Bioequivalence of Liquid and Reconstituted Lyophilized Subcutaneous Formulations of Caplacizumab.

Study Overview
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Brief Summary
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The primary objective of the study is to evaluate the pharmacokinetic characteristics and demonstrate bioequivalence of a reconstituted new lyophilized formulation of caplacizumab for subcutaneous (s.c.) injection as compared to an equal nominal s.c. dose of the reference liquid formulation of caplacizumab. The secondary objective of the study is to compare the safety and tolerability, and the pharmacodynamic parameters of the new formulation with those of the reference formulation.

Official Title
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A Phase I, Single Center, Open-Label, Randomized, Single Dose Cross-Over Study in Healthy Male Subjects to Investigate the Bioequivalence and Tolerability of Liquid and Reconstituted Lyophilized Subcutaneous Formulations of Caplacizumab.

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Biological: Caplacizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male Caucasians aged 18 to 55 years, inclusive. Body weight 55 - 100 kg and body mass index (BMI) between 18.5 and 30.0, extremes included. Coagulation and bleeding diathesis variables (as defined in the protocol) within the normal range at screening and on Day -1. Others as defined in the protocol. Exclusion Criteria: History or presence of diseases in the kidneys and/or heart, lungs, liver, skin, endocrine organs or other condition known to interfere with the absorption, distribution, metabolism or excretion of drugs. History of and/or any sign or symptom indicating current abnormal hemostasis or blood dyscrasia. Others as defined in the protocol

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Caplacizumab - Treatment A<br>Single s.c. dose of reconstituted lyophilized solution of caplacizumab followed by single s.c. dose of liquid formulation of caplacizumab | Biological: Caplacizumab<br>* Comparison of reconstituted lyophilised formulation versus liquid formulation of caplacizumab<br>|
| Experimental: Caplacizumab - Treatment B<br>Single s.c. dose of liquid formulation of caplacizumab followed by single s.c. dose of reconstituted lyophilized solution of caplacizumab | Biological: Caplacizumab<br>* Comparison of reconstituted lyophilised formulation versus liquid formulation of caplacizumab<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics: concentration of caplacizumab in plasma |  | Day 1 (pre-dose) until Day 7 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacodynamics as measured by Ristocetin cofactor activity in plasma |  | During screening until day 29 +/-1 | 
| Safety and Tolerability: safety markers | Adverse events, local tolerability, laboratory assessments, urinalysis, vital signs, 12-lead ECG, physical examinations | From signing of informed consent form until day 43 +/- 2 | 
| Pharmacodynamics as measured by von Willebrand factor antigen in plasma |  | During screening until Day 29 +/- 1 | 
| Pharmacodynamics as measured by Factor VIII clotting activity in plasma |  | During screening until day 29 +/- 1 |