Study Of Diabetic Nephropathy With Atrasentan (SONAR)

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by AbbVie
Sponsor:
Information provided by (Responsible Party):
AbbVie
ClinicalTrials.gov Identifier:
NCT01858532
First received: May 17, 2013
Last updated: July 23, 2014
Last verified: July 2014
  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 (needing chronic dialysis or renal transplantation or renal death).


Secondary Outcome Measures:
  • Change from baseline to Month 24 post-randomization visit on urine albumin creatinine ratio. [ Time Frame: From Day 0 to 24 months. ] [ Designated as safety issue: Yes ]
  • Time to a 30% estimated glomerular filtration rate reduction after 3 months post-randomization treatment. [ Time Frame: Approximately 24 months. ] [ Designated as safety issue: Yes ]
  • Time to cardio-renal composite endpoint: 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 ]

Estimated Enrollment: 4148
Study Start Date: March 2013
Estimated Study Completion Date: March 2017
Estimated Primary Completion Date: February 2017 (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
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Subject has type 2 diabetes and has been treated with at least one anti-hyperglycemic medication and angiotensin converting enzyme (ACE) inhibitor or angiotensin receptor blockers (ARB) (Renin Angiotensin System inhibitor) for at least 3 months prior to the Screening Period.
  • Glucosylated hemoglobin A1c (HbA1c) less than or equal to 12%.
  • 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 (The number of subjects with eGFR between 60 to 75 mL/min/1.73 m2 will be capped to 10% of the total population);
    • Serum albumin greater than or equal to 3.0 g/dL (30 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 160 mmHg;
    • Serum Potassium greater than or equal to 3.5 (3.5 mmol/L) and less than or equal to 5.5 mEq/L (5.5 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);
    • Weight change less than 3 kg and absolute serum BNP less than 300 pg/mL (300 ng/L) at Enrichment Week 6 from the beginning of Enrichment;
    • Subjects must not have an acute kidney injury (AKI) event at the end of the Enrichment period, as defined by an increase from baseline in serum Creatinine greater than 0.5 mg/dL and greater than 20% increase at Enrichment Week 6 (visit E5) from baseline.

Exclusion Criteria:

  • Subject has a history of moderate or severe peripheral edema, pulmonary edema or facial edema unrelated to trauma or a history of myxedema in the prior 6 months to Screening.
  • Subject has a history of pulmonary hypertension requiring oxygen therapy, and/or endothelin receptor antagonist or phosphodiesterase therapy or any lung diseases requiring oxygen therapy (e.g., chronic obstructive pulmonary disease, emphysema, pulmonary fibrosis).
  • 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).
  • Subject has a history of symptomatic hypotension within the last 6 months.
  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: Blai Coll, MD 847-937-6156 blai.coll@abbvie.com
Contact: Renee Heuser, BS 847-938-5887 renee.heuser@abbvie.com

  Show 699 Study Locations
Sponsors and Collaborators
AbbVie
Investigators
Study Director: Blai Coll, MD AbbVie
  More Information

No publications provided

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: July 23, 2014
Health Authority: United States: Food and Drug Administration
Peru: Instituto Nacional de Salud
Slovakia: State Institute for Drug Control
Switzerland: Swissmedic
Malaysia: Ministry of Health
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Canada: Health Canada
Israel: Ministry of Health
Greece: National Organization of Medicines
Russia: Ministry of Health of the Russian Federation
Poland: Ministry of Health
Hong Kong: Department of Health
Sweden: Medical Products Agency
Denmark: Danish Medicines Agency
Turkey: Ministry of Health
Italy: Ethics Committee
Portugal: National Pharmacy and Medicines Institute
Australia: Department of Health and Ageing Therapeutic Goods Administration
Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica
Ireland: Irish Medicines Board
Taiwan : Food and Drug Administration
South Africa: Medicines Control Council
Finland: Finnish Medicines Agency
Ukraine: Ministry of Health
New Zealand: Medsafe
Czech Republic: State Institute for Drug Control
Japan: Pharmaceuticals and Medical Devices Agency
Germany: Federal Institute for Drugs and Medical Devices
Belgium: Federal Agency for Medicinal Products and Health Products
Spain: Agencia Española de Medicamentos y Productos Sanitarios
Brazil: National Health Surveillance Agency
Netherlands: Medicines Evaluation Board (MEB)
Bulgaria: Bulgarian Drug Agency
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
Mexico: Federal Commission for Protection Against Health Risks
Chile: Instituto de Salud Pública de Chile
Singapore: Health Sciences Authority
Romania: National Agency for Medicines and Medical Devices
France: Agence Nationale de Sécurité du Médicament et des produits de santé

Keywords provided by AbbVie:
Nephropathy
Diabetes

Additional relevant MeSH terms:
Diabetic Nephropathies
Kidney Diseases
Diabetes Complications
Diabetes Mellitus
Endocrine System Diseases
Urologic Diseases

ClinicalTrials.gov processed this record on October 23, 2014