A Study in Healthy Men to Compare 2 Different Formulations of Alteplase

Bioequivalence of Alteplase Derived From Two Different Manufacturing Processes Following Intravenous Administration in Healthy Male Volunteers

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

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Alteplase (from modified manufacturing process); Drug: Heparin-Natrium-5000-ratiopharm (unfractionated heparin); Drug: Alteplase (from current manufacturing process)

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Biberach, Germany, 88397
    • Humanpharmakologisches Zentrum Biberach

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part B: Alteplase, TPA-02 then Alteplase, TPA-05	Drug: Alteplase (from modified manufacturing process); Alteplase, TPA-05; Drug: Heparin-Natrium-5000-ratiopharm (unfractionated heparin); Heparin-Natrium-5000-ratiopharm (unfractionated heparin)
Active Comparator: Part B: Alteplase, TPA-05 then Alteplase, TPA-02	Drug: Heparin-Natrium-5000-ratiopharm (unfractionated heparin); Heparin-Natrium-5000-ratiopharm (unfractionated heparin); Drug: Alteplase (from current manufacturing process); Alteplase, TPA-02
Experimental: Part A: Alteplase, TPA-05 then Alteplase, TPA-02; Open-label	Drug: Alteplase (from modified manufacturing process); Alteplase, TPA-05; Drug: Heparin-Natrium-5000-ratiopharm (unfractionated heparin); Heparin-Natrium-5000-ratiopharm (unfractionated heparin)
Active Comparator: Part A: Alteplase, TPA-02 then Alteplase, TPA-05	Drug: Heparin-Natrium-5000-ratiopharm (unfractionated heparin); Heparin-Natrium-5000-ratiopharm (unfractionated heparin); Drug: Alteplase (from current manufacturing process); Alteplase, TPA-02

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part A: Area Under the Concentration-time Curve of Alteplase in Plasma Over the Time Interval From 0 up to the Last Quantifiable Data Point (AUC0-tz)	The area under the concentration-time curve of alteplase in plasma over the time interval from 0 to the last quantifiable data point (AUC0-tz) is reported.	Within 3 hours (h) before and 5 minutes (min), 10min, 15min, 20min, 25min, 30min, 32min, 34min, 36min, 40min, 45min, 50min, 1h, 1.33h, 1.67h, 2h, 3h, 4h and 6h after start of alteplase infusion.
Part B: Area Under the Concentration-time Curve of Alteplase in Plasma Over the Time Interval From 0 up to the Last Quantifiable Data Point (AUC0-tz)	The area under the concentration-time curve of Alteplase in plasma over the time interval from 0 to the last quantifiable data point (AUC0-tz) is reported.	Within 3 hours (h) before and 5 minutes (min), 10min, 15min, 20min, 25min, 30min, 32min, 34min, 36min, 40min, 45min, 50min, 1h, 1.33h, 1.67h, 2h, 3h, 4h and 6h after start of alteplase infusion.
Part A: Maximum Measured Concentration of Alteplase in Plasma (Cmax)	Maximum measured concentration of alteplase in plasma is reported.	Within 3 hours (h) before and 5 minutes (min), 10min, 15min, 20min, 25min, 30min, 32min, 34min, 36min, 40min, 45min, 50min, 1h, 1.33h, 1.67h, 2h, 3h, 4h and 6h after start of alteplase infusion.
Part B: Maximum Measured Concentration of Alteplase in Plasma (Cmax)	Maximum measured concentration of Alteplase in plasma (Cmax) is reported.	Within 3 hours (h) before and 5 minutes (min), 10min, 15min, 20min, 25min, 30min, 32min, 34min, 36min, 40min, 45min, 50min, 1h, 1.33h, 1.67h, 2h, 3h, 4h and 6h after start of alteplase infusion.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part A: Area Under the Concentration-time Curve of Alteplase in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞)	Area under the concentration-time curve of alteplase in plasma over interval from 0 extrapolated to infinity is reported.	Within 3 hours (h) before and 5 minutes (min), 10min, 15min, 20min, 25min, 30min, 32min, 34min, 36min, 40min, 45min, 50min, 1h, 1.33h, 1.67h, 2h, 3h, 4h and 6h after start of alteplase infusion.
Part B: Area Under the Concentration-time Curve of Alteplase in Plasma Over the Interval From 0 Extrapolated to Infinity (AUC0-∞)	Area under the concentration-time curve of alteplase in plasma over the interval from 0 extrapolated to infinity is reported.	Within 3 hours (h) before and 5 minutes (min), 10min, 15min, 20min, 25min, 30min, 32min, 34min, 36min, 40min, 45min, 50min, 1h, 1.33h, 1.67h, 2h, 3h, 4h and 6h after start of alteplase infusion.

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): June 23, 2020
• Primary Completion (Actual): June 21, 2021
• Study Completion (Actual): June 21, 2021

Study Registration Dates

• First Submitted: June 4, 2020
• First Submitted That Met QC Criteria: June 4, 2020
• First Posted (Actual): June 5, 2020

Study Record Updates

• Last Update Posted (Actual): April 26, 2023
• Last Update Submitted That Met QC Criteria: April 25, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Fibrinolytic Agents; Fibrin Modulating Agents; Anticoagulants; Heparin; Calcium heparin; Tissue Plasminogen Activator
• Other Study ID Numbers: 0135-0340; 2019-004932-40 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

IPD Plan Description

Clinical studies sponsored by Boehringer Ingelheim, phases I to IV, interventional and non-interventional, are in scope for sharing of the raw clinical study data and clinical study documents, except for the following exclusions:

1. studies in products where Boehringer Ingelheim is not the license holder;
2. studies regarding pharmaceutical formulations and associated analytical methods, and studies pertinent to pharmacokinetics using human biomaterials;
3. studies conducted in a single center or targeting rare diseases (because of limitations with anonymization).

For more details refer to: https://www.mystudywindow.com/msw/datasharing

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No