Acute Decompensated Heart Failure and Renal Insufficiency MedDRA version: 9.1 Level: LLT Classification code 10064653 Term: Acute decompensated heart failure
Conditions
Interventions
Product Name: BG9928
Product Code: BG9928
Pharmaceutical Form: Powder for solution for injection
INN or Proposed INN: 3-[4-(2,6-dioxo-1,3-dipropyl-2,3,6,7-tetrahydro-1H-purin-8-yl)-
CAS Number: 340021
Sponsors
Biogen Idec Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
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. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
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 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 i
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 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. ;Secondary Objective: 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 ;Primary end point(s): Change in body weight at 24 hours following the first dose in subjects hospitalized with ADHF and renal insufficiency. | — |
Countries
Bulgaria, Czech Republic, Finland, Germany, Italy, Netherlands, Sweden
Outcome results
None listed