NCT04384653

Crossover Study to Compare the Pharmacokinetics and Bioavailability of a Novel Furosemide Regimen Administered Subcutaneously vs. the Same Dose Administered Intravenously in Subjects With Chronic Heart Failure

An Open-label, Single-dose, Randomized, Two-way, Two-period Crossover Study to Compare the Pharmacokinetics and Bioavailability of a Novel Furosemide Regimen Administered Subcutaneously Versus the Same Dose (80 mg) Administered Intravenously in Subjects With Chronic Heart Failure

• Status: Completed
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 20 (actual)
• Sponsor: SQ Innovation, Inc. · Industry
• Sex: All
• Age: 18 Years – 80 Years
• Healthy volunteers: Not accepted

Summary

The proposed study aims to compare the pharmacokinetics and bioavailability of intravenous and subcutaneous Furosemide. Although these regimens are not intended to be bioequivalent, they are both expected to achieve therapeutic plasma levels and induce effective diuresis. The test formulation in this study is a buffered solution, Furosemide Injection Solution at 30 mg/mL at pH 7.4 (range 7.0 to 7.8) and is intended for SC injection according to the instructions in the protocol. A commercial formulation of Furosemide Injection, USP will serve as the reference drug in this study, which will be administered by IV bolus. It contains furosemide 10 mg/mL in solution at alkaline pH of 8.0 to 9.3 and is marketed for IV and IM injection. The primary objective of the study is to estimate the absolute bioavailability of furosemide administered by subcutaneous infusion compared with an equivalent dose of furosemide administered by IV bolus administration.

Detailed description

This study will be an open-label, single-dose, randomized, two-way, two-period crossover study in 20 adult subjects previously diagnosed with mild to moderate heart failure (New York Health Association \[NYHA\] class II/III) being treated with oral furosemide therapy at a dose of ≥40 mg/day. Each subject will complete Screening, Admission, Treatment, and Follow-up Phone Call phases. The Screening Phase will be conducted on an outpatient basis between 28 and 3 days prior to admission. Subjects will be instructed to reduce sodium intake (target \<2 g sodium/day) starting 3 days prior to each of the clinical research unit (CRU) admissions. Admission (Day -1) consists of CRU admission and final qualification assessments. The Treatment Phase will comprise two crossover periods separated by a 7-day outpatient fluid re-equilibration washout. Subjects will discontinue oral furosemide at least 24 hours prior to administration of study drug for each Crossover Period (e.g., no oral furosemide should be administered after 10pm the night prior to CRU admission). Subjects will be randomly assigned in a 1:1 ratio to 1 of 2 treatment sequences (AB or BA) to receive both subcutaneous furosemide (Treatment A; Test) and IV furosemide (Treatment B; Reference) in Crossover Periods (i.e., subcutaneous followed by IV or vice versa). Subjects will remain domiciled in the CRU for each treatment Period during the Treatment Phase through 24 hours after administration of study drug, after which time they will be discharged from the CRU if safety parameters are acceptable to the Investigator. Oral furosemide therapy will be re-initiated at discharge after Treatment 1 (i.e., during the 7-day fluid re-equilibration washout) and after Treatment 2 (i.e., between discharge and Follow-up Phone Call). The Follow-up Phone Call Phase will occur 7 days (± 1) after discharge from the CRU following Treatment 2, completing subjects' study participation.

Conditions

• Heart Failure

Interventions

Type	Name	Description
DRUG	Furosemide Injection Solution for subcutaneous administration (80 mg)	Furosemide Injection Solution for subcutaneous administration (80 mg)
DRUG	Furosemide Injection, USP	Furosemide Injection, USP (10 mg/mL), 80 mg by intravenous administration
DEVICE	Medfusion 3500 (v6) precision infusion pump	Furosemide Injection Solution for subcutaneous administration (80 mg)

Timeline

• Start date: 2020-10-17
• Primary completion: 2021-06-12
• Completion: 2021-06-12
• First posted: 2020-05-12
• Last updated: 2021-09-20

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study
• FDA-regulated device study