E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Angina pectoris and renal insufficiency whilst undergoing percutaneous coronary intervention (PCI). |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10063886 |
E.1.2 | Term | Renal insufficiency aggravated |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10002384 |
E.1.2 | Term | Angina pectoris aggravated |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The objective of this study will be to evaluate the potential efficacy and safety of BID dosing of DNB-001 (750 mg) given over 72 hours in patients with angina pectoris and chronic kidney disease undergoing elective PCI. The primary objectives include:
• To evaluate the cardio-protective efficacy of DNB-001 versus placebo, as measured by the change in cardiac biomarkers of myonecrosis (cTnI) from baseline to peak levels post-PCI.
• To evaluate the safety of DNB-001 when used in a patient population with angina pectoris and moderate chronic kidney disease undergoing elective percutaneous coronary intervention (angioplasty +/- stent deployment).
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E.2.2 | Secondary objectives of the trial |
•To evaluate the renal-protective efficacy of DNB-001 versus placebo, as measured by the change in SCr (renal function) from baseline to peak level post-PCI.
•Composite endpoint of death, MI, or re-hospitalization for acute coronary syndrome within 28 days of treatment.
•To evaluate the difference in additional potential biomarkers (CKMB). |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
•Males and sterile/post-menopausal ≥ 1 year females aged 18 to 80 years inclusive.
•Scheduled for elective percutaneous coronary intervention for angina pectoris (angioplasty with or without stents).
•Planned administration of an iodine based contrast agent.
•Angina pectoris as classified by the CCS grading system.
•Stage III chronic kidney failure as defined by the National Kidney Foundation (NKF). * eGFR calculated by the MDRD equation of 30 to 59 mL/min/1.73 m2.
•Provide written informed consent.
•Ability to return for all trial visits.
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E.4 | Principal exclusion criteria |
•Emergency cardiac catheterization.
•Hemodynamic instability (Systolic Blood Pressure < 80 mm Hg, or > 200 mm Hg; Heart Rate < 50 bpm, or > 120 bpm).
•Hemodynamic instability (SBP < 80, or > 200; HR < 50, or > 120).
•Cardiac biomarkers (cTnI, cTnT) out of reference ranges at the time of screening.
•Severe/unstable diabetes requiring emergency room or inpatient therapy for control of diabetes within previous 30 days.
•Patients with liver function enzymes (AST, ALT, GGT) out of the normal range at the time of screening.
•Serum creatinine greater than 5 mg/dL for males or greater than 4 mg/dL for females.
•End-stage renal disease requiring dialysis.
•Known acute renal failure at the time of screening.
•Acute pulmonary edema.
•Administration of contrast agent within previous 48 hours.
•Planned re-administration of contrast agent for 28 days post-PCI.
•Known allergy to the planned contrast agent.
•Planned administration of dopamine, mannitol, or fenoldopam during study.
•New therapy or change in dose of a diuretic, ACE inhibitor, or ARB within previous 14 days or during the study.
•Planned new therapy or titration of dose of a diuretic, ACE inhibitor, or ARB within previous 14 days, or during the study, EXCEPT as indicated for the periprocedural period.
•Any treatment with an investigational agent in the past 60 days for any condition. |
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E.5 End points |
E.5.1 | Primary end point(s) |
•The change in cardiac cTnI between the active and placebo arms of the trial from baseline to peak levels post-PCI
•The change in renal function (SCr) between the active and placebo arms of the trial from baseline to peak levels post-PCI
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 4 |
E.8.9.2 | In all countries concerned by the trial days | 0 |