Pharmacokinetics and Pharmacodynamics of Subcutaneous vs Intravenous Furosemide in Healthy Volunteers

NCT06167707 | Completed Phase 1 Results FDA Drug

• 1 other identifier: scP-04-001
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

Brief Summary

This study aims to compare the pharmacokinetics and pharmacodynamics of subcutaneous (SC) and intravenous (IV) furosemide. The test formulation in this study is furosemide injection, 80 mg/1 mL, buffered to a neutral pH for SC administration via an autoinjector. A commercial formulation of furosemide injection, USP, solution 10 mg/mL administered as a 40 mg IV injection over 2 minutes followed by a second dose of 40 mg, 2 hours later, will serve as the reference drug. The objectives of this study are:

• To estimate the bioavailability and describe the pharmacokinetics and pharmacodynamics of furosemide administered as SC injection via autoinjector compared with equivalent dose of furosemide administered as two 40 mg IV injections, two hours apart.
• To describe the safety and tolerability of furosemide administered as SC injection via an autoinjector.

Conditions

Heart Failure; Fluid Overload

Outcome Measures

Primary Outcomes (18)

• AUClast

  Area under the plasma concentration-time curve from time 0 (pre-dose) to time of last measurable plasma concentration.

  SC SCP-111: 0, 5, 15, 30, 45 minutes and 1, 1.25, 1.5, 2, 3, 4, 5, 6, 8, 12 hours post-dose. IV Furosemide: 0, 5, 15, 30, 45 minutes and 1, 1.5, 2 hours after 1st IV dose; 5, 15, 30, 45 minutes and 1, 1.5, 2, 3, 4, 6, 8, 10 hours after 2nd IV dose. IV:

• AUCinf

  Area under the plasma concentration-time curve from time 0 (pre-dose) extrapolated to infinity.

  SC SCP-111: 0, 5, 15, 30, 45 minutes and 1, 1.25, 1.5, 2, 3, 4, 5, 6, 8, 12 hours post-dose. IV Furosemide: 0, 5, 15, 30, 45 minutes and 1, 1.5, 2 hours after 1st IV dose; 5, 15, 30, 45 minutes and 1, 1.5, 2, 3, 4, 6, 8, 10 hours after 2nd IV dose.

• AUCext

  The percentage of the AUC that is extrapolated beyond the last measurable concentration.

  SC SCP-111: 0, 5, 15, 30, 45 minutes and 1, 1.25, 1.5, 2, 3, 4, 5, 6, 8, 12 hours post-dose. IV Furosemide: 0, 5, 15, 30, 45 minutes and 1, 1.5, 2 hours after 1st IV dose; 5, 15, 30, 45 minutes and 1, 1.5, 2, 3, 4, 6, 8, 10 hours after 2nd IV dose.

• Cmax

  Maximum observed plasma concentration of Furosemide

  SC SCP-111: 0, 5, 15, 30, 45 minutes and 1, 1.25, 1.5, 2, 3, 4, 5, 6, 8, 12 hours post-dose. IV Furosemide: 0, 5, 15, 30, 45 minutes and 1, 1.5, 2 hours after 1st IV dose; 5, 15, 30, 45 minutes and 1, 1.5, 2, 3, 4, 6, 8, 10 hours after 2nd IV dose.

• Tmax

  Time of maximum observed Furosemide plasma concentration

  SC SCP-111: 0, 5, 15, 30, 45 minutes and 1, 1.25, 1.5, 2, 3, 4, 5, 6, 8, 12 hours post-dose. IV Furosemide: 0, 5, 15, 30, 45 minutes and 1, 1.5, 2 hours after 1st IV dose; 5, 15, 30, 45 minutes and 1, 1.5, 2, 3, 4, 6, 8, 10 hours after 2nd IV dose.

• λz

  Apparent plasma terminal-phase elimination rate constant

  SC SCP-111: 0, 5, 15, 30, 45 minutes and 1, 1.25, 1.5, 2, 3, 4, 5, 6, 8, 12 hours post-dose. IV Furosemide: 0, 5, 15, 30, 45 minutes and 1, 1.5, 2 hours after 1st IV dose; 5, 15, 30, 45 minutes and 1, 1.5, 2, 3, 4, 6, 8, 10 hours after 2nd IV dose.

• t½

  Terminal-phase half-life

  SC SCP-111: 0, 5, 15, 30, 45 minutes and 1, 1.25, 1.5, 2, 3, 4, 5, 6, 8, 12 hours post-dose. IV Furosemide: 0, 5, 15, 30, 45 minutes and 1, 1.5, 2 hours after 1st IV dose; 5, 15, 30, 45 minutes and 1, 1.5, 2, 3, 4, 6, 8, 10 hours after 2nd IV dose.

• Clearance

  Systemic clearance for IV furosemide (CL) and Apparent systemic clearance for SC furosemide (CL/F)

  SC SCP-111: 0, 5, 15, 30, 45 minutes and 1, 1.25, 1.5, 2, 3, 4, 5, 6, 8, 12 hours post-dose. IV Furosemide: 0, 5, 15, 30, 45 minutes and 1, 1.5, 2 hours after 1st IV dose; 5, 15, 30, 45 minutes and 1, 1.5, 2, 3, 4, 6, 8, 10 hours after 2nd IV dose.

• Volume of Distribution, Terminal Phase

  Systemic Volume of distribution, terminal phase for IV furosemide (V) and Apparent Volume of distribution, terminal phase for SC furosemide (Vz/F)

  SC SCP-111: 0, 5, 15, 30, 45 minutes and 1, 1.25, 1.5, 2, 3, 4, 5, 6, 8, 12 hours post-dose. IV Furosemide: 0, 5, 15, 30, 45 minutes and 1, 1.5, 2 hours after 1st IV dose; 5, 15, 30, 45 minutes and 1, 1.5, 2, 3, 4, 6, 8, 10 hours after 2nd IV dose.

• Urine Output 0-6 Hours

  Total Urine Output from 0 to 6 hours

  0-1, 1-2, 2-3, 3-4, 4-5, 5-6 hours post-dose

• Urine Output 0-8 Hours

  Total Urine Output from 0 to 8 hours

  0-1, 1-2, 2-3, 3-4, 4-5, 5-6, 6-7, 7-8 hours post-dose

• Urine Output 0-12 Hours

  Total Urine Output from 0 to 12 hours

  0-1, 1-2, 2-3, 3-4, 4-5, 5-6, 6-7, 7-8, 8-10, 10-12 hours post-dose

• Urinary Sodium 0-6 Hours

  Urinary sodium excretion from 0 to 6 hours

  0-1, 1-2, 2-3, 3-4, 4-5, 5-6 hours post-dose

• Urinary Sodium 0-8 Hours

  Urinary sodium excretion from 0 to 8 hours

  0-1, 1-2, 2-3, 3-4, 4-5, 5-6, 6-7, 7-8 hours post-dose

• Urinary Sodium 0-12 Hours

  Urinary sodium excretion from 0 to 12 hours

  0-1, 1-2, 2-3, 3-4, 4-5, 5-6, 6-7, 7-8, 8-10, 10-12 hours post-dose

• Urinary Potassium 0-6 Hours

  Urinary potassium excretion from 0 to 6 hours

  0-1, 1-2, 2-3, 3-4, 4-5, 5-6 hours post-dose

• Urinary Potassium 0-8 Hours

  Urinary potassium excretion from 0 to 8 hours

  0-1, 1-2, 2-3, 3-4, 4-5, 5-6, 6-7, 7-8 hours post-dose

• Urinary Potassium 0-12 Hours

  Urinary potassium excretion from 0 to 12 hours

  0-1, 1-2, 2-3, 3-4, 4-5, 5-6, 6-7, 7-8, 8-10, 10-12 hours post-dose

Secondary Outcomes (1)

• Injection Site Pain

  SC SCP-111: pre-dose, immediately after dose, 15, 30 minutes and 6,12 hours post-dose. IV Furosemide: pre-dose, after place IV needle, immediately after 1st IV dose; 15, 30, minutes, immediately after 2nd dose,15, 30 minutes and 4, 10 hours after 2nd dose

Study Arms (2)

Treatment Sequence 1

EXPERIMENTAL

Period 1: SC Period 2: IV

Drug: SCP-111; Drug: Furosemide USP

Treatment Sequence 2

EXPERIMENTAL

Period 1: IV Period 2: SC

Drug: SCP-111; Drug: Furosemide USP

Interventions

SCP-111 DRUG

Furosemide injection 80 mg/mL, 80 mg SC via autoinjector x 1 dose

Treatment Sequence 1; Treatment Sequence 2

Furosemide USP DRUG

Furosemide injection, USP 10 mg/mL, 40 mg IV over 2 minutes followed by 40 mg 2 hours later

Treatment Sequence 1; Treatment Sequence 2

Eligibility Criteria

• Age: 45 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• An Institutional Review Board (IRB) approved informed consent is signed and dated prior to any study-related activities.
• Male and female subjects 45 to 80 years of age.
• Has the ability to understand the requirements of the study and is willing to comply with all study procedures.
• In the opinion of the Investigator, able to participate in the study.

You may not qualify if:

• Pregnant or lactating women or women of childbearing age who are not willing to use an adequate form of contraception.
• Systolic BP (SBP) \< 90 mmHg at screening or baseline.
• Heart rate \> 110 beats per minute (BPM) at screening or baseline.
• Temperature \> 38°C (oral or equivalent).
• Serum potassium \< 3.0 or \> 5.5 mEq/L at screening.
• Other significant cardiac abnormalities which may interfere with study participation or study assessments.
• Current or planned treatment during the study with any IV therapies, including inotropic agents, vasopressors, levosimendan, nesiritide or analogues. scPharmaceuticals, Inc. SCP-111 PK/PD Study Protocol Number: scP-04-001 Confidential Page 14 of 56
• Presence of implanted ventricular assist device, cardiac defibrillator or pacemaker.
• Severely impaired renal function, defined as an estimated glomerular filtration rate (eGFR) at screening admission \< 30 mL/min/1.73m2, calculated using the simplified Modification of Diet in Renal Disease (sMDRD) equation.
• Urinary retention due to bladder emptying disorders and/or urethral narrowing.
• Presence or need for urinary catheterization.
• Reported history of hepatic cirrhosis.
• Administration of intravenous radiographic contrast agent within 72 hours prior to Screening.
• Concomitant or any use within past 30 days of drugs known to interact with furosemide (aminoglycoside antibiotics, ethacrynic acid, high doses of salicylates, cisplatin, tubocurarine, succinylcholine, chloral hydrate, phenytoin, methotrexate, indomethacin, or lithium).
• Administration of an investigational drug or implantation of investigational device, or participation in another interventional clinical trial, within 30 days prior to Screening.

Sponsors & Collaborators

• scPharmaceuticals, Inc.: lead

Study Sites (1)

Elixia EPCT, LLC

Tampa, Florida, 33618, United States

Location

MeSH Terms

Conditions

Heart Failure; Edema

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Senior Vice President, Therapeutic Area Head, Respiratory and Cardiorenal
• Organization: MannKind Corporation

wfares@mannkindcorp.com

203-796-3407

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 4, 2023
• First Posted: December 12, 2023
• Study Start: April 19, 2024
• Primary Completion: June 14, 2024
• Study Completion: June 14, 2024
• Last Updated: March 30, 2026
• Results First Posted: March 11, 2026

Record last verified: 2026-03

Locations

US (1)