The ELiSA Study - Evaluation of Lixivaptan in Subjects With Autosomal Dominant Polycystic Kidney Disease

A Phase 2, Open-Label, Multi-Center Study to Evaluate the Safety, Pharmacokinetics and Pharmacodynamics of Lixivaptan in Subjects With Autosomal Dominant Polycystic Kidney Disease

This is a Phase 2, open-label, parallel-group, multiple dose study designed to evaluate the pharmacokinetics, pharmacodynamics, safety and tolerability of multiple doses of lixivaptan in Autosomal Dominant Polycystic Kidney Disease subjects with chronic kidney disease (CKD) in stages CKD1, CKD2 or CKD3.

Therapeutic interventions aimed at counterbalancing the effect of vasopressin and/or normalizing intracellular levels of cAMP may be effective in delaying disease progression in autosomal dominant polycystic kidney disease (ADPKD).

The primary objectives of this study in subjects with ADPKD are:

• To characterize the safety and tolerability of lixivaptan following multiple doses in ADPKD subjects with relatively preserved kidney function (chronic kidney disease CKD1 and CKD2) and moderately impaired renal function (CKD3).

The secondary objectives of this study are:

• To characterize the PK profile of lixivaptan and its major metabolites following multiple doses of lixivaptan in ADPKD subjects with relatively preserved kidney function (CKD1 and CKD2) and moderately impaired renal function (CKD3).
• To characterize the pharmacodynamic effect of lixivaptan on urine output, urine osmolality, total kidney volume, serum vasopressin, and serum creatinine following multiple doses of lixivaptan in ADPKD subjects with relatively preserved kidney function (CKD1 and CKD2) and moderately impaired renal function (CKD3).

Inclusion Criteria:

• Male or female, between 18 and 65 years of age at the time of screening
• Estimated glomerular filtration rate (eGFR) ≥ 30 mL/min/1.73 m2 with eGFR calculated by the CKD EPI equation
• Diagnosed with ADPKD by modified Ravine criteria
• Considered by Investigator to be in good health relative to underlying CKD status and clinically stable with respect to underlying CKD

Exclusion Criteria:

• Known sensitivity or idiosyncratic reaction to lixivaptan, its related compounds such as benzazepines (e.g., tolvaptan, conivaptan, benazepril, fenoldopam, or mirtazapine), or any compound listed as being present in the study formulation
• Women who are pregnant or breast feeding
• Subjects have taken tolvaptan, oral or intravenous antibiotics, or any investigational drug or used an investigational device within 30 days or 5 half-lives, whichever is longer, prior to first study dose
• Subject has a transplanted kidney, or absence of a kidney
• Subjects with clinically significant incontinence, overactive bladder, or urinary retention (e.g., benign prostatic hyperplasia)
• Subjects with clinically significant liver disease, or clinically significant liver function abnormalities or serology other than that expected for ADPKD with cystic liver disease at baseline
• Subjects with any clinically significant concomitant disease or condition other than ADPKD (including treatment for such conditions) that, in the opinion of the Investigator, could either interfere with the study drug or pose an unacceptable risk to the subject