Diabetic NephropathyPhase 2NCT00734253
Safety and Efficacy Study of Pyridorin in Patients With Nephropathy Due to Type 2 Diabetes
A Phase 2 study testing Pyridoxamine Dihydrochloride in people with Diabetic Nephropathy, run by NephroGenex, Inc. at 1 site in United States.
Trial summary
The primary objective of this study is to evaluate the efficacy of two different doses of Pyridorin (150 mg and 300 mg)compared to placebo in retarding the progression of diabetic nephropathy. Read more about this study
- Who is it for?
- Ages 25 years and older
- Conditions the study is for
- Diabetic Nephropathy
- What is being tested?
- Pyridoxamine Dihydrochloride
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 317 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2008to Aug 2010
- 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 25 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients who have given voluntary written consent to participate in this study prior to conducting Screening Visit procedures;
- Male and female patients 25 years of age or older with a diagnosis of type 2 diabetes; • If a woman is of childbearing potential (WOCBP) she must agree to use appropriate birth control (double barrier methods, hormonal contraceptives, or intrauterine device)for the duration of the study (WOCBP is defined as all women who are not surgically sterile or are not at least 1 year post-menopausal). All WOCBP must have a negative serum pregnancy test at the Screening Visit;
- At the Screening Visit, ALL patients must have a history of overt diabetic nephropathy, as defined by the following:
- A SCr measurement of 1.3 mg/dL to 3.3 mg/dL (women) or 1.5 mg/dL to 3.5 mg/dL (men) inclusive, and
- A 24-hour urine collection PCR ≥1200 mg/g;
- Patients must be receiving an ACE-I or an ARB, for at least 3 months prior to the Qualifying Visit (Screening Visit for those patients not entering into the Optional Run-in Period), where the dose of the ACE-I or the ARB is considered appropriate for that patient and has been stable for at least 2 months;
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- Patients must be on stable blood pressure medications for 2 months prior to the Qualifying Visit (Screening Visit for those patients not entering into the Optional Run-in Period), with a seated blood pressure at the Qualifying Visit of ≤160/90 mmHg;
- At the Qualifying Visit (only applies to those patients who enter into the Optional Run-in Period), the following eligibility parameters must be met in order to be randomized:
- A SCr measurement within 25% of the SCr measurement at the Screening Visit; and
- A 24-hour urine collection PCR ≥600 mg/g.
Who cannot join
- Patients with type 1 diabetes;
- Patients with a diagnosis of chronic renal disease other than diabetic renal disease with or without hypertensive renal disease;
- Patients receiving a renin inhibitor or an aldosterone antagonist or a combination of an ACE-I and an ARB within 2 months of the Qualifying Visit (Screening Visit for those patients not entering into the Optional Run-in Period);
- Patients with a history of solid organ transplantation;
- Patients with a history of myocardial infarction, coronary re-vascularization procedures (including percutaneous transluminal coronary angioplasty), cerebrovascular accident ortransient ischemic attack within 1 month prior to the Screening Visit;
- Patients with a diagnosis of Class III or IV congestive heart failure at any time (as defined by the New York Heart Association);
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- Patients with a history of neoplastic disease (except basal or squamous cell carcinoma of the skin) within 5 years prior to the Screening Visit;
- Patients with any history of dialysis within 2 years prior to the Screening Visit;
- Patients in whom dialysis or renal transplantation is anticipated by their physician within 1 year after the Screening Visit;
- Patients who used SCr altering drugs within 1 month prior to the Screening Visit;
- Patients who require systemic immunosuppression therapy for >2 weeks (except for inhalant steroids);
- Patients with clinically significant liver disease or transaminase (alanine aminotransferase and aspartate aminotransferase) levels >2.5 x upper limit of normal measured at the Screening Visit;
- Patients with bilirubin levels >1.5 x upper limit of normal measured at the Screening Visit;
- Patients with a history of allergic or other adverse response to vitamin B preparations;
- Patients who require >50 mg of vitamin B6 daily;
- Patients who have a history of dysphasia and swallowing disorders;
- Patients with a history of hypersensitivity to Pyridorin or any of the excipients in the Pyridorin formulation;
- Patients who have taken pyridoxamine or any other investigational drug within 30 days prior to the Screening Visit, or have participated in a previous Pyridorin trial or another clinical trial within 30 days prior to the Screening Visit;
- Patients with a current history of drug or alcohol abuse;
- Patients unlikely to comply with the study protocol (e.g., an inability and unwillingness to participate in adequate training, an uncooperative attitude, inability to return for follow-up visits, or unlikelihood of completing the study);
- Women who are lactating, pregnant or intend to become pregnant during the course of the study; and
- Patients who are employees of NephroGenex or its representatives.
Trial locations and contacts
1 site in 1 country.
United States1 site
The Collaborative Study Group
Chicago, Illinois, 60607
About this study
Official title: A Randomized, Double-Blind, Placebo-Controlled, Multi-Center, Phase 2b Study to Evaluate the Safety and Efficacy of Pyridorin (Pyridoxamine Dihydrochloride) in Patients With Nephropathy Due to Type 2 Diabetes
The primary objective of this study is to evaluate the efficacy of two different doses of Pyridorin (150 mg and 300 mg)compared to placebo in retarding the progression of diabetic nephropathy. This will be assessed by measuring the change in serum creatinine and other biomarkers of kidney disease during the course of the 1-year study.
Read the detailed description
Diabetic kidney disease afflicts about 20% of all diabetics and is the major cause of end-stage renal disease (ESRD). There are an estimated 1.2 million diabetic overt nephropathy patients in the US, and approximately 5.1 million diabetic patients exhibiting signs of developing kidney disease.
Hyperglycemia-induced microvascular disease is the fundamental cause of diabetic kidney disease. More specifically, hyperglycemia perturbs metabolic pathways, particularly in tissues that do not regulate intracellular glucose levels. This favors a broad range of pathogenic oxidative chemistries including the formation of advanced glycation end-products (AGEs), toxic carbonyls, and reactive oxygen species (ROS) that are considered to be the principal causative factors in the development of diabetic microvascular disease.
Pyridorin™ has been shown to inhibit AGE formation and to scavenge ROS and toxic carbonyl compounds in extensive in vitro studies. The therapeutic potential of Pyridorin™ has been demonstrated in vivo by extensive preclinical studies that have been carried out in a number of independent laboratories by prominent investigators. In addition, Pyridorin™ has demonstrated a significant treatment effect in slowing the progression of diabetic nephropathy in two Phase 2 clinical trials. Thus, a solid scientific rationale and clinical evidence exists for the application of Pyridorin™ therapy to slow the progression of diabetic kidney disease.
NephroGenex is initiating a new Phase 2b clinical trial (PYR-210) that is evaluating the safety and efficacy of Pyridorin™ in slowing the progression of overt nephropathy in patients with type 2 diabetes. This trial incorporates the latest discussion with the FDA regarding the use of an approvable surrogate marker that would be subsequently confirmed with hard clinical endpoints.
In this double-blind, placebo-controlled study, eligible type 2 diabetic patients with overt nephropathy will be treated for one year with bid doses of either Pyridorin™ 150 mg, Pyridorin™ 300 mg, or placebo. The primary endpoint in the study is the change in serum creatinine (SCr) from baseline after 1 year of therapy. Secondary 1-year endpoints include the slope of SCr, the change in protein/creatinine ratio (PCR) derived from 24-hour urine collections, and the change from baseline and slope of serum cystatin C.
The patient population studied will be type 2 diabetics with overt nephropathy defined as having a SCr between 1.3 and 3.3 mg/dl in females and between 1.5 and 3.5 mg/dl in males, accompanied by proteinuria in the macroalbuminuric range (PCR at least 1200 mg/g). In order to reduce confounding variables, careful control of blood pressure (BP) will be required. If not yet controlled, each patient's BP will brought to a level that the investigator believes is appropriate for the patient prior to randomization, and this will remain the target BP for that patient for the remainder of the study. Also, patients will be permitted to be on only one ACE inhibitor or angiotensin receptor blocker (ARB) and no other drugs that inhibit the renin-angiotensin-aldosterone axis throughout the study. A run-in period will be required in some patients to achieve the BP and ACEi/ARB requirements.
This study will be conducted with the leadership of the Collaborative Study Group.
- Conditions
- Diabetic Nephropathy
- Being tested
- Pyridoxamine Dihydrochloride, Placebo
- Keywords
- Nephropathy, Kidney Disease, Diabetes, Pyridoxamine, Pyridorin, NephroGenex, PYR-210
- Medical subject headings
- Diabetic Nephropathies, Kidney Diseases, Diabetes Mellitus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Pyridoxamine DihydrochlorideDrug
150 mg capsules taken orally twice a day for 1-year.
Pyridoxamine DihydrochlorideDrug
300 mg capsules taken twice a day for 1-year.
PlaceboDrug
Placebo capsules taken twice a day for 1-year
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Pyridorin 150 mg bid Receives: Drug: Pyridoxamine Dihydrochloride |
| 2 | Experimental | Pyridorin 300 mg bid Receives: Drug: Pyridoxamine Dihydrochloride |
| 3 | Placebo comparator | Placebo bid Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in serum creatinine from baseline to end of study.
Measured: 1 year
Secondary outcomes (1)
SCr slope, change in PCR, Cystatin C slope and change from baseline.
Measured: 1 Year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Aug 2008 (estimated)
- Study startAug 2008
- Primary completionAug 2010
- Study completionAug 2010
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.
- 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
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 317 participants (actual)
Sponsor and investigators
- Lead sponsor
- NephroGenex, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Collaborative Study Group (CSG), Medpace, Inc.
- Responsible party
- Sponsor
- Investigators
- Edmund J. Lewis, MD, Study chair, Collaborative Study Group
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00734253
- Sponsor's protocol ID
- PYR-210
- Status last verified
- May 2014
- First submitted
- 12 Aug 2008
- Last updated
- 28 Oct 2015
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 28 Oct 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double-Blind, Placebo-Controlled, Multi-Center, Phase 2b Study to Evaluate the Safety and Efficacy of Pyridorin (Pyridoxamine Dihydrochloride) in Patients With Nephropathy Due to Type 2 Diabetes
- ClinicalTrials.gov ID
- NCT00734253
- Acronym / sponsor ID
- PYR-210
- Conditions
- Diabetic Nephropathy
- Keywords
- Nephropathy, Kidney Disease, Diabetes, Pyridoxamine, Pyridorin, NephroGenex, PYR-210
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 317 participants (actual)
- Lead sponsor
- NephroGenex, Inc.Industry (pharma, biotech, devices)
- Collaborators
- Collaborative Study Group (CSG), Medpace, Inc.
- Study start
- Aug 2008
- Primary completion
- Aug 2010 (actual)
- Study completion
- Aug 2010 (actual)
- First posted
- 14 Aug 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.
The primary objective of this study is to evaluate the efficacy of two different doses of Pyridorin (150 mg and 300 mg)compared to placebo in retarding the progression of diabetic nephropathy. This will be assessed by measuring the change in serum creatinine and other biomarkers of kidney disease during the course of the 1-year study.
Detailed description
Diabetic kidney disease afflicts about 20% of all diabetics and is the major cause of end-stage renal disease (ESRD). There are an estimated 1.2 million diabetic overt nephropathy patients in the US, and approximately 5.1 million diabetic patients exhibiting signs of developing kidney disease.
Hyperglycemia-induced microvascular disease is the fundamental cause of diabetic kidney disease. More specifically, hyperglycemia perturbs metabolic pathways, particularly in tissues that do not regulate intracellular glucose levels. This favors a broad range of pathogenic oxidative chemistries including the formation of advanced glycation end-products (AGEs), toxic carbonyls, and reactive oxygen species (ROS) that are considered to be the principal causative factors in the development of diabetic microvascular disease.
Pyridorin™ has been shown to inhibit AGE formation and to scavenge ROS and toxic carbonyl compounds in extensive in vitro studies. The therapeutic potential of Pyridorin™ has been demonstrated in vivo by extensive preclinical studies that have been carried out in a number of independent laboratories by prominent investigators. In addition, Pyridorin™ has demonstrated a significant treatment effect in slowing the progression of diabetic nephropathy in two Phase 2 clinical trials. Thus, a solid scientific rationale and clinical evidence exists for the application of Pyridorin™ therapy to slow the progression of diabetic kidney disease.
NephroGenex is initiating a new Phase 2b clinical trial (PYR-210) that is evaluating the safety and efficacy of Pyridorin™ in slowing the progression of overt nephropathy in patients with type 2 diabetes. This trial incorporates the latest discussion with the FDA regarding the use of an approvable surrogate marker that would be subsequently confirmed with hard clinical endpoints.
In this double-blind, placebo-controlled study, eligible type 2 diabetic patients with overt nephropathy will be treated for one year with bid doses of either Pyridorin™ 150 mg, Pyridorin™ 300 mg, or placebo. The primary endpoint in the study is the change in serum creatinine (SCr) from baseline after 1 year of therapy. Secondary 1-year endpoints include the slope of SCr, the change in protein/creatinine ratio (PCR) derived from 24-hour urine collections, and the change from baseline and slope of serum cystatin C.
The patient population studied will be type 2 diabetics with overt nephropathy defined as having a SCr between 1.3 and 3.3 mg/dl in females and between 1.5 and 3.5 mg/dl in males, accompanied by proteinuria in the macroalbuminuric range (PCR at least 1200 mg/g). In order to reduce confounding variables, careful control of blood pressure (BP) will be required. If not yet controlled, each patient's BP will brought to a level that the investigator believes is appropriate for the patient prior to randomization, and this will remain the target BP for that patient for the remainder of the study. Also, patients will be permitted to be on only one ACE inhibitor or angiotensin receptor blocker (ARB) and no other drugs that inhibit the renin-angiotensin-aldosterone axis throughout the study. A run-in period will be required in some patients to achieve the BP and ACEi/ARB requirements.
This study will be conducted with the leadership of the Collaborative Study Group.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: Pyridoxamine DihydrochloridePyridorin 150 mg bid |
| 2 | Experimental | Drug: Pyridoxamine DihydrochloridePyridorin 300 mg bid |
| 3 | Placebo comparator | Drug: PlaceboPlacebo bid |
Who may qualify
- Ages
- 25 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Patients who have given voluntary written consent to participate in this study prior to conducting Screening Visit procedures;
- Male and female patients 25 years of age or older with a diagnosis of type 2 diabetes; • If a woman is of childbearing potential (WOCBP) she must agree to use appropriate birth control (double barrier methods, hormonal contraceptives, or intrauterine device)for the duration of the study (WOCBP is defined as all women who are not surgically sterile or are not at least 1 year post-menopausal). All WOCBP must have a negative serum pregnancy test at the Screening Visit;
- At the Screening Visit, ALL patients must have a history of overt diabetic nephropathy, as defined by the following:
- Patients must be receiving an ACE-I or an ARB, for at least 3 months prior to the Qualifying Visit (Screening Visit for those patients not entering into the Optional Run-in Period), where the dose of the ACE-I or the ARB is considered appropriate for that patient and has been stable for at least 2 months;
- Patients must be on stable blood pressure medications for 2 months prior to the Qualifying Visit (Screening Visit for those patients not entering into the Optional Run-in Period), with a seated blood pressure at the Qualifying Visit of ≤160/90 mmHg;
Key exclusion criteria (22 listed)
- Patients with type 1 diabetes;
- Patients with a diagnosis of chronic renal disease other than diabetic renal disease with or without hypertensive renal disease;
- Patients receiving a renin inhibitor or an aldosterone antagonist or a combination of an ACE-I and an ARB within 2 months of the Qualifying Visit (Screening Visit for those patients not entering into the Optional Run-in Period);
- Patients with a history of solid organ transplantation;
- Patients with a history of myocardial infarction, coronary re-vascularization procedures (including percutaneous transluminal coronary angioplasty), cerebrovascular accident ortransient ischemic attack within 1 month prior to the Screening Visit;
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 |
|---|---|---|
| Pyridoxamine Dihydrochloride150 mg capsules taken orally twice a day for 1-year. | Drug | 1 |
| Pyridoxamine Dihydrochloride300 mg capsules taken twice a day for 1-year. | Drug | 2 |
| PlaceboPlacebo capsules taken twice a day for 1-year | Drug | 3 |
Primary outcome
Change in serum creatinine from baseline to end of study.
Time frame: 1 year
1 secondary outcome
SCr slope, change in PCR, Cystatin C slope and change from baseline.
Time frame: 1 Year
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 28 Oct 2015.
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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.
Edmund J. Lewis, MD study chair
Collaborative Study Group
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Pyridoxamine Dihydrochloride in people with Diabetic Nephropathy, run by NephroGenex, Inc. at 1 site 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 10 inclusion and 22 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 28 Oct 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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. Some participants in this study may receive a placebo. 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?
Change in serum creatinine from baseline to end of study. (time frame: 1 year). 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 28 Oct 2015.