A Study to Evaluate the Safety, Tolerability, and Efficacy of IMB-1018972 in Patients With Refractory Angina
Study Details
Study Description
Brief Summary
The objectives of the study are to assess the safety, tolerability, and potential efficacy of IMB-1018972 on patients with refractory angina. Study will assess functional capacity employing a modified Bruce Protocol treadmill ETT, patient reports of angina symptoms via an electronic diary, and activity using an accelerometer.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: IMB-1018972 Participants will receive IMB-1018972 (200 mg) MR tablets twice daily for 16 weeks |
Drug: IMB-1018972
IMB-1018972 200 mg tablet for oral administration
|
| Placebo Comparator: Placebo Participants will receive matching placebo tablets twice daily for 16 weeks |
Drug: Placebo oral tablet
Matched placebo tablet for oral administration
|
Outcome Measures
Primary Outcome Measures
- Modified Bruce Protocol Treadmill ETT [8 weeks]
Change from baseline to Week 8 in total exercise duration (seconds)
- Safety and Tolerability of IMB-1018972 in Patients with Refractory Angina [16 weeks]
Incidence of AEs, changes from baseline in physical examinations, vital signs, clinical laboratories, and ECG
Secondary Outcome Measures
- Assess the benefit of IMB-1018972 on patient report of angina symptoms employing an electronic diary [16 weeks]
Change from baseline per week in the incidence of angina symptoms
- Assess the potential treatment benefit of IMB-1018972 on patient report of rescue NTG use employing an electronic diary [16 weeks]
Change from baseline in daily counts of NTG use
- Assess the potential treatment benefit of IMB-1018972 on patient activity employing a wearable device [16 weeks]
Change from baseline in total daily activity at Week 16 (activity units)
Eligibility Criteria
Criteria
Inclusion Criteria:
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Is between the ages of 18 and 85 years, inclusive.
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Is capable of understanding the written informed consent, and providing signed, dated, and witnessed written informed consent.
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Has complied with and is willing to continue to comply with the specified procedures (eg, angina diary during screening) and complete specific follow-up evaluations.
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Has coronary artery disease confirmed by at least one of the following:
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Documented prior MI, CABG surgery, or PCI -OR-
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Angiography performed within the 24 months prior to Visit 1 confirming CAD (eg, evidence of ≥70% stenosis of at least one major coronary artery or diffuse CAD).
- Has evidence of stress induced ischemia documented by either:
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Protocol-specified ETT ECG demonstrating at least 0.5 mm exercise-induced ST segment depression with onset <9 minutes on at least 1 of the screening ETTs -OR-
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Prior evidence of stress-induced reversible perfusion defect in the last 24 months (without intervening revascularization) identified by at least one of the following:
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Radionuclide imaging study
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Echocardiographic imaging study
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FFR <0.8
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IFR <0.89
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FFR CT <0.8
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CFR <2.5
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Has a minimum 3 month history of exertional angina, including angina with a minimum frequency of 2 anginal episodes per week on average for the 2 weeks prior to enrolling in the study while on optimal guideline directed medical therapy for their angina.
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Is on optimal, dual agent, antianginal therapy for their angina for at least 1 month prior to the first screening ETT. Consistent with ACC/AHA and ESC Class I guideline directed medical therapy (GDMT), criteria for optimal therapy include treatment with both: (a) a beta-adrenergic blocking agent and treatment with (b) a calcium channel blocker OR a long-acting nitrate. If unacceptable side effects are intolerable and documented with a therapy listed in (a) or (b), treatment with only 1 antianginal medication is acceptable. Additionally, patients should be treated with short-acting nitrates per GDMT.
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Is currently not clinically indicated for coronary revascularization (ie, PCI or CABG) in the opinion of the principle investigator at the time of screening through 6 months after randomization.
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Has a CCS score of II, III or stabilized IV for 1 month prior to screening.
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Meets the following requirements after 2 screening modified Bruce protocol ETTs:
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Stopping the treadmill test due to angina on each test b. Total exercise duration must fall between 3 and 9 minutes on each test c. To document inducible myocardial ischemia: i. For those patients with interpretable ECGs, at least 0.5 mm exercise induced ST segment depression must occur with onset <9 minutes on at least 1 of the screening ETTs.
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Difference in TED between the 2 qualifying ETTs must not exceed 20% of the longer test or 1 minute, whichever limit is smaller.
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Consideration of a third ETT may be discussed by the investigator with the study medical monitor, who may authorize the performance of a third ETT a minimum of 5 days and no more than 10 days after the second ETT
Exclusion Criteria:
- If any of the following have occurred:
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Use of TMZ anytime in prior history
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In the prior 6 months:
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Diagnosis of NYHA Class 3 or 4 (heart failure)
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Hospitalization for heart failure
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Coronary artery bypass graft surgery
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Cardiac resynchronization therapy placement or adjustments to CRT parameters
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Implantable cardioverter defibrillator or biventricular pacemaker placement
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In the prior 3 months:
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Hospitalization for a cardiovascular indication
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Cerebral vascular accident
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Transient ischemic attack
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Percutaneous coronary intervention
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In the prior 1 month:
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Use of perhexiline or meldonium.
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Has a history of moderate to severe valvular heart disease defined as aortic stenosis (valve area <1.5 cm2), aortic insufficiency, mitral stenosis (valve area <1.5 cm2), or mitral valve regurgitation of grade 3 or worse.
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Has significant hepatic disease, with increased liver function tests such as total bilirubin, aspartate aminotransferase, or alanine aminotransferase more than 2 times of ULN at baseline (excluding patients with documented history of Gilbert syndrome).
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Has severe renal impairment (ie, creatinine clearance <30 mL/min at screening, measured using 4-variable modification of diet in renal disease equation).
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Has a history of Parkinson disease, Parkinsonian symptoms, tremors, restless leg syndrome, or other related movement disorders.
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Has a history of vasospastic angina or microvascular angina.
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Has an exacerbating cause for angina (eg, anemia [ie, hemoglobin <10 g/dL], uncontrolled hypertension [ie, BP ≥160/90 mmHg], hyperthyroid, or rapid AF [ie, AF with average rate >120 beats per minute]) at screening.
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Has long-QT and life-threatening LV arrhythmia.
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Has comorbidities limiting life expectancy to less than 3 years.
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Is pregnant, planning pregnancy, or lactating.
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Has a history of alcohol abuse or drug addiction.
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Has a positive test for drugs (eg, opiates, methadone, cocaine, amphetamines [including ecstasy], or barbiturates) at screening.
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Has a positive test for HBsAg, HCV antibodies, or HIV1/2 antibodies at screening.
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Is participating in another research study.
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Is an employee or family member of the investigator or study site personnel.
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Imbria Pharmaceuticals, Inc.
Investigators
- Study Director: Paul Chamberlin, MD, Imbria Pharmaceuticals
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- CIMB-8972-201