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CompletedNCT03487913Updated Dec 5, 2022Results posted

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

A Phase 2 interventional study of Lixivaptan in Autosomal Dominant Polycystic Kidney Disease, sponsored by Palladio Biosciences. Completed at 13 sites in United States. Open to participants aged 18 Years to 65 Years. Per ClinicalTrials.gov, last updated 2022-12-05.

Sponsored by Palladio Biosciences · Phase 2, Interventional, and Treatment

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Phase
Phase 2
Study type
Interventional
Enrollment
31
Allocation
Non-randomized
Ages
18 Years to 65 Years
Sex
All
01

Where this study stands

Counted across the records on this site · 2026-11-13

Among 85 studies in Polycystic Kidney, Autosomal Dominant with a site in United States — 14 open to participants now, 25 under way, 1 of them phase 3. Polycystic Kidney, Autosomal Dominant · United States.

Enrollment
40th of 63
31 · median 48
Started
2018
with 5 others
Phase 2
18 of 85
3 open now
Registered
42nd of 85
by date
Lead sponsor
4 of 85
Palladio Biosciences

Among the 85 studies in Polycystic Kidney, Autosomal Dominant with a site in United States, this one is the 40th largest by enrollment of the 63 interventional ones that give a count, is one of 6 that started in 2018, is one of 18 in phase 2, and was the 42nd registered.

Polycystic Kidney, Autosomal Dominant

185 studies on the registry are indexed under Polycystic Kidney, Autosomal Dominant; 42 are open to participants now.

Browse Polycystic Kidney, Autosomal Dominant studies →

Open to participants now

14 of the 85 studies in Polycystic Kidney, Autosomal Dominant with a site in United States are open now. Recruiting first, the newest first:

9 more — sign in →

All 14 open studies →

A study can be open while its sites in United States have not opened yet or have stopped. Only those recruiting at a site in United States →

Who these studies take

Of the 30 Polycystic Kidney, Autosomal Dominant studies recruiting now, 8 (27%) set no upper age limit and 19 (63%) stop at 75 or younger; 7 take children under 18; 9 take healthy volunteers.

This study: 18 Years to 65 Years · all sexes · no healthy volunteers.

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02

Study summary

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.

Read the detailed 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).
03

Conditions studied

  • Autosomal Dominant Polycystic Kidney Disease
04

Who can participate

Ages eligible
18 Years to 65 Years
Sexes eligible
All
Accepts healthy volunteers
No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

  • Male or female, between 18 and 65 years of age at the time of screening
  • Estimated (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

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 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 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
Terms in these criteria, in plain language(3)

Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.

GFR and eGFR (kidney filtering)

GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².

Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.

Investigational drug or device

A drug or device being studied in a clinical trial.

It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.

Clinically significant

Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.

05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
31 participants (actual)

Study arms

  • Experimental
    High dose lixivaptan / CKD1 or CKD2

    Oral high dose lixivaptan in participants with CKD1 or CKD2

    Drug: Lixivaptan

  • Experimental
    Low dose lixivaptan / CKD1 or CKD2

    Oral low dose lixivaptan in participants with CKD1 or CKD2

    Drug: Lixivaptan

  • Experimental
    High dose lixivaptan / CKD3

    Oral high dose lixivaptan in participants with CKD3

    Drug: Lixivaptan

  • Experimental
    Low dose lixivaptan / CKD3

    Oral low dose lixivaptan in participants with CKD3

    Drug: Lixivaptan

Interventions

  • DrugLixivaptan

    Oral vasopressin V2 receptor antagonist

    Also known as: VPA-985

06

What researchers measure

Primary outcomes

  1. Maximum Observed Plasma Concentration (Cmax) of Lixivaptan in ADPKD Patients

    The pharmacokinetic parameter Cmax, the highest concentration of lixivaptan measured in plasma after multiple doses of drug, will be calculated from the observed concentration of lixivaptan and summarized by cohort.

    Time frame: Day 1 (am and pm) and Day 7 (am and pm)

  2. Maximum Observed Plasma Concentration (Cmax) of WAY-141624 in ADPKD Patients

    The pharmacokinetic parameter Cmax, the highest concentration of WAY-141624 measured in plasma after multiple doses of drug, will be calculated from the observed concentration of WAY-141624 and summarized by cohort.

    Time frame: Day 1 (am and pm) and Day 7 (am and pm)

  3. Maximum Observed Plasma Concentration (Cmax) of WAY-138451 in ADPKD Patients

    The pharmacokinetic parameter Cmax, the highest concentration of WAY-138451 measured in plasma after multiple doses of drug, will be calculated from the observed concentration of WAY-138451 and summarized by cohort.

    Time frame: Day 1 (am and pm) and Day 7 (am and pm)

  4. Maximum Observed Plasma Concentration (Cmax) of WAY-138758 in ADPKD Patients

    The pharmacokinetic parameter Cmax, the highest concentration of WAY-138758 measured in plasma after multiple doses of drug, will be calculated from the observed concentration of WAY-138758 and summarized by cohort.

    Time frame: Day 1 (am and pm) and Day 7 (am and pm)

  5. Time to Reach Maximum Plasma Concentration (Tmax) of Lixivaptan in ADPKD Patients

    The pharmacokinetic parameter tmax, the time taken to reach the highest concentration of lixivaptan in plasma after multiple doses of drug, will be calculated from the observed concentration of lixivaptan and summarized by cohort.

    Time frame: Day 1 (am and pm) and Day 7 (am and pm)

  6. Time to Reach Maximum Plasma Concentration (Tmax) of WAY-141624 in ADPKD Patients

    The pharmacokinetic parameter tmax, the time taken to reach the highest concentration of WAY-141624 in plasma after multiple doses of drug, will be calculated from the observed concentration of WAY-141624 and summarized by cohort.

    Time frame: Day 1 (am and pm) and Day 7 (am and pm)

  7. Time to Reach Maximum Plasma Concentration (Tmax) of WAY-138451 in ADPKD Patients

    The pharmacokinetic parameter tmax, the time taken to reach the highest concentration of WAY-138451 in plasma after multiple doses of drug, will be calculated from the observed concentration of WAY-138451 and summarized by cohort.

    Time frame: Day 1 (am and pm) and Day 7 (am and pm)

  8. Time to Reach Maximum Plasma Concentration (Tmax) of WAY-138758 in ADPKD Patients

    The pharmacokinetic parameter tmax, the time taken to reach the highest concentration of WAY-138758 in plasma after multiple doses of drug, will be calculated from the observed concentration of WAY-138758 and summarized by cohort.

    Time frame: Day 1 (am and pm) and Day 7 (am and pm)

  9. Area Under the Concentration-time Curve From Time 0 Until the Last Quantifiable Concentration (AUC[0-last]) of Lixivaptan in ADPKD Patients

    The pharmacokinetic parameter AUC(0-last) for lixivaptan will be calculated using the linear trapezoidal rule for increasing values and the log trapezoidal rule for decreasing values, summarized by cohort.

    Time frame: Day 1 (am and pm) and Day 7 (am and pm)

  10. Area Under the Concentration-time Curve From Time 0 Until the Last Quantifiable Concentration (AUC[0-last]) of WAY-141624 in ADPKD Patients

    The pharmacokinetic parameter AUC(0-last) for WAY-141624 will be calculated using the linear trapezoidal rule for increasing values and the log trapezoidal rule for decreasing values and summarized by cohort.

    Time frame: Day 1 (am and pm) and Day 7 (am and pm)

  11. Area Under the Concentration-time Curve From Time 0 Until the Last Quantifiable Concentration (AUC[0-last]) of WAY-138451 in ADPKD Patients

    The pharmacokinetic parameter AUC(0-last) for WAY-138451 will be calculated using the linear trapezoidal rule for increasing values and the log trapezoidal rule for decreasing values and summarized by cohort.

    Time frame: Day 1 (am and pm) and Day 7 (am and pm)

  12. Area Under the Concentration-time Curve From Time 0 Until the Last Quantifiable Concentration (AUC[0-last]) of WAY-138758 in ADPKD Patients

    The pharmacokinetic parameter AUC(0-last) for WAY-138758 will be calculated using the linear trapezoidal rule for increasing values and the log trapezoidal rule for decreasing values and summarized by cohort.

    Time frame: Day 1 (am and pm) and Day 7 (am and pm)

  13. Area Under the Concentration-time Curve From Time 0 Extrapolated to Infinity (AUC[0-inf]) of Lixivaptan in ADPKD Patients

    The pharmacokinetic parameter AUC(0-inf) for lixivaptan will be calculated using the linear trapezoidal rule for increasing values, the log trapezoidal rule for decreasing values, and extrapolated to infinity by addition of the last quantifiable observed concentration divided by the elimination rate constant and summarized by cohort.

    Time frame: Day 1 (am)

  14. Area Under the Concentration-time Curve From Time 0 Extrapolated to Infinity (AUC[0-inf]) of WAY-141624 in ADPKD Patients

    The pharmacokinetic parameter AUC(0-inf) for WAY-141624 will be calculated using the linear trapezoidal rule for increasing values, the log trapezoidal rule for decreasing values, and extrapolated to infinity by addition of the last quantifiable observed concentration divided by the elimination rate constant and summarized by cohort.

    Time frame: Day 1 (am)

  15. Area Under the Concentration-time Curve From Time 0 Extrapolated to Infinity (AUC[0-inf]) of WAY-138451 in ADPKD Patients

    The pharmacokinetic parameter AUC(0-inf) for WAY-138451 will be calculated using the linear trapezoidal rule for increasing values, the log trapezoidal rule for decreasing values, and extrapolated to infinity by addition of the last quantifiable observed concentration divided by the elimination rate constant and summarized by cohort.

    Time frame: Day 1 (am)

  16. Area Under the Concentration-time Curve From Time 0 Extrapolated to Infinity (AUC[0-inf]) of WAY-138758 in ADPKD Patients

    The pharmacokinetic parameter AUC(0-inf) for WAY-138758 will be calculated using the linear trapezoidal rule for increasing values, the log trapezoidal rule for decreasing values, and extrapolated to infinity by addition of the last quantifiable observed concentration divided by the elimination rate constant and summarized by cohort.

    Time frame: Day 1 (am)

  17. Terminal Elimination Phase Half-life (t1/2) of Lixivaptan in ADPKD Patients

    The pharmacokinetic parameter t1/2 for lixivaptan, determined as ln2/apparent terminal elimination rate constant, will be calculated and summarized by cohort.

    Time frame: Day 1 (am) and Day 7 (pm)

  18. Terminal Elimination Phase Half-life (t1/2) of WAY-141624 in ADPKD Patients

    The pharmacokinetic parameter t1/2 for WAY-141624, determined as ln2/apparent terminal elimination rate constant, will be calculated and summarized by cohort.

    Time frame: Day 1 (am) and Day 7 (pm)

  19. Terminal Elimination Phase Half-life (t1/2) of WAY-138451 in ADPKD Patients

    The pharmacokinetic parameter t1/2 for WAY-138451, determined as ln2/apparent terminal elimination rate constant, will be calculated and summarized by cohort.

    Time frame: Day 1 (am) and Day 7 (pm)

  20. Terminal Elimination Phase Half-life (t1/2) of WAY-138758 in ADPKD Patients

    The pharmacokinetic parameter t1/2 for WAY-138758, determined as ln2/apparent terminal elimination rate constant, will be calculated and summarized by cohort.

    Time frame: Day 1 (am) and Day 7 (pm)

  21. Apparent Terminal Elimination Rate Constant (λZ) of Lixivaptan in ADPKD Patients

    The pharmacokinetic parameter λZ for lixivaptan will be determined by linear regression of the terminal points of the log-linear concentration-time curve. The Best Fit method utilized by WinNonlin will be used to identify the terminal linear phase of the concentration-time profile, with visual assessment and adjustment of the selected data points by the PK scientist if warranted. A minimum of 3 data points will be used for determination. Results will be summarized by cohort.

    Time frame: Day 1 (am) and Day 7 (pm)

  22. Apparent Terminal Elimination Rate Constant (λZ) of WAY-141624 in ADPKD Patients

    The pharmacokinetic parameter λZ for WAY-141624 will be determined by linear regression of the terminal points of the log-linear concentration-time curve. The Best Fit method utilized by WinNonlin will be used to identify the terminal linear phase of the concentration-time profile, with visual assessment and adjustment of the selected data points by the PK scientist if warranted. A minimum of 3 data points will be used for determination. Results will be summarized by cohort.

    Time frame: Day 1 (am) and Day 7 (pm)

  23. Apparent Terminal Elimination Rate Constant (λZ) of WAY-138451 in ADPKD Patients

    The pharmacokinetic parameter λZ for WAY-138451 will be determined by linear regression of the terminal points of the log-linear concentration-time curve. The Best Fit method utilized by WinNonlin will be used to identify the terminal linear phase of the concentration-time profile, with visual assessment and adjustment of the selected data points by the PK scientist if warranted. A minimum of 3 data points will be used for determination. Results will be summarized by cohort.

    Time frame: Day 1 (am) and Day 7 (pm)

  24. Apparent Terminal Elimination Rate Constant (λZ) of WAY-138758 in ADPKD Patients

    The pharmacokinetic parameter λZ for WAY-138758 will be determined by linear regression of the terminal points of the log-linear concentration-time curve. The Best Fit method utilized by WinNonlin will be used to identify the terminal linear phase of the concentration-time profile, with visual assessment and adjustment of the selected data points by the PK scientist if warranted. A minimum of 3 data points will be used for determination. Results will be summarized by cohort.

    Time frame: Day 1 (am) and Day 7 (pm)

  25. Apparent Systemic Clearance After Extravascular Dosing (CL/F) of Lixivaptan in ADPKD Patients

    The pharmacokinetic parameter CL/F for lixivaptan, calculated as: Day 1 AM: dose divided by AUC(0-inf), or Day 7 AM: dose divided by AUC(0-last), will be summarized by cohort.

    Time frame: Day 1 (am) and Day 7 (am)

  26. Volume of Distribution After Extravascular Dosing (VZ/F) of Lixivaptan in ADPKD Patients

    The pharmacokinetic parameter VZ/F for lixivaptan, calculated as CL/F divided by λZ, will be summarized by cohort.

    Time frame: Day 1 (am) and Day 7 (am)

  27. Accumulation Ratio for Cmax (RCmax) of Lixivaptan in ADPKD Patients

    The pharmacokinetic parameter RCmax for lixivaptan, calculated as \[Cmax on Day 7\]/\[Cmax on Day 1\], will be summarized by cohort.

    Time frame: Day 7 (am)

  28. Accumulation Ratio for AUC(0-last) (RAUC[0-last]) of Lixivaptan in ADPKD Patients

    The pharmacokinetic parameter RAUC(0-last) for lixivaptan, calculated as \[AUC(0-last) on Day 7\]/\[AUC(0-last) on Day 1\], will be summarized by cohort.

    Time frame: Day 7 (am)

  29. Area Under the Concentration-time Curve From Time 0 Until 14 Hours Postdose (AUC[0-14]) of Lixivaptan in ADPKD Patients

    The pharmacokinetic parameter AUC(0-14) for lixivaptan will be calculated using the linear trapezoidal rule for increasing values and the log trapezoidal rule for decreasing values. The actual elapsed time for the nominal 14-hour sample will be used for the calculation. Results will be summarized by cohort.

    Time frame: Day 7 (pm)

  30. Area Under the Concentration-time Curve From Time 0 Until 14 Hours Postdose (AUC[0-14]) of WAY-141624 in ADPKD Patients

    The pharmacokinetic parameter AUC(0-14) for WAY-141624 will be calculated using the linear trapezoidal rule for increasing values and the log trapezoidal rule for decreasing values. The actual elapsed time for the nominal 14-hour sample will be used for the calculation. Results will be summarized by cohort.

    Time frame: Day 7 (pm)

  31. Area Under the Concentration-time Curve From Time 0 Until 14 Hours Postdose (AUC[0-14]) of WAY-138451 in ADPKD Patients

    The pharmacokinetic parameter AUC(0-14) for WAY-138451 will be calculated using the linear trapezoidal rule for increasing values and the log trapezoidal rule for decreasing values. The actual elapsed time for the nominal 14-hour sample will be used for the calculation. Results will be summarized by cohort.

    Time frame: Day 7 (pm)

  32. Area Under the Concentration-time Curve From Time 0 Until 14 Hours Postdose (AUC[0-14]) of WAY-138758 in ADPKD Patients

    The pharmacokinetic parameter AUC(0-14) for WAY-138758 will be calculated using the linear trapezoidal rule for increasing values and the log trapezoidal rule for decreasing values. The actual elapsed time for the nominal 14-hour sample will be used for the calculation. Results will be summarized by cohort.

    Time frame: Day 7 (pm)

  33. Ratio of WAY-141624 Cmax to Parent Lixivaptan Cmax (MRCmax) in ADPKD Patients

    The pharmacokinetic parameter MRCmax for WAY-141624 will be calculated and corrected for molecular weight of WAY-141624 and parent lixivaptan as: (Cmax,m/Cmax,p)(MWp/MWm), where Cmax,m and MWm are Cmax and molecular weight of WAY-141624, respectively, and Cmax,p and MWp are Cmax and molecular weight of parent lixivaptan, respectively. The following molecular weights are to be used in all MRCmax calculations: * lixivaptan: 473.93 g/mol * WAY-141624: 505.95 g/mol Results will be summarized by cohort.

    Time frame: Day 7 (pm)

  34. Ratio of WAY-138451 Cmax to Parent Lixivaptan Cmax (MRCmax) in ADPKD Patients

    The pharmacokinetic parameter MRCmax for WAY-138451 will be calculated and corrected for molecular weight of WAY-138451 and parent lixivaptan as: (Cmax,m/Cmax,p)(MWp/MWm), where Cmax,m and MWm are Cmax and molecular weight of WAY-138451, respectively, and Cmax,p and MWp are Cmax and molecular weight of parent lixivaptan, respectively. The following molecular weights are to be used in all MRCmax calculations: * lixivaptan: 473.93 g/mol * WAY-138451: 488.92 g/mol Results will be summarized by cohort.

    Time frame: Day 7 (pm)

  35. Ratio of WAY-138758 Cmax to Parent Lixivaptan Cmax (MRCmax) in ADPKD Patients

    The pharmacokinetic parameter MRCmax for WAY-138758 will be calculated and corrected for molecular weight of WAY-138758 and parent lixivaptan as: (Cmax,m/Cmax,p)(MWp/MWm), where Cmax,m and MWm are Cmax and molecular weight of WAY-138758, respectively, and Cmax,p and MWp are Cmax and molecular weight of parent lixivaptan, respectively. The following molecular weights are to be used in all MRCmax calculations: * lixivaptan: 473.93 g/mol * WAY-138758: 426.82 g/mol Results will be summarized by cohort.

    Time frame: Day 7 (pm)

  36. Ratio of Metabolite AUC(0-14) to Parent Lixivaptan AUC(0-14) (MRAUC[0-14]) of WAY-141624 in ADPKD Patients

    The pharmacokinetic parameter MRAUC(0-14) for WAY-141624 will be calculated and corrected for molecular weight of WAY-141624 and parent lixivaptan as: (AUC(0-14),m/AUC(0-14),p)(MWp/MWm), where AUC(0-14),m and MWm are AUC(0-14) and molecular weight of WAY-141624, respectively, and AUC(0-14),p and MWp are AUC(0-14) and molecular weight of parent lixivaptan, respectively. The following molecular weights are to be used in all MRAUC(0-14) calculations: * lixivaptan: 473.93 g/mol * WAY-141624: 505.95 g/mol Results will be summarized by cohort.

    Time frame: Day 7 (pm)

  37. Ratio of Metabolite AUC(0-14) to Parent Lixivaptan AUC(0-14) (MRAUC[0-14]) of WAY-138451 in ADPKD Patients

    The pharmacokinetic parameter MRAUC(0-14) for WAY-138451 will be calculated and corrected for molecular weight of WAY-138451 and parent lixivaptan as: (AUC(0-14),m/AUC(0-14),p)(MWp/MWm), where AUC(0-14),m and MWm are AUC(0-14) and molecular weight of WAY-138451, respectively, and AUC(0-14),p and MWp are AUC(0-14) and molecular weight of parent lixivaptan, respectively. The following molecular weights are to be used in all MRAUC(0-14) calculations: * lixivaptan: 473.93 g/mol * WAY-138451: 488.92 g/mol Results will be summarized by cohort.

    Time frame: Day 7 (pm)

  38. Ratio of Metabolite AUC(0-14) to Parent Lixivaptan AUC(0-14) (MRAUC[0-14]) of WAY-138758 in ADPKD Patients

    The pharmacokinetic parameter MRAUC(0-14) for WAY-138758 will be calculated and corrected for molecular weight of WAY-138758 and parent lixivaptan as: (AUC(0-14),m/AUC(0-14),p)(MWp/MWm), where AUC(0-14),m and MWm are AUC(0-14) and molecular weight of WAY-138758, respectively, and AUC(0-14),p and MWp are AUC(0-14) and molecular weight of parent lixivaptan, respectively. The following molecular weights are to be used in all MRAUC(0-14) calculations: * lixivaptan: 473.93 g/mol * WAY-138758: 426.82 g/mol Results will be summarized by cohort.

    Time frame: Day 7 (pm)

  39. Number of Study Participants With Treatment-emergent Adverse Events

    The number of study participants who experience treatment-emergent adverse events during the study will be counted and summarized by dose level.

    Time frame: 35 days

  40. Number of Study Participants With Clinically Significant Physical Examination Findings

    The number of study participants who experience clinically significant physical examination findings during the study will be counted and summarized by cohort.

    Time frame: 35 days

  41. Number of Study Participants With Clinically Significant Vital Signs

    The number of study participants who experience vital signs (systolic blood pressure, diastolic blood pressure, pulse rate, respiratory rate, and body temperature) meeting the predefined markedly abnormal criteria during the study will be counted and summarized by cohort.

    Time frame: 35 days

  42. Number of Study Participants With Clinically Significant Changes in 12-lead Electrocardiograms

    The number of study participants who experience 12-lead electrocardiograms meeting the predefined markedly abnormal criteria during the study will be counted and summarized by cohort.

    Time frame: Baseline (Day 1) to Day 8 (8 days)

  43. Number of Study Participants With Abnormal Clinical Laboratory Findings (Including Clinical Chemistry, Hematology, and Urinalysis)

    The number of study participants who experience clinically meaningful laboratory findings, relating to clinical chemistry, hematology, and urinalysis, during the study will be counted and summarized by cohort.

    Time frame: 35 days

  44. Aquaretic Tolerability of Lixivaptan Measured by a Tolerability Questionnaire Relating to the Symptom Burden of Nocturia, Urgency, and Frequency at Day 7: Questions 1, 2, 6, and 10

    The number of study participants who answered "yes" to the following questions at Day 7 will be counted and summarized by dose level: * Could you tolerate taking this dose of study drug for the next 12 months? * Did the study drug make you feel thirsty more often than usual? * Did the study drug make you go to the bathroom (urinate) more often than usual during the night? * Would you be comfortable recommending the study drug to another patient with your kidney condition?

    Time frame: Day 7

  45. Aquaretic Tolerability of Lixivaptan Measured by a Tolerability Questionnaire Relating to the Symptom Burden of Nocturia, Urgency, and Frequency at Day 7: Question 3

    The number of study participants who answered "not at all" and "slightly" to the following question at Day 7 will be measured: • If the study drug made you feel thirsty more often than usual, were you bothered by it?

    Time frame: Day 7

  46. Aquaretic Tolerability of Lixivaptan Measured by a Tolerability Questionnaire Relating to the Symptom Burden of Nocturia, Urgency, and Frequency at Day 7: Question 7

    The number of study participants who answered "not at all" and "slightly" to the following question at Day 7 will be measured: • If the study drug made you go to the bathroom (urinate) more often than usual during the night, did it bother you?

    Time frame: Day 7

Secondary outcomes

  1. Change From Baseline in Spot Urine Osmolality

    Changes from baseline in spot urine measurements for samples taken at 0, 1, 2, 4, 6, 9, 10, 11, 12, 14, and 24 hours after the Day 1 and Day 7 doses will be summarized by cohort. The baseline value for each time point after first administration of study drug is the value observed at the corresponding time point on Day -1 (or Day 1 for the AM predose assessment only).

    Time frame: At time of dose, and at 1, 2, 4, 6, 9, 10, 11, 12, 14, and 24 hours after the Day 1 and Day 7 doses

  2. Change From Baseline in 24-hour Urine Output

    Changes from baseline in 24-hour urine output for samples taken on Day 1 and Day 7 will be summarized by cohort. The baseline value was the last value observed prior to first administration of study drug on Day -1.

    Time frame: Baseline (Day -1), Day 1, and Day 7

  3. Change From Baseline of the Estimated Glomerular Filtration Rate (eGFR)

    Changes from baseline of eGFR derived from the serum creatinine concentrations for samples taken at Day 1 (postdose), Day 2, Day 7, Day 8, and Day 35 will summarized by cohort

    Time frame: Baseline (Day 1) to end of study (35 days)

  4. Change From Baseline in Total Kidney Volume

    Changes from baseline (Day -1) in total kidney volume, measured by abdominal MRI on Day 7 and Day 35, will be summarized by cohort.

    Time frame: Baseline (Day -1) to end of study (36 days)

  5. Change From Baseline in Liver Volume

    Changes from baseline (Day -1) in liver volume, measured by abdominal MRI on Day 7 and Day 35, will be summarized by cohort.

    Time frame: Baseline (Day -1) to end of study (36 days)

  6. Change From Baseline of Plasma Copeptin

    Changes from baseline (Day -1) in plasma copeptin, a marker for circulating vasopressin, at Day 2, Day 7, and Day 35 will be summarized by cohort.

    Time frame: Baseline (Day -1) to end of study (36 days)

  7. Change From Baseline in Serum Creatinine

    Changes from baseline in serum creatinine for samples taken at Day 2, Day 7, Day 8, and Day 35 will be summarized by cohort.

    Time frame: Baseline (Day 1, predose) to end of study (35 days)

  8. Change From Baseline in Blood Urea Nitrogen (BUN)

    Changes from baseline in BUN for samples taken at Day 2, Day 7, Day 8, and Day 35 will be summarized by cohort.

    Time frame: Baseline (Day 1, predose) to end of study (35 days)

Other outcomes

  1. Volume of Distribution Over 24 Hours After Extravascular Dosing (VZ/F24H) of Lixivaptan in ADPKD Patients

    The pharmacokinetic parameter VZ/F24H for lixivaptan, calculated as CL/F24H divided by Day 7 PM λZ, will be summarized by cohort. VZ/F24H was not specified in the statistical analysis plan and was calculated for the combined 24-hour period including AM and PM dosing intervals on Day 7. This parameter replaces VZ/F initially planned for the Day 7 AM dose.

    Time frame: Day 7 (am)

07

Results

Posted Dec 5, 2022

Participant flow

Participant flow — Overall Study
MilestoneHigh Dose Lixivaptan / CKD1 or CKD2Low Dose Lixivaptan / CKD1 or CKD2High Dose Lixivaptan / CKD3Low Dose Lixivaptan / CKD3
Started9787
Completed9787
Not completed0000

Outcome measures

PrimaryMaximum Observed Plasma Concentration (Cmax) of Lixivaptan in ADPKD Patients

The pharmacokinetic parameter Cmax, the highest concentration of lixivaptan measured in plasma after multiple doses of drug, will be calculated from the observed concentration of lixivaptan and summarized by cohort.

Time frame:
Day 1 (am and pm) and Day 7 (am and pm)
Reported as:
Geometric mean · ng/mL
Maximum Observed Plasma Concentration (Cmax) of Lixivaptan in ADPKD Patients
ng/mLHigh Dose Lixivaptan / CKD1 or CKD2Low Dose Lixivaptan / CKD1 or CKD2High Dose Lixivaptan / CKD3Low Dose Lixivaptan / CKD3
Day 1 (am)656.8 ± 28.1190.9 ± 52.0681.3 ± 45.9156.9 ± 66.9
Day 1 (pm)1007 ± 36.6211.5 ± 33.5930.2 ± 44.5159.5 ± 51.9
Day 7 (am)1442 ± 34.3339.5 ± 19.51422 ± 48.3276.9 ± 33.7
Day 7 (pm)1582 ± 45.8301.0 ± 13.71211 ± 90.5258.8 ± 38.4
PrimaryMaximum Observed Plasma Concentration (Cmax) of WAY-141624 in ADPKD Patients

The pharmacokinetic parameter Cmax, the highest concentration of WAY-141624 measured in plasma after multiple doses of drug, will be calculated from the observed concentration of WAY-141624 and summarized by cohort.

Time frame:
Day 1 (am and pm) and Day 7 (am and pm)
Reported as:
Geometric mean · ng/mL
Maximum Observed Plasma Concentration (Cmax) of WAY-141624 in ADPKD Patients
ng/mLHigh Dose Lixivaptan / CKD1 or CKD2Low Dose Lixivaptan / CKD1 or CKD2High Dose Lixivaptan / CKD3Low Dose Lixivaptan / CKD3
Day 1 (am)455.3 ± 33.3123.7 ± 69.7381.7 ± 46.6135.3 ± 55.5
Day 1 (pm)561.7 ± 35.4160.8 ± 56.0417.8 ± 41.4142.3 ± 28.7
Day 7 (am)535.8 ± 34.4213.8 ± 75.4652.1 ± 49.0233.7 ± 50.8
Day 7 (pm)612.6 ± 42.3200.1 ± 63.0588.5 ± 69.2224.8 ± 44.7
PrimaryMaximum Observed Plasma Concentration (Cmax) of WAY-138451 in ADPKD Patients

The pharmacokinetic parameter Cmax, the highest concentration of WAY-138451 measured in plasma after multiple doses of drug, will be calculated from the observed concentration of WAY-138451 and summarized by cohort.

Time frame:
Day 1 (am and pm) and Day 7 (am and pm)
Reported as:
Geometric least squares mean · ng/mL
Maximum Observed Plasma Concentration (Cmax) of WAY-138451 in ADPKD Patients
ng/mLHigh Dose Lixivaptan / CKD1 or CKD2Low Dose Lixivaptan / CKD1 or CKD2High Dose Lixivaptan / CKD3Low Dose Lixivaptan / CKD3
Day 1 (am)84.33 ± 28.328.83 ± 21.482.23 ± 56.324.74 ± 38.6
Day 1 (pm)117.1 ± 38.125.93 ± 25.4103.3 ± 38.320.95 ± 35.4
Day 7 (am)177.4 ± 22.840.79 ± 27.6165.4 ± 43.133.61 ± 36.2
Day 7 (pm)189.1 ± 35.235.36 ± 10.4155.2 ± 74.031.64 ± 20.2
PrimaryMaximum Observed Plasma Concentration (Cmax) of WAY-138758 in ADPKD Patients

The pharmacokinetic parameter Cmax, the highest concentration of WAY-138758 measured in plasma after multiple doses of drug, will be calculated from the observed concentration of WAY-138758 and summarized by cohort.

Time frame:
Day 1 (am and pm) and Day 7 (am and pm)
Reported as:
Geometric mean · ng/mL
Maximum Observed Plasma Concentration (Cmax) of WAY-138758 in ADPKD Patients
ng/mLHigh Dose Lixivaptan / CKD1 or CKD2Low Dose Lixivaptan / CKD1 or CKD2High Dose Lixivaptan / CKD3Low Dose Lixivaptan / CKD3
Day 1 (am)239.3 ± 40.385.11 ± 36.5185.2 ± 49.764.26 ± 53.9
Day 1 (pm)354.6 ± 32.8125.5 ± 53.8275.0 ± 26.5107.1 ± 43.5
Day 7 (am)822.3 ± 54.4320.4 ± 60.4833.6 ± 25.0343.9 ± 35.8
Day 7 (pm)861.4 ± 56.0326.8 ± 56.7825.2 ± 24.0342.2 ± 36.0
PrimaryTime to Reach Maximum Plasma Concentration (Tmax) of Lixivaptan in ADPKD Patients

The pharmacokinetic parameter tmax, the time taken to reach the highest concentration of lixivaptan in plasma after multiple doses of drug, will be calculated from the observed concentration of lixivaptan and summarized by cohort.

Time frame:
Day 1 (am and pm) and Day 7 (am and pm)
Reported as:
Median · hours
Time to Reach Maximum Plasma Concentration (Tmax) of Lixivaptan in ADPKD Patients
hoursHigh Dose Lixivaptan / CKD1 or CKD2Low Dose Lixivaptan / CKD1 or CKD2High Dose Lixivaptan / CKD3Low Dose Lixivaptan / CKD3
Day 1 (am)1.000 (1.00 to 1.00)1.000 (1.00 to 1.05)1.000 (1.00 to 2.00)1.020 (0.67 to 2.00)
Day 1 (pm)1.000 (0.97 to 2.00)1.000 (1.00 to 1.93)1.000 (1.00 to 5.97)0.980 (0.95 to 5.62)
Day 7 (am)1.000 (1.00 to 1.00)1.000 (1.00 to 1.02)1.000 (1.00 to 2.00)1.000 (0.78 to 1.05)
Day 7 (pm)1.000 (1.00 to 2.00)1.000 (0.95 to 1.03)1.000 (0.97 to 13.95)0.920 (0.83 to 1.67)
PrimaryTime to Reach Maximum Plasma Concentration (Tmax) of WAY-141624 in ADPKD Patients

The pharmacokinetic parameter tmax, the time taken to reach the highest concentration of WAY-141624 in plasma after multiple doses of drug, will be calculated from the observed concentration of WAY-141624 and summarized by cohort.

Time frame:
Day 1 (am and pm) and Day 7 (am and pm)
Reported as:
Median · hours
Time to Reach Maximum Plasma Concentration (Tmax) of WAY-141624 in ADPKD Patients
hoursHigh Dose Lixivaptan / CKD1 or CKD2Low Dose Lixivaptan / CKD1 or CKD2High Dose Lixivaptan / CKD3Low Dose Lixivaptan / CKD3
Day 1 (am)2.000 (1.00 to 4.00)2.000 (1.05 to 2.00)2.000 (1.00 to 4.00)2.000 (1.67 to 4.00)
Day 1 (pm)2.000 (2.00 to 4.00)2.000 (1.93 to 4.03)2.000 (0.00 to 4.00)1.950 (1.92 to 13.58)
Day 7 (am)2.000 (1.00 to 2.00)2.000 (2.00 to 2.03)2.000 (1.00 to 4.08)2.000 (1.83 to 2.00)
Day 7 (pm)2.000 (2.00 to 4.00)2.010 (1.93 to 5.95)2.025 (0.00 to 13.95)1.920 (1.67 to 2.00)
PrimaryTime to Reach Maximum Plasma Concentration (Tmax) of WAY-138451 in ADPKD Patients

The pharmacokinetic parameter tmax, the time taken to reach the highest concentration of WAY-138451 in plasma after multiple doses of drug, will be calculated from the observed concentration of WAY-138451 and summarized by cohort.

Time frame:
Day 1 (am and pm) and Day 7 (am and pm)
Reported as:
Median · hours
Time to Reach Maximum Plasma Concentration (Tmax) of WAY-138451 in ADPKD Patients
hoursHigh Dose Lixivaptan / CKD1 or CKD2Low Dose Lixivaptan / CKD1 or CKD2High Dose Lixivaptan / CKD3Low Dose Lixivaptan / CKD3
Day 1 (am)1.000 (1.00 to 2.00)1.010 (1.00 to 1.05)1.000 (1.00 to 2.00)1.020 (0.67 to 2.00)
Day 1 (pm)1.000 (0.97 to 2.00)1.475 (1.00 to 2.00)2.000 (0.92 to 5.97)0.975 (0.95 to 1.93)
Day 7 (am)1.000 (1.00 to 1.00)1.000 (1.00 to 2.00)2.000 (1.00 to 2.08)1.050 (0.95 to 2.00)
Day 7 (pm)1.000 (1.00 to 2.00)1.015 (1.00 to 1.95)3.000 (1.00 to 13.95)1.000 (0.83 to 2.00)
PrimaryTime to Reach Maximum Plasma Concentration (Tmax) of WAY-138758 in ADPKD Patients

The pharmacokinetic parameter tmax, the time taken to reach the highest concentration of WAY-138758 in plasma after multiple doses of drug, will be calculated from the observed concentration of WAY-138758 and summarized by cohort.

Time frame:
Day 1 (am and pm) and Day 7 (am and pm)
Reported as:
Median · hours
Time to Reach Maximum Plasma Concentration (Tmax) of WAY-138758 in ADPKD Patients
hoursHigh Dose Lixivaptan / CKD1 or CKD2Low Dose Lixivaptan / CKD1 or CKD2High Dose Lixivaptan / CKD3Low Dose Lixivaptan / CKD3
Day 1 (am)4.000 (2.00 to 6.00)4.030 (4.00 to 6.00)9.460 (6.00 to 10.00)4.020 (3.68 to 9.93)
Day 1 (pm)4.000 (2.00 to 13.87)4.000 (2.00 to 13.83)4.000 (4.00 to 13.95)13.400 (3.98 to 13.87)
Day 7 (am)4.000 (0.00 to 6.00)2.030 (2.00 to 4.00)3.000 (0.00 to 9.92)5.980 (0.00 to 9.75)
Day 7 (pm)2.000 (1.00 to 13.98)3.010 (2.00 to 6.10)4.000 (0.00 to 13.95)3.900 (0.00 to 5.97)
PrimaryArea Under the Concentration-time Curve From Time 0 Until the Last Quantifiable Concentration (AUC[0-last]) of Lixivaptan in ADPKD Patients

The pharmacokinetic parameter AUC(0-last) for lixivaptan will be calculated using the linear trapezoidal rule for increasing values and the log trapezoidal rule for decreasing values, summarized by cohort.

Time frame:
Day 1 (am and pm) and Day 7 (am and pm)
Reported as:
Geometric mean · ng*hour/mL
Area Under the Concentration-time Curve From Time 0 Until the Last Quantifiable Concentration (AUC[0-last]) of Lixivaptan in ADPKD Patients
ng*hour/mLHigh Dose Lixivaptan / CKD1 or CKD2Low Dose Lixivaptan / CKD1 or CKD2High Dose Lixivaptan / CKD3Low Dose Lixivaptan / CKD3
Day 1 (am)1688 ± 43.5506.7 ± 45.02281 ± 37.9428.8 ± 46.6
Day 1 (pm)3619 ± 48.5782.1 ± 15.75208 ± 46.3782.8 ± 24.7
Day 7 (am)4237 ± 36.81007 ± 27.75395 ± 35.3889.4 ± 29.7
Day 7 (pm)8467 ± 47.21958 ± 80.212870 ± 56.21666 ± 56.0
PrimaryArea Under the Concentration-time Curve From Time 0 Until the Last Quantifiable Concentration (AUC[0-last]) of WAY-141624 in ADPKD Patients

The pharmacokinetic parameter AUC(0-last) for WAY-141624 will be calculated using the linear trapezoidal rule for increasing values and the log trapezoidal rule for decreasing values and summarized by cohort.

Time frame:
Day 1 (am and pm) and Day 7 (am and pm)
Reported as:
Geometric mean · ng*hour/mL
Area Under the Concentration-time Curve From Time 0 Until the Last Quantifiable Concentration (AUC[0-last]) of WAY-141624 in ADPKD Patients
ng*hour/mLHigh Dose Lixivaptan / CKD1 or CKD2Low Dose Lixivaptan / CKD1 or CKD2High Dose Lixivaptan / CKD3Low Dose Lixivaptan / CKD3
Day 1 (am)2339 ± 44.1669.1 ± 48.82300 ± 43.1716.5 ± 54.2
Day 1 (pm)3963 ± 48.71214 ± 49.33894 ± 29.01266 ± 45.7
Day 7 (am)3440 ± 40.41349 ± 58.14196 ± 37.71560 ± 56.9
Day 7 (pm)11330 ± 56.44174 ± 56.315160 ± 54.84731 ± 81.2
PrimaryArea Under the Concentration-time Curve From Time 0 Until the Last Quantifiable Concentration (AUC[0-last]) of WAY-138451 in ADPKD Patients

The pharmacokinetic parameter AUC(0-last) for WAY-138451 will be calculated using the linear trapezoidal rule for increasing values and the log trapezoidal rule for decreasing values and summarized by cohort.

Time frame:
Day 1 (am and pm) and Day 7 (am and pm)
Reported as:
Geometric mean · ng*hour/mL
Area Under the Concentration-time Curve From Time 0 Until the Last Quantifiable Concentration (AUC[0-last]) of WAY-138451 in ADPKD Patients
ng*hour/mLHigh Dose Lixivaptan / CKD1 or CKD2Low Dose Lixivaptan / CKD1 or CKD2High Dose Lixivaptan / CKD3Low Dose Lixivaptan / CKD3
Day 1 (am)284.7 ± 50.377.23 ± 24.8373.6 ± 44.970.01 ± 21.6
Day 1 (pm)532.8 ± 65.580.14 ± 36.1764.5 ± 40.174.00 ± 26.9
Day 7 (am)736.8 ± 31.2139.7 ± 45.1919.2 ± 39.8132.9 ± 42.4
Day 7 (pm)1444 ± 52.6194.6 ± 138.31867 ± 58.8137.3 ± 46.5
PrimaryArea Under the Concentration-time Curve From Time 0 Until the Last Quantifiable Concentration (AUC[0-last]) of WAY-138758 in ADPKD Patients

The pharmacokinetic parameter AUC(0-last) for WAY-138758 will be calculated using the linear trapezoidal rule for increasing values and the log trapezoidal rule for decreasing values and summarized by cohort.

Time frame:
Day 1 (am and pm) and Day 7 (am and pm)
Reported as:
Geometric mean · ng*hour/mL
Area Under the Concentration-time Curve From Time 0 Until the Last Quantifiable Concentration (AUC[0-last]) of WAY-138758 in ADPKD Patients
ng*hour/mLHigh Dose Lixivaptan / CKD1 or CKD2Low Dose Lixivaptan / CKD1 or CKD2High Dose Lixivaptan / CKD3Low Dose Lixivaptan / CKD3
Day 1 (am)1792 ± 36.9669.7 ± 37.11412 ± 51.3485.1 ± 65.0
Day 1 (pm)4281 ± 35.31449 ± 50.73418 ± 24.51212 ± 49.2
Day 7 (am)7471 ± 54.52919 ± 59.27660 ± 24.63162 ± 36.3
Day 7 (pm)46910 ± 62.818940 ± 51.952560 ± 28.023890 ± 38.1
PrimaryArea Under the Concentration-time Curve From Time 0 Extrapolated to Infinity (AUC[0-inf]) of Lixivaptan in ADPKD Patients

The pharmacokinetic parameter AUC(0-inf) for lixivaptan will be calculated using the linear trapezoidal rule for increasing values, the log trapezoidal rule for decreasing values, and extrapolated to infinity by addition of the last quantifiable observed concentration divided by the elimination rate constant and summarized by cohort.

Time frame:
Day 1 (am)

No measurements were reported for this outcome.

PrimaryArea Under the Concentration-time Curve From Time 0 Extrapolated to Infinity (AUC[0-inf]) of WAY-141624 in ADPKD Patients

The pharmacokinetic parameter AUC(0-inf) for WAY-141624 will be calculated using the linear trapezoidal rule for increasing values, the log trapezoidal rule for decreasing values, and extrapolated to infinity by addition of the last quantifiable observed concentration divided by the elimination rate constant and summarized by cohort.

Time frame:
Day 1 (am)

No measurements were reported for this outcome.

PrimaryArea Under the Concentration-time Curve From Time 0 Extrapolated to Infinity (AUC[0-inf]) of WAY-138451 in ADPKD Patients

The pharmacokinetic parameter AUC(0-inf) for WAY-138451 will be calculated using the linear trapezoidal rule for increasing values, the log trapezoidal rule for decreasing values, and extrapolated to infinity by addition of the last quantifiable observed concentration divided by the elimination rate constant and summarized by cohort.

Time frame:
Day 1 (am)

No measurements were reported for this outcome.

PrimaryArea Under the Concentration-time Curve From Time 0 Extrapolated to Infinity (AUC[0-inf]) of WAY-138758 in ADPKD Patients

The pharmacokinetic parameter AUC(0-inf) for WAY-138758 will be calculated using the linear trapezoidal rule for increasing values, the log trapezoidal rule for decreasing values, and extrapolated to infinity by addition of the last quantifiable observed concentration divided by the elimination rate constant and summarized by cohort.

Time frame:
Day 1 (am)

No measurements were reported for this outcome.

PrimaryTerminal Elimination Phase Half-life (t1/2) of Lixivaptan in ADPKD Patients

The pharmacokinetic parameter t1/2 for lixivaptan, determined as ln2/apparent terminal elimination rate constant, will be calculated and summarized by cohort.

Time frame:
Day 1 (am) and Day 7 (pm)
Reported as:
Geometric mean · hours
Terminal Elimination Phase Half-life (t1/2) of Lixivaptan in ADPKD Patients
hoursHigh Dose Lixivaptan / CKD1 or CKD2Low Dose Lixivaptan / CKD1 or CKD2High Dose Lixivaptan / CKD3Low Dose Lixivaptan / CKD3
Day 7 (pm)9.696 ± 24.27.688 ± 51.611.39 ± 28.910.25 ± 27.4
PrimaryTerminal Elimination Phase Half-life (t1/2) of WAY-141624 in ADPKD Patients

The pharmacokinetic parameter t1/2 for WAY-141624, determined as ln2/apparent terminal elimination rate constant, will be calculated and summarized by cohort.

Time frame:
Day 1 (am) and Day 7 (pm)
Reported as:
Geometric mean · hours
Terminal Elimination Phase Half-life (t1/2) of WAY-141624 in ADPKD Patients
hoursHigh Dose Lixivaptan / CKD1 or CKD2Low Dose Lixivaptan / CKD1 or CKD2High Dose Lixivaptan / CKD3Low Dose Lixivaptan / CKD3
Day 7 (pm)20.48 ± 33.322.41 ± 56.120.81 ± 30.418.79 ± 22.2
PrimaryTerminal Elimination Phase Half-life (t1/2) of WAY-138451 in ADPKD Patients

The pharmacokinetic parameter t1/2 for WAY-138451, determined as ln2/apparent terminal elimination rate constant, will be calculated and summarized by cohort.

Time frame:
Day 1 (am) and Day 7 (pm)
Reported as:
Geometric mean · hours
Terminal Elimination Phase Half-life (t1/2) of WAY-138451 in ADPKD Patients
hoursHigh Dose Lixivaptan / CKD1 or CKD2Low Dose Lixivaptan / CKD1 or CKD2High Dose Lixivaptan / CKD3Low Dose Lixivaptan / CKD3
Day 7 (pm)6.439 ± 36.7—9.426 ± 22.6NA ± NA
PrimaryTerminal Elimination Phase Half-life (t1/2) of WAY-138758 in ADPKD Patients

The pharmacokinetic parameter t1/2 for WAY-138758, determined as ln2/apparent terminal elimination rate constant, will be calculated and summarized by cohort.

Time frame:
Day 1 (am) and Day 7 (pm)
Reported as:
Geometric mean · hours
Terminal Elimination Phase Half-life (t1/2) of WAY-138758 in ADPKD Patients
hoursHigh Dose Lixivaptan / CKD1 or CKD2Low Dose Lixivaptan / CKD1 or CKD2High Dose Lixivaptan / CKD3Low Dose Lixivaptan / CKD3
Day 7 (pm)48.80 ± 25.850.70 ± 8.659.93 ± 32.865.11 ± 30.2
PrimaryApparent Terminal Elimination Rate Constant (λZ) of Lixivaptan in ADPKD Patients

The pharmacokinetic parameter λZ for lixivaptan will be determined by linear regression of the terminal points of the log-linear concentration-time curve. The Best Fit method utilized by WinNonlin will be used to identify the terminal linear phase of the concentration-time profile, with visual assessment and adjustment of the selected data points by the PK scientist if warranted. A minimum of 3 data points will be used for determination. Results will be summarized by cohort.

Time frame:
Day 1 (am) and Day 7 (pm)
Reported as:
Geometric mean · 1/hour
Apparent Terminal Elimination Rate Constant (λZ) of Lixivaptan in ADPKD Patients
1/hourHigh Dose Lixivaptan / CKD1 or CKD2Low Dose Lixivaptan / CKD1 or CKD2High Dose Lixivaptan / CKD3Low Dose Lixivaptan / CKD3
Day 7 (pm)0.07149 ± 24.20.09016 ± 51.60.06085 ± 28.90.06762 ± 27.4
PrimaryApparent Terminal Elimination Rate Constant (λZ) of WAY-141624 in ADPKD Patients

The pharmacokinetic parameter λZ for WAY-141624 will be determined by linear regression of the terminal points of the log-linear concentration-time curve. The Best Fit method utilized by WinNonlin will be used to identify the terminal linear phase of the concentration-time profile, with visual assessment and adjustment of the selected data points by the PK scientist if warranted. A minimum of 3 data points will be used for determination. Results will be summarized by cohort.

Time frame:
Day 1 (am) and Day 7 (pm)
Reported as:
Geometric mean · 1/hour
Apparent Terminal Elimination Rate Constant (λZ) of WAY-141624 in ADPKD Patients
1/hourHigh Dose Lixivaptan / CKD1 or CKD2Low Dose Lixivaptan / CKD1 or CKD2High Dose Lixivaptan / CKD3Low Dose Lixivaptan / CKD3
Day 7 (pm)0.03384 ± 33.30.03093 ± 56.10.03330 ± 30.40.03690 ± 22.2
PrimaryApparent Terminal Elimination Rate Constant (λZ) of WAY-138451 in ADPKD Patients

The pharmacokinetic parameter λZ for WAY-138451 will be determined by linear regression of the terminal points of the log-linear concentration-time curve. The Best Fit method utilized by WinNonlin will be used to identify the terminal linear phase of the concentration-time profile, with visual assessment and adjustment of the selected data points by the PK scientist if warranted. A minimum of 3 data points will be used for determination. Results will be summarized by cohort.

Time frame:
Day 1 (am) and Day 7 (pm)
Reported as:
Geometric mean · 1/hour
Apparent Terminal Elimination Rate Constant (λZ) of WAY-138451 in ADPKD Patients
1/hourHigh Dose Lixivaptan / CKD1 or CKD2Low Dose Lixivaptan / CKD1 or CKD2High Dose Lixivaptan / CKD3Low Dose Lixivaptan / CKD3
Day 7 (pm)0.1077 ± 36.7—0.07353 ± 22.6NA ± NA
PrimaryApparent Terminal Elimination Rate Constant (λZ) of WAY-138758 in ADPKD Patients

The pharmacokinetic parameter λZ for WAY-138758 will be determined by linear regression of the terminal points of the log-linear concentration-time curve. The Best Fit method utilized by WinNonlin will be used to identify the terminal linear phase of the concentration-time profile, with visual assessment and adjustment of the selected data points by the PK scientist if warranted. A minimum of 3 data points will be used for determination. Results will be summarized by cohort.

Time frame:
Day 1 (am) and Day 7 (pm)
Reported as:
Geometric mean · 1/hour
Apparent Terminal Elimination Rate Constant (λZ) of WAY-138758 in ADPKD Patients
1/hourHigh Dose Lixivaptan / CKD1 or CKD2Low Dose Lixivaptan / CKD1 or CKD2High Dose Lixivaptan / CKD3Low Dose Lixivaptan / CKD3
Day 7 (pm)0.01421 ± 25.80.01367 ± 8.60.01157 ± 32.80.01065 ± 30.2
PrimaryApparent Systemic Clearance After Extravascular Dosing (CL/F) of Lixivaptan in ADPKD Patients

The pharmacokinetic parameter CL/F for lixivaptan, calculated as: Day 1 AM: dose divided by AUC(0-inf), or Day 7 AM: dose divided by AUC(0-last), will be summarized by cohort.

Time frame:
Day 1 (am) and Day 7 (am)
Reported as:
Geometric mean · L/hour
Apparent Systemic Clearance After Extravascular Dosing (CL/F) of Lixivaptan in ADPKD Patients
L/hourHigh Dose Lixivaptan / CKD1 or CKD2Low Dose Lixivaptan / CKD1 or CKD2High Dose Lixivaptan / CKD3Low Dose Lixivaptan / CKD3
Day 7 (am)47.20 ± 36.849.65 ± 27.737.07 ± 35.356.22 ± 29.7
PrimaryVolume of Distribution After Extravascular Dosing (VZ/F) of Lixivaptan in ADPKD Patients

The pharmacokinetic parameter VZ/F for lixivaptan, calculated as CL/F divided by λZ, will be summarized by cohort.

Time frame:
Day 1 (am) and Day 7 (am)
Reported as:
Geometric mean · L

No measurements were reported for this outcome.

PrimaryAccumulation Ratio for Cmax (RCmax) of Lixivaptan in ADPKD Patients

The pharmacokinetic parameter RCmax for lixivaptan, calculated as \[Cmax on Day 7\]/\[Cmax on Day 1\], will be summarized by cohort.

Time frame:
Day 7 (am)
Reported as:
Geometric mean · Ratio
Accumulation Ratio for Cmax (RCmax) of Lixivaptan in ADPKD Patients
RatioHigh Dose Lixivaptan / CKD1 or CKD2Low Dose Lixivaptan / CKD1 or CKD2High Dose Lixivaptan / CKD3Low Dose Lixivaptan / CKD3
Accumulation Ratio for Cmax (RCmax) of Lixivaptan in ADPKD Patients2.287 ± 24.11.687 ± 68.42.087 ± 36.21.765 ± 50.1
PrimaryAccumulation Ratio for AUC(0-last) (RAUC[0-last]) of Lixivaptan in ADPKD Patients

The pharmacokinetic parameter RAUC(0-last) for lixivaptan, calculated as \[AUC(0-last) on Day 7\]/\[AUC(0-last) on Day 1\], will be summarized by cohort.

Time frame:
Day 7 (am)
Reported as:
Geometric mean · Ratio
Accumulation Ratio for AUC(0-last) (RAUC[0-last]) of Lixivaptan in ADPKD Patients
RatioHigh Dose Lixivaptan / CKD1 or CKD2Low Dose Lixivaptan / CKD1 or CKD2High Dose Lixivaptan / CKD3Low Dose Lixivaptan / CKD3
Accumulation Ratio for AUC(0-last) (RAUC[0-last]) of Lixivaptan in ADPKD Patients2.643 ± 28.61.795 ± 25.62.365 ± 28.92.074 ± 31.5
PrimaryArea Under the Concentration-time Curve From Time 0 Until 14 Hours Postdose (AUC[0-14]) of Lixivaptan in ADPKD Patients

The pharmacokinetic parameter AUC(0-14) for lixivaptan will be calculated using the linear trapezoidal rule for increasing values and the log trapezoidal rule for decreasing values. The actual elapsed time for the nominal 14-hour sample will be used for the calculation. Results will be summarized by cohort.

Time frame:
Day 7 (pm)
Reported as:
Geometric mean · ng*h/mL
Area Under the Concentration-time Curve From Time 0 Until 14 Hours Postdose (AUC[0-14]) of Lixivaptan in ADPKD Patients
ng*h/mLHigh Dose Lixivaptan / CKD1 or CKD2Low Dose Lixivaptan / CKD1 or CKD2High Dose Lixivaptan / CKD3Low Dose Lixivaptan / CKD3
Area Under the Concentration-time Curve From Time 0 Until 14 Hours Postdose (AUC[0-14]) of Lixivaptan in ADPKD Patients6530 ± 44.31280 ± 26.97800 ± 55.21069 ± 29.0
PrimaryArea Under the Concentration-time Curve From Time 0 Until 14 Hours Postdose (AUC[0-14]) of WAY-141624 in ADPKD Patients

The pharmacokinetic parameter AUC(0-14) for WAY-141624 will be calculated using the linear trapezoidal rule for increasing values and the log trapezoidal rule for decreasing values. The actual elapsed time for the nominal 14-hour sample will be used for the calculation. Results will be summarized by cohort.

Time frame:
Day 7 (pm)
Reported as:
Geometric mean · ng*h/mL
Area Under the Concentration-time Curve From Time 0 Until 14 Hours Postdose (AUC[0-14]) of WAY-141624 in ADPKD Patients
ng*h/mLHigh Dose Lixivaptan / CKD1 or CKD2Low Dose Lixivaptan / CKD1 or CKD2High Dose Lixivaptan / CKD3Low Dose Lixivaptan / CKD3
Area Under the Concentration-time Curve From Time 0 Until 14 Hours Postdose (AUC[0-14]) of WAY-141624 in ADPKD Patients5227 ± 46.61717 ± 46.65871 ± 50.71959 ± 54.0
PrimaryArea Under the Concentration-time Curve From Time 0 Until 14 Hours Postdose (AUC[0-14]) of WAY-138451 in ADPKD Patients

The pharmacokinetic parameter AUC(0-14) for WAY-138451 will be calculated using the linear trapezoidal rule for increasing values and the log trapezoidal rule for decreasing values. The actual elapsed time for the nominal 14-hour sample will be used for the calculation. Results will be summarized by cohort.

Time frame:
Day 7 (pm)
Reported as:
Geometric mean · ng*h/mL
Area Under the Concentration-time Curve From Time 0 Until 14 Hours Postdose (AUC[0-14]) of WAY-138451 in ADPKD Patients
ng*h/mLHigh Dose Lixivaptan / CKD1 or CKD2Low Dose Lixivaptan / CKD1 or CKD2High Dose Lixivaptan / CKD3Low Dose Lixivaptan / CKD3
Area Under the Concentration-time Curve From Time 0 Until 14 Hours Postdose (AUC[0-14]) of WAY-138451 in ADPKD Patients1107 ± 39.2182.8 ± 33.41270 ± 50.8154.4 ± 37.7
PrimaryArea Under the Concentration-time Curve From Time 0 Until 14 Hours Postdose (AUC[0-14]) of WAY-138758 in ADPKD Patients

The pharmacokinetic parameter AUC(0-14) for WAY-138758 will be calculated using the linear trapezoidal rule for increasing values and the log trapezoidal rule for decreasing values. The actual elapsed time for the nominal 14-hour sample will be used for the calculation. Results will be summarized by cohort.

Time frame:
Day 7 (pm)
Reported as:
Geometric mean · ng*h/mL
Area Under the Concentration-time Curve From Time 0 Until 14 Hours Postdose (AUC[0-14]) of WAY-138758 in ADPKD Patients
ng*h/mLHigh Dose Lixivaptan / CKD1 or CKD2Low Dose Lixivaptan / CKD1 or CKD2High Dose Lixivaptan / CKD3Low Dose Lixivaptan / CKD3
Area Under the Concentration-time Curve From Time 0 Until 14 Hours Postdose (AUC[0-14]) of WAY-138758 in ADPKD Patients10900 ± 55.64121 ± 56.910730 ± 25.34509 ± 36.2
PrimaryRatio of WAY-141624 Cmax to Parent Lixivaptan Cmax (MRCmax) in ADPKD Patients

The pharmacokinetic parameter MRCmax for WAY-141624 will be calculated and corrected for molecular weight of WAY-141624 and parent lixivaptan as: (Cmax,m/Cmax,p)(MWp/MWm), where Cmax,m and MWm are Cmax and molecular weight of WAY-141624, respectively, and Cmax,p and MWp are Cmax and molecular weight of parent lixivaptan, respectively. The following molecular weights are to be used in all MRCmax calculations: * lixivaptan: 473.93 g/mol * WAY-141624: 505.95 g/mol Results will be summarized by cohort.

Time frame:
Day 7 (pm)
Reported as:
Geometric mean · Ratio
Ratio of WAY-141624 Cmax to Parent Lixivaptan Cmax (MRCmax) in ADPKD Patients
RatioHigh Dose Lixivaptan / CKD1 or CKD2Low Dose Lixivaptan / CKD1 or CKD2High Dose Lixivaptan / CKD3Low Dose Lixivaptan / CKD3
Ratio of WAY-141624 Cmax to Parent Lixivaptan Cmax (MRCmax) in ADPKD Patients0.3627 ± 40.00.6225 ± 57.50.4554 ± 31.00.8137 ± 41.5
PrimaryRatio of WAY-138451 Cmax to Parent Lixivaptan Cmax (MRCmax) in ADPKD Patients

The pharmacokinetic parameter MRCmax for WAY-138451 will be calculated and corrected for molecular weight of WAY-138451 and parent lixivaptan as: (Cmax,m/Cmax,p)(MWp/MWm), where Cmax,m and MWm are Cmax and molecular weight of WAY-138451, respectively, and Cmax,p and MWp are Cmax and molecular weight of parent lixivaptan, respectively. The following molecular weights are to be used in all MRCmax calculations: * lixivaptan: 473.93 g/mol * WAY-138451: 488.92 g/mol Results will be summarized by cohort.

Time frame:
Day 7 (pm)
Reported as:
Geometric mean · Ratio
Ratio of WAY-138451 Cmax to Parent Lixivaptan Cmax (MRCmax) in ADPKD Patients
RatioHigh Dose Lixivaptan / CKD1 or CKD2Low Dose Lixivaptan / CKD1 or CKD2High Dose Lixivaptan / CKD3Low Dose Lixivaptan / CKD3
Ratio of WAY-138451 Cmax to Parent Lixivaptan Cmax (MRCmax) in ADPKD Patients0.1159 ± 17.70.1139 ± 14.90.1243 ± 27.50.1185 ± 29.3
PrimaryRatio of WAY-138758 Cmax to Parent Lixivaptan Cmax (MRCmax) in ADPKD Patients

The pharmacokinetic parameter MRCmax for WAY-138758 will be calculated and corrected for molecular weight of WAY-138758 and parent lixivaptan as: (Cmax,m/Cmax,p)(MWp/MWm), where Cmax,m and MWm are Cmax and molecular weight of WAY-138758, respectively, and Cmax,p and MWp are Cmax and molecular weight of parent lixivaptan, respectively. The following molecular weights are to be used in all MRCmax calculations: * lixivaptan: 473.93 g/mol * WAY-138758: 426.82 g/mol Results will be summarized by cohort.

Time frame:
Day 7 (pm)
Reported as:
Geometric mean · Ratio
Ratio of WAY-138758 Cmax to Parent Lixivaptan Cmax (MRCmax) in ADPKD Patients
RatioHigh Dose Lixivaptan / CKD1 or CKD2Low Dose Lixivaptan / CKD1 or CKD2High Dose Lixivaptan / CKD3Low Dose Lixivaptan / CKD3
Ratio of WAY-138758 Cmax to Parent Lixivaptan Cmax (MRCmax) in ADPKD Patients0.6045 ± 61.71.205 ± 56.90.7569 ± 86.01.468 ± 51.2
PrimaryRatio of Metabolite AUC(0-14) to Parent Lixivaptan AUC(0-14) (MRAUC[0-14]) of WAY-141624 in ADPKD Patients

The pharmacokinetic parameter MRAUC(0-14) for WAY-141624 will be calculated and corrected for molecular weight of WAY-141624 and parent lixivaptan as: (AUC(0-14),m/AUC(0-14),p)(MWp/MWm), where AUC(0-14),m and MWm are AUC(0-14) and molecular weight of WAY-141624, respectively, and AUC(0-14),p and MWp are AUC(0-14) and molecular weight of parent lixivaptan, respectively. The following molecular weights are to be used in all MRAUC(0-14) calculations: * lixivaptan: 473.93 g/mol * WAY-141624: 505.95 g/mol Results will be summarized by cohort.

Time frame:
Day 7 (pm)
Reported as:
Geometric mean · Ratio
Ratio of Metabolite AUC(0-14) to Parent Lixivaptan AUC(0-14) (MRAUC[0-14]) of WAY-141624 in ADPKD Patients
RatioHigh Dose Lixivaptan / CKD1 or CKD2Low Dose Lixivaptan / CKD1 or CKD2High Dose Lixivaptan / CKD3Low Dose Lixivaptan / CKD3
Ratio of Metabolite AUC(0-14) to Parent Lixivaptan AUC(0-14) (MRAUC[0-14]) of WAY-141624 in ADPKD Patients0.7498 ± 41.01.256 ± 69.70.7050 ± 24.11.717 ± 42.7
PrimaryRatio of Metabolite AUC(0-14) to Parent Lixivaptan AUC(0-14) (MRAUC[0-14]) of WAY-138451 in ADPKD Patients

The pharmacokinetic parameter MRAUC(0-14) for WAY-138451 will be calculated and corrected for molecular weight of WAY-138451 and parent lixivaptan as: (AUC(0-14),m/AUC(0-14),p)(MWp/MWm), where AUC(0-14),m and MWm are AUC(0-14) and molecular weight of WAY-138451, respectively, and AUC(0-14),p and MWp are AUC(0-14) and molecular weight of parent lixivaptan, respectively. The following molecular weights are to be used in all MRAUC(0-14) calculations: * lixivaptan: 473.93 g/mol * WAY-138451: 488.92 g/mol Results will be summarized by cohort.

Time frame:
Day 7 (pm)
Reported as:
Geometric mean · Ratio
Ratio of Metabolite AUC(0-14) to Parent Lixivaptan AUC(0-14) (MRAUC[0-14]) of WAY-138451 in ADPKD Patients
RatioHigh Dose Lixivaptan / CKD1 or CKD2Low Dose Lixivaptan / CKD1 or CKD2High Dose Lixivaptan / CKD3Low Dose Lixivaptan / CKD3
Ratio of Metabolite AUC(0-14) to Parent Lixivaptan AUC(0-14) (MRAUC[0-14]) of WAY-138451 in ADPKD Patients0.1643 ± 10.90.1384 ± 11.30.1579 ± 17.50.1401 ± 23.9
PrimaryRatio of Metabolite AUC(0-14) to Parent Lixivaptan AUC(0-14) (MRAUC[0-14]) of WAY-138758 in ADPKD Patients

The pharmacokinetic parameter MRAUC(0-14) for WAY-138758 will be calculated and corrected for molecular weight of WAY-138758 and parent lixivaptan as: (AUC(0-14),m/AUC(0-14),p)(MWp/MWm), where AUC(0-14),m and MWm are AUC(0-14) and molecular weight of WAY-138758, respectively, and AUC(0-14),p and MWp are AUC(0-14) and molecular weight of parent lixivaptan, respectively. The following molecular weights are to be used in all MRAUC(0-14) calculations: * lixivaptan: 473.93 g/mol * WAY-138758: 426.82 g/mol Results will be summarized by cohort.

Time frame:
Day 7 (pm)
Reported as:
Geometric mean · Ratio
Ratio of Metabolite AUC(0-14) to Parent Lixivaptan AUC(0-14) (MRAUC[0-14]) of WAY-138758 in ADPKD Patients
RatioHigh Dose Lixivaptan / CKD1 or CKD2Low Dose Lixivaptan / CKD1 or CKD2High Dose Lixivaptan / CKD3Low Dose Lixivaptan / CKD3
Ratio of Metabolite AUC(0-14) to Parent Lixivaptan AUC(0-14) (MRAUC[0-14]) of WAY-138758 in ADPKD Patients1.854 ± 64.23.573 ± 83.11.528 ± 53.74.685 ± 39.7
PrimaryNumber of Study Participants With Treatment-emergent Adverse Events

The number of study participants who experience treatment-emergent adverse events during the study will be counted and summarized by dose level.

Time frame:
35 days
Reported as:
Count of participants · Participants
Number of Study Participants With Treatment-emergent Adverse Events
ParticipantsHigh Dose Lixivaptan / CKD1 or CKD2Low Dose Lixivaptan / CKD1 or CKD2High Dose Lixivaptan / CKD3Low Dose Lixivaptan / CKD3
Number of Study Participants With Treatment-emergent Adverse Events2444
PrimaryNumber of Study Participants With Clinically Significant Physical Examination Findings

The number of study participants who experience clinically significant physical examination findings during the study will be counted and summarized by cohort.

Time frame:
35 days
Reported as:
Count of participants · Participants
Number of Study Participants With Clinically Significant Physical Examination Findings
ParticipantsHigh Dose Lixivaptan / CKD1 or CKD2Low Dose Lixivaptan / CKD1 or CKD2High Dose Lixivaptan / CKD3Low Dose Lixivaptan / CKD3
Number of Study Participants With Clinically Significant Physical Examination Findings0001
PrimaryNumber of Study Participants With Clinically Significant Vital Signs

The number of study participants who experience vital signs (systolic blood pressure, diastolic blood pressure, pulse rate, respiratory rate, and body temperature) meeting the predefined markedly abnormal criteria during the study will be counted and summarized by cohort.

Time frame:
35 days
Reported as:
Count of participants · Participants
Number of Study Participants With Clinically Significant Vital Signs
ParticipantsHigh Dose Lixivaptan / CKD1 or CKD2Low Dose Lixivaptan / CKD1 or CKD2High Dose Lixivaptan / CKD3Low Dose Lixivaptan / CKD3
Number of Study Participants With Clinically Significant Vital Signs0000
PrimaryNumber of Study Participants With Clinically Significant Changes in 12-lead Electrocardiograms

The number of study participants who experience 12-lead electrocardiograms meeting the predefined markedly abnormal criteria during the study will be counted and summarized by cohort.

Time frame:
Baseline (Day 1) to Day 8 (8 days)
Reported as:
Count of participants · Participants
Number of Study Participants With Clinically Significant Changes in 12-lead Electrocardiograms
ParticipantsHigh Dose Lixivaptan / CKD1 or CKD2Low Dose Lixivaptan / CKD1 or CKD2High Dose Lixivaptan / CKD3Low Dose Lixivaptan / CKD3
Number of Study Participants With Clinically Significant Changes in 12-lead Electrocardiograms0000
PrimaryNumber of Study Participants With Abnormal Clinical Laboratory Findings (Including Clinical Chemistry, Hematology, and Urinalysis)

The number of study participants who experience clinically meaningful laboratory findings, relating to clinical chemistry, hematology, and urinalysis, during the study will be counted and summarized by cohort.

Time frame:
35 days
Reported as:
Count of participants · Participants
Number of Study Participants With Abnormal Clinical Laboratory Findings (Including Clinical Chemistry, Hematology, and Urinalysis)
ParticipantsHigh Dose Lixivaptan / CKD1 or CKD2Low Dose Lixivaptan / CKD1 or CKD2High Dose Lixivaptan / CKD3Low Dose Lixivaptan / CKD3
Clinical chemistry0000
Hematology0000
Urinalysis0000
PrimaryAquaretic Tolerability of Lixivaptan Measured by a Tolerability Questionnaire Relating to the Symptom Burden of Nocturia, Urgency, and Frequency at Day 7: Questions 1, 2, 6, and 10

The number of study participants who answered "yes" to the following questions at Day 7 will be counted and summarized by dose level: * Could you tolerate taking this dose of study drug for the next 12 months? * Did the study drug make you feel thirsty more often than usual? * Did the study drug make you go to the bathroom (urinate) more often than usual during the night? * Would you be comfortable recommending the study drug to another patient with your kidney condition?

Time frame:
Day 7
Reported as:
Count of participants · Participants
Aquaretic Tolerability of Lixivaptan Measured by a Tolerability Questionnaire Relating to the Symptom Burden of Nocturia, Urgency, and Frequency at Day 7: Questions 1, 2, 6, and 10
ParticipantsHigh Dose Lixivaptan / CKD1 or CKD2Low Dose Lixivaptan / CKD1 or CKD2High Dose Lixivaptan / CKD3Low Dose Lixivaptan / CKD3
Could you tolerate taking this dose of study drug for the next 12 months?7677
Did the study drug make you feel thirsty more often than usual?7684
Did the study drug make you go to the bathroom (urinate) more often than usual during the night?6364
Would you be comfortable recommending the study drug to another patient with your kidney condition?9787
PrimaryAquaretic Tolerability of Lixivaptan Measured by a Tolerability Questionnaire Relating to the Symptom Burden of Nocturia, Urgency, and Frequency at Day 7: Question 3

The number of study participants who answered "not at all" and "slightly" to the following question at Day 7 will be measured: • If the study drug made you feel thirsty more often than usual, were you bothered by it?

Time frame:
Day 7
Reported as:
Count of participants · Participants
Aquaretic Tolerability of Lixivaptan Measured by a Tolerability Questionnaire Relating to the Symptom Burden of Nocturia, Urgency, and Frequency at Day 7: Question 3
ParticipantsHigh Dose Lixivaptan / CKD1 or CKD2Low Dose Lixivaptan / CKD1 or CKD2High Dose Lixivaptan / CKD3Low Dose Lixivaptan / CKD3
Answered "not at all"2242
Answered "slightly"4230
SecondaryChange From Baseline in Spot Urine Osmolality

Changes from baseline in spot urine measurements for samples taken at 0, 1, 2, 4, 6, 9, 10, 11, 12, 14, and 24 hours after the Day 1 and Day 7 doses will be summarized by cohort. The baseline value for each time point after first administration of study drug is the value observed at the corresponding time point on Day -1 (or Day 1 for the AM predose assessment only).

Time frame:
At time of dose, and at 1, 2, 4, 6, 9, 10, 11, 12, 14, and 24 hours after the Day 1 and Day 7 doses
Reported as:
Mean · mOsm/kg
Change From Baseline in Spot Urine Osmolality
mOsm/kgHigh Dose Lixivaptan / CKD1 or CKD2Low Dose Lixivaptan / CKD1 or CKD2High Dose Lixivaptan / CKD3Low Dose Lixivaptan / CKD3
Time of Day 1 dose-27.7 ± 253.8-28.4 ± 183.5-52.3 ± 56.1-167.3 ± 63.4
1 hour post Day 1 dose-101.9 ± 150.26.1 ± 60.1-44.2 ± 68.7-114.7 ± 95.0
2 hours post Day 1 dose-10.1 ± 25.1-41.6 ± 64.3-86.0 ± 147.1-68.1 ± 69.8
4 hours post Day 1 dose-64.9 ± 124.3-43.7 ± 36.1-26.6 ± 16.6-48.7 ± 77.5
6 hours post Day 1 dose-68.8 ± 80.5-6.0 ± 73.5-72.9 ± 89.6-40.7 ± 87.0
9 hours post Day 1 dose-62.8 ± 85.3-46.6 ± 240.7-84.6 ± 78.6-54.1 ± 93.2
10 hours post Day 1 dose-7.7 ± 99.4-8.4 ± 114.7-45.0 ± 73.2-5.7 ± 127.9
11 hours post Day 1 dose-35.6 ± 60.9-41.1 ± 84.5-70.3 ± 58.3-55.0 ± 113.8
12 hours post Day 1 dose-49.6 ± 48.1-61.9 ± 88.1-112.1 ± 144.6-76.6 ± 90.3
14 hours post Day 1 dose-139.0 ± 248.4-60.9 ± 124.3-99.7 ± 82.1-67.3 ± 63.7
24 hours post Day 1 dose-115.2 ± 118.820.4 ± 252.6-110.4 ± 111.7-37.9 ± 104.5
Time of Day 7 dose-173.1 ± 306.8-23.7 ± 296.2-150.7 ± 91.2-97.4 ± 176.7
1 hour post Day 7 dose-101.1 ± 169.1-22.6 ± 63.4-114.7 ± 173.3-100.7 ± 135.0
2 hours post Day 7 dose-2.9 ± 20.6-13.0 ± 69.7-88.1 ± 158.9-63.1 ± 86.7
4 hours post Day 7 dose-78.3 ± 185.0-5.3 ± 98.8-13.4 ± 33.7-31.1 ± 77.4
6 hours post Day 7 dose-86.4 ± 122.316.6 ± 167.4-57.6 ± 96.7-6.9 ± 122.6
9 hours post Day 7 dose-100.4 ± 152.3-80.6 ± 211.5-44.3 ± 71.7-36.3 ± 137.6
10 hours post Day 7 dose-54.9 ± 238.4-8.6 ± 189.4-7.0 ± 72.130.4 ± 176.4
11 hours post Day 7 dose-37.0 ± 49.1-51.3 ± 106.2-63.0 ± 48.7-48.7 ± 118.8
12 hours post Day 7 dose-52.3 ± 42.6-67.0 ± 55.5-128.7 ± 141.0-80.3 ± 97.3
14 hours post Day 7 dose-141.4 ± 271.8-25.0 ± 21.5-83.0 ± 100.9-47.3 ± 51.2
24 hours post Day 7 dose-219.8 ± 202.5104.3 ± 257.0-199.4 ± 135.535.4 ± 66.4
SecondaryChange From Baseline in 24-hour Urine Output

Changes from baseline in 24-hour urine output for samples taken on Day 1 and Day 7 will be summarized by cohort. The baseline value was the last value observed prior to first administration of study drug on Day -1.

Time frame:
Baseline (Day -1), Day 1, and Day 7
Reported as:
Mean · mL
Change From Baseline in 24-hour Urine Output
mLHigh Dose Lixivaptan / CKD1 or CKD2Low Dose Lixivaptan / CKD1 or CKD2High Dose Lixivaptan / CKD3Low Dose Lixivaptan / CKD3
Day 12175.3 ± 2629.21794.4 ± 1697.03041.1 ± 889.21329.9 ± 916.7
Day 71995.6 ± 2294.01744.6 ± 1658.71843.6 ± 1027.7458.4 ± 2233.7
SecondaryChange From Baseline of the Estimated Glomerular Filtration Rate (eGFR)

Changes from baseline of eGFR derived from the serum creatinine concentrations for samples taken at Day 1 (postdose), Day 2, Day 7, Day 8, and Day 35 will summarized by cohort

Time frame:
Baseline (Day 1) to end of study (35 days)
Reported as:
Mean · mL/min/1.73 m²
Change From Baseline of the Estimated Glomerular Filtration Rate (eGFR)
mL/min/1.73 m²High Dose Lixivaptan / CKD1 or CKD2Low Dose Lixivaptan / CKD1 or CKD2High Dose Lixivaptan / CKD3Low Dose Lixivaptan / CKD3
Day 2-7.4 ± 7.2-3.9 ± 8.8-2.1 ± 4.3-1.9 ± 3.1
Day 7-11.9 ± 10.0-3.0 ± 3.7-5.3 ± 3.7-3.4 ± 4.1
Day 8-9.1 ± 12.5-2.9 ± 3.3-5.5 ± 4.8-3.4 ± 3.5
Day 35-0.9 ± 8.40.0 ± 8.32.1 ± 4.3-3.7 ± 3.2
SecondaryChange From Baseline in Total Kidney Volume

Changes from baseline (Day -1) in total kidney volume, measured by abdominal MRI on Day 7 and Day 35, will be summarized by cohort.

Time frame:
Baseline (Day -1) to end of study (36 days)
Reported as:
Mean · mL
Change From Baseline in Total Kidney Volume
mLHigh Dose Lixivaptan / CKD1 or CKD2Low Dose Lixivaptan / CKD1 or CKD2High Dose Lixivaptan / CKD3Low Dose Lixivaptan / CKD3
Day 7-8.75 ± 42.474.97 ± 30.84-66.19 ± 141.4723.58 ± 33.69
Day 35-26.63 ± 77.84-3.78 ± 26.06-4.29 ± 81.2728.88 ± 68.16
SecondaryChange From Baseline in Liver Volume

Changes from baseline (Day -1) in liver volume, measured by abdominal MRI on Day 7 and Day 35, will be summarized by cohort.

Time frame:
Baseline (Day -1) to end of study (36 days)
Reported as:
Mean · mL
Change From Baseline in Liver Volume
mLHigh Dose Lixivaptan / CKD1 or CKD2Low Dose Lixivaptan / CKD1 or CKD2High Dose Lixivaptan / CKD3Low Dose Lixivaptan / CKD3
Day 753.04 ± 125.5143.02 ± 92.15104.01 ± 131.21-0.03 ± 40.98
Day 35-6.70 ± 86.7428.66 ± 99.7753.51 ± 82.52-11.00 ± 109.04
SecondaryChange From Baseline of Plasma Copeptin

Changes from baseline (Day -1) in plasma copeptin, a marker for circulating vasopressin, at Day 2, Day 7, and Day 35 will be summarized by cohort.

Time frame:
Baseline (Day -1) to end of study (36 days)
Reported as:
Mean · pmol/L
Change From Baseline of Plasma Copeptin
pmol/LHigh Dose Lixivaptan / CKD1 or CKD2Low Dose Lixivaptan / CKD1 or CKD2High Dose Lixivaptan / CKD3Low Dose Lixivaptan / CKD3
Day 25.072 ± 4.7981.986 ± 3.28612.655 ± 15.527-1.986 ± 10.893
Day 79.745 ± 4.9103.016 ± 3.39217.906 ± 10.32134.519 ± 89.262
Day 352.111 ± 2.8292.786 ± 5.498-0.943 ± 8.435-3.337 ± 13.993
SecondaryChange From Baseline in Serum Creatinine

Changes from baseline in serum creatinine for samples taken at Day 2, Day 7, Day 8, and Day 35 will be summarized by cohort.

Time frame:
Baseline (Day 1, predose) to end of study (35 days)
Reported as:
Mean · umol/L
Change From Baseline in Serum Creatinine
umol/LHigh Dose Lixivaptan / CKD1 or CKD2Low Dose Lixivaptan / CKD1 or CKD2High Dose Lixivaptan / CKD3Low Dose Lixivaptan / CKD3
Day 26.7778 ± 6.139584.1429 ± 7.174694.7500 ± 13.498684.5714 ± 5.62308
Day 712.6667 ± 9.733962.7143 ± 3.4503319.2500 ± 16.884066.5714 ± 8.86674
Day 811.1111 ± 11.941992.2857 ± 3.1471817.6250 ± 12.816707.5714 ± 7.48013
Day 352.4004 ± 6.876570.8571 ± 6.59365-8.5000 ± 14.040767.5714 ± 5.12696
SecondaryChange From Baseline in Blood Urea Nitrogen (BUN)

Changes from baseline in BUN for samples taken at Day 2, Day 7, Day 8, and Day 35 will be summarized by cohort.

Time frame:
Baseline (Day 1, predose) to end of study (35 days)
Reported as:
Mean · mmol/L
Change From Baseline in Blood Urea Nitrogen (BUN)
mmol/LHigh Dose Lixivaptan / CKD1 or CKD2Low Dose Lixivaptan / CKD1 or CKD2High Dose Lixivaptan / CKD3Low Dose Lixivaptan / CKD3
Day 20.0644 ± 0.82257-0.1743 ± 0.43535-0.1563 ± 1.15821-0.1300 ± 1.16973
Day 7-0.2000 ± 1.17573-0.0614 ± 1.29029-0.7488 ± 1.662070.2014 ± 1.59194
Day 8-0.5711 ± 1.14740-0.1043 ± 1.22296-0.2338 ± 1.43097-0.1229 ± 0.99856
Day 350.0008 ± 1.61696-0.1886 ± 1.36772-0.2338 ± 2.087290.2286 ± 1.94233
Other pre-specifiedVolume of Distribution Over 24 Hours After Extravascular Dosing (VZ/F24H) of Lixivaptan in ADPKD Patients

The pharmacokinetic parameter VZ/F24H for lixivaptan, calculated as CL/F24H divided by Day 7 PM λZ, will be summarized by cohort. VZ/F24H was not specified in the statistical analysis plan and was calculated for the combined 24-hour period including AM and PM dosing intervals on Day 7. This parameter replaces VZ/F initially planned for the Day 7 AM dose.

Time frame:
Day 7 (am)
Reported as:
Geometric mean · L
Volume of Distribution Over 24 Hours After Extravascular Dosing (VZ/F24H) of Lixivaptan in ADPKD Patients
LHigh Dose Lixivaptan / CKD1 or CKD2Low Dose Lixivaptan / CKD1 or CKD2High Dose Lixivaptan / CKD3Low Dose Lixivaptan / CKD3
Volume of Distribution Over 24 Hours After Extravascular Dosing (VZ/F24H) of Lixivaptan in ADPKD Patients547.4 ± 57.4546.0 ± 48.2515.1 ± 50.7731.8 ± 38.4
PrimaryAquaretic Tolerability of Lixivaptan Measured by a Tolerability Questionnaire Relating to the Symptom Burden of Nocturia, Urgency, and Frequency at Day 7: Question 7

The number of study participants who answered "not at all" and "slightly" to the following question at Day 7 will be measured: • If the study drug made you go to the bathroom (urinate) more often than usual during the night, did it bother you?

Time frame:
Day 7
Reported as:
Count of participants · Participants
Aquaretic Tolerability of Lixivaptan Measured by a Tolerability Questionnaire Relating to the Symptom Burden of Nocturia, Urgency, and Frequency at Day 7: Question 7
ParticipantsHigh Dose Lixivaptan / CKD1 or CKD2Low Dose Lixivaptan / CKD1 or CKD2High Dose Lixivaptan / CKD3Low Dose Lixivaptan / CKD3
Answered "not at all"2121
Answered "slightly"3011

Adverse events

Collected over 35 days. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
High Dose Lixivaptan / CKD1 or CKD20/9 (0%)0/9 (0%)2/9 (22.2%)
Low Dose Lixivaptan / CKD1 or CKD20/7 (0%)0/7 (0%)4/7 (57.1%)
High Dose Lixivaptan / CKD30/8 (0%)0/8 (0%)4/8 (50%)
Low Dose Lixivaptan / CKD30/7 (0%)0/7 (0%)4/7 (57.1%)
Most frequent other events
Showing 10 of 23
Most frequent other events
EventHigh Dose Lixivaptan / CKD1 or CKD2Low Dose Lixivaptan / CKD1 or CKD2High Dose Lixivaptan / CKD3Low Dose Lixivaptan / CKD3
HeadacheNervous system disorders0/93/70/80/7
Dry mouthGastrointestinal disorders0/92/71/80/7
NauseaGastrointestinal disorders1/90/70/82/7
DiarrhoeaGastrointestinal disorders0/90/70/82/7
SyncopeNervous system disorders0/90/70/82/7
DyspepsiaGastrointestinal disorders0/91/70/80/7
VomitingGastrointestinal disorders0/90/70/81/7
ThirstGeneral disorders0/91/71/80/7
ImpetigoInfections and infestations0/91/70/80/7
Back painMusculoskeletal and connective tissue disorders0/90/70/81/7

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)High Dose Lixivaptan / CKD1 or CKD2Low Dose Lixivaptan / CKD1 or CKD2High Dose Lixivaptan / CKD3Low Dose Lixivaptan / CKD3Total
<=18 years00000
Between 18 and 65 years978731
>=65 years00000
Age, Continuous
Age, Continuous(years)High Dose Lixivaptan / CKD1 or CKD2Low Dose Lixivaptan / CKD1 or CKD2High Dose Lixivaptan / CKD3Low Dose Lixivaptan / CKD3Total
Mean40.1 ± 16.9934.9 ± 10.8554.0 ± 9.0751.6 ± 10.5445.1 ± 14.31
Sex: Female, Male
Sex: Female, Male(Participants)High Dose Lixivaptan / CKD1 or CKD2Low Dose Lixivaptan / CKD1 or CKD2High Dose Lixivaptan / CKD3Low Dose Lixivaptan / CKD3Total
Female554418
Male424313
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)High Dose Lixivaptan / CKD1 or CKD2Low Dose Lixivaptan / CKD1 or CKD2High Dose Lixivaptan / CKD3Low Dose Lixivaptan / CKD3Total
Hispanic or Latino02428
Not Hispanic or Latino954523
Unknown or Not Reported00000
Race (NIH/OMB)
Race (NIH/OMB)(Participants)High Dose Lixivaptan / CKD1 or CKD2Low Dose Lixivaptan / CKD1 or CKD2High Dose Lixivaptan / CKD3Low Dose Lixivaptan / CKD3Total
American Indian or Alaska Native00000
Asian00000
Native Hawaiian or Other Pacific Islander00000
Black or African American00000
White978731
More than one race00000
Unknown or Not Reported00000
08

Study locations

13 sites
  • Palladio Biosciences Clinical Site
    Los Angeles, California 90022, United States
  • Palladio Biosciences Clinical Site
    Jacksonville, Florida 32216, United States
  • Palladio Biosciences Clinical Site
    Miami, Florida 33155, United States
  • Palladio Biosciences Clinical Site
    Miami, Florida 33165, United States
  • Palladio Biosciences Clinical Site
    Palmetto Bay, Florida 33157, United States
  • Palladio Biosciences Clinical Site
    Tampa, Florida 33612, United States
  • Palladio Biosciences Clinical Site
    Baltimore, Maryland 21201, United States
  • Palladio Biosciences Clinical Site
    Rochester, Minnesota 55902, United States
  • Palladio Biosciences Clinical Site
    Kansas City, Missouri 64111, United States
  • Palladio Biosciences Clinical Site
    Laurelton, New York 11413, United States
  • Palladio Biosciences Clinical Site
    Indiana, Pennsylvania 15701, United States
  • Palladio Biosciences Clinical Site
    Nashville, Tennessee 66160, United States
  • Palladio Biosciences Clinical Site
    Salt Lake City, Utah 84115, United States
09

References and documents

Publications

  • Shusterman NH, Hogan LC, Pellegrini L: Effect of lixivaptan on pharmacokinetic (PK) and pharmacodynamic (PD) end points in patients with autosomal dominant polycystic kidney disease (ADPKD) in the ELiSA Study (PA-102) [Abstract]. J Am Soc Nephrol 30, 2019 (abstract supplement issue): page 339.

Study documents

PDFs hosted by the registry, ClinicalTrials.gov.

Individual participant data

Plan to share: No

10

Timeline

Tracking since Sep 25, 2026
ElapsedEstimatedEstimated, not yet reachedSimilar studies: half by the dot; the band is the middle halfHalf of similar studies reached it by the dot; the band is the middle half, from a quarter to three quarters

Ran from Sep 2018 to primary completion in Dec 2019, 14 months.

Results were first posted in Dec 2022, 3 years after primary completion. A results delay was requested in Nov 2020.

Of 17 phase 2 interventional studies under Polycystic Kidney, Autosomal Dominant, half reached primary completion within 39 months of starting (the median), counting those still running; a quarter within 18 and three quarters within 53. This study's 14 months is below that.

How these figures are worked out, and which studies are left out of them.

Registered
Mar 16, 2018
First posted
Apr 4, 2018
StartActual
Sep 14, 2018
Primary completionActual
Dec 2, 2019
CompletionActual
Feb 11, 2020
Results delay requested
Nov 24, 2020
Results first posted
Dec 5, 2022
Last update
Dec 5, 2022
What these dates mean
Start.
When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.
When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.
When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.
Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.
No changes since tracking began. The registry record was last updated on Dec 5, 2022, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT03487913
Lead sponsor
Palladio Biosciences
Responsible party
Sponsor
First posted
Apr 4, 2018
Start date
Sep 14, 2018
Primary completion
Dec 2, 2019
Completion
Feb 11, 2020
Results posted
Dec 5, 2022
Last update
Dec 5, 2022

Study contacts

Vicente E Torres, MD, PhD
principal investigator · Mayo Clinic

Oversight

FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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This study is completed, as verified in Nov 2022. You cannot join it, but the record below documents what was studied.

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Studies of the drug tested here: Lixivaptan

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