A Study to Evaluate ASP8232 as Add-On Therapy to Angiotensin Converting Enzyme Inhibitor (ACEi) or Angiotensin Receptor Blocker (ARB) in Reducing Albuminuria in Patients With Type 2 Diabetes and Chronic Kidney Disease

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy of ASP8232 in reducing Urinary Albumin to Creatinine Ratio (UACR) in subjects with Type 2 Diabetes Mellitus (T2DM) and Chronic Kidney Disease (CKD) at 12 weeks compared to placebo.

Official Title
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A Phase 2, Double-Blind, Randomized, Placebo Controlled Study to Evaluate the Efficacy and Safety of ASP8232 as Add-On Therapy to Angiotensin Converting Enzyme Inhibitor (ACEi) or Angiotensin Receptor Blocker (ARB) in Reducing Albuminuria in Patients With Type 2 Diabetes and Chronic Kidney Disease

Conditions
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Chronic Kidney Disease, Type 2 Diabetes

Intervention / Treatment
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* Drug: ASP8232
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject must have an estimated glomerular filtration rate (eGFR) ) >=25 and <75 ml/min/1.73m2. Subject must have a documented diagnosis of T2DM and received anti-diabetic medication (oral and/or parenteral) for at least 1 year prior to screening Subject's glycated hemoglobin (HbA1c) level is < 11.0% (<97 mmol/mol) at screening. Subject is on a stable therapy with an angiotensin-converting-enzyme (ACE) inhibitor or angiotensin receptor blockers (ARB) for at least 3 months prior to screening. Subject who receives anti-hypertensive treatment, non-insulin anti-diabetic agents and/or vitamin D receptor activators at screening needs to be on stable therapy for at least 3 months prior to screening. Subjects on insulin therapy may have the insulin type/dose/schedule adjusted even during the 3 months prior to screening. If the subject has been subjected to specific dietary interventions then this has to be stable over the past 3 months prior to screening visit. Subject's UACR is ≥ 200 and ≤ 3000 mg/g in a first morning void (FMV) sample at screening AND the geometric mean UACR of all FMV samples at visit 4 and at visit 5 is ≥ 200 and ≤ 3000 mg/g AND the UACR in at least 3 FMV samples at visit 4 and visit 5 is ≥ 200 mg/g. Exclusion Criteria: Subject is on, or previously received, renal replacement therapy (e.g. dialysis or kidney transplantation). Subject has obstructive uropathy or other causes of renal impairment not related to parenchymal renal disorder and/or disease of the kidney; or subject currently has or has had in the past renal disease secondary to malignancy. Subject's renal impairment and/or albuminuria is considered to be of other origin than Diabetic Kidney Disease. Subject has known (auto-) immune disorder and/or received immunosuppression for more than 2 weeks, cumulatively, within 12 weeks prior to screening or anticipated need for immuno-suppressive therapy during the study. Subject has active urinary tract infection which requires treatment or clinically significant infection at the time of screening or randomization Subject is diagnosed with type 1 diabetes mellitus or diabetes mellitus with unclear etiology. Subject has a sitting systolic blood pressure (SBP) <90 or >160 mmHg and/or a diastolic blood pressure (DBP) >90 mmHg at screening.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ASP8232<br>ASP8232 administered once daily | Drug: ASP8232<br>* oral capsule<br>|
| Placebo Comparator: Placebo<br>Placebo administered once daily | Drug: Placebo<br>* oral capsule<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean change of log transformed urinary albumin to creatinine ratio (UACR) from baseline to end of treatment |  | Baseline and end of treatment (12 weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of subjects with either >30% or >40% or >50% reduction in UACR from baseline to end of treatment |  | Baseline and end of treatment (12 weeks) | 
| Mean change of log transformed albumin excretion rate (AER) from baseline to end of treatment |  | Baseline and end of treatment (12 weeks) | 
| Proportion of subjects with either >30% or >40% or >50% reduction in AER from baseline to end of treatment |  | Baseline and end of treatment (12 weeks) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chronic Kidney Disease, Type 2 Diabetes, ASP8232