Study to Evaluate the Safety, Tolerability, PK, and PD of PB2452 in Healthy Volunteers

• Sponsor: PhaseBio Pharmaceuticals Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03492385
• Collaborator: (none)
• Enrollment: 64
• Location: 1
• Arms: 10
• Actual Duration (Months): 5.5
• Patients Per Site Per Month: 11.6

Study Details

Study Description

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.

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 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 64 participants
• Allocation: Randomized
• Intervention Model: Sequential Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Single Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of MEDI2452 (PB2452) With and Without Ticagrelor Pretreatment in Healthy Volunteers
• Actual Study Start Date: Apr 3, 2018
• Actual Primary Completion Date: Sep 18, 2018
• Actual Study Completion Date: Sep 18, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1: 100 mg PB2452 or Placebo (no Ticagrelor) PB2452 Infusion or Placebo - Sodium Chloride	Drug: PB2452 Infusion; 30 minute - 12 hour infusion; Drug: Placebo - Sodium Chloride; 30 minute - 12 hour infusion
Experimental: 2: 300 mg PB2452 or Placebo (no Ticagrelor) PB2452 Infusion or Placebo - Sodium Chloride	Drug: PB2452 Infusion; 30 minute - 12 hour infusion; Drug: Placebo - Sodium Chloride; 30 minute - 12 hour infusion
Experimental: 3: 1000 mg PB2452 or Placebo (no Ticagrelor) PB2452 Infusion or Placebo - Sodium Chloride	Drug: PB2452 Infusion; 30 minute - 12 hour infusion; Drug: Placebo - Sodium Chloride; 30 minute - 12 hour infusion
Experimental: 4: 1000 mg 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: PB2452 Infusion; 30 minute - 12 hour infusion; Drug: Placebo - Sodium Chloride; 30 minute - 12 hour infusion
Experimental: 5: 3000 mg 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: PB2452 Infusion; 30 minute - 12 hour infusion; Drug: Placebo - Sodium Chloride; 30 minute - 12 hour infusion; Drug: Ticagrelor Oral Tablet - Pre-Treatment; Ticagrelor 180 mg + 90 mg BID for 5 doses prior to MEDI2452 (PB2452) or Placebo
Experimental: 6: 9000 mg 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: PB2452 Infusion; 30 minute - 12 hour infusion; Drug: Placebo - Sodium Chloride; 30 minute - 12 hour infusion; Drug: Ticagrelor Oral Tablet - Pre-Treatment; Ticagrelor 180 mg + 90 mg BID for 5 doses prior to MEDI2452 (PB2452) or Placebo
Experimental: 7: 18000 mg 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: PB2452 Infusion; 30 minute - 12 hour infusion; Drug: Placebo - Sodium Chloride; 30 minute - 12 hour infusion; Drug: Ticagrelor Oral Tablet - Pre-Treatment; Ticagrelor 180 mg + 90 mg BID for 5 doses prior to MEDI2452 (PB2452) or Placebo
Experimental: 8: Dose TBD mg PB2452 or Placebo (Ticagrelor Pre-Trx) PB2452 Infusion or Placebo - Sodium Chloride with Ticagrelor Oral Tablet: 180 mg+90 mg BID for 5 doses	Drug: PB2452 Infusion; 30 minute - 12 hour infusion; Drug: Placebo - Sodium Chloride; 30 minute - 12 hour infusion; Drug: Ticagrelor Oral Tablet - Pre-Treatment; Ticagrelor 180 mg + 90 mg BID for 5 doses prior to MEDI2452 (PB2452) or Placebo
Experimental: 9: Dose TBD mg PB2452 or Placebo (Ticagrelor Pre and Post-Trx) PB2452 Infusion or Placebo - Sodium Chloride with Ticagrelor Oral Tablet: 180 mg+90 mg BID for 5 doses and 180 mg 24 hours post-dose	Drug: PB2452 Infusion; 30 minute - 12 hour infusion; Drug: Placebo - Sodium Chloride; 30 minute - 12 hour infusion; Drug: Ticagrelor Oral Tablet - Pre-Treatment and Post-Treatment; 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
Experimental: 10: Dose TBD mg PB2452 or Placebo (Ticagrelor Pre-Txt) PB2452 Infusion or Placebo - Sodium Chloride with Ticagrelor Oral Tablet: 180 mg+90 mg BID for 5 doses	Drug: PB2452 Infusion; 30 minute - 12 hour infusion; Drug: Placebo - Sodium Chloride; 30 minute - 12 hour infusion; Drug: Ticagrelor Oral Tablet - Pre-Treatment; Ticagrelor 180 mg + 90 mg BID for 5 doses prior to MEDI2452 (PB2452) or Placebo

Outcome Measures

Primary Outcome Measures

1. Incidence and severity of AEs [60 days - Starting up to 28 days prior to dosing]

2. Incidence of Clinical Laboratory Abnormalities [30 Day - Starting day of dosing]

3. Vital Sign Measurements - Changes in Diastolic Blood Pressure [60 days - Starting up to 28 days prior to dosing]

4. Vital Sign Measurements - Changes in Systolic Blood Pressure [60 days - Starting up to 28 days prior to dosing]

5. Vital Sign Measurements - Changes in Oral Body Temperature [60 days - Starting up to 28 days prior to dosing]

6. Vital Sign Measurements - Changes in Respiratory Rate [60 days - Starting up to 28 days prior to dosing]

7. Vital Sign Measurements - Changes in Heart Rate [60 days - Starting up to 28 days prior to dosing]

8. 12-Lead ECG - Incidence of clinically significant findings [60 days - Starting up to 28 days prior to dosing]

9. Cardiac Telemetry - Incidence of clinically significant findings [3 Days - Starting day 1 day prior to dosing up to 2 days after dosing]

10. Immunogenicity [60 days - Starting up to 28 days prior to dosing. May be extended in the event that result does not return to baseline in time allotted.]

    Incidence of Immunogenicity

11. Effectiveness of single ascending doses of PB2452 - IPA (Cohorts 1-6) [Before dosing and at 0.5, 1, 2, 3, 6, 12, 24, and 48 hours after PB2452 infusion and 5th ticagrelor dose.]

    Inhibition of platelet aggregation (IPA) (max and final extent) induced by 20µM adenosine diphosphate (ADP) at each assessment point

12. Effectiveness of single ascending doses of PB2452 - IPAmax (Cohorts 1-6) [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).]

    Inhibition of maximal platelet aggregation

13. Effectiveness of single ascending doses of PB2452 - IPAmax time (Cohorts 1-6) [Before dosing and at 0.5, 1, 2, 3, 6, 12, 24, and 48 hours after PB2452 infusion and 5th ticagrelor dose.]

    Time to IPAmax

14. Effectiveness of single ascending doses of PB2452 - IPA (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 (if required).]

    Inhibition of platelet aggregation (IPA) (max and final extent) induced by 20µM adenosine diphosphate (ADP) at each assessment point

15. Effectiveness of single ascending doses of PB2452 - IPAmax (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 (if required).]

    Inhibition of maximal platelet aggregation

16. Effectiveness of single ascending doses of PB2452 - IPAmax time (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 (if required).]

    Time to IPAmax

Secondary Outcome Measures

1. PB2452 Pharmacokinetic profile - (AUC) (Cohort 1-6) [Before dosing and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours, and at 7 and 28 days after PB2452 infusion]

   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 - (AUC) (Cohort 7-10) [Before dosing and at 5 min, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 8.25, 8.5, 9, 10, 11, 12, 16, 20, 24, 32, and 48 hours, and at 7 and 28 days after PB2452 infusion]

   Area under the plasma concentration versus time curve from time 0 to the time of the last quantifiable concentration (AUC0-t)

3. PB2452 Pharmacokinetic profile - Cmax (Cohorts 1-6) [Before dosing and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours, and at 7 and 28 days after PB2452 infusion]

   Observed maximum plasma concentration

4. PB2452 Pharmacokinetic profile - Cmax (Cohorts 7-10) [Before dosing and at 5 min, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 8.25, 8.5, 9, 10, 11, 12, 16, 20, 24, 32, and 48 hours, and at 7 and 28 days after PB2452 infusion]

   Observed maximum plasma concentration

5. PB2452 Pharmacokinetic profile - Tmax (Cohorts 1-6) [Before dosing and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours, and at 7 and 28 days after PB2452 infusion]

   Time to reach the observed maximum plasma concentration

6. PB2452 Pharmacokinetic profile - Tmax (Cohorts 7-10) [Before dosing and at 5 min, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 8.25, 8.5, 9, 10, 11, 12, 16, 20, 24, 32, and 48 hours, and at 7 and 28 days after PB2452 infusion]

   Time to reach the observed maximum plasma concentration

7. PB2452 Pharmacokinetic profile - AUC0-inf (Cohorts 1-6) [Before dosing and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours, and at 7 and 28 days after PB2452 infusion]

   AUC from time 0 extrapolated to infinity if data permit)

8. PB2452 Pharmacokinetic profile - AUC0-inf (Cohorts 7-10) [Before dosing and at 5 min, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 8.25, 8.5, 9, 10, 11, 12, 16, 20, 24, 32, and 48 hours, and at 7 and 28 days after PB2452 infusion]

   AUC from time 0 extrapolated to infinity if data permit)

9. PB2452 Pharmacokinetic profile - t½ (Cohorts 1-6) [Before dosing and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours, and at 7 and 28 days after PB2452 infusion]

   Terminal elimination half-life (if data permit)

10. PB2452 Pharmacokinetic profile - t½ (Cohorts 7-10) [Before dosing and at 5 min, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 8.25, 8.5, 9, 10, 11, 12, 16, 20, 24, 32, and 48 hours, and at 7 and 28 days after PB2452 infusion]

    Terminal elimination half-life (if data permit)

11. PB2452 Pharmacokinetic profile - CL (Cohorts 1-6) [Before dosing and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours, and at 7 and 28 days after PB2452 infusion]

    Apparent clearance (if data permit)

12. PB2452 Pharmacokinetic profile - CL (Cohorts 7-10) [Before dosing and at 5 min, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 8.25, 8.5, 9, 10, 11, 12, 16, 20, 24, 32, and 48 hours, and at 7 and 28 days after PB2452 infusion]

    Apparent clearance (if data permit)

13. Ticagrelor and Ticagrelor Active Metabolite (TAM) Pharmacokinetic profile - Cmax (Cohorts 1-6) [Before dosing and at 0.5, 1, 2, 3, 6, 12, and 24 hours after PB2452 infusion and 5th ticagrelor dose.]

    Observed maximum plasma concentration

14. Ticagrelor and Ticagrelor Active Metabolite (TAM) Pharmacokinetic profile - Cmax (Cohorts 7-10) [Before dosing and at 5 min, 0.25, 0.5, 1, 2, 3, 6, 8, 10, 12, 14, 16, 20, 24, 32 and 48 hours after PB2452 infusion and 5th ticagrelor dose. And 0.5, 1, 2, 3, 6, 12, and 24 hours after the Day 2 post-PB2452 6th ticagrelor dose (if received).]

    Observed maximum plasma concentration

15. Ticagrelor and Ticagrelor Active Metabolite (TAM) Pharmacokinetic profile - Tmax (Cohorts 1-6) [Before dosing and at 0.5, 1, 2, 3, 6, 12, and 24 hours after PB2452 infusion and 5th ticagrelor dose.]

    Time to reach the observed maximum plasma concentration

16. Ticagrelor and Ticagrelor Active Metabolite (TAM) Pharmacokinetic profile - Tmax (Cohorts 7-10) [Before dosing and at 5 min, 0.25, 0.5, 1, 2, 3, 6, 8, 10, 12, 14, 16, 20, 24, 32 and 48 hours after PB2452 infusion and 5th ticagrelor dose. And 0.5, 1, 2, 3, 6, 12, and 24 hours after the Day 2 post-PB2452 6th ticagrelor dose (if received).]

    Time to reach the observed maximum plasma concentration

17. Ticagrelor and Ticagrelor Active Metabolite (TAM) Pharmacokinetic profile - AUC(0-12) (Cohorts 1-6) [Before dosing and at 0.5, 1, 2, 3, 6, 12, and 24 hours after PB2452 infusion and 5th ticagrelor dose.]

    AUC from time 0 to 12 hours after dosing

18. Ticagrelor and Ticagrelor Active Metabolite (TAM) Pharmacokinetic profile - AUC(0-12) (Cohorts 7-10) [Before dosing and at 5 min, 0.25, 0.5, 1, 2, 3, 6, 8, 10, 12, 14, 16, 20, 24, 32 and 48 hours after PB2452 infusion and 5th ticagrelor dose. And 0.5, 1, 2, 3, 6, 12, and 24 hours after the Day 2 post-PB2452 6th ticagrelor dose (if received).]

    AUC from time 0 to 12 hours after dosing

19. Ticagrelor and Ticagrelor Active Metabolite (TAM) Pharmacokinetic profile - AUC(0-24) (Cohorts 1-6) [Before dosing and at 0.5, 1, 2, 3, 6, 12, and 24 hours after PB2452 infusion and 5th ticagrelor dose.]

    AUC from time 0 to 24 hours after dosing

20. Ticagrelor and Ticagrelor Active Metabolite (TAM) Pharmacokinetic profile - AUC(0-24) (Cohorts 7-10) [Before dosing and at 5 min, 0.25, 0.5, 1, 2, 3, 6, 8, 10, 12, 14, 16, 20, 24, 32 and 48 hours after PB2452 infusion and 5th ticagrelor dose. And 0.5, 1, 2, 3, 6, 12, and 24 hours after the Day 2 post-PB2452 6th ticagrelor dose (if received).]

    AUC from time 0 to 24 hours after dosing

21. Ticagrelor and Ticagrelor Active Metabolite (TAM) Pharmacokinetic profile - AUC0-inf (Cohorts 1-6) [Before dosing and at 0.5, 1, 2, 3, 6, 12, and 24 hours after PB2452 infusion and 5th ticagrelor dose.]

    AUC from time 0 extrapolated to infinity if data permit)

22. Ticagrelor and Ticagrelor Active Metabolite (TAM) Pharmacokinetic profile - AUC0-inf (Cohorts 7-10) [Before dosing and at 5 min, 0.25, 0.5, 1, 2, 3, 6, 8, 10, 12, 14, 16, 20, 24, 32 and 48 hours after PB2452 infusion and 5th ticagrelor dose. And 0.5, 1, 2, 3, 6, 12, and 24 hours after the Day 2 post-PB2452 6th ticagrelor dose (if received).]

    AUC from time 0 extrapolated to infinity if data permit)

23. Ticagrelor and Ticagrelor Active Metabolite (TAM) Pharmacokinetic profile - t½ (Cohorts 1-6) [Before dosing and at 0.5, 1, 2, 3, 6, 12, and 24 hours after PB2452 infusion and 5th ticagrelor dose.]

    Terminal elimination half-life (if data permit)

24. Ticagrelor and Ticagrelor Active Metabolite (TAM) Pharmacokinetic profile - t½ (Cohorts 7-10) [Before dosing and at 5 min, 0.25, 0.5, 1, 2, 3, 6, 8, 10, 12, 14, 16, 20, 24, 32 and 48 hours after PB2452 infusion and 5th ticagrelor dose. And 0.5, 1, 2, 3, 6, 12, and 24 hours after the Day 2 post-PB2452 6th ticagrelor dose (if received).]

    Terminal elimination half-life (if data permit)

25. Ticagrelor Active Metabolite (TAM) Pharmacokinetic profile - Cmax ratio (metabolite:parent) (Cohorts 1-6) [Before dosing and at 0.5, 1, 2, 3, 6, 12, and 24 hours after PB2452 infusion.]

26. Ticagrelor Active Metabolite (TAM) Pharmacokinetic profile - Cmax ratio (metabolite:parent) (Cohorts 7-10) [Before dosing and at 5 min, 0.25, 0.5, 1, 2, 3, 6, 8, 10, 12, 14, 16, 20, 24, 32 and 48 hours after PB2452 infusion and 5th ticagrelor dose. And 0.5, 1, 2, 3, 6, 12, and 24 hours after the Day 2 post-PB2452 6th ticagrelor dose (if received).]

27. Ticagrelor Active Metabolite (TAM) Pharmacokinetic profile - AUC0-24 ratio (metabolite:parent) (Cohorts 1-6) [Before dosing and at 0.5, 1, 2, 3, 6, 12, and 24 hours after PB2452 infusion.]

28. Ticagrelor Active Metabolite (TAM) Pharmacokinetic profile - AUC0-24 ratio (metabolite:parent) (Cohorts 7-10) [Before dosing and at 5 min, 0.25, 0.5, 1, 2, 3, 6, 8, 10, 12, 14, 16, 20, 24, 32 and 48 hours after PB2452 infusion and 5th ticagrelor dose. And 0.5, 1, 2, 3, 6, 12, and 24 hours after the Day 2 post-PB2452 6th ticagrelor dose (if received).]

29. Ticagrelor and Ticagrelor Active Metabolite (TAM) Urine Pharmacokinetic profile - Ae (Cohorts 1-6) [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.]

    Total amount of drug excreted in urine

30. Ticagrelor and Ticagrelor Active Metabolite (TAM) Urine Pharmacokinetic profile - Ae (Cohorts 7-10) [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.]

    Total amount of drug excreted in urine

31. Ticagrelor and Ticagrelor Active Metabolite (TAM) Urine Pharmacokinetic profile - Aet1-t2 [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.]

    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

32. Ticagrelor and Ticagrelor Active Metabolite (TAM) Urine Pharmacokinetic profile - Fe [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

33. Ticagrelor and Ticagrelor Active Metabolite (TAM) Urine Pharmacokinetic profile - CLr [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

34. Effectiveness of single ascending doses of PB2452 - PRU at each assessment point (Cohorts 1-6) [Before dosing and at 0.5, 1, 2, 3, 6, 12, 24, and 48 hours after PB2452 infusion and 5th ticagrelor dose.]

    P2Y12 Reaction Units with VerifyNow P2Y12 Assay

35. Effectiveness of single ascending doses of PB2452 - PRU at each assessment point (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 (if required).]

    P2Y12 Reaction Units with VerifyNow P2Y12 Assay

36. Effectiveness of single ascending doses of PB2452 - P2Y12 Reaction Units with VerifyNow P2Y12 Assay (Cohorts 1-6) [Before dosing and again before dosing and at 0.5, 1, 2, 3, 6, 12, 24, and 48 hours after PB2452 infusion and 5th ticagrelor dose.]

37. Effectiveness of single ascending doses of PB2452 - P2Y12 Reaction Units with VerifyNow P2Y12 Assay (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 (if required).]

38. Effectiveness of single ascending doses of PB2452 - VASP by ELISA (Cohorts 1-6) [Before dosing and again before dosing and at 0.5, 1, 2, 3, 6, 12, 24, and 48 hours after PB2452 infusion and 5th ticagrelor dose.]

    Vasodilator stimulated response by ELISA

39. Effectiveness of single ascending doses of PB2452 - VASP by ELISA (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 (if required).]

    Vasodilator stimulated response by ELISA

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 50 Years
• Sexes Eligible for Study: All
• Accepts 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

1. 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.

2. The subject agrees to comply with all protocol requirements.

3. 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

1. 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

1. 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.

2. 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.

3. 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).

4. 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.

5. 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.

6. 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.

7. 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.

8. 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).

9. The subject has previously received MEDI2452 (PB2452).

10. 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.

11. 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.

12. 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.

13. 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.

14. 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.

15. 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	PPD	Austin	Texas	United States	78744

Sponsors and Collaborators

• PhaseBio Pharmaceuticals Inc.

Investigators

• Principal Investigator: LuAnn Bundrant, MD, PPD

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: PhaseBio Pharmaceuticals Inc.
• ClinicalTrials.gov Identifier: NCT03492385
• Other Study ID Numbers: PB2452-PT-CL-0001
• First Posted: Apr 10, 2018
• Last Update Posted: Feb 8, 2019
• Last Verified: Feb 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Ticagrelor

Study Results

No Results Posted as of Feb 8, 2019