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Gomberg-Maitland M, Schilz R, Mediratta A, et al. Phase I safety study of ranolazine in pulmonary arterial hypertension. Pulm Circ. 2015;5(4):691-700doi: 10.1086/683813.
Gomberg-Maitland, M., Schilz, R., Mediratta, A., Addetia, K., Coslet, S., Thomeas, V., Gillies, H., & Oudiz, R. J. (2015). Phase I safety study of ranolazine in pulmonary arterial hypertension. Pulmonary circulation, 5(4), 691-700. https://doi.org/10.1086/683813
Gomberg-Maitland, Mardi, et al. "Phase I safety study of ranolazine in pulmonary arterial hypertension." Pulmonary circulation vol. 5,4 (2015): 691-700. doi: https://doi.org/10.1086/683813
Gomberg-Maitland M, Schilz R, Mediratta A, Addetia K, Coslet S, Thomeas V, Gillies H, Oudiz RJ. Phase I safety study of ranolazine in pulmonary arterial hypertension. Pulm Circ. 2015 Dec;5(4):691-700. doi: 10.1086/683813. PMID: 26697176; PMCID: PMC4671743.
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Pulm Circ. 2015 Dec;5(4):691-700. doi: 10.1086/683813.

Phase I safety study of ranolazine in pulmonary arterial hypertension.

Pulmonary circulation

Mardi Gomberg-Maitland, Robert Schilz, Anuj Mediratta, Karima Addetia, Sandra Coslet, Vasiliki Thomeas, Hunter Gillies, Ronald J Oudiz

Affiliations

  1. Section of Cardiology, Department of Medicine, University of Chicago, Chicago, Illinois, USA ; Committee on Clinical Pharmacology and Pharmacogenomics, Department of Medicine, University of Chicago, Chicago, Illinois, USA.
  2. Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, School of Medicine, Case Western University, Cleveland, Ohio, USA.
  3. Section of Cardiology, Department of Medicine, University of Chicago, Chicago, Illinois, USA.
  4. Gilead Sciences, Foster City, California, USA.
  5. Division of Cardiology, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, California, USA.

PMID: 26697176 PMCID: PMC4671743 DOI: 10.1086/683813

Abstract

UNLABELLED: Pulmonary arterial hypertension (PAH) causes right ventricular ischemia, dysfunction, and failure. PAH patients may benefit from antianginal agents based on a shared pathophysiology with left ventricular ischemia. A single-center, randomized, placebo-controlled trial (1∶1) to assess the acute vasoreactivity and safety of ranolazine in PAH was conducted. Plasma samples for pharmacokinetic (PK) studies were drawn during hemodynamic measurements at 0, 60, 90, 120, 240, and 360 minutes from a Swan-Ganz catheter. All patients received 500-mg doses, uptitrated to 1,000 mg at week 4, monthly evaluations, and a complete objective assessment after 12 weeks, followed by an open-label extension. Thirteen patients were randomized and 12 enrolled (6 ranolazine, 6 placebo). All patients completed the acute phase; 10 completed the 12-week study. There were no acute changes in invasive hemodynamics. At 12 weeks ranolazine was well tolerated. Only 1 of the 5 patients on ranolazine had a serum concentration considered to be in the therapeutic range. Two serious adverse events required early withdrawal (both in the ranolazine group); gastrointestinal complaints were the most common adverse event. Efficacy measures did not demonstrate any differences between treatment groups. During the open-label trial, 2 additional patients reached a therapeutic concentration. Ranolazine in PAH appears safe, without acute hemodynamic effects after a 500-mg dose. Ranolazine administrated to PAH patients receiving background PAH therapies did not consistently reach therapeutic levels. Future studies should first perform PK analysis in PAH patients receiving PAH therapies and explore the safety and tolerability of the higher doses perhaps necessary to achieve therapeutic levels in PAH patients. (

TRIAL REGISTRATION: Clinicaltrials.gov identifier NCT01757808.).

Keywords: pulmonary arterial hypertension; right ventricular failure

References

  1. Circulation. 2002 May 21;105(20):2398-403 - PubMed
  2. Circulation. 1994 Aug;90(2):726-34 - PubMed
  3. N Engl J Med. 2013 Jul 25;369(4):330-40 - PubMed
  4. Am J Respir Crit Care Med. 2002 Jul 1;166(1):111-7 - PubMed
  5. J Am Coll Cardiol. 2013 Dec 24;62(25 Suppl):D42-50 - PubMed
  6. Am J Cardiol. 1972 Nov;30(7):757-62 - PubMed
  7. J Am Soc Echocardiogr. 1995 Jan-Feb;8(1):55-60 - PubMed
  8. J Heart Lung Transplant. 2008 Jan;27(1):124-30 - PubMed
  9. J Am Coll Cardiol. 2013 Dec 24;62(25 Suppl):D4-12 - PubMed
  10. Chest. 2004 Sep;126(3):816-24 - PubMed
  11. JACC Cardiovasc Imaging. 2009 Nov;2(11):1301-9 - PubMed
  12. J Am Soc Echocardiogr. 2003 Jul;16(7):777-802 - PubMed
  13. Chest. 1995 Jan;107(1):54-7 - PubMed
  14. Int J Sports Med. 1990 Feb;11(1):26-32 - PubMed
  15. Qual Life Res. 2006 Feb;15(1):103-15 - PubMed
  16. Chest. 2005 May;127(5):1637-46 - PubMed
  17. J Appl Physiol (1985). 1986 Jun;60(6):2020-7 - PubMed
  18. J Am Coll Cardiol. 2013 Dec 24;62(25 Suppl):D60-72 - PubMed
  19. Cardiovasc Res. 1994 Aug;28(8):1231-7 - PubMed
  20. Heart. 2006 Jul;92 Suppl 4:iv6-iv14 - PubMed
  21. Eur Heart J Cardiovasc Imaging. 2012 Jan;13(1):1-46 - PubMed
  22. Eur Respir J. 2009 Apr;33(4):785-92 - PubMed
  23. J Am Coll Cardiol. 2013 Dec 24;62(25 Suppl):D34-41 - PubMed
  24. J Clin Pharmacol. 2009 Nov;49(11):1343-52 - PubMed
  25. Am J Cardiol. 1990 Dec 1;66(19):1363-7 - PubMed
  26. J Pharmacol Exp Ther. 2013 Sep;346(3):343-9 - PubMed
  27. N Engl J Med. 2013 Aug 29;369(9):809-18 - PubMed

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