Parkinson's Disease

Part 1: To determine the safety and tolerability of 4, 8, and 15 milligrams of GZ/SAR402671 (venglustat) administered orally for 4 weeks, as compared to placebo in participants with early-stage Parkinson's disease (PD) carrying a glucocerebrosidase gene (GBA) mutation or other pre-specified variants.

GZ/SAR402671

GZ/SAR402671

cap

4, 8 or 15

Change From Baseline to Week 52 in Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part II+III Total Score

Inclusion criteria:

Male and female adults with a diagnosis of PD and who were heterozygous carriers of a GBA mutation associated with PD.
Participants carrying known sequence variants associated with GBA-PD must had rapid eye movement (REM) sleep behavior disorder (RBD) confirmed by historically documented polysomnography or by questionnaire.
Age greater than or equal to (>=) 18 years to 80 years inclusive at the time of informed consent signing (FOR JAPANESE PARTICIPANTS ONLY: Age >=20 years to 80 years, inclusive, at the time of signing the informed consent. Note: Japanese participants refers only to Japanese participants enrolled and living in Japan).
Had symptoms of PD >=2 years.
Hoehn and Yahr (H and Y) stage of 2 or lower at baseline.
Stable medication regimen of PD drugs for at least 30 days (at least 60 days for rasagiline) prior to randomization.
The participant was willing to abstain from grapefruit containing products for 72 hours prior to administration of the first dose of GZ/SAR402671 and for the duration of the entire treatment period (Part 1 and Part 2, Periods 2 and 3).
Signed written consent.

Exclusion criteria:

Parkinsonism due to drug(s) or toxin(s).
Participants carrying the LRRK2 G2019S mutation.
Participants with Gaucher disease (GD) as defined by clinical signs and symptoms (i.e., hepatosplenomegaly, cytopenia, skeletal disease) and/or marked deficiency of GCase activity compatible with GD.
Montreal Cognitive Assessment score less than 20.
Participants with prior surgical history of deep brain stimulation (DBS).
Participants with baseline brain MRI without contrast showing a structural abnormality that is a possible cause of their PD signs or symptoms.
Hepatic insufficiency with liver function tests (LFT) greater than (>) 2 times upper limit of normal at Screening Visit.
The participant had a documented diagnosis, as per local regulations, of any of the following infections: hepatitis B, hepatitis C, human immunodeficiency virus 1 or 2.
Renal insufficiency as defined by creatine >1.5 times normal at Screening Visit.
The participant had received strong or moderate inducers or inhibitors of CYP3A4 within 30 days or 5 half-lives prior to randomization, whichever is longer.
The participant had, according to World Health Organization (WHO) Grading, a cortical cataract > one-quarter the lens circumference (grade cortical catact-2 [COR-2]) or a posterior subcapsular cataract >2 millimeters (grade posterior subscapsular cataract [PSC-2]). Participant with nuclear cataracts would not be excluded.
The participant was currently receiving potentially cataractogenic medications, including chronic regimen (more frequently than every 2 weeks) of any dose or route of corticosteroids or any medication that could cause cataract or worsen the vision of participants with cataract (eg, glaucoma medications) according to the Prescribing Information.
If female, pregnant (defined as positive beta-human chorionic gonadotrophin [Beta-HCG] blood test) or lactating or breast-feeding.
Any medical disorders and/or clinically relevant findings that, in the opinion of the Investigator, could interfere with study-related procedures. This included condition(s) that precluded the safe performance of routine lumbar punctures, such as prohibitive spinal diseases, bleeding diasthesis, or clinically significant coagulopathy or thrombocytopenia.
Current participation in another investigational interventional study.
Any medications specifically used for treating memory dysfunction, such as, but not limited to cholinesterase inhibitors or memantine, within 30 days or 5 half-lives of these medications prior to randomization, whichever was longer.