A Phase IV, Two-part, Open-label Study Assessing the Pharmacokinetics, Safety and Pharmacodynamics of Spironolactone Oral Suspension in Pediatric Patients

Prior treatment

• Have received spironolactone or eplerenone in the past 14 days before Screening.
• Patients who have received blood transfusions within 2 weeks prior to Screening, and for the duration of treatment.
• Any prior solid organ transplant.
• Major surgery (as determined in the Investigator's judgement) within 1 month of dosing unless approved by the investigator and medical monitor.
• Has known contraindication to treatment with spironolactone.
• Requires treatment with a medication known to affect spironolactone exposure as indicated in the contraindications and drug interaction recommendations listed in the label.
• Participation in a drug study or exposure to any other investigational drug or placebo within 2 months of study drug administration in the current study.
• Concomitant prescription medications outside the stable standard of care regimen for edematous conditions and other chronic comorbidities administered within 2 weeks prior to study drug administration.
• Patients who have smoked or used smoking-cessation or nicotine-containing products within 3 months of the first dose of the study drug until last/End of Study Visit.
• Consumption of caffeine, energy drinks, alcohol, or recreational drugs (including marijuana) within 72 hours prior to administration of study drug on Day 1 and for the duration of the study.
• Uncontrolled (with treatment), active bacterial, fungal, or viral infections within 72 hours prior to Screening.

Other illness

• Has known history of hypersensitivity or intolerance to spironolactone or other ingredients in the study drug formulation.

Lab values

• Electrocardiogram corrected QT interval of \>460 msec.
• Has poorly controlled diabetes (HbA1c \>8.5%).
• Screening laboratory tests positive for HIV, hepatitis B, and hepatitis C.

Age

• Chronic renal insufficiency: estimated glomerular filtration rate calculated using the modified Schwartz formula \<30% of expected for age and size.

Other

• Prematurity, defined as babies not born out of full-term pregnancy (Group 4 only) (˂38 weeks of gestation).
• Current acute renal injury (as determined by the Investigator).
• Electrolyte disturbances (at Screening):
• Requires circulatory assistance device.
• Is pregnant or lactating.
• Use of thiazide diuretics, K-sparing diuretics, any hormonal contraceptive agent, or consumption of any nutrients known to modulate the activity of CYP450 enzymes outside of the permitted use.

• Patient or patient's parent or legal guardian (if applicable) provides written consent to participate in the study and provides written informed consent prior to any study procedures being performed.
• Female patients of childbearing potential may be enrolled if they are practicing abstinence and have a negative urine pregnancy test at Screening and/or Day 1, or using 2 forms of highly effective contraception.
• Male patients with female partners of childbearing potential may be enrolled if they are practicing abstinence or using 2 forms of highly effective contraception.
• Patients must agree to stay in clinic or the supervised care unit on specified days.
• Patients must have past diagnosis of edema (includes peripheral and/or pulmonary edema) due to heart failure or hepatic cirrhosis requiring, or expected to require, treatment with spironolactone in the investigator's judgment.
• Stable therapy for chronic comorbidities (unrelated to HF or cirrhosis, and as approved by the Investigator and Medical Monitor) is allowed, with no changes to these medications in the 72 hours prior to administration of study drug on Day 1 and for the duration of the study.
• Loop diuretics (such as furosemide), if taken, must be stable for 72 hours prior to dosing of spironolactone on Day 1 and to the extent possible for the remainder of the study.