Clinical trial NCT06167707: Pharmacokinetics and Pharmacodynamics of Subcutaneous vs Intravenous Furosemide in Healthy Volunteers
Official title: Open-label, Single-dose, Randomized, Two-way Crossover Study to Compare the Pharmacokinetics and Pharmacodynamics of Subcutaneous Injection of SCP-111 (Furosemide) vs Intravenous Injection of Furosemide in Healthy Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Heart Failure
Fluid Overload
Lead sponsor: scPharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2023-12-12
Enrollment: 21
Sex: ALL
Minimum age (years): 45
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: This study aims to compare the pharmacokinetics and pharmacodynamics of intravenous (IV) and subcutaneous (SC) 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.

Detailed description: This is an open-label, single-center, single-dose, randomized, two-way crossover study in healthy volunteers. Each Subject will complete Screening, Baseline, Treatment, and Follow-up Phases.

After a Screening Phase, Subjects meeting entry criteria will be admitted to the clinical research unit (CRU) and undergo baseline assessments. Subjects will be randomly assigned in a 1:1 ratio to 1 of 2 treatment sequences (IV furosemide followed by SC or vice versa). Subjects will remain domiciled in the CRU for each treatment period which will be about 12-hours. After final assessments are performed, Subjects may be discharged from the CRU if safety parameters are acceptable to the Investigator and return to the CRU after a 3-day washout period to receive the second treatment sequence. The Follow-up Phase will occur 24-48 hours after discharge from the CRU following treatment sequence 2, completing Subjects' study participation.

Eligibility criteria: Inclusion Criteria:

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

Exclusion Criteria:

1. Pregnant or lactating women or women of childbearing age who are not willing to use an adequate form of contraception.
2. Systolic BP (SBP) \< 90 mmHg at screening or baseline.
3. Heart rate \> 110 beats per minute (BPM) at screening or baseline.
4. Temperature \> 38°C (oral or equivalent).
5. Serum potassium \< 3.0 or \> 5.5 mEq/L at screening.
6. Other significant cardiac abnormalities which may interfere with study participation or study assessments.
7. 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
8. Presence of implanted ventricular assist device, cardiac defibrillator or pacemaker.
9. 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.
10. Urinary retention due to bladder emptying disorders and/or urethral narrowing.
11. Presence or need for urinary catheterization.
12. Reported history of hepatic cirrhosis.
13. Administration of intravenous radiographic contrast agent within 72 hours prior to Screening.
14. 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).
15. Administration of an investigational drug or implantation of investigational device, or participation in another interventional clinical trial, within 30 days prior to Screening.
16. Any surgical or medical condition which in the opinion of the investigator may interfere with participation in the study or which may affect the outcome of the study.
17. Positive urine drug screen at Screening or Baseline.
18. Blood alcohol concentration \> 2 mg/dL (0.02%) at Screening.
19. Alcohol breath test \> 2 mg/dL (0.02%) on admission to the CRU.
20. History of severe allergic or hypersensitivity reactions to furosemide or any component of the SCP-111 formulation (tromethamine or benzyl alcohol)

Primary outcomes:
measure: AUClast
timeFrame: 12 hours
measure: AUCinf
timeFrame: 12 hours
measure: Cmax
timeFrame: 12 hours
measure: Tmax
timeFrame: 12 hours
measure: λz
timeFrame: 12 hours
measure: t½
timeFrame: 12 hours
measure: V
timeFrame: 12 hours
measure: Vz/F
timeFrame: 12 hours
measure: CL
timeFrame: 12 hours
measure: CL/F
timeFrame: 12 hours
measure: Urine Output
timeFrame: 6 hour, 8 hour and 12 hour
measure: Urinary Sodium
timeFrame: 6 hour, 8 hour and 12 hour
measure: Urinary Potassium
timeFrame: 6 hour, 8 hour and 12 hour
Secondary outcomes:
measure: Adverse Events
timeFrame: Day 0 through Day 5 visit
measure: Injection Site Pain
timeFrame: 12 hours
Other outcomes:
Locations:
city: Tampa
country: United States
facility: Elixia EPCT, LLC
state: Florida
Study officials:
References: