Patient case: 54-year-old male with Gastric cancer. Genetic variant: PIK3CA (E545K). Other conditions: Depression.

Clinical trial: A Global Study to Assess the Drug Dynamics, Efficacy, and Safety of GZ/SAR402671 in Parkinson's Disease Patients Carrying a Glucocerebrosidase (GBA) Gene Mutation

Summary: Primary Objectives:
  -  Part 1: To determine the safety and tolerability of GZ/SAR402671 administered orally, as compared to placebo in patients with early-stage Parkinson's disease (PD) carrying a GBA mutation or other pre-specified variants.
  -  Part 2: To determine the efficacy of GZ/SAR402671 administered orally daily, as compared to placebo in patients with early-stage Parkinson's disease carrying a GBA mutation or other pre-specified variants.
  Secondary Objectives:
  Part 1:
  -  To assess the pharmacokinetic (PK) profile of oral dosing of GZ/SAR4027671 in plasma when administered in early-stage Parkinson's disease patients carrying a GBA mutation.
  -  To assess the exposure of GZ/SAR402671 in cerebrospinal fluid (CSF) when administered in early-stage Parkinson's disease patients carrying a GBA mutation.
  Part 2:
  -  To demonstrate overall safety and tolerability of GZ/SAR4027671 administered orally in early-stage Parkinson's disease patients carrying a GBA mutation as compared to placebo.
  -  To assess the pharmacodynamic response to daily oral dosing of GZ/SAR402671 in plasma and CSF as measured by glucosylceramide (GL-1) when administered in early-stage Parkinson's disease patients carrying a GBA mutation.

Detailed description: The total study duration per subject in Part 2 will be approximately 168 weeks that will consist of 6.5 weeks of screening period, 52 weeks of treatment period, 104 weeks of follow-up period, and 6 weeks of post-treatment observation period. Part 1 maximal treatment duration will be up to 48 weeks in Japan, and up to 64 weeks outside Japan.

Eligibility: Inclusion criteria :
  -  Male and female adults with a diagnosis of PD and who are heterozygous carriers of a GBA mutation associated with PD or patients carrying known sequence variants associated with GBA-PD (such as E326K), in addition to have a diagnosis of PD (with at least 2 of the following signs: resting tremor, postural instability, akinesia/hypokinesia or muscle rigidity), must have rapid eye movement (REM) sleep behavior disorder (RBD) confirmed by historically documented polysomnography or by questionnaire.
  -  Age ≥18 years to 70 years inclusive at the time of informed consent signing (for Japanese patients only: Age ≥20 years to 70 years, inclusive, at the time of signing the informed consent. Note: Japanese patients refers only to Japanese patients enrolled and living in Japan).
  -  Has symptoms of PD ≥2 years.
  -  Hoehn and Yahr (H and Y) stage of 2 or lower at baseline; for patients on a stable dose of PI medication, this should be done in the "ON" state.
  -  Stable medication regimen of PD drugs for at least 30 days (at least 60 days for rasagiline) prior to randomization.
  -  The patient is willing to abstain from grapefruit containing products for 72 hours prior to administration of the first dose of GZ/SAR402671 and for duration of the entire treatment period (Periods 2 and 3).
  -  Signed written consent.
  Exclusion criteria:
  -  Parkinsonism due to drug(s) or toxin(s).
  -  Patients carrying mutations in genes other than GBA that have been associated with an increased risk for PD, specifically LRKK2 (G2019S).
  -  Patients with Gaucher disease (GD), defined by the presence of 2 mutated GBA alleles.
  -  Montreal Cognitive Assessment score <20 at Screening Visit.
  -  Patients with prior surgical history of deep brain stimulation (DBS).
  -  Patients 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) >2 times upper limit of normal at Screening Visit.
  -  The patient has prior known positive result on any of the following tests: hepatitis B surface antigen (HBsAg), anti-hepatitis C virus (anti-HCV) antibodies, anti-human immunodeficiency virus 1 and 2 antibodies (anti-HIV 1 and anti-HIV 2 Ab). Patients with a positive hepatitis B surface antibody (HBsAb) test with a history of prior hepatitis B immunization are eligible if other criteria are met (ie, negative tests for : HBsAg, hepatitis B core antibody [HBcAb],and hepatitis C [HCVAb].
  -  Renal insufficiency as defined by creatine >1.5 times normal at Screening Visit.
  -  The patient has received strong or moderate inducers or inhibitors of CYP3A4 within 30 days or 5 half-lives from screening, whichever is longer, prior to randomization.
  -  The patient has, according to World Health Organization (WHO) Grading, a cortical cataract > one-quarter the lens circumference (grade cortical cataract-2 [COR-2]) or a posterior subcapsular cataract >2 mm (grade posterior subscapsular cataract [PSC-2]). Patient with nuclear cataracts will not be excluded.
  -  The patient is 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 can cause cataract, according to the prescribing information.
  -  If female, pregnancy (defined as positive beta-human chorionic gonadotrophin [Beta-HCG] blood test) or lactating or breast-feeding.
  -  Any medical disorders that, in the opinion of the Investigator, could interfere with study-related procedures. This includes condition(s) that preclude the safety 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.
  The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Relevance to patient case: not relevant