Pyridorin in Diabetic Nephropathy (PIONEER)

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2014 by NephroGenex, Inc.
Sponsor:
Collaborators:
Collaborative Study Group (CSG)
Medpace, Inc.
Information provided by (Responsible Party):
NephroGenex, Inc.
ClinicalTrials.gov Identifier:
NCT02156843
First received: May 28, 2014
Last updated: October 15, 2014
Last verified: October 2014
  Purpose

The purpose of this study is to evaluate the safety and efficacy of oral Pyridorin 300 mg BID in reducing the rate of progression of nephropathy due to type 2 diabetes mellitus.


Condition Intervention Phase
Diabetic Nephropathy
Diabetic Kidney Disease
Drug: Pyridorin
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 3 Randomized, Double-Blind, Placebo-Controlled, Multi-Center Study to Evaluate the Safety and Efficacy of Pyridorin (Pyridoxamine Dihydrochloride) in Subjects With Nephropathy Due to Type 2 Diabetes

Resource links provided by NLM:


Further study details as provided by NephroGenex, Inc.:

Primary Outcome Measures:
  • Time to composite endpoint of >=50% SCr increase from baseline or ESRD [ Time Frame: Approximately 42 Months ] [ Designated as safety issue: No ]
    Time to the composite endpoint consisting of the earliest event amongst a SCr increase of 50% from baseline that occurs during follow-up; or End Stage Renal Disease. ESRD is defined as the initiation of permanent dialysis, receiving a kidney transplant, or a SCr value >= 6.0 mg/dL (528 umol/L) with a second SCr confirmation value >=6.0 mg/dL (528 umol/L) obtained 4-6 weeks later.


Secondary Outcome Measures:
  • Time to the composite endpoint >=100% SCr increase or ESRD [ Time Frame: Approximately 42 Months ] [ Designated as safety issue: No ]
    A SCr increase of >=100% that occurs during follow-up; or ESRD


Other Outcome Measures:
  • Change in serum cystatin-C [ Time Frame: Change from baseline to Week 52 and from baseline to Week 104 ] [ Designated as safety issue: No ]
  • Change in urine protein/creatinine ratio (PCR) [ Time Frame: From baseline to Week 52 and from baseline to Week 104 ] [ Designated as safety issue: No ]
  • Change in urinary transforming growth factor-beta (TGF-Beta) excretion [ Time Frame: From baseline to Week 52 and from baseline to Week 104 ] [ Designated as safety issue: No ]
  • Change in SCr [ Time Frame: From baseline to Week 52 and from baseline to Week 104 ] [ Designated as safety issue: No ]

Estimated Enrollment: 600
Study Start Date: June 2014
Estimated Study Completion Date: March 2018
Estimated Primary Completion Date: December 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Pyridorin
Pyridorin (pyridoxamine dihydrochloride) 300 mg oral BID (twice daily, every 12 hours) Capsule
Drug: Pyridorin
300 mg BID (twice daily, every 12 hours), oral capsule taken until end stage renal disease or death occurs, or the study is terminated by the sponsor.
Other Name: pyridoxamine dihydrochloride
Placebo Comparator: Placebo
Placebo Oral Capsule taken BID (twice daily, every 12 hours)
Drug: Placebo
Placebo excipients without the active drug, oral capsule taken BID (twice daily, every 12 hours), until end stage renal disease or death occurs, or the study is terminated by the sponsor.

Detailed Description:

This is a randomized, double-blind, placebo-controlled, multi-center Phase 3 study to evaluate the safety and efficacy of Pyridorin 300 mg BID (twice daily, every 12 hours) in subjects with nephropathy due to type 2 diabetes mellitus. In this study, nephropathy is defined as a Serum Creatinine (SCr) >= 1.3 mg/dL (115 umol/L) for female and >=1.5 mg/dL (133 umol/L) for male subjects and a 24-hour urine collection protein/creatinine ration (PCR) >=1200 mg/g (136 mg/mmol). Subjects must have a baseline SCr < 3.0 mg/dL (265 umol/L) and must be on previously established standard of care at screening.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Patients meeting all of the following criteria will be eligible to participate in the study:

  1. Patients who have given voluntary written informed consent to participate in this study prior to conducting Screening (Visit 1) procedures
  2. Patients 18 years of age or older with a diagnosis of type 2 diabetes
  3. Women of childbearing potential (WOCBP) who agree to use appropriate birth control (double-barrier methods, hormonal contraceptives, or intrauterine device) for the duration of the study (women of childbearing potential is defined as all women who are not surgically sterile or are not at least 1 year post menopausal) All women of childbearing potential must have a negative serum pregnancy test at Visit 1
  4. All men (unless surgically sterile, as defined below) who have sexual intercourse with a WOCBP must agree and commit to use a highly effective method of contraception for the duration of the study (defined as the time of the signing of the informed consent form through the conclusion of patient participation). Highly effective methods of contraception include i. Male subjects agreeing that they and their female spouse/partners will use adequate contraception (2 forms of birth control, one of which must be barrier method) or be of non-childbearing potential

    ii. To be considered surgically sterilized, a male partner must have had a vasectomy at least 24 weeks before Visit 1

  5. At Visit 1, patients must have a history of overt diabetic nephropathy, as defined by the following

    • A SCr measurement ≥1.3 mg/dL (115 umol/L) for females or ≥1.5 mg/dL (133 umol/L) for males
    • A 24-hour urine collection PCR ≥1200 mg/g (136 mg/mmol)
  6. Patients must have a SCr measurement <3.0 mg/dL (265 umol/L)
  7. Patients must have an eGFR of ≥20 mL/min/1.73m2, using the 4-variable Modification of Diet in Renal Disease equation in which eGFR = 175 x (SCr(mg/dL))-1.154 x (Age(years))-0.203 x (0.742 if female) x (1.212 if African American)
  8. Patient must have a second screening SCr measurement at Visit 1.1 or 1.1S taken 1 week (± 2 days) after screening (Visit 1 or 1.1). The value of the second screening SCr measurement must be <3.0 mg/dL (265 umol/L) for both genders and within 25% of the first screening measurement
  9. Patients must be taking a single ACE-I or ARB at a constant dose for at least 26 weeks prior to Visit 1, where the dose of the ACE-I or the ARB is considered appropriate for that patient and it is anticipated that the same dose can and will be maintained throughout the course of the study
  10. Patients taking any blood pressure medications in addition to an ACE-I or ARB, including diuretics, must be: (1) on a stable dose for 26 weeks prior to Visit 1 with a seated blood pressure of <=150/90 mmHg; or (2) on a stable dose for 13 weeks prior to Visit 1 with a seated blood pressure of <=140/90 mmHg
  11. Patients not taking any blood pressure medications other than an ACE-I or ARB must have a seated blood pressure <=150/90 mmHg at Visit 1 and a seated blood pressure considered appropriate for the patient and one that can be sustained throughout the study

Exclusion Criteria:

Patients are excluded from participation in the study if any of the following criteria apply

  1. Patients with type 1 diabetes
  2. Patients with a diagnosis of chronic kidney disease other than diabetic renal disease with or without hypertensive renal disease
  3. Patients receiving a renin inhibitor or an aldosterone antagonist or a combination of an ACE-I and an ARB within 26 weeks of Visit 1
  4. Patients with a history of solid organ transplantation
  5. Patients with a history of myocardial infarction, coronary re-vascularization procedures (including percutaneous transluminal coronary angioplasty), stroke, or transient ischemic attack within 30 days prior to Visit 1
  6. Patients with a diagnosis of New York Heart Association Class III or IV congestive heart failure at any time
  7. Patients with a history of being treated for neoplastic disease (except basal or squamous cell carcinoma of the skin) within 5 years prior to Visit 1
  8. Patients with any history of dialysis within 2 years prior to Visit 1
  9. Patients in whom dialysis or renal transplantation is anticipated by their physician within 1 year after Visit 1
  10. Patients who used SCr-altering drugs within 30 days prior to Visit 1
  11. Patients who require systemic immunosuppression therapy for >2 weeks (except for inhalant steroids)
  12. Patients with clinically significant liver disease or transaminase (alanine aminotransferase and aspartate aminotransferase) levels >2.5 × the upper limit of normal (ULN) measured at Visit 1.1 or Visit 1.1S
  13. Patients with bilirubin levels >1.5 × ULN measured at Visit 1.1 or Visit 1.1S
  14. Patients with a history of allergic or other adverse response to vitamin B preparations
  15. Patients who require >50 mg of vitamin B6 daily
  16. Patients who have an active history of dysphagia or swallowing disorders
  17. Patients with a history of hypersensitivity to Pyridorin or any of the excipients (non-active ingredients) in the Pyridorin formulation
  18. Patients who have taken pyridoxamine or any other investigational drug within 30 days prior to Visit 1, or have participated in a previous Pyridorin study or another interventional clinical study within 30 days prior to Visit 1
  19. Patients with an active history of drug or alcohol abuse
  20. Patients unlikely to comply with the study protocol (eg, 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)
  21. Women who are lactating, pregnant, or intend to become pregnant during the course of the study
  22. Patients who are investigational site staff members and their families or patients who are employees of the Sponsor or the Sponsor's designees and are directly involved in the conduct of the study
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02156843

Contacts
Contact: Mohammed Sika, PhD 615-936-1179 CSG@vanderbilt.edu
Contact: Laura Craft, PhD 513-579-9911 ext 2180 L.Craft@medpace.com

  Show 33 Study Locations
Sponsors and Collaborators
NephroGenex, Inc.
Collaborative Study Group (CSG)
Medpace, Inc.
Investigators
Study Chair: Edmund J. Lewis, MD The Collaborative Study Group (CSG)
Study Chair: Julia B. Lewis, MD The Collaborative Study Group (CSG)
  More Information

No publications provided

Responsible Party: NephroGenex, Inc.
ClinicalTrials.gov Identifier: NCT02156843     History of Changes
Other Study ID Numbers: PYR-311, 2014-001641-24, CSG-17, PYR-311 (PIONEER)
Study First Received: May 28, 2014
Last Updated: October 15, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by NephroGenex, Inc.:
Diabetic Kidney Disease
Nephropathy
Diabetic Nephropathy
Kidney Disease
Type 2 Diabetes

Additional relevant MeSH terms:
Kidney Diseases
Diabetic Nephropathies
Urologic Diseases
Diabetes Complications
Diabetes Mellitus
Endocrine System Diseases
Pyridoxamine
Vitamin B Complex
Vitamins
Micronutrients
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on October 16, 2014