Phase 2
N=31
The ELiSA Study - Evaluation of Lixivaptan in Subjects With Autosomal Dominant Polycystic Kidney Disease
Autosomal Dominant Polycystic Kidney Disease
Bottom Line
View on ClinicalTrials.gov: NCT03487913 ↗Enrolled (actual)
31
Serious AEs
0.0%
Results posted
Dec 2022
Primary outcome: Primary: Maximum Observed Plasma Concentration (Cmax) of Lixivaptan in ADPKD Patients — 656.8; 190.9; 681.3; 156.9 ng/mL
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Lixivaptan (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Palladio Biosciences
- Primary completion
- Dec 2019
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Maximum Observed Plasma Concentration (Cmax) of Lixivaptan in ADPKD Patients |
656.8; 190.9; 681.3; 156.9; 1007; 211.5 | — |
| PRIMARY Maximum Observed Plasma Concentration (Cmax) of WAY-141624 in ADPKD Patients |
455.3; 123.7; 381.7; 135.3; 561.7; 160.8 | — |
| PRIMARY Maximum Observed Plasma Concentration (Cmax) of WAY-138451 in ADPKD Patients |
84.33; 28.83; 82.23; 24.74; 117.1; 25.93 | — |
| PRIMARY Maximum Observed Plasma Concentration (Cmax) of WAY-138758 in ADPKD Patients |
239.3; 85.11; 185.2; 64.26; 354.6; 125.5 | — |
| PRIMARY Time to Reach Maximum Plasma Concentration (Tmax) of Lixivaptan in ADPKD Patients |
1.000; 1.000; 1.000; 1.020; 1.000; 1.000 | — |
| PRIMARY Time to Reach Maximum Plasma Concentration (Tmax) of WAY-141624 in ADPKD Patients |
2.000; 2.000; 2.000; 2.000; 2.000; 2.000 | — |
| PRIMARY Time to Reach Maximum Plasma Concentration (Tmax) of WAY-138451 in ADPKD Patients |
1.000; 1.010; 1.000; 1.020; 1.000; 1.475 | — |
| PRIMARY Time to Reach Maximum Plasma Concentration (Tmax) of WAY-138758 in ADPKD Patients |
4.000; 4.030; 9.460; 4.020; 4.000; 4.000 | — |
| PRIMARY Area Under the Concentration-time Curve From Time 0 Until the Last Quantifiable Concentration (AUC[0-last]) of Lixivaptan in ADPKD Patients |
1688; 506.7; 2281; 428.8; 3619; 782.1 | — |
| PRIMARY Area Under the Concentration-time Curve From Time 0 Until the Last Quantifiable Concentration (AUC[0-last]) of WAY-141624 in ADPKD Patients |
2339; 669.1; 2300; 716.5; 3963; 1214 | — |
| PRIMARY Area Under the Concentration-time Curve From Time 0 Until the Last Quantifiable Concentration (AUC[0-last]) of WAY-138451 in ADPKD Patients |
284.7; 77.23; 373.6; 70.01; 532.8; 80.14 | — |
| PRIMARY Area Under the Concentration-time Curve From Time 0 Until the Last Quantifiable Concentration (AUC[0-last]) of WAY-138758 in ADPKD Patients |
1792; 669.7; 1412; 485.1; 4281; 1449 | — |
| PRIMARY Area Under the Concentration-time Curve From Time 0 Extrapolated to Infinity (AUC[0-inf]) of Lixivaptan in ADPKD Patients |
— | — |
| PRIMARY Area Under the Concentration-time Curve From Time 0 Extrapolated to Infinity (AUC[0-inf]) of WAY-141624 in ADPKD Patients |
— | — |
| PRIMARY Area Under the Concentration-time Curve From Time 0 Extrapolated to Infinity (AUC[0-inf]) of WAY-138451 in ADPKD Patients |
— | — |
| PRIMARY Area Under the Concentration-time Curve From Time 0 Extrapolated to Infinity (AUC[0-inf]) of WAY-138758 in ADPKD Patients |
— | — |
| PRIMARY Terminal Elimination Phase Half-life (t1/2) of Lixivaptan in ADPKD Patients |
9.696; 7.688; 11.39; 10.25 | — |
| PRIMARY Terminal Elimination Phase Half-life (t1/2) of WAY-141624 in ADPKD Patients |
20.48; 22.41; 20.81; 18.79 | — |
| PRIMARY Terminal Elimination Phase Half-life (t1/2) of WAY-138451 in ADPKD Patients |
6.439; 9.426; NA | — |
| PRIMARY Terminal Elimination Phase Half-life (t1/2) of WAY-138758 in ADPKD Patients |
48.80; 50.70; 59.93; 65.11 | — |
| PRIMARY Apparent Terminal Elimination Rate Constant (λZ) of Lixivaptan in ADPKD Patients |
0.07149; 0.09016; 0.06085; 0.06762 | — |
| PRIMARY Apparent Terminal Elimination Rate Constant (λZ) of WAY-141624 in ADPKD Patients |
0.03384; 0.03093; 0.03330; 0.03690 | — |
| PRIMARY Apparent Terminal Elimination Rate Constant (λZ) of WAY-138451 in ADPKD Patients |
0.1077; 0.07353; NA | — |
| PRIMARY Apparent Terminal Elimination Rate Constant (λZ) of WAY-138758 in ADPKD Patients |
0.01421; 0.01367; 0.01157; 0.01065 | — |
| PRIMARY Apparent Systemic Clearance After Extravascular Dosing (CL/F) of Lixivaptan in ADPKD Patients |
47.20; 49.65; 37.07; 56.22 | — |
| PRIMARY Volume of Distribution After Extravascular Dosing (VZ/F) of Lixivaptan in ADPKD Patients |
— | — |
| PRIMARY Accumulation Ratio for Cmax (RCmax) of Lixivaptan in ADPKD Patients |
2.287; 1.687; 2.087; 1.765 | — |
| PRIMARY Accumulation Ratio for AUC(0-last) (RAUC[0-last]) of Lixivaptan in ADPKD Patients |
2.643; 1.795; 2.365; 2.074 | — |
| PRIMARY Area Under the Concentration-time Curve From Time 0 Until 14 Hours Postdose (AUC[0-14]) of Lixivaptan in ADPKD Patients |
6530; 1280; 7800; 1069 | — |
| PRIMARY Area Under the Concentration-time Curve From Time 0 Until 14 Hours Postdose (AUC[0-14]) of WAY-141624 in ADPKD Patients |
5227; 1717; 5871; 1959 | — |
| PRIMARY Area Under the Concentration-time Curve From Time 0 Until 14 Hours Postdose (AUC[0-14]) of WAY-138451 in ADPKD Patients |
1107; 182.8; 1270; 154.4 | — |
| PRIMARY Area Under the Concentration-time Curve From Time 0 Until 14 Hours Postdose (AUC[0-14]) of WAY-138758 in ADPKD Patients |
10900; 4121; 10730; 4509 | — |
| PRIMARY Ratio of WAY-141624 Cmax to Parent Lixivaptan Cmax (MRCmax) in ADPKD Patients |
0.3627; 0.6225; 0.4554; 0.8137 | — |
| PRIMARY Ratio of WAY-138451 Cmax to Parent Lixivaptan Cmax (MRCmax) in ADPKD Patients |
0.1159; 0.1139; 0.1243; 0.1185 | — |
| PRIMARY Ratio of WAY-138758 Cmax to Parent Lixivaptan Cmax (MRCmax) in ADPKD Patients |
0.6045; 1.205; 0.7569; 1.468 | — |
| PRIMARY Ratio of Metabolite AUC(0-14) to Parent Lixivaptan AUC(0-14) (MRAUC[0-14]) of WAY-141624 in ADPKD Patients |
0.7498; 1.256; 0.7050; 1.717 | — |
| PRIMARY Ratio of Metabolite AUC(0-14) to Parent Lixivaptan AUC(0-14) (MRAUC[0-14]) of WAY-138451 in ADPKD Patients |
0.1643; 0.1384; 0.1579; 0.1401 | — |
| PRIMARY Ratio of Metabolite AUC(0-14) to Parent Lixivaptan AUC(0-14) (MRAUC[0-14]) of WAY-138758 in ADPKD Patients |
1.854; 3.573; 1.528; 4.685 | — |
| PRIMARY Number of Study Participants With Treatment-emergent Adverse Events |
2; 4; 4; 4 | — |
| PRIMARY Number of Study Participants With Clinically Significant Physical Examination Findings |
0; 0; 0; 1 | — |
| PRIMARY Number of Study Participants With Clinically Significant Vital Signs |
0; 0; 0; 0 | — |
| PRIMARY Number of Study Participants With Clinically Significant Changes in 12-lead Electrocardiograms |
0; 0; 0; 0 | — |
| PRIMARY Number of Study Participants With Abnormal Clinical Laboratory Findings (Including Clinical Chemistry, Hematology, and Urinalysis) |
0; 0; 0; 0; 0; 0 | — |
| PRIMARY 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 |
7; 6; 7; 7; 7; 6 | — |
| PRIMARY Aquaretic Tolerability of Lixivaptan Measured by a Tolerability Questionnaire Relating to the Symptom Burden of Nocturia, Urgency, and Frequency at Day 7: Question 3 |
2; 2; 4; 2; 4; 2 | — |
| PRIMARY Aquaretic Tolerability of Lixivaptan Measured by a Tolerability Questionnaire Relating to the Symptom Burden of Nocturia, Urgency, and Frequency at Day 7: Question 7 |
2; 1; 2; 1; 3; 0 | — |
| SECONDARY Change From Baseline in Spot Urine Osmolality |
-27.7; -28.4; -52.3; -167.3; -101.9; 6.1 | — |
| SECONDARY Change From Baseline in 24-hour Urine Output |
2175.3; 1794.4; 3041.1; 1329.9; 1995.6; 1744.6 | — |
| SECONDARY Change From Baseline of the Estimated Glomerular Filtration Rate (eGFR) |
-7.4; -3.9; -2.1; -1.9; -11.9; -3.0 | — |
| SECONDARY Change From Baseline in Total Kidney Volume |
-8.75; 4.97; -66.19; 23.58; -26.63; -3.78 | — |
| SECONDARY Change From Baseline in Liver Volume |
53.04; 43.02; 104.01; -0.03; -6.70; 28.66 | — |
| SECONDARY Change From Baseline of Plasma Copeptin |
5.072; 1.986; 12.655; -1.986; 9.745; 3.016 | — |
| SECONDARY Change From Baseline in Serum Creatinine |
6.7778; 4.1429; 4.7500; 4.5714; 12.6667; 2.7143 | — |
| SECONDARY Change From Baseline in Blood Urea Nitrogen (BUN) |
0.0644; -0.1743; -0.1563; -0.1300; -0.2000; -0.0614 | — |
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.
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
Data sourced from ClinicalTrials.gov (NCT03487913). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.