Healthy Volunteers, Polycystic Kidney, Autosomal Dominant
Conditions
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.
Interventions
Pharmaceutical form: Hard Capsule Route of administration: Oral
Sponsors
Genzyme, a Sanofi Company
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 79 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Assessment of pharmacokinetic (PK) parameters of Venglustat: Area under the curve (AUC) | Day 1 to Day 10 | Venglustat area under the plasma concentration versus time curve (AUC) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Venglustat plasma pharmacokinetic (PK) parameter: Rac,pred | Day 1 to Day 10 | Predicted accumulation ratio (Rac,pred) |
| Venglustat plasma pharmacokinetic (PK) parameter: Cmax | Day 1 | Maximum plasma concentration observed (Cmax) |
| Venglustat plasma pharmacokinetic (PK) parameter: AUClast | Day 1 to Day 10 | 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 | Day 1 to Day 10 | Maximum plasma concentration observed of unbound drug (unbound Cmax) |
| Venglustat plasma pharmacokinetic (PK) parameter: unbound AUC | Day 1 to Day 10 | Change in unbound Venglustat area under the plasma concentration versus time curve (unbound AUC) |
| Venglustat plasma pharmacokinetic (PK) parameter: CL/F | Day 1 to Day 10 | Apparent total body clearance of Venglustat from plasma (CL/F) |
| Venglustat urine pharmacokinetic (PK) parameter: CLR(0-24) | Day 1 and Day 2 | Renal clearance of the drug determined in the 0-24h interval (CLR(0-24)) |
| Venglustat plasma pharmacokinetic (PK) parameter: fu | Day 1 to Day 10 | Fraction of unbound venglustat in plasma (fu) |
| Venglustat plasma pharmacokinetic (PK) parameter: t1/2z | Day 1 to Day 10 | Terminal half-life associated with the terminal slope (t1/2z) |
| Venglustat plasma pharmacokinetic (PK) parameter: t1/2eff | Day 1 to Day 10 | Effective half-life (t1/2eff) |
| Venglustat urine pharmacokinetic (PK) parameter: Ae(0-24) | Day 1 and Day 2 | Cumulated amount excreted in urine from time 0 to time 24h after Venglustat administration |
| Venglustat urine pharmacokinetic (PK) parameter: fe(0-24) | Day 1 and Day 2 | Fraction of dose excreted in urine from time 0 to time 24h after Venglustat administration |
| Venglustat plasma pharmacokinetic (PK) parameter: Vss/F | Day 1 to Day 10 | Apparent volume of distribution of Venglustat at steady state (Vss/F) |
Countries
United States
Outcome results
None listed