A Randomized, Single-blind, Placebo-controlled Study to Assess the Safety, Tolerability, and Pharmacokinetics of M6229 Administered as a 120-hour Continuous Infusion at Three Sequential Dose Levels Versus Placebo in Healthy Subjects
Overview
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- Matisse Pharmaceuticals
- Enrollment
- 15
- Locations
- 1
- Primary Endpoint
- Incidence and type of Adverse Events (AEs)
Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Sequential
- Primary Purpose
- Other
- Masking
- Single (Participant)
Eligibility Criteria
- Ages
- 18 Years to 55 Years (Adult)
- Sex
- All
- Accepts 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
Arms & Interventions
M6229
A low-anticoagulant heparin in low, mid, and high dose. IV administration.
Intervention: M6229 (Drug)
Placebo
Saline solution; IV administration
Intervention: Placebo (Drug)
Outcomes
Primary Outcomes
Incidence and type of Adverse Events (AEs)
Time Frame: 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
Time Frame: 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
Time Frame: Until End of Study (Day 14-18)
Changes in systolic and diastolic blood pressure in mmHg
Change in vital signs - pulse rate
Time Frame: Until End of Study (Day 14-18)
Change in pulse rate measured in beat per minute
Change in vital signs - respiratory rate
Time Frame: Until End of Study (Day 14-18)
Change in respiratory rate measured in breaths per minute
Change in vital signs - body temperature
Time Frame: Until End of Study (Day 14-18)
Changes in body temperature measured in degrees Celcius
Pharmacokinetics: Maximum observed analyte concentration (Cmax)
Time Frame: Until Day 9 (192 hours)
Pharmacokinetics: Maximum observed analyte concentration (tmax)
Time Frame: Until Day 9 (192 hours)
Pharmacokinetics: Last measured quantifiable concentration (tlast)
Time Frame: Until Day 9 (192 hours)
Pharmacokinetics: Area under the curve (AUC)
Time Frame: Until Day 9 (192 hours)
Pharmacokinetics: Elimination half-life (t1/2)
Time Frame: Until Day 9 (192 hours)
Pharmacokinetics: Volume of distribution (Vd)
Time Frame: Until Day 9 (192 hours)
Pharmacokinetics: Clearance (Cl)
Time Frame: Until Day 9 (192 hours)
Pharmacokinetics: Amount excreted (Ae) in urine
Time Frame: Until Day 9 (192 hours)
Secondary Outcomes
No secondary outcomes reported