Clinical trial NCT03492385 (phase 1, status: completed)
Conditions: healthy
ICD codes: Z76.3, Z76.2
Drugs: pb2452 infusion, placebo - sodium chloride, ticagrelor oral tablet - pre-treatment, ticagrelor oral tablet - pre-treatment and post-treatment
SMILES: CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O, [H][C@@](N1CCC2=C(C1)C=CS2)(C(=O)OC)C1=CC=CC=C1Cl, [H][C@@](N1CCC2=C(C1)C=CS2)(C(=O)OC)C1=CC=CC=C1Cl
Eligibility criteria:

        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

          4. 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.

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

          6. 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

          6. 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

          7. 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.

          8. 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.

          9. 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).

         10. 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.

         11. 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.

         12. 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.

         13. 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.

         14. 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).

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

         16. 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.

         17. 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.

         18. 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.

         19. 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.

         20. 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.

         21. 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.