Safety and Efficacy of Oral GKT137831 in Patient With Type 2 Diabetes and Albuminuria

Study Overview
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Brief Summary
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NADPH oxidase enzymes (NOX) have been implicated in the development of several diabetic complications including diabetic nephropathy. GKT137831 is the first in class NOX1/4 inhibitor. The primary objective of this study is to evaluate the efficacy of oral GKT137831 in patients with residual albuminuria despite maximal inhibition of the renin angiotensin aldosterone system.

Detailed Description
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A double-blind, placebo-controlled, randomized, multicenter, parallel group Phase 2 study assessing a 12-week period of treatment with oral GKT137831 administered in addition to standard of care for patients with type 2 diabetes.

Official Title
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A Double-Blind, Randomized, Placebo-Controlled, Phase 2 Study Evaluating the Safety and Efficacy of Oral GKT137831 in Patients With Type 2 Diabetes and Albuminuria

Conditions
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Type 2 Diabetes Mellitus With Diabetic Nephropathy

Intervention / Treatment
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* Drug: GKT137831
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Male or female aged 18 to 80 years History of type 2 diabetes, defined as fasting plasma glucose ≥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. Albuminuria defined as a UACR of 300 to 3500 mg/g. An eGFR ≥30 mL/min/1.73 m2, as calculated by the CKD-EPI formula. 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. Key Exclusion Criteria: History of type 1 diabetes Any other non-diabetic kidney disease(s) except for hypertensive nephropathy which is acceptable. Diagnostic or interventional procedure requiring a contrast agent within 4 weeks of the first screening visit (Visit 1) or planned during the study. History of renal transplant or planned renal transplant during the study. 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) HbA1c level >11% (97 mmol/mol). History of hypothyroidism requiring hormone replacement therapy. History of active cardiovascular disease A personal or family history of long QT syndrome. Administration of any investigational product within 30 days or within 5 half-lives of the investigational agent

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GKT137831<br>GKT137831 100 mg capsules twice a day | Drug: GKT137831<br>* 1 capsule of 100 mg twice a day for the first 6 weeks of treatment, and 2 capsules of 100 mg twice a day for next 6 weeks of treatment<br>|
| Placebo Comparator: Placebo<br>Placebo capsule twice a day | Drug: Placebo<br>* 1 capsule of Placebo, twice a day, oral treatment self-administered by the patient for the 12 weeks of treatment.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Albuminuria | Change in UACR from baseline to Visits 9, 10, and 11 (i.e. weeks 8, 10 and 12 of the treatment period, respectively) | Visits 4 (week -2), 5 (week 0), 6 (week 2), 7 (week 4), 8 (week 6), 9 (week 8), 10 (week 10), 11 (week 12), and 12 (week 16) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Glucose metabolism | Change in HOMA-B, HOMA-IR and HbA1c from baseline | Visits 5 (week 0), 8 (week 6), and 11 (week 12) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Type 2 diabetes, Proteinuria, Albuminuria