Study to Find the Highest Safe Dose of Soluble Guanylate Cyclase (sGC) Activator, BAY 1211163 Administered as Multiple Doses by Inhalation to Patients Who Cannot Breathe by Their Own and Suffer From a Type of Lung Failure That Causes Fluid to Build up in the Lungs Making Breathing Difficult (ARDS)

Study Overview
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Brief Summary
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With this study researchers want to find the highest safe dose of the soluble Guanylate Cyclase (sGC) Activator, BAY 1211163 and how safe and well the study drug works. Furthermore researchers want to gather information on the way the body absorbs, distributes and gets rid of the study drug given as increasing multiple doses by inhalation to patients who cannot breathe by their own and suffer from a type of lung failure that causes fluid to build up in the lungs making breathing difficult (ARDS)

Official Title
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Safety and Tolerability of Adaptive Escalating Multiple Doses (Three Times Daily) of a Soluble Guanylate Cyclase (sGC) Activator Inhale, BAY 1211163, as Inhalation in Intubated and Mechanically Ventilated Adult Patients With Moderate and Severe Acute Respiratory Distress Syndrome (ARDS). A Pilot (Phase Ib), First in Patient, Open Label Study

Conditions
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Acute Respiratory Distress Syndrome

Intervention / Treatment
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* Drug: BAY1211163


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Intubated, mechanically ventilated moderate or severe ARDS patients [diagnosed according to Berlin definition of ARDS, including PEEP ≥ 5 cmH2O, X-ray, with PaO2/FiO2 between 80 and 200 mmHg (inclusive). Initial diagnosis of ARDS prior to study inclusion, confirmation of ongoing moderate or severe ARDS with PaO2/FiO2 between 80 and 200 mmHg (inclusive) during this time under maintained invasive mechanical ventilation. Hypoxemia with PaO2/FiO2 between 80 and 200 mmHg (inclusive) maintained for at least 8 hours (recommend to be 12 hours) after screening, despite consent to follow recommendation on ventilator strategy and PEEP management. Time from intubation must be ≤ 96h. Male and non-pregnant female. Informed consent of capable patient or, in case of patient being incapable of giving informed consent, consent for study inclusion will be sought according to applicable laws and regulations. Exclusion Criteria: PaO2/FiO2 > 200 mmHg or < 80 mmHg at time of evaluation for inclusion. Moribund participants not expected to survive 24 hours (clinical decision). Expected duration of invasive mechanical ventilation less than 96 hours (clinical decision). History of pneumectomy or lung transplant. Current lung malignancy (including lung metastasis), or other malignancy requiring chemotherapy or radiation within the last month. History of chronic kidney disease and requiring renal replacement therapy dialysis at screening and/or baseline. Chronic liver disease Child-Pugh Class B and C. Hypoalbuminemia - serum albumin < 2.0 g/dL. Acute left ventricular failure and/or Left Ventricular Ejection Fraction < 30 %. Severe bronchopulmonal fistula. Clinical suspicion of pulmonary veno-occlusive disease. Heart right-sided endocarditis, tumors or mass. Rescue procedures already initiated at screening and/or Day 1. Use of co-medications involving moderate and strong inhibitors for CYP2C8 liver enzymes one week before assignment to intervention or during intervention. Off-label use of medication to treat Coronavirus SARS-CoV-2 virus unless recommended by scientific guidelines and accepted by DMC, investigator and sponsor. Plan to participate or past participation (within 30 days prior to Study Day 1) in other interventional studies.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BAY1211163<br>Adult patients with moderate or severe Acute Respiratory Distress Syndrome (ARDS) diagnosis before study inclusion will receive BAY1211163. | Drug: BAY1211163<br>* Participants will receive one of the drug doses of BAY1211163 solution three times per day (TID) by inhalation for seven days.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Numbers of participants with treatment emergent adverse events (TEAEs) |  | Up to 9 days | 
| Numbers of participants with dose limiting events (DLEs) | A dose limiting event is defined as any of the TEAEs occurring during dosing with BAY1211163 and regarded by the investigators to be related to BAY1211163. | Day 1 to 7 (may include Day 8) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Values of oxygenation index (OI) | The Oxygenation Index (OI) is calculated by using the fraction of inspired oxygen (FiO2), the partial pressure of oxygen in arterial blood (PaO2) and the mean airway pressure (MPAW) | Up to 28 days |