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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 1: 100 mg PB2452 or Placebo (no Ticagrelor) | Experimental | PB2452 Infusion or Placebo - Sodium Chloride |
|
| 2: 300 mg PB2452 or Placebo (no Ticagrelor) | Experimental | PB2452 Infusion or Placebo - Sodium Chloride |
|
| 3: 1000 mg PB2452 or Placebo (no Ticagrelor) | Experimental | PB2452 Infusion or Placebo - Sodium Chloride |
|
| 4: 1000 mg PB2452 or Placebo (Ticagrelor Pre-Trx) | Experimental | PB2452 Infusion or Placebo - Sodium Chloride With Ticagrelor Oral Tablet: 180 mg+90 mg BID for a total of 5 doses |
|
| 5: 3000 mg PB2452 or Placebo (Ticagrelor Pre-Trx) | Experimental | PB2452 Infusion or Placebo - Sodium Chloride with Ticagrelor Oral Tablet: 180 mg+90 mg BID for a total of 5 doses |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| PB2452 Infusion | Drug | 30 minute - 12 hour infusion |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Adverse Events (AEs) | An AE is defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug-related. | Day -3 (Cohorts 4 through 10) or Day -1 (Cohorts 1 through 3) until Day 28 |
| Number of Participants With Clinically Significant Laboratory Abnormalities | Number of participants with clinically significant abnormal laboratory findings for hematology, coagulation, serum chemistry, urinalysis and drug tests. | 30 Day - Starting day of dosing |
| Change in Diastolic Blood Pressure | Diastolic blood pressure measurements were measured at specific time points. | Days 1, 2, 3, 4, 7 and 28 |
| Change in Systolic Blood Pressure | Systolic blood pressure measurements were measured at specific time points. | Days 1, 2, 3, 4, 7 and 28 |
| Change In Oral Body Temperature | Body temperature measurements were measured at specific time points. | Days 1, 2, 3, 4, 7 and 28 |
| Change In Respiratory Rate | Respiratory rate measurements were measured at specific time points. | Days 1, 2, 3, 4, 7 and 28 |
| Change In Heart Rate | Heart rate measurements were measured at specific time points. |
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Inclusion Criteria:
The subject is male or female between 18 and 50 years of age, inclusive.
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.
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:
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.
The subject agrees to comply with all protocol requirements.
The subject is able to provide written informed consent.
Exclusion Criteria:
History of any clinically significant acute or chronic disease or medical disorder.
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.
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).
Any clinically significant abnormal findings in physical examination, vital signs, laboratory assessments, and ECG parameters identified during screening or check-in.
Any history of arterial or venous thrombosis, including any of the following:
Any increased risk of bleeding, including the following:
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.
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.
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).
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.
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.
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.
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.
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).
The subject has previously received MEDI2452 (PB2452).
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.
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.
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.
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.
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.
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.
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| Name | Affiliation | Role |
|---|---|---|
| LuAnn Bundrant, MD | PPD Development, LP | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| PPD | Austin | Texas | 78744 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 30883047 | Derived | Bhatt DL, Pollack CV, Weitz JI, Jennings LK, Xu S, Arnold SE, Umstead BR, Mays MC, Lee JS. Antibody-Based Ticagrelor Reversal Agent in Healthy Volunteers. N Engl J Med. 2019 May 9;380(19):1825-1833. doi: 10.1056/NEJMoa1901778. Epub 2019 Mar 17. |
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Healthy participants who met all the inclusion criteria and none of the exclusion criteria were randomly assigned to receive either PB2452 or placebo in a ratio of 3:1 in all treatment cohorts.
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| ID | Title | Description |
|---|---|---|
| FG000 | Cohort 1: 100 mg PB2452 (no Ticagrelor) | PB2452 Infusion: single 30-minute intravenous (IV) infusion of 100 mg PB2452 |
| FG001 | Cohort 2: 300 mg PB2452 (no Ticagrelor) | PB2452 Infusion: single 30-minute IV infusion of 300 mg PB2452 |
| FG002 | Cohort 3: 1000 mg PB2452 (no Ticagrelor) | PB2452 Infusion: single 30-minute IV infusion of 1000 mg PB2452 |
| FG003 | Cohort 1 to 3: Placebo | Placebo - Sodium Chloride: single 30-minute IV infusion of placebo |
| FG004 | Cohort 4: 1000 mg PB2452 (Ticagrelor Pre-Trx) | PB2452 Infusion: single 30-minute IV infusion of 1000 mg PB2452 Ticagrelor Oral Tablet - Pre-Treatment: Ticagrelor 180 mg + 90 mg twice daily (BID) for 5 doses prior to administration of a single IV dose of PB2452 |
| FG005 | Cohort 5: 3000 mg PB2452 (Ticagrelor Pre-Trx) | PB2452 Infusion: single 30-minute IV infusion of 3000 mg PB2452 Ticagrelor Oral Tablet - Pre-Treatment: Ticagrelor 180 mg + 90 mg BID for 5 doses prior to administration of a single IV dose of PB2452 |
| FG006 | Cohort 6: 9000 mg PB2452 (Ticagrelor Pre-Trx) | PB2452 Infusion: single 30-minute IV infusion of 9000 mg PB2452 Ticagrelor Oral Tablet - Pre-Treatment: Ticagrelor 180 mg + 90 mg BID for 5 doses prior to administration of a single IV dose of PB2452 |
| FG007 | Cohort 4 to 6: Placebo | Placebo - Sodium Chloride: single 30-minute IV infusion of placebo |
| FG008 | Cohort 7: 18000 mg PB2452 (Ticagrelor Pre-Trx) | PB2452 Infusion: single IV infusion of 18000 mg PB2452 for 8 hours Ticagrelor Oral Tablet - Pre-Treatment: Ticagrelor 180 mg + 90 mg BID for 5 doses prior to administration of a single IV dose of PB2452 |
| FG009 | Cohort 8: 18000 mg PB2452 (Ticagrelor Pre-Trx) | PB2452 Infusion: single IV infusion of 18000 mg PB2452 for 12 hours Ticagrelor Oral Tablet - Pre-Treatment: Ticagrelor 180 mg + 90 mg BID for 5 doses prior to administration of a single IV dose of PB2452 |
| FG010 | Cohort 9: 18000 mg PB2452 (Ticagrelor Pre-Trx) | PB2452 Infusion: single IV infusion of 18000 mg PB2452 for 16 hours and 20 minutes Ticagrelor Oral Tablet - Pre-Treatment: Ticagrelor 180 mg + 90 mg BID for 5 doses prior to administration of a single IV dose of PB2452 |
| FG011 | Cohort 10: 18000 mg PB2452 (Ticagrelor Pre-Trx) | PB2452 Infusion: single IV infusion of 18000 mg PB2452 for 16 hours and 12 minutes Ticagrelor Oral Tablet - Pre-Treatment: Ticagrelor 180 mg + 90 mg BID for 5 doses prior to administration of a single IV dose of PB2452 |
| FG012 | Cohort 7 to 10: Placebo | Placebo - Sodium Chloride: single 8-hour to 16.5-hour IV infusion of placebo |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
Safety population: all participants who received any amount of study drug.
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| ID | Title | Description |
|---|---|---|
| BG000 | Cohort 1: 100 mg PB2452 (no Ticagrelor) | PB2452 Infusion: single 30-minute IV infusion of 100 mg PB2452 |
| BG001 | Cohort 2: 300 mg PB2452 (no Ticagrelor) | PB2452 Infusion: single 30-minute IV infusion of 300 mg PB2452 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Participants With Adverse Events (AEs) | An AE is defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug-related. | Safety population: all participants who received any amount of study drug. | Posted | Count of Participants | Participants | Day -3 (Cohorts 4 through 10) or Day -1 (Cohorts 1 through 3) until Day 28 |
|
Adverse events were assessed from Day -3 (Cohorts 4 through 10) or Day -1 (Cohorts 1 through 3) until completion of all study procedures and EOS assessments (Day 28).
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Cohort 1: 100 mg PB2452 (no Ticagrelor) | PB2452 Infusion: single 30-minute IV infusion of 100 mg PB2452 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Alcohol poisoning | Injury, poisoning and procedural complications | MedDRA (21.0) | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Infusion site bruising | General disorders | MedDRA (21.0) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Michele LaRussa SVP, Chief Regulatory Officer | SFJ Pharmaceuticals, Inc. | 925-223-6233 | Bentracimab.General@SFJ-Pharma.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Feb 1, 2018 | Jan 9, 2024 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Oct 12, 2018 | Jan 9, 2024 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D000359 | Aftercare |
| ID | Term |
|---|---|
| D003266 | Continuity of Patient Care |
| D005791 | Patient Care |
| D013812 | Therapeutics |
| D006296 | Health Services |
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| 6: 9000 mg PB2452 or Placebo (Ticagrelor Pre-Trx) | Experimental | PB2452 Infusion or Placebo - Sodium Chloride with Ticagrelor Oral Tablet: 180 mg+90 mg BID for a total of 5 doses |
|
| 7: 18000 mg PB2452 or Placebo (Ticagrelor Pre-Trx) | Experimental | PB2452 Infusion or Placebo - Sodium Chloride with Ticagrelor Oral Tablet: 180 mg+90 mg BID for a total of 5 doses |
|
| 8: Dose TBD mg PB2452 or Placebo (Ticagrelor Pre-Trx) | Experimental | PB2452 Infusion or Placebo - Sodium Chloride with Ticagrelor Oral Tablet: 180 mg+90 mg BID for 5 doses |
|
| 9: Dose TBD mg PB2452 or Placebo (Ticagrelor Pre and Post-Trx) | Experimental | 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 |
|
| 10: Dose TBD mg PB2452 or Placebo (Ticagrelor Pre-Txt) | Experimental | PB2452 Infusion or Placebo - Sodium Chloride with Ticagrelor Oral Tablet: 180 mg+90 mg BID for 5 doses |
|
| Placebo - Sodium Chloride | Drug | 30 minute - 12 hour infusion |
|
| Ticagrelor Oral Tablet - Pre-Treatment | Drug | Ticagrelor 180 mg + 90 mg BID for 5 doses prior to MEDI2452 (PB2452) or Placebo |
|
| Ticagrelor Oral Tablet - Pre-Treatment and Post-Treatment | Drug | 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 |
|
| Days 1, 2, 3, 4, 7 and 28 |
| Incidence of Clinically Significant 12-Lead Electrocardiogram (ECG) Findings | Number of participants per cohort with clinically significant ECG findings. | 60 days - Starting up to 28 days prior to dosing |
| Incidence of Clinically Significant Cardiac Telemetry Findings | Number of participants per cohort with clinically significant cardiac telemetry findings. | 3 Days - Starting 1 day prior to dosing up to 2 days after dosing |
| Participants Experiencing Anti-drug Antibodies (ADAs) | Incidence of Immunogenicity. | Day -3, Day -1, Day 7, and Day 28 |
| Maximal Percent of Baseline Platelet Aggregation (PA(Max)) in Cohorts 4-6 | Effectiveness Of Single Ascending Doses Of PB2452. IPA [maximum (max)] induced by 20 µM adenosine diphosphate (ADP) at each assessment point. | Before dosing and at 0.5, 1, 2, 3, 6, 12, 24, and 48 hours after PB2452 infusion and 5th ticagrelor dose. |
| Final Extent Percent of Baseline Platelet Aggregation in Cohorts 4-6 | Effectiveness Of Single Ascending Doses Of PB2452. IPA [final extent] induced by 20 µM adenosine diphosphate (ADP) at each assessment point. | Before dosing and at 0.5, 1, 2, 3, 6, 12, 24, and 48 hours after PB2452 infusion and 5th ticagrelor dose. |
| Maximal Actual Platelet Aggregation (APA(Max)) (Cohorts 4-6) | Effectiveness Of Single Ascending Doses Of PB2452 - Inhibition of maximal platelet aggregation. | 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). |
| Time to Maximum Platelet Aggregation (TPA(Max)) (Cohorts 4-6) | Effectiveness Of Single Ascending Doses Of PB2452 - Time to IPAmax. | Before dosing and at 0.5, 1, 2, 3, 6, 12, 24, and 48 hours after PB2452 infusion and 5th ticagrelor dose. |
| Maximal Percent of Baseline Platelet Aggregation (PA(Max)) (Cohorts 7-10) | Effectiveness Of Single Ascending Doses Of PB2452 - IPA (max) induced by 20 µM ADP at each assessment point. | 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. |
| Final Extent Percent of Baseline Platelet Aggregation (Cohorts 7-10) | Effectiveness Of Single Ascending Doses Of PB2452 - IPA (max) induced by 20 µM ADP at each assessment point. | 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. |
| Maximal Actual Platelet Aggregation (APA(Max)) (Cohorts 7-10) | Effectiveness Of Single Ascending Doses Of PB2452 - Inhibition of maximal platelet aggregation. | 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 |
| Time to Maximum Platelet Aggregation (TPA(Max))(Cohorts 7-10) | Effectiveness Of Single Ascending Doses Of PB2452 - Time to IPAmax | 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. |
| BG002 | Cohort 3: 1000 mg PB2452 (no Ticagrelor) | PB2452 Infusion: single 30-minute IV infusion of 1000 mg PB2452 |
| BG003 | Cohort 1 to 3: Placebo | Placebo - Sodium Chloride: single 30-minute IV infusion of placebo |
| BG004 | Cohort 4: 1000 mg PB2452 (Ticagrelor Pre-Trx) | PB2452 Infusion: single 30-minute IV infusion of 1000 mg PB2452 Ticagrelor Oral Tablet - Pre-Treatment: Ticagrelor 180 mg + 90 mg BID for 5 doses prior to administration of a single IV dose of PB2452 |
| BG005 | Cohort 5: 3000 mg PB2452 (Ticagrelor Pre-Trx) | PB2452 Infusion: single 30-minute IV infusion of 3000 mg PB2452 Ticagrelor Oral Tablet - Pre-Treatment: Ticagrelor 180 mg + 90 mg BID for 5 doses prior to administration of a single IV dose of PB2452 |
| BG006 | Cohort 6: 9000 mg PB2452 (Ticagrelor Pre-Trx) | PB2452 Infusion: single 30-minute IV infusion of 9000 mg PB2452 Ticagrelor Oral Tablet - Pre-Treatment: Ticagrelor 180 mg + 90 mg BID for 5 doses prior to administration of a single IV dose of PB2452 |
| BG007 | Cohort 4 to 6: Placebo | Placebo - Sodium Chloride: single 30-minute IV infusion of placebo |
| BG008 | Cohort 7: 18000 mg PB2452 (Ticagrelor Pre-Trx) | PB2452 Infusion: single IV infusion of 18000 mg PB2452 for 8 hours Ticagrelor Oral Tablet - Pre-Treatment: Ticagrelor 180 mg + 90 mg BID for 5 doses prior to administration of a single IV dose of PB2452 |
| BG009 | Cohort 8: 18000 mg PB2452 (Ticagrelor Pre-Trx) | PB2452 Infusion: single IV infusion of 18000 mg PB2452 for 12 hours Ticagrelor Oral Tablet - Pre-Treatment: Ticagrelor 180 mg + 90 mg BID for 5 doses prior to administration of a single IV dose of PB2452 |
| BG010 | Cohort 9: 18000 mg PB2452 (Ticagrelor Pre-Trx) | PB2452 Infusion: single IV infusion of 18000 mg PB2452 for 16 hours and 20 minutes Ticagrelor Oral Tablet - Pre-Treatment: Ticagrelor 180 mg + 90 mg BID for 5 doses prior to administration of a single IV dose of PB2452 |
| BG011 | Cohort 10: 18000 mg PB2452 (Ticagrelor Pre-Trx) | PB2452 Infusion: single IV infusion of 18000 mg PB2452 for 16 hours and 12 minutes Ticagrelor Oral Tablet - Pre-Treatment: Ticagrelor 180 mg + 90 mg BID for 5 doses prior to administration of a single IV dose of PB2452 |
| BG012 | Cohort 7 to 10: Placebo | Placebo - Sodium Chloride: single 8-hour to 16.5-hour IV infusion of placebo |
| BG013 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Population of participants based on their ethnicity. | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Population of participants based on their race. | Count of Participants | Participants |
|
| OG002 | Cohort 3: 1000 mg PB2452 (no Ticagrelor) | PB2452 Infusion: single 30-minute IV infusion of 1000 mg PB2452 |
| OG003 | Cohort 1 to 3: Placebo | Placebo - Sodium Chloride: single 30-minute IV infusion of placebo |
| OG004 | Cohort 4: 1000 mg PB2452 (Ticagrelor Pre-Trx) | PB2452 Infusion: single 30-minute IV infusion of 1000 mg PB2452 Ticagrelor Oral Tablet - Pre-Treatment: Ticagrelor 180 mg + 90 mg BID for 5 doses prior to administration of a single IV dose of PB2452 |
| OG005 | Cohort 5: 3000 mg PB2452 (Ticagrelor Pre-Trx) | PB2452 Infusion: single 30-minute IV infusion of 3000 mg PB2452 Ticagrelor Oral Tablet - Pre-Treatment: Ticagrelor 180 mg + 90 mg BID for 5 doses prior to administration of a single IV dose of PB2452 |
| OG006 | Cohort 6: 9000 mg PB2452 (Ticagrelor Pre-Trx) | PB2452 Infusion: single 30-minute IV infusion of 9000 mg PB2452 Ticagrelor Oral Tablet - Pre-Treatment: Ticagrelor 180 mg + 90 mg BID for 5 doses prior to administration of a single IV dose of PB2452 |
| OG007 | Cohort 4 to 6: Placebo | Placebo - Sodium Chloride: single 30-minute IV infusion of placebo |
| OG008 | Cohort 7: 18000 mg PB2452 (Ticagrelor Pre-Trx) | PB2452 Infusion: single IV infusion of 18000 mg PB2452 for 8 hours Ticagrelor Oral Tablet - Pre-Treatment: Ticagrelor 180 mg + 90 mg BID for 5 doses prior to administration of a single IV dose of PB2452 |
| OG009 | Cohort 8: 18000 mg PB2452 (Ticagrelor Pre-Trx) | PB2452 Infusion: single IV infusion of 18000 mg PB2452 for 12 hours Ticagrelor Oral Tablet - Pre-Treatment: Ticagrelor 180 mg + 90 mg BID for 5 doses prior to administration of a single IV dose of PB2452 |
| OG010 | Cohort 9: 18000 mg PB2452 (Ticagrelor Pre-Trx) | PB2452 Infusion: single IV infusion of 18000 mg PB2452 for 16 hours and 20 minutes Ticagrelor Oral Tablet - Pre-Treatment: Ticagrelor 180 mg + 90 mg BID for 5 doses prior to administration of a single IV dose of PB2452 |
| OG011 | Cohort 10: 18000 mg PB2452 (Ticagrelor Pre-Trx) | PB2452 Infusion: single IV infusion of 18000 mg PB2452 for 16 hours and 12 minutes Ticagrelor Oral Tablet - Pre-Treatment: Ticagrelor 180 mg + 90 mg BID for 5 doses prior to administration of a single IV dose of PB2452 |
| OG012 | Cohort 7 to 10: Placebo | Placebo - Sodium Chloride: single 8-hour to 16.5-hour IV infusion of placebo |
|
|
| Primary | Number of Participants With Clinically Significant Laboratory Abnormalities | Number of participants with clinically significant abnormal laboratory findings for hematology, coagulation, serum chemistry, urinalysis and drug tests. | Safety population: all participants who received any amount of study drug. | Posted | Count of Participants | Participants | 30 Day - Starting day of dosing |
|
|
|
| Primary | Change in Diastolic Blood Pressure | Diastolic blood pressure measurements were measured at specific time points. | Safety population: all participants who received any amount of study drug. | Posted | Mean | Standard Deviation | mmHg | Days 1, 2, 3, 4, 7 and 28 |
|
|
|
| Primary | Change in Systolic Blood Pressure | Systolic blood pressure measurements were measured at specific time points. | Safety population: all participants who received any amount of study drug. | Posted | Mean | Standard Deviation | mmHg | Days 1, 2, 3, 4, 7 and 28 |
|
|
|
| Primary | Change In Oral Body Temperature | Body temperature measurements were measured at specific time points. | Safety population: all participants who received any amount of study drug. | Posted | Mean | Standard Deviation | Degrees Celsius | Days 1, 2, 3, 4, 7 and 28 |
|
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| Primary | Change In Respiratory Rate | Respiratory rate measurements were measured at specific time points. | Safety population: all participants who received any amount of study drug. | Posted | Mean | Standard Deviation | Breaths per minute | Days 1, 2, 3, 4, 7 and 28 |
|
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| Primary | Change In Heart Rate | Heart rate measurements were measured at specific time points. | Safety population: all participants who received any amount of study drug. | Posted | Mean | Standard Deviation | Beats per minute | Days 1, 2, 3, 4, 7 and 28 |
|
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| Primary | Incidence of Clinically Significant 12-Lead Electrocardiogram (ECG) Findings | Number of participants per cohort with clinically significant ECG findings. | Safety population: all participants who received any amount of study drug. | Posted | Count of Participants | Participants | 60 days - Starting up to 28 days prior to dosing |
|
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| Primary | Incidence of Clinically Significant Cardiac Telemetry Findings | Number of participants per cohort with clinically significant cardiac telemetry findings. | Safety population: all participants who received any amount of study drug. | Posted | Count of Participants | Participants | 3 Days - Starting 1 day prior to dosing up to 2 days after dosing |
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| Primary | Participants Experiencing Anti-drug Antibodies (ADAs) | Incidence of Immunogenicity. | Safety population: all participants who received any amount of study drug. | Posted | Count of Participants | Participants | Day -3, Day -1, Day 7, and Day 28 |
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| Primary | Maximal Percent of Baseline Platelet Aggregation (PA(Max)) in Cohorts 4-6 | Effectiveness Of Single Ascending Doses Of PB2452. IPA [maximum (max)] induced by 20 µM adenosine diphosphate (ADP) at each assessment point. | Pharmacodynamic (PD) Population: all participants who received at least 1 dose of ticagrelor and had at least 1 measurable post dose light transmission aggregometry (LTA) value. PD samples were not collected for participants in Cohorts 1 to 3; therefore, they were not included in the PD Population. | Posted | Mean | Standard Deviation | percentage | Before dosing and at 0.5, 1, 2, 3, 6, 12, 24, and 48 hours after PB2452 infusion and 5th ticagrelor dose. |
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| Primary | Final Extent Percent of Baseline Platelet Aggregation in Cohorts 4-6 | Effectiveness Of Single Ascending Doses Of PB2452. IPA [final extent] induced by 20 µM adenosine diphosphate (ADP) at each assessment point. | Pharmacodynamic (PD) Population: all participants who received at least 1 dose of ticagrelor and had at least 1 measurable post dose light transmission aggregometry (LTA) value. PD samples were not collected for participants in Cohorts 1 to 3; therefore, they were not included in the PD Population. | Posted | Mean | Standard Deviation | percentage | Before dosing and at 0.5, 1, 2, 3, 6, 12, 24, and 48 hours after PB2452 infusion and 5th ticagrelor dose. |
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| Primary | Maximal Actual Platelet Aggregation (APA(Max)) (Cohorts 4-6) | Effectiveness Of Single Ascending Doses Of PB2452 - Inhibition of maximal platelet aggregation. | PD Population: all participants who received at least 1 dose of ticagrelor and had at least 1 measurable post dose LTA value. PD samples were not collected for participants in Cohorts 1 to 3, therefore, they were not included in the PD Population. | Posted | Mean | Standard Deviation | percentage | 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). |
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| Primary | Time to Maximum Platelet Aggregation (TPA(Max)) (Cohorts 4-6) | Effectiveness Of Single Ascending Doses Of PB2452 - Time to IPAmax. | PD Population: all participants who received at least 1 dose of ticagrelor and had at least 1 measurable post dose LTA value. PD samples were not collected for participants in Cohorts 1 to 3, therefore, they were not included in the PD Population. | Posted | Median | Full Range | hours | Before dosing and at 0.5, 1, 2, 3, 6, 12, 24, and 48 hours after PB2452 infusion and 5th ticagrelor dose. |
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| Primary | Maximal Percent of Baseline Platelet Aggregation (PA(Max)) (Cohorts 7-10) | Effectiveness Of Single Ascending Doses Of PB2452 - IPA (max) induced by 20 µM ADP at each assessment point. | PD Population: all participants who received at least 1 dose of ticagrelor and had at least 1 measurable post dose LTA value. | Posted | Mean | Standard Deviation | percentage | 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. |
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| Primary | Final Extent Percent of Baseline Platelet Aggregation (Cohorts 7-10) | Effectiveness Of Single Ascending Doses Of PB2452 - IPA (max) induced by 20 µM ADP at each assessment point. | PD Population: all participants who received at least 1 dose of ticagrelor and had at least 1 measurable post dose LTA value. | Posted | Mean | Standard Deviation | percentage | 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. |
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| Primary | Maximal Actual Platelet Aggregation (APA(Max)) (Cohorts 7-10) | Effectiveness Of Single Ascending Doses Of PB2452 - Inhibition of maximal platelet aggregation. | PD Population: all participants who received at least 1 dose of ticagrelor and had at least 1 measurable post dose LTA value. | Posted | Mean | Standard Deviation | percentage | 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 |
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| Primary | Time to Maximum Platelet Aggregation (TPA(Max))(Cohorts 7-10) | Effectiveness Of Single Ascending Doses Of PB2452 - Time to IPAmax | PD Population: all participants who received at least 1 dose of ticagrelor and had at least 1 measurable post dose LTA value. | Posted | Median | Full Range | hours | 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. |
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| 0 |
| 3 |
| 0 |
| 3 |
| 0 |
| 3 |
| EG001 | Cohort 2: 300 mg PB2452 (no Ticagrelor) | PB2452 Infusion: single 30-minute IV infusion of 300 mg PB2452 | 0 | 3 | 0 | 3 | 0 | 3 |
| EG002 | Cohort 3: 1000 mg PB2452 (no Ticagrelor) | PB2452 Infusion: single 30-minute IV infusion of 1000 mg PB2452 | 0 | 3 | 0 | 3 | 1 | 3 |
| EG003 | Cohort 1 to 3: Placebo | Placebo - Sodium Chloride: single 30-minute IV infusion of placebo | 0 | 3 | 0 | 3 | 1 | 3 |
| EG004 | Cohort 4: 1000 mg PB2452 (Ticagrelor Pre-Trx) | PB2452 Infusion: single 30-minute IV infusion of 1000 mg PB2452 Ticagrelor Oral Tablet - Pre-Treatment: Ticagrelor 180 mg + 90 mg BID for 5 doses prior to administration of a single IV dose of PB2452 | 0 | 6 | 1 | 6 | 3 | 6 |
| EG005 | Cohort 5: 3000 mg PB2452 (Ticagrelor Pre-Trx) | PB2452 Infusion: single 30-minute IV infusion of 3000 mg PB2452 Ticagrelor Oral Tablet - Pre-Treatment: Ticagrelor 180 mg + 90 mg BID for 5 doses prior to administration of a single IV dose of PB2452 | 0 | 6 | 0 | 6 | 0 | 6 |
| EG006 | Cohort 6: 9000 mg PB2452 (Ticagrelor Pre-Trx) | PB2452 Infusion: single 30-minute IV infusion of 9000 mg PB2452 Ticagrelor Oral Tablet - Pre-Treatment: Ticagrelor 180 mg + 90 mg BID for 5 doses prior to administration of a single IV dose of PB2452 | 0 | 6 | 0 | 6 | 6 | 6 |
| EG007 | Cohort 4 to 6: Placebo | Placebo - Sodium Chloride: single 30-minute IV infusion of placebo | 0 | 6 | 0 | 6 | 1 | 6 |
| EG008 | Cohort 7: 18000 mg PB2452 (Ticagrelor Pre-Trx) | PB2452 Infusion: single IV infusion of 18000 mg PB2452 for 8 hours Ticagrelor Oral Tablet - Pre-Treatment: Ticagrelor 180 mg + 90 mg BID for 5 doses prior to administration of a single IV dose of PB2452 | 0 | 6 | 0 | 6 | 2 | 6 |
| EG009 | Cohort 8: 18000 mg PB2452 (Ticagrelor Pre-Trx) | PB2452 Infusion: single IV infusion of 18000 mg PB2452 for 12 hours Ticagrelor Oral Tablet - Pre-Treatment: Ticagrelor 180 mg + 90 mg BID for 5 doses prior to administration of a single IV dose of PB2452 | 0 | 6 | 0 | 6 | 2 | 6 |
| EG010 | Cohort 9: 18000 mg PB2452 (Ticagrelor Pre-Trx) | PB2452 Infusion: single IV infusion of 18000 mg PB2452 for 16 hours and 20 minutes Ticagrelor Oral Tablet - Pre-Treatment: Ticagrelor 180 mg + 90 mg BID for 5 doses prior to administration of a single IV dose of PB2452 | 0 | 3 | 0 | 3 | 1 | 3 |
| EG011 | Cohort 10: 18000 mg PB2452 (Ticagrelor Pre-Trx) | PB2452 Infusion: single IV infusion of 18000 mg PB2452 for 16 hours and 12 minutes Ticagrelor Oral Tablet - Pre-Treatment: Ticagrelor 180 mg + 90 mg BID for 5 doses prior to administration of a single IV dose of PB2452 | 0 | 6 | 0 | 6 | 2 | 6 |
| EG012 | Cohort 7 to 10: Placebo | Placebo - Sodium Chloride: single 8-hour to 16.5-hour IV infusion of placebo | 0 | 7 | 0 | 7 | 0 | 7 |
| EG013 | All PB2452 | All participants in any cohorts who received PB2452. | 0 | 48 | 1 | 48 | 17 | 48 |
| EG014 | All Placebo | All participants in any cohorts who received placebo. | 0 | 16 | 0 | 16 | 2 | 16 |
| Acute respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA (21.0) | Systematic Assessment |
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| Medical device site reaction | General disorders | MedDRA (21.0) | Systematic Assessment |
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| Infusion site extravasation | General disorders | MedDRA (21.0) | Systematic Assessment |
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| Vessel puncture site bruise | General disorders | MedDRA (21.0) | Systematic Assessment |
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| Infusion site reaction | General disorders | MedDRA (21.0) | Systematic Assessment |
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| Conjunctivitis | Infections and infestations | MedDRA (21.0) | Systematic Assessment |
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| Gastroenteritis | Infections and infestations | MedDRA (21.0) | Systematic Assessment |
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| Nasopharyngitis | Infections and infestations | MedDRA (21.0) | Systematic Assessment |
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| Pharyngitis streptococcal | Infections and infestations | MedDRA (21.0) | Systematic Assessment |
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| Contusion | Injury, poisoning and procedural complications | MedDRA (21.0) | Systematic Assessment |
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| Skin abrasion | Injury, poisoning and procedural complications | MedDRA (21.0) | Systematic Assessment |
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| Upper limb fracture | Injury, poisoning and procedural complications | MedDRA (21.0) | Systematic Assessment |
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| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA (21.0) | Systematic Assessment |
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| Aspiration Pneumonitis | Respiratory, thoracic and mediastinal disorders | MedDRA (21.0) | Systematic Assessment |
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| Eyelid irritation | Eye disorders | MedDRA (21.0) | Systematic Assessment |
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| Abdominal pain | Gastrointestinal disorders | MedDRA (21.0) | Systematic Assessment |
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| Blood urine present | Investigations | MedDRA (21.0) | Systematic Assessment |
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| Musculoskeletal chest pain | Musculoskeletal and connective tissue disorders | MedDRA (21.0) | Systematic Assessment |
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| Dizziness | Nervous system disorders | MedDRA (21.0) | Systematic Assessment |
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| Hematuria | Renal and urinary disorders | MedDRA (21.0) | Systematic Assessment |
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Not provided
Not provided
| D005159 |
| Health Care Facilities Workforce and Services |
| D011320 | Primary Health Care |
| D003191 | Comprehensive Health Care |
| D010346 | Patient Care Management |
| D006298 | Health Services Administration |
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| Change from Baseline - Day 1/0.75 Hour |
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| Change from Baseline - Day 1/2 Hour |
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| Change from Baseline - Day 1/4 Hour |
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| Change from Baseline - Day 1/8 Hour |
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| Change from Baseline - Day 2/24 Hour |
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| Change from Baseline - Day 2/30 Hour |
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| Change from Baseline - Day 2/36 Hour |
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| Change from Baseline - Day 3/42 Hour |
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| Change from Baseline - Day 3/48 Hour |
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| Change from Baseline - Day 4 |
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| Change from Baseline - Day 7 |
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| Change from Baseline - Day 28 |
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| Change from Baseline - Day 1/0.75 Hour |
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| Change from Baseline - Day 1/1 Hour |
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| Change from Baseline - Day 1/2 Hour |
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| Change from Baseline - Day 1/4 Hour |
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| Change from Baseline - Day 1/8 Hour |
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| Change from Baseline - Day 2/24 Hour |
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| Change from Baseline - Day 2/30 Hour |
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| Change from Baseline - Day 2/36 Hour |
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| Change from Baseline - Day 3/42 Hour |
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| Change from Baseline - Day 3/48 Hour |
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| Change from Baseline - Day 4 |
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| Change from Baseline - Day 7 |
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| Change from Baseline - Day 28 |
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| Day -1 |
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| Day 7 |
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| Day 28 |
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