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NCT01858532: SONAR

Study Of Diabetic Nephropathy With Atrasentan

Terminated Phase 3 Results posted Last updated 24 April 2019
What this trial tests

Phase 3 trial testing Atrasentan in Diabetic Nephropathy in 5,107 participants. Terminated before completion.

Timeline
17 May 2013
Primary endpoint
29 March 2018
29 March 2018

Quick facts

Lead sponsorAbbVie
PhasePhase 3
StatusTerminated
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingquadruple
Primary purposetreatment
Enrollment5,107
Start date17 May 2013
Primary completion29 March 2018
Estimated completion29 March 2018

Drugs / interventions tested

Conditions studied

Sponsor

AbbVie — full company profile →

Who can join

Adults 18 to 85, any sex, with Diabetic Nephropathy. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Time to the First Occurrence of a Component of the Composite Renal Endpoint in the Intent-to-Treat (ITT) Responder Set (as Randomized) Primary · From randomization to individual end of observation, up to 53 months

Time to the first occurrence of a component of the composite renal endpoint was defined as doubling of serum creatinine (confirmed by a 30-day serum creatinine measurement) or the onset of end stage renal disease (estimated glomerular filtration rate \[eGFR\] less than 15 ml/min/1.73 m\^2 confirmed by a 90-day eGFR measurement, receiving chronic dialysis, renal transplantation, or renal death). Only events adjudicated by the Events Adjudication Committee (EAC) were considered in defining this endpoint. Data are presented as number of participants with a primary renal composite event (first eve

GroupValue95% CI
Intent-to-Treat (ITT) Responder Atrasentan79
Intent-to-Treat (ITT) Responder Placebo105
Time to a 50% Estimated Glomerular Filtration Rate Reduction in the Intent-to-Treat (ITT) Responder Set (as Randomized) Secondary · From randomization to individual end of observation, up to 53 months

The event of interest for this outcome was a 50% reduction in a participant's estimated glomerular filtration rate (eGFR) value as compared to baseline, confirmed by a repeated value at least 20 days apart. The event time was defined as the first time that a 50% reduction in eGFR was observed. Data are presented as number of participants with a 50% reduction in eGFR (first event per participant).

GroupValue95% CI
Intent-to-Treat (ITT) Responder Atrasentan78
Intent-to-Treat (ITT) Responder Placebo88
Time to Cardio-renal Composite Endpoint in the Intent-to-Treat (ITT) Responder Set (as Randomized) Secondary · From randomization to individual end of observation, up to 53 months

The composite event of interest for this outcome consisted of doubling of serum creatinine, end-stage renal disease (ESRD), cardiovascular (CV) death (including CV death and presumed CV death), nonfatal myocardial infarction (MI; heart attack) and nonfatal stroke. Presumed sudden cardiac death was included as a subcategory of presumed CV death. Only events adjudicated by the Events Adjudication Committee (EAC) were considered in defining this endpoint. Data are presented as number of participants with a cardio-renal composite event (first event per participant).

GroupValue95% CI
Intent-to-Treat (ITT) Responder Atrasentan147
Intent-to-Treat (ITT) Responder Placebo172
Time to First Occurrence of a Component of Composite Renal Endpoint for All Randomized Participants (Pooled) Secondary · From randomization to individual end of observation, up to 53 months

Time to the first occurrence of a component of the composite renal endpoint was defined as doubling of serum creatinine (confirmed by a 30-day serum creatinine measurement) or the onset of end stage renal disease (estimated glomerular filtration rate \[eGFR\] less than 15 ml/min/1.73 m\^2 confirmed by a 90-day eGFR measurement, receiving chronic dialysis, renal transplantation, or renal death). Data for all randomized participants were pooled by treatment and analyzed. Data are presented as number of participants with a renal composite event (first event per participant).

GroupValue95% CI
Intent-to-Treat (ITT) Atrasentan152
Intent-to-Treat Placebo192
Time to the Cardiovascular Composite Endpoint in the Intent-to-Treat (ITT) Responder Set (as Randomized) Secondary · From randomization to individual end of observation, up to 53 months

The composite event of interest for this outcome was cardiovascular (CV) death (CV death, presumed CV death), nonfatal myocardial infarction (MI; heart attack), and nonfatal stroke. Presumed sudden cardiac death was included as a sub-category of presumed CV death. Only events adjudicated by the Events Adjudication Committee (EAC) were used. Data are presented as number of participants with a cardiovascular composite event (first event per participant).

GroupValue95% CI
Intent-to-Treat (ITT) Responder Atrasentan72
Intent-to-Treat (ITT) Responder Placebo81

Adverse events — posted to ClinicalTrials.gov

Time frame: Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were reported from the time of study drug administration until 45 days after the last dose of study drug (up to 24 weeks for the All Atrasentan Set in the Enrichment Period; up to 54 months for the ITT sets in the Double-Blind Period). Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Enrichment Atrasentan
Serious: 292/5107 (6%)
Deaths: 25/5107
Double-Blind Atrasentan
Serious: 685/1829 (37%)
Deaths: 84/1829
Double-Blind Placebo
Serious: 626/1830 (34%)
Deaths: 79/1830

Serious adverse events (787 terms)

ReactionSystemEnrichment AtrasentanDouble-Blind AtrasentanDouble-Blind Placebo
PNEUMONIAInfections and infestations
ACUTE KIDNEY INJURYRenal and urinary disorders
CARDIAC FAILURE CONGESTIVECardiac disorders
ACUTE MYOCARDIAL INFARCTIONCardiac disorders
CORONARY ARTERY DISEASECardiac disorders
ANAEMIABlood and lymphatic system disorders
END STAGE RENAL DISEASERenal and urinary disorders
CELLULITISInfections and infestations
HYPOGLYCAEMIAMetabolism and nutrition disorders
URINARY TRACT INFECTIONInfections and infestations
CARDIAC FAILURECardiac disorders
CATARACTEye disorders
SEPSISInfections and infestations
DIABETIC NEPHROPATHYRenal and urinary disorders
ATRIAL FIBRILLATIONCardiac disorders
HYPERKALAEMIAMetabolism and nutrition disorders
OSTEOARTHRITISMusculoskeletal and connective tissue disorders
CEREBROVASCULAR ACCIDENTNervous system disorders
MYOCARDIAL INFARCTIONCardiac disorders
CHRONIC KIDNEY DISEASERenal and urinary disorders
RENAL IMPAIRMENTRenal and urinary disorders
FALLInjury, poisoning and procedural complications
DEHYDRATIONMetabolism and nutrition disorders
SYNCOPENervous system disorders
ACUTE RESPIRATORY FAILURERespiratory, thoracic and mediastinal disorders
Other adverse events (11 terms — click to expand)

ReactionSystemEnrichment AtrasentanDouble-Blind AtrasentanDouble-Blind Placebo
OEDEMA PERIPHERALGeneral disorders
HYPERTENSIONVascular disorders
ANAEMIABlood and lymphatic system disorders
NASOPHARYNGITISInfections and infestations
HYPERKALAEMIAMetabolism and nutrition disorders
HYPOGLYCAEMIAMetabolism and nutrition disorders
BACK PAINMusculoskeletal and connective tissue disorders
UPPER RESPIRATORY TRACT INFECTIONInfections and infestations
HYPERURICAEMIAMetabolism and nutrition disorders
DIARRHOEAGastrointestinal disorders
URINARY TRACT INFECTIONInfections and infestations

Most-reported serious reactions: PNEUMONIA, ACUTE KIDNEY INJURY, CARDIAC FAILURE CONGESTIVE, ACUTE MYOCARDIAL INFARCTION, CORONARY ARTERY DISEASE, ANAEMIA, END STAGE RENAL DISEASE, CELLULITIS.

Data from ClinicalTrials.gov NCT01858532 adverse events section.

Sponsor's own description

The study objective was to evaluate the effect of atrasentan compared with placebo on time to doubling of serum creatinine (DBSC) or the onset of end-stage renal disease (ESRD) in participants with type 2 diabetes and nephropathy who were treated with the maximum tolerated labeled daily dose (MTLDD) of a renin-angiotensin system (RAS) inhibitor. In addition, the study assessed the effects of atrasentan compared with placebo on cardiovascular (CV) morbidity and mortality, urine albumin excretion, changes in estimated glomerular filtration rate (eGFR), as well as the impact on quality of life in participants with type 2 diabetes and nephropathy.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Atrasentan and renal events in patients with type 2 diabetes and chronic kidney disease (SONAR): a double-blind, randomised, placebo-controlled trial.
    Heerspink HJL, Parving HH, Andress DL, Bakris G, et al · · 2019 · cited 476× · PMID 30995972 · DOI 10.1016/s0140-6736(19)30772-x
  2. Diabetic vascular diseases: molecular mechanisms and therapeutic strategies.
    Li Y, Liu Y, Liu S, Gao M, et al · · 2023 · cited 392× · PMID 37037849 · DOI 10.1038/s41392-023-01400-z
  3. Diabetic nephropathy - complications and treatment.
    Lim AKh. · · 2014 · cited 381× · PMID 25342915 · DOI 10.2147/ijnrd.s40172
  4. Diagnosis and Management of Type 2 Diabetic Kidney Disease.
    Doshi SM, Friedman AN. · · 2017 · cited 253× · PMID 28280116 · DOI 10.2215/cjn.11111016
  5. The next generation of therapeutics for chronic kidney disease.
    Breyer MD, Susztak K. · · 2016 · cited 223× · PMID 27230798 · DOI 10.1038/nrd.2016.67
  6. The endothelin antagonist atrasentan lowers residual albuminuria in patients with type 2 diabetic nephropathy.
    de Zeeuw D, Coll B, Andress D, Brennan JJ, et al · · 2014 · cited 212× · PMID 24722445 · DOI 10.1681/asn.2013080830
  7. Drug-Induced Reduction in Albuminuria Is Associated with Subsequent Renoprotection: A Meta-Analysis.
    Heerspink HJ, Kröpelin TF, Hoekman J, de Zeeuw D, et al · · 2015 · cited 184× · PMID 25421558 · DOI 10.1681/asn.2014070688
  8. Fast renal decline to end-stage renal disease: an unrecognized feature of nephropathy in diabetes.
    Krolewski AS, Skupien J, Rossing P, Warram JH. · · 2017 · cited 166× · PMID 28366227 · DOI 10.1016/j.kint.2016.10.046

Verify or expand the search:

Other trials of Atrasentan

Trials testing the same drug.

Other recruiting trials for Diabetic Nephropathy

Currently open trials in the same condition.

Other AbbVie trials

Trials by the same sponsor.

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Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing