METHOD FOR TREATING PULMONARY ARTERIAL HYPERTENSION IN A PATIENT NOT HAVING IDIOPATHIC PULMONARY FIBROSIS

• US 20130225595A1
• Filed: 03/14/2013
• Published: 08/29/2013
• Est. Priority Date: 02/29/2012
• Status: Abandoned Application

• Current Assignee: Gilead Sciences Inc.
• Original Assignee: Gilead Sciences Inc.
• Inventors: Gillies, Hunter Campbell, Peschel, Tobias, Pizzuti, David J.
• Application Number:
  US13/830,211
• Publication Number:
  US 20130225595A1
• Time in Patent Office: Days
• US Class Current: 514/250
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/4985 Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
• CPC Class Codes: A61K 31/505 Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
• CPC Class Codes: A61K 31/506 not condensed and containing further heterocyclic rings
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: Y02A 50/30 Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

There is provided a method of treating pulmonary hypertension in a patient in need thereof, said method comprising: administering a therapeutically effective amount of ambrisentan to the patient with pulmonary arterial hypertension, wherein the patient has been determined not to have idiopathic pulmonary fibrosis.

Claims

1. A method of treating pulmonary hypertension in a patient in need thereof, said method comprising:

administering a therapeutically effective amount of ambrisentan to the patient with pulmonary arterial hypertension;

wherein the patient has been determined not to have idiopathic pulmonary fibrosis.

2. The method of claim 1, wherein the subject is administered ambrisentan to improve exercise ability and delay clinical worsening without causing treatment-limiting liver injury.

3. The method of claim 1, wherein the pulmonary hypertension comprises left-sided atrial or ventricular heart disease or left-sided valvular heart disease.

4. The method of claim 1, wherein the pulmonary hypertension is associated with one or more of chronic obstructive pulmonary disease (COPD), sleep-disordered breathing, an alveolar hypoventilation disorder, chronic exposure to high altitude, a developmental abnormality, thromboembolic obstruction of proximal and/or distal pulmonary arteries, a non-thrombotic pulmonary embolism, sarcoidosis, histiocytosis X, lymphangiomatosis or compression of pulmonary vessels.

5. The method of claim 1, wherein the pulmonary hypertension is pulmonary arterial hypertension (PAH).

6. The method of claim 5, wherein the PAH is associated with a connective tissue disease, HIV infection, portal hypertension, a congenital heart disease, schistosomiasis or chronic hemolytic anemia.

7. The method of claim 5, wherein the PAH is associated with one or more of (a) a congenital heart defect, (b) portal hypertension, (c) use of a drug or toxin other than an anorexigen, (d) thyroid disorder, (e) glycogen storage disease, (f) Gaucher disease, (g) hereditary hemorrhagic telangiectasia, (h) hemoglobinopathy, (i) myeloproliferative disorder, (j) splenectomy, (k) pulmonary veno-occlusive disease and (l) pulmonary capillary hemangiomatosis.

8. The method of claim 1, wherein the subject experiences at least one of

(a) adjustment of one or more hemodynamic parameters indicative of improvement of the pulmonary hypertension condition towards a more normal level versus baseline;

(b) increase in exercise capacity versus baseline;

(c) lowering of Borg dyspnea index (BDI) versus baseline;

(d) improvement of one or more quality of life parameters versus baseline;

(e) movement to a lower WHO functional class; and

(f) a reduction in plasma natriuretic peptide levels versus baseline.

9. The method of claim 1, wherein the daily dose of ambrisentan is about 2.5 mg.

10. The method of claim 1, wherein the daily dose of ambrisentan is about 5 mg.

11. The method of claim 10, wherein the daily dose of ambrisentan is increased from about 5 mg to about 10 mg if the about 5 mg ambrisentan daily dose is tolerated by the subject.

12. The method of claim 1, wherein the method consists essentially of:

administering a therapeutically effective amount of ambrisentan to the patient with pulmonary arterial hypertension;

wherein the patient has been determined not to have idiopathic pulmonary fibrosis.

13. The method of claim 1, wherein the ambrisentan is administered in combination therapy with a second active agent effective for treatment of the pulmonary hypertension condition or a condition related thereto, and

wherein the second active agent comprises at least one drug selected from the group consisting of prostanoid, a phosphodiesterase (PDE) inhibitor, a guanylate cyclase activator, a calcium channel blocker, a diuretic, an anticoagulant, oxygen and a combination thereof.

14. The method of claim 13, wherein the PDE5 inhibitor is tadalafil.

15. The method of claim 14, wherein the weight ratio of ambrisentan and the PDE5 inhibitor is in a range from about 1:

1.5 to about 1;

10.

16. The method of claim 13, wherein the guanylate cyclase activator is riociguat.

17. A method of treating pulmonary arterial hypertension in a patient in need thereof, comprising:

administering a therapeutically effective amount of ambrisentan to the patient with pulmonary arterial hypertension;

wherein the patient has been determined not to have idiopathic pulmonary fibrosis, and

wherein the method is carried out without drug labeling instruction to monitor one or more biomarkers of liver function during ambrisentan treatment.

18. The method of claim 17, wherein the one or more biomarkers include liver aminotransferase or bilirubin.

19. The method of claim 17, wherein the method is carried out without mandatory drug labeling instruction imposed by a regulatory agency to monitor the one or more biomarkers of liver function during ambrisentan treatment.

20. The method of claim 17, wherein the method is carried out without drug labeling instruction to monitor the one or more biomarkers of liver function prior to and during ambrisentan treatment.

21. The method of claim 17, wherein the method is carried out without drug labeling instruction to measure the one or more biomarkers of liver function monthly during ambrisentan treatment.

22. The method of claim 17, wherein the subject has exhibited a grade 1 abnormality in one or more biomarkers of liver function.

23. The method of claim 17, wherein the subject in need thereof has exhibited a grade 2, 3 or 4 abnormality in one or more biomarkers of liver function.

24. The method of claim 17, wherein the ambrisentan is administered in combination therapy with a PDE5 inhibitor effective for treatment of the pulmonary hypertension condition or a condition related thereto.

25. The method of claim 24, wherein the PDE5 inhibitor is tadalafil, and the weight ratio of ambrisentan and tadalafil is in a range from about 1:

1.5 to about 1;

10.

26. The method of claim 17, wherein the method consists essentially of:

administering a therapeutically effective amount of ambrisentan to the patient with pulmonary arterial hypertension;

wherein the patient has been determined not to have idiopathic pulmonary fibrosis, and

wherein the method is carried out without drug labeling instruction to monitor one or more biomarkers of liver function during ambrisentan treatment.

27. A method of treating pulmonary arterial hypertension in a patient in need thereof, comprising:

diagnosing a patient with pulmonary arterial hypertension;

screening the patient for idiopathic pulmonary fibrosis;

determining that the patient does not have idiopathic pulmonary fibrosis; and

administering a therapeutically effective amount of ambrisentan to the patient with pulmonary arterial hypertension.

28. The method of claim 27, wherein the screening is carried out by performing a diagnostic test on the patient.

29. The method of claim 28, wherein the diagnostic test selected from the group consisting of an imaging technique, lung biopsy, a pulmonary function test, chest X-Ray, CT scan, echocardiogram, blood test, and spirometry.