1. Efficacy and Safety of Firibastat, A First-in-Class Brain Aminopeptidase A Inhibitor, in Hypertensive Overweight Patients of Multiple Ethnic Origins
- Author
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Keith C. Ferdinand, Stephanie Desbrandes, Henry R. Black, Bruno Besse, Howard C. Dittrich, Shawna D. Nesbitt, and Fabrice Balavoine
- Subjects
medicine.medical_specialty ,business.industry ,Angiotensin III ,Ethnic group ,030204 cardiovascular system & hematology ,Overweight ,medicine.disease ,Obesity ,Angiotensin II ,03 medical and health sciences ,0302 clinical medicine ,Aminopeptidase A ,Blood pressure ,Physiology (medical) ,Internal medicine ,medicine ,030212 general & internal medicine ,medicine.symptom ,Cardiology and Cardiovascular Medicine ,business - Abstract
Background: Despite existing therapy, successful control of hypertension in the United States is estimated at less than 50%. In blacks, hypertension occurs earlier, is more severe, controlled less often and has a higher morbidity and mortality than in whites. Blacks are also less responsive to monotherapy with angiotensin-I converting enzyme inhibitors or angiotensin-II receptor type 1 blockers. Obesity, higher salt-sensitivity and low plasma renin activity are possible reasons of this poor blood pressure (BP) control, especially in blacks. The aim of the study was to assess efficacy and safety of firibastat, a first-in-class aminopeptidase A inhibitor preventing conversion of brain angiotensin-II into angiotensin-III, in BP lowering in a high-risk diverse hypertensive population. Methods: Two hundred fifty-six overweight or obese hypertensive patients, including 54% black and Hispanic individuals, were enrolled in a multicenter, open-label, phase II study. After a 2-week wash-out period, subjects received firibastat for 8 weeks (250 mg BID orally for 2 weeks, then 500 mg BID if automated office blood pressure (AOBP) >140/90 mm Hg; hydrochlorothiazide 25 mg QD was added after 1 month if AOBP ≥160/110 mm Hg). The primary end point was change from baseline in systolic AOBP after 8 weeks of treatment, and secondary end points include diastolic AOBP, 24-hour mean ambulatory BP and safety. Results: Firibastat lowered systolic AOBP by 9.5 mm Hg ( P P P P P Conclusions: Our results demonstrate the efficacy of firibastat in lowering BP in a high-risk diverse population where monotherapy with angiotensin-I converting enzyme inhibitors or angiotensin-II receptor type 1 blockers may be less effective and support the strategy to further investigate firibastat in subjects with difficult-to-treat or potentially resistant hypertension. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique Identifier: NCT03198793. more...
- Published
- 2019
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