Pharmacokinetics of Inhaled Levosimendan

NCT06387862 | Unknown Phase 2 DMC

• 1 other identifier: 2022SIMBIOV
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

Determination of biological availability, time-to-peak and elimination half-life of inhaled levosimendan by administration of an inhaled- and intravenous dose of levosimendan.

Conditions

Left Ventricular Dysfunction

Keywords

levosimendan; inhalation; pharmakokinetic

Outcome Measures

Primary Outcomes (3)

• Bioavailability of inhaled levosimendan

  Assessment of bioavailability of inhaled levosimendan in spontaneous breathing patients,

  Baseline, plasma samples at 5 minutes, 10 minutes, 15 minutes, 20 minutes, 30 minutes, 45 minutes, 1 hour, 1hour 30 minutes, 2 hours , 3 hours , 6 hours, 10 hours after end of infusion/inhalation

• Time-to-peak of inhaled levosimendan

  Assessment of time-to-peak plasma concentration of inhaled levosimendan in spontaneous breathing patients

  Baseline, plasma samples at 5 minutes, 10 minutes, 15 minutes, 20 minutes, 30 minutes, 45 minutes, 1 hour, 1hour 30 minutes, 2 hours , 3 hours , 6 hours, 10 hours after end of infusion/inhalation

• Elimination half-life of inhaled levosimenan

  Assessment of elimination half-life of inhaled levosimendan in spontaneous breathing patients

  Baseline, plasma samples at 5 minutes, 10 minutes, 15 minutes, 20 minutes, 30 minutes, 45 minutes, 1 hour, 1hour 30 minutes, 2 hours , 3 hours , 6 hours, 10 hours after end of infusion/inhalation

Secondary Outcomes (7)

• Effect of inhaled levosimendan on MAP

  Baseline, plasma samples at 5 minutes, 10 minutes, 15 minutes, 20 minutes, 30 minutes, 45 minutes, 1 hour, 1hour 30 minutes, 2 hours , 3 hours , 6 hours, 10 hours after end of infusion/inhalation

• Effect of inhaled levosimendan on TVR

  Baseline, plasma samples at 5 minutes, 10 minutes, 15 minutes, 20 minutes, 30 minutes, 45 minutes, 1 hour, 1hour 30 minutes, 2 hours , 3 hours , 6 hours, 10 hours after end of infusion/inhalation

• Effect of inhaled levosimendan on CO

  Baseline, plasma samples at 5 minutes, 10 minutes, 15 minutes, 20 minutes, 30 minutes, 45 minutes, 1 hour, 1hour 30 minutes, 2 hours , 3 hours , 6 hours, 10 hours after end of infusion/inhalation

• Effect of inhaled levosimendan on LVOT VTI

  Baseline, plasma samples at 5 minutes, 10 minutes, 15 minutes, 20 minutes, 30 minutes, 45 minutes, 1 hour, 1hour 30 minutes, 2 hours , 3 hours , 6 hours, 10 hours after end of infusion/inhalation

• Effect of inhaled levosimendan on FAC of the right vetricle

  Baseline, plasma samples at 5 minutes, 10 minutes, 15 minutes, 20 minutes, 30 minutes, 45 minutes, 1 hour, 1hour 30 minutes, 2 hours , 3 hours , 6 hours, 10 hours after end of infusion/inhalation

Study Arms (2)

Levosimendan inhalation

EXPERIMENTAL

Levosimendan 12µg/kg inhalation over 10 minutes, once

Drug: Levosimendan 2.5 milligram/milliliter Injectable Solutiondose Inhaled

Levosimendan intravenous

ACTIVE COMPARATOR

Levosimendan 12µg/kg intravenous over 10 minutes, once

Drug: Levosimendan 2.5 milligram/milliliter Injectable Solutiondose Intravenous

Interventions

Levosimendan 2.5 milligram/milliliter Injectable Solutiondose Inhaled DRUG

Each patient will receive 12µg/kg of levosimendan by inhalation over 10 min. During 10h following inhaled dose, plasma concentrations will be measured.

Levosimendan inhalation

Levosimendan 2.5 milligram/milliliter Injectable Solutiondose Intravenous DRUG

Each patient will receive 12µg/kg of levosimendan by intravenous (IV) administration over 10 min and at the same timepoints plasma samples will be measured

Levosimendan intravenous

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subject \>18 years of age
• Scheduled for elective coronary artery bypass grafting (CABG)
• Provided written informed consent
• Impaired left ventricular function (LVEF \<40%)

You may not qualify if:

• Known allergy for levosimendan or solutes
• Persistent angina, defined as Canadian Cardiovascular Society score \> I
• History of valvular intervention or uncorrected primary stenotic valve disease
• Uncorrected thyroid disease
• Infiltrative, hypertrophic or restrictive cardiomyopathy
• Pericardial disease
• Active myocarditis
• Chronic obstructive pulmonary disease requiring long-term treatment with β-agonists, Theophylline, or corticosteroids (FEV1 \< 80%; Tiffeneau-index \<0.7)
• History of serious arrhythmias, defined as a history of ventricular tachycardia or fibrillation other than that occurring within 24 hours after acute myocardial infarction (MI)
• resting heart rate \> 115 bpm for at least 10 minutes on repeated measurements
• Supine systolic blood pressure \< 85 mm Hg or \>200 mm Hg
• patients with implanted pacemaker/defibrillator or cardiac resynchronisation therapy (CRT-device)
• primary renal or hepatic impairment (creatinine \> 2.5 mg/dL or aspartate aminotransferase/alanine aminotransferase \>2 times upper limit of normal and/or increased level of bilirubin (\> 2 times the upper limit of normal and increase of international normalised ratio (INR) above the upper limit of normal, respectively)
• Uncorrected hypokalemia or hyperkalemia (potassium \<3.5 mmol/L or \>5.5 mmol/L)
• Uncorrected hypomagnesemia (magnesium \<0.65mmol/L)

Sponsors & Collaborators

• Universitair Ziekenhuis Brussel: lead

Study Sites (1)

UZ Brussel

Brussels, 1090, Belgium

RECRUITING

MeSH Terms

Conditions

Ventricular Dysfunction, Left; Respiratory Aspiration

Condition Hierarchy (Ancestors)

Ventricular Dysfunction; Heart Diseases; Cardiovascular Diseases; Respiration Disorders; Respiratory Tract Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Matthias Raes, MD

  Universitair Ziekenhuis Brussel

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Matthias Raes, MD

CONTACT

024749872; matthias.raes@uzbrussel.be

Marie-Claire Van Malderen, SC

CONTACT

024763110; marieclaire.vanmalderen@uzbrussel.be

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 9, 2024
• First Posted: April 29, 2024
• Study Start: February 1, 2024
• Primary Completion: November 1, 2024
• Study Completion: January 1, 2025
• Last Updated: May 20, 2024

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share

Locations

BE (1)