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

NCT06021860 | Unknown Phase 4 FDA Drug

• 1 other identifier: PREA 3256-4
• Study Type: interventional
• Target: 96
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Edema Due to Heart Failure or Cirrhosis

Outcome Measures

Primary Outcomes (22)

• Part 1: Absorption rate constant (Ka) of spironolactone (time^-1) in the multiple-dose period

  Patients will be assigned to a pharmacokinetic sampling schedule as follows: Group 1, Subgroup 1 - Day 1: pre-dose; Day 10; 0.08-0.5 hours, 1-1.5 hours, 2-3 hours, 4-6 hours, 10-13 hours post-dose; Day 11: 22-26 hours post-dose Group 1, Subgroup 2 - Day 1: pre-dose; Day 10: pre-dose, 0.5-1 hour, 1.5-2 hours, 3-4 hours, 6-8 hours post-dose; Day 11: 22-26 hours post-dose Groups 2 and 3, Subgroup 1 - Day 1: pre-dose; Day 10: 0.08-0.75 hours, 1.5-2.5 hours, 3.5-6 hours, 10-13 hours; Day 11: 22-26 hours post-dose Groups 2 and 3, Subgroup 2 - Day 1: pre-dose; Day 10: pre-dose, 0.75-1.5 hours, 2.5-3.5 hours, 6-8 hours, 10-13 hours post-dose Group 4: the pharmacokinetic sampling schedule during the multiple-dose period for Group 4 will be determined following Safety Review Committee of data from Groups 1 through 3.

  Pre-dose (Day 1) to 22-26 hours post-dose (Day 11)

• Part 2: Absorption rate constant (Ka) of spironolactone (time^-1) in the multiple-dose period

  Patients will be assigned to a pharmacokinetic sampling schedule as follows: Group 1, Subgroup 1 - Day 1: pre-dose; Day 10; 0.08-0.5 hours, 1-1.5 hours, 2-3 hours, 4-6 hours, 10-13 hours post-dose; Day 11: 22-26 hours post-dose Group 1, Subgroup 2 - Day 1: pre-dose; Day 10: pre-dose, 0.5-1 hour, 1.5-2 hours, 3-4 hours, 6-8 hours post-dose; Day 11: 22-26 hours post-dose Groups 2 and 3, Subgroup 1 - Day 1: pre-dose; Day 10: 0.08-0.75 hours, 1.5-2.5 hours, 3.5-6 hours, 10-13 hours; Day 11: 22-26 hours post-dose Groups 2 and 3, Subgroup 2 - Day 1: pre-dose; Day 10: pre-dose, 0.75-1.5 hours, 2.5-3.5 hours, 6-8 hours, 10-13 hours post-dose Group 4: the pharmacokinetic sampling schedule during the multiple-dose period for Group 4 will be determined following Safety Review Committee of data from Groups 1 through 3.

  Pre-dose (Day 1) to 22-26 hours post-dose (Day 11)

• Part 1: Total clearance from plasma after oral administration (CL/F) of spironolactone in the multiple-dose period

  Patients will be assigned to a pharmacokinetic sampling schedule as follows: Group 1, Subgroup 1 - Day 1: pre-dose; Day 10; 0.08-0.5 hours, 1-1.5 hours, 2-3 hours, 4-6 hours, 10-13 hours post-dose; Day 11: 22-26 hours post-dose Group 1, Subgroup 2 - Day 1: pre-dose; Day 10: pre-dose, 0.5-1 hour, 1.5-2 hours, 3-4 hours, 6-8 hours post-dose; Day 11: 22-26 hours post-dose Groups 2 and 3, Subgroup 1 - Day 1: pre-dose; Day 10: 0.08-0.75 hours, 1.5-2.5 hours, 3.5-6 hours, 10-13 hours; Day 11: 22-26 hours post-dose Groups 2 and 3, Subgroup 2 - Day 1: pre-dose; Day 10: pre-dose, 0.75-1.5 hours, 2.5-3.5 hours, 6-8 hours, 10-13 hours post-dose Group 4: the pharmacokinetic sampling schedule during the multiple-dose period for Group 4 will be determined following Safety Review Committee of data from Groups 1 through 3.

  Pre-dose (Day 1) to 22-26 hours post-dose (Day 11)

• Part 2: Total clearance from plasma after oral administration (CL/F) of spironolactone in the multiple-dose period

  Patients will be assigned to a pharmacokinetic sampling schedule as follows: Group 1, Subgroup 1 - Day 1: pre-dose; Day 10; 0.08-0.5 hours, 1-1.5 hours, 2-3 hours, 4-6 hours, 10-13 hours post-dose; Day 11: 22-26 hours post-dose Group 1, Subgroup 2 - Day 1: pre-dose; Day 10: pre-dose, 0.5-1 hour, 1.5-2 hours, 3-4 hours, 6-8 hours post-dose; Day 11: 22-26 hours post-dose Groups 2 and 3, Subgroup 1 - Day 1: pre-dose; Day 10: 0.08-0.75 hours, 1.5-2.5 hours, 3.5-6 hours, 10-13 hours; Day 11: 22-26 hours post-dose Groups 2 and 3, Subgroup 2 - Day 1: pre-dose; Day 10: pre-dose, 0.75-1.5 hours, 2.5-3.5 hours, 6-8 hours, 10-13 hours post-dose Group 4: the pharmacokinetic sampling schedule during the multiple-dose period for Group 4 will be determined following Safety Review Committee of data from Groups 1 through 3.

  Pre-dose (Day 1) to 22-26 hours post-dose (Day 11)

• Part 1: Volume of distribution after oral administration (V/F) of spironolactone in the multiple-dose period

  Patients will be assigned to a pharmacokinetic sampling schedule as follows: Group 1, Subgroup 1 - Day 1: pre-dose; Day 10; 0.08-0.5 hours, 1-1.5 hours, 2-3 hours, 4-6 hours, 10-13 hours post-dose; Day 11: 22-26 hours post-dose Group 1, Subgroup 2 - Day 1: pre-dose; Day 10: pre-dose, 0.5-1 hour, 1.5-2 hours, 3-4 hours, 6-8 hours post-dose; Day 11: 22-26 hours post-dose Groups 2 and 3, Subgroup 1 - Day 1: pre-dose; Day 10: 0.08-0.75 hours, 1.5-2.5 hours, 3.5-6 hours, 10-13 hours; Day 11: 22-26 hours post-dose Groups 2 and 3, Subgroup 2 - Day 1: pre-dose; Day 10: pre-dose, 0.75-1.5 hours, 2.5-3.5 hours, 6-8 hours, 10-13 hours post-dose Group 4: the pharmacokinetic sampling schedule during the multiple-dose period for Group 4 will be determined following Safety Review Committee of data from Groups 1 through 3.

  Pre-dose (Day 1) to 22-26 hours post-dose (Day 11)

• Part 2: Volume of distribution after oral administration (V/F) of spironolactone in the multiple-dose period

  Patients will be assigned to a pharmacokinetic sampling schedule as follows: Group 1, Subgroup 1 - Day 1: pre-dose; Day 10; 0.08-0.5 hours, 1-1.5 hours, 2-3 hours, 4-6 hours, 10-13 hours post-dose; Day 11: 22-26 hours post-dose Group 1, Subgroup 2 - Day 1: pre-dose; Day 10: pre-dose, 0.5-1 hour, 1.5-2 hours, 3-4 hours, 6-8 hours post-dose; Day 11: 22-26 hours post-dose Groups 2 and 3, Subgroup 1 - Day 1: pre-dose; Day 10: 0.08-0.75 hours, 1.5-2.5 hours, 3.5-6 hours, 10-13 hours; Day 11: 22-26 hours post-dose Groups 2 and 3, Subgroup 2 - Day 1: pre-dose; Day 10: pre-dose, 0.75-1.5 hours, 2.5-3.5 hours, 6-8 hours, 10-13 hours post-dose Group 4: the pharmacokinetic sampling schedule during the multiple-dose period for Group 4 will be determined following Safety Review Committee of data from Groups 1 through 3.

  Pre-dose (Day 1) to 22-26 hours post-dose (Day 11)

• Part 1: Total clearance from plasma after oral administration (CL/F) of canrenone in the multiple-dose period

  Patients will be assigned to a pharmacokinetic sampling schedule as follows: Group 1, Subgroup 1 - Day 1: pre-dose; Day 10; 0.08-0.5 hours, 1-1.5 hours, 2-3 hours, 4-6 hours, 10-13 hours post-dose; Day 11: 22-26 hours post-dose Group 1, Subgroup 2 - Day 1: pre-dose; Day 10: pre-dose, 0.5-1 hour, 1.5-2 hours, 3-4 hours, 6-8 hours post-dose; Day 11: 22-26 hours post-dose Groups 2 and 3, Subgroup 1 - Day 1: pre-dose; Day 10: 0.08-0.75 hours, 1.5-2.5 hours, 3.5-6 hours, 10-13 hours; Day 11: 22-26 hours post-dose Groups 2 and 3, Subgroup 2 - Day 1: pre-dose; Day 10: pre-dose, 0.75-1.5 hours, 2.5-3.5 hours, 6-8 hours, 10-13 hours post-dose Group 4: the pharmacokinetic sampling schedule during the multiple-dose period for Group 4 will be determined following Safety Review Committee of data from Groups 1 through 3.

  Pre-dose (Day 1) to 22-26 hours post-dose (Day 11)

• Part 2: Total clearance from plasma after oral administration (CL/F) of canrenone in the multiple-dose period

  Patients will be assigned to a pharmacokinetic sampling schedule as follows: Group 1, Subgroup 1 - Day 1: pre-dose; Day 10; 0.08-0.5 hours, 1-1.5 hours, 2-3 hours, 4-6 hours, 10-13 hours post-dose; Day 11: 22-26 hours post-dose Group 1, Subgroup 2 - Day 1: pre-dose; Day 10: pre-dose, 0.5-1 hour, 1.5-2 hours, 3-4 hours, 6-8 hours post-dose; Day 11: 22-26 hours post-dose Groups 2 and 3, Subgroup 1 - Day 1: pre-dose; Day 10: 0.08-0.75 hours, 1.5-2.5 hours, 3.5-6 hours, 10-13 hours; Day 11: 22-26 hours post-dose Groups 2 and 3, Subgroup 2 - Day 1: pre-dose; Day 10: pre-dose, 0.75-1.5 hours, 2.5-3.5 hours, 6-8 hours, 10-13 hours post-dose Group 4: the pharmacokinetic sampling schedule during the multiple-dose period for Group 4 will be determined following Safety Review Committee of data from Groups 1 through 3.

  Pre-dose (Day 1) to 22-26 hours post-dose (Day 11)

• Part 1: Volume of distribution after oral administration (V/F) of canrenone in the multiple-dose period

  Patients will be assigned to a pharmacokinetic sampling schedule as follows: Group 1, Subgroup 1 - Day 1: pre-dose; Day 10; 0.08-0.5 hours, 1-1.5 hours, 2-3 hours, 4-6 hours, 10-13 hours post-dose; Day 11: 22-26 hours post-dose Group 1, Subgroup 2 - Day 1: pre-dose; Day 10: pre-dose, 0.5-1 hour, 1.5-2 hours, 3-4 hours, 6-8 hours post-dose; Day 11: 22-26 hours post-dose Groups 2 and 3, Subgroup 1 - Day 1: pre-dose; Day 10: 0.08-0.75 hours, 1.5-2.5 hours, 3.5-6 hours, 10-13 hours; Day 11: 22-26 hours post-dose Groups 2 and 3, Subgroup 2 - Day 1: pre-dose; Day 10: pre-dose, 0.75-1.5 hours, 2.5-3.5 hours, 6-8 hours, 10-13 hours post-dose Group 4: the pharmacokinetic sampling schedule during the multiple-dose period for Group 4 will be determined following Safety Review Committee of data from Groups 1 through 3.

  Pre-dose (Day 1) to 22-26 hours post-dose (Day 11)

• Part 2: Volume of distribution after oral administration (V/F) of canrenone in the multiple-dose period

  Patients will be assigned to a pharmacokinetic sampling schedule as follows: Group 1, Subgroup 1 - Day 1: pre-dose; Day 10; 0.08-0.5 hours, 1-1.5 hours, 2-3 hours, 4-6 hours, 10-13 hours post-dose; Day 11: 22-26 hours post-dose Group 1, Subgroup 2 - Day 1: pre-dose; Day 10: pre-dose, 0.5-1 hour, 1.5-2 hours, 3-4 hours, 6-8 hours post-dose; Day 11: 22-26 hours post-dose Groups 2 and 3, Subgroup 1 - Day 1: pre-dose; Day 10: 0.08-0.75 hours, 1.5-2.5 hours, 3.5-6 hours, 10-13 hours; Day 11: 22-26 hours post-dose Groups 2 and 3, Subgroup 2 - Day 1: pre-dose; Day 10: pre-dose, 0.75-1.5 hours, 2.5-3.5 hours, 6-8 hours, 10-13 hours post-dose Group 4: the pharmacokinetic sampling schedule during the multiple-dose period for Group 4 will be determined following Safety Review Committee of data from Groups 1 through 3.

  Pre-dose (Day 1) to 22-26 hours post-dose (Day 11)

• Part 1: Change from baseline in body weight (kg) (Groups 1 through 3)

  Body weight should be measured using the same scale each time and will be reported at: Screening; Day 1: pre-dose (baseline) and anytime between 6 and 8 hours post-dose; Day 5: pre-dose; Day 10: pre-dose and 6 to 8 hours post-dose; Day 11: 22 to 26 hours post-dose; Day 18: during visit.

  Day 1 to Day 18

• Part 1: Change from baseline in body weight (kg) (Group 4)

  Body weight should be measured using the same scale each time and will be reported at: Screening; Day 1: pre-dose (baseline), and anytime between 6 and 8 hours post-dose; Day 3: anytime between 46 and 50 hours post-dose; Day 8: 166 to 170 hours post-dose; Day 8: 166 to 170 hours post-dose; Day 9: pre-dose and anytime between 6 and 8 hours post-dose; Day 13: pre-dose; Day 18: pre-dose and 6 to 8 hours post-dose; Day 19: 22 to 26 hours post-dose; Day 26: during visit.

  Day 1 to Day 26

• Part 2: Change from baseline in body weight (kg) (Groups 1 through 3)

  Body weight should be measured using the same scale each time and will be reported at: Screening; Day 1: pre-dose (baseline) and anytime between 6 and 8 hours post-dose; Day 5: pre-dose; Day 10: pre-dose and 6 to 8 hours post-dose; Day 11: 22 to 26 hours post-dose; Day 18: during visit.

  Day 1 to Day 18

• Part 2: Change from baseline in body weight (kg) (Group 4)

  Body weight should be measured using the same scale each time and will be reported at: Screening; Day 1: pre-dose (baseline), and anytime between 6 and 8 hours post-dose; Day 3: anytime between 46 and 50 hours post-dose; Day 8: 166 to 170 hours post-dose; Day 8: 166 to 170 hours post-dose; Day 9: pre-dose and anytime between 6 and 8 hours post-dose; Day 13: pre-dose; Day 18: pre-dose and 6 to 8 hours post-dose; Day 19: 22 to 26 hours post-dose; Day 26: during visit.

  Day 1 to Day 26

• Part 1: Change from baseline in sodium/potassium (Na/K) ratio (Groups 1 through 3)

  The Na/K ratio (mmol/mmol) will be calculated using data from spot urine (all groups) and 24-hour urine chemistry (Groups 1 and 2) collection. Spot urine will be collected for analysis of electrolytes at the following timepoints in all groups: Day -1: late afternoon/prior to dinner and last void prior to bedtime; Day 1: first morning void; Day 10: late afternoon/prior to dinner and last void prior to bedtime; Day 11: first morning void. 24-hour urine will be collected for analysis of electrolytes in Groups 1 and 2 only. Urine collection begins on Day -1 AFTER the first morning void and ends AFTER the first morning void on Day 1. Urine collection should start AFTER the first morning void on Day 10 and end AFTER the first morning void on Day 11.

  Day -1 to Day 11

• Part 1: Change from baseline in sodium/potassium (Na/K) ratio (Group 4)

  The Na/K ratio (mmol/mmol) will be calculated using data from spot urine (all groups) and 24-hour urine chemistry (Groups 1 and 2) collection. Spot urine will be collected for analysis of electrolytes at the following timepoints: Day 8: late afternoon/prior to dinner and last void prior to bedtime; Day 9: first morning void; Day 18: late afternoon/prior to dinner and last void prior to bedtime; Day 19: first morning void.

  Day 8 to Day 19

• Part 2: Change from baseline in sodium/potassium (Na/K) ratio (Groups 1 through 3)

  The Na/K ratio (mmol/mmol) will be calculated using data from spot urine (all groups) and 24-hour urine chemistry (Groups 1 and 2) collection. Spot urine will be collected for analysis of electrolytes at the following timepoints in all groups: Day -1: late afternoon/prior to dinner and last void prior to bedtime; Day 1: first morning void; Day 10: late afternoon/prior to dinner and last void prior to bedtime; Day 11: first morning void. 24-hour urine will be collected for analysis of electrolytes in Groups 1 and 2 only. Urine collection begins on Day -1 AFTER the first morning void and ends AFTER the first morning void on Day 1. Urine collection should start AFTER the first morning void on Day 10 and end AFTER the first morning void on Day 11.

  Day -1 to Day 11

• Part 2: Change from baseline in sodium/potassium (Na/K) ratio (Group 4)

  The Na/K ratio (mmol/mmol) will be calculated using data from spot urine (all groups) and 24-hour urine chemistry (Groups 1 and 2) collection. Spot urine will be collected for analysis of electrolytes at the following timepoints: Day 8: late afternoon/prior to dinner and last void prior to bedtime; Day 9: first morning void; Day 18: late afternoon/prior to dinner and last void prior to bedtime; Day 19: first morning void.

  Day 8 to Day 19

• Part 1: Change from baseline in fractional excretion of sodium (FENa; %) (Groups 1 through 3)

  FENa will be calculated using data from spot urine (all groups) and 24-hour urine chemistry (Groups 1 and 2) collection. Spot urine will be collected for analysis of electrolytes at the following timepoints in all groups: Day -1: late afternoon/prior to dinner and last void prior to bedtime; Day 1: first morning void; Day 10: late afternoon/prior to dinner and last void prior to bedtime; Day 11: first morning void. 24-hour urine will be collected for analysis of electrolytes in Groups 1 and 2 only. Urine collection begins on Day -1 AFTER the first morning void and ends AFTER the first morning void on Day 1. Urine collection should start AFTER the first morning void on Day 10 and end AFTER the first morning void on Day 11. FENa will be calculated as follows: \[(urine sodium × plasma creatinine)/plasma sodium × urine creatinine) × 100\]

  Day -1 to Day 11

• Part 1: Change from baseline in fractional excretion of sodium (FENa; %) (Group 4)

  FENa will be calculated using data from spot urine (all groups) and 24-hour urine chemistry (Groups 1 and 2) collection. Spot urine will be collected for analysis of electrolytes at the following timepoints: Day 8: late afternoon/prior to dinner and last void prior to bedtime; Day 9: first morning void; Day 18: late afternoon/prior to dinner and last void prior to bedtime; Day 19: first morning void. FENa will be calculated as follows: \[(urine sodium × plasma creatinine)/plasma sodium × urine creatinine) × 100\]

  Day 8 to Day 19

• Part 2: Change from baseline in fractional excretion of sodium (FENa; %) (Groups 1 through 3)

  FENa will be calculated using data from spot urine (all groups) and 24-hour urine chemistry (Groups 1 and 2) collection. Spot urine will be collected for analysis of electrolytes at the following timepoints in all groups: Day -1: late afternoon/prior to dinner and last void prior to bedtime; Day 1: first morning void; Day 10: late afternoon/prior to dinner and last void prior to bedtime; Day 11: first morning void. 24-hour urine will be collected for analysis of electrolytes in Groups 1 and 2 only. Urine collection begins on Day -1 AFTER the first morning void and ends AFTER the first morning void on Day 1. Urine collection should start AFTER the first morning void on Day 10 and end AFTER the first morning void on Day 11. FENa will be calculated as follows: \[(urine sodium × plasma creatinine)/plasma sodium × urine creatinine) × 100\]

  Day -1 to Day 11

• Part 2: Change from baseline in fractional excretion of sodium (FENa; %) (Group 4)

  FENa will be calculated using data from spot urine (all groups) and 24-hour urine chemistry (Groups 1 and 2) collection. Spot urine will be collected for analysis of electrolytes at the following timepoints: Day 8: late afternoon/prior to dinner and last void prior to bedtime; Day 9: first morning void; Day 18: late afternoon/prior to dinner and last void prior to bedtime; Day 19: first morning void. FENa will be calculated as follows: \[(urine sodium × plasma creatinine)/plasma sodium × urine creatinine) × 100\]

  Day 8 to Day 19

Secondary Outcomes (31)

• Parts 1 and 2: Incidence of adverse events, serious adverse events, and adverse events leading to discontinuation during the single-dose periods (Group 4 only)

  Day 1 to Day 8

• Parts 1 and 2: Number of patients with clinically significant findings from clinical laboratory tests, vital signs, and physical examinations during the single-dose periods (Group 4 only)

  Day 1 to Day 8

• Parts 1 and 2: Absorption rate constant (Ka) of spironolactone (time^-1) in the single-dose period (Group 4 only)

  Day 1 to Day 8

• Parts 1 and 2: Total clearance from plasma after oral administration (CL/F) of spironolactone in the single-dose period (Group 4 only)

  Day 1 to Day 8

• Parts 1 and 2: Volume of distribution after oral administration (V/F) of spironolactone in the single-dose period (Group 4 only)

  Day 1 to Day 8

Study Arms (8)

Part 1: multiple doses spironolactone oral suspension (Group 1)

EXPERIMENTAL

Patients aged ≥12 to ≤17 years of age in Part 1 of the study, administered spironolactone oral suspension QD for 10 days

Drug: Spironolactone Oral Suspension

Part 1: multiple doses spironolactone oral suspension (Group 2)

EXPERIMENTAL

Patients aged ≥6 to \<12 years of age in Part 1 of the study, administered spironolactone oral suspension QD for 10 days

Drug: Spironolactone Oral Suspension

Part 1: multiple doses spironolactone oral suspension (Group 3)

EXPERIMENTAL

Patients aged ≥2 to \<6 years of age in Part 1 of the study, administered spironolactone oral suspension QD for 10 days

Drug: Spironolactone Oral Suspension

Part 1: single and multiple doses spironolactone oral suspension (Group 4)

EXPERIMENTAL

Patients aged from birth to \<2 years of age in Part 1 of the study, administered spironolactone oral suspension as a single dose, and then QD for 10 days

Drug: Spironolactone Oral Suspension

Part 2: multiple doses spironolactone oral suspension (Group 1)

EXPERIMENTAL

Patients aged ≥12 to ≤17 years of age in Part 2 of the study, administered low or high dose spironolactone oral suspension QD for 10 days

Drug: Spironolactone Oral Suspension

Part 2: multiple doses spironolactone oral suspension (Group 2)

EXPERIMENTAL

Patients aged ≥6 to ≤12 years of age in Part 2 of the study, administered low of high dose spironolactone oral suspension QD for 10 days

Drug: Spironolactone Oral Suspension

Part 2: multiple doses spironolactone oral suspension (Group 3)

EXPERIMENTAL

Patients aged ≥2 to ≤6 years of age in Part 2 of the study, administered low or high dose spironolactone oral suspension QD for 10 days

Drug: Spironolactone Oral Suspension

Part 2: single and multiple doses spironolactone oral suspension (Group 4)

EXPERIMENTAL

Patients aged from birth to \<2 years of age in Part 2 of the study, administered low or high dose spironolactone oral suspension as a single dose, and then QD for 10 days

Drug: Spironolactone Oral Suspension

Interventions

Spironolactone Oral Suspension DRUG

Spironolactone will be dosed on a mg/kg basis, with actual weight on Day 1 (pre-dose) determining the spironolactone suspension volume administered. Therefore, for a given patient, the dose administered on Day 1, based on the weight measured on Day 1, will be administered throughout their participation in the study. Spironolactone will be administered as a single dose in the single-dose periods (Group 4, Parts 1 and 2), and as QD dosing in the multiple-dose periods (Groups 1 to 4, Parts 1 and 2). The low and high doses to be administered during Part 2 of the study will be determined by the Safety Review Committee following their review of Part 1 data.

Also known as: Carospir®

Part 1: multiple doses spironolactone oral suspension (Group 1); Part 1: multiple doses spironolactone oral suspension (Group 2); Part 1: multiple doses spironolactone oral suspension (Group 3); Part 1: single and multiple doses spironolactone oral suspension (Group 4); Part 2: multiple doses spironolactone oral suspension (Group 1); Part 2: multiple doses spironolactone oral suspension (Group 2); Part 2: multiple doses spironolactone oral suspension (Group 3); Part 2: single and multiple doses spironolactone oral suspension (Group 4)

Eligibility Criteria

• Age: Up to 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• Prematurity, defined as babies not born out of full-term pregnancy (Group 4 only) (˂38 weeks of gestation).
• Have received spironolactone or eplerenone in the past 14 days before Screening.
• Current acute renal injury (as determined by the Investigator).
• Chronic renal insufficiency: estimated glomerular filtration rate calculated using the modified Schwartz formula \<30% of expected for age and size.
• Electrocardiogram corrected QT interval of \>460 msec.
• Patients who have received blood transfusions within 2 weeks prior to Screening, and for the duration of treatment.
• Electrolyte disturbances (at Screening):
• Has poorly controlled diabetes (HbA1c \>8.5%).
• Requires circulatory assistance device.
• 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 history of hypersensitivity or intolerance to spironolactone or other ingredients in the study drug formulation.
• 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.
• Is pregnant or lactating.

Sponsors & Collaborators

• CMP Development, LLC: lead

MeSH Terms

Conditions

Fibrosis

Interventions

Canrenoic Acid

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Gerald Sakowski

  CMP Pharma

  STUDY DIRECTOR

Central Study Contacts

Paul Sudhakar, M.Pharm

CONTACT

816-507-8249; pauls@ptspharma.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 28, 2023
• First Posted: September 1, 2023
• Study Start: June 1, 2024
• Primary Completion: March 1, 2025
• Study Completion: March 1, 2025
• Last Updated: September 28, 2023

Record last verified: 2023-09