Trial Outcomes & Findings for Safety and Pharmacokinetics of Ifetroban in Hepatorenal Syndrome Patients (NCT NCT01436500)

Last Updated: 2017-03-01

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

55 participants

Primary outcome timeframe

3 days

Results posted on

2017-03-01

Participant Flow

Participant milestones

Participant milestones
Measure	5 mg Ifetroban 5 mg Ifetroban Injection administered IV over 60 minutes once daily x 3 days	15 mg Ifetroban 15 mg Ifetroban Injection administered IV over 60 minutes once daily x 3 days	50 mg Ifetroban 50 mg Ifetroban Injection administered IV over 60 minutes once daily x 3 days	150 mg Ifetroban 150 mg Ifetroban Injection administered IV over 60 minutes once daily x 3 days	Placebo 5% Dextrose in Water administered IV over 60 minutes once daily x 3 days
Overall Study STARTED	12	12	12	6	13
Overall Study COMPLETED	9	9	7	5	9
Overall Study NOT COMPLETED	3	3	5	1	4

Reasons for withdrawal

Reasons for withdrawal
Measure	5 mg Ifetroban 5 mg Ifetroban Injection administered IV over 60 minutes once daily x 3 days	15 mg Ifetroban 15 mg Ifetroban Injection administered IV over 60 minutes once daily x 3 days	50 mg Ifetroban 50 mg Ifetroban Injection administered IV over 60 minutes once daily x 3 days	150 mg Ifetroban 150 mg Ifetroban Injection administered IV over 60 minutes once daily x 3 days	Placebo 5% Dextrose in Water administered IV over 60 minutes once daily x 3 days
Overall Study Death	1	0	0	0	0
Overall Study Adverse Event	0	2	2	0	1
Overall Study Withdrawal by Subject	0	0	2	0	2
Overall Study Physician Decision	0	0	1	0	0
Overall Study liver transplant	1	0	0	0	0
Overall Study initiation of dialysis	0	0	0	0	1
Overall Study discontinued study drug	1	0	0	0	0
Overall Study Other	0	1	0	1	0

Baseline Characteristics

Safety and Pharmacokinetics of Ifetroban in Hepatorenal Syndrome Patients

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Ifetroban Injection n=42 Participants 5, 15, 50, or 150 mg Ifetroban Injection administered IV over 60 minutes once daily x 3 days	Placebo n=13 Participants 5% Dextrose in Water administered IV over 60 minutes once daily x 3 days	Total n=55 Participants Total of all reporting groups
Age, Continuous	57 years STANDARD_DEVIATION 9.7 • n=5 Participants	56 years STANDARD_DEVIATION 6.4 • n=7 Participants	57 years STANDARD_DEVIATION 9.0 • n=5 Participants
Sex: Female, Male Female	17 Participants n=5 Participants	5 Participants n=7 Participants	22 Participants n=5 Participants
Sex: Female, Male Male	25 Participants n=5 Participants	8 Participants n=7 Participants	33 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	8 Participants n=5 Participants	6 Participants n=7 Participants	14 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	34 Participants n=5 Participants	7 Participants n=7 Participants	41 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Asian	3 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) White	37 Participants n=5 Participants	12 Participants n=7 Participants	49 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	5 mg Ifetroban, Type 1 n=5 Participants 60-minute intravenous infusion of 5 mg ifetroban given once daily for 3 days to subjects with Type 1 HRS. Ifetroban Injection: Ifetroban sodium injectable, diluted in sterile water with 5% dextrose	5 mg Ifetroban, Type 2 n=5 Participants 60-minute intravenous infusion of 5 mg ifetroban given once daily for 3 days to subjects with Type 1 HRS. Ifetroban Injection: Ifetroban sodium injectable, diluted in sterile water with 5% dextrose	15 mg Ifetroban, Type 1 n=5 Participants 60-minute intravenous infusion of 15 mg ifetroban given once daily for 3 days to subjects with Type 1 HRS. Ifetroban Injection: Ifetroban sodium injectable, diluted in sterile water with 5% dextrose	15 mg Ifetroban, Type 2 n=5 Participants 60-minute intravenous infusion of 15 mg ifetroban given once daily for 3 days to subjects with Type 2 HRS. Ifetroban Injection: Ifetroban sodium injectable, diluted in sterile water with 5% dextrose	50 mg Ifetroban, Type 1 n=3 Participants 60-minute intravenous infusion of 50 mg ifetroban given once daily for 3 days to subjects with Type 1 HRS. Ifetroban Injection: Ifetroban sodium injectable, diluted in sterile water with 5% dextrose	50 mg Ifetroban, Type 2 n=5 Participants 60-minute intravenous infusion of 50 mg ifetroban given once daily for 3 days to subjects with Type 2 HRS. Ifetroban Injection: Ifetroban sodium injectable, diluted in sterile water with 5% dextrose	150 mg Ifetroban, Type 2 n=3 Participants 60-minute intravenous infusion of 150 mg ifetroban given once daily for 3 days to subjects with Type 2 HRS. Ifetroban Injection: Ifetroban sodium injectable, diluted in sterile water with 5% dextrose
Half-life (T-1/2) of Ifetroban and Ifetroban Acylglucuronide half-life ifetroban	36.0 hours Standard Deviation NA No SD available with a sample of 2.	11.9 hours Standard Deviation 18.4	15.7 hours Standard Deviation 16.7	10.5 hours Standard Deviation 8.6	18.1 hours Standard Deviation 14.8	13.5 hours Standard Deviation 8.2	17.4 hours Standard Deviation 11.7
Half-life (T-1/2) of Ifetroban and Ifetroban Acylglucuronide half-life ifetroban acylglucuronide	17.1 hours Standard Deviation 17.5	14.7 hours Standard Deviation 19.9	22.1 hours Standard Deviation 9.5	18.6 hours Standard Deviation 10.9	26.4 hours Standard Deviation 22.0	15.2 hours Standard Deviation 9.5	12.6 hours Standard Deviation 12.4

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	5 mg Ifetroban, Type 1 n=5 Participants 60-minute intravenous infusion of 5 mg ifetroban given once daily for 3 days to subjects with Type 1 HRS. Ifetroban Injection: Ifetroban sodium injectable, diluted in sterile water with 5% dextrose	5 mg Ifetroban, Type 2 n=5 Participants 60-minute intravenous infusion of 5 mg ifetroban given once daily for 3 days to subjects with Type 1 HRS. Ifetroban Injection: Ifetroban sodium injectable, diluted in sterile water with 5% dextrose	15 mg Ifetroban, Type 1 n=5 Participants 60-minute intravenous infusion of 15 mg ifetroban given once daily for 3 days to subjects with Type 1 HRS. Ifetroban Injection: Ifetroban sodium injectable, diluted in sterile water with 5% dextrose	15 mg Ifetroban, Type 2 n=5 Participants 60-minute intravenous infusion of 15 mg ifetroban given once daily for 3 days to subjects with Type 2 HRS. Ifetroban Injection: Ifetroban sodium injectable, diluted in sterile water with 5% dextrose	50 mg Ifetroban, Type 1 n=3 Participants 60-minute intravenous infusion of 50 mg ifetroban given once daily for 3 days to subjects with Type 1 HRS. Ifetroban Injection: Ifetroban sodium injectable, diluted in sterile water with 5% dextrose	50 mg Ifetroban, Type 2 n=5 Participants 60-minute intravenous infusion of 50 mg ifetroban given once daily for 3 days to subjects with Type 2 HRS. Ifetroban Injection: Ifetroban sodium injectable, diluted in sterile water with 5% dextrose	150 mg Ifetroban, Type 2 n=3 Participants 60-minute intravenous infusion of 150 mg ifetroban given once daily for 3 days to subjects with Type 2 HRS. Ifetroban Injection: Ifetroban sodium injectable, diluted in sterile water with 5% dextrose
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	779 ng*hr/mL Standard Deviation 326	2025 ng*hr/mL Standard Deviation 639	2463 ng*hr/mL Standard Deviation 1497	5151 ng*hr/mL Standard Deviation 3579	6634 ng*hr/mL Standard Deviation 2166	18612 ng*hr/mL Standard Deviation 8408
Pharmacokinetic Parameters (Exposure) of Ifetroban and Ifetroban Acylglucuronide After Three Days of Treatment Ifetroban AUC to infinity	2476 ng*hr/mL Standard Deviation NA Only 2 subjects were deemed evaluable for this analysis by the pharmacokineticist and SD cannot be calculated with a sample size of 2.	906 ng*hr/mL Standard Deviation 481	2959 ng*hr/mL Standard Deviation 1941	3259 ng*hr/mL Standard Deviation 2866	6505 ng*hr/mL Standard Deviation 4032	8204 ng*hr/mL Standard Deviation 3461	24657 ng*hr/mL Standard Deviation 13425
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	4145 ng*hr/mL Standard Deviation 781	12192 ng*hr/mL Standard Deviation 2102	12038 ng*hr/mL Standard Deviation 2734	46455 ng*hr/mL Standard Deviation 2906	42051 ng*hr/mL Standard Deviation 18567	109915 ng*hr/mL Standard Deviation 32895
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	6128 ng*hr/mL Standard Deviation 3721	21962 ng*hr/mL Standard Deviation 7404	29857 ng*hr/mL Standard Deviation 27688	86457 ng*hr/mL Standard Deviation 44928	61673 ng*hr/mL Standard Deviation 25672	144951 ng*hr/mL Standard Deviation 61311

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	5 mg Ifetroban, Type 1 n=5 Participants 60-minute intravenous infusion of 5 mg ifetroban given once daily for 3 days to subjects with Type 1 HRS. Ifetroban Injection: Ifetroban sodium injectable, diluted in sterile water with 5% dextrose	5 mg Ifetroban, Type 2 n=5 Participants 60-minute intravenous infusion of 5 mg ifetroban given once daily for 3 days to subjects with Type 1 HRS. Ifetroban Injection: Ifetroban sodium injectable, diluted in sterile water with 5% dextrose	15 mg Ifetroban, Type 1 n=5 Participants 60-minute intravenous infusion of 15 mg ifetroban given once daily for 3 days to subjects with Type 1 HRS. Ifetroban Injection: Ifetroban sodium injectable, diluted in sterile water with 5% dextrose	15 mg Ifetroban, Type 2 n=5 Participants 60-minute intravenous infusion of 15 mg ifetroban given once daily for 3 days to subjects with Type 2 HRS. Ifetroban Injection: Ifetroban sodium injectable, diluted in sterile water with 5% dextrose	50 mg Ifetroban, Type 1 n=3 Participants 60-minute intravenous infusion of 50 mg ifetroban given once daily for 3 days to subjects with Type 1 HRS. Ifetroban Injection: Ifetroban sodium injectable, diluted in sterile water with 5% dextrose	50 mg Ifetroban, Type 2 n=5 Participants 60-minute intravenous infusion of 50 mg ifetroban given once daily for 3 days to subjects with Type 2 HRS. Ifetroban Injection: Ifetroban sodium injectable, diluted in sterile water with 5% dextrose	150 mg Ifetroban, Type 2 n=3 Participants 60-minute intravenous infusion of 150 mg ifetroban given once daily for 3 days to subjects with Type 2 HRS. Ifetroban Injection: Ifetroban sodium injectable, diluted in sterile water with 5% dextrose
Pharmacokinetic Parameters (Concentration) of Ifetroban and Ifetroban Acylglucuronide After Three Days of Treatment Minimum Concentration Ifetroban	1.8 ng/mL Standard Deviation 4.1	3.4 ng/mL Standard Deviation 4.0	14.1 ng/mL Standard Deviation 22.6	23.5 ng/mL Standard Deviation 33.7	43.3 ng/mL Standard Deviation 36.2	51.1 ng/mL Standard Deviation 44.5	150.0 ng/mL Standard Deviation 115.5
Pharmacokinetic Parameters (Concentration) of Ifetroban and Ifetroban Acylglucuronide After Three Days of Treatment Maximum Concentration Ifetroban	483 ng/mL Standard Deviation 445	251 ng/mL Standard Deviation 107	581 ng/mL Standard Deviation 114	785 ng/mL Standard Deviation 225	1666 ng/mL Standard Deviation 1478	2599 ng/mL Standard Deviation 838	6790 ng/mL Standard Deviation 2777
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	41.4 ng/mL Standard Deviation 33.1	241.9 ng/mL Standard Deviation 89.0	200.2 ng/mL Standard Deviation 114.3	778.0 ng/mL Standard Deviation 583.2	632.9 ng/mL Standard Deviation 302.9	1755.0 ng/mL Standard Deviation 792.4
Pharmacokinetic Parameters (Concentration) of Ifetroban and Ifetroban Acylglucuronide After Three Days of Treatment Maximum Concentration Ifetroban Acylglucuronide	384 ng/mL Standard Deviation 103	448 ng/mL Standard Deviation 101	912 ng/mL Standard Deviation 194	1214 ng/mL Standard Deviation 255	4737 ng/mL Standard Deviation 543	4666 ng/mL Standard Deviation 1748	10447 ng/mL Standard Deviation 2113

SECONDARY outcome

Timeframe: 28 days

Outcome measures

Outcome measures
Measure	5 mg Ifetroban, Type 1 n=42 Participants 60-minute intravenous infusion of 5 mg ifetroban given once daily for 3 days to subjects with Type 1 HRS. Ifetroban Injection: Ifetroban sodium injectable, diluted in sterile water with 5% dextrose	5 mg Ifetroban, Type 2 n=13 Participants 60-minute intravenous infusion of 5 mg ifetroban given once daily for 3 days to subjects with Type 1 HRS. Ifetroban Injection: Ifetroban sodium injectable, diluted in sterile water with 5% dextrose	15 mg Ifetroban, Type 1 60-minute intravenous infusion of 15 mg ifetroban given once daily for 3 days to subjects with Type 1 HRS. Ifetroban Injection: Ifetroban sodium injectable, diluted in sterile water with 5% dextrose	15 mg Ifetroban, Type 2 60-minute intravenous infusion of 15 mg ifetroban given once daily for 3 days to subjects with Type 2 HRS. Ifetroban Injection: Ifetroban sodium injectable, diluted in sterile water with 5% dextrose	50 mg Ifetroban, Type 1 60-minute intravenous infusion of 50 mg ifetroban given once daily for 3 days to subjects with Type 1 HRS. Ifetroban Injection: Ifetroban sodium injectable, diluted in sterile water with 5% dextrose	50 mg Ifetroban, Type 2 60-minute intravenous infusion of 50 mg ifetroban given once daily for 3 days to subjects with Type 2 HRS. Ifetroban Injection: Ifetroban sodium injectable, diluted in sterile water with 5% dextrose	150 mg Ifetroban, Type 2 60-minute intravenous infusion of 150 mg ifetroban given once daily for 3 days to subjects with Type 2 HRS. Ifetroban Injection: Ifetroban sodium injectable, diluted in sterile water with 5% dextrose
Safety: Day 28 Mortality	17 percentage of participants	15 percentage of participants	—	—	—	—	—

SECONDARY outcome

Timeframe: Day 0 through Day 5

Outcome measures

Outcome measures
Measure	5 mg Ifetroban, Type 1 n=42 Participants 60-minute intravenous infusion of 5 mg ifetroban given once daily for 3 days to subjects with Type 1 HRS. Ifetroban Injection: Ifetroban sodium injectable, diluted in sterile water with 5% dextrose	5 mg Ifetroban, Type 2 n=13 Participants 60-minute intravenous infusion of 5 mg ifetroban given once daily for 3 days to subjects with Type 1 HRS. Ifetroban Injection: Ifetroban sodium injectable, diluted in sterile water with 5% dextrose	15 mg Ifetroban, Type 1 60-minute intravenous infusion of 15 mg ifetroban given once daily for 3 days to subjects with Type 1 HRS. Ifetroban Injection: Ifetroban sodium injectable, diluted in sterile water with 5% dextrose	15 mg Ifetroban, Type 2 60-minute intravenous infusion of 15 mg ifetroban given once daily for 3 days to subjects with Type 2 HRS. Ifetroban Injection: Ifetroban sodium injectable, diluted in sterile water with 5% dextrose	50 mg Ifetroban, Type 1 60-minute intravenous infusion of 50 mg ifetroban given once daily for 3 days to subjects with Type 1 HRS. Ifetroban Injection: Ifetroban sodium injectable, diluted in sterile water with 5% dextrose	50 mg Ifetroban, Type 2 60-minute intravenous infusion of 50 mg ifetroban given once daily for 3 days to subjects with Type 2 HRS. Ifetroban Injection: Ifetroban sodium injectable, diluted in sterile water with 5% dextrose	150 mg Ifetroban, Type 2 60-minute intravenous infusion of 150 mg ifetroban given once daily for 3 days to subjects with Type 2 HRS. Ifetroban Injection: Ifetroban sodium injectable, diluted in sterile water with 5% dextrose
Percentage of Patients Achieving a Treatment-period Serum Creatinine Reduction Below 1.5 mg/dL	21 percentage of participants	15 percentage of participants	—	—	—	—	—

SECONDARY outcome

Timeframe: Day 0 to Day 5

Outcome measures

Outcome measures
Measure	5 mg Ifetroban, Type 1 n=42 Participants 60-minute intravenous infusion of 5 mg ifetroban given once daily for 3 days to subjects with Type 1 HRS. Ifetroban Injection: Ifetroban sodium injectable, diluted in sterile water with 5% dextrose	5 mg Ifetroban, Type 2 n=13 Participants 60-minute intravenous infusion of 5 mg ifetroban given once daily for 3 days to subjects with Type 1 HRS. Ifetroban Injection: Ifetroban sodium injectable, diluted in sterile water with 5% dextrose	15 mg Ifetroban, Type 1 60-minute intravenous infusion of 15 mg ifetroban given once daily for 3 days to subjects with Type 1 HRS. Ifetroban Injection: Ifetroban sodium injectable, diluted in sterile water with 5% dextrose	15 mg Ifetroban, Type 2 60-minute intravenous infusion of 15 mg ifetroban given once daily for 3 days to subjects with Type 2 HRS. Ifetroban Injection: Ifetroban sodium injectable, diluted in sterile water with 5% dextrose	50 mg Ifetroban, Type 1 60-minute intravenous infusion of 50 mg ifetroban given once daily for 3 days to subjects with Type 1 HRS. Ifetroban Injection: Ifetroban sodium injectable, diluted in sterile water with 5% dextrose	50 mg Ifetroban, Type 2 60-minute intravenous infusion of 50 mg ifetroban given once daily for 3 days to subjects with Type 2 HRS. Ifetroban Injection: Ifetroban sodium injectable, diluted in sterile water with 5% dextrose	150 mg Ifetroban, Type 2 60-minute intravenous infusion of 150 mg ifetroban given once daily for 3 days to subjects with Type 2 HRS. Ifetroban Injection: Ifetroban sodium injectable, diluted in sterile water with 5% dextrose
The Percentage of Patients Achieving a Reduction of Creatinine Clearance to Below Baseline on Two Consecutive Daily Measurements	62 percentage of participants	77 percentage of participants	—	—	—	—	—

SECONDARY outcome

Timeframe: 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.

The volume of urine collected in a 24-hour post-treatment period minus the volume collected in a 24-hour pre-treatment period.

Outcome measures

Outcome measures
Measure	5 mg Ifetroban, Type 1 n=33 Participants 60-minute intravenous infusion of 5 mg ifetroban given once daily for 3 days to subjects with Type 1 HRS. Ifetroban Injection: Ifetroban sodium injectable, diluted in sterile water with 5% dextrose	5 mg Ifetroban, Type 2 n=10 Participants 60-minute intravenous infusion of 5 mg ifetroban given once daily for 3 days to subjects with Type 1 HRS. Ifetroban Injection: Ifetroban sodium injectable, diluted in sterile water with 5% dextrose	15 mg Ifetroban, Type 1 60-minute intravenous infusion of 15 mg ifetroban given once daily for 3 days to subjects with Type 1 HRS. Ifetroban Injection: Ifetroban sodium injectable, diluted in sterile water with 5% dextrose	15 mg Ifetroban, Type 2 60-minute intravenous infusion of 15 mg ifetroban given once daily for 3 days to subjects with Type 2 HRS. Ifetroban Injection: Ifetroban sodium injectable, diluted in sterile water with 5% dextrose	50 mg Ifetroban, Type 1 60-minute intravenous infusion of 50 mg ifetroban given once daily for 3 days to subjects with Type 1 HRS. Ifetroban Injection: Ifetroban sodium injectable, diluted in sterile water with 5% dextrose	50 mg Ifetroban, Type 2 60-minute intravenous infusion of 50 mg ifetroban given once daily for 3 days to subjects with Type 2 HRS. Ifetroban Injection: Ifetroban sodium injectable, diluted in sterile water with 5% dextrose	150 mg Ifetroban, Type 2 60-minute intravenous infusion of 150 mg ifetroban given once daily for 3 days to subjects with Type 2 HRS. Ifetroban Injection: Ifetroban sodium injectable, diluted in sterile water with 5% dextrose
Change in 24-hour Urine Volume	267.3 mL Standard Deviation 613.3	-118.5 mL Standard Deviation 452.2	—	—	—	—	—

Adverse Events

Ifetroban

Serious events: 21 serious events

Other events: 25 other events

Deaths: 7 deaths

Placebo

Serious events: 8 serious events

Other events: 5 other events

Deaths: 2 deaths

Serious adverse events

Other adverse events

Additional Information

Jerry Fox, DVM

Cumberland Pharmaceuticals Inc

Phone: 615-255-0068

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee PI can publish data generated at their study site after multi=center study data have already been published, or after 18 months have elapsed following database lock. The sponsor may review manuscripts before submission and delay publication by an additional 60 days, if necessary.
Publication restrictions are in place

Restriction type: OTHER

Measure	Ifetroban n=42 participants at risk 5, 15, 50 or 150 mg Ifetroban Injection administered IV over 60 minutes once daily x 3 days	Placebo n=13 participants at risk 5% Dextrose in Water administered IV over 60 minutes once daily x 3 days
Endocrine disorders hyperglycaemia	0.00% 0/42 • Day 0 through Day 28 A secondary objective of the study was to evaluate the tolerability and safety of ifetroban in HRS patients. All ifetroban patients are grouped together for comparison to all placebo patients for the purpose of maximizing the significance of the evaluation.	7.7% 1/13 • Day 0 through Day 28 A secondary objective of the study was to evaluate the tolerability and safety of ifetroban in HRS patients. All ifetroban patients are grouped together for comparison to all placebo patients for the purpose of maximizing the significance of the evaluation.
Gastrointestinal disorders worsening ascites	0.00% 0/42 • Day 0 through Day 28 A secondary objective of the study was to evaluate the tolerability and safety of ifetroban in HRS patients. All ifetroban patients are grouped together for comparison to all placebo patients for the purpose of maximizing the significance of the evaluation.	7.7% 1/13 • Day 0 through Day 28 A secondary objective of the study was to evaluate the tolerability and safety of ifetroban in HRS patients. All ifetroban patients are grouped together for comparison to all placebo patients for the purpose of maximizing the significance of the evaluation.
Gastrointestinal disorders haematemesis	2.4% 1/42 • Day 0 through Day 28 A secondary objective of the study was to evaluate the tolerability and safety of ifetroban in HRS patients. All ifetroban patients are grouped together for comparison to all placebo patients for the purpose of maximizing the significance of the evaluation.	0.00% 0/13 • Day 0 through Day 28 A secondary objective of the study was to evaluate the tolerability and safety of ifetroban in HRS patients. All ifetroban patients are grouped together for comparison to all placebo patients for the purpose of maximizing the significance of the evaluation.
Gastrointestinal disorders haematochezia	2.4% 1/42 • Day 0 through Day 28 A secondary objective of the study was to evaluate the tolerability and safety of ifetroban in HRS patients. All ifetroban patients are grouped together for comparison to all placebo patients for the purpose of maximizing the significance of the evaluation.	0.00% 0/13 • Day 0 through Day 28 A secondary objective of the study was to evaluate the tolerability and safety of ifetroban in HRS patients. All ifetroban patients are grouped together for comparison to all placebo patients for the purpose of maximizing the significance of the evaluation.
Gastrointestinal disorders peritoneal haemorrhage	4.8% 2/42 • Day 0 through Day 28 A secondary objective of the study was to evaluate the tolerability and safety of ifetroban in HRS patients. All ifetroban patients are grouped together for comparison to all placebo patients for the purpose of maximizing the significance of the evaluation.	0.00% 0/13 • Day 0 through Day 28 A secondary objective of the study was to evaluate the tolerability and safety of ifetroban in HRS patients. All ifetroban patients are grouped together for comparison to all placebo patients for the purpose of maximizing the significance of the evaluation.
General disorders catheter site haemorrhage	2.4% 1/42 • Day 0 through Day 28 A secondary objective of the study was to evaluate the tolerability and safety of ifetroban in HRS patients. All ifetroban patients are grouped together for comparison to all placebo patients for the purpose of maximizing the significance of the evaluation.	0.00% 0/13 • Day 0 through Day 28 A secondary objective of the study was to evaluate the tolerability and safety of ifetroban in HRS patients. All ifetroban patients are grouped together for comparison to all placebo patients for the purpose of maximizing the significance of the evaluation.
General disorders device failure	2.4% 1/42 • Day 0 through Day 28 A secondary objective of the study was to evaluate the tolerability and safety of ifetroban in HRS patients. All ifetroban patients are grouped together for comparison to all placebo patients for the purpose of maximizing the significance of the evaluation.	0.00% 0/13 • Day 0 through Day 28 A secondary objective of the study was to evaluate the tolerability and safety of ifetroban in HRS patients. All ifetroban patients are grouped together for comparison to all placebo patients for the purpose of maximizing the significance of the evaluation.
Hepatobiliary disorders chronic hepatic failure	7.1% 3/42 • Day 0 through Day 28 A secondary objective of the study was to evaluate the tolerability and safety of ifetroban in HRS patients. All ifetroban patients are grouped together for comparison to all placebo patients for the purpose of maximizing the significance of the evaluation.	0.00% 0/13 • Day 0 through Day 28 A secondary objective of the study was to evaluate the tolerability and safety of ifetroban in HRS patients. All ifetroban patients are grouped together for comparison to all placebo patients for the purpose of maximizing the significance of the evaluation.
Hepatobiliary disorders hepatic cirrhosis	0.00% 0/42 • Day 0 through Day 28 A secondary objective of the study was to evaluate the tolerability and safety of ifetroban in HRS patients. All ifetroban patients are grouped together for comparison to all placebo patients for the purpose of maximizing the significance of the evaluation.	7.7% 1/13 • Day 0 through Day 28 A secondary objective of the study was to evaluate the tolerability and safety of ifetroban in HRS patients. All ifetroban patients are grouped together for comparison to all placebo patients for the purpose of maximizing the significance of the evaluation.
Hepatobiliary disorders hepatorenal syndrome	2.4% 1/42 • Day 0 through Day 28 A secondary objective of the study was to evaluate the tolerability and safety of ifetroban in HRS patients. All ifetroban patients are grouped together for comparison to all placebo patients for the purpose of maximizing the significance of the evaluation.	7.7% 1/13 • Day 0 through Day 28 A secondary objective of the study was to evaluate the tolerability and safety of ifetroban in HRS patients. All ifetroban patients are grouped together for comparison to all placebo patients for the purpose of maximizing the significance of the evaluation.
Hepatobiliary disorders liver disorder	2.4% 1/42 • Day 0 through Day 28 A secondary objective of the study was to evaluate the tolerability and safety of ifetroban in HRS patients. All ifetroban patients are grouped together for comparison to all placebo patients for the purpose of maximizing the significance of the evaluation.	0.00% 0/13 • Day 0 through Day 28 A secondary objective of the study was to evaluate the tolerability and safety of ifetroban in HRS patients. All ifetroban patients are grouped together for comparison to all placebo patients for the purpose of maximizing the significance of the evaluation.
Infections and infestations bacteraemia	2.4% 1/42 • Day 0 through Day 28 A secondary objective of the study was to evaluate the tolerability and safety of ifetroban in HRS patients. All ifetroban patients are grouped together for comparison to all placebo patients for the purpose of maximizing the significance of the evaluation.	0.00% 0/13 • Day 0 through Day 28 A secondary objective of the study was to evaluate the tolerability and safety of ifetroban in HRS patients. All ifetroban patients are grouped together for comparison to all placebo patients for the purpose of maximizing the significance of the evaluation.
Infections and infestations peritonitis bacterial	2.4% 1/42 • Day 0 through Day 28 A secondary objective of the study was to evaluate the tolerability and safety of ifetroban in HRS patients. All ifetroban patients are grouped together for comparison to all placebo patients for the purpose of maximizing the significance of the evaluation.	0.00% 0/13 • Day 0 through Day 28 A secondary objective of the study was to evaluate the tolerability and safety of ifetroban in HRS patients. All ifetroban patients are grouped together for comparison to all placebo patients for the purpose of maximizing the significance of the evaluation.
Infections and infestations pneumonia	0.00% 0/42 • Day 0 through Day 28 A secondary objective of the study was to evaluate the tolerability and safety of ifetroban in HRS patients. All ifetroban patients are grouped together for comparison to all placebo patients for the purpose of maximizing the significance of the evaluation.	7.7% 1/13 • Day 0 through Day 28 A secondary objective of the study was to evaluate the tolerability and safety of ifetroban in HRS patients. All ifetroban patients are grouped together for comparison to all placebo patients for the purpose of maximizing the significance of the evaluation.
Injury, poisoning and procedural complications complications of transplanted liver	2.4% 1/42 • Day 0 through Day 28 A secondary objective of the study was to evaluate the tolerability and safety of ifetroban in HRS patients. All ifetroban patients are grouped together for comparison to all placebo patients for the purpose of maximizing the significance of the evaluation.	0.00% 0/13 • Day 0 through Day 28 A secondary objective of the study was to evaluate the tolerability and safety of ifetroban in HRS patients. All ifetroban patients are grouped together for comparison to all placebo patients for the purpose of maximizing the significance of the evaluation.
Injury, poisoning and procedural complications post procedural haematoma	2.4% 1/42 • Day 0 through Day 28 A secondary objective of the study was to evaluate the tolerability and safety of ifetroban in HRS patients. All ifetroban patients are grouped together for comparison to all placebo patients for the purpose of maximizing the significance of the evaluation.	0.00% 0/13 • Day 0 through Day 28 A secondary objective of the study was to evaluate the tolerability and safety of ifetroban in HRS patients. All ifetroban patients are grouped together for comparison to all placebo patients for the purpose of maximizing the significance of the evaluation.
Investigations Blood Creatinine Increased	0.00% 0/42 • Day 0 through Day 28 A secondary objective of the study was to evaluate the tolerability and safety of ifetroban in HRS patients. All ifetroban patients are grouped together for comparison to all placebo patients for the purpose of maximizing the significance of the evaluation.	7.7% 1/13 • Day 0 through Day 28 A secondary objective of the study was to evaluate the tolerability and safety of ifetroban in HRS patients. All ifetroban patients are grouped together for comparison to all placebo patients for the purpose of maximizing the significance of the evaluation.
Psychiatric disorders mental status changes	0.00% 0/42 • Day 0 through Day 28 A secondary objective of the study was to evaluate the tolerability and safety of ifetroban in HRS patients. All ifetroban patients are grouped together for comparison to all placebo patients for the purpose of maximizing the significance of the evaluation.	7.7% 1/13 • Day 0 through Day 28 A secondary objective of the study was to evaluate the tolerability and safety of ifetroban in HRS patients. All ifetroban patients are grouped together for comparison to all placebo patients for the purpose of maximizing the significance of the evaluation.
Renal and urinary disorders renal failure	2.4% 1/42 • Day 0 through Day 28 A secondary objective of the study was to evaluate the tolerability and safety of ifetroban in HRS patients. All ifetroban patients are grouped together for comparison to all placebo patients for the purpose of maximizing the significance of the evaluation.	0.00% 0/13 • Day 0 through Day 28 A secondary objective of the study was to evaluate the tolerability and safety of ifetroban in HRS patients. All ifetroban patients are grouped together for comparison to all placebo patients for the purpose of maximizing the significance of the evaluation.
Respiratory, thoracic and mediastinal disorders hypoxia	2.4% 1/42 • Day 0 through Day 28 A secondary objective of the study was to evaluate the tolerability and safety of ifetroban in HRS patients. All ifetroban patients are grouped together for comparison to all placebo patients for the purpose of maximizing the significance of the evaluation.	0.00% 0/13 • Day 0 through Day 28 A secondary objective of the study was to evaluate the tolerability and safety of ifetroban in HRS patients. All ifetroban patients are grouped together for comparison to all placebo patients for the purpose of maximizing the significance of the evaluation.
Respiratory, thoracic and mediastinal disorders respiratory failure	2.4% 1/42 • Day 0 through Day 28 A secondary objective of the study was to evaluate the tolerability and safety of ifetroban in HRS patients. All ifetroban patients are grouped together for comparison to all placebo patients for the purpose of maximizing the significance of the evaluation.	0.00% 0/13 • Day 0 through Day 28 A secondary objective of the study was to evaluate the tolerability and safety of ifetroban in HRS patients. All ifetroban patients are grouped together for comparison to all placebo patients for the purpose of maximizing the significance of the evaluation.
Vascular disorders deep vein thrombosis	2.4% 1/42 • Day 0 through Day 28 A secondary objective of the study was to evaluate the tolerability and safety of ifetroban in HRS patients. All ifetroban patients are grouped together for comparison to all placebo patients for the purpose of maximizing the significance of the evaluation.	0.00% 0/13 • Day 0 through Day 28 A secondary objective of the study was to evaluate the tolerability and safety of ifetroban in HRS patients. All ifetroban patients are grouped together for comparison to all placebo patients for the purpose of maximizing the significance of the evaluation.
Vascular disorders shock haemorrhagic	2.4% 1/42 • Day 0 through Day 28 A secondary objective of the study was to evaluate the tolerability and safety of ifetroban in HRS patients. All ifetroban patients are grouped together for comparison to all placebo patients for the purpose of maximizing the significance of the evaluation.	0.00% 0/13 • Day 0 through Day 28 A secondary objective of the study was to evaluate the tolerability and safety of ifetroban in HRS patients. All ifetroban patients are grouped together for comparison to all placebo patients for the purpose of maximizing the significance of the evaluation.
Vascular disorders subarachnoid haemorrhage	0.00% 0/42 • Day 0 through Day 28 A secondary objective of the study was to evaluate the tolerability and safety of ifetroban in HRS patients. All ifetroban patients are grouped together for comparison to all placebo patients for the purpose of maximizing the significance of the evaluation.	7.7% 1/13 • Day 0 through Day 28 A secondary objective of the study was to evaluate the tolerability and safety of ifetroban in HRS patients. All ifetroban patients are grouped together for comparison to all placebo patients for the purpose of maximizing the significance of the evaluation.
Vascular disorders upper gastrointestinal haemorrhage	2.4% 1/42 • Day 0 through Day 28 A secondary objective of the study was to evaluate the tolerability and safety of ifetroban in HRS patients. All ifetroban patients are grouped together for comparison to all placebo patients for the purpose of maximizing the significance of the evaluation.	0.00% 0/13 • Day 0 through Day 28 A secondary objective of the study was to evaluate the tolerability and safety of ifetroban in HRS patients. All ifetroban patients are grouped together for comparison to all placebo patients for the purpose of maximizing the significance of the evaluation.
Renal and urinary disorders Renal failure chronic	2.4% 1/42 • Day 0 through Day 28 A secondary objective of the study was to evaluate the tolerability and safety of ifetroban in HRS patients. All ifetroban patients are grouped together for comparison to all placebo patients for the purpose of maximizing the significance of the evaluation.	0.00% 0/13 • Day 0 through Day 28 A secondary objective of the study was to evaluate the tolerability and safety of ifetroban in HRS patients. All ifetroban patients are grouped together for comparison to all placebo patients for the purpose of maximizing the significance of the evaluation.
Cardiac disorders Atrial fibrillation	2.4% 1/42 • Day 0 through Day 28 A secondary objective of the study was to evaluate the tolerability and safety of ifetroban in HRS patients. All ifetroban patients are grouped together for comparison to all placebo patients for the purpose of maximizing the significance of the evaluation.	0.00% 0/13 • Day 0 through Day 28 A secondary objective of the study was to evaluate the tolerability and safety of ifetroban in HRS patients. All ifetroban patients are grouped together for comparison to all placebo patients for the purpose of maximizing the significance of the evaluation.

Measure	Ifetroban n=42 participants at risk 5, 15, 50 or 150 mg Ifetroban Injection administered IV over 60 minutes once daily x 3 days	Placebo n=13 participants at risk 5% Dextrose in Water administered IV over 60 minutes once daily x 3 days
Gastrointestinal disorders abdominal pain	9.5% 4/42 • Day 0 through Day 28 A secondary objective of the study was to evaluate the tolerability and safety of ifetroban in HRS patients. All ifetroban patients are grouped together for comparison to all placebo patients for the purpose of maximizing the significance of the evaluation.	0.00% 0/13 • Day 0 through Day 28 A secondary objective of the study was to evaluate the tolerability and safety of ifetroban in HRS patients. All ifetroban patients are grouped together for comparison to all placebo patients for the purpose of maximizing the significance of the evaluation.
Cardiac disorders Dyspnoea	11.9% 5/42 • Day 0 through Day 28 A secondary objective of the study was to evaluate the tolerability and safety of ifetroban in HRS patients. All ifetroban patients are grouped together for comparison to all placebo patients for the purpose of maximizing the significance of the evaluation.	0.00% 0/13 • Day 0 through Day 28 A secondary objective of the study was to evaluate the tolerability and safety of ifetroban in HRS patients. All ifetroban patients are grouped together for comparison to all placebo patients for the purpose of maximizing the significance of the evaluation.
Cardiac disorders atrial fibrillation	7.1% 3/42 • Day 0 through Day 28 A secondary objective of the study was to evaluate the tolerability and safety of ifetroban in HRS patients. All ifetroban patients are grouped together for comparison to all placebo patients for the purpose of maximizing the significance of the evaluation.	0.00% 0/13 • Day 0 through Day 28 A secondary objective of the study was to evaluate the tolerability and safety of ifetroban in HRS patients. All ifetroban patients are grouped together for comparison to all placebo patients for the purpose of maximizing the significance of the evaluation.
Hepatobiliary disorders chronic hepatic failure	7.1% 3/42 • Day 0 through Day 28 A secondary objective of the study was to evaluate the tolerability and safety of ifetroban in HRS patients. All ifetroban patients are grouped together for comparison to all placebo patients for the purpose of maximizing the significance of the evaluation.	0.00% 0/13 • Day 0 through Day 28 A secondary objective of the study was to evaluate the tolerability and safety of ifetroban in HRS patients. All ifetroban patients are grouped together for comparison to all placebo patients for the purpose of maximizing the significance of the evaluation.
Gastrointestinal disorders nausea	7.1% 3/42 • Day 0 through Day 28 A secondary objective of the study was to evaluate the tolerability and safety of ifetroban in HRS patients. All ifetroban patients are grouped together for comparison to all placebo patients for the purpose of maximizing the significance of the evaluation.	0.00% 0/13 • Day 0 through Day 28 A secondary objective of the study was to evaluate the tolerability and safety of ifetroban in HRS patients. All ifetroban patients are grouped together for comparison to all placebo patients for the purpose of maximizing the significance of the evaluation.
Blood and lymphatic system disorders anaemia	7.1% 3/42 • Day 0 through Day 28 A secondary objective of the study was to evaluate the tolerability and safety of ifetroban in HRS patients. All ifetroban patients are grouped together for comparison to all placebo patients for the purpose of maximizing the significance of the evaluation.	0.00% 0/13 • Day 0 through Day 28 A secondary objective of the study was to evaluate the tolerability and safety of ifetroban in HRS patients. All ifetroban patients are grouped together for comparison to all placebo patients for the purpose of maximizing the significance of the evaluation.
Respiratory, thoracic and mediastinal disorders dyspnoea	4.8% 2/42 • Day 0 through Day 28 A secondary objective of the study was to evaluate the tolerability and safety of ifetroban in HRS patients. All ifetroban patients are grouped together for comparison to all placebo patients for the purpose of maximizing the significance of the evaluation.	7.7% 1/13 • Day 0 through Day 28 A secondary objective of the study was to evaluate the tolerability and safety of ifetroban in HRS patients. All ifetroban patients are grouped together for comparison to all placebo patients for the purpose of maximizing the significance of the evaluation.
Respiratory, thoracic and mediastinal disorders respiratory failure	0.00% 0/42 • Day 0 through Day 28 A secondary objective of the study was to evaluate the tolerability and safety of ifetroban in HRS patients. All ifetroban patients are grouped together for comparison to all placebo patients for the purpose of maximizing the significance of the evaluation.	7.7% 1/13 • Day 0 through Day 28 A secondary objective of the study was to evaluate the tolerability and safety of ifetroban in HRS patients. All ifetroban patients are grouped together for comparison to all placebo patients for the purpose of maximizing the significance of the evaluation.
Metabolism and nutrition disorders hyperkalaemia	2.4% 1/42 • Day 0 through Day 28 A secondary objective of the study was to evaluate the tolerability and safety of ifetroban in HRS patients. All ifetroban patients are grouped together for comparison to all placebo patients for the purpose of maximizing the significance of the evaluation.	7.7% 1/13 • Day 0 through Day 28 A secondary objective of the study was to evaluate the tolerability and safety of ifetroban in HRS patients. All ifetroban patients are grouped together for comparison to all placebo patients for the purpose of maximizing the significance of the evaluation.
Cardiac disorders Bradycardia	2.4% 1/42 • Day 0 through Day 28 A secondary objective of the study was to evaluate the tolerability and safety of ifetroban in HRS patients. All ifetroban patients are grouped together for comparison to all placebo patients for the purpose of maximizing the significance of the evaluation.	7.7% 1/13 • Day 0 through Day 28 A secondary objective of the study was to evaluate the tolerability and safety of ifetroban in HRS patients. All ifetroban patients are grouped together for comparison to all placebo patients for the purpose of maximizing the significance of the evaluation.
Investigations INR increased	0.00% 0/42 • Day 0 through Day 28 A secondary objective of the study was to evaluate the tolerability and safety of ifetroban in HRS patients. All ifetroban patients are grouped together for comparison to all placebo patients for the purpose of maximizing the significance of the evaluation.	7.7% 1/13 • Day 0 through Day 28 A secondary objective of the study was to evaluate the tolerability and safety of ifetroban in HRS patients. All ifetroban patients are grouped together for comparison to all placebo patients for the purpose of maximizing the significance of the evaluation.
Musculoskeletal and connective tissue disorders pain in extremity	0.00% 0/42 • Day 0 through Day 28 A secondary objective of the study was to evaluate the tolerability and safety of ifetroban in HRS patients. All ifetroban patients are grouped together for comparison to all placebo patients for the purpose of maximizing the significance of the evaluation.	7.7% 1/13 • Day 0 through Day 28 A secondary objective of the study was to evaluate the tolerability and safety of ifetroban in HRS patients. All ifetroban patients are grouped together for comparison to all placebo patients for the purpose of maximizing the significance of the evaluation.
Renal and urinary disorders worsening renal function	2.4% 1/42 • Day 0 through Day 28 A secondary objective of the study was to evaluate the tolerability and safety of ifetroban in HRS patients. All ifetroban patients are grouped together for comparison to all placebo patients for the purpose of maximizing the significance of the evaluation.	7.7% 1/13 • Day 0 through Day 28 A secondary objective of the study was to evaluate the tolerability and safety of ifetroban in HRS patients. All ifetroban patients are grouped together for comparison to all placebo patients for the purpose of maximizing the significance of the evaluation.
Vascular disorders hypotension	7.1% 3/42 • Day 0 through Day 28 A secondary objective of the study was to evaluate the tolerability and safety of ifetroban in HRS patients. All ifetroban patients are grouped together for comparison to all placebo patients for the purpose of maximizing the significance of the evaluation.	7.7% 1/13 • Day 0 through Day 28 A secondary objective of the study was to evaluate the tolerability and safety of ifetroban in HRS patients. All ifetroban patients are grouped together for comparison to all placebo patients for the purpose of maximizing the significance of the evaluation.
Blood and lymphatic system disorders worsening coagulopathy	0.00% 0/42 • Day 0 through Day 28 A secondary objective of the study was to evaluate the tolerability and safety of ifetroban in HRS patients. All ifetroban patients are grouped together for comparison to all placebo patients for the purpose of maximizing the significance of the evaluation.	7.7% 1/13 • Day 0 through Day 28 A secondary objective of the study was to evaluate the tolerability and safety of ifetroban in HRS patients. All ifetroban patients are grouped together for comparison to all placebo patients for the purpose of maximizing the significance of the evaluation.