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Study Of Diabetic Nephropathy With Atrasentan (SONAR)

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2016 by AbbVie
Sponsor:
Information provided by (Responsible Party):
AbbVie
ClinicalTrials.gov Identifier:
NCT01858532
First received: May 17, 2013
Last updated: October 19, 2016
Last verified: October 2016
  Purpose
This study is being conducted to evaluate the effects of Atrasentan on Renal Outcomes in Subjects with Type 2 Diabetes and Nephropathy.

Condition Intervention Phase
Diabetic Nephropathy
Drug: Atrasentan
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Multicountry, Multicenter, Double-Blind, Parallel, Placebo-Controlled Study of the Effects of Atrasentan on Renal Outcomes in Subjects With Type 2 Diabetes and Nephropathy SONAR: Study Of Diabetic Nephropathy With Atrasentan

Resource links provided by NLM:


Further study details as provided by AbbVie:

Primary Outcome Measures:
  • Time to the first occurrence of a component of the composite renal endpoint. [ Time Frame: Approximately 48 months. ] [ Designated as safety issue: Yes ]
    Time to the first occurrence of a component of the composite renal endpoint: doubling of serum creatinine (confirmed by a 30-day serum creatinine) or the onset of end stage renal disease (estimated glomerular filtration rate (eGFR) less than 15 ml/min/1.73 m2 confirmed by a 90-day eGFR, receiving chronic dialysis, renal transplantation or renal death).


Secondary Outcome Measures:
  • Time to a 50% estimated glomerular filtration rate reduction. [ Time Frame: Approximately 48 months. ] [ Designated as safety issue: Yes ]
  • Time to cardio-renal composite endpoint: confirmed doubling of serum creatinine, end stage renal disease, cardiovascular death, nonfatal myocardial infarction, nonfatal stroke. [ Time Frame: Approximately 48 months. ] [ Designated as safety issue: Yes ]
  • Time to the cardiovascular composite endpoint: cardiovascular death, nonfatal myocardial infarction and nonfatal stroke. [ Time Frame: Approximately 48 months. ] [ Designated as safety issue: Yes ]
  • Time to first occurrence of a component of composite renal endpoint: confirmed doubling of serum creatinine or the onset of end stage renal disease for all randomized subjects (pooled). [ Time Frame: Approximately 48 months. ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 4148
Study Start Date: May 2013
Estimated Study Completion Date: November 2018
Estimated Primary Completion Date: July 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Atrasentan
Subjects randomized to the atrasentan arm will receive active drug, atrasentan.
Drug: Atrasentan
Oral daily low dose for 48 months.
Placebo Comparator: Placebo
Subjects randomized to the placebo arm will receive placebo.
Drug: Placebo
Oral daily dosing for 48 months.

Detailed Description:
The study objective is to evaluate the effect of atrasentan compared with placebo on time to doubling of serum creatinine or the onset of end stage renal disease (ESRD) in subjects with type 2 diabetes and nephropathy who are treated with the maximum tolerated labeled daily dose (MTLDD) of a Renin Angiotensin System (RAS) inhibitor. In addition, the study will assess the effects of atrasentan compared with placebo on cardiovascular morbidity and mortality, urine albumin excretion, changes in estimated glomerular filtration rate (eGFR), as well as on the impact on quality of life in subjects with type 2 diabetes and nephropathy.
  Eligibility

Ages Eligible for Study:   18 Years to 85 Years   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Subject has type 2 diabetes (including patients with latent autoimmune diabetes or insulin-treated patients without a history of diabetic ketoacidosis who also have a negative anti-glutamic acid decarboxylase test AND an elevated post-prandial serum C-peptide level) and has been treated with at least one anti-hyperglycemic medication and ACEi/or ARB (RAS inhibitor) for at least 4 weeks prior to the Screening S2 visit.
  • For entry into the Run-In Period the subject must satisfy the following criteria based on the Screening laboratory values:

    • Estimated glomerular filtration rate (eGFR) 25 to 75 mL/min/1.73 m2 and a urine albumin creatinine ratio (UACR) greater than or equal to 300 and less than 5,000 mg/g (greater than or equal to 34 mg/mmol and less than 565 mg/mmol);
    • Serum albumin greater than or equal to 2.5 g/dL (25 g/L);
    • Brain natriuretic peptide (BNP) less than or equal to 200 pg/mL (200 ng/L);
    • Systolic blood pressure (SBP) greater than or equal to 110 and less than or equal to 180 mmHg;
    • Serum Potassium greater than or equal to 3.5 mEq/L (3.5 mmol/L) and less than or equal to 6.0 mEq/L (6.0 mmol/L);
    • Subjects on a maximum tolerated labeled daily dose (MTLDD) of a RAS inhibitor for greater than or equal to 4 weeks and on a diuretic at the time of screening and who satisfy the above criteria may proceed to the last visit in Run-In Period (R6);
    • Subjects already on a MTLDD of a RAS inhibitor for greater than or equal to 4 weeks and not on a diuretic (unless medically contraindicated) at the time of Screening will start with a diuretic and proceed to Run-In for at least 2 weeks.
  • For entry into the Enrichment Period the subject must satisfy the following criteria based on the last visit of the Run-In Period:

    • RAS inhibitor at the MTLDD for the previous 4 weeks with no adjustments of the dose;
    • Subjects that were on a MTLDD RAS inhibitor and not on a diuretic (unless medically contraindicated) at the time of Screening must have been in Run-In for at least 2 weeks.
  • For entry into the Double-Blind Treatment Period, the subject must satisfy the following criteria based on the last visit of the Enrichment Period:

    • RAS inhibitor at the MTLDD for the previous 6 weeks during the Enrichment Period with no adjustments of the dose;
    • Diuretic at any dose unless medically contraindicated or clinically intolerable in the investigator's judgement (i.e., hypotension or hypokalemia);
    • Subject must not have a weight change greater than or equal to 3 kg from the beginning of Enrichment to the end of the Enrichment Period and absolute serum BNP greater than or equal to 300 pg/mL (300 ng/L) at the last Enrichment visit;
    • Subject must not have an increase in serum creatinine greater than 0.5 mg/dL and greater than 20% increase from the beginning of Enrichment to the end of the Enrichment Period.

Exclusion Criteria:

  • Subject has a history of severe peripheral edema or facial edema requiring diuretics unrelated to trauma or a history of myxedema in the prior 4 weeks to the initial Screening S1 visit.
  • Subject has a history of pulmonary hypertension, pulmonary fibrosis or any lung diseases requiring oxygen therapy (e.g., chronic obstructive pulmonary disease, emphysema).
  • Subject has a documented diagnosis of heart failure, previous hospitalization for heart failure or current or constellation of symptoms (dyspnea on exertion, pedal edema, orthopnea, paroxysmal nocturnal dyspnea) felt to be compatible with heart failure, that was not explained by other causes, and for which there was a change in medication or other management directed at heart failure.
  • Subject has known non-diabetic kidney disease (other than kidney stones).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01858532

Contacts
Contact: Melissa Wigderson, MD 847-935-7479 melissa.wigderson@abbvie.com
Contact: Mark Song, BS 847-935-6911 mark.song@abbvie.com

  Show 912 Study Locations
Sponsors and Collaborators
AbbVie
Investigators
Study Director: Melissa Wigderson, MD AbbVie
  More Information

Responsible Party: AbbVie
ClinicalTrials.gov Identifier: NCT01858532     History of Changes
Other Study ID Numbers: M11-352  2012-005848-21 
Study First Received: May 17, 2013
Last Updated: October 19, 2016
Health Authority: Finland: Finnish Medicines Agency
Chile: Instituto de Salud Pública de Chile
Germany: Federal Institute for Drugs and Medical Devices
Spain: Agencia Española de Medicamentos y Productos Sanitarios
Slovakia: State Institute for Drug Control
Poland: Ministry of Health
Greece: National Organization of Medicines
South Africa: Medicines Control Council
Switzerland: Swissmedic
Russia: Ministry of Health of the Russian Federation
Italy: Ethics Committee
Brazil: National Health Surveillance Agency
Australia: Department of Health and Ageing Therapeutic Goods Administration
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
Ukraine: Ministry of Health
Portugal: National Pharmacy and Medicines Institute
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Singapore: Health Sciences Authority
Romania: National Agency for Medicines and Medical Devices
Czech Republic: State Institute for Drug Control
Turkey: Ministry of Health
Mexico: Federal Commission for Protection Against Health Risks
Netherlands: Medicines Evaluation Board (MEB)
Bulgaria: Bulgarian Drug Agency
Peru: Instituto Nacional de Salud
France: Agence Nationale de Sécurité du Médicament et des produits de santé
Japan: Pharmaceuticals and Medical Devices Agency
Israel: Ministry of Health
Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica
Denmark: Danish Medicines Agency
Malaysia: Ministry of Health
New Zealand: Medsafe
Sweden: Medical Products Agency
Hong Kong: Department of Health
Ireland: Irish Medicines Board
Canada: Health Canada
Belgium: Federal Agency for Medicinal Products and Health Products
United States: Food and Drug Administration
Taiwan : Food and Drug Administration

Keywords provided by AbbVie:
Diabetes
Nephropathy

Additional relevant MeSH terms:
Kidney Diseases
Diabetic Nephropathies
Urologic Diseases
Diabetes Complications
Diabetes Mellitus
Endocrine System Diseases
Atrasentan
Endothelin Receptor Antagonists
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on December 05, 2016