A Phase I Clinical Trial to Evaluate the Effect of Renal Impairment on Pharmacokinetics of NOX-E36

Study Overview
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Brief Summary
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This is a multi center, open label, parallel group, single administration, phase I trial, in subjects with mild, moderate or severe renal impairment and a control group with normal renal function.

Detailed Description
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Current diabetes therapy does not stop progression of the disease and the development of diabetes mellitus (DM)-associated complications. A major concern in DM-patients is renal impairment due to nephropathy leading to a reduced glomerular filtration rate (GFR). It has been established that chronic (sub)clinical inflammation is crucial for the onset and progression of DM. CCL2, also known as Monocyte chemoattractant protein 1 (MCP 1) is a chemokine from the cysteine-cysteine family, secreted by leukocytes or tissue cells. CCL2 promotes monocyte emigration from the bone marrow, activates monocytes and macrophages and directs their migration to sites of inflammation. Recent animal studies and clinical trials indicate a critical involvement of CCL2 in DM and diabetic nephropathy, suggesting that CCL2 may be a potential target for therapeutic intervention in DM. Finally, protein overload and oxidative challenge of the diseased kidney was suggested to stimulate CCL2 expression in renal tubuli, thereby accelerating the progression of diabetic nephropathy. As NOX E36 is designed to specifically target human MCP-1/CCL2. This study is performed to evaluate the role of renal impairment for adequate dosing recommendations in the planned target population.

Official Title
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A Phase I, Open Label, Parallel Group, Multi-center Single Dose Trial to Evaluate the Effect of Renal Impairment on Pharmacokinetics of NOX-E36

Conditions
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Renal Impairment

Intervention / Treatment
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* Drug: NOX-E36


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female subjects (age 18-75 years, both inclusive) Male subjects who agree to sexual abstinence and/or use a highly effective method of birth control. Female partners of male subjects must be of non-child bearing potential or must practice an adequate non-hormonal contraceptive method to prevent pregnancies. Subjects will be categorized as follows based on creatinine clearance(mL/min/1.73m2): Normal renal function: CrCl > 80; mild renal impairment: 50 ≤ CrCl ≤ 80; moderate renal impairment: 30 ≤ CrCl ≤ 50; severe renal impairment: CrCl < 30 Body Mass Index (BMI) between 22 and 40 kg/m², both inclusive. Exclusion Criteria: Women of childbearing potential Patients who have received kidney transplantation. Patients receiving hemodialysis to control their disease. Any clinically significant abnormality other than related to the renal impairment following the investigator's review of the physical examination, ECG and clinical laboratory tests at screening. Not able to communicate meaningfully with the investigator and staff.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NOX-E36<br>All subjects included in this study will receive the same dose of NOX E36. | Drug: NOX-E36<br>* All subjects included in this study will receive the same dose of NOX E36. In previous clinical trials, single intravenous doses of NOX E36 up to 2 mg/kg body weight and single subcutaneous doses of up to 0.5 mg/kg body weight appeared to be safe and well tolerated in healthy volunteers. Pharmacokinetic analyses have shown dose linearity<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Renal impairment, NOX-E36