Study of Efficacy, Safety, Tolerability and Pharmacokinetics of GZ/SAR402671 in Patients at risk of Rapidly Progressive Autosomal Dominant Polycystic Kidney Disease (ADPKD)

Gender:
Female: yes
Male: yes

Inclusion criteria:
-Male or adult female between ages of 18-50 years (both inclusive).
-Diagnosis of ADPKD by unified Pei criteria.
-Mayo Imaging Classification of Autosomal Dominant Polycystic Kidney Disease (ADPKD) Class 1C, 1D or 1E.
-Estimated glomerular filtration rate between 45-90 mL/min/1.73 m2 at screening (Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI]).
-Stable treatment regimen of antihypertensive therapy for at least 30 days prior to screening visit for hypertensive patient.
-Able to read, comprehend and respond to the study questionnaires.
-Able to provide a signed written informed consent.
- Patient does not have access to tolvaptan at the time of study start or tolvaptan is not indicated for treatment of patient according to treating physician (patient does not meet recommended criteria for treatment or does not tolerate treatment with tolvaptan).
-The patient, if female of childbearing potential, must have a negative blood pregnancy test [betahuman chorionic gonadotropin (?-hCG)] at the screening visit and a negative urine pregnancy test at the baseline visit.
-Sexually active female patients of childbearing potential and sexually mature male patients must agree to practice true abstinence in line with their preferred and usual lifestyle or to use 2 acceptable effective methods of contraception for the entire duration of the study and for at least 6
weeks for females and 90 days for males following their last dose of study drug.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 836
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
-Systolic blood pressure >160 mm Hg at Run-in and Baseline visits.
-History of administration of tolvaptan or other Polycystic Kidney Disease-modifying agents (somatostatin analogues) within 3 months prior to screening visit.
-Current participation in another investigational interventional study or use of investigational medicinal product (IMP), within 3 months or 5 half lives, whichever is longer, before randomization.
-The patient has a documented diagnosis of any of the following infections: hepatitis B, hepatitis C, human immunodeficiency virus 1 or 2. 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 virus antibody [HCVAb]).
-A history of drug and/or alcohol abuse within the past year prior to the screening visit.
-The patient is scheduled for in-patient hospitalization including elective surgery, during the study.
-The patient has a medical condition, including significant intercurrent illness or any other extenuating circumstance that may significantly interfere with study compliance, including all prescribed evaluations and follow-up activities.
-The patient, in the opinion of the investigator, is unable to adhere to the requirements of the study or unable to undergo study assessments (eg, has contraindications to pupillary dilation or unable to undergo magnetic resonance imaging (MRI ) [For example: patient?s weight exceeds weight capacity of the MRI, ferromagnetic metal prostheses, aneurysm clips, severe claustrophobia, large abdominal/back tattoos, etc]).
-Any country-related specific regulation that would prevent the patient from entering the study.
-The patients did not adhere to treatment (<70% compliance rate) in the run-in.
-The patient has, according to World Health Organization (WHO) Grading, a cortical cataract >onequarter of the lens circumference (Grade cortical cataract-2 [COR-2]) or a posterior subcapsular cataract >2 mm (Grade posterior subcapsular cataract-2 [PSC-2]). Patients with nuclear cataracts will not be excluded.
-The patient is currently receiving potentially cataractogenic medications, including a chronic regimen (more frequently than every 2 weeks) of any route of corticosteroids (including medium and high potency topical steroids) or any medication that may cause cataract, according to the Prescribing Information.
-The patient has received strong or moderate inducers or inhibitors of CYP3A4 within 14 days or 5 half-lives, whichever is longer, prior to randomization. This also includes the consumption of grapefruit, grapefruit juice, or grapefruit containing products within 72 hours of starting GZ/SAR402671 administration.
-The patient is pregnant, or lactating.
-Liver enzymes (alanine aminotransferase [ALT]/aspartate aminotransferase [AST]) or total bilirubin >2 times the upper limit of normal unless the patient has the diagnosis of Gilbert syndrome.
-Presence of severe depression as measured by BDI-II >28 and/or a history of a major affective disorder within 1 year of the screening visit.
-Known hypersensitivity to GZ/SAR402671 or any component of the excipients.