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

NCT04419493 | Completed Phase 1 Results

• 2 other identifiers: 0135-03402019-004932-40
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Healthy

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (2)

• Part A: Area Under the Concentration-time Curve of Alteplase in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞)

  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-∞)

  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.

Study Arms (4)

Part B: Alteplase, TPA-02 then Alteplase, TPA-05

EXPERIMENTAL

Drug: Alteplase (from modified manufacturing process); Drug: Heparin-Natrium-5000-ratiopharm (unfractionated heparin)

Part B: Alteplase, TPA-05 then Alteplase, TPA-02

ACTIVE COMPARATOR

Drug: Alteplase (from current manufacturing process); Drug: Heparin-Natrium-5000-ratiopharm (unfractionated heparin)

Part A: Alteplase, TPA-05 then Alteplase, TPA-02

EXPERIMENTAL

Open-label

Drug: Alteplase (from modified manufacturing process); Drug: Heparin-Natrium-5000-ratiopharm (unfractionated heparin)

Part A: Alteplase, TPA-02 then Alteplase, TPA-05

ACTIVE COMPARATOR

Drug: Alteplase (from current manufacturing process); Drug: Heparin-Natrium-5000-ratiopharm (unfractionated heparin)

Interventions

Alteplase (from modified manufacturing process) DRUG

Alteplase, TPA-05

Part A: Alteplase, TPA-05 then Alteplase, TPA-02; Part B: Alteplase, TPA-02 then Alteplase, TPA-05

Alteplase (from current manufacturing process) DRUG

Alteplase, TPA-02

Part A: Alteplase, TPA-02 then Alteplase, TPA-05; Part B: Alteplase, TPA-05 then Alteplase, TPA-02

Heparin-Natrium-5000-ratiopharm (unfractionated heparin) DRUG

Heparin-Natrium-5000-ratiopharm (unfractionated heparin)

Part A: Alteplase, TPA-02 then Alteplase, TPA-05; Part A: Alteplase, TPA-05 then Alteplase, TPA-02; Part B: Alteplase, TPA-02 then Alteplase, TPA-05; Part B: Alteplase, TPA-05 then Alteplase, TPA-02

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (1)

Humanpharmakologisches Zentrum Biberach

Biberach, 88397, Germany

Location

Related Publications (1)

• Glund S, Hoefler J, Lang B, Cafiero S, Panova-Noeva M, Place C, Wolff M. Bioequivalence of Intravenous Alteplase from Two Different Manufacturing Processes in Healthy Male Volunteers: Results from a Two-Stage, Adaptive-Design Study. Clin Pharmacokinet. 2023 Jul;62(7):1023-1030. doi: 10.1007/s40262-023-01253-3. Epub 2023 May 30.

  PMID: 37248330 DERIVED

Related Links

• Related Info

MeSH Terms

Interventions

Tissue Plasminogen Activator; Heparin

Intervention Hierarchy (Ancestors)

Serine Endopeptidases; Endopeptidases; Peptide Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Serine Proteases; Plasminogen Activators; Blood Coagulation Factors; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Biological Factors; Glycosaminoglycans; Polysaccharides; Carbohydrates

Limitations and Caveats

For study Part A three subjects underwent only one treatment period, thereafter the trial was put on-hold. Trial Part B was performed as planned. There were no important protocol deviations (IPDs). Each entered subject met all of the inclusion criteria and none of the exclusion criteria.

Results Point of Contact

• Title: Boehringer Ingelheim, Call Center
• Organization: Boehringer Ingelheim

clintriage.rdg@boehringer-ingelheim.com

1-800-243-0127

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Part A: Open label Part B: Adaptive two-stage group-sequential design

Study Record Dates

• First Submitted: June 4, 2020
• First Posted: June 5, 2020
• Study Start: June 23, 2020
• Primary Completion: June 21, 2021
• Study Completion: June 21, 2021
• Last Updated: April 26, 2023
• Results First Posted: April 26, 2023

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)