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Effect of Venglustat in Patients With Renal Impairment

Primary Purpose

Healthy Volunteers, Polycystic Kidney, Autosomal Dominant

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Venglustat GZ/SAR402671
Sponsored by
Genzyme, a Sanofi Company
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Healthy Volunteers

Eligibility Criteria

18 Years - 79 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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.

Sites / Locations

  • Investigational Site Number 8400001

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Venglustat

Arm Description

Single dose of Venglustat is given, orally under fasting conditions

Outcomes

Primary Outcome Measures

Assessment of pharmacokinetic (PK) parameters of Venglustat: Area under the curve (AUC)
Venglustat area under the plasma concentration versus time curve (AUC)

Secondary Outcome Measures

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

Full Information

First Posted
September 26, 2018
Last Updated
April 21, 2022
Sponsor
Genzyme, a Sanofi Company
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1. Study Identification

Unique Protocol Identification Number
NCT03687554
Brief Title
Effect of Venglustat in Patients With Renal Impairment
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
April 2022
Overall Recruitment Status
Completed
Study Start Date
October 5, 2018 (Actual)
Primary Completion Date
February 27, 2019 (Actual)
Study Completion Date
February 27, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Genzyme, a Sanofi Company

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Healthy Volunteers, Polycystic Kidney, Autosomal Dominant

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
24 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Venglustat
Arm Type
Experimental
Arm Description
Single dose of Venglustat is given, orally under fasting conditions
Intervention Type
Drug
Intervention Name(s)
Venglustat GZ/SAR402671
Intervention Description
Pharmaceutical form: Hard Capsule Route of administration: Oral
Primary Outcome Measure Information:
Title
Assessment of pharmacokinetic (PK) parameters of Venglustat: Area under the curve (AUC)
Description
Venglustat area under the plasma concentration versus time curve (AUC)
Time Frame
Day 1 to Day 10
Secondary Outcome Measure Information:
Title
Venglustat plasma pharmacokinetic (PK) parameter: Cmax
Description
Maximum plasma concentration observed (Cmax)
Time Frame
Day 1
Title
Venglustat plasma pharmacokinetic (PK) parameter: AUClast
Description
Area under the plasma concentration versus time curve calculated from time zero to the real time tlast (AUClast)
Time Frame
Day 1 to Day 10
Title
Venglustat plasma pharmacokinetic (PK) parameter: unbound Cmax
Description
Maximum plasma concentration observed of unbound drug (unbound Cmax)
Time Frame
Day 1 to Day 10
Title
Venglustat plasma pharmacokinetic (PK) parameter: unbound AUC
Description
Change in unbound Venglustat area under the plasma concentration versus time curve (unbound AUC)
Time Frame
Day 1 to Day 10
Title
Venglustat plasma pharmacokinetic (PK) parameter: CL/F
Description
Apparent total body clearance of Venglustat from plasma (CL/F)
Time Frame
Day 1 to Day 10
Title
Venglustat plasma pharmacokinetic (PK) parameter: Vss/F
Description
Apparent volume of distribution of Venglustat at steady state (Vss/F)
Time Frame
Day 1 to Day 10
Title
Venglustat plasma pharmacokinetic (PK) parameter: fu
Description
Fraction of unbound venglustat in plasma (fu)
Time Frame
Day 1 to Day 10
Title
Venglustat plasma pharmacokinetic (PK) parameter: t1/2z
Description
Terminal half-life associated with the terminal slope (t1/2z)
Time Frame
Day 1 to Day 10
Title
Venglustat plasma pharmacokinetic (PK) parameter: t1/2eff
Description
Effective half-life (t1/2eff)
Time Frame
Day 1 to Day 10
Title
Venglustat urine pharmacokinetic (PK) parameter: Ae(0-24)
Description
Cumulated amount excreted in urine from time 0 to time 24h after Venglustat administration
Time Frame
Day 1 and Day 2
Title
Venglustat urine pharmacokinetic (PK) parameter: fe(0-24)
Description
Fraction of dose excreted in urine from time 0 to time 24h after Venglustat administration
Time Frame
Day 1 and Day 2
Title
Venglustat urine pharmacokinetic (PK) parameter: CLR(0-24)
Description
Renal clearance of the drug determined in the 0-24h interval (CLR(0-24))
Time Frame
Day 1 and Day 2
Title
Venglustat plasma pharmacokinetic (PK) parameter: Rac,pred
Description
Predicted accumulation ratio (Rac,pred)
Time Frame
Day 1 to Day 10

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
79 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Sciences & Operations
Organizational Affiliation
Sanofi
Official's Role
Study Director
Facility Information:
Facility Name
Investigational Site Number 8400001
City
Miami
State/Province
Florida
ZIP/Postal Code
33014
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing 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

Learn more about this trial

Effect of Venglustat in Patients With Renal Impairment

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