Back to resultsThe ELiSA Study - Evaluation of Lixivaptan in Subjects With Autosomal Dominant Polycystic Kidney Disease
Primary Purpose
Autosomal Dominant Polycystic Kidney Disease
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Lixivaptan
Sponsored by
About this trial
This is an interventional treatment trial for Autosomal Dominant Polycystic Kidney Disease
Eligibility Criteria
Inclusion Criteria:
- Male or female, between 18 and 65 years of age at the time of screening
- Estimated glomerular filtration rate (eGFR) ≥ 30 mL/min/1.73 m2 with eGFR calculated by the CKD EPI equation
- Diagnosed with ADPKD by modified Ravine criteria
- Considered by Investigator to be in good health relative to underlying CKD status and clinically stable with respect to underlying CKD
Exclusion Criteria:
- Known sensitivity or idiosyncratic reaction to lixivaptan, its related compounds such as benzazepines (e.g., tolvaptan, conivaptan, benazepril, fenoldopam, or mirtazapine), or any compound listed as being present in the study formulation
- Women who are pregnant or breast feeding
- Subjects have taken tolvaptan, oral or intravenous antibiotics, or any investigational drug or used an investigational device within 30 days or 5 half-lives, whichever is longer, prior to first study dose
- Subject has a transplanted kidney, or absence of a kidney
- Subjects with clinically significant incontinence, overactive bladder, or urinary retention (e.g., benign prostatic hyperplasia)
- Subjects with clinically significant liver disease, or clinically significant liver function abnormalities or serology other than that expected for ADPKD with cystic liver disease at baseline
- Subjects with any clinically significant concomitant disease or condition other than ADPKD (including treatment for such conditions) that, in the opinion of the Investigator, could either interfere with the study drug or pose an unacceptable risk to the subject
Sites / Locations
- Palladio Biosciences Clinical Site
- Palladio Biosciences Clinical Site
- Palladio Biosciences Clinical Site
- Palladio Biosciences Clinical Site
- Palladio Biosciences Clinical Site
- Palladio Biosciences Clinical Site
- Palladio Biosciences Clinical Site
- Palladio Biosciences Clinical Site
- Palladio Biosciences Clinical Site
- Palladio Biosciences Clinical Site
- Palladio Biosciences Clinical Site
- Palladio Biosciences Clinical Site
- Palladio Biosciences Clinical Site
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Experimental
Arm Label
High dose lixivaptan / CKD1 or CKD2
Low dose lixivaptan / CKD1 or CKD2
High dose lixivaptan / CKD3
Low dose lixivaptan / CKD3
Arm Description
Oral high dose lixivaptan in participants with CKD1 or CKD2
Oral low dose lixivaptan in participants with CKD1 or CKD2
Oral high dose lixivaptan in participants with CKD3
Oral low dose lixivaptan in participants with CKD3
Outcomes
Primary Outcome Measures
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.
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.
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.
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 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 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 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 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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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?
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?
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?
Secondary Outcome Measures
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).
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.
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
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.
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.
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.
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.
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03487913
Brief Title
The ELiSA Study - Evaluation of Lixivaptan in Subjects With Autosomal Dominant Polycystic Kidney Disease
Official Title
A Phase 2, Open-Label, Multi-Center Study to Evaluate the Safety, Pharmacokinetics and Pharmacodynamics of Lixivaptan in Subjects With Autosomal Dominant Polycystic Kidney Disease
Study Type
Interventional
2. Study Status
Record Verification Date
November 2022
Overall Recruitment Status
Completed
Study Start Date
September 14, 2018 (Actual)
Primary Completion Date
December 2, 2019 (Actual)
Study Completion Date
February 11, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Palladio Biosciences
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
Brief 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.
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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Autosomal Dominant Polycystic Kidney Disease
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
31 (Actual)
8. Arms, Groups, and Interventions
Arm Title
High dose lixivaptan / CKD1 or CKD2
Arm Type
Experimental
Arm Description
Oral high dose lixivaptan in participants with CKD1 or CKD2
Arm Title
Low dose lixivaptan / CKD1 or CKD2
Arm Type
Experimental
Arm Description
Oral low dose lixivaptan in participants with CKD1 or CKD2
Arm Title
High dose lixivaptan / CKD3
Arm Type
Experimental
Arm Description
Oral high dose lixivaptan in participants with CKD3
Arm Title
Low dose lixivaptan / CKD3
Arm Type
Experimental
Arm Description
Oral low dose lixivaptan in participants with CKD3
Intervention Type
Drug
Intervention Name(s)
Lixivaptan
Other Intervention Name(s)
VPA-985
Intervention Description
Oral vasopressin V2 receptor antagonist
Primary Outcome Measure Information:
Title
Maximum Observed Plasma Concentration (Cmax) of Lixivaptan in ADPKD Patients
Description
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)
Title
Maximum Observed Plasma Concentration (Cmax) of WAY-141624 in ADPKD Patients
Description
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)
Title
Maximum Observed Plasma Concentration (Cmax) of WAY-138451 in ADPKD Patients
Description
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)
Title
Maximum Observed Plasma Concentration (Cmax) of WAY-138758 in ADPKD Patients
Description
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)
Title
Time to Reach Maximum Plasma Concentration (Tmax) of Lixivaptan in ADPKD Patients
Description
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)
Title
Time to Reach Maximum Plasma Concentration (Tmax) of WAY-141624 in ADPKD Patients
Description
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)
Title
Time to Reach Maximum Plasma Concentration (Tmax) of WAY-138451 in ADPKD Patients
Description
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)
Title
Time to Reach Maximum Plasma Concentration (Tmax) of WAY-138758 in ADPKD Patients
Description
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)
Title
Area Under the Concentration-time Curve From Time 0 Until the Last Quantifiable Concentration (AUC[0-last]) of Lixivaptan in ADPKD Patients
Description
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)
Title
Area Under the Concentration-time Curve From Time 0 Until the Last Quantifiable Concentration (AUC[0-last]) of WAY-141624 in ADPKD Patients
Description
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)
Title
Area Under the Concentration-time Curve From Time 0 Until the Last Quantifiable Concentration (AUC[0-last]) of WAY-138451 in ADPKD Patients
Description
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)
Title
Area Under the Concentration-time Curve From Time 0 Until the Last Quantifiable Concentration (AUC[0-last]) of WAY-138758 in ADPKD Patients
Description
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)
Title
Area Under the Concentration-time Curve From Time 0 Extrapolated to Infinity (AUC[0-inf]) of Lixivaptan in ADPKD Patients
Description
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)
Title
Area Under the Concentration-time Curve From Time 0 Extrapolated to Infinity (AUC[0-inf]) of WAY-141624 in ADPKD Patients
Description
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)
Title
Area Under the Concentration-time Curve From Time 0 Extrapolated to Infinity (AUC[0-inf]) of WAY-138451 in ADPKD Patients
Description
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)
Title
Area Under the Concentration-time Curve From Time 0 Extrapolated to Infinity (AUC[0-inf]) of WAY-138758 in ADPKD Patients
Description
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)
Title
Terminal Elimination Phase Half-life (t1/2) of Lixivaptan in ADPKD Patients
Description
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)
Title
Terminal Elimination Phase Half-life (t1/2) of WAY-141624 in ADPKD Patients
Description
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)
Title
Terminal Elimination Phase Half-life (t1/2) of WAY-138451 in ADPKD Patients
Description
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)
Title
Terminal Elimination Phase Half-life (t1/2) of WAY-138758 in ADPKD Patients
Description
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)
Title
Apparent Terminal Elimination Rate Constant (λZ) of Lixivaptan in ADPKD Patients
Description
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)
Title
Apparent Terminal Elimination Rate Constant (λZ) of WAY-141624 in ADPKD Patients
Description
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)
Title
Apparent Terminal Elimination Rate Constant (λZ) of WAY-138451 in ADPKD Patients
Description
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)
Title
Apparent Terminal Elimination Rate Constant (λZ) of WAY-138758 in ADPKD Patients
Description
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)
Title
Apparent Systemic Clearance After Extravascular Dosing (CL/F) of Lixivaptan in ADPKD Patients
Description
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)
Title
Volume of Distribution After Extravascular Dosing (VZ/F) of Lixivaptan in ADPKD Patients
Description
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)
Title
Accumulation Ratio for Cmax (RCmax) of Lixivaptan in ADPKD Patients
Description
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)
Title
Accumulation Ratio for AUC(0-last) (RAUC[0-last]) of Lixivaptan in ADPKD Patients
Description
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)
Title
Area Under the Concentration-time Curve From Time 0 Until 14 Hours Postdose (AUC[0-14]) of Lixivaptan in ADPKD Patients
Description
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)
Title
Area Under the Concentration-time Curve From Time 0 Until 14 Hours Postdose (AUC[0-14]) of WAY-141624 in ADPKD Patients
Description
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)
Title
Area Under the Concentration-time Curve From Time 0 Until 14 Hours Postdose (AUC[0-14]) of WAY-138451 in ADPKD Patients
Description
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)
Title
Area Under the Concentration-time Curve From Time 0 Until 14 Hours Postdose (AUC[0-14]) of WAY-138758 in ADPKD Patients
Description
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)
Title
Ratio of WAY-141624 Cmax to Parent Lixivaptan Cmax (MRCmax) in ADPKD Patients
Description
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)
Title
Ratio of WAY-138451 Cmax to Parent Lixivaptan Cmax (MRCmax) in ADPKD Patients
Description
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)
Title
Ratio of WAY-138758 Cmax to Parent Lixivaptan Cmax (MRCmax) in ADPKD Patients
Description
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)
Title
Ratio of Metabolite AUC(0-14) to Parent Lixivaptan AUC(0-14) (MRAUC[0-14]) of WAY-141624 in ADPKD Patients
Description
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)
Title
Ratio of Metabolite AUC(0-14) to Parent Lixivaptan AUC(0-14) (MRAUC[0-14]) of WAY-138451 in ADPKD Patients
Description
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)
Title
Ratio of Metabolite AUC(0-14) to Parent Lixivaptan AUC(0-14) (MRAUC[0-14]) of WAY-138758 in ADPKD Patients
Description
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)
Title
Number of Study Participants With Treatment-emergent Adverse Events
Description
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
Title
Number of Study Participants With Clinically Significant Physical Examination Findings
Description
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
Title
Number of Study Participants With Clinically Significant Vital Signs
Description
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
Title
Number of Study Participants With Clinically Significant Changes in 12-lead Electrocardiograms
Description
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)
Title
Number of Study Participants With Abnormal Clinical Laboratory Findings (Including Clinical Chemistry, Hematology, and Urinalysis)
Description
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
Title
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
Description
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
Title
Aquaretic Tolerability of Lixivaptan Measured by a Tolerability Questionnaire Relating to the Symptom Burden of Nocturia, Urgency, and Frequency at Day 7: Question 3
Description
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
Title
Aquaretic Tolerability of Lixivaptan Measured by a Tolerability Questionnaire Relating to the Symptom Burden of Nocturia, Urgency, and Frequency at Day 7: Question 7
Description
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 Outcome Measure Information:
Title
Change From Baseline in Spot Urine Osmolality
Description
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
Title
Change From Baseline in 24-hour Urine Output
Description
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
Title
Change From Baseline of the Estimated Glomerular Filtration Rate (eGFR)
Description
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)
Title
Change From Baseline in Total Kidney Volume
Description
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)
Title
Change From Baseline in Liver Volume
Description
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)
Title
Change From Baseline of Plasma Copeptin
Description
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)
Title
Change From Baseline in Serum Creatinine
Description
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)
Title
Change From Baseline in Blood Urea Nitrogen (BUN)
Description
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 Pre-specified Outcome Measures:
Title
Volume of Distribution Over 24 Hours After Extravascular Dosing (VZ/F24H) of Lixivaptan in ADPKD Patients
Description
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)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Male or female, between 18 and 65 years of age at the time of screening
Estimated glomerular filtration rate (eGFR) ≥ 30 mL/min/1.73 m2 with eGFR calculated by the CKD EPI equation
Diagnosed with ADPKD by modified Ravine criteria
Considered by Investigator to be in good health relative to underlying CKD status and clinically stable with respect to underlying CKD
Exclusion Criteria:
Known sensitivity or idiosyncratic reaction to lixivaptan, its related compounds such as benzazepines (e.g., tolvaptan, conivaptan, benazepril, fenoldopam, or mirtazapine), or any compound listed as being present in the study formulation
Women who are pregnant or breast feeding
Subjects have taken tolvaptan, oral or intravenous antibiotics, or any investigational drug or used an investigational device within 30 days or 5 half-lives, whichever is longer, prior to first study dose
Subject has a transplanted kidney, or absence of a kidney
Subjects with clinically significant incontinence, overactive bladder, or urinary retention (e.g., benign prostatic hyperplasia)
Subjects with clinically significant liver disease, or clinically significant liver function abnormalities or serology other than that expected for ADPKD with cystic liver disease at baseline
Subjects with any clinically significant concomitant disease or condition other than ADPKD (including treatment for such conditions) that, in the opinion of the Investigator, could either interfere with the study drug or pose an unacceptable risk to the subject
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Vicente E Torres, MD, PhD
Organizational Affiliation
Mayo Clinic
Official's Role
Principal Investigator
Facility Information:
Facility Name
Palladio Biosciences Clinical Site
City
Los Angeles
State/Province
California
ZIP/Postal Code
90022
Country
United States
Facility Name
Palladio Biosciences Clinical Site
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32216
Country
United States
Facility Name
Palladio Biosciences Clinical Site
City
Miami
State/Province
Florida
ZIP/Postal Code
33155
Country
United States
Facility Name
Palladio Biosciences Clinical Site
City
Miami
State/Province
Florida
ZIP/Postal Code
33165
Country
United States
Facility Name
Palladio Biosciences Clinical Site
City
Palmetto Bay
State/Province
Florida
ZIP/Postal Code
33157
Country
United States
Facility Name
Palladio Biosciences Clinical Site
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States
Facility Name
Palladio Biosciences Clinical Site
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21201
Country
United States
Facility Name
Palladio Biosciences Clinical Site
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55902
Country
United States
Facility Name
Palladio Biosciences Clinical Site
City
Kansas City
State/Province
Missouri
ZIP/Postal Code
64111
Country
United States
Facility Name
Palladio Biosciences Clinical Site
City
Laurelton
State/Province
New York
ZIP/Postal Code
11413
Country
United States
Facility Name
Palladio Biosciences Clinical Site
City
Indiana
State/Province
Pennsylvania
ZIP/Postal Code
15701
Country
United States
Facility Name
Palladio Biosciences Clinical Site
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
66160
Country
United States
Facility Name
Palladio Biosciences Clinical Site
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84115
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
Citation
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.
Results Reference
result
Learn more about this trial
The ELiSA Study - Evaluation of Lixivaptan in Subjects With Autosomal Dominant Polycystic Kidney Disease
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