IK-1001 (Sodium Sulfide (Na2S) for Injection) in Subjects With Acute ST-Segment Elevation Myocardial Infarction
ST-Segment Elevation Myocardial Infraction
Drug: Sodium Sulfide (Na2S) for Injection
|Study Design:||Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
|Official Title:||A Phase 2, Randomized. Double-Blind, Dose-Escalation, Dose-Expansion, Placebo-Controlled, Multi-Center Study of IK-1001 to Evaluate Safety, Pharmacokinetics , and Proof-of-Concept Efficacy in Subjects With Acute ST-Segment Elevation Myocardial Infarction (STEMI) Undergoing Primary Percutaneous Coronary Intervention|
- Creatine Kinase, Muscle and Brain (CK-MB) Troponin T [ Time Frame: Days 1 through 4, end of treatment ]
- 12-Lead ECG [ Time Frame: Study duration ]
- Vital Signs [ Time Frame: Study duration ]
- Adverse Events [ Time Frame: Study Duration ]
- Cardiac magnetic resonance imaging (MRI) [ Time Frame: Day 4, end of treatment ]
|Study Start Date:||December 2009|
|Estimated Study Completion Date:||December 2009|
|Estimated Primary Completion Date:||December 2009 (Final data collection date for primary outcome measure)|
IK-1001 Sodium Sulfide (Na2S) for Injection
Drug: Sodium Sulfide (Na2S) for Injection
IK-1001 is Na2S administered as an isotonic solution for intravenous (IV) injection or continuous infusion. IK-1001 will be administered as a 3-hour continuous IV infusion started > 5 minutes but < 20 minutes (approximately) prior to coronary artery reperfusion.
Other Name: IK-1001
Placebo Comparator: Placebo
0.9% Sodium Chloride (NaCl)
0.9% Sodium Chloride (NaCl) will be administered in the same manner as the experimental drug.
This is a Phase 2, randomized, dose-escalation, dose-expansion, double-blind, placebo-controlled, multi-center study that will evaluate safety, PK, and POC efficacy in subjects with acute STEMI undergoing PCI.
The study will be conducted in two parts. Part 1 is the dose escalation portion of the study. A minimum of 24 evaluable subjects will be enrolled into Part 1 to receive either IK-1001 (n = 18) or placebo (n = 6). Each subject will receive a continuous infusion of study drug at one of three dose escalating levels of 0.5, 1.0, or 1.5 mg/kg/hr infusion for 3 hours. At each dose level, 8 subjects will be enrolled (6 will receive IK-1001 and 2 will receive placebo). Placebo will consist of commercially available normal saline (NS) [0.9% sodium chloride (NaCl)].
Treatment with study drug (either IK-1001 or placebo) will be initiated only after informed consent is obtained and STEMI diagnosis is made based on clinical and ECG findings. ECG criteria for STEMI diagnosis include:
- Subjects presenting with ≥ 30 minutes of ischemic chest pain but within 12 hours of symptom onset
- Subjects having persistent ST-segment elevation of ≥ 2 mm in at least 2 contiguous leads in ECG
All subjects who receive study drug and have a successful PCI (defined as subjects in whom Grade 3 reperfusion was achieved) will be followed up for safety and efficacy for up to 6 months post-PCI and study drug infusion. Study samples will be collected from all subjects over the first 4 days following PCI for determination of PK parameters of sulfide in blood and thiosulfate in plasma. In Part 1, subjects who do not undergo a PCI for any reason will have study drug discontinued, will be excluded from the efficacy assessments but will be followed up for safety for 7 days, and will be replaced with a new subject.
Part 2 of the study will be an expansion of the highest safe continuous infusion dose evaluated in Part 1. Part 2 aims to further evaluate safety and establish POC efficacy at this dosing level. Initially, up to 190 eligible subjects will be randomized to receive either IK-1001 or placebo at a 1:1 ratio. Two interim analyses (IAs) will be done after 64 and 128 subjects complete the MI size evaluation at Day 4 (range 3 to 5 days), respectively. If there is a safety concern at any dose level, then enrollment in Part 2 will restart at the next lower safe dosing level determined from Part 1. If there is only an adequate or no efficacy signal at any dose level, then enrollment in Part 2 may restart at either an increased dose level (e.g., 1.75 mg/kg/hr for 3 hours) or at a longer duration of infusion (1.5 mg/kg/hr for 6 hours). A decision to stop the trial for safety, efficacy, or futility will be assessed at each IA. No more than 446 subjects will be enrolled in Part 2 of the study.
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