Safety and Efficacy of Pyridorin® in Subjects with Nephropathy Due to Type 2 Diabetes

• Register: EUCTR
• Last refreshed on: 17 May 2016
• Main ID: EUCTR2014-001641-24-DE
• Date of registration: 30/07/2014
• Prospective Registration: Yes
• Primary sponsor: NephroGenex
• Public title: Safety and Efficacy of Pyridorin® in Subjects with Nephropathy Due to Type 2 Diabetes
• Scientific 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 (PIONEER)
• Date of first enrolment: 29/09/2014
• Target sample size: 600
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-001641-24
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Australia, France, Germany, Hong Kong, Hungary, Israel, Poland, Spain, United States

Contacts

• Name: Clinical Trials Information
• Affiliation: Medpace Finland OY

• Name: Clinical Trials Information
• Affiliation: Medpace Finland OY

Key inclusion & exclusion criteria

Inclusion criteria:
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 greater than or equal to 1.3(greater than or equal to 1.25) mg/dL (111 micro mol/L) for females or greater than or equal to 1.5(greater than or equal to 1.45) mg/dL (128 micro mol/L) for males;
• At visit 1 or 1.1 24-hour urine collection PCR greater than or equal to 1200 mg/g (136 mg/mmol) and, if applicable for PS phase, at Visit 1S or 1.1S a 24-hour urine collection PCR greater than or equal to 600 mg/g (68mg/mmol);
•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),
6. Patients must have a SCr measurement less than 3.0 mg/dL (265 micro mol/L);
7. Patients must have an eGFR of greater than or equal to 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 1S). The value of the second screening SCr measurement must be less than 3.0 mg/dL (265 micro mol/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 on a stable dose for 13 weeks
prior to Visit 1 (and Visit 1S if applicable) with a seated blood pressure of less than or equal to 150/90 mmHg;
11. Patients not taking any blood pressure medications, including diuretics, other than an ACE-I or ARB must have a seated blood pressure less than or equal to 150/90 mmHg at Visit 1(and Visit 1S if applicable) and a seated blood pressure considered appr
Exclusion criteria:
1. Patients with type 1 diabetes or MODY (a monogenic form of 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 (See Section 7.2.2);
11. Patients who require systemic immunosuppression therapy for greater than 2 weeks (except for inhalant steroids);
12. Patients with clinically significant liver disease or transaminase (alanine aminotransferase and aspartate aminotransferase) levels greater than 2.5 × the upper limit of normal (ULN) measured at Visit 1;
13. Patients with bilirubin levels greater than 1.5 × ULN measured at Visit 1;
14. Patients with a history of allergic or other adverse response to vitamin B preparations;
15. Patients who require greater than 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 Visit 1S, or have participated in a previous Pyridorin study or another interventional clinical study within 30 days prior to Visit 1 or Visit 1S;
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; and
22. Persons employed with the sponsor, CRO, or one of the study investigative sites must be excluded from participation, even if they are not involved directly in the conduct of the study.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Nephropathy Due to Type 2 Diabetes
MedDRA version: 18.1 Level: PT Classification code 10061835 Term: Diabetic nephropathy System Organ Class: 10038359 - Renal and urinary disorders

Therapeutic area: Not possible to specify

Intervention(s)

Product Name: Pyridorin®
Product Code: Pyridorin®
Pharmaceutical Form: Capsule
INN or Proposed INN: Pyridorin
CAS Number: 524-36-7
Other descriptive name: PYRIDOXAMINE DIHYDROCHLORIDE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 300 -
Pharmaceutical form of the placebo: Capsule
Route of administration of the placebo: Oral use

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: These endpoints are evaluated with each central lab draw for SCr.

Main Objective: To determine the efficacy of Pyridorin 300 mg BID compared to placebo in reducing the rate of progression of renal disease due to type 2 diabetes mellitus.

Primary end point(s): Time to the composite endpoint consisting of the earliest event amongst:
- A SCr increase of =50% from baseline that occurs during follow-up;
or
- ESRD.

Secondary Objective: Comparisons of Pyridorin 300 mg BID to placebo for:
Time to the composite endpoint event of:
- A SCr increase of =100% from baseline that occurs during follow-up; or
- ESRD.
The safety of Pyridorin compared to placebo, as assessed by adverse events, 12-lead electrocardiograms (ECGs), vital signs, physical examination, clinical chemistries, glycosylated hemoglobin (HbA1c), and hematology.

Comparisons of Pyridorin 300 mg BID to placebo for:
- Change in serum cystatin-C from baseline to Week 52 and from baseline to Week 104 (Month 24);
- 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-ß) excretion from baseline to Week 52 and from baseline to Week 104; and
- Change in SCr from baseline to Week 52 and from baseline to Week 104.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: These endpoints are evaluated with each central lab draw for SCr.

Secondary end point(s): Time to the composite endpoint consisting of the earliest event amongst:
- A SCr increase of =100% from baseline that occurs during follow-up;
or
- ESRD.

Secondary ID(s)

58,684

PYR-311

Source(s) of Monetary Support

NephroGenex, Inc.