Efficacy and Safety of Lixivaptan in the Treatment of Autosomal Dominant Polycystic Kidney Disease

Overview

About this study

The purpose of this trial will assess the effectiveness and safety of lixivaptan in a broad population of adult participants with Autosomal Dominant Polycystic Kidney Disease (ADPKD).

The vasopressin V2 receptor antagonist lixivaptan has also been shown to ameliorate polycystic disease manifestations in animal models of the disease. Evidence from quantitative systems toxicology modeling and simulation have demonstrated that lixivaptan does not have the same potential for liver injury as tolvaptan. 

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Inclusion Criteria:

- Diagnosis of ADPKD by appropriate imaging or genetic testing

- Mayo Clinic MRI imaging classification of 1C, 1D or 1E

- eGFR ≥25 mL/min/1.73 m2 and ≤90 mL/min/1.73 m2

- Body mass index (BMI) between 18 and 40 kg/m2

- Control of hypertension consistent with KDIGO guidelines without a diuretic

- Willing to practice acceptable methods of birth control (both males who have partners
of child-bearing potential and females of childbearing potential)

Exclusion Criteria:

- Known sensitivity or idiosyncratic reaction to any compound present in lixivaptan and
related compounds.

- Hypovolemia or inability to perceive thirst

- Abnormal serum sodium concentration at Screening

- Subjects who have taken any investigational drug or used an investigational device
within 30 days, or 5 half-lives, whichever is longer, prior to Screening

- Subjects who are taking, have taken within the past 2 weeks, or are expected to be
taking, strong or moderate CYP3A4 or CYP2C8 inhibitors or inducers including regular
use of grapefruit juice or Seville oranges

- Prior use of tolvaptan or lixivaptan within the past 2 months.

- Prior use of conivaptan, somatostatin analogs (e.g. lanreotide, pasireotide,
octreotide, etc.), metformin, nicotinamide, bardoxolone, venglustat, demeclocycline,
or mammalian target of rapamycin (mTOR) kinase inhibitors (e.g. everolimus, sirolimus,
etc.) to treat ADPKD within the past 2 months

- Prior use of a sodium-glucose cotransporter 2 (SGLT2) inhibitor (e.g., canagliflozin,
dapagliflozin, empagliflozin, etc.) within the past 2 months or expected need for
initiation of treatment with a SGLT2 inhibitor during the study.

- Prior use of a hypoxia-inducible factor prolyl hydroxylase (HIF-PH) inhibitor within
the past 2 months or expected need for initiation of treatment with a HIF-PH inhibitor
during the study.

- Requirement for chronic diuretic use

- Advanced diabetes (e.g., glycosylated hemoglobin [HgbA1c] >7.5%, and/or glycosuria by
dipstick, significant proteinuria [>300 mcg albumin/mg creatinine]), other significant
renal disease, renal cancer, transplanted kidney, single kidney, recent kidney surgery
within the past 6 months (including cyst drainage or fenestration) or acute kidney
injury within past 6 months

- Clinically significant incontinence, overactive bladder, or urinary retention (e.g.,
benign prostatic hyperplasia).

- New York Heart Association Functional Class 3 or 4 heart failure or other significant
cardiac or electrocardiogram (ECG) findings that could pose a safety risk to the
subject.

- Positive test results for hepatitis B surface antigen (HBsAg) or hepatitis C (HCV).

- History of infection with human immunodeficiency virus (HIV) unless the participant is
stable and doing well on a non-CYP interacting anti-retroviral therapy (ART) regimen
and who has not required more than 2 changes in their ART regimen since treatment
inception.

- History of clinically significant drug or alcohol abuse in the past 2 years.

- Contraindication to or interference with MRI assessments.

- Malignancy within the past 5 years except for those not considered to affect
participant survival.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Eligibility last updated 6/15/22.  Questions regarding updates should be directed to the study team contact.

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status

Rochester, Minn.

Mayo Clinic principal investigator

Vicente Torres, M.D., Ph.D.

Closed for enrollment

More information

Publications

Publications are currently not available
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CLS-20528749

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