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

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ClinicalTrials.gov Identifier: NCT03928353
Recruitment Status : Recruiting
First Posted : April 26, 2019
Last Update Posted : August 20, 2019
Sponsor:
Information provided by (Responsible Party):
PhaseBio Pharmaceuticals Inc.

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 Intervention/treatment Phase
Healthy Drug: PB2452 Infusion Drug: Placebo - Sodium Chloride Drug: Ticagrelor Oral Tablet - Pre-Treatment Drug: Ticagrelor Oral Tablet - Pre-Treatment and Post-Treatment 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).


Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 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 16, 2019
Estimated Primary Completion Date : December 2019
Estimated Study Completion Date : December 2019

Resource links provided by the National Library of Medicine

Drug Information available for: Ticagrelor

Arm Intervention/treatment
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

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




Primary Outcome Measures :
  1. Incidence and severity of AEs [ Time Frame: 73 days - Starting up to 45 days prior to dosing ]
  2. Incidence of Clinical Laboratory Abnormalities [ Time Frame: 28 days - Starting day of dosing ]
  3. Vital Sign Measurements - Changes in Diastolic Blood Pressure [ Time Frame: 73 days - Starting up to 45 days prior to dosing ]
  4. Vital Sign Measurements - Changes in Systolic Blood Pressure [ Time Frame: 73 days - Starting up to 45 days prior to dosing ]
  5. Vital Sign Measurements - Changes in Oral Body Temperature [ Time Frame: 73 days - Starting up to 45 days prior to dosing ]
  6. Vital Sign Measurements - Changes in Respiratory Rate [ Time Frame: 73 days - Starting up to 45 days prior to dosing ]
  7. Vital Sign Measurements - Changes in Heart Rate [ Time Frame: 73 days - Starting up to 45 days prior to dosing ]
  8. 12-Lead ECG - Incidence of clinically significant findings [ Time Frame: 73 days - Starting up to 45 days prior to dosing ]
  9. 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

  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



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years 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 <160 mg/dL)
  5. Specific inclusionary laboratory values at Screening and Check-in require:

    • White blood cell (WBC) count, platelet count, hemoglobin (Hgb) level within normal range, as defined by the clinical laboratory
    • Thyroid stimulating hormone (TSH) level within normal range, as defined by the clinical laboratory at Screening
    • Prothrombin time (PT) and partial thromboplastin time (PTT) level within normal range, as defined by the clinical laboratory
  6. Subjects taking medications for well-controlled medical conditions must have been on a stable dose (meaning no changes in dose) for at least 30 days prior to Screening visit.
  7. Older and elderly subjects entering the study who are not already taking daily ASA must be willing to start an 81 mg daily dose of ASA on Day -7 and continue daily dosing until the final dose is administered on the morning of Day 1. Subjects entering the study who are already taking ASA daily will be administered 81 mg ASA daily between Day -7 and Day 1 and must suspend further ASA dosing until discharge from the clinical facility.
  8. Female subjects of childbearing potential must not be pregnant, lactating, or planning to become pregnant for 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 from 30 days before study drug administration through to the end of the study.

    • Effective birth control methods include oral, implantable, patch, or injectable contraceptive hormone treatment, hormone-containing intrauterine device that has been in place ≥2 months prior to Screening, sponge, diaphragm, or cervical cap with spermicidal gel or cream for female subjects or condom or vasectomy for male subjects.
    • Women are considered to not be of childbearing potential if they have fulfilled one of these criteria: documentation of irreversible surgical sterilization (i.e., hysterectomy or bilateral oophorectomy [not tubal ligation]) or are postmenopausal (defined as amenorrhea for 12 consecutive months following cessation of all exogenous hormonal treatments, and documented plasma follicle-stimulating hormone (FSH) 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 (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) <100 or >160 mm Hg
    • Diastolic blood pressure (DBP) <40 or >95 mm Hg
    • Resting heart rate (HR) <50 or >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 <340 msec, or pause >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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03928353


Contacts
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Contact: PPD Austin, TX 877-773-3707 AustinPPD_PhoneRecruitingSupport.SM@ppdi.com

Locations
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United States, Texas
PPD Recruiting
Austin, Texas, United States, 78744
Contact: Luann Bundrant, MD         
Sponsors and Collaborators
PhaseBio Pharmaceuticals Inc.
Investigators
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Principal Investigator: LuAnn Bundrant, MD PPD

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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: August 20, 2019
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Ticagrelor
Platelet Aggregation Inhibitors
Purinergic P2Y Receptor Antagonists
Purinergic P2 Receptor Antagonists
Purinergic Antagonists
Purinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs