NCT03909529

Drug-drug Interaction (DDI) Study of Spironolactone (Perpetrator) and Digoxin (Substrate Drug)

Two Way Crossover Oral Drug-drug Interaction Study of Spironolactone (Perpetrator) and Digoxin (Substrate Drug) in Healthy Adult Human Subjects Under Fasting Condition

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 28 (actual)
• Sponsor: CMP Development, LLC · Industry
• Sex: All
• Age: 20 Years – 35 Years
• Healthy volunteers: Accepted

Summary

An open label, balanced, randomized, single-dose, two-treatment, two-sequence, two-period, crossover oral drug-drug interaction study of spironolactone (perpetrator) and Digoxin (substrate drug) in healthy adult human subjects under fasting condition.

Detailed description

Drug interaction studies between spironolactone and digoxin, particularly studies in which digoxin was administered intravenously (Waldorf, S 1978; Fenster, P.E. 1984), indicate that spironolactone may decrease the renal clearance of digoxin by 18-25%, and increase the (area under curve) AUC of digoxin by 35-44%. Although the radioimmunoassay used in the study may be confounded, these results suggest that inhibition of P-gp in the renal proximal tubules may be possible. To account for possible renal P-gp inhibition, subjects in the test group will be pretreated with spironolactone for about 5 days to allow accumulation of some of the metabolites which have a long half-life (e.g., canrenone \~33 hours) and continue to be treated with spironolactone while digoxin is renally eliminated from the body. Based on this assessment, the FDA suggested study design is Treatment A: Single dose of digoxin alone. Treatment B: Digoxin + Spironolactone; Day 1- 9: Spironolactone single dose; Day 6: Digoxin single oral dose. Also, digoxin has a long half-life of 1.5-2 days, and the Pharmacokinetic (PK) sampling scheme of up to 72 hours may not be enough to characterize the elimination kinetics of digoxin. Hence, the plasma concentrations of digoxin up to 96 hours (4 days) postdose is considered This will allow you to detect possible differences in the clearance of digoxin mediated by an interaction with P-gp in the renal proximal tubules. The study also involves collecting urine samples and measuring renal clearance (CLR) and unchanged drug excreted in urine (fe) for digoxin.

Conditions

• Drug Drug Interaction

Interventions

Type	Name	Description
DRUG	Digoxin 250 MCG Oral Tablet	The intervention is for study of drug drug interaction of digoxin when administered with spironolactone oral suspension
DRUG	Spironolactone 25 mg/ 5 mL S/F Suspension	The intervention is for study of drug drug interaction of digoxin when administered with spironolactone oral suspension

Timeline

• Start date: 2019-03-10
• Primary completion: 2019-04-19
• Completion: 2019-04-30
• First posted: 2019-04-10
• Last updated: 2023-05-01
• Results posted: 2023-05-01

Locations

1 site across 1 country: India

Regulatory

• FDA-regulated drug study