Healthy Subjects
Conditions
Keywords
M6229, Unfractioned Heparin, Sepsis, Septic Shock
Brief summary
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.
Detailed description
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.
Interventions
DRUGM6229
Continuous 120-hour intravenous infusion of M6229
DRUGPlacebo
Continuous 120-hour intravenous infusion of placebo (saline)
Sponsors
Matisse Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
OTHER
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Provision of written informed consent * Male or female, aged 18 - 55 years at time of informed consent * BMI between 18.0 - 30.0 kg/m2 * Normal vital signs (resting pulse rate and resting blood pressure) * Normal ECG parameters (PR, QRS, QTc) * Normal coagulation parameters (aPTT, PTT/INR and thrombin time) * Female subjects must have a negative serum pregnancy test * Willing and able to adhere to contraceptive requirements
Exclusion criteria
* History of clinically significant medical illness * Laboratory abnormalities * Major surgery or trauma in previous 6 months * Positive test for HIV, HBsAg, or HCV * History of heart arrhythmias, tachycardia at rest, or history of risk factors for Torsade de Pointes syndrome * Clinically relevant allergy or drug hypersensitivity (incl. heparin) * Smokes daily more than 5 cigarettes or equivalent * History of postural disorders * Lack of adequate venous access * Current or ongoing history of urinary retention * Use of prescription or nonprescription medication within 7 days prior to Day 1 * Received an investigational drug or medical device recently, or \>3 investigational agents in last 12 months, or currently enrolled in an investigational study * Donated blood or substantial blood loss within 60 days prior to Day 1 * Any condition, preplanned surgery or procedure that would interfere with the study conduct and/or with the subject's best interest * Subject is vulnerable * Subject is an employee of the investigator, clinical site, or Sponsor
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence and type of Adverse Events (AEs) | Until End of Study (Day 14-18) | 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. |
| Change in electrocardiograms (ECGs) from baseline | Until End of Study (Day 14-18) | Clinically significant changes in PR interval, QRS interval, QT interval, and QTcF |
| Change in vital signs - blood pressure | Until End of Study (Day 14-18) | Changes in systolic and diastolic blood pressure in mmHg |
| Change in vital signs - pulse rate | Until End of Study (Day 14-18) | Change in pulse rate measured in beat per minute |
| Change in vital signs - respiratory rate | Until End of Study (Day 14-18) | Change in respiratory rate measured in breaths per minute |
| Change in vital signs - body temperature | Until End of Study (Day 14-18) | Changes in body temperature measured in degrees Celcius |
| Pharmacokinetics: Maximum observed analyte concentration (Cmax) | Until Day 9 (192 hours) | — |
| Pharmacokinetics: Maximum observed analyte concentration (tmax) | 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) | — |
Countries
Germany
Outcome results
None listed