Exploratory Study on the Safety, Tolerability, and Pharmacodynamics of IMB-1018972 in Subjects With Angina Due to Obstructive Coronary Artery Disease (IMPROVE-Ischemia)

Study Overview
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Brief Summary
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The purpose of this study is to assess the safety and tolerability of IMB-1018972 in subjects with obstructive CAD and inducible ischemia.

Official Title
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A Randomized, Double-Blind, Placebo-Controlled, Exploratory Study on the Safety, Tolerability, and Pharmacodynamics of IMB-1018972 in Subjects With Angina Due to Obstructive Coronary Artery Disease

Conditions
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Ischemia, Coronary Artery Disease

Intervention / Treatment
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* Drug: IMB-1018972
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Documented history of stable angina (CCS grading I-III) or anginal equivalent for ≥1 month prior to screening Ability to safely abstain from beta blockers for 48 hours prior to echo examinations in the opinion of the Investigator Preserved LV systolic function, defined as LVEF≥50% by any imaging modality Obstructive CAD and recent evidence of stress-induced myocardial ischemia Exclusion Criteria: Women of childbearing potential or who are currently pregnant or breast-feeding Clinically indicated for coronary revascularization (PCI/CABG) at time of screening or clinically significant LMS or proximal LAD stenosis likely to warrant revascularization during the study period in the opinion of the investigator. Type 1 insulin dependent diabetes mellitus (IDDM) Presence of pacemaker, cardiac resynchronization therapy and/or implantable cardioverter defibrillator Severe or clinically significant valvular heart disease Clinically significant concurrent condition which could prevent the patient from performing any of the protocol-specified assessments, represent a safety concern if the patient participates in the trial or could confound trial assessments of safety or tolerability

Ages Eligible for Study
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Minimum Age: 35 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: IMB-1018972 200mg<br> | Drug: IMB-1018972<br>* Modified release (MR) oral tablet<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Matching oral tablet<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability of IMB-1018972 as measured by incidence and severity of treatment emergent AEs (including AEs leading to study drug discontinuation and AEs leading to death), as well as incidence of treatment emergent SAEs |  | Randomization through Week 10 Safety Follow-up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in number of ischemic segments during hyperemia (ischemia defined as absolute MBF ≤2.0 ml/kg/min) as measured by adenosine stress 15O-H2O PET | Ischemia score defined on the basis of absolute hyperemic MBF as: (1) MBF 2.0-2.3 ml/g/min; (2) 1.7- 2.0 ml/g/min; (3) MBF <1.7 ml/g/min | Baseline through Week 8 | 
| Change in total ischemia burden measured as ischemia score summed across all segments as measured by adenosine stress 15O-H2O PET |  | Baseline through Week 8 | 
| Change in inducible perfusion defect expressed as % of myocardium as measured by adenosine stress 15O-H2O PET |  | Baseline through Week 8 |