Clinical trial NCT03687554: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Polycystic Kidney, Autosomal Dominant
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2018-09-27
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 79
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Assessment of pharmacokinetic (PK) parameters of Venglustat: Area under the curve (AUC)
timeFrame: Day 1 to Day 10
Secondary outcomes:
measure: Venglustat plasma pharmacokinetic (PK) parameter: Cmax
timeFrame: Day 1
measure: Venglustat plasma pharmacokinetic (PK) parameter: AUClast
timeFrame: Day 1 to Day 10
measure: Venglustat plasma pharmacokinetic (PK) parameter: unbound Cmax
timeFrame: Day 1 to Day 10
measure: Venglustat plasma pharmacokinetic (PK) parameter: unbound AUC
timeFrame: Day 1 to Day 10
measure: Venglustat plasma pharmacokinetic (PK) parameter: CL/F
timeFrame: Day 1 to Day 10
measure: Venglustat plasma pharmacokinetic (PK) parameter: Vss/F
timeFrame: Day 1 to Day 10
measure: Venglustat plasma pharmacokinetic (PK) parameter: fu
timeFrame: Day 1 to Day 10
measure: Venglustat plasma pharmacokinetic (PK) parameter: t1/2z
timeFrame: Day 1 to Day 10
measure: Venglustat plasma pharmacokinetic (PK) parameter: t1/2eff
timeFrame: Day 1 to Day 10
measure: Venglustat urine pharmacokinetic (PK) parameter: Ae(0-24)
timeFrame: Day 1 and Day 2
measure: Venglustat urine pharmacokinetic (PK) parameter: fe(0-24)
timeFrame: Day 1 and Day 2
measure: Venglustat urine pharmacokinetic (PK) parameter: CLR(0-24)
timeFrame: Day 1 and Day 2
measure: Venglustat plasma pharmacokinetic (PK) parameter: Rac,pred
timeFrame: Day 1 to Day 10
Other outcomes:
Locations:
city: Miami
country: United States
facility: Investigational Site Number 8400001
state: Florida
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References: