Patients with type 2 diabetes and albuminuria. MedDRA version: 17.0 Level: PT Classification code 10061835 Term: Diabetic nephropathy System Organ Class: 10038359 - Renal and urinary disorders MedDRA version: 17.0 Level: PT Classification code 10067585 Term: Type 2 diabetes mellitus System Organ Class: 10027433 - Metabolism and nutrition disorders MedDRA version: 17.0 Level: PT Classification code 10001580 Term: Albuminuria System Organ Class: 10038359 - Renal and urinary disorders
Conditions
Interventions
Product Name: GKT137831
Product Code: GKT137831
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Not applicable
CAS Number: 1218942-37-0
Current Sponsor code: GKT137831
Other descriptive name:
Sponsors
Genkyotex Innovation SAS
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female aged 18 to 80 years, inclusive. 2. Willing and able to give written informed consent and to comply with the requirements of the study. 3. History of type 2 diabetes, defined as fasting plasma glucose > or equal to 7.0 mmol/L (126 mg/dL) or a glycated hemoglobin (HbA1c) >6.5% (48 mmol/mol) on at least 2 occasions prior to screening. If the diagnosis of type 2 diabetes has been made before 30 years of age, an optional fasting C-peptide level will be obtained during the second screening visit (Visit 2) and must be > or equal to 0.1 ng/mL to confirm type 2 diabetes. 4. Albuminuria defined as a urinary albumin to creatinine ratio (UACR) of: - (a) 300 to 3500 mg/g (33.9 to 395.5 mg/mmol) during the screening period to be eligible to enter the run-in period, determined as described in the Methodology section. - (b) 200 to 3500 mg/g (22.6 to 395.5 mg/mmol) by Week-2 (Visit 4) of the run-in period to be eligible to enter the double-blind treatment period, determined as described in the Methodology section. 5. An eGFR > or equal to 30 mL/min/1.73 m2, as calculated by the CKD-EPI formula. 6. Must be taking an ACEI or an ARB for at least 6 weeks prior to the first screening visit (Visit 1) and during the screening period. The dose must have been stable for at least 4 weeks prior to the first screening visit (Visit 1). Combination therapy associating an ACEI and an ARB is not permitted. 7. Willing to practice highly effective methods of birth control (both males who have partners of childbearing potential and females of childbearing potential) during the screening period and the run-in period, while taking investigational product and for at least 90 days since the last dose of investigational product is ingested. Women of childbearing potential are female patients who are not surgically sterile (no history of bilateral tubal ligation, hysterectomy, or bilateral salpingo-oophorectomy), and are not postmenopausal for at least 1 year. Furthermore, male study patients must also not donate sperm from Day 1/Baseline (Visit 5) until 90 days after the last dose of investigational product. In the German territory, women of childbearing potential are not eligible to enter the study. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 160 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 40
Exclusion criteria
Exclusion criteria: 1. A positive pregnancy test or breast-feeding for female patients. 2. History of type 1 diabetes. 3. Any other non-diabetic kidney disease(s) except for hypertensive nephropathy which is acceptable. 4. Diagnostic or interventional procedure requiring a contrast agent within 4 weeks of the first screening visit (Visit 1) or planned during the study. 5. History of renal transplant or planned renal transplant during the study. 6. A history of acute renal dialysis or acute kidney injury (defined according to the Kidney Disease: Improving Global Outcomes [KDIGO] definition) within 12 weeks of the first screening visit (Visit 1) 7. A body mass index (BMI) 3 x the upper limit of normal (ULN), or bilirubin >1.5 x the ULN) during the screening period (to enter the run-in period) and during the run-in period (to enter the double-blind treatment period). 9. HA1c level >11% (97 mmol/mol). 10. Inadequately controlled arterial blood pressure, defined as: a) SBP >180 mmHg and 160 mmHg and 450 milliseconds for males and >470 milliseconds for females. - A second or third degree atrioventricular block not successfully treated with a pacemaker. 15. History of cancer in the preceding 5 years, except adequately treated non-melanoma skin cancer, carcinoma in situ of the cervix, in situ prostate cancer, in situ breast ductal carcinoma, or superficial bladder cancer (stage 0). 16. Current history of drug or alcohol abuse, as assessed by the Investigator. 17. The occurrence of any acute infection requiring systemic antibiotic therapy within the 2 weeks prior to the first day of the run-in period, Week -4 (Visit 3), or infection with hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) infection. 18. A history of bone marrow disorder including aplastic anemia, or markes anemia defined as hemoglobin <10 g/dl (or 6.2 mmol/L) during screening. 19. Administration of any investigational product within 30 days or within 5 half-lives of the investigational agent (whichever is longer) of the first day of the run-in period, Week -4 (Visit 3). 20. Any condition which, in the opinion of the Investigator, constitute a risk or contraindication for the participation of the patient in the study, or that could i
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of oral GKT137831 in comparison with placebo, in patients with type 2 diabetes and albuminuria.;Secondary Objective: To evaluate the safety of oral GKT137831 in comparison with placebo, in patients with type 2 diabetes and albuminuria. To characterize the Pharmacodynamics of GKT137831 in this patient population, along with GKT137831 plasma concentrations, and any Pharmacokinetic/Pharmacodynamic relationship.;Primary end point(s): The primary variable for the evaluation of therapeutic efficacy will be albuminuria. Albuminuria will be characterized as the geometric mean of 2 consecutive early morning urine albumin/creatinine ratios (UACRs) collected twice during the baseline period (Visits 4 and 5), and then during the double-blind treatment period (Visits 6, 7, 8, 9, 10, 11, and 12). The primary efficacy endpoint will be defined as the change from baseline to the log-transformed geometric mean of the UACR measurements during Visits 9, 10, and 11. Baseline UACR will be defined as the geometric mean of UACR measurements at Visit 4 and Visit 5. If there is at least 1 UACR value available at Visits 9, 10 or 11 the primary endpoint will be computed using all the available values. If all UACR measurements are missing at Visits 9, 10 and 11 the last non-missing value from Visit 8 will be used.;Timepoint(s) of evaluation of this end point: The primary efficacy endpoint will be defined as the change from baseline to the log-transformed geometric mean of the urine albumin/creatinine ratios (UACR) measurements during Visits 9, 10, and 11 (study weeks 8, 10 and 12). | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Efficacy end points: 24-hour albumin excretion will be determined at Baseline (Visit 5) and end of treatment (Visit 11). eGFR will be analyzed on an exploratory basis to verify that changes in UACR are not due to changes in eGFR. Glucose metabolism: - In patients not receiving insulin or secretagogues, homeostasis model assessment-estimated insulin resistance (HOMA-IR) and HOMA-estimated B-cell function (HOMA-B) determined at Day 1/Baseline (Visit 5) and Weeks 6 and 12 (Visits 8 and 11). - Glycemic control, as determined from HbA1c at second screening visit (Visit 2), Day 1/Baseline (Visit 5) and at Weeks 6 and 12 (Visits 8 and 11). - Diabetic peripheral neuropathy assessed using a 100 mm visual analogue scale (VAS) at Day 1/Baseline (Visit 5) and Week 12 (Visit 11). - Erectile dysfunction assessed using the International Index of Erectile Function (IIEF) questionnaire at Day 1/Baseline (Visit 5) and Week 12 (Visit 11). Safety End points: Adverse events (AEs). Monitoring for AEs at all visits. Laboratory tests: - Clinical safety tests at the second screening visit (Visit 2), Weeks -2 to 16 (Visits 4 to 12): - Hematology: hematocrit, hemoglobin, reticulocyte count, red blood cell (RBC) count, white blood cell (WBC) count, differential WBC count, and platelet count. - A plasma sample for the determination of erythropoietin will be taken from all patients at Day 1/Baseline (Visit 5), Week 6 (Visit 8) and Week 12 (Visit 11). In case a retest is necessary due to a reduction in reticulocyte count the retest sample will be used to measure the standard hematology parameters and eythropoietin. - Biochemistry: fasting glucose, creatinine, urea, sodium, potassium, chloride, aspartate aminotransferase (AST), ALT, total bilirubin, alkaline phosphatase, and gamma-glutamyl transferase (GGT), and total bile acids. - Urinalysis: quantitative test for pH and protein; qualitative tests for glucose, ketones, bilirubin, blood; microscopic examina | — |
Countries
Australia, Canada, Czech Republic, Germany, Poland, United States
Contacts
Public ContactPhilippe Wiesel
Genkyotex Innovation SAS
Outcome results
None listed