A Pharmacodynamic Study of Measured Glomerular Filtration Rate in Patients With Chronic Kidney Disease and Type 2 Diabetes

NCT01500798 | Terminated Phase 1

• 1 other identifier: 402-C-1005
• Study Type: interventional
• Target: 18
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a 24-week multi-center, double-blind, randomized, exploratory study of bardoxolone methyl treatment in 18 patients with Stage 3 CKD (eGFR greater than or equal to 30.0 to less than 60.0 ml/min/1.73m2) and diabetes to ensure at least 15 patients complete the study for evaluation of the primary endpoints.

Conditions

Chronic Kidney Disease; Type 2 Diabetes

Outcome Measures

Primary Outcomes (1)

• Measured GFR assessed by plasma clearance of Tc99m-DTPA

  Measured GFR assessed by plasma clearance of Tc99m-DTPA at Baseline mGFR assessment 1, Baseline mGFR assessment 2, and at Weeks 8, 16 and 20

  24 weeks

Secondary Outcomes (2)

• Measured GFR assessed by gama camera assessment of renal uptake of Tc99m-DTPA

  24 weeks

• Circulating endothelial cell assessments

  24 weeks

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Bardoxolone methyl

EXPERIMENTAL

Drug: 20 mg bardoxolone methyl

Interventions

20 mg bardoxolone methyl DRUG

20 mg, oral, once daily

Bardoxolone methyl

Placebo DRUG

Oral, once daily

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Screening eGFR ≥ 30.0 and \< 60.0 mL/min/1.73 m2;
• A history of type 2 diabetes; diagnosis should have been made at ≥ 30 years of age (if diabetes developed at a younger age, a fasting C-peptide level must be ≥ 0.1 ng/mL to confirm type 2 diabetes);
• Male or female patients at least 18 years of age;
• Treatment with an angiotensin converting enzyme (ACE) inhibitor and/or an angiotensin II receptor blocker (ARB) for at least 6 weeks prior to Screening Visit and during screening. The dosage of ACE inhibitor and/or ARB must be stable for 2 weeks prior to Screening Visit A and during screening (i.e., no change in dosage or medication). Patients not taking an ACE inhibitor and/or ARB, or taking an ACE inhibitor and/or ARB at levels below the goal dose set by K/DOQI guidelines (See Appendix 3) should have a documented medical contraindication (e.g., hyperkalemia, dry cough, angioedema), which the investigator must discuss with the appropriate medical monitor;
• Albumin/creatinine ratio (ACR) \< 300 mg/g;
• Mean systolic blood pressure (SBP) must be ≤ 160 mmHg and ≥ 105 mmHg and mean diastolic blood pressure (DBP) must be \< 90 mmHg during screening; both mean SBP and mean DBP (determined as the average of three readings) must be within the described range;
• Willing to practice methods of birth control (both males who have partners of childbearing potential and females of childbearing potential, \[see Section 9.7\]) during screening, while taking study drug and for at least 30 days after the last dose of study drug is ingested;
• Willing and able to cooperate with all aspects of the protocol;
• Willing and able to give written informed consent for study participation and provide consent for access to medical data according to appropriate local data protection legislation, allowing authorization to access medical records that describe events captured in the endpoints.

You may not qualify if:

• Type 1 diabetes mellitus (juvenile onset). If a history of diabetic ketoacidosis exists, a C-peptide level must confirm type 2 diabetes;
• Known non-diabetic renal disease (e.g., known polycystic kidney disease or family history of a hereditary form of kidney disease) \[nephrosclerosis superimposed on diabetic kidney disease is acceptable\];
• Ongoing clinical investigation with evidence (e.g., unexplained hematuria or red blood cell or white blood cell casts) suggesting non-diabetic renal disease other than nephrosclerosis;
• History of a renal donation, transplant or a planned transplant from a living donor during the study;
• Hemoglobin A1c level \> 9.0% (75 mmol/mol) during screening;
• Acute dialysis or acute kidney injury within 12 weeks prior to screening or during screening;
• Clinical signs and/or symptoms of uremia and expected need for renal replacement therapy within 12 weeks following randomization, as assessed by the investigator;
• Recently active cardiovascular disease defined as:
• Unstable angina pectoris within 12 weeks before study randomization;
• Myocardial infarction, coronary artery bypass graft surgery, or percutaneous transluminal coronary angioplasty/stent within 12 weeks before study randomization;
• Cerebrovascular accident, including transient ischemic attack within 12 weeks before study randomization;
• Current diagnosis of Class III or IV NYHA congestive heart failure (Appendix 4);
• Clinical diagnosis of severe obstructive valvular heart disease or severe obstructive hypertrophic cardiomyopathy;
• Atrioventricular block, 2o or 3o, not successfully treated with a pacemaker;
• Diagnostic or interventional procedure that required a contrast agent within 30 days prior to baseline mGFR visit 1 or planned during the study;

Sponsors & Collaborators

• Biogen: lead

MeSH Terms

Conditions

Renal Insufficiency, Chronic; Diabetes Mellitus, Type 2

Interventions

bardoxolone methyl

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 22, 2011
• First Posted: December 28, 2011
• Study Start: January 31, 2012
• Primary Completion: November 1, 2012
• Study Completion: October 1, 2013
• Last Updated: October 27, 2023

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will share