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This is a Phase I, single-center, randomized, single-blind, placebo-controlled study in healthy subjects assessing the safety, tolerability and pharmacokinetic profile of three different dose levels of M6229 when administered continuously for 120 hours.
Three dose levels of M6229 will be assessed in sequential study cohorts. Each cohort will consist of up to 3 male and 3 female subjects (2 male and 2 female subjects on M6229, 1 male and 1 female subject on placebo). Following a screening period of up to 28 days during which eligibility will be assessed, subjects will be randomized to M6229 or placebo and start a 120-hour continuous infusion on Day 1. Subjects will undergo safety assessments (incl. laboratory assessments) and pharmacokinetic sampling following a predefined schedule from Day 1 until Day 9. Subjects will be discharged on Day 9. The clinical study will be completed with an end-of-study visit, which will take place between 5 to 9 days after the last treatment-defined assessment.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| M6229 | Experimental | A low-anticoagulant heparin in low, mid, and high dose. IV administration. |
|
| Placebo | Placebo Comparator | Saline solution; IV administration |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| M6229 | Drug | Continuous 120-hour intravenous infusion of M6229 |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Incidence and type of Adverse Events (AEs) | Any unfavorable and unintended sign (including abnormal laboratory findings), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. | Until End of Study (Day 14-18) |
| Change in electrocardiograms (ECGs) from baseline | Clinically significant changes in PR interval, QRS interval, QT interval, and QTcF | Until End of Study (Day 14-18) |
| Change in vital signs - blood pressure | Changes in systolic and diastolic blood pressure in mmHg | Until End of Study (Day 14-18) |
| Change in vital signs - pulse rate | Change in pulse rate measured in beat per minute | Until End of Study (Day 14-18) |
| Change in vital signs - respiratory rate | Change in respiratory rate measured in breaths per minute | Until End of Study (Day 14-18) |
| Change in vital signs - body temperature | Changes in body temperature measured in degrees Celcius | Until End of Study (Day 14-18) |
| Pharmacokinetics: Maximum observed analyte concentration (Cmax) | Until Day 9 (192 hours) | |
| Pharmacokinetics: Maximum observed analyte concentration (tmax) |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Charité Research | Berlin | Germany |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 38338654 | Background | Reutelingsperger CPM, Gijbels MJ, Spronk H, Van Oerle R, Schrijver R, Ekhart P, de Kimpe S, Nicolaes GAF. M6229 Protects against Extracellular-Histone-Induced Liver Injury, Kidney Dysfunction, and Mortality in a Rat Model of Acute Hyperinflammation. Int J Mol Sci. 2024 Jan 23;25(3):1376. doi: 10.3390/ijms25031376. | |
| 40824474 | Background |
| Label | URL |
|---|---|
| Related Info | View source |
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| ID | Term |
|---|---|
| D018805 | Sepsis |
| D012772 | Shock, Septic |
| ID | Term |
|---|---|
| D007239 | Infections |
| D018746 | Systemic Inflammatory Response Syndrome |
| D007249 | Inflammation |
| D010335 | Pathologic Processes |
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| Placebo |
| Drug |
Continuous 120-hour intravenous infusion of placebo (saline) |
|
| Until Day 9 (192 hours) |
| Pharmacokinetics: Last measured quantifiable concentration (tlast) | Until Day 9 (192 hours) |
| Pharmacokinetics: Area under the curve (AUC) | Until Day 9 (192 hours) |
| Pharmacokinetics: Elimination half-life (t1/2) | Until Day 9 (192 hours) |
| Pharmacokinetics: Volume of distribution (Vd) | Until Day 9 (192 hours) |
| Pharmacokinetics: Clearance (Cl) | Until Day 9 (192 hours) |
| Pharmacokinetics: Amount excreted (Ae) in urine | Until Day 9 (192 hours) |
| van Mourik N, van Amstel RBE, Slim MA, van Vught LA, van der Poll T, Huckriede J, de Vries F, de Kimpe SJ, Crabbe R, van Leeuwen SJM, Ekhart PF, Reutelingsperger CPM, Nicolaes GAF, Vlaar APJ, Muller MCA. A phase I trial evaluating the safety, tolerability, pharmacokinetics and pharmacodynamics of intravenously administered low-anticoagulant heparin (M6229) in critically ill sepsis patients. Intensive Care Med Exp. 2025 Aug 18;13(1):84. doi: 10.1186/s40635-025-00790-4. |
| D013568 |
| Pathological Conditions, Signs and Symptoms |
| D012769 | Shock |