Repeated Dosing Study to Assess Safety and Tolerability in CKD-3 Patients on Stable ACE-I Treatment

Study Overview
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Brief Summary
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Primary Objective: To assess the tolerability and safety of repeated oral ascending doses of SAR407899A in patients with moderate chronic kidney disease (CKD) on stable angiotensin converting enzyme-inhibitor (ACE-I) Secondary Objectives: To assess in patients with moderate CKD the effect of concomitant multiple dose of SAR407899A and ACE-Is on office and 24-hr ambulatory blood pressure and heart rate The effect of repeated multiple doses of SAR407899A on the pharmacodynamic response to ACE-Is (AcSDKP) The pharmacokinetic profile of repeated oral administration of SAR407899A during co-administration of ACE-Is

Detailed Description
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The total duration for this study will be around 8 weeks.

Official Title
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A Randomized, Double-blind, Placebo-controlled Study to Evaluate the Safety, Tolerability and Hemodynamics of Ascending Repeated Oral Doses of SAR407899A in Patients With Moderate Chronic Kidney Disease on Stable Angiotensin Converting Enzyme-inhibitor (ACE-I) Treatment

Conditions
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Chronic Kidney Disease

Intervention / Treatment
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* Drug: SAR407899A


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Male and female patients aged between 18 and 79 Patients with chronic kidney disease (CKD-3) Patients should be on stable ACE-I treatment (same type and regimen) for at least 2 months prior to screening Body weight between 50.0 kg and 115.0 kg inclusive if male, between 40.0 kg and 100 kg inclusive if female If female, patients must be permanently sterilized for more than 3 months or postmenopausal Having given written informed consent prior to the study. Exclusion criteria: Women of child bearing potential. Uncontrolled clinically relevant cardiovascular, pulmonary, gastro-intestinal, metabolic, hematological, neurological, psychiatric, systemic, ocular, gynecologic (if female) or infectious disease, or signs of acute illness Active hepatitis, hepatic insufficiency Acute renal failure Patients requiring dialysis during the study Presence or history of drug hypersensitivity, or allergic disease diagnosed and treated by a physician. Any history of orthostatic dysregulation (including but not limited to neurocardiogenic syncope, postural orthostatic tachycardia syndrome) The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 79 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>Dose 1: 20 days 3-step uptitration with doses A, B, and C of SAR407899 vs. placebo | Drug: SAR407899A<br>* Pharmaceutical form:capsule Route of administration: oral<br>|
| Experimental: Cohort 2<br>Dose 2: 20 days 3-step uptitration with doses B, C and D of SAR407899 vs. placebo | Drug: SAR407899A<br>* Pharmaceutical form:capsule Route of administration: oral<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients reporting Adverse Events (AEs) |  | 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical safety laboratory measurement including hematology and biochemistry |  | 8 weeks | 
| urine and blood renal function markers |  | 8 weeks | 
| ECG, vital signs measurements (Heart rate and systolic and diastolic blood pressure) |  | 8 weeks | 
| AcSDKP (tetrapeptide of the composition N-Acetyl-Ser-Asp-Lys-Pro) |  | 8 weeks | 
| AUC |  | 8 weeks | 
| Cmax |  | 8 weeks | 
| t1/2z |  | 8 weeks | 
| 24-hr ambulatory blood pressure |  | Day-1, Day 14 and Day 19 |