ASCEND - A Randomised, Double Blind, Placebo Controlled, Parallel Group Study to Assess the Effect of the Endothelin Receptor Antagonist Avosentan on Time to Doubling of Serum Creatinine, End Stage Renal Disease or Death in Patients With Type 2 Diabetes Mellitus and Diabetic Nephropathy

The purpose of this study is to determine whether avosentan (SPP301) is effective in decreasing morbidity and mortality in patients with diabetic nephropathy.

Start Date01 Jul 2005

Sponsor / Collaborator

Speedel Pharma AG

100 Clinical Results associated with Avosentan

100 Translational Medicine associated with Avosentan

100 Patents (Medical) associated with Avosentan

Literatures (Medical) associated with Avosentan

07 Nov 2021·Cureus

Endothelin Receptor Antagonists as a Potential Treatment of Diabetic Nephropathy: A Systematic Review

Review

Author: Veerapalli, Harish ; Castaneda, Everardo E ; Lankala, Chetan Reddy ; Aziz, Afia ; Rockferry, Amy G ; Ahmad, Noorain ; Hamid, Pousette

Diabetic nephropathy is becoming a more predominant cause of end-stage renal disease, as the prevalence of diabetes mellitus worldwide is on the rise. In this systematic review, we aimed to define the role of endothelin receptor antagonists, in the prevention and treatment of diabetic nephropathy, in addition to determining their safety. For this review, PubMed, Google Scholar, and Cochrane Library databases, in addition to ClinicalTrials.gov, were searched for publications in the last 20 years. We included 14 studies, seven randomized control trials, and seven post hoc analyses in this paper. Atrasentan decreased albuminuria, reduced blood pressure, and improved lipid profiles with more manageable fluid overload-related adverse events than avosentan and bosentan. Overall, endothelin receptor antagonists, in combination with renin-angiotensin-aldosterone system inhibitors, effectively reduce albuminuria and prevent the progression of diabetic kidney disease. However, more extensive clinical trials still need to be conducted to confirm these relationships and to learn more about the specific factors affecting their efficacy in individual patients.

01 Jan 2021·Diabetic MedicineQ2 · MEDICINE

Efficacy and safety of endothelin receptor antagonists in type 2 diabetic kidney disease: A systematic review and meta‐analysis of randomized controlled trials

Q2 · MEDICINE

Review

Author: Chi, J. ; Zhou, Y. ; Huang, Y. ; Lv, W. ; Wang, Y. G. ; Dong, B.

AbstractAimTo analyse the efficacy and safety of endothelin receptor antagonists for people with diabetic kidney disease.MethodsRandomized controlled trials comparing endothelin receptor antagonists with placebo in people with diabetic kidney disease were identified through PubMed, Embase and the Cochrane Library. We used a random‐effect model to calculate the mean difference or risk ratio with the 95% CI.ResultsSeven studies with a total of 4730 participants were included. Overall, endothelin receptor antagonists significantly reduced albuminuria compared with placebo (standardized mean difference –0.48, 95% CI –0.64 to –0.33). Atrasentan, in particular, effectively reduced albuminuria (standardized mean difference –0.58, 95% CI –1.00 to –0.17) and the risk of composite renal endpoints (risk ratio 0.65; 95% CI 0.49 to 0.88), with insignificant change in the rate of congestive heart failure (risk ratio 1.40, 95% CI 0.76 to 2.56) and mortality (risk ratio 1.11, 95% CI 0.77 to 1.61). In contrast, although avosentan reduced albuminuria (standardized mean difference –0.47, 95% CI –0.57 to –0.36) and the risk of composite renal endpoints (risk ratio 0.63, 95% CI 0.42 to 0.94), it was associated with a significant increase in congestive heart failure risk (risk ratio 2.61, 95% CI 1.36 to 5.00) and an insignificant increase in mortality risk (risk ratio 1.50, 95% CI 0.81, 2.78). No significant change in efficacy or safety outcomes with bosentan was detected. Dose–response analysis indicated that 0.75 mg/day atrasentan is expected to be optimal for renoprotection, with maximal albuminuria reduction and minimal fluid retention events.ConclusionsAmong the endothelin receptor antagonists, atrasentan and avosentan, but not bosentan, are effective for renoprotection in people with diabetic kidney disease. Compared with other types and doses, atrasentan 0.75 mg/day is the most promising, with maximal albuminuria reduction and minimal fluid retention. Vigilant monitoring of congestive heart failure risk is needed in future clinical practice. (PROSPERO registration no. CRD42020169840).

03 Jun 2017·Expert Opinion on Investigational DrugsQ2 · MEDICINE

Atrasentan for the treatment of diabetic nephropathy

Q2 · MEDICINE

Review

Author: Ruiz-Ortega, Marta ; Egido, Jesus ; Mas, Sebastian ; Sanz, Ana Belen ; Rojas-Rivera, Jorge ; Gonzalez Parra, Emilio ; Gomez-Guerrero, Carmen

INTRODUCTIONEndothelin-1 (ET-1) is the most potent vasoconstrictor, and is involved in the renal regulation of salt and water homeostasis. When produced in excess in the kidney, ET-1 promotes proteinuria and tubulointerstitial injury. There is great interest in the clinical use of endothelin receptor antagonists (ERAs) in chronic kidney disease (CKD), mainly in diabetic nephropathy (DN). Areas covered: Physiopathological actions of ET-1 on the kidney. Both dual ETAR/ET_BR (bosentan) or ET_AR specific endothelin antagonists (avosentan and atrasentan, among others), which have progressed to early clinical development, with particular emphasis on atrasentan. Expert opinion: Different phase I and II clinical trials with ERAs in DN, mostly with atrasentan, have shown that these drugs have a marked anti-proteinuric effect on residual proteinuria when administered as add-on therapy in addition to ACEi or ARAII treatment. In the past few years, a series of randomized controlled trials investigating new approaches to DN have provided negative or inconclusive data, or even were terminated due to safety concerns or lack of efficacy. Therefore, we eagerly but cautiously await the results of the ongoing SONAR trial with atrasentan in more than 4,000 patients including assessment of renal and cardiovascular hard-end points (estimated primary completion date, July 2018).

100 Deals associated with Avosentan

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R&D Status

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Indication	Highest Phase	Country/Location	Organization	Date
Diabetes Mellitus, Type 2	Phase 1	US	Speedel Pharma AG	01 Jul 2005
Diabetic Nephropathies	Phase 1	US	Speedel Pharma AG	01 Jul 2005
Diabetic Nephropathies	Phase 1	US	Spera Pharma, Inc.Startup	01 Jul 2005
Kidney Failure, Chronic	Phase 1	US	Speedel Pharma AG	01 Jul 2005
Glaucoma	Preclinical	CH	Speedel Experimenta Ltd	01 Apr 2009
Glaucoma	Preclinical	US	Icahn School of Medicine at Mount Sinai	01 Apr 2009

Clinical Result

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT00120328 (ASCEND, EASD2013)	Phase 3	Heart Failure body weight \| haemoglobin \| cholesterol levels ... View more	1,392	Avosentan	rzeasmaffs(oidmarfcvc) = cfucovcbqf frjqgguwwo (jupbkwsyas, 0.0 - 2.0) View more	Negative	25 Sep 2013
				Placebo	-
ASCEND (ASN2012)	Not Applicable	Heart Failure	761	Avosentan 25mg	erturnldco(vcfkvatxln) = an excess of congestive heart failure (CHF) events occurred in the avosentan treatment arms which was likely due to increased sodium/fluid retention and led to premature termination of the trial domqncifwc (klryiggogv )	Negative	30 Oct 2012
				Avosentan 50mg

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