Diabetic NephropathyPhase 2NCT00664027
Phase IIa Trial to Determine the Effects of Bardoxolone Methyl on Renal Function in Patients With Diabetic Nephropathy
A Phase 2 study testing RTA 402 (Bardoxolone Methyl) in people with Diabetic Nephropathy, run by Biogen at 3 sites in United States.
Trial summary
To determine the effects of three different doses of bardoxolone methyl administered orally on the kidney function (glomular filtration rate) in patients with diabetic nephropathy. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Diabetic Nephropathy
- What is being tested?
- RTA 402 (Bardoxolone Methyl)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 80 participants
- Where
- 3 sitesUnited States
- Study dates
- 30 Apr 2008to 31 May 2009
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Diagnosis of type 2 diabetes;
- Serum creatinine in women 1.3 - 3.0 mg/dL (115-265 μmol/L), inclusive, and in men 1.5 - 3.0 mg/dL (133-265 μmol/L), inclusive;
- Patient must agree to practice effective contraception.
- Patient must have a negative urine pregnancy test within 72 hours prior to the first dose of study medication.
- Patient is willing and able to cooperate with all aspects of the protocol and is able to communicate effectively.
- Patient is willing and able to provide written informed consent to participate in this clinical study.
Who cannot join
- Type 1 (insulin-dependent; juvenile onset) diabetes.
- Patients with known non-diabetic renal disease (nephrosclerosis superimposed on diabetic nephropathy acceptable), or with renal allograft.
- Cardiovascular disease as follows: unstable angina pectoris within 3 mo of study entry; myocardial infarction, coronary artery bypass graft surgery, or percutaneous transluminal coronary angioplasty/stent within 3 mo of study entry; transient ischemic attack within 3 mo of study entry; cerebrovascular accident within 3 mo of study entry; obstructive valvular heart disease or hypertrophic cardiomyopathy; second or third degree atrioventricular block not successfully treated with a pacemaker.
- Need for chronic (>2 weeks) immunosuppressive therapy, including corticosteroids (excluding inhaled or nasal steroids) within 3 mo of study entry.
- Evidence of hepatic dysfunction including total bilirubin >1.5 mg/dL (>26 micromole/L); elevation of liver transaminase (aspartate aminotransferase [AST] or alanine transferase [ALT])above the upper limit of normal(ULN) within the 14-day screening period; documented elevation (above ULN) of AST or ALT within 3 months prior to screening; elevation of alkaline phosphatase (ALP) above 1.5 x ULN; documented elevation of gamma-glutamyl transpeptidase (GGT) above 1.5 X ULN.
- If female, patient is pregnant, nursing or planning a pregnancy.
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- Patient has any concurrent clinical conditions that in the judgment of the investigator could either potentially pose a health risk to the patient while involved in the study or could potentially influence the study outcome;
- Patient has known hypersensitivity to any component of the study drug;
- Patient has known allergy to iodine;
- Patient has undergone diagnostic or intervention procedure requiring a contrast agent within the last 30 days prior to entry into the study;
- Change or dose-adjustment in any of the following medications: ACE inhibitors, angiotensin II blockers, non-steroidal anti inflammatory drugs (NSAIDs), or COX-2 inhibitors within 3 months; other anti-hypertensive, and other anti-diabetic medications within 6 weeks prior to entry into the study;
- Patient has a history of drug or alcohol abuse or has positive test results for any drug of abuse (positive urine drug test and/or alcohol breathalyzer test).
- Patients who are unable or unwilling to discontinue the following medications until 1 week following last dose of study treatment: Nicotinic acid, Isoniazid, Dantrolene, Labetalol, Pemoline, Felbamate, Zileutan, Tolcapone, Trovafloxacin, Vitamin D, Vitamin D analogues (such as Calcitriol, paricalcitol, doxercalciferol), or multivitamins containing vitamin D or related analogs, or Fenofibrate. Patient must have been off the aforementioned medications for a minimum of two weeks prior to enrollment.
- Patient with an intact parathyroid hormone (iPTH) level > 300 pg/mL.
- Patient has participated in another clinical study involving investigational or marketed products within 30 days prior to entry into the study or would concomitantly participate in such a study.
- Patient is unable to communicate or cooperate with the Investigator due to language problems, poor mental development or impaired cerebral function.
Trial locations and contacts
3 sites in 1 country.
United States3 sites
West Houston Clinical Research Services
Houston, Texas, 77055
Renal Associates, PA
San Antonio, Texas, 78215
DGD Research
San Antonio, Texas, 78229
About this study
Official title: An Open-Label, Randomized, Dose-ranging Phase IIa Trial to Determine the Effects of RTA 402 (Bardoxolone Methyl) on Renal Function in Patients With Diabetic Nephropathy
To determine the effects of three different doses of bardoxolone methyl administered orally on the kidney function (glomular filtration rate) in patients with diabetic nephropathy.
Read the detailed description
Bardoxolone methyl is an Antioxidant Inflammation Modulator in clinical development for inflammation and cancer-related indications that inhibits immune-mediated inflammation by restoring redox homeostasis in inflamed tissues. It induces the cytoprotective transcription factor Nrf2 and suppresses the activities of the pro-oxidant and pro-inflammatory transcription factors NF-kB and the STATs. In vivo, bardoxolone has demonstrated significant single agent anti-inflammatory activity in several animal models of inflammation such as renal damage in the cisplatin model and ischemia-reperfusion model of acute renal injury. In addition, significant reductions in serum creatinine have been observed in patients treated with bardoxolone. Based on these data, it is hypothesized that bardoxolone can improve renal function in patients with diabetic nephropathy through suppression of renal inflammation and improvement of glomerular filtration.
- Conditions
- Diabetic Nephropathy
- Being tested
- RTA 402 (Bardoxolone Methyl)
- Medical subject headings
- Diabetic Nephropathies
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RTA 402 (Bardoxolone Methyl)Drug
Stratum 1: 25, 75, 150mg/day, orally, 28 consecutive days Stratum 2: 25 mg/day, orally, 28 consecutive days followed by 75 mg/day, orally, 28 consecutive days
| Study group | Role | What they receive |
|---|---|---|
| 25 mg | Experimental | 25 mg RTA 402 (Bardoxolone methyl)/Stratum 1 Receives: Drug: RTA 402 (Bardoxolone Methyl) |
| 75 mg | Experimental | 75 mg RTA 402 (Bardoxolone methyl)/Stratum 1 Receives: Drug: RTA 402 (Bardoxolone Methyl) |
| 150 mg | Experimental | 150 mg RTA 402 (Bardoxolone methyl)/Stratum 1 Receives: Drug: RTA 402 (Bardoxolone Methyl) |
| 25/75 mg | Experimental | 25 mg -> 75 mg RTA 402 (Bardoxolone methyl)/Stratum 2 Receives: Drug: RTA 402 (Bardoxolone Methyl) |
What is being measured
The primary outcome is the main question the study is designed to answer.
To determine the effects of RTA 402 administered orally at three dose strengths on the glomerular filtration rate (as estimated by the MDRD formula) in patients with diabetic nephropathy (stratum 1).
Measured: 28 days
To determine the effects of RTA 402 on glomerular filtration rate (as estimated by the MDRD formula) when administered for 28 days at dose of 25 mg followed by a dose of 75 mg for another 28 days in patients with diabetic nephropathy (stratum 2).
Measured: 56 days
Secondary outcomes (5)
To evaluate the safety and tolerability of oral RTA 402 administered orally at three dose strengths in patients with diabetic nephropathy.
Measured: 28 days
To evaluate the effects of RTA 402 on the serum creatinine level, iohexol serum clearance (one study center only), creatinine clearance, and urine albumin/creatinine ratio in patients with diabetic nephropathy.
Measured: 28 days (stratum 1), 56 days (stratum 2)
To evaluate the effects of RTA 402 on hemoglobin A1c in all patients enrolled and on insulin response by the hyperinsulinemic euglycemic clamp test in patients enrolled at only one of the study centers.
Measured: 28 days (stratum 1), 56 days (stratum 2)
To evaluate the effects of RTA 402 on a panel of markers of inflammation, renal injury, oxidative stress, and endothelial cell dysfunction.
Measured: 28 days (stratum 1), 56 days (stratum 2)
To determine the safety and tolerability of RTA 402 when the dose is escalated after 28 days in patients with diabetic nephropathy from 25 mg to 75 mg and continued for another 28 consecutive days.
Measured: 28 days (stratum 1), 56 days (stratum 2)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Apr 2008 (estimated)
- Study start30 Apr 2008
- Primary completion31 May 2009
- Study completion31 May 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Diabetic NephropathyStudies of the same condition, open and under way.
- More trials run by BiogenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 80 participants (actual)
Sponsor and investigators
- Lead sponsor
- Biogen
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00664027
- Sponsor's protocol ID
- RTA 402-C-0801
- Status last verified
- May 2025
- First submitted
- 18 Apr 2008
- Last updated
- 29 May 2025
- Results posted
- No
- Individual data sharing
- Yes: In accordance with Biogen's Clinical Trial Transparency and Data Sharing Policy on https://www.biogentrialtransparency.com/
Study at a glance
From the registry record, last updated by the sponsor on 29 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-Label, Randomized, Dose-ranging Phase IIa Trial to Determine the Effects of RTA 402 (Bardoxolone Methyl) on Renal Function in Patients With Diabetic Nephropathy
- ClinicalTrials.gov ID
- NCT00664027
- Acronym / sponsor ID
- RTA 402-C-0801
- Conditions
- Diabetic Nephropathy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 80 participants (actual)
- Lead sponsor
- BiogenIndustry (pharma, biotech, devices)
- Study start
- 30 Apr 2008 (actual)
- Primary completion
- 31 May 2009 (actual)
- Study completion
- 31 May 2009 (actual)
- First posted
- 22 Apr 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
To determine the effects of three different doses of bardoxolone methyl administered orally on the kidney function (glomular filtration rate) in patients with diabetic nephropathy.
Detailed description
Bardoxolone methyl is an Antioxidant Inflammation Modulator in clinical development for inflammation and cancer-related indications that inhibits immune-mediated inflammation by restoring redox homeostasis in inflamed tissues. It induces the cytoprotective transcription factor Nrf2 and suppresses the activities of the pro-oxidant and pro-inflammatory transcription factors NF-kB and the STATs. In vivo, bardoxolone has demonstrated significant single agent anti-inflammatory activity in several animal models of inflammation such as renal damage in the cisplatin model and ischemia-reperfusion model of acute renal injury. In addition, significant reductions in serum creatinine have been observed in patients treated with bardoxolone. Based on these data, it is hypothesized that bardoxolone can improve renal function in patients with diabetic nephropathy through suppression of renal inflammation and improvement of glomerular filtration.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| 25 mg | Experimental | Drug: RTA 402 (Bardoxolone Methyl)25 mg RTA 402 (Bardoxolone methyl)/Stratum 1 |
| 75 mg | Experimental | Drug: RTA 402 (Bardoxolone Methyl)75 mg RTA 402 (Bardoxolone methyl)/Stratum 1 |
| 150 mg | Experimental | Drug: RTA 402 (Bardoxolone Methyl)150 mg RTA 402 (Bardoxolone methyl)/Stratum 1 |
| 25/75 mg | Experimental | Drug: RTA 402 (Bardoxolone Methyl)25 mg -> 75 mg RTA 402 (Bardoxolone methyl)/Stratum 2 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Diagnosis of type 2 diabetes;
- Serum creatinine in women 1.3 - 3.0 mg/dL (115-265 μmol/L), inclusive, and in men 1.5 - 3.0 mg/dL (133-265 μmol/L), inclusive;
- Patient must agree to practice effective contraception.
- Patient must have a negative urine pregnancy test within 72 hours prior to the first dose of study medication.
- Patient is willing and able to cooperate with all aspects of the protocol and is able to communicate effectively.
Key exclusion criteria (16 listed)
- Type 1 (insulin-dependent; juvenile onset) diabetes.
- Patients with known non-diabetic renal disease (nephrosclerosis superimposed on diabetic nephropathy acceptable), or with renal allograft.
- Cardiovascular disease as follows: unstable angina pectoris within 3 mo of study entry; myocardial infarction, coronary artery bypass graft surgery, or percutaneous transluminal coronary angioplasty/stent within 3 mo of study entry; transient ischemic attack within 3 mo of study entry; cerebrovascular accident within 3 mo of study entry; obstructive valvular heart disease or hypertrophic cardiomyopathy; second or third degree atrioventricular block not successfully treated with a pacemaker.
- Need for chronic (>2 weeks) immunosuppressive therapy, including corticosteroids (excluding inhaled or nasal steroids) within 3 mo of study entry.
- Evidence of hepatic dysfunction including total bilirubin >1.5 mg/dL (>26 micromole/L); elevation of liver transaminase (aspartate aminotransferase [AST] or alanine transferase [ALT])above the upper limit of normal(ULN) within the 14-day screening period; documented elevation (above ULN) of AST or ALT within 3 months prior to screening; elevation of alkaline phosphatase (ALP) above 1.5 x ULN; documented elevation of gamma-glutamyl transpeptidase (GGT) above 1.5 X ULN.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RTA 402 (Bardoxolone Methyl)Stratum 1: 25, 75, 150mg/day, orally, 28 consecutive days Stratum 2: 25 mg/day, orally, 28 consecutive days followed by 75 mg/day, orally, 28 consecutive days | Drug | 150 mg, 25 mg, 25/75 mg, 75 mg |
Primary outcome
To determine the effects of RTA 402 administered orally at three dose strengths on the glomerular filtration rate (as estimated by the MDRD formula) in patients with diabetic nephropathy (stratum 1).
Time frame: 28 days
To determine the effects of RTA 402 on glomerular filtration rate (as estimated by the MDRD formula) when administered for 28 days at dose of 25 mg followed by a dose of 75 mg for another 28 days in patients with diabetic nephropathy (stratum 2).
Time frame: 56 days
5 secondary outcomes
To evaluate the safety and tolerability of oral RTA 402 administered orally at three dose strengths in patients with diabetic nephropathy.
Time frame: 28 days
To evaluate the effects of RTA 402 on the serum creatinine level, iohexol serum clearance (one study center only), creatinine clearance, and urine albumin/creatinine ratio in patients with diabetic nephropathy.
Time frame: 28 days (stratum 1), 56 days (stratum 2)
To evaluate the effects of RTA 402 on hemoglobin A1c in all patients enrolled and on insulin response by the hyperinsulinemic euglycemic clamp test in patients enrolled at only one of the study centers.
Time frame: 28 days (stratum 1), 56 days (stratum 2)
To evaluate the effects of RTA 402 on a panel of markers of inflammation, renal injury, oxidative stress, and endothelial cell dysfunction.
Time frame: 28 days (stratum 1), 56 days (stratum 2)
To determine the safety and tolerability of RTA 402 when the dose is escalated after 28 days in patients with diabetic nephropathy from 25 mg to 75 mg and continued for another 28 consecutive days.
Time frame: 28 days (stratum 1), 56 days (stratum 2)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 May 2025.
- Individual participant dataSharing planned: Yes. In accordance with Biogen's Clinical Trial Transparency and Data Sharing Policy on https://www.biogentrialtransparency.com/
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing RTA 402 (Bardoxolone Methyl) in people with Diabetic Nephropathy, run by Biogen at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 May 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To determine the effects of RTA 402 administered orally at three dose strengths on the glomerular filtration rate (as estimated by the MDRD formula) in patients with diabetic nephropathy (stratum 1). (time frame: 28 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 May 2025.