A Study of INO-1001, an Intravenous PARP (Poly [ADP Ribose] Polymerase) Inhibitor in Acute Heart Attack Patients Undergoing Primary Percutaneous Coronary Intervention - Full Text View

Purpose

The primary purpose of this study is to assess the safety of INO-1001 in subjects who have experienced a heart attack and are to be treated with coronary angioplasty.

Condition	Intervention	Phase
Acute Myocardial Infarction	Drug: INO-1001	Phase 2

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety Study Intervention Model: Parallel Assignment Masking: Single Blind Primary Purpose: Prevention
Official Title:	A Phase II Randomized, Placebo-Controlled, Single-Blind, Multi-Center Dose-Escalation Study to Evaluate Tolerability, Safety, Pharmacokinetics, and Pharmacodynamics of a Single Intravenous Administration of INO-1001 in Subjects With ST-Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention

Resource links provided by NLM:

MedlinePlus related topics: Angioplasty Heart Attack

U.S. FDA Resources

Further study details as provided by Inotek Pharmaceuticals Corporation:

Primary Outcome Measures:

The safety of INO-1001 will be measured by evaluation of symptoms, vital signs, physical examination, laboratory data, electrocardiograms, etc.

Secondary Outcome Measures:

The effect of INO-1001 on heart muscle damage will be evaluated by blood tests. Other blood tests will measure how INO-1001 is absorbed and removed by the body after exposure to different doses.

Estimated Enrollment:	40
Study Start Date:	January 2004
Estimated Study Completion Date:	June 2006

Detailed Description:

Currently, heart attacks may be treated with clot-dissolving medicines, coronary angioplasty, or a combination of both. Unblocking of blood flow to the heart following coronary angioplasty can cause side effects such as heart tissue and blood vessel damage, abnormal heart rhythms and death of heart muscle cells.

In animal studies, the PARP enzyme has been shown to be involved in damaging heart muscle after the sudden unblocking of coronary arteries. INO-1001 blocks the PARP enzyme, and so it may reduce heart damage in humans who have had their coronary arteries unblocked after a heart attack.

A total of 40 patients will be selected and randomly assigned to either INO-1001 or placebo (sugar water). One dose only of the drug will be given prior to coronary angioplasty. Patients will be followed until 30 days after surgery.

The following information will be gathered: vital signs, symptoms, physical examination, blood and urine tests, electrocardiograms, and other information from medical charts.

The information provided in this listing is disclosed solely to comply with regulatory requirements. The drug INO-1001 has not yet been approved for marketing and is only available to patients who participate in a clinical trial and are chosen for the treatment group.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Subjects with acute myocardial infarction (as defined in protocol) with onset within 24 hours prior to randomization.
Scheduled for primary percutaneous coronary intervention within 3 hours of presentation at a hospital participating in this study.
Males and non-pregnant, non-lactating females.

Exclusion Criteria:

Subjects will be required to undergo a full medical review in order to exclude serious medical, or psychological illness prior to inclusion.
History of a hypersensitivity reaction to more than three drugs or mannitol.
Participation in any investigational study within 30 days of randomization
Treatment with certain restricted medications within a specified time prior to participation in the study.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00271765

Locations

United States, Florida
Holy Cross Hospital
Fort Lauderdale, Florida, United States, 33308
United States, Indiana
Porter Hospital
Valparaiso, Indiana, United States, 46383
United States, Minnesota
St. Paul Heart Clinic
St. Paul, Minnesota, United States, 55102
United States, New Jersey

Newark, New Jersey, United States
United States, Ohio
Toledo Hospital
Toledo, Ohio, United States, 43606
United States, Pennsylvania
Hospital of the University of Pennsylvania
Philadelphia, Pennsylvania, United States
United States, South Dakota
Black Hills Cardiovascular Research
Rapid City, South Dakota, United States, 57701
United States, Vermont

Burlington, Vermont, United States
United States, Virginia
Sentara Norfolk General Hospital
Norfolk, Virginia, United States
United States, West Virginia
West Virginia University
Morgantown, West Virginia, United States, 26506
Israel
Rambam Medical Center
Haifa, Israel, 31096
Meir Medical Center
Kfar Saba, Israel, 95847
Rabin Medical Center
Petach Tikva, Israel, 49100
Hasharon Medical Center
Petach Tikva, Israel, 49100

Rehovot, Israel
Assaf Harofe Medical Centre
Zerifin, Israel

Sponsors and Collaborators

Inotek Pharmaceuticals Corporation

More Information

Publications:

Liaudet L, Szabo E, Timashpolsky L, Virag L, Cziraki A, Szabo C. Suppression of poly (ADP-ribose) polymerase activation by 3-aminobenzamide in a rat model of myocardial infarction: long-term morphological and functional consequences. Br J Pharmacol. 2001 Aug;133(8):1424-30.

Zingarelli B, Cuzzocrea S, Zsengeller Z, Salzman AL, Szabo C. Protection against myocardial ischemia and reperfusion injury by 3-aminobenzamide, an inhibitor of poly (ADP-ribose) synthetase. Cardiovasc Res. 1997 Nov;36(2):205-15.

Zingarelli B, Salzman AL, Szabo C. Genetic disruption of poly (ADP-ribose) synthetase inhibits the expression of P-selectin and intercellular adhesion molecule-1 in myocardial ischemia/reperfusion injury. Circ Res. 1998 Jul 13;83(1):85-94.

Grupp IL, Jackson TM, Hake P, Grupp G, Szabo C. Protection against hypoxia-reoxygenation in the absence of poly (ADP-ribose) synthetase in isolated working hearts. J Mol Cell Cardiol. 1999 Jan;31(1):297-303.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Morrow DA, Brickman CM, Murphy SA, Baran K, Krakover R, Dauerman H, Kumar S, Slomowitz N, Grip L, McCabe CH, Salzman AL. A randomized, placebo-controlled trial to evaluate the tolerability, safety, pharmacokinetics, and pharmacodynamics of a potent inhibitor of poly(ADP-ribose) polymerase (INO-1001) in patients with ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention: results of the TIMI 37 trial. J Thromb Thrombolysis. 2009 May;27(4):359-64. Epub 2008 Jun 6.

ClinicalTrials.gov Identifier:	NCT00271765 History of Changes
Other Study ID Numbers:	IPC-15-2003
Study First Received:	January 3, 2006
Last Updated:	November 27, 2006
Health Authority:	United States: Food and Drug Administration Israel: Ministry of Health

Keywords provided by Inotek Pharmaceuticals Corporation:

Myocardial infarction
Coronary angioplasty
PARP inhibitor
PARP inhibition
Heart Attack

Additional relevant MeSH terms:

Infarction
Myocardial Infarction
Ischemia
Pathologic Processes
Necrosis

Myocardial Ischemia
Heart Diseases
Cardiovascular Diseases
Vascular Diseases

ClinicalTrials.gov processed this record on May 23, 2013