 39. Effectiveness of single ascending doses of PB2452 - Time to 60% reversal in platelet aggregation by LTA [ Time Frame: Before dosing and at 5, 15 and 30 minutes and 4 hours after the start of infusion (exact sample times may be adjusted) ]
    Time to 60% reversal in platelet aggregation by LTA within 30 minutes or 4 hours
  • 40. Effectiveness of single ascending doses of PB2452 - Time to 80% reversal in platelet aggregation by LTA [ Time Frame: Before dosing and at 5, 15 and 30 minutes and 4 hours after the start of infusion (exact sample times may be adjusted) ]
    Time to 80% reversal in platelet aggregation by LTA within 30 minutes or 4 hours
  • 41. Effectiveness of single ascending doses of PB2452 - Time to 90% reversal in platelet aggregation by LTA [ Time Frame: Before dosing and at 5, 15 and 30 minutes and 4 hours after the start of infusion (exact sample times may be adjusted) ]
    Time to 90% reversal in platelet aggregation by LTA within 30 minutes or 4 hours
  • 42. Effectiveness of single ascending doses of PB2452 - VASP by ELISA - PRI at each assessment point [ Time Frame: Before dosing and at 5, 15 and 30 minutes, 1, 2, 4, 8, 12, 20, 24, 36 and 48 hours after the start of infusion (exact sample times may be adjusted) ]
    Vasodilator stimulated response by ELISA at each assessment point
  • 43. Effectiveness of single ascending doses of PB2452 - VASP by ELISA - % Reversal at each assessment point [ Time Frame: Before dosing and at 5, 15 and 30 minutes, 1, 2, 4, 8, 12, 20, 24, 36 and 48 hours after the start of infusion (exact sample times may be adjusted) ]
    Vasodilator stimulated response by ELISA percent reversal at each assessment point
  • 44. Effectiveness of single ascending doses of PB2452 - VASP by ELISA - Maximum PRI [ Time Frame: Before dosing and at 5, 15 and 30 minutes, 1, 2, 4, 8, 12, 20, 24, 36 and 48 hours after the start of infusion (exact sample times may be adjusted) ]
    Vasodilator stimulated response by ELISA maximum PRI
  • 45. Effectiveness of single ascending doses of PB2452 - VASP by ELISA - Time to Maximum PRI [ Time Frame: Before dosing and at 5, 15 and 30 minutes, 1, 2, 4, 8, 12, 20, 24, 36 and 48 hours after the start of infusion (exact sample times may be adjusted) ]
    Vasodilator stimulated response by ELISA time to maximum PRI
  • 46. Effectiveness of single ascending doses of PB2452 - VASP by ELISA - Maximum PRI within 4 hours [ Time Frame: Before dosing and at 5, 15 and 30 minutes, 1, 2, and 4 hours after the start of infusion (exact sample times may be adjusted) ]
    Vasodilator stimulated response by ELISA maximum PRI within 4 hours
  • 47. Effectiveness of single ascending doses of PB2452 - VASP by ELISA - Time to 60% of reversal by PRI [ Time Frame: Before dosing and at 5, 15 and 30 minutes, 1, 2, 4, 8, 12, 20, 24, 36 and 48 hours after the start of infusion (exact sample times may be adjusted) ]
    Vasodilator stimulated response by ELISA time to 60% of reversal by PRI
  • 48. Effectiveness of single ascending doses of PB2452 - VASP by ELISA - Time to 80% of reversal by PRI [ Time Frame: Before dosing and at 5, 15 and 30 minutes, 1, 2, 4, 8, 12, 20, 24, 36 and 48 hours after the start of infusion (exact sample times may be adjusted) ]
    Vasodilator stimulated response by ELISA time to 80% of reversal by PRI
  • 49. Effectiveness of single ascending doses of PB2452 - VASP by ELISA - Time to 90% of reversal by PRI [ Time Frame: Before dosing and at 5, 15 and 30 minutes, 1, 2, 4, 8, 12, 20, 24, 36 and 48 hours after the start of infusion (exact sample times may be adjusted) ]
    Vasodilator stimulated response by ELISA time to 90% of reversal by PRI
  • 50. Effectiveness of single ascending doses of PB2452 - VASP by ELISA - Number of subjects achieving 60% reversal by PRI within 30 minutes to 4 hours [ Time Frame: Before dosing and at 5, 15 and 30 minutes, 1, 2, and 4 hours after the start of infusion (exact sample times may be adjusted) ]
    Vasodilator stimulated response by ELISA Number of subjects achieving 60% reversal by PRI within 30 minutes to 4 hours
  • 51. Effectiveness of single ascending doses of PB2452 - VASP by ELISA - Number of subjects achieving 90% reversal by PRI within 30 minutes to 4 hours [ Time Frame: Before dosing and at 5, 15 and 30 minutes, 1, 2, and 4 hours after the start of infusion (exact sample times may be adjusted) ]
    Vasodilator stimulated response by ELISA Number of subjects achieving 90% reversal by PRI within 30 minutes to 4 hours
  • 52. Effectiveness of single ascending doses of PB2452 - VASP by ELISA - Number of subjects achieving 80% reversal by PRI within 30 minutes to 4 hours [ Time Frame: Before dosing and at 5, 15 and 30 minutes, 1, 2, and 4 hours after the start of infusion (exact sample times may be adjusted) ]
    Vasodilator stimulated response by ELISA Number of subjects achieving 80% reversal by PRI within 30 minutes to 4 hours
  • 53. Effectiveness of single ascending doses of PB2452 - VASP by ELISA - % of subjects achieving 80% reversal by PRI within 30 minutes to 4 hours [ Time Frame: Before dosing and at 5, 15 and 30 minutes, 1, 2, and 4 hours after the start of infusion (exact sample times may be adjusted) ]
    Vasodilator stimulated response by ELISA percentage of subjects achieving 60% reversal by PRI within 30 minutes to 4 hours
  • 54. Effectiveness of single ascending doses of PB2452 - VASP by ELISA - % of subjects achieving 60% reversal by PRI within 30 minutes to 4 hours [ Time Frame: Before dosing and at 5, 15 and 30 minutes, 1, 2, and 4 hours after the start of infusion (exact sample times may be adjusted) ]
    Vasodilator stimulated response by ELISA percentage of subjects achieving 80% reversal by PRI within 30 minutes to 4 hours
  • 55. Effectiveness of single ascending doses of PB2452 - VASP by ELISA - % of subjects achieving 90% reversal by PRI within 30 minutes to 4 hours [ Time Frame: Before dosing and at 5, 15 and 30 minutes, 1, 2, and 4 hours after the start of infusion (exact sample times may be adjusted) ]
    Vasodilator stimulated response by ELISA percentage of subjects achieving 90% reversal by PRI within 30 minutes to 4 hours
Eligibility Criteria
  • Ages Eligible for Study: 18 to 80 Years (Adult, Older Adult)
  • Sexes Eligible for Study: All
  • Accepts Healthy Volunteers: Yes
Criteria

Inclusion Criteria:

1. The subject provides written informed consent and agrees to comply with all protocol
requirements.

2. The subject is male or female between 18 and 80 years of age, inclusive (50 to 80
years for Cohorts 1-2, 18 to 50 years for Cohorts 3-5).

3. The subject has a body mass index (BMI) between 18 and 35 kg/m2 and a weight of ≥50 kg
but ≤120 kg, inclusive, at Screening.

4. 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.
Older and elderly subjects with chronic, stable, and well-controlled medical
conditions are eligible provided they meet all other inclusion/exclusion criteria.
Some examples of stable and well-controlled medical conditions include but are not
limited to:

- Hypertension (HTN) controlled with ≤2 antihypertensive drugs

- Diabetes controlled with diet/exercise or treated with up to 2 oral diabetes
medications

- Subjects with diabetes must have a glycated hemoglobin HbA1c ≤8 mg/dL at
Screening.

- Mild hepatic enzyme elevation (AST or ALT <1.5 x ULN or total bilirubin <1.2 x ULN) - Controlled hyperlipidemia (defined with a Screening low density lipoprotein LDL 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 (e.g., condom plus diaphragm
with spermicide, condom plus spermicide) during the study and for 30 days after
the last dose of study drug, and refrain from donating sperm for ≥90 days
following the last dose of study drug.

Exclusion Criteria:

1. Concern the subject may be unable 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

2. History of any acute or chronic medical disorder expected to decrease the life
expectancy of the subject

3. History or presence of gastrointestinal (GI), hepatic (with the exception of Gilbert's
syndrome), or any other condition known to interfere with absorption, distribution,
metabolism, or excretion of drugs

4. Significant renal insufficiency, as indicated by estimated glomerular filtration rate
(eGFR) <30 mL/min/1.73m2 according to the Modification of Diet in Renal Disease (MDRD) equation 5. Any CS acute illness, medical/surgical procedure, or trauma within 4 weeks of administration of study drug or any planned surgical procedure that will occur during the study (from Screening through the Day 28 [±2 days] Follow-up visit) 6. Any CS abnormal findings in physical examination, vital signs, laboratory assessments, and ECG parameters identified during Screening or Check-in. Note: abnormal results may be repeated for confirmation immediately after the first out of range measurement. Abnormal vital signs may be repeated twice if needed, immediately after the first abnormal result and/or after the subject has rested for at least 10 minutes. Specific vital sign exclusionary criteria occurring after 10 minutes of supine rest are any of the following: - Systolic blood pressure (SBP) 160 mm Hg

- Diastolic blood pressure (DBP) 95 mm Hg

- Resting heart rate (HR) 100 beats per minute (bpm)

Specific exclusionary criteria for ECG parameters at Screening or Check-in include any
of the following:

- Prolonged Fridericia-corrected QT interval (QTcF) >450 milliseconds (msec)

- Shortened QTcF 3 seconds

- Family history of long QT syndrome

7. Any specific contraindication to Brilinta® as described in the Brilinta® prescribing
information and:

- History of intracranial hemorrhage, active bleeding, or hypersensitivity or
allergic reaction to ticagrelor or any component of the product

- Any history of severe head trauma, intracranial neoplasm, arteriovenous
malformation, aneurysm, or proliferative retinopathy

- Any history of intraocular, retroperitoneal, or spinal bleeding

- Have taken, within 30 days of Screening, any oral or parenteral anticoagulant,
including low molecular-weight heparin

- Stool sample testing positive for occult blood within 3 months of Screening or at
any time during the Screening Period

8. Receiving chronic treatment with nonsteroidal anti-inflammatory drugs (NSAIDS;
[including ASA >100 mg daily]), anticoagulants, or other antiplatelet agents that
cannot be discontinued 14 days prior to randomization (including clopidogrel,
prasugrel, ticlopidine, dipyridamole, or cilostazol)

9. Positive test result for hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV)
antibody, or human immunodeficiency virus (HIV) types 1 or 2 antibodies at Screening

10. Concomitant oral or IV therapy with strong cytochrome P450 3A4 (CYP3A) inhibitors,
CYP3A substrates with narrow therapeutic indices, or strong CYP3A inducers, which
cannot be stopped within at least 5 half-lives, but not fewer than 10 days, before
randomization

11. Consumption of grapefruit or grapefruit juice, Seville orange or Seville orange
containing products (e.g., marmalade), or xanthine containing products within 48 hours
before dosing with study drug

12. Prescription or over the counter (OTC) medications within 14 days before the first
dose of study drug unless specifically allowed by protocol. (Permitted medications
include multivitamins, paracetamol [up to 2g per day], and/or treatments for chronic
stable diseases, provided the drug and dose have been stable for ≥30 days prior to
administration of study drug)

13. Has received another investigational drug (defined as a small molecule or biologic
compound which has not been approved for marketing) within 30 days of the
administration of study drug in this study or within 5 half-lives of the prior study
drug, whichever is longer

14. Positive test result for alcohol or drugs of abuse at Screening or Check-in

15. Participated in strenuous activity or contact sports within 24 hours before the
infusion of study drug or while confined in the clinical site

16. History of severe or ongoing allergy/hypersensitivity to any drug or biologic
therapeutic agent

17. Involvement with any PhaseBio or study site employee or their close relatives (e.g.,
spouse, parents, siblings, or children whether biological or legally adopted)

18. Previously received PB2452 or had been randomized to receive study drug in an earlier
cohort for this study

Contacts and Locations
Contacts
Locations

United States, Texas
PPD
Austin

Sponsors and Collaborators

PhaseBio Pharmaceuticals Inc.

Investigators

Principal Investigator: LuAnn Bundrant, MD PPD

More Information
  • Responsible Party: PhaseBio Pharmaceuticals Inc.
  • ClinicalTrials.gov Identifier: NCT03928353 History of Changes
  • Other Study ID Numbers: PB2452-PT-CL-0002
  • First Posted: April 26, 2019 Key Record Dates
  • Last Update Posted: February 17, 2020
  • Last Verified: February 2020
  • Individual Participant
    Data (IPD) Sharing
    Statement:
  • Plan to Share IPD: No
  • Studies a U.S. FDA-regulated Drug Product: Yes
  • Studies a U.S. FDA-regulated Device Product: No