E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Acute Decompensated Heart Failure and Renal Insufficiency |
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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 | 10064653 |
E.1.2 | Term | Acute decompensated heart failure |
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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 |
Primary Objective: To assess the effect of BG9928, when added to standard therapy, on the change in body weight at 24 hours following the first dose in subjects hospitalized with ADHF and renal insufficiency.
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E.2.2 | Secondary objectives of the trial |
Secondary Efficacy Objectives: The secondary objectives of this study are to assess the effect of BG9928 when added to standard therapy in subjects with ADHF and renal insufficiency on: • Worsening renal function during the double-blind treatment period up to Day 5 (or discharge if prior to Day 5). • Days of hospital-free survival (DHFS) over 30 days after the first dose of study treatment. • Improvement in Dyspnea Symptom Score at 6 hours following the first dose. • Improvement in Subject Global Clinical Assessments at 24 hours following the first dose.
Safety Objectives: This study will also assess the safety and tolerability of BG9928, when added to standard therapy in subjects hospitalized with ADHF and renal insufficiency as determined by: • The incidence of clinical and laboratory adverse events (AEs) and serious adverse events (SAEs) to 30 days following initial dosing
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Must give written informed consent and any authorizations required by local law (e.g., Protected Health Information [PHI]). 2. Aged 18 years or older at the time of informed consent. 3. Must have previous diagnosis of systolic or diastolic heart failure. 4. Must have ADHF, requiring hospitalization, with clinical evidence for volume overload as demonstrated by at least 2 of the following features: a. Dyspnea or orthopnea b. Rales c. Peripheral edema d. Increased jugular venous pressure e. Chest X-ray consistent with CHF f. Plasma BNP ≥150 pg/mL or NT pro-BNP ≥450 pg/mL 5. Subject requires hospitalization for treatment with IV diuretics for the current episode of ADHF and meets both of the following: a. has received at least 40 mg of furosemide (or equivalent) for the treatment of the current episode of ADHF within 24 hours prior to randomization unless a rationalefor a lower dose is provided by the enrolling Investigator, and b. is randomized within 24 hours of first dose of IV diuretic administered for this episode of ADHF. 6. Renal insufficiency at the time of screening as defined by eGFR ≥20 and ≤70 mL/min/1.73 m2 (determined at the site according to the formula in Appendix 1). 7. Must be able to stand on a standardized scale for weight measurement. 8. All female subjects of child-bearing potential must practice effective contraception during the study and be willing and able to continue contraception for 2 months after their last dose of study treatment. For further details of contraceptive requirements for this study. |
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E.4 | Principal exclusion criteria |
1. History of an allergic reaction to any xanthine-containing substance. 2. History of seizure within the past 10 years or use of any medications for the suppression of seizures within the past 5 years. 3. Within the past 6 months, history of stroke, transient ischemic attack, brain surgery, meningitis/encephalitis, head injury with loss of consciousness or penetrating head trauma. 4. History consistent with illicit use of drugs or alcohol abuse within 6 months prior to Screening. 5. Myocardial infarction (MI) or hemodynamically destabilizing arrhythmia (e.g., ventricular fibrillation or hemodynamically significant ventricular or supraventricular tachycardia) within 30 days of Screening. 6. Cardiac surgery or pacemaker placement within 60 days prior to Screening. 7. Uncorrected hemodynamically significant primary valvular disease or known obstructive or restrictive cardiomyopathy. 8. Serious systemic infection (e.g., septicemia) or major surgical procedures within the 30 days prior to Day 1. 9. Evidence of malignancy within 6 months prior to screening. Subjects with a history of stable prostate cancer, basal cell carcinomas, or fewer than 3 squamous cell carcinomas of the skin are eligible. 10. Receiving adenosine or xanthine-based agents (e.g., aminophylline, theophylline, pentoxifylline, and dyphylline.) 11. Receiving clozapine or metronidazole within 5 days of screening (or anticipated use during study drug treatment period). 12. Current hospitalization initiated by transfer from another acute care inpatient setting. 13. Acute coronary syndrome (ACS) within 48 hours prior to screening evidenced by significant changes in cardiac biomarkers and electrocardiogram (ECG) changes consistent with ischemia. 14. Cardiogenic shock as indicated by a systolic blood pressure <80 mmHg or the need for IV inotropes or vasopressors or an intra-aortic balloon pump to maintain adequate blood pressure and/or systemic perfusion. 15. Respiratory failure at Screening or impending respiratory failure likely requiringinvasive ventilatory support within 8 hours of screening, in the judgment of the enrolling Investigator. 16. Anticipated need for <48 hours hospitalization from Screening (as judged by the enrolling Investigator). 17. Anticipated need for cardiac catheterization during the current hospitalization (as judged at Screening by the enrolling Investigator). 18. Likely to undergo cardiac transplantation, left ventricular assist device (LVAD) or other device implantation, or other cardiac surgery within next 3 months. 19. Anticipated need for use of ultrafiltration or renal replacement therapy (e.g.,hemodialysis or peritoneal dialysis). 20. Baseline body weight >150 kg. 21. Fever, with body temperature >38oC, within the 48 hours prior to first dose. 22. Screening laboratory findings as follows: a. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≥3 times the upper limit of normal b. Total bilirubin >2.0 mg/dL c. Hematocrit <28% or an anticipated need for a blood transfusion 23. Participation in any other investigational study of drugs or devices within 30 days prior to Screening. 24. Nursing mothers, pregnant women, or women planning on becoming pregnant during the study. 25. Presence of any clinically significant (as determined by the Investigator)endocrinologic, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, neurologic, dermatologic, psychiatric, and/or other major disease that might interfere with optimal safe participation in this study. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Change in body weight at 24 hours following the first dose in subjects hospitalized with ADHF and renal insufficiency. |
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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 | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | Yes |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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 | Yes |
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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 250 |
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 | Yes |
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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The Sponsor has defined the End of Study as last subject last visit (LSLV). |
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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 | 2 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |