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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01858532




Registration number
NCT01858532
Ethics application status
Date submitted
17/05/2013
Date registered
21/05/2013

Titles & IDs
Public title
Study Of Diabetic Nephropathy With Atrasentan
Scientific 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
Secondary ID [1] 0 0
2012-005848-21
Secondary ID [2] 0 0
M11-352
Universal Trial Number (UTN)
Trial acronym
SONAR
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Diabetic Nephropathy 0 0
Condition category
Condition code
Renal and Urogenital 0 0 0 0
Kidney disease
Metabolic and Endocrine 0 0 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Atrasentan
Treatment: Drugs - Placebo

Active comparator: Atrasentan - 0.75 mg atrasentan once daily by mouth for up to 52 months

Placebo comparator: Placebo - Placebo once daily by mouth for up to 52 months


Treatment: Drugs: Atrasentan
Film-coated tablet

Treatment: Drugs: Placebo
Film-coated tablet
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Time to the First Occurrence of a Component of the Composite Renal Endpoint in the Intent-to-Treat (ITT) Responder Set (as Randomized)
Timepoint [1] 0 0
From randomization to individual end of observation, up to 53 months
Secondary outcome [1] 0 0
Time to a 50% Estimated Glomerular Filtration Rate Reduction in the Intent-to-Treat (ITT) Responder Set (as Randomized)
Timepoint [1] 0 0
From randomization to individual end of observation, up to 53 months
Secondary outcome [2] 0 0
Time to Cardio-renal Composite Endpoint in the Intent-to-Treat (ITT) Responder Set (as Randomized)
Timepoint [2] 0 0
From randomization to individual end of observation, up to 53 months
Secondary outcome [3] 0 0
Time to First Occurrence of a Component of Composite Renal Endpoint for All Randomized Participants (Pooled)
Timepoint [3] 0 0
From randomization to individual end of observation, up to 53 months
Secondary outcome [4] 0 0
Time to the Cardiovascular Composite Endpoint in the Intent-to-Treat (ITT) Responder Set (as Randomized)
Timepoint [4] 0 0
From randomization to individual end of observation, up to 53 months

Eligibility
Key inclusion criteria
* Participant, or legal representative, had voluntarily signed and dated an Informed Consent Form, approved by an Institutional Review Board (IRB)/Independent Ethics Committee (IEC), after the nature of the study had been explained and the participant had the opportunity to ask questions. The informed consent must have been signed before any study-specific procedures were performed.
* Participant had type 2 diabetes (including participants with latent autoimmune diabetes or insulin-treated participants without a history of diabetic ketoacidosis who also had a negative anti-glutamic acid decarboxylase test AND an elevated post-prandial serum C-peptide level) and had been treated with at least one anti-hyperglycemic medication and an angiotensin-converting enzyme inhibitor (ACEi) or Angiotensin II receptor blocker (ARB; RAS inhibitor) for at least 4 weeks prior to the Screening S2 visit.
* For entry into the Run-In Period the participant must have satisfied the following criteria based on the Screening laboratory values:

* Estimated glomerular filtration rate (eGFR) 25 to 75 mL/min/1.73 m^2 [until the eGFR cap on participants (approximately 300) with a baseline of > 60 mL/min/1.73 m^2 was reached] 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);
* Participants 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 satisfied the above criteria may have proceeded to the last visit in the Run-In Period (R6);
* Participants 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 were to start with a diuretic and participate in Run-In for at least 2 weeks.
* For entry into the Enrichment Period the participant must have satisfied 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;
* Participants 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, participants must have satisfied 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);
* Participants must not have had 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;
* Participants must not have had 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.
Minimum age
18 Years
Maximum age
85 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
A participant was not eligible for entry into the Run-in Period if he/she met any of the following criteria:

* Participant had 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.
* Participant had a history of pulmonary hypertension, pulmonary fibrosis or any lung diseases requiring oxygen therapy (e.g., chronic obstructive pulmonary disease, emphysema).
* Participant had 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.
* Participant had known non-diabetic kidney disease (other than kidney stones).
* Participant had elevated liver enzymes (serum alanine aminotransaminase [ALT] and/or serum aspartate aminotransaminase [AST]) > 3 × the upper limit of normal (ULN).
* Participant had hemoglobin < 9 g/dL (90 g/L).
* Participant had a sensitivity to loop diuretics.
* Participant had a history of an allergic reaction or significant sensitivity to atrasentan (or its excipients) or similar compounds.
* Participant had a history of chronic gastrointestinal disease, which, in the Investigator's opinion, may have caused significant GI malabsorption.
* Participant had a history of secondary hypertension (i.e., hemodynamically significant renal artery stenosis, primary aldosteronism or pheochromocytoma).
* Participant had significant comorbidities (e.g., advanced malignancy, advanced liver disease) with a life expectancy of less than 1 year.
* Participant had clinically significant cerebrovascular disease (CVD) or coronary artery disease (CAD) within 3 months prior to the Screening S1 visit, defined as one of the following:

* Hospitalization for MI or unstable angina; or
* New onset angina with positive functional study or coronary angiogram revealing stenosis; or
* Coronary revascularization procedure; or
* Transient Ischemic Attack or Stroke.
* Participant had received any investigational drug including atrasentan within 3 months prior to the Screening S1 visit.
* Participant received dialysis treatments or was expected to receive dialysis or renal transplant within 6 months of screening.
* Participant was currently receiving rosiglitazone, moxonidine, aldosterone blockers, aliskiren or a combination of ACEi and ARB.
* Participant was a premenopausal woman defined as (for study purposes) any female subject with a menses in the past 2 years. For women who were < 50 years old, serum FSH must have been greater than 35 IU/L. Women who were surgically sterile or had a history of hysterectomy may not have necessarily be postmenopausal, and must also have had an FSH > 35 IU/L.
* Participant was at high risk for QT/QTc prolongation such as a family history of Long QT Syndrome, defined as QTc prolongation exceeding 450 ms in men, or 460 ms in women.
* Participant had type 1 diabetes.
* Participant was considered to be clinically unstable regarding general, metabolic or cardiovascular health as determined by the Investigator.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
17/05/2013
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
29/03/2018
Sample size
Target
Accrual to date
Final
5107
Recruitment in Australia
Recruitment state(s)

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
AbbVie
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
AbbVie Inc.
Address 0 0
AbbVie
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Undecided
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?




Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results are available at https://clinicaltrials.gov/study/NCT01858532