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A randomized, double-blind, placebo-controlled, parallel-group study to assess the efficacy and safety of dual ACE/NEP inhibitor GW660511X in mild-to-moderate hypertensive patients

Journal of Human Hypertension volume 20, pages 496–503 (2006)Cite this article

Abstract

This multicentre, double-blind, placebo-controlled, parallel-group study determined the efficacy and safety of GW660511 200 mg, a dual inhibitor of angiotensin-converting enzyme (ACE) and neutral endopeptidase (NEP), in mild-to-moderate hypertensive patients (diastolic blood pressure (DBP), ⩾90 and ⩽109 mm Hg; systolic blood pressure (SBP), ⩾150 and ⩽180 mm Hg). After a single-blind 2- to 4-week placebo run-in period, 123 patients (aged 18–65 years) were randomized to either placebo (n=62) or to active treatment (n=61) consisting of two consecutive 3-day dose titration periods of GW660511X 50 mg once daily and 100 mg once daily followed by GW660511X 200 mg once daily for 14 days. GW660511X 200 mg significantly lowered (baseline and placebo-corrected) both trough mean cuff SBP (−8.00 mm Hg, P=0.002) and DBP (−5.38 mm Hg, P=0.003). GW660511X 200 mg significantly reduced placebo-corrected mean 24-h and daytime but not night-time ambulatory SBP and DBP. Over the 0–24 h time period following GW660511X 200 mg, there were significant (P<0.001) reductions in serum ACE activity and significant (P<0.001) increases in plasma ANP concentration compared with placebo in terms of both peak and trough effects. In addition, treatment with GW660511X 200 mg significantly (P=0.003) increased (placebo-corrected, 1.52-fold) urinary excretion of cGMP over the 0–24 h interval. Treatment-related adverse events were experienced by 43% of the patients administered GW660511X 200 mg and 44% of those dosed with placebo with headache the most commonly reported. In conclusion, GW660511X 200 mg is an effective antihypertensive in mild-to-moderate hypertensive patients with potent effects on biological markers of ACE and NEP inhibition.

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Acknowledgements

This study was supported by GlaxoSmithKline pharmaceuticals.

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Authors and Affiliations

  1. Cardiovascular and Urogenital Clinical Pharmacology and Discovery Medicine, GlaxoSmithKline Pharmaceuticals, King of Prussia, PA, USA

    A G Johnson & T M Danoff

  2. Innovative Data Resources, Asheville, NC, USA

    G L Pearce

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  1. A G Johnson
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  2. G L Pearce
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  3. T M Danoff
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Correspondence to A G Johnson.

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Johnson, A., Pearce, G. & Danoff, T. A randomized, double-blind, placebo-controlled, parallel-group study to assess the efficacy and safety of dual ACE/NEP inhibitor GW660511X in mild-to-moderate hypertensive patients. J Hum Hypertens 20, 496–503 (2006). https://doi.org/10.1038/sj.jhh.1002009

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