Heart Failure and Renal Insufficiency. MedDRA version: 9.1 Level: LLT Classification code 10038474 Term: Renal insufficiency MedDRA version: 9.1 Level: LLT Classification code 10019279 Term: Heart failure
Conditions
Interventions
Product Name: Adentri
Product Code: Tonapofylline
Pharmaceutical Form: Capsule, hard
CAS Number: 340021-17-2
Current Sponsor code: Tonap
Sponsors
Biogen Idec
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). 2. Must be 18 years of age or older. 3. Must have a previous diagnosis of HF with symptoms of HF present at screening (i.e., subjects must be graded as NYHA Class II, III, or IV). 4. Must meet the following criteria (subjects graded as NYHA Class III or IV at screening must meet one of the following, while subjects graded as NYHA Class II at screening must meet both of the following): • history of hospitalization for HF >1 month and =12 months prior to the screening visit, or documented, unscheduled outpatient treatment with intravenous (IV) diuretics, IV vasodilators, or IV inotropic medications >1 month and =12 months prior to the screening visit • documented BNP =150 pg/mL, or NTproBNP =500 pg/mL, within the 12 months prior to Day 1. 5. Must have renal insufficiency as defined by a reduced estimated glomerular filtration rate (eGFR) at the time of screening =20 and =70 mL/min/1.73 m2, as determined by the Modification of Diet in Renal Disease (MDRD) equation (abbreviated version). 6. Must be on an oral loop diuretic for at least the 4 weeks prior to Day 1. Dose adjustments are allowed within the 4 weeks prior to Day 1, but the dose on Day 1 must be within 50% to 200% of the dose the subject was receiving at 4 weeks prior to Day 1. The introduction or withdrawal of any other class of diuretic (i.e., thiazide diuretics) is not allowed within the 4 weeks prior to Day 1 7. Subjects with a reduced LVEF (=40%) documented during screening must be on a pharmacological treatment regimen for HF for at least the 4 weeks prior to Day 1. The HF regimen must include: • treatment with a beta-blocker, unless contraindicated due to intolerance, and • treatment with an angiotensin converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB), unless contraindicated due to intolerance. Note: The dose of any of the HF medications listed above may be adjusted once within the 4 weeks prior to Day 1. This restriction also applies to subjects with LVEF >40% if they are receiving treatment with beta-blockers, ACE inhibitors, and/or ARBs. 8. Women of childbearing 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, please refer to Section 15.5.3. All female subjects of childbearing potential must have a negative pregnancy test on Screening Day and Day 1. 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 compound. 2. History of seizure within the past 10 years or use of any medication for the suppression of seizures within the past 5 years. 3. Within the past 2 years, history of head injury with loss of consciousness, stroke, or transient ischemic attack. 4. History of multiple sclerosis, Alzheimer’s disease, mental retardation, meningitis/encephalitis, brain surgery, or penetrating head trauma. 5. History of, or prior neuroimaging evidence of, intracranial pathology known to increase the risk of seizure such as brain tumors of any kind (including meningioma), arteriovenous malformation, cerebral cavernous malformation, hydrocephalus, or encephalomalacia. 6. History consistent with illicit use of drugs or alcohol abuse within 6 months prior to Day 1. 7. Hospitalization for HF within 30 days of Day 1. 8. Myocardial infarction (MI) within 30 days of Day 1. 9. Hemodynamically destabilizing arrhythmia (e.g., ventricular tachycardia or ventricular fibrillation) within 30 days of Day 1. 10. Cardiac surgery within 60 days prior to Day 1. 11. Uncorrected hemodynamically significant primary valvular disease. 12. Known obstructive or restrictive cardiomyopathy. 13. Currently receiving chronic renal replacement therapy (e.g., hemodialysis or peritoneal dialysis). 14. Receiving adenosine or xanthine-based agents (e.g., aminophylline, theophylline, pentoxifylline, or dyphylline). 15. Receiving clozapine or metronidazole within 5 days of screening, during the screening period, or anticipated use during study drug treatment. 16. Regular consumption of excessive amounts of caffeinated beverages (e.g., >72 ounces [2.13 liters or 9 cups] of coffee/day). 17. Initiation of cardiac resynchronization treatment within 30 days prior to Day 1. 18. Serious systemic infection (e.g., septicemia) or major surgical procedures within the 30 days prior to Day 1. 19. Fever, with body temperature >38oC, within the 48 hours prior to first dose. 20. Evidence of malignancy within 6 months prior to Day 1. Subjects with a history of stable prostate cancer, basal cell carcinomas, or fewer than 3 squamous cell carcinomas are eligible. 21. Likelihood, in the Investigator’s opinion, of undergoing cardiac transplantation, left ventricular assist device (LVAD) or other device implantation, or other cardiac surgerywithin next 3 months; or of requiring continuous IV inotropic treatment, or referral for hospice or end of life treatment. 22. Sustained systolic blood pressure >170 or 2.0 mg/dL. 24. Nursing mothers, pregnant women, or women planning on becoming pregnant during the study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this study is to assess the safety and tolerability of Tonapofylline administered to subjects with heart failure and renal insufficiency; Secondary Objective: The secondary objectives of this study are to assess the effect of Tonapofylline on the following in subjects with heart failure and renal insufficiency: • Quality of life as assessed by the Kansas City Cardiomyopathy Questionnaire (KCCQ) • Exercise capacity as measured by 6-minute walk distance • Renal function as assessed by serum creatinine and Cystatin-C • Concomitant medications used to treat heart failure ;Primary end point(s): The safety and tolerability of Tonapofylline administered to subjects with stable heart failure and renal insufficiency. This objective will be evaluated by the incidence of AEs and SAEs, clinically abnormal physical examinations and vital signs, shifts to outside the normal ranges in laboratory parameters, and electrocardiogram results. | — |
Countries
Germany, United Kingdom
Outcome results
None listed