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

Acute Myocardial Infarction Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00271765
• Other study ID #: IPC-15-2003
• Status: Completed
• Phase: Phase 2
• First received: January 3, 2006
• Last updated: November 27, 2006
• Start date: January 2004
• Est. completion date: June 2006

Study information

• Verified date: November 2006
• Source: Inotek Pharmaceuticals Corporation
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationIsrael: Ministry of Health
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: June 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Single Blind, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Acute Myocardial Infarction
• Infarction
• Myocardial Infarction

Intervention

Drug:
• INO-1001

Locations

Country	Name	City	State
Israel	Rambam Medical Center	Haifa
Israel	Meir Medical Center	Kfar Saba
Israel	Hasharon Medical Center	Petach Tikva
Israel	Rabin Medical Center	Petach Tikva
Israel	Assaf Harofe Medical Centre	Zerifin
United States	Holy Cross Hospital	Fort Lauderdale	Florida
United States	West Virginia University	Morgantown	West Virginia
United States	Sentara Norfolk General Hospital	Norfolk	Virginia
United States	Hospital of the University of Pennsylvania	Philadelphia	Pennsylvania
United States	Black Hills Cardiovascular Research	Rapid City	South Dakota
United States	St. Paul Heart Clinic	St. Paul	Minnesota
United States	Toledo Hospital	Toledo	Ohio
United States	Porter Hospital	Valparaiso	Indiana

Sponsors (1)

Lead Sponsor	Collaborator
Inotek Pharmaceuticals Corporation

Countries where clinical trial is conducted

United States,  Israel, 

References & Publications (4)

Grupp IL, Jackson TM, Hake P, Grupp G, Szabó 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. — View Citation

Liaudet L, Szabó E, Timashpolsky L, Virág L, Cziráki A, Szabó 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. — View Citation

Zingarelli B, Cuzzocrea S, Zsengellér Z, Salzman AL, Szabó 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. — View Citation

Zingarelli B, Salzman AL, Szabó 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The safety of INO-1001 will be measured by evaluation of symptoms, vital signs, physical examination, laboratory data, electrocardiograms, etc.
Secondary	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.