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

Palladio Biosciences

Status and phase: Completed; Phase 2

Conditions: Autosomal Dominant Polycystic Kidney Disease

Treatments: Drug: Lixivaptan

Study type: Interventional

Funder types: Industry

Identifiers

NCT03487913

PA-102

Details and patient eligibility

About

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.

Full description

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).

Enrollment: 31 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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31 participants in 4 patient groups

High dose lixivaptan / CKD1 or CKD2

Experimental group

Description:

Oral high dose lixivaptan in participants with CKD1 or CKD2

Treatment:

Drug: Lixivaptan

Low dose lixivaptan / CKD1 or CKD2

Experimental group

Description:

Oral low dose lixivaptan in participants with CKD1 or CKD2

Treatment:

Drug: Lixivaptan

High dose lixivaptan / CKD3

Experimental group

Description:

Oral high dose lixivaptan in participants with CKD3

Treatment:

Drug: Lixivaptan

Low dose lixivaptan / CKD3

Experimental group

Description:

Oral low dose lixivaptan in participants with CKD3

Treatment:

Drug: Lixivaptan