Clinical Trials

Inclusion Criteria:

• Male or female, between 18 and 65 years of age (inclusive) at the time of Screening.
• Female subjects must:
  • not be pregnant, lactating, or breastfeeding;
  • be either postmenopausal (defined as amenorrhea for ≥ 12 months), surgically sterile (defined as having undergone hysterectomy and/or bilateral oophorectomy), or if of child-bearing potential (WOCBP) must agree to practice appropriate methods of birth control or remain abstinent during the study and for 30 days after the last dose of study drug;
  • Acceptable forms of contraception include any of the following:
  • oral contraceptives;
  • double barrier methods of non-hormonal contraception are permitted in this study:
  • female condom with spermicide (cream, spray, gel, suppository, contraceptive sponge, or polymer film)
  • diaphragm with spermicide (with or without a condom)
  • cervical cap with spermicide (with or without a condom)
  • male sexual partner who agrees to use a male condom in addition to female subject’s use of spermicide (cream, spray, gel, suppository, contraceptive
  • other explanation for the ALT elevations and the agreement of the medical monitor and sponsor.
  • Permanent discontinuation of prior tolvaptan treatment because of the abnormal liver chemistry test results.
  • If re-challenge with tolvaptan was performed, the ALT level should have increased to >2 x ULN upon re-challenge or the ALT level was increasing but tolvaptan was stopped for patient safety reasons before it reached > 2 x ULN after having previously normalized.
  • Appropriate control of hypertension including an angiotensin converting enzyme inhibitor or angiotensin receptor blocker (unless not considered appropriate for the subject) without the use of a diuretic in concert with KDIGO “Clinical Practice Guideline for the Management of Blood Pressure in Chronic Kidney Disease”.
  • Have read, understood, and provided written informed consent after the nature of the study has been fully explained and must be willing to comply with protocol requirements and study- related procedures.

Exclusion Criteria:

• Known sensitivity or idiosyncratic reaction to any compound present in lixivaptan and related compounds.
• Hypovolemia or inability to perceive thirst.
• 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, Seville oranges, or St. John's wort.
• Prior use of tolvaptan within the past 3 months or until a previously elevated ALT level has returned to ≤ 1 x ULN.
• 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 3 months.
• 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, transplanted 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.
• Clinically significant liver disease or impairment or active chronic hepatitis at Screening.
• Elevated baseline levels of serum ALT or total bilirubin.
• History of drug or alcohol abuse in the past 2 years.