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

NCT02329834 | Completed Phase 2 Results

• 1 other identifier: scP-01-002
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Heart Failure

Outcome Measures

Primary Outcomes (9)

• Cmax

  Maximum observed plasma concentration of Furosemide

  0, 5 min, 15 min, 30 min, 45 min, 60 min, 1.5 hours, 2 hours, 2:05 min, 2:15 min, 2:30 min, 2:45 min, 3 hours, 3:30 min, 4, 5, 6, 8, 10, 12, 14, and 16 hours post-dose

• Tmax

  Time to achieve maximum observed Furosemide plasma concentration

  0, 5 min, 15 min, 30 min, 45 min, 60 min, 1.5 hours, 2 hours, 2:05 min, 2:15 min, 2:30 min, 2:45 min, 3 hours, 3:30 min, 4, 5, 6, 8, 10, 12, 14, and 16 hours post-dose

• AUClast

  The area under the plasma concentration versus time curve from time 0 (pre-dose) to the last quantifiable time point.

  0, 5 min, 15 min, 30 min, 45 min, 60 min, 1.5 hours, 2 hours, 2:05 min, 2:15 min, 2:30 min, 2:45 min, 3 hours, 3:30 min, 4, 5, 6, 8, 10, 12, 14, and 16 hours post-dose

• AUCinf

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

  0, 5 min, 15 min, 30 min, 45 min, 60 min, 1.5 hours, 2 hours, 2:05 min, 2:15 min, 2:30 min, 2:45 min, 3 hours, 3:30 min, 4, 5, 6, 8, 10, 12, 14, and 16 hours post-dose

• AUCext

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

  0, 5 min, 15 min, 30 min, 45 min, 60 min, 1.5 hours, 2 hours, 2:05 min, 2:15 min, 2:30 min, 2:45 min, 3 hours, 3:30 min, 4, 5, 6, 8, 10, 12, 14, and 16 hours post-dose

• λz

  Apparent plasma terminal-phase elimination rate constant

  24 hours

• t 1/2

  Terminal-phase half life

  24 hours

• Volume of Distribution, Terminal Phase

  Systemic Volume of distribution, terminal phase for IV furosemide and Apparent Volume of distribution, terminal phase for SC furosemide

  24 hours

• CL

  Systemic Clearance for IV furosemide and Apparent Systemic Clearance for SC furosemide

  24 hours

Study Arms (2)

Treatment Sequence 1

EXPERIMENTAL

Furosemide Injection Solution for subcutaneous administration (80mg) over 5 hours followed by i.v. Furosemide Injection, USP (80 mg)by i.v. bolus in second period

Drug: Fursemide Injection Solution for subcutaneous administration (80 mg); Drug: Furosemide Injection, USP

Treatment Sequence 2

EXPERIMENTAL

Furosemide Injection, USP (80 mg) by i.v. bolus, followed by Furosemide Injection Solution for subcutaneous administration (80mg) over 5 hours in second period.

Drug: Fursemide Injection Solution for subcutaneous administration (80 mg); Drug: Furosemide Injection, USP

Interventions

Fursemide Injection Solution for subcutaneous administration (80 mg) DRUG

Furosemide Injection Solution, 10mL of undiluted buffered furosemide solution (8mg/mL)

Treatment Sequence 1; Treatment Sequence 2

Furosemide Injection, USP DRUG

Furosemide Injection, USP (10mg/mL), 80 mg by intravenous administration.

Treatment Sequence 1; Treatment Sequence 2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• 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 ≥18 years of age, with body volume and weight \<130 kg and body mass index (BMI) \<38 kg/m2
• Females will be non-pregnant, non-lactating, and post-menopausal, surgically sterile (e.g., tubal ligation, hysterectomy), or use TWO (2) of the following forms of contraception: IUD, IUD with spermicide, female condom with spermicide, contraceptive sponge with spermicide, an intravaginal system, diaphragm with spermicide, cervical cap with spermicide, a male sexual partner who agrees to use a male condom with spermicide, a sterile sexual partner, OR abstinence
• History of at least 3 months treated heart failure (NYHA class II/III) with presence of symptoms of chronic volume overload requiring ongoing treatment with oral furosemide at a dose of ≥ 40 mg per day for at least 30 days prior to baseline
• NT-proBNP \> 300 pg/mL or BNP \> 100 pg/mL
• Agrees to abstain from using alcohol, caffeine-containing products, and tobacco-/nicotine-containing products through CRU discharge (period 2).
• Able to participate in the study in the opinion of the investigator
• Has the ability to understand the requirements of the study and is willing to comply with all study procedures

You may not qualify if:

• Acute Decompensated Heart Failure (ADHF) or recent history of hospitalization for heart failure in the last 4 weeks
• Worsening of signs or symptoms of heart failure in the two weeks prior to the Screening, or those expected to require intravenous loop diuretics or in-patient treatment for heart failure during the study
• Systolic BP (SBP) \< 90 mm Hg
• Temperature \> 38°C (oral or equivalent) or sepsis or active infection requiring IV anti-microbial treatment
• Serum sodium \< 130 mEq/L and Serum potassium \< 3.0 mEq/L
• Significant other 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; or mechanical support (intra-aortic balloon pump, endotracheal intubation, mechanical ventilation, or any ventricular assist device)
• Diagnosed with Type I diabetes mellitus or Type II diabetes requiring insulin therapy
• Presence or need for urinary catheterization, urinary tract abnormality, or disorder interfering with urination
• Impaired renal function, defined as an estimated glomerular filtration rate (eGFR) on admission \< 45 mL/min/1.73m2, calculated using the simplified Modification of Diet in Renal Disease (sMDRD) equation
• Indication of moderate-to-severe hepatic dysfunctions as determined by the investigator
• Administration of intravenous radiographic contrast agent within 72 hours prior to Screening or acute contrast-induced nephropathy at the time of Screening
• Major surgery within 30 days prior to Screening
• Administration of an investigational drug or implantation of investigational device, or participation in another interventional trial, within 30 days prior to Screening
• 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

Sponsors & Collaborators

• scPharmaceuticals, Inc.: lead

Study Sites (1)

Avail Clinical Research, LLC

DeLand, Florida, 32720, United States

Location

MeSH Terms

Conditions

Heart Failure

Interventions

Furosemide

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Sulfanilamides; Sulfonamides; Amides; Organic Chemicals; Aniline Compounds; Amines; Sulfones; Sulfur Compounds

Results Point of Contact

• Title: Sr. Vice President of Clinical Development and Medical Affairs
• Organization: scPharmaceuticals

jmohr@scpharma.com

Study Officials

• Bruce G. Rankin, DO, CPI, MRO, FACOFP

  Avail Clnical Research, LLC

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 22, 2014
• First Posted: January 1, 2015
• Study Start: April 1, 2015
• Primary Completion: October 1, 2015
• Study Completion: October 1, 2015
• Last Updated: December 2, 2022
• Results First Posted: December 2, 2022

Record last verified: 2022-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)