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

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

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

Study Overview

• Status: Completed
• Conditions: Chronic Kidney Disease
• Intervention / Treatment: Drug: SAR407899A

Detailed Description

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

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 1

Contacts and Locations

Study Locations

• Moldova, Republic of
  • Chisinau, Moldova, Republic of, 2025
    • Investigational Site Number 498002
• Romania
  • Bucuresti, Romania
    • Investigational Site Number 642001

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 79 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Sanofi

Study record dates

Study Major Dates

• Study Start: November 1, 2011
• Primary Completion (Actual): August 1, 2012
• Study Completion (Actual): August 1, 2012

Study Registration Dates

• First Submitted: November 24, 2011
• First Submitted That Met QC Criteria: December 5, 2011
• First Posted (Estimate): December 6, 2011

Study Record Updates

• Last Update Posted (Estimate): August 23, 2012
• Last Update Submitted That Met QC Criteria: August 22, 2012
• Last Verified: August 1, 2012

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urologic Diseases; Renal Insufficiency; Kidney Diseases; Renal Insufficiency, Chronic
• Other Study ID Numbers: TDR12446; 2011-003793-83 (EudraCT Number); U1111-1123-5699 (Other Identifier: UTN)