A Phase 3 Trial of the Efficacy and Safety of Bardoxolone Methyl in Patients with Polycystic Kidney Disease
- Conditions
- Autosomal dominant polycystic kidney diseaseMedDRA version: 20.0 Level: LLT Classification code 10036046 Term: Polycystic kidney, autosomal dominant System Organ Class: 100000004850Therapeutic area: Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]
- Registration Number
- EUCTR2018-004651-20-ES
- Lead Sponsor
- Reata Pharmaceuticals, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- Not specified
- Target Recruitment
- 300
1. Male and female patients 18 = age = 70 upon study consent;
2. Diagnosis of ADPKD by modified Pei-Ravine criteria: 1) at least 3 cysts per kidney by sonography or at least 5 cysts by CT or MRI with family history of ADPKD or 2) at least 10cysts per kidney by any radiologic method and exclusion of other cystic kidney diseases if without family history;
3. Screening eGFR (average of Screen A and Screen B eGFR values) = 30 to = 90 mL/min/1.73 m2 (18 to 55 years) or = 30 to = 44 mL/min/1.73 m2 (56 to 70 years):
a. Patients with either screening eGFR = 60 to = 90 mL/min/1.73 m2 or age 56 to 70 years, must have evidence of ADPKD progression (i.e., eGFR decline of = 2.0 mL/min/1.73 m2 per year, based on historical eGFR data and medical monitor discretion);
b. The two eGFR values collected at Screen A and Screen B visits used to determine eligibility must have a percent difference = 25%;
4. Albumin to creatinine ratio (ACR) = 2500 mg/g at Screen B visit;
5. Systolic blood pressure = 140 mmHg and diastolic blood pressure = 80 mmHg at Screen A visit after a period of rest. Patients receiving an angiotensin-converting enzyme (ACE) inhibitor and/or an angiotensin II receptor blocker (ARB) must be on a stable dose for at least 6 weeks prior to the Screen A visit;
6. Adequate bone marrow reserve and organ function at the Screen A visit as follows:
a. Hematologic: Absolute neutrophil count > 1.5 x 10^9/L, platelets > 100 x 10^9/L, hemoglobin (Hgb) = 9 g/dL;
b. Hepatic: Total bilirubin (TBL), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) = the upper limit of normal (ULN);
7. Able to swallow capsules;
8. Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures;
9. Evidence of a personally signed and dated informed consent document indicating that the patient has been informed of all pertinent aspects of the study prior to initiation of any protocol-mandated procedures.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 270
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 30
1. Prior exposure to bardoxolone methyl;
2. Concomitant use of tolvaptan is excluded. Patients previously treated with tolvaptan must have discontinued drug for at least 3 months prior to Screen A visit and had no history of elevations of ALT or AST > ULN while they were receiving tolvaptan. Initiation of concomitant tolvaptan use during the study is not permitted;
3. History of administration of polycystic kidney disease-modifying agents (somatostatin analogues) within 3 months prior to the Screen A visit.
4. B-type natriuretic peptide (BNP) level > 200 pg/mL at Screen A visit;
5. Uncontrolled diabetes (HbA1c > 11.0%) at Screen A visit;
6. Serum albumin < 3 g/dL at Screen A visit;
7. History of intracranial aneurysms;
8. Kidney or any other solid organ transplant recipient or a planned transplant during the study;
9. Acute dialysis or acute kidney injury within 12 weeks prior to Screen A visit or during Screening;
10. History of clinically significant left-sided heart disease and/or clinically significant cardiac disease, including but not limited to any of the following:
a. Clinically significant congenital or acquired valvular disease;
b. Left ventricular ejection fraction < 40% (based on echocardiogram performed at Screen A visit or within 6 months prior to Day 1);
c. Pericardial constriction (based on echocardiogram performed at Screen A visit or within 6 months prior to Day 1);
d. Restrictive or congestive cardiomyopathy (based on echocardiogram performed at Screen A visit or within 6 months prior to Day 1);
e. Symptomatic coronary disease (prior myocardial infarction, percutaneous coronary intervention, coronary artery bypass graft surgery, or angina);
f. History of hospitalization for heart failure;
g. Cardiac insufficiency, defined as New York Heart Association Class III or IV;
h. History of untreated atrial fibrillation;
i. History of unstable arrhythmias;
11. Systolic BP < 90 mm Hg at Screen A visit after a period of rest;
12. BMI < 18.5 kg/m2 at the Screen A visit;
13. History of malignancy within 5 years prior to Screen A visit, with the exception of localized skin or cervical carcinomas;
14. Systemic immunosuppression for more than 2 weeks, cumulatively, within the 12 weeks prior to randomization or anticipated need for immunosuppression during the study;
15. Untreated or uncontrolled active bacterial, fungal, or viral infection;
16. Participation in other interventional clinical studies within 30 days prior to Day 1;
17. Unwilling to practice acceptable methods of birth control (both males who have partners of child-bearing potential and females of childbearing potential) during Screening, while taking study drug, and for at least 30 days after the last dose of study drug is ingested;
18. Women who are pregnant or breastfeeding;
19. Known hypersensitivity to any component of the study drug;
20. Any abnormal laboratory level that, in the opinion of the investigator, would put the patient at risk by trial enrollment;
21. Patient is, in the opinion of t
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method