Pyridorin in Diabetic Nephropathy

NCT02156843 | Terminated Phase 3 DMC

• 4 other identifiers: PYR-3112014-001641-24CSG-17PYR-311 (PIONEER)
• Study Type: interventional
• Target: 328
• Locations: 12 countries
• Sites: 137

Brief Summary

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.

Conditions

Diabetic Nephropathy; Diabetic Kidney Disease

Keywords

Diabetic Kidney Disease; Nephropathy; Diabetic Nephropathy; Kidney Disease; Type 2 Diabetes

Outcome Measures

Primary Outcomes (1)

• Time to composite endpoint of >=50% SCr increase from baseline or ESRD

  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 (530 umol/L) with a second SCr confirmation value \>=6.0 mg/dL (530 umol/L) obtained 4-6 weeks later. A confirmation of SCr value for subjects with ESRD and initiation of permanent dialysis or kidney transplant will not be collected.

  Approximately 45 Months

Secondary Outcomes (1)

• Time to the composite endpoint >=100% SCr increase or ESRD

  Approximately 45 Months

Other Outcomes (4)

• Change in serum cystatin-C

  Change from baseline to Week 52 and from baseline to Week 104

• Change in urine protein/creatinine ratio (PCR)

  From baseline to Week 52 and from baseline to Week 104

• Change in urinary transforming growth factor-beta (TGF-Beta) excretion

  From baseline to Week 52 and from baseline to Week 104

Study Arms (2)

Pyridorin

EXPERIMENTAL

Pyridorin (pyridoxamine dihydrochloride) 300 mg oral BID (twice daily, every 12 hours) Capsule

Drug: Pyridorin

Placebo

PLACEBO COMPARATOR

Placebo Oral Capsule taken BID (twice daily, every 12 hours)

Drug: Placebo

Interventions

Pyridorin DRUG

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.

Also known as: pyridoxamine dihydrochloride

Pyridorin

Placebo DRUG

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.

Placebo

Eligibility Criteria

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

You may qualify if:

• Patients meeting all of the following criteria will be eligible to participate in the study:
• Patients who have given voluntary written informed consent to participate in this study prior to conducting Screening (Visit 1) procedures;
• Patients 18 years of age or older with a diagnosis of type 2 diabetes;
• 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;
• 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;
• At Visit 1, patients must have a history of overt diabetic nephropathy, as defined by the following:
• A SCr measurement ≥1.3 (≥1.25)mg/dL (111 µmol/L) for females or ≥1.5 (≥1.45) mg/dL (128 µmol/L) for males;
• At Visit 1 or 1.1 24-hour urine collection PCR \>1200 mg/g (130 mg/µmol) and, if applicable for PS phase, at Visit 1S or 1.1S a 24-urine collection PCR \>600 mg/g (67 mg/µmol)
• For eligibility determination, laboratory reported values of PCR will be rounded up to 2 significant digits (e.g. ≥1150 mg/g to 1200 mg/g; ≥595 mg/g to 600 mg/g),
• Patients must have a SCr measurement \<3.0 mg/dL (265 µmol/L);
• 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);
• 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 1S). The value of the second screening SCr measurement must be \<3.0 mg/dL (265 µmol/L) for both genders and within 25% of the first screening measurement;
• 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 (can be zero to max dose approved by the FDA) and it is anticipated that the same dose can and will be maintained throughout the course of the study;

You may not qualify if:

• Patients are excluded from participation in the study if any of the following criteria apply
• Patients with type 1 diabetes or MODY (a monogenic form of diabetes);
• Patients with a diagnosis of chronic kidney 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 26 weeks of Visit 1
• Patients with a history of solid organ transplantation
• 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
• Patients with a diagnosis of New York Heart Association Class III or IV congestive heart failure at any time
• 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
• Patients with any history of dialysis within 2 years prior to Visit 1
• Patients in whom dialysis or renal transplantation is anticipated by their physician within 1 year after Visit 1
• Patients who used SCr-altering drugs within 30 days prior to Visit 1
• 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 × the upper limit of normal (ULN) measured at Visit 1.1 or Visit 1.1S
• Patients with bilirubin levels \>1.5 × ULN measured at Visit 1.1 or Visit 1.1S
• Patients with a history of allergic or other adverse response to vitamin B preparations

Sponsors & Collaborators

• NephroGenex, Inc.: lead
• Collaborative Study Group (CSG): collaborator
• Medpace, Inc.: collaborator

Study Sites (137)

CSG Investigational Site (#157)

Birmingham, Alabama, 35294, United States

Location

CSG Investigational Site (#130)

Phoenix, Arizona, 85012, United States

Location

CSG Investigational Site (#150)

Phoenix, Arizona, 85054, United States

Location

CSG Investigational Site (#145)

Prescott, Arizona, 86301, United States

Location

CSG Investigational Site (#142)

Tucson, Arizona, 85745, United States

Location

CSG Investigational Site (#160)

Los Angeles, California, 90048, United States

Location

CSG Investigational Site (#143)

Riverside, California, 92505, United States

Location

CSG Investigational Site (#159)

Roseville, California, 95661, United States

Location

CSG Investigational Site (#153)

Arvada, Colorado, 80002, United States

Location

CSG Investigational Site (#118)

Aurora, Colorado, 80045, United States

Location

CSG Investigational Site (#120)

Westminster, Colorado, 80031, United States

Location

CSG Investigational Site (#158)

Waterbury, Connecticut, 06708, United States

Location

CSG Investigational Site (#156)

Columbus, Georgia, 31901, United States

Location

CSG Investigational Site (#113)

Chicago, Illinois, 60607, United States

Location

CSG Investigational Site (#102)

Michigan City, Indiana, 46360, United States

Location

CSG Investigational Site (#115)

New Orleans, Louisiana, 70112, United States

Location

CSG Investigational Site (#147)

Greenbelt, Maryland, 20770, United States

Location

CSG Investigational Site (#117)

Boston, Massachusetts, 02111, United States

Location

CSG Investigational Site (#114)

Springfield, Massachusetts, 01107, United States

Location

CSG Investigational Site (#111)

Detroit, Michigan, 48202, United States

Location

CSG Investigational Site (#134)

Pontiac, Michigan, 48341, United States

Location

CSG Investigational Site (#162)

Kansas City, Missouri, 64111, United States

Location

CSG Investigational Site (#152)

Kansas City, Missouri, 64128, United States

Location

CSG Investigational Site (#141)

Las Vegas, Nevada, 89115, United States

Location

CSG Investigational Site (#128)

Buffalo, New York, 14215, United States

Location

CSG Investigational Site (#136)

Northport, New York, 11768, United States

Location

CSG Investigational Site (#154)

West Nyack, New York, 10994, United States

Location

CSG Investigational Site (#108)

Asheville, North Carolina, 28801, United States

Location

CSG Investigational Site (#116)

Charlotte, North Carolina, 28207, United States

Location

CSG Investigational Site (#125)

Durham, North Carolina, 27710, United States

Location

CSG Investigational Site (#155)

New Bern, North Carolina, 28562, United States

Location

CSG Investigational Site (#127)

Winston-Salem, North Carolina, 27157, United States

Location

CSG Investigational Site (#124)

Cincinnati, Ohio, 45267, United States

Location

CSG Investigational Site (#151)

Cleveland, Ohio, 44106, United States

Location

CSG Investigational Site (#123)

Cleveland, Ohio, 44195, United States

Location

CSG Investigational Site (#106)

Columbus, Ohio, 43210, United States

Location

CSG Investigational Site (#148)

Parma Heights, Ohio, 44130, United States

Location

CSG Investigational Site (#101)

Philadelphia, Pennsylvania, 19104, United States

Location

CSG Investigational Site (#149)

Pittsburgh, Pennsylvania, 15240, United States

Location

CSG Investigational Site (#146)

Providence, Rhode Island, 02903, United States

Location

CSG Investigational Site (#131)

Chattanooga, Tennessee, 37408, United States

Location

CSG Investigational Site (#105)

Nashville, Tennessee, 37205, United States

Location

CSG Investigational Site (#119)

Dallas, Texas, 75390, United States

Location

CSG Investigational Site (#139)

Houston, Texas, 77004, United States

Location

CSG Investigational Site (#133)

Houston, Texas, 77076, United States

Location

CSG Investigational Site (#109)

Midland, Texas, 79707, United States

Location

CSG Investigational Site (#132)

Salt Lake City, Utah, 84112, United States

Location

CSG Investigational Site (#107)

Burlington, Vermont, 05401, United States

Location

CSG Investigational Site (#129)

Charlottesville, Virginia, 22908, United States

Location

CSG Investigational Site (#137)

Fairfax, Virginia, 22030, United States

Location

CSG Investigational Site (#103)

Fairfax, Virginia, 22033, United States

Location

CSG Investigational Site (#104)

Hampton, Virginia, 23666, United States

Location

CSG Investigational Site (#144)

Richmond, Virginia, 23249, United States

Location

CSG Investigational Site (#121)

Spokane, Washington, 99204, United States

Location

CSG Investigational Site (#122)

Milwaukee, Wisconsin, 53295, United States

Location

CSG Investigational Site (#205)

Camperdown, New South Wales, 2050, Australia

Location

CSG Investigational Site (#201)

Gosford, New South Wales, 2250, Australia

Location

CSG Investigational Site (#206)

Liverpool, New South Wales, 2170, Australia

Location

CSG Investigational Site (#208)

St Leonards, New South Wales, 2065, Australia

Location

CSG Investigative Site (#204)

Adelaide, South Australia, 5000, Australia

Location

CSG Investigational Site (#207)

Footscray, Victoria, 2011, Australia

Location

CSG Investigational Site (#200)

Reservoir, Victoria, 3073, Australia

Location

CSG Investigational Site (#202)

Richmond, Victoria, 3121, Australia

Location

CSG Investigational Site (#209)

Parkville, 3050, Australia

Location

CSG Investigational Site (#757)

Plovdiv, Bulgaria

Location

CSG Investigational Site (# 750)

Sofia, Bulgaria

Location

CSG Investigational Site (# 755)

Sofia, Bulgaria

Location

CSG Investigational Site (# 756)

Sofia, Bulgaria

Location

CSG Investigational Site (#751)

Sofia, Bulgaria

Location

CSG Investigational Site (#752)

Sofia, Bulgaria

Location

CSG Investigational Site (#753)

Sofia, Bulgaria

Location

CSG Investigational Site (#754)

Stara Zagora, Bulgaria

Location

CSG Investigational Site (#801)

Grenoble, Cedex, 38043, France

Location

CSG Investigational Site (#802)

Paris, Cedex, 75877, France

Location

CSG Investigational Site (#800)

Boulogne-sur-Mer, 62321, France

Location

CSG Investigational Site (#803)

Colmar, 68024, France

Location

CSG Investigational Site (#806)

Montpellier, 34295, France

Location

CSG Investigational Site (#804)

Rhone, 69310, France

Location

CSG Investigational Site (#805)

Valenciennes, 59322, France

Location

CSG Investigational Site (#709)

Aschaffenburg, 63739, Germany

Location

CSG Investigative Site (#702)

Berlin, 10249, Germany

Location

CSG Investigational Site (#706)

Elsterwerda, 04910, Germany

Location

CSG Investigational Site (#703)

Heidelberg, 69115, Germany

Location

CSG Investigational Site (#707)

Herzberg, 04916, Germany

Location

CSG Investigational Site (#701)

Hoyerswerda, 02977, Germany

Location

CSG Investigational Site (#708)

Mainz, 55116, Germany

Location

CSG Investigational Site (#700)

München, 81675, Germany

Location

CSG Investigational Site (#400)

Hong Kong, Hong Kong

Location

CSG Investigational Site (#402)

Kwai Chung, Hong Kong

Location

CSG Investigational Site (#401)

Shatin, Hong Kong

Location

CSG Investigational Site (#501)

Balatonfüred, 8230, Hungary

Location

CSG Investigational Site (#509)

Budapest, 1032, Hungary

Location

CSG Investigational Site (#513)

Budapest, 1036, Hungary

Location

CSG Investigational Site (#505)

Budapest, 1096, Hungary

Location

CSG Investigational Site (#507)

Debrecen, 4032, Hungary

Location

CSG Investigational Site (#508)

Gyula, 5701, Hungary

Location

CSG Investigational Site (#502)

Hatvan, 3000, Hungary

Location

CSG Investigational Site (#504)

Kaposvár, 7400, Hungary

Location

CSG Investigational Site (#510)

Kisvárda, 4600, Hungary

Location

CSG Investigational Site (#506)

Pécs, 7623, Hungary

Location

CSG Investigational Site (#514)

Székesfehérvár, 8000, Hungary

Location

CSG Investigational Site (#500)

Szikszó, 3800, Hungary

Location

CSG Investigational Site (#503)

Zalaegerszeg, 8900, Hungary

Location

CSG Investigational Site (#308)

Safed, Zefad, 13100, Israel

Location

CSG Investigational Site (#307)

Ashkelon, 78278, Israel

Location

CSG Investigational Site (#313)

Beersheba, 84101, Israel

Location

CSG Investigational Site (#300)

Haifa, 31096, Israel

Location

CSG Investigational Site (#304)

Holon, 58100, Israel

Location

CSG Investigational Site (#306)

Jerusalem, 91120, Israel

Location

CSG Investigational Site (#314)

Jerusalem, 93106, Israel

Location

CSG Investigational Site (#309)

Kfar Saba, 44281, Israel

Location

CSG Investigational Site (#302)

Nahariya, 22100, Israel

Location

CSG Investigational Site (#312)

Petah Tikva, 49100, Israel

Location

CSG Investigational Site (#315)

Poria – Neve Oved, 15208, Israel

Location

CSG Investigational Site (#311)

Rishon LeZiyyon, 75650, Israel

Location

CSG Investigational Site (#305)

Tel Aviv, 62039, Israel

Location

CSG Investigational Site (#303)

Tel Aviv, Israel

Location

CSG Investigational Site (#310)

Tel Hasomer, 52621, Israel

Location

CSG Investigational Site (#301)

Ẕerifin, 70300, Israel

Location

CSG Investigational Site (# 850)

Phoenix, Mauritius

Location

CSG Investigational Site (#651)

Bydgoszcz, Poland

Location

CSG Investigational Site (#655)

Chojnice, Poland

Location

CSG Investigational Site (#653)

Kielce, Poland

Location

CSG Investigational Site (#657)

Nowy Sącz, Poland

Location

CSG Investigational Site (#652)

Poznan, Poland

Location

CSG Investigational Site (#656)

Poznan, Poland

Location

CSG Investigational Site (#112)

Rio Piedras, 00935, Puerto Rico

Location

CSG Investigational Site (#110)

San Juan, 00918, Puerto Rico

Location

CSG Investigational Site (#135)

Toa Baja, 00949, Puerto Rico

Location

CSG Investigational Site (#601)

San Sebastián de los Reyes, Madrid, 28702, Spain

Location

CSG Investigational Site (#605)

Barcelona, 08003, Spain

Location

CSG Investigational Site (#606)

Barcelona, 08022, Spain

Location

CSG Investigational Site (#603)

Barcelona, 08025, Spain

Location

CSG Investigational Site (#604)

Barcelona, 08907, Spain

Location

CSG Investigational Site (#600)

Girona, 17007, Spain

Location

CSG Investigational Site (# 607)

Lleida, 25198, Spain

Location

CSG Investigational Site (#602)

Valencia, 46017, Spain

Location

MeSH Terms

Conditions

Diabetic Nephropathies; Kidney Diseases; Diabetes Mellitus, Type 2

Interventions

pyridoxamine dihydrochloride

Condition Hierarchy (Ancestors)

Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Diabetes Complications; Diabetes Mellitus; Endocrine System Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Jamie Dwyer, MD

  The Collaborative Study Group (CSG) [Co-Chair]

  STUDY CHAIR

• Julia B. Lewis, MD

  The Collaborative Study Group (CSG)

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• 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: May 28, 2014
• First Posted: June 5, 2014
• Study Start: June 1, 2014
• Primary Completion: December 1, 2017
• Study Completion: March 1, 2018
• Last Updated: March 9, 2016

Record last verified: 2016-03

Locations

AU (9); BU (8); DE (8); HU (13); US (55); IL (16); FR (7); PR (3); MA (1); PL (6); ES (8); HK (3)