Autosomal Dominant Polycystic Kidney DiseasePhase 2NCT03487913

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

A Phase 2 study testing Lixivaptan in people with Autosomal Dominant Polycystic Kidney Disease, run by Palladio Biosciences at 13 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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 more about this study

Who is it for?: Ages 18 to 65 years
Conditions the study is for: Autosomal Dominant Polycystic Kidney Disease
What is being tested?: Lixivaptan
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 31 participants
Where: 13 sitesUnited States
Study dates: 14 Sep 2018to 11 Feb 2020
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 65 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

Who cannot join

Known sensitivity or idiosyncratic reaction to lixivaptan, its related compounds such as benzazepines (e.g., tolvaptan, conivaptan, benazepril, fenoldopam, or mirtazapine), or any compound listed as being present in the study formulation
Women who are pregnant or breast feeding
Subjects have taken tolvaptan, oral or intravenous antibiotics, or any investigational drug or used an investigational device within 30 days or 5 half-lives, whichever is longer, prior to first study dose
Subject has a transplanted kidney, or absence of a kidney
Subjects with clinically significant incontinence, overactive bladder, or urinary retention (e.g., benign prostatic hyperplasia)
Subjects with clinically significant liver disease, or clinically significant liver function abnormalities or serology other than that expected for ADPKD with cystic liver disease at baseline
Subjects with any clinically significant concomitant disease or condition other than ADPKD (including treatment for such conditions) that, in the opinion of the Investigator, could either interfere with the study drug or pose an unacceptable risk to the subject

Trial locations and contacts

13 sites in 1 country.

City, postcode or hospital

13 sites in 1 country

United States13 sites

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

Other trials in United States

About this study

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

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).

Conditions: Autosomal Dominant Polycystic Kidney Disease
Being tested: Lixivaptan
Medical subject headings: Polycystic Kidney, Autosomal Dominant

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

LixivaptanDrug
Also called VPA-985
Oral vasopressin V2 receptor antagonist

Study groups in NCT03487913
Study group	Role	What they receive
High dose lixivaptan / CKD1 or CKD2	Experimental	Oral high dose lixivaptan in participants with CKD1 or CKD2 Receives: Drug: Lixivaptan
Low dose lixivaptan / CKD1 or CKD2	Experimental	Oral low dose lixivaptan in participants with CKD1 or CKD2 Receives: Drug: Lixivaptan
High dose lixivaptan / CKD3	Experimental	Oral high dose lixivaptan in participants with CKD3 Receives: Drug: Lixivaptan
Low dose lixivaptan / CKD3	Experimental	Oral low dose lixivaptan in participants with CKD3 Receives: Drug: Lixivaptan

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: Day 1 (am and pm) and Day 7 (am and pm)
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.
Measured: Day 1 (am and pm) and Day 7 (am and pm)
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.
Measured: Day 1 (am and pm) and Day 7 (am and pm)
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.
Measured: Day 1 (am and pm) and Day 7 (am and pm)
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.
Measured: Day 1 (am and pm) and Day 7 (am and pm)
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.
Measured: Day 1 (am and pm) and Day 7 (am and pm)
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.
Measured: Day 1 (am and pm) and Day 7 (am and pm)
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.
Measured: Day 1 (am and pm) and Day 7 (am and pm)
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.
Measured: Day 1 (am and pm) and Day 7 (am and pm)
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.
Measured: Day 1 (am and pm) and Day 7 (am and pm)
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.
Measured: Day 1 (am and pm) and Day 7 (am and pm)
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.
Measured: Day 1 (am and pm) and Day 7 (am and pm)
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.
Measured: Day 1 (am)
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.
Measured: Day 1 (am)
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.
Measured: Day 1 (am)
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.
Measured: Day 1 (am)
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.
Measured: Day 1 (am) and Day 7 (pm)
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.
Measured: Day 1 (am) and Day 7 (pm)
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.
Measured: Day 1 (am) and Day 7 (pm)
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.
Measured: Day 1 (am) and Day 7 (pm)
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.
Measured: Day 1 (am) and Day 7 (pm)
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.
Measured: Day 1 (am) and Day 7 (pm)
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.
Measured: Day 1 (am) and Day 7 (pm)
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.
Measured: Day 1 (am) and Day 7 (pm)
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.
Measured: Day 1 (am) and Day 7 (am)
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.
Measured: Day 1 (am) and Day 7 (am)
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.
Measured: Day 7 (am)
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.
Measured: Day 7 (am)
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.
Measured: Day 7 (pm)
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.
Measured: Day 7 (pm)
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.
Measured: Day 7 (pm)
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.
Measured: Day 7 (pm)
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.
Measured: Day 7 (pm)
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.
Measured: Day 7 (pm)
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.
Measured: Day 7 (pm)
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.
Measured: Day 7 (pm)
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.
Measured: Day 7 (pm)
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.
Measured: Day 7 (pm)
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.
Measured: 35 days
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.
Measured: 35 days
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.
Measured: 35 days
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.
Measured: Baseline (Day 1) to Day 8 (8 days)
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.
Measured: 35 days
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?
Measured: Day 7
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?
Measured: Day 7
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?
Measured: Day 7

Secondary outcomes (8)

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).
Measured: 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
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.
Measured: Baseline (Day -1), Day 1, and Day 7
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
Measured: Baseline (Day 1) to end of study (35 days)
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.
Measured: Baseline (Day -1) to end of study (36 days)
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.
Measured: Baseline (Day -1) to end of study (36 days)
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.
Measured: Baseline (Day -1) to end of study (36 days)
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.
Measured: Baseline (Day 1, predose) to end of study (35 days)
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.
Measured: Baseline (Day 1, predose) to end of study (35 days)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

14 Sep 201811 Feb 2020

First posted4 Apr 2018
Study start14 Sep 2018
Primary completion2 Dec 2019
Study completion11 Feb 2020

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Autosomal Dominant Polycystic Kidney DiseaseStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 31 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03487913
Sponsor's protocol ID: PA-102
Status last verified: Nov 2022
First submitted: 16 Mar 2018
Last updated: 5 Dec 2022
Results posted: Yes, on ClinicalTrials.gov
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

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.

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Autosomal Dominant Polycystic Kidney Disease (ADPKD)
RecruitingObservational study
Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
Rare Disorders, Undiagnosed Disorders

All Autosomal Dominant Polycystic Kidney Disease trials

Study at a glance

From the registry record, last updated by the sponsor on 5 Dec 2022. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT03487913
Acronym / sponsor ID: PA-102
Conditions: Autosomal Dominant Polycystic Kidney Disease
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 31 participants (actual)
Lead sponsor: Palladio BiosciencesIndustry (pharma, biotech, devices)
Study start: 14 Sep 2018 (actual)
Primary completion: 2 Dec 2019 (actual)
Study completion: 11 Feb 2020 (actual)
First posted: 4 Apr 2018 (actual)
Results: Posted 5 Dec 2022

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

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).

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 4

Arm	Type	Receives
High dose lixivaptan / CKD1 or CKD2	Experimental	Drug: LixivaptanOral high dose lixivaptan in participants with CKD1 or CKD2
Low dose lixivaptan / CKD1 or CKD2	Experimental	Drug: LixivaptanOral low dose lixivaptan in participants with CKD1 or CKD2
High dose lixivaptan / CKD3	Experimental	Drug: LixivaptanOral high dose lixivaptan in participants with CKD3
Low dose lixivaptan / CKD3	Experimental	Drug: LixivaptanOral low dose lixivaptan in participants with CKD3

Who may qualify

Ages: 18 to 65 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (4 listed)

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

Key exclusion criteria (7 listed)

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)

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
LixivaptanAlso: VPA-985Oral vasopressin V2 receptor antagonist	Drug	High dose lixivaptan / CKD1 or CKD2, High dose lixivaptan / CKD3, Low dose lixivaptan / CKD1 or CKD2, Low dose lixivaptan / CKD3

Primary outcome

Maximum Observed Plasma Concentration (Cmax) of Lixivaptan in ADPKD Patients
Time frame: Day 1 (am and pm) and Day 7 (am and pm)
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
Time frame: Day 1 (am and pm) and Day 7 (am and pm)
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
Time frame: Day 1 (am and pm) and Day 7 (am and pm)
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
Time frame: Day 1 (am and pm) and Day 7 (am and pm)
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
Time frame: Day 1 (am and pm) and Day 7 (am and pm)
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
Time frame: Day 1 (am and pm) and Day 7 (am and pm)
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
Time frame: Day 1 (am and pm) and Day 7 (am and pm)
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
Time frame: Day 1 (am and pm) and Day 7 (am and pm)
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
Time frame: Day 1 (am and pm) and Day 7 (am and pm)
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
Time frame: Day 1 (am and pm) and Day 7 (am and pm)
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
Time frame: Day 1 (am and pm) and Day 7 (am and pm)
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
Time frame: Day 1 (am and pm) and Day 7 (am and pm)
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
Time frame: Day 1 (am)
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
Time frame: Day 1 (am)
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
Time frame: Day 1 (am)
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
Time frame: Day 1 (am)
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
Time frame: Day 1 (am) and Day 7 (pm)
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
Time frame: Day 1 (am) and Day 7 (pm)
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
Time frame: Day 1 (am) and Day 7 (pm)
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
Time frame: Day 1 (am) and Day 7 (pm)
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
Time frame: Day 1 (am) and Day 7 (pm)
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
Time frame: Day 1 (am) and Day 7 (pm)
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
Time frame: Day 1 (am) and Day 7 (pm)
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
Time frame: Day 1 (am) and Day 7 (pm)
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
Time frame: Day 1 (am) and Day 7 (am)
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
Time frame: Day 1 (am) and Day 7 (am)
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
Time frame: Day 7 (am)
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
Time frame: Day 7 (am)
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
Time frame: Day 7 (pm)
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
Time frame: Day 7 (pm)
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
Time frame: Day 7 (pm)
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
Time frame: Day 7 (pm)
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
Time frame: Day 7 (pm)
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
Time frame: Day 7 (pm)
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
Time frame: Day 7 (pm)
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
Time frame: Day 7 (pm)
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
Time frame: Day 7 (pm)
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
Time frame: Day 7 (pm)
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
Time frame: 35 days
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
Time frame: 35 days
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
Time frame: 35 days
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
Time frame: Baseline (Day 1) to Day 8 (8 days)
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)
Time frame: 35 days
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
Time frame: Day 7
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
Time frame: Day 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 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
Time frame: Day 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?

8 secondary outcomes

Change From Baseline in Spot Urine Osmolality
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
Change From Baseline in 24-hour Urine Output
Time frame: Baseline (Day -1), Day 1, and Day 7
Change From Baseline of the Estimated Glomerular Filtration Rate (eGFR)
Time frame: Baseline (Day 1) to end of study (35 days)
Change From Baseline in Total Kidney Volume
Time frame: Baseline (Day -1) to end of study (36 days)
Change From Baseline in Liver Volume
Time frame: Baseline (Day -1) to end of study (36 days)
Change From Baseline of Plasma Copeptin
Time frame: Baseline (Day -1) to end of study (36 days)
Change From Baseline in Serum Creatinine
Time frame: Baseline (Day 1, predose) to end of study (35 days)
Change From Baseline in Blood Urea Nitrogen (BUN)
Time frame: Baseline (Day 1, predose) to end of study (35 days)

Results and safety

Results posted to the registry on 5 Dec 2022, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
High Dose Lixivaptan / CKD1 or CKD2	9	9
Low Dose Lixivaptan / CKD1 or CKD2	7	7
High Dose Lixivaptan / CKD3	8	8
Low Dose Lixivaptan / CKD3	7	7

Primary outcome: Maximum Observed Plasma Concentration (Cmax) of Lixivaptan in ADPKD Patients

Time frame: Day 1 (am and pm) and Day 7 (am and pm). Geometric mean (Geometric Coefficient of Variation). Unit: ng/mL

Measure	High Dose Lixivaptan / CKD1 or CKD2 n = 9	Low Dose Lixivaptan / CKD1 or CKD2 n = 7	High Dose Lixivaptan / CKD3 n = 8	Low Dose Lixivaptan / CKD3 n = 7
Day 1 (am)	656.8 (28.1)	190.9 (52.0)	681.3 (45.9)	156.9 (66.9)
Day 1 (pm)	1007 (36.6)	211.5 (33.5)	930.2 (44.5)	159.5 (51.9)
Day 7 (am)	1442 (34.3)	339.5 (19.5)	1422 (48.3)	276.9 (33.7)
Day 7 (pm)	1582 (45.8)	301.0 (13.7)	1211 (90.5)	258.8 (38.4)

Population analysed: The PKAS consisted of all 31 subjects in the Safety analysis set who received lixivaptan, underwent plasma PK sampling, and were evaluable for this PK outcome. Of these, all 31 subjects contributed to the PK data on Day 1 (am); 30 contributed data to Day 1 (pm); and 29 contributed data to Day 7 (am) and (pm).

Primary outcome: Maximum Observed Plasma Concentration (Cmax) of WAY-141624 in ADPKD Patients

Time frame: Day 1 (am and pm) and Day 7 (am and pm). Geometric mean (Geometric Coefficient of Variation). Unit: ng/mL

Measure	High Dose Lixivaptan / CKD1 or CKD2 n = 9	Low Dose Lixivaptan / CKD1 or CKD2 n = 7	High Dose Lixivaptan / CKD3 n = 8	Low Dose Lixivaptan / CKD3 n = 7
Day 1 (am)	455.3 (33.3)	123.7 (69.7)	381.7 (46.6)	135.3 (55.5)
Day 1 (pm)	561.7 (35.4)	160.8 (56.0)	417.8 (41.4)	142.3 (28.7)
Day 7 (am)	535.8 (34.4)	213.8 (75.4)	652.1 (49.0)	233.7 (50.8)
Day 7 (pm)	612.6 (42.3)	200.1 (63.0)	588.5 (69.2)	224.8 (44.7)

Population analysed: The PKAS consisted of all 31 subjects in the Safety analysis set who received lixivaptan, underwent plasma PK sampling, and were evaluable for this PK outcome. Missing values and substantial deviations from planned dosing interval durations meant results were excluded from subjects at various time points.

Primary outcome: Maximum Observed Plasma Concentration (Cmax) of WAY-138451 in ADPKD Patients

Time frame: Day 1 (am and pm) and Day 7 (am and pm). Geometric least squares mean (Geometric Coefficient of Variation). Unit: ng/mL

Measure	High Dose Lixivaptan / CKD1 or CKD2 n = 9	Low Dose Lixivaptan / CKD1 or CKD2 n = 7	High Dose Lixivaptan / CKD3 n = 8	Low Dose Lixivaptan / CKD3 n = 7
Day 1 (am)	84.33 (28.3)	28.83 (21.4)	82.23 (56.3)	24.74 (38.6)
Day 1 (pm)	117.1 (38.1)	25.93 (25.4)	103.3 (38.3)	20.95 (35.4)
Day 7 (am)	177.4 (22.8)	40.79 (27.6)	165.4 (43.1)	33.61 (36.2)
Day 7 (pm)	189.1 (35.2)	35.36 (10.4)	155.2 (74.0)	31.64 (20.2)

Population analysed: The PKAS consisted of all 31 subjects in the Safety analysis set who received lixivaptan, underwent plasma PK sampling, and were evaluable for this PK outcome. Missing values, substantial deviations, and \<3 quantifiable postdose WAY-138451 concentrations meant results were excluded from subjects at various time points.

Primary outcome: Maximum Observed Plasma Concentration (Cmax) of WAY-138758 in ADPKD Patients

Time frame: Day 1 (am and pm) and Day 7 (am and pm). Geometric mean (Geometric Coefficient of Variation). Unit: ng/mL

Measure	High Dose Lixivaptan / CKD1 or CKD2 n = 9	Low Dose Lixivaptan / CKD1 or CKD2 n = 7	High Dose Lixivaptan / CKD3 n = 8	Low Dose Lixivaptan / CKD3 n = 7
Day 1 (am)	239.3 (40.3)	85.11 (36.5)	185.2 (49.7)	64.26 (53.9)
Day 1 (pm)	354.6 (32.8)	125.5 (53.8)	275.0 (26.5)	107.1 (43.5)
Day 7 (am)	822.3 (54.4)	320.4 (60.4)	833.6 (25.0)	343.9 (35.8)
Day 7 (pm)	861.4 (56.0)	326.8 (56.7)	825.2 (24.0)	342.2 (36.0)

8 secondary outcomes are reported in the full results.

Adverse events

Time frame: 35 days. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
High Dose Lixivaptan / CKD1 or CKD2	0 of 9 (0%)	2 of 9 (22.2%)	0 of 9
Low Dose Lixivaptan / CKD1 or CKD2	0 of 7 (0%)	4 of 7 (57.1%)	0 of 7
High Dose Lixivaptan / CKD3	0 of 8 (0%)	4 of 8 (50%)	0 of 8
Low Dose Lixivaptan / CKD3	0 of 7 (0%)	4 of 7 (57.1%)	0 of 7

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 5 Dec 2022.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publicationShusterman 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.
Individual participant dataSharing planned: No

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Vicente E Torres, MD, PhD principal investigator

Mayo Clinic

13 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Lixivaptan in people with Autosomal Dominant Polycystic Kidney Disease, run by Palladio Biosciences at 13 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 5 Dec 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 13 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 5 Dec 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Maximum Observed Plasma Concentration (Cmax) of Lixivaptan in ADPKD Patients (time frame: Day 1 (am and pm) and Day 7 (am and pm)). The study lists 46 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03487913, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Dec 2022.