NCT02329834

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

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 (80mg) Administered Intravenously in Subjects With Chronic Heart Failure

• Status: Completed
• Phase: Phase 2 / Phase 3
• Study type: Interventional
• Enrollment: 23 (actual)
• Sponsor: scPharmaceuticals, Inc. · Industry
• Sex: All
• Age: 18 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 8 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 objectives of this study are: * To characterize the pharmacokinetics of furosemide administered by continuous subcutaneous infusion using a biphasic delivery profile. * To estimate the absolute bioavailability of furosemide administered by continuous subcutaneous infusion compared with an equivalent dose of furosemide administered by intravenous bolus administration.

Detailed description

This study will be an open-label, single-center, single-dose, randomized, two-way (two-period) crossover study in 16 adult subjects previously diagnosed with mild to moderate heart failure (NYHA class II/III) being treated concomitantly with oral furosemide therapy at a dose of ≥ 40 mg/day. Each subject will complete Screening, Baseline, Treatment, and Follow-Up Phases. The Screening Phase will be conducted on an outpatient basis between 14 and 3 days prior to Baseline. Subjects will be instructed to maintain a \< 2 gm sodium diet within 3 days prior to Baseline. Baseline (Day 0) consists of clinical research unit (CRU) admission and final qualification assessments. The Treatment Phase will comprise two crossover periods separated by a 7-day outpatient fluid re-equilibration washout. Following CRU admission, subjects will discontinue oral furosemide at least 24 hours prior to administration of study drug for each Crossover Period. Subjects will be randomly assigned in a 1:1 ratio to 1 of 2 treatment sequences to receive both intravenous (IV) and subcutaneous (SC) furosemide in Crossover Periods (i.e., IV followed by SC or vice versa). Subjects will remain domiciled in the CRU for each Crossover Period during the Treatment Phase through 24 hours after administration of study drug, after which time they will be discharged if safety parameters are acceptable to the Investigator. Oral furosemide therapy will be re-initiated at discharge after Crossover Period 1 (i.e., during the 7-day fluid re-equilibration washout) and after Crossover Period 2. The Follow-Up Phase will occur 7 days (± 1) after discharge from the CRU following Crossover Period 2, completing subjects' study participation.

Conditions

• Heart Failure

Interventions

Type	Name	Description
DRUG	Fursemide Injection Solution for subcutaneous administration (80 mg)	Furosemide Injection Solution, 10mL of undiluted buffered furosemide solution (8mg/mL)
DRUG	Furosemide Injection, USP	Furosemide Injection, USP (10mg/mL), 80 mg by intravenous administration.

Timeline

• Start date: 2015-04-01
• Primary completion: 2015-10-01
• Completion: 2015-10-01
• First posted: 2015-01-01
• Last updated: 2022-12-02
• Results posted: 2022-12-02

Locations

1 site across 1 country: United States