Effect of Venglustat in Patients With Renal Impairment

A Phase I, Single-Center, Open-label, Single Dose Pharmacokinetic and Tolerability Study of GZ402671 in Subjects With Mild, Moderate and Severe Renal Impairment, and in Matched Subjects With Normal Renal Function

Primary Objective:

To study the effect of mild, moderate and severe renal impairment on the pharmacokinetics (PK) of Venglustat following a single dose.

Secondary Objective:

To assess the tolerability of Venglustat given as a single dose in subjects with mild, moderate and severe renal impairment in comparison with matched subjects with normal renal function.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers; Polycystic Kidney, Autosomal Dominant
• Intervention / Treatment: Drug: Venglustat GZ/SAR402671

Detailed Description

Approximately 41 days, including a 21-day screening period, a 1-day treatment period, followed by a 9-day period of plasma sampling for assessment of primary endpoints.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33014
      • Investigational Site Number 8400001

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:

For all Subjects:

• Male and/or female subjects, between 18 and 79 years of age, inclusive.
• Body weight between 50.0 and 115.0 kg, inclusive, if male, and between 40.0 and 100.0 kg, inclusive, if female, body mass index between 18.0 and 34.9 kg/m2, inclusive
• Normal electrocardiogram (ECG)
• Having given written informed consent prior to undertaking any study-related procedure
• Not under any administrative or legal supervision
• Male subject, whose partners are of childbearing potential (including lactating women), must accept to use, during sexual intercourse, a double contraception method according to the following algorithm: (condom) plus (spermicide or intra-uterine device or hormonal contraceptive) from the inclusion up to 4 months after the last dosing
• Male subject, whose partners are pregnant, must use, during sexual intercourse, a condom from the inclusion up to 4 months after the last dosing
• Male subject has agreed not to donate sperm from the inclusion up to 4 months after the last dosing
• Female subject must use a double contraception method including a highly effective method of birth control from at least 30 days prior to the inclusion to 30 days after the last IMP administration, except if she has undergone sterilization (documented) at least 3 months earlier or is postmenopausal

Specific for subjects with renal impairment:

• Stable chronic renal impairment
• Vital signs and laboratory parameters within acceptable range for subjects with renal impairment

Specific for matched healthy subjects:

• Normal renal function
• Certified as healthy by a comprehensive clinical assessment (detailed medical history and complete physical exam)
• Normal vital signs and laboratory parameters

Exclusion criteria:

• Frequent headaches and/or migraine, recurrent nausea and/or vomiting (for vomiting only: more than twice a month)
• Blood donation, any volume, within 2 months before inclusion
• Symptomatic postural hypotension, irrespective of the decrease in blood pressure, or asymptomatic postural hypotension judged clinically relevant by the Investigator
• Any significant change in chronic treatment medication within 14 days before inclusion
• Any drug which could impact by any mechanism of action, the pharmacokinetics of the investigational medicinal product, including moderate and strong cytochrome P3A (CYP3A) inhibitors or inducers; any vaccination within the last 28 days and any biologics (antibody or its derivatives) given within 4 months before inclusion
• Positive result on any of the following tests: hepatitis B surface (HBs Ag) antigen, anti-hepatitis C virus (anti-HCV) antibodies, anti-human immunodeficiency virus 1 and 2 antibodies (anti-HIV1 and anti HIV2 Ab)
• Positive result on urine drug screen or plasma alcohol test
• Active hepatitis, hepatic insufficiency
• If female, pregnancy [defined as positive β-Human Chorionic Gonadotropin (β-HCG) blood test], breast-feeding

Specific for subjects with renal impairment:

• Uncontrolled clinically relevant cardiovascular, pulmonary, gastrointestinal, metabolic, hematological, neurological, osteomuscular, articular, psychiatric, systemic, ocular, or infectious disease, or signs of acute illness
• Acute renal failure (de novo or superimposed on preexisting chronic renal impairment), nephrotic syndrome
• History of or current hematuria of urologic origin that limits the subject's participation in the study
• Subjects requiring dialysis during the study

Specific for matched healthy controls:

- Any history or presence of clinically relevant cardiovascular, pulmonary, gastrointestinal, hepatic, renal, metabolic, hematological, neurological, osteomuscular, articular, psychiatric, systemic, ocular, gynecologic (if female) or infectious disease, or signs of acute illness

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: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Venglustat; Single dose of Venglustat is given, orally under fasting conditions	Drug: Venglustat GZ/SAR402671; Pharmaceutical form: Hard Capsule Route of administration: Oral

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessment of pharmacokinetic (PK) parameters of Venglustat: Area under the curve (AUC)	Venglustat area under the plasma concentration versus time curve (AUC)	Day 1 to Day 10

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Venglustat plasma pharmacokinetic (PK) parameter: Cmax	Maximum plasma concentration observed (Cmax)	Day 1
Venglustat plasma pharmacokinetic (PK) parameter: AUClast	Area under the plasma concentration versus time curve calculated from time zero to the real time tlast (AUClast)	Day 1 to Day 10
Venglustat plasma pharmacokinetic (PK) parameter: unbound Cmax	Maximum plasma concentration observed of unbound drug (unbound Cmax)	Day 1 to Day 10
Venglustat plasma pharmacokinetic (PK) parameter: unbound AUC	Change in unbound Venglustat area under the plasma concentration versus time curve (unbound AUC)	Day 1 to Day 10
Venglustat plasma pharmacokinetic (PK) parameter: CL/F	Apparent total body clearance of Venglustat from plasma (CL/F)	Day 1 to Day 10
Venglustat plasma pharmacokinetic (PK) parameter: Vss/F	Apparent volume of distribution of Venglustat at steady state (Vss/F)	Day 1 to Day 10
Venglustat plasma pharmacokinetic (PK) parameter: fu	Fraction of unbound venglustat in plasma (fu)	Day 1 to Day 10
Venglustat plasma pharmacokinetic (PK) parameter: t1/2z	Terminal half-life associated with the terminal slope (t1/2z)	Day 1 to Day 10
Venglustat plasma pharmacokinetic (PK) parameter: t1/2eff	Effective half-life (t1/2eff)	Day 1 to Day 10
Venglustat urine pharmacokinetic (PK) parameter: Ae(0-24)	Cumulated amount excreted in urine from time 0 to time 24h after Venglustat administration	Day 1 and Day 2
Venglustat urine pharmacokinetic (PK) parameter: fe(0-24)	Fraction of dose excreted in urine from time 0 to time 24h after Venglustat administration	Day 1 and Day 2
Venglustat urine pharmacokinetic (PK) parameter: CLR(0-24)	Renal clearance of the drug determined in the 0-24h interval (CLR(0-24))	Day 1 and Day 2
Venglustat plasma pharmacokinetic (PK) parameter: Rac,pred	Predicted accumulation ratio (Rac,pred)	Day 1 to Day 10

Collaborators and Investigators

• Sponsor: Genzyme, a Sanofi Company

Study record dates

Study Major Dates

• Study Start (Actual): October 5, 2018
• Primary Completion (Actual): February 27, 2019
• Study Completion (Actual): February 27, 2019

Study Registration Dates

• First Submitted: September 26, 2018
• First Submitted That Met QC Criteria: September 26, 2018
• First Posted (Actual): September 27, 2018

Study Record Updates

• Last Update Posted (Actual): April 25, 2022
• Last Update Submitted That Met QC Criteria: April 21, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Congenital Abnormalities; Genetic Diseases, Inborn; Abnormalities, Multiple; Kidney Diseases, Cystic; Ciliopathies; Polycystic Kidney Diseases; Polycystic Kidney, Autosomal Dominant
• Other Study ID Numbers: POP14499; U1111-1205-3215 (Other Identifier: UTN)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No