A Study in Healthy Men to Compare 2 Different Formulations of Alteplase
Condition: Healthy
Intervention: Alteplase (from modified manufacturing process); Alteplase (from current manufacturing process); Heparin-Natrium-5000-ratiopharm (unfractionated heparin)
Intervention description: Alteplase, TPA-05; Alteplase, TPA-02; Heparin-Natrium-5000-ratiopharm (unfractionated heparin)
Intervention MeSH terms: Heparin; Calcium heparin; Tissue Plasminogen Activator
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: Part A: Open label Part B: Adaptive two-stage group-sequential design
Masking: None (Open Label)
Enrollment: 30.0
Sex: Male
Minimum age: 18 Years
Maximum age: 45 Years
Healthy volunteers: Accepts Healthy Volunteers

Summary:

      To establish the bioequivalence of alteplase derived from two different manufacturing
      processes.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Healthy male subjects according to the assessment of the investigator, as based on a
             complete medical history including a physical examination, vital signs (blood pressure
             (BP), pulse rate (PR)), 12-lead electrocardiogram (ECG), and clinical laboratory tests

          -  Age of 18 to 45 years (inclusive)

          -  Body mass index (weight divided by height squared) (BMI) of 18.5 to 29.9 kg/m2
             (inclusive)

          -  Body weight of 65 - 100 kg (inclusive) at screening

          -  Signed and dated written informed consent prior to admission to the study, in
             accordance with Good Clinical Practice (GCP) and local legislation

        Exclusion Criteria:

          -  Any finding in the medical examination (including BP, PR or ECG) deviating from normal
             and assessed as clinically relevant by the investigator

          -  Repeated measurement of systolic blood pressure outside the range of 90 to 140 mmHg,
             diastolic blood pressure outside the range of 50 to 90 mmHg, or pulse rate outside the
             range of 45 to 90 bpm

          -  Any laboratory value outside the reference range that the investigator considers to be
             of clinical relevance, e.g. thrombotic predisposition according to thrombophilic
             testing

          -  Any evidence of a concomitant disease assessed as clinically relevant by the
             investigator

          -  Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic,
             immunological or hormonal disorders

          -  Diseases of the central nervous system (including but not limited to any kind of
             seizures or stroke), and other relevant neurological or psychiatric disorders

          -  History of relevant orthostatic hypotension, fainting spells, or blackouts

          -  Chronic or relevant acute infections

          -  History of relevant allergy or hypersensitivity

          -  During COVID-19 pandemic: laboratory test indicative of an ongoing SARS-CoV-2
             infection Further exclusion criteria apply.