Hepatorenal Syndrome
Conditions
Keywords
Hepatorenal Syndrome, HRS, ifetroban
Brief summary
A study of ifetroban in the treatment of hepatorenal syndrome (HRS) in hospitalized adult patients to assess the safety and pharmacokinetics of 3 days of intravenous ifetroban.
Interventions
DRUGIfetroban Injection
Ifetroban sodium injectable, diluted in sterile water with 5% dextrose
DRUGPlacebo
Sterile water with 5% Dextrose
Sponsors
Cumberland Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Chronic liver disease, defined as cirrhosis with ascites based on clinical findings (biopsy not necessary). 2. Subjects with either Type 1 or Type 2 HRS defined in a and b below: a. Type 1: i. At least a doubling of the serum creatinine to a minimum of 220 µmol/L (2.5 mg/dL) at enrollment, occurring over a period of less than 14 days, OR ii. A 50% or greater reduction in the estimated glomerular filtration rate (GFR - calculated by the method of Cockcroft-Gault) to below 20 mL/min at enrollment occurring over a period of less than 14 days. iii. A projected doubling of serum creatinine to a minimum of 2.5 mg/dL, expected to occur in less than 14 days based on the rate of change observed. b. Type 2: defined as at least a 33% reduction in creatinine clearance occurring over a period of greater than 2 weeks, with a serum creatinine (SCr) \> 133µmol/L (1.5 mg/dL). 3. Oliguria occurring within 48 hours prior to the first administration CTM. Oliguria is defined as an average urine output of \< 35 mL/hr (measured for a minimum of 4 hours) under either of the following circumstances: a. When measured central venous pressure (CVP) \> 12 mmHg, OR b. following a fluid challenge consisting of either: i. at minimum 20 mL/kg isotonic fluid (e.g. any combination of 5% albumin, normal saline, blood or blood products) given over no more than 6 hours ii. at minimum 1 g/kg of hypertonic fluid (e.g. 25% albumin) given over no more than 24 hours iii. an equivalent combination of 3.b.i and 3.b.ii
Exclusion criteria
1. History of allergy or hypersensitivity to ifetroban 2. Pregnant or nursing 3. Less than 18 years of age 4. Serum creatinine at the time of enrollment greater than or equal to 5.0 mg/dL 5. Platelet count at screening less than 30 x 10\^3 platelets/µL 6. Anticipated of planned need for dialysis within 5 days of first CTM dose. 7. Active gastrointestinal hemorrhage (where active is defined as evidence of bleeding within 48 hours of the first dose of CTM) 8. Evidence of current (within past 30 days) obstructive (post-renal) or intrinsic renal disease \[including but not limited to: acute tubular necrosis (ATN), glomerular diseases/glomerulonephritis, acute interstitial nephritis (AIN), known urinary obstruction, proteinuria \> 500 mg/day, microhematuria (\> 50 RBCs/high power field), abnormal renal ultrasound, fractional excretion of sodium (FeNa) \> 2.0%, any urinary casts other than hyaline. 9. Current or recent (within the preceding 5 days) treatment with nephrotoxic drugs including but not limited to: NSAIDs (prior 48 hours), angiotensin converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARB), calcineurin inhibitors (cyclosporine, tacrolimus), aminoglycosides, amphotericin B, antiretrovirals and antivirals (adefovir, cidofovir, tenofovir, acyclovir, indinavir), cisplatin, methotrexate, cyclosporine, amphotericin B contrast agents, foscarnet, zoledronate, etc. 10. Presence of shock defined as hypotension, with a mean arterial pressure less than 50 mmHG. 11. New York Heart Association class 3 or 4 heart failure. 12. Presence of hepatocellular carcinoma not transplantable by Milan criteria 13. Cardiopulmonary arrest without full recovery of mental status 14. Moribund and death expected within five days 15. Bacterial or fungal infections which have been unresponsive to at least 24 hours of appropriate antimicrobial therapy 16. Burns \> 30% body surface area 17. Exposed to investigational drugs within 30 days before 1st CTM administration. 18. Inability to understand the requirements of the study. (Subjects must be willing to provide written informed consent or consent of legally recognized representative, as evidenced by signature on an informed consent document approved by an Institutional Review Board \[IRB\], and agree to abide by the study restrictions. If the subject is incapacitated, informed consent will be sought from a legally recognized representative). 19. Refusal to provide written authorization for use and disclosure of protected health information. 20. Be otherwise unsuitable for the study, in the opinion of the Investigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Half-life (T-1/2) of Ifetroban and Ifetroban Acylglucuronide | 3 days | Plasma concentrations of ifetroban and its major active metabolite were measured at Baseline and Study Hours 1, 2, 4, 8, 12, 24, 48, 49, 50, 52, 56, 60, and 72 to determine the Pharmacokinetic parameters. |
| Pharmacokinetic Parameters (Exposure) of Ifetroban and Ifetroban Acylglucuronide After Three Days of Treatment | 3 days | Plasma concentrations of ifetroban and its primary active metabolite were measured at Baseline and Study Hours 1, 2, 4, 8, 12, 24, 48, 49, 50, 52, 56, 60, and 72 to determine the Pharmacokinetic parameters. |
| Pharmacokinetic Parameters (Concentration) of Ifetroban and Ifetroban Acylglucuronide After Three Days of Treatment | 3 days | Plasma concentrations of ifetroban and it's major active metabolite were measured at Baseline and Study Hours 1, 2, 4, 8, 12, 24, 48, 49, 50, 52, 56, 60, and 72 to determine the Pharmacokinetic parameters. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Safety: Day 28 Mortality | 28 days | — |
| Change in 24-hour Urine Volume | Baseline to Hour 96 | The volume of urine collected in a 24-hour post-treatment period minus the volume collected in a 24-hour pre-treatment period. |
| Percentage of Patients Achieving a Treatment-period Serum Creatinine Reduction Below 1.5 mg/dL | Day 0 through Day 5 | — |
| The Percentage of Patients Achieving a Reduction of Creatinine Clearance to Below Baseline on Two Consecutive Daily Measurements | Day 0 to Day 5 | — |
Countries
India, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Ifetroban Injection 5, 15, 50, or 150 mg Ifetroban Injection administered IV over 60 minutes once daily x 3 days | 42 |
| Placebo 5% Dextrose in Water administered IV over 60 minutes once daily x 3 days | 13 |
| Total | 55 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 2 | 2 | 0 | 1 |
| Overall Study | Death | 1 | 0 | 0 | 0 | 0 |
| Overall Study | discontinued study drug | 1 | 0 | 0 | 0 | 0 |
| Overall Study | initiation of dialysis | 0 | 0 | 0 | 0 | 1 |
| Overall Study | liver transplant | 1 | 0 | 0 | 0 | 0 |
| Overall Study | Other | 0 | 1 | 0 | 1 | 0 |
| Overall Study | Physician Decision | 0 | 0 | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 2 | 0 | 2 |
Baseline characteristics
| Characteristic | Placebo | Total | Ifetroban Injection |
|---|---|---|---|
| Age, Continuous | 56 years STANDARD_DEVIATION 6.4 | 57 years STANDARD_DEVIATION 9 | 57 years STANDARD_DEVIATION 9.7 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 6 Participants | 14 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 7 Participants | 41 Participants | 34 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 4 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 12 Participants | 49 Participants | 37 Participants |
| Sex: Female, Male Female | 5 Participants | 22 Participants | 17 Participants |
| Sex: Female, Male Male | 8 Participants | 33 Participants | 25 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 7 / 42 | 2 / 13 |
| other Total, other adverse events | 25 / 42 | 5 / 13 |
| serious Total, serious adverse events | 21 / 42 | 8 / 13 |
Outcome results
Primary
Half-life (T-1/2) of Ifetroban and Ifetroban Acylglucuronide
Plasma concentrations of ifetroban and its major active metabolite were measured at Baseline and Study Hours 1, 2, 4, 8, 12, 24, 48, 49, 50, 52, 56, 60, and 72 to determine the Pharmacokinetic parameters.
Time frame: 3 days
Population: Patients from which a full series of plasma samples were obtained from baseline through Hour 72 were included in the calculations of the PK parameters. Where the number of participants analyzed in an arm is lower than the number exposed for that arm, the patients with missing data did not contribute to the calculation of the PK parameters.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 5 mg Ifetroban, Type 1 | Half-life (T-1/2) of Ifetroban and Ifetroban Acylglucuronide | half-life ifetroban | 36.0 hours | — |
| 5 mg Ifetroban, Type 1 | Half-life (T-1/2) of Ifetroban and Ifetroban Acylglucuronide | half-life ifetroban acylglucuronide | 17.1 hours | Standard Deviation 17.5 |
| 5 mg Ifetroban, Type 2 | Half-life (T-1/2) of Ifetroban and Ifetroban Acylglucuronide | half-life ifetroban | 11.9 hours | Standard Deviation 18.4 |
| 5 mg Ifetroban, Type 2 | Half-life (T-1/2) of Ifetroban and Ifetroban Acylglucuronide | half-life ifetroban acylglucuronide | 14.7 hours | Standard Deviation 19.9 |
| 15 mg Ifetroban, Type 1 | Half-life (T-1/2) of Ifetroban and Ifetroban Acylglucuronide | half-life ifetroban | 15.7 hours | Standard Deviation 16.7 |
| 15 mg Ifetroban, Type 1 | Half-life (T-1/2) of Ifetroban and Ifetroban Acylglucuronide | half-life ifetroban acylglucuronide | 22.1 hours | Standard Deviation 9.5 |
| 15 mg Ifetroban, Type 2 | Half-life (T-1/2) of Ifetroban and Ifetroban Acylglucuronide | half-life ifetroban | 10.5 hours | Standard Deviation 8.6 |
| 15 mg Ifetroban, Type 2 | Half-life (T-1/2) of Ifetroban and Ifetroban Acylglucuronide | half-life ifetroban acylglucuronide | 18.6 hours | Standard Deviation 10.9 |
| 50 mg Ifetroban, Type 1 | Half-life (T-1/2) of Ifetroban and Ifetroban Acylglucuronide | half-life ifetroban | 18.1 hours | Standard Deviation 14.8 |
| 50 mg Ifetroban, Type 1 | Half-life (T-1/2) of Ifetroban and Ifetroban Acylglucuronide | half-life ifetroban acylglucuronide | 26.4 hours | Standard Deviation 22 |
| 50 mg Ifetroban, Type 2 | Half-life (T-1/2) of Ifetroban and Ifetroban Acylglucuronide | half-life ifetroban | 13.5 hours | Standard Deviation 8.2 |
| 50 mg Ifetroban, Type 2 | Half-life (T-1/2) of Ifetroban and Ifetroban Acylglucuronide | half-life ifetroban acylglucuronide | 15.2 hours | Standard Deviation 9.5 |
| 150 mg Ifetroban, Type 2 | Half-life (T-1/2) of Ifetroban and Ifetroban Acylglucuronide | half-life ifetroban | 17.4 hours | Standard Deviation 11.7 |
| 150 mg Ifetroban, Type 2 | Half-life (T-1/2) of Ifetroban and Ifetroban Acylglucuronide | half-life ifetroban acylglucuronide | 12.6 hours | Standard Deviation 12.4 |
Primary
Pharmacokinetic Parameters (Concentration) of Ifetroban and Ifetroban Acylglucuronide After Three Days of Treatment
Plasma concentrations of ifetroban and it's major active metabolite were measured at Baseline and Study Hours 1, 2, 4, 8, 12, 24, 48, 49, 50, 52, 56, 60, and 72 to determine the Pharmacokinetic parameters.
Time frame: 3 days
Population: Patients from which a full series of plasma samples were obtained from baseline through Hour 72 were included in the calculations of the PK parameters. Where the number of participants analyzed in an arm is lower than the number exposed for that arm, the patients with missing data did not contribute to the calculation of the PK parameters.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 5 mg Ifetroban, Type 1 | Pharmacokinetic Parameters (Concentration) of Ifetroban and Ifetroban Acylglucuronide After Three Days of Treatment | Minimum Concentration Ifetroban | 1.8 ng/mL | Standard Deviation 4.1 |
| 5 mg Ifetroban, Type 1 | Pharmacokinetic Parameters (Concentration) of Ifetroban and Ifetroban Acylglucuronide After Three Days of Treatment | Maximum Concentration Ifetroban Acylglucuronide | 384 ng/mL | Standard Deviation 103 |
| 5 mg Ifetroban, Type 1 | Pharmacokinetic Parameters (Concentration) of Ifetroban and Ifetroban Acylglucuronide After Three Days of Treatment | Minimum Concentration Ifetroban Acylglucuronide | 78.4 ng/mL | Standard Deviation 56.7 |
| 5 mg Ifetroban, Type 1 | Pharmacokinetic Parameters (Concentration) of Ifetroban and Ifetroban Acylglucuronide After Three Days of Treatment | Maximum Concentration Ifetroban | 483 ng/mL | Standard Deviation 445 |
| 5 mg Ifetroban, Type 2 | Pharmacokinetic Parameters (Concentration) of Ifetroban and Ifetroban Acylglucuronide After Three Days of Treatment | Minimum Concentration Ifetroban Acylglucuronide | 41.4 ng/mL | Standard Deviation 33.1 |
| 5 mg Ifetroban, Type 2 | Pharmacokinetic Parameters (Concentration) of Ifetroban and Ifetroban Acylglucuronide After Three Days of Treatment | Minimum Concentration Ifetroban | 3.4 ng/mL | Standard Deviation 4 |
| 5 mg Ifetroban, Type 2 | Pharmacokinetic Parameters (Concentration) of Ifetroban and Ifetroban Acylglucuronide After Three Days of Treatment | Maximum Concentration Ifetroban Acylglucuronide | 448 ng/mL | Standard Deviation 101 |
| 5 mg Ifetroban, Type 2 | Pharmacokinetic Parameters (Concentration) of Ifetroban and Ifetroban Acylglucuronide After Three Days of Treatment | Maximum Concentration Ifetroban | 251 ng/mL | Standard Deviation 107 |
| 15 mg Ifetroban, Type 1 | Pharmacokinetic Parameters (Concentration) of Ifetroban and Ifetroban Acylglucuronide After Three Days of Treatment | Minimum Concentration Ifetroban | 14.1 ng/mL | Standard Deviation 22.6 |
| 15 mg Ifetroban, Type 1 | Pharmacokinetic Parameters (Concentration) of Ifetroban and Ifetroban Acylglucuronide After Three Days of Treatment | Minimum Concentration Ifetroban Acylglucuronide | 241.9 ng/mL | Standard Deviation 89 |
| 15 mg Ifetroban, Type 1 | Pharmacokinetic Parameters (Concentration) of Ifetroban and Ifetroban Acylglucuronide After Three Days of Treatment | Maximum Concentration Ifetroban | 581 ng/mL | Standard Deviation 114 |
| 15 mg Ifetroban, Type 1 | Pharmacokinetic Parameters (Concentration) of Ifetroban and Ifetroban Acylglucuronide After Three Days of Treatment | Maximum Concentration Ifetroban Acylglucuronide | 912 ng/mL | Standard Deviation 194 |
| 15 mg Ifetroban, Type 2 | Pharmacokinetic Parameters (Concentration) of Ifetroban and Ifetroban Acylglucuronide After Three Days of Treatment | Maximum Concentration Ifetroban | 785 ng/mL | Standard Deviation 225 |
| 15 mg Ifetroban, Type 2 | Pharmacokinetic Parameters (Concentration) of Ifetroban and Ifetroban Acylglucuronide After Three Days of Treatment | Minimum Concentration Ifetroban | 23.5 ng/mL | Standard Deviation 33.7 |
| 15 mg Ifetroban, Type 2 | Pharmacokinetic Parameters (Concentration) of Ifetroban and Ifetroban Acylglucuronide After Three Days of Treatment | Minimum Concentration Ifetroban Acylglucuronide | 200.2 ng/mL | Standard Deviation 114.3 |
| 15 mg Ifetroban, Type 2 | Pharmacokinetic Parameters (Concentration) of Ifetroban and Ifetroban Acylglucuronide After Three Days of Treatment | Maximum Concentration Ifetroban Acylglucuronide | 1214 ng/mL | Standard Deviation 255 |
| 50 mg Ifetroban, Type 1 | Pharmacokinetic Parameters (Concentration) of Ifetroban and Ifetroban Acylglucuronide After Three Days of Treatment | Maximum Concentration Ifetroban | 1666 ng/mL | Standard Deviation 1478 |
| 50 mg Ifetroban, Type 1 | Pharmacokinetic Parameters (Concentration) of Ifetroban and Ifetroban Acylglucuronide After Three Days of Treatment | Maximum Concentration Ifetroban Acylglucuronide | 4737 ng/mL | Standard Deviation 543 |
| 50 mg Ifetroban, Type 1 | Pharmacokinetic Parameters (Concentration) of Ifetroban and Ifetroban Acylglucuronide After Three Days of Treatment | Minimum Concentration Ifetroban Acylglucuronide | 778.0 ng/mL | Standard Deviation 583.2 |
| 50 mg Ifetroban, Type 1 | Pharmacokinetic Parameters (Concentration) of Ifetroban and Ifetroban Acylglucuronide After Three Days of Treatment | Minimum Concentration Ifetroban | 43.3 ng/mL | Standard Deviation 36.2 |
| 50 mg Ifetroban, Type 2 | Pharmacokinetic Parameters (Concentration) of Ifetroban and Ifetroban Acylglucuronide After Three Days of Treatment | Maximum Concentration Ifetroban | 2599 ng/mL | Standard Deviation 838 |
| 50 mg Ifetroban, Type 2 | Pharmacokinetic Parameters (Concentration) of Ifetroban and Ifetroban Acylglucuronide After Three Days of Treatment | Maximum Concentration Ifetroban Acylglucuronide | 4666 ng/mL | Standard Deviation 1748 |
| 50 mg Ifetroban, Type 2 | Pharmacokinetic Parameters (Concentration) of Ifetroban and Ifetroban Acylglucuronide After Three Days of Treatment | Minimum Concentration Ifetroban Acylglucuronide | 632.9 ng/mL | Standard Deviation 302.9 |
| 50 mg Ifetroban, Type 2 | Pharmacokinetic Parameters (Concentration) of Ifetroban and Ifetroban Acylglucuronide After Three Days of Treatment | Minimum Concentration Ifetroban | 51.1 ng/mL | Standard Deviation 44.5 |
| 150 mg Ifetroban, Type 2 | Pharmacokinetic Parameters (Concentration) of Ifetroban and Ifetroban Acylglucuronide After Three Days of Treatment | Maximum Concentration Ifetroban Acylglucuronide | 10447 ng/mL | Standard Deviation 2113 |
| 150 mg Ifetroban, Type 2 | Pharmacokinetic Parameters (Concentration) of Ifetroban and Ifetroban Acylglucuronide After Three Days of Treatment | Minimum Concentration Ifetroban | 150.0 ng/mL | Standard Deviation 115.5 |
| 150 mg Ifetroban, Type 2 | Pharmacokinetic Parameters (Concentration) of Ifetroban and Ifetroban Acylglucuronide After Three Days of Treatment | Maximum Concentration Ifetroban | 6790 ng/mL | Standard Deviation 2777 |
| 150 mg Ifetroban, Type 2 | Pharmacokinetic Parameters (Concentration) of Ifetroban and Ifetroban Acylglucuronide After Three Days of Treatment | Minimum Concentration Ifetroban Acylglucuronide | 1755.0 ng/mL | Standard Deviation 792.4 |
Primary
Pharmacokinetic Parameters (Exposure) of Ifetroban and Ifetroban Acylglucuronide After Three Days of Treatment
Plasma concentrations of ifetroban and its primary active metabolite were measured at Baseline and Study Hours 1, 2, 4, 8, 12, 24, 48, 49, 50, 52, 56, 60, and 72 to determine the Pharmacokinetic parameters.
Time frame: 3 days
Population: Patients from which a full series of plasma samples were obtained from baseline through Hour 72 were included in the calculations of the PK parameters. Where the number of participants analyzed in an arm is lower than the number exposed for that arm, the patients with missing data did not contribute to the calculation of the PK parameters.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 5 mg Ifetroban, Type 1 | Pharmacokinetic Parameters (Exposure) of Ifetroban and Ifetroban Acylglucuronide After Three Days of Treatment | Ifetroban area under the curve (AUC) to 24 hours | 964 ng*hr/mL | Standard Deviation 683 |
| 5 mg Ifetroban, Type 1 | Pharmacokinetic Parameters (Exposure) of Ifetroban and Ifetroban Acylglucuronide After Three Days of Treatment | Ifetroban AUC to infinity | 2476 ng*hr/mL | — |
| 5 mg Ifetroban, Type 1 | Pharmacokinetic Parameters (Exposure) of Ifetroban and Ifetroban Acylglucuronide After Three Days of Treatment | Ifetroban acylglucuronide AUC to 24 hours to | 4371 ng*hr/mL | Standard Deviation 2050 |
| 5 mg Ifetroban, Type 1 | Pharmacokinetic Parameters (Exposure) of Ifetroban and Ifetroban Acylglucuronide After Three Days of Treatment | Ifetroban acylglucuronide AUC to infinity | 8440 ng*hr/mL | Standard Deviation 8730 |
| 5 mg Ifetroban, Type 2 | Pharmacokinetic Parameters (Exposure) of Ifetroban and Ifetroban Acylglucuronide After Three Days of Treatment | Ifetroban acylglucuronide AUC to infinity | 6128 ng*hr/mL | Standard Deviation 3721 |
| 5 mg Ifetroban, Type 2 | Pharmacokinetic Parameters (Exposure) of Ifetroban and Ifetroban Acylglucuronide After Three Days of Treatment | Ifetroban acylglucuronide AUC to 24 hours to | 4145 ng*hr/mL | Standard Deviation 781 |
| 5 mg Ifetroban, Type 2 | Pharmacokinetic Parameters (Exposure) of Ifetroban and Ifetroban Acylglucuronide After Three Days of Treatment | Ifetroban area under the curve (AUC) to 24 hours | 779 ng*hr/mL | Standard Deviation 326 |
| 5 mg Ifetroban, Type 2 | Pharmacokinetic Parameters (Exposure) of Ifetroban and Ifetroban Acylglucuronide After Three Days of Treatment | Ifetroban AUC to infinity | 906 ng*hr/mL | Standard Deviation 481 |
| 15 mg Ifetroban, Type 1 | Pharmacokinetic Parameters (Exposure) of Ifetroban and Ifetroban Acylglucuronide After Three Days of Treatment | Ifetroban acylglucuronide AUC to 24 hours to | 12192 ng*hr/mL | Standard Deviation 2102 |
| 15 mg Ifetroban, Type 1 | Pharmacokinetic Parameters (Exposure) of Ifetroban and Ifetroban Acylglucuronide After Three Days of Treatment | Ifetroban AUC to infinity | 2959 ng*hr/mL | Standard Deviation 1941 |
| 15 mg Ifetroban, Type 1 | Pharmacokinetic Parameters (Exposure) of Ifetroban and Ifetroban Acylglucuronide After Three Days of Treatment | Ifetroban area under the curve (AUC) to 24 hours | 2025 ng*hr/mL | Standard Deviation 639 |
| 15 mg Ifetroban, Type 1 | Pharmacokinetic Parameters (Exposure) of Ifetroban and Ifetroban Acylglucuronide After Three Days of Treatment | Ifetroban acylglucuronide AUC to infinity | 21962 ng*hr/mL | Standard Deviation 7404 |
| 15 mg Ifetroban, Type 2 | Pharmacokinetic Parameters (Exposure) of Ifetroban and Ifetroban Acylglucuronide After Three Days of Treatment | Ifetroban area under the curve (AUC) to 24 hours | 2463 ng*hr/mL | Standard Deviation 1497 |
| 15 mg Ifetroban, Type 2 | Pharmacokinetic Parameters (Exposure) of Ifetroban and Ifetroban Acylglucuronide After Three Days of Treatment | Ifetroban AUC to infinity | 3259 ng*hr/mL | Standard Deviation 2866 |
| 15 mg Ifetroban, Type 2 | Pharmacokinetic Parameters (Exposure) of Ifetroban and Ifetroban Acylglucuronide After Three Days of Treatment | Ifetroban acylglucuronide AUC to 24 hours to | 12038 ng*hr/mL | Standard Deviation 2734 |
| 15 mg Ifetroban, Type 2 | Pharmacokinetic Parameters (Exposure) of Ifetroban and Ifetroban Acylglucuronide After Three Days of Treatment | Ifetroban acylglucuronide AUC to infinity | 29857 ng*hr/mL | Standard Deviation 27688 |
| 50 mg Ifetroban, Type 1 | Pharmacokinetic Parameters (Exposure) of Ifetroban and Ifetroban Acylglucuronide After Three Days of Treatment | Ifetroban area under the curve (AUC) to 24 hours | 5151 ng*hr/mL | Standard Deviation 3579 |
| 50 mg Ifetroban, Type 1 | Pharmacokinetic Parameters (Exposure) of Ifetroban and Ifetroban Acylglucuronide After Three Days of Treatment | Ifetroban acylglucuronide AUC to infinity | 86457 ng*hr/mL | Standard Deviation 44928 |
| 50 mg Ifetroban, Type 1 | Pharmacokinetic Parameters (Exposure) of Ifetroban and Ifetroban Acylglucuronide After Three Days of Treatment | Ifetroban AUC to infinity | 6505 ng*hr/mL | Standard Deviation 4032 |
| 50 mg Ifetroban, Type 1 | Pharmacokinetic Parameters (Exposure) of Ifetroban and Ifetroban Acylglucuronide After Three Days of Treatment | Ifetroban acylglucuronide AUC to 24 hours to | 46455 ng*hr/mL | Standard Deviation 2906 |
| 50 mg Ifetroban, Type 2 | Pharmacokinetic Parameters (Exposure) of Ifetroban and Ifetroban Acylglucuronide After Three Days of Treatment | Ifetroban AUC to infinity | 8204 ng*hr/mL | Standard Deviation 3461 |
| 50 mg Ifetroban, Type 2 | Pharmacokinetic Parameters (Exposure) of Ifetroban and Ifetroban Acylglucuronide After Three Days of Treatment | Ifetroban area under the curve (AUC) to 24 hours | 6634 ng*hr/mL | Standard Deviation 2166 |
| 50 mg Ifetroban, Type 2 | Pharmacokinetic Parameters (Exposure) of Ifetroban and Ifetroban Acylglucuronide After Three Days of Treatment | Ifetroban acylglucuronide AUC to 24 hours to | 42051 ng*hr/mL | Standard Deviation 18567 |
| 50 mg Ifetroban, Type 2 | Pharmacokinetic Parameters (Exposure) of Ifetroban and Ifetroban Acylglucuronide After Three Days of Treatment | Ifetroban acylglucuronide AUC to infinity | 61673 ng*hr/mL | Standard Deviation 25672 |
| 150 mg Ifetroban, Type 2 | Pharmacokinetic Parameters (Exposure) of Ifetroban and Ifetroban Acylglucuronide After Three Days of Treatment | Ifetroban acylglucuronide AUC to 24 hours to | 109915 ng*hr/mL | Standard Deviation 32895 |
| 150 mg Ifetroban, Type 2 | Pharmacokinetic Parameters (Exposure) of Ifetroban and Ifetroban Acylglucuronide After Three Days of Treatment | Ifetroban area under the curve (AUC) to 24 hours | 18612 ng*hr/mL | Standard Deviation 8408 |
| 150 mg Ifetroban, Type 2 | Pharmacokinetic Parameters (Exposure) of Ifetroban and Ifetroban Acylglucuronide After Three Days of Treatment | Ifetroban AUC to infinity | 24657 ng*hr/mL | Standard Deviation 13425 |
| 150 mg Ifetroban, Type 2 | Pharmacokinetic Parameters (Exposure) of Ifetroban and Ifetroban Acylglucuronide After Three Days of Treatment | Ifetroban acylglucuronide AUC to infinity | 144951 ng*hr/mL | Standard Deviation 61311 |
Secondary
Change in 24-hour Urine Volume
The volume of urine collected in a 24-hour post-treatment period minus the volume collected in a 24-hour pre-treatment period.
Time frame: Baseline to Hour 96
Population: Data were missing for the post-treatment urine volume measurements in 9 of 42 ifetroban patients and 3 of 13 placebo patients so they were excluded from the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 5 mg Ifetroban, Type 1 | Change in 24-hour Urine Volume | 267.3 mL | Standard Deviation 613.3 |
| 5 mg Ifetroban, Type 2 | Change in 24-hour Urine Volume | -118.5 mL | Standard Deviation 452.2 |
Secondary
Percentage of Patients Achieving a Treatment-period Serum Creatinine Reduction Below 1.5 mg/dL
Time frame: Day 0 through Day 5
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 5 mg Ifetroban, Type 1 | Percentage of Patients Achieving a Treatment-period Serum Creatinine Reduction Below 1.5 mg/dL | 21 percentage of participants |
| 5 mg Ifetroban, Type 2 | Percentage of Patients Achieving a Treatment-period Serum Creatinine Reduction Below 1.5 mg/dL | 15 percentage of participants |
Secondary
Safety: Day 28 Mortality
Time frame: 28 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 5 mg Ifetroban, Type 1 | Safety: Day 28 Mortality | 17 percentage of participants |
| 5 mg Ifetroban, Type 2 | Safety: Day 28 Mortality | 15 percentage of participants |
Secondary
The Percentage of Patients Achieving a Reduction of Creatinine Clearance to Below Baseline on Two Consecutive Daily Measurements
Time frame: Day 0 to Day 5
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 5 mg Ifetroban, Type 1 | The Percentage of Patients Achieving a Reduction of Creatinine Clearance to Below Baseline on Two Consecutive Daily Measurements | 62 percentage of participants |
| 5 mg Ifetroban, Type 2 | The Percentage of Patients Achieving a Reduction of Creatinine Clearance to Below Baseline on Two Consecutive Daily Measurements | 77 percentage of participants |