Edema Due to Heart Failure or Cirrhosis Clinical Trial
Official title:
A Phase IV, Two-part, Open-label Study Assessing the Pharmacokinetics, Safety and Pharmacodynamics of Single and Multiple Doses of Spironolactone Oral Suspension in Pediatric Patients With Edema Due to Heart Failure or Cirrhosis
This is a 2-part, 2 periods per part, open-label study with spironolactone oral suspension in pediatric patients with edema due to HF or hepatic cirrhosis. Both study parts will evaluate the safety, PK and PD of multiple doses of spironolactone in patients aged from birth to ≤17 years of age.
This is a 2-part, 2 periods per part, open-label study with spironolactone oral suspension in pediatric patients with edema due to heart failure or hepatic cirrhosis. Both study parts will evaluate the safety, PK and PD of multiple doses of spironolactone. In Part 1 of the study, a single dose of spironolactone oral suspension will be administered. In Part 2 of the study, a low and a high dose of spironolactone oral suspension will be selected based on the results of Part 1, and will be administered to patients. Part 1 During a 14-day screening period, 18 patients will be enrolled in parallel to 1 of 3 groups, with 6 patients in each group (Group 1: adolescents: ≥12 to ≤17 years of age; Group 2: children: ≥6 to <12 years of age; and Group 3: children: ≥2 to <6 years of age). For these patients the study will begin with a multiple-dose period, where patients will be administered a once-daily (QD) 1.5 mg/kg dose of spironolactone oral suspension for a total of 10 days. There will then be a 30-day follow-up period. Following the conclusion of Groups 1 though 3 in the multiple-dose period of Part 1 of the study, a Safety Review Committee will review all data from Groups 1 though 3 and determine whether and how the study should proceed. If the study proceeds as planned, 6 patients aged from birth to <2 years of age will be enrolled into Group 4 during a 14-day screening period. These patients will begin the study with a single-dose period, during which they will be administered a single dose of spironolactone oral suspension at a dose determined by the Safety Review Committee. They will be followed for 7 days. They will proceed into the multiple-dose period, and will be administered a QD dose (at the same level received in the single-dose period), for a total of 10 days. There will then be a 30-day follow-up period. Part 2 After reviewing data from Part 1 of the study, the Safety Review Committee will make the decision whether to open enrollment in Part 2 of the study, whether to open enrollment to all age groups, and the low and high doses of spironolactone oral suspension to be used. If the study proceeds as planned, 54 patients will be enrolled in parallel to either Group 1, 2, or 3, with 18 patients in each. Nine patients in each group will be assigned a low dose of spironolactone oral suspension, and 9 patients will be assigned to a high dose. These patients will proceed as described in Part 1, with a multiple-dose period where spironolactone oral suspension is administered QD at either a low or high dose for a total of 10 days, followed by a 30-day follow-up period. Following the conclusion of Groups 1 through 3 in the multiple-dose period of Part 2, eighteen patients aged from birth to <2 years of age will be enrolled into Group 4. Nine patients will be assigned to a low dose of spironolactone oral suspension, and 9 patients will be assigned to a high dose. As described for Part 1, these patients will begin the study with a single-dose period during which they will be administered a single dose (low or high) of spironolactone oral suspension and then followed for 7 days before being administered a QD dose (at the same level received in the single-dose period), for a total of 10 days. There will then be a 30-day follow-up period. ;