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EP-4740988-A2 - USE OF INHALED NITRIC OXIDE (INO) FOR IMPROVING ACTIVITY LEVELS IN PATIENTS WITH LUNG-RELATED CONDITIONS

EP4740988A2EP 4740988 A2EP4740988 A2EP 4740988A2EP-4740988-A2

Abstract

Described are methods for maintaining or improving activity levels in patients lung-related conditions.

Inventors

  • SHAH, PARAG
  • FERNANDES, PETER PAUL
  • KIM, BOBAE
  • DEKKER, Martin

Assignees

  • Mallinckrodt Pharmaceuticals Ireland Limited

Dates

Publication Date
20260513
Application Date
20200103

Claims (15)

  1. Inhaled nitric oxide (iNO) for use in a method for improving or maintaining activity levels in a patient in need thereof, the method comprising: administering inhaled nitric oxide to the patient by: (a) detecting a breath pattern in the patient including a total inspiratory time; (b) correlating the breath pattern with an algorithm to determine a timing of administration of a dose of nitric oxide; and (c) administering the dose of nitric oxide to the patient in a pulsatile manner over a portion of the total inspiratory time, wherein the patient has interstitial lung disease, wherein the algorithm uses a breath level trigger and a slope algorithm, wherein the slope algorithm detects a breath when a rate of pressure drop reaches a predetermined threshold, wherein the breath level trigger detects the breath when a threshold negative pressure is reached upon inspiration, and wherein at least 90% of the dose of nitric oxide is delivered in a first third of the total inspiratory time.
  2. The iNO for use of claim 1, wherein the dose is about 25 micrograms (mcg)/kg ideal body weight (IBW)/hr to about 50 mcg/kg IBW/hr.
  3. The iNO for use of claim 1 or 2, wherein the dose is about 30 mcg/kg IBW/hr to about 45 mcg/kg IBW/hr.
  4. The iNO for use of any one of claims 1-3, wherein the dose is about 30 mcg/kg IBW/hr.
  5. The iNO for use of any one of claims 1-3, wherein the dose is about 45 mcg/kg IBW/hr.
  6. The iNO for use of any one of claims 1-5, wherein the method further comprises measuring changes in the activity levels using actigraphy.
  7. The iNO for use of any one of claims 1-6, wherein the interstitial lung disease comprises one or more subtypes selected from idiopathic interstitial pneumonia (IIP), chronic hypersensitivity pneumonia, occupational or environmental lung disease, idiopathic pulmonary fibrosis (IPF), non-IPF IIPs, granulomatous, and connective tissue disease related ILD.
  8. The iNO for use of any one of claims 1-7, wherein the interstitial lung disease comprises idiopathic pulmonary fibrosis (IPF).
  9. The iNO for use of any one of claims 1-8, wherein the patient is at high risk of developing pulmonary hypertension.
  10. The iNO for use of any one of claims 1-9, wherein the patient is administered iNO for at least 16 hours per day.
  11. The iNO for use of any one of claims 1-9, wherein the patient is administered iNO for at least 12 hours per day.
  12. The iNO for use of any one of claims 1-9, wherein the patient is administered iNO for a minimum course of treatment of 5 days.
  13. The iNO for use of any one of claims 1-9, wherein the patient is administered iNO for at least 12 hours per day for at least 8 weeks.
  14. The iNO for use of any one of claims 1-9, wherein the patient is administered iNO for at least 12 hours per day for at least 16 weeks.
  15. The iNO for use of any one of claims 1-9, wherein the patient is administered iNO for at least 12 hours per day for at least 5 days.

Description

FIELD OF THE INVENTION The present application relates generally to apparatus and methods for administration of nitric oxide, in particular, pulsatile delivery of nitric oxide to patients in need of therapeutic treatment, and also relates generally to methods for administration of nitric oxide, in particular, pulsatile delivery of nitric oxide to patients with lung-related conditions to maintain and/or increase activity levels. BACKGROUND OF THE INVENTION Nitric oxide (NO) is a gas that, when inhaled, acts to dilate blood vessels in the lungs, improving oxygenation of the blood and reducing pulmonary hypertension. Because of this, nitric oxide is provided as a therapeutic gas in the inspiratory breathing phase for patients having shortness of breath (dyspnea) due to a disease state, for example, pulmonary arterial hypertension (PAH), chronic obstructive pulmonary disease (COPD), combined pulmonary fibrosis and emphysema (CPFE), cystic fibrosis (CF), idiopathic pulmonary fibrosis (IPF), emphysema, interstitial lung disease (ILD), chronic thromboembolic pulmonary hypertension (CTEPH), chronic high altitude sickness, or other lung disease. While NO may be therapeutically effective when administered under the appropriate conditions, it can also become toxic if not administered correctly. NO reacts with oxygen to form nitrogen dioxide (NO2), and NO2 can be formed when oxygen or air is present in the NO delivery conduit. NO2 is a toxic gas which may cause numerous side effects, and the Occupational Safety & Health Administration (OSHA) provides that the permissible exposure limit for general industry is only 5 ppm. Thus, it is desirable to limit exposure to NO2 during NO therapy. SUMMARY OF THE INVENTION In an embodiment of the present invention, a method of administering a dose of nitric oxide is described. In an embodiment of the invention, at least a single pulse dose is administered to a patient and is therapeutically effective to treat or alleviate symptoms of a pulmonary disease. In an embodiment of the invention, an aggregate of two or more pulse doses is therapeutically effective to treat or alleviate symptoms of a pulmonary disease. In an embodiment of the invention, nitric oxide is delivered on a periodic basis for a minimum of five minutes per day to twenty-four hours per day. In an embodiment of the invention, the nitric oxide may be delivered at the convenience of the patient, for example, over a period of time while sleeping. In an embodiment of the invention, administration of pulses of nitric oxide may be evenly or unevenly spaced over a time period (e.g., ten minutes, one hour or for twenty-four hours). In another embodiment, administration of a therapeutically effective dose of nitric oxide may be continuous for a fixed period of time. In one embodiment, a method comprises detecting a breath pattern in a patient. In an embodiment of the invention, the breath pattern includes the total inspiratory time (e.g., the time duration of a single inspiration of a patient). In an embodiment of the invention, the breath pattern is detected using a device comprising a breath sensitivity control. In an embodiment of the invention, the breath pattern is correlated with an algorithm to calculate the timing of administration of a dose of nitric oxide. In an embodiment of the present invention, the volume of nitric oxide containing gas necessary for administration of an amount of nitric oxide on a per pulse basis is calculated. In an embodiment, the nitric oxide is delivered to the patient in a pulsatile manner over a portion of a total inspiratory time. In an embodiment of the invention, nitric oxide doses are delivered to the patient over a period of time sufficient to deliver a therapeutic dose of nitric oxide to the patient. In an embodiment of the invention, the device calculates the total time sufficient to deliver a therapeutic dose of nitric oxide to the patient. In an embodiment of the invention, the total time required for a therapeutic dose of nitric oxide to be delivered to the patient is at least partially dependent upon the breath pattern of said patient. In an embodiment of the invention, nitric oxide is delivered during the first third of the total inspiratory time. In an embodiment, nitric oxide is delivered during the first half of the total inspiratory time. In an embodiment, nitric oxide is delivered during the first two-thirds of the total inspiratory time. In an embodiment of the invention, at least fifty percent (50%) of the nitric oxide dose is delivered during the first third of the total inspiratory time. In an embodiment of the invention, at least seventy percent (70%) of the nitric oxide dose is delivered to the patient during the first half of the total inspiratory time. In an embodiment, at least ninety percent (90%) of the nitric oxide dose is delivered to the patient during the first two-thirds of the total inspiratory time. In an embodiment of the invention, at least ninety perce