Safety and Pharmacokinetics of Ifetroban in Hepatorenal Syndrome Patients
This study is currently recruiting participants.
Verified April 2013 by Cumberland Pharmaceuticals
Sponsor:
Cumberland Pharmaceuticals
Information provided by (Responsible Party):
Cumberland Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT01436500
First received: August 31, 2011
Last updated: April 24, 2013
Last verified: April 2013
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Purpose
Cumberland Pharmaceuticals Inc. (CPI) is developing ifetroban for treatment of hepatorenal syndrome (HRS) and proposes to conduct a study in hospitalized adult patients with HRS to assess the safety and pharmacokinetics of escalating doses of ifetroban.
| Condition | Intervention | Phase |
|---|---|---|
|
Hepatorenal Syndrome |
Drug: 5mg Ifetroban Injection Drug: 15mg Ifetroban Injection Drug: 50mg Ifetroban Injection Drug: 150mg Ifetroban Injection Other: 5% Dextrose in Water |
Phase 2 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Pharmacokinetics Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator) Primary Purpose: Basic Science |
| Official Title: | A Multi-Center, Double-Blind, Randomized, Controlled Study to Determine the Safety and Pharmacokinetics of Ifetroban Injection in Hepatorenal Syndrome |
Resource links provided by NLM:
Further study details as provided by Cumberland Pharmaceuticals:
Primary Outcome Measures:
- Pharmacokinetic profile (Cmax, Cmin, Vdss, T1/2, AUC 0-24, and AUC 0-inf) of ifetroban and ifetroban acylglucuronide [ Time Frame: 5 days ] [ Designated as safety issue: No ]
To evaluate the primary objective of determining the pharmacokinetic profile of multiple daily intravenous doses of ifetroban, the following endpoints will be measured:
• Pharmacokinetic parameters, including serum concentration versus time profile of ifetroban and its major metabolite ifetroban acylglucuronide for the 24-hour period after the first dose, Cmax, Cmin, Vdss, T1/2, AUC 0-24 (area under the curve during 24 hours), and AUC 0-inf (area under the curve extrapolated to infinity), will be determined from analysis of collected blood samples.
- Vital signs, clinical chemistry, urine electrolytes, coagulation/hematology assessments, treatment emergent adverse events, and Day 28 mortality of ifetroban injection in patients with HRS. [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]
To evaluate the primary objective of determining the tolerability and safety of ifetroban injection in patients with HRS, the following endpoints will be measured:
- Vital signs (heart rate, respiratory rate, blood pressure, temperature, pulse oximetry saturation)
- Clinical chemistry, urine electrolytes, coagulation and hematology assessments
- Treatment emergent adverse events
- Day 28 mortality
Secondary Outcome Measures:
- Serum creatinine, Creatinine clearance, BUN, urine output, estimated GFR, Urinary TxB2-M, and plasma F2-isoprostane levels of ifetroban injection in patients with HRS. [ Time Frame: Baseline and 5 days ] [ Designated as safety issue: No ]
To evaluate the secondary objective of evaluating the incidence and magnitude of renal function change relative to criteria for HRS reversal, the following endpoint will be measured:
- Serum creatinine reduction below 1.5 mg/dL
- Creatinine clearance improvement over baseline confirmed in two sequential measurements
- BUN, urine output, estimated GFR, and dialysis requirement
- Urinary TxB2-M and plasma F2-isoprostane levels
| Estimated Enrollment: | 64 |
| Study Start Date: | October 2011 |
| Estimated Study Completion Date: | December 2014 |
| Estimated Primary Completion Date: | December 2013 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
| Experimental: Ifetroban Injection |
Drug: 5mg Ifetroban Injection
Cohort 1: 5 mg Ifetroban Injection administered IV over 60 minutes once daily; During 72-hr treatment period. Total of 3 doses of CTM will be administered.
Drug: 15mg Ifetroban Injection
Cohort 2: 15 mg Ifetroban Injection administered IV over 60 minutes once daily During 72-hr treatment period. Total of 3 doses of CTM will be administered.
Drug: 50mg Ifetroban Injection
Cohort 3: 50 mg Ifetroban Injection administered IV over 60 minutes once daily During 72-hr treatment period. Total of 3 doses of CTM will be administered.
Drug: 150mg Ifetroban Injection
Cohort 4: 150 mg Ifetroban Injection administered IV over 60 minutes once daily During 72-hr treatment period. Total of 3 doses of CTM will be administered.
|
| Placebo Comparator: Placebo |
Other: 5% Dextrose in Water
5% Dextrose in Water
Other Name: D5W
|
Detailed Description:
Ifetroban sodium (ifetroban) is an investigational drug that has been studied previously in healthy volunteers and patients with cardiovascular diseases. Cumberland Pharmaceuticals Inc. (CPI) is developing ifetroban for treatment of type 1 and type 2 hepatorenal syndrome (HRS) and proposed to conduct a study in hospitalized adult patients with HRS to assess the safety and pharmacokinetics of escalating doses of ifetroban. The primary objective of this study is as follows:
- To determine the pharmacokinetic profile of multiple daily intravenous doses of ifetroban and its major metabolite ifetroban acylglucuronide.
- To determine the tolerability and safety of ifetroban injection in patients with HRS.
The secondary objective of this study is as follows:
• To determine if ifetroban changes renal function, showing evidence of HRS reversal.
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- Chronic liver disease, defined as cirrhosis with ascites based on clinical findings (biopsy not necessary).
Subjects with either Type 1 or Type 2 renal dysfunction defined as follows:
Type 1:
i. At least a doubling of the initial serum creatinine to > 220 µmol/L (2.5 mg/dL), occurring over a period of less than 2 week, OR ii. A 50% or greater reduction in the initial 24-hour creatinine clearance to < 20 mL/min occurring over a period of less than 2 weeks.
- 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).
Oliguria occurring within 48 hours prior to 1st administration CTM. Oliguria is defined as either of the following:
- An average urine output of < 35 mL/hr measured for at least 4 hours, occurring with a measured central venous pressure (CVP) > 12 mmHg, OR
- In the absence of CVP monitoring, oliguria that is not corrected by a fluid challenge of at least 20mL/kg isotonic crystalloid or comparable volume of colloid.
Exclusion Criteria:
- History of allergy or hypersensitivity to ifetroban
- Pregnant or nursing
- Less than 18 years of age
- Serum creatinine (SCr) > 5.0 mg/dL
- Platelet count at screening of < 30,000/ µL
- Active gastrointestinal hemorrhage
- Evidence of obstructive or parenchymal renal disease (e.g., acute tubular necrosis, glomerular diseases, interstitial nephritis, and urinary obstruction, or lab results indicating proteinuria > 500 mg/day, microhematuria [> 50 RBCs/high power field], and/or abnormal renal ultrasound scanning).
- Current or recent (within the preceding 5 days) treatment with any of the following drugs: aminoglycosides, acyclovir, cisplatin, methotrexate, cyclosporine, amphotericin B.
- Presence of shock defined as hypotension, with a mean arterial pressure less than 50 mmHG.
- New York Heart Association class 3 or 4 heart failure.
- Presence of hepatocellular carcinoma not transplantable by Milan criteria
- Cardiopulmonary arrest without full recovery of mental status
- Moribund and death expected within five days
- Uncontrolled bacterial or fungal infections, defined as receiving appropriate antimicrobial therapy for > 24 hours
- Burns > 30% body surface area
- Exposed to investigational drugs within 30 days before 1st CTM administration.
- 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).
- Refusal to provide written authorization for use and disclosure of protected health information.
- Be otherwise unsuitable for the study, in the opinion of the Investigator.
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01436500
Locations
| United States, Alabama | |
| UAB Hospital | Withdrawn |
| Birmingham, Alabama, United States, 35233 | |
| United States, Arizona | |
| Mayo Clinic - Arizona | Recruiting |
| Phoenix, Arizona, United States, 85054 | |
| Contact: Jennifer McGrew, RN, BSN 480-342-2479 McGrew.Jennifer@mayo.edu | |
| Principal Investigator: Hugo E Vargas, MD | |
| Sub-Investigator: Bashar A. Mahmoud Aqel, MD | |
| Sub-Investigator: Thomas J. Byrne, MD | |
| Sub-Investigator: Elizabeth J Carey, MD | |
| Sub-Investigator: Hasan A Khamash, MD | |
| United States, California | |
| UCSD, Hillcrest Medical Center Hospital | Recruiting |
| La Jolla, California, United States, 92093 | |
| Contact: Cynthia Knott, RD/CCRC/XRT 858-657-5123 cknott@ucsd.edu | |
| Principal Investigator: Michel Mendler, MD | |
| UCSF (University of California-San Francisco) | Recruiting |
| San Francisco, California, United States, 94143 | |
| Contact: Sharon Blaschka, RN, MSN, NPC 415-476-3229 sharon.blaschka@ucsfmedctr.org | |
| Principal Investigator: Sandy Feng, MD, PhD | |
| Sub-Investigator: Nancy Ascher, MD | |
| Sub-Investigator: John Roberts, MD | |
| Sub-Investigator: Peter Stock, MD, PhD | |
| Sub-Investigator: Chris Freise, MD | |
| Sub-Investigator: Ryutaro Hirose, MD | |
| Sub-Investigator: Sang Mo Kang, MD | |
| Sub-Investigator: Andy Posselt, MD, PhD | |
| United States, Connecticut | |
| Yale University, School of Medicine 333 Cedar Street, FMB 121 | Withdrawn |
| New Haven, Connecticut, United States, 06520 | |
| United States, Florida | |
| University of Miami (Center for Liver Diseases) | Withdrawn |
| Miami, Florida, United States, 33136 | |
| United States, Georgia | |
| Emory University Hospital | Recruiting |
| Atlanta, Georgia, United States, 30322 | |
| Contact: Sallie Carpentier, RN, BSN 404-712-8341 scarpe3@emory.edu | |
| Contact: Elizabeth Ferry, RN 404-712-1816 elizabeth.ferry@emoryhealthcare.org | |
| Principal Investigator: Ram Subramanian, MD | |
| United States, Indiana | |
| Indiana University (Division of Gastroenterology/Hepatology) | Recruiting |
| Indianapolis, Indiana, United States, 46202 | |
| Contact: Linda Ragozzino 317-278-9296 lragozzi@iupui.edu | |
| Principal Investigator: Naga P Chalasani, MD, FACG | |
| United States, Massachusetts | |
| Massachusetts General Hospital | Withdrawn |
| Boston, Massachusetts, United States, 02114 | |
| United States, Michigan | |
| University of Michigan Hospital | Recruiting |
| Ann Arbor, Michigan, United States, 48109 | |
| Contact: LaDonna Austin, CCRC 734-936-4780 ladonna@med.umich.edu | |
| Principal Investigator: Pratima Sharma, MD | |
| United States, Nebraska | |
| University of Nebraska Medical Center | Withdrawn |
| Omaha, Nebraska, United States, 68198 | |
| United States, New York | |
| NYU Langone Medical Center | Recruiting |
| New York, New York, United States, 10016 | |
| Contact: Christelle Sommervil, MPH, CCRP 212-263-8391 Christelle.Sommervil@nyumc.org | |
| Principal Investigator: Lewis Teperman, MD | |
| United States, Ohio | |
| The Ohio State University | Recruiting |
| Columbus, Ohio, United States, 43210 | |
| Contact: Andrew Otey, BS 614-293-3559 Andrew.otey@osumc.edu | |
| Principal Investigator: Anthony Michaels, MD | |
| United States, Texas | |
| Baylor (University Medical Center Transplant Research) | Recruiting |
| Dallas, Texas, United States, 75246 | |
| Contact: Martha P Mueller, RN, BSN 214-820-1771 martha.mueller1@baylorhealth.edu | |
| Principal Investigator: James F Trotter, MD | |
| UTSW A: UT Parkland Memorial Hospital | Recruiting |
| Dallas, Texas, United States, 75235 | |
| Contact: Jody Balko, PhD, MT/ASCP 214-645-6113 jody.balko@utsouthwestern.edu | |
| Principal Investigator: William M Lee, MD | |
| UTSW B: UT St. Paul | Recruiting |
| Dallas, Texas, United States, 75390 | |
| Contact: Jody Balko, PhD, MT/ASCP 214-645-6113 jody.balko@utsouthwestern.edu | |
| Principal Investigator: William M Lee, MD | |
| United States, Wisconsin | |
| University of Wisconsin (GI Research Office) | Recruiting |
| Madison, Wisconsin, United States, 53792 | |
| Contact: Kelly Richie, BS 608-262-5404 kr2@medicine.wisc.edu | |
| Principal Investigator: Adnan Said, MD | |
Sponsors and Collaborators
Cumberland Pharmaceuticals
Investigators
| Principal Investigator: | Brendan McGuire, MD | University of Alabama at Birmingham |
More Information
No publications provided
| Responsible Party: | Cumberland Pharmaceuticals |
| ClinicalTrials.gov Identifier: | NCT01436500 History of Changes |
| Other Study ID Numbers: | CPI-IFE-001 |
| Study First Received: | August 31, 2011 |
| Last Updated: | April 24, 2013 |
| Health Authority: | United States: Food and Drug Administration |
Keywords provided by Cumberland Pharmaceuticals:
|
Type 1 Hepatorenal Syndrome Type 2 Hepatorenal Syndrome Hepatorenal Syndrome |
Type 1 HRS Type 2 HRS HRS |
Additional relevant MeSH terms:
|
Hepatorenal Syndrome Liver Diseases Digestive System Diseases Kidney Diseases Urologic Diseases |
Ifetroban Platelet Aggregation Inhibitors Hematologic Agents Therapeutic Uses Pharmacologic Actions |
ClinicalTrials.gov processed this record on May 23, 2013