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

NCT04384653 | Completed Phase 1 FDA Drug FDA Device

• 1 other identifier: SQI-01-01
• Study Type: interventional
• Target: 20
• 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 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.

Conditions

Heart Failure

Outcome Measures

Primary Outcomes (1)

• Bioavailability

  Relative absolute bioavailability following 5-hour subcutaneous infusion based on a comparison of AUC (subcutaneous: IV) of furosemide

  0 to 24 hours

Secondary Outcomes (6)

• Pharmacokinetic parameters

  0 to 24 hours

• Pharmacokinetic parameters

  0 to 24 hours

• Urine volume

  0 to 24 hours

• Sodium concentration in urine

  0 to 24 hours

• Pain and discomfort

  0 to 5 hours

Study Arms (2)

Treatment A

EXPERIMENTAL

Furosemide Injection Solution for subcutaneous administration (80 mg) over 5 hours for Treatment Period 1 and IV Furosemide Injection, USP (80 mg) by IV bolus for Treatment Period 2

Drug: Furosemide Injection Solution for subcutaneous administration (80 mg); Drug: Furosemide Injection, USP; Device: Medfusion 3500 (v6) precision infusion pump

Treatment B

EXPERIMENTAL

IV Furosemide Injection, USP (80 mg) by IV bolus for Treatment Period 1 and Furosemide Injection Solution for subcutaneous administration (80 mg) over 5 hours for Treatment Period 2

Drug: Furosemide Injection Solution for subcutaneous administration (80 mg); Drug: Furosemide Injection, USP; Device: Medfusion 3500 (v6) precision infusion pump

Interventions

Furosemide Injection Solution for subcutaneous administration (80 mg) DRUG

Furosemide Injection Solution for subcutaneous administration (80 mg)

Treatment A; Treatment B

Furosemide Injection, USP DRUG

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

Treatment A; Treatment B

Medfusion 3500 (v6) precision infusion pump DEVICE

Furosemide Injection Solution for subcutaneous administration (80 mg)

Treatment A; Treatment B

Eligibility Criteria

• Age: 18 Years - 80 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 and ≤ 80 years of age, with body weight \<130 kg and body mass index (BMI) \<38 kg/m2.
• Females will be non-pregnant, non-lactating, or post-menopausal, or surgically sterile (e.g., tubal ligation, hysterectomy),
• Females of childbearing potential will use TWO of the following forms of contraception: intrauterine device (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.
• 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 Day -1.
• Agrees to abstain from using alcohol, caffeine-containing products, and tobacco-/nicotine-containing products while in residence at the CRU.
• 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 IV loop diuretics or inpatient treatment for heart failure during the study.
• Systolic blood pressure (SBP) \<90 mmHg.
• Temperature ≥38°C (oral or equivalent) or sepsis or active infection requiring IV anti-microbial treatment.
• Serum sodium \<130 mEq/L and serum potassium \<3.5 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 (intraaortic balloon pump, endotracheal intubation, mechanical ventilation, or any ventricular assist device).
• Subject is cachectic.
• 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 IV 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.

Sponsors & Collaborators

• SQ Innovation, Inc.: lead
• Accel Clinical Services: collaborator

Study Sites (1)

Accel Research Sites - DeLand Clinical Research Unit

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

Study Officials

• Bruce G Rankin, DO, CPI, FACOFP

  Accel Research Sites - DeLand Clinical Research Unit

  PRINCIPAL INVESTIGATOR

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: April 30, 2020
• First Posted: May 12, 2020
• Study Start: October 17, 2020
• Primary Completion: June 12, 2021
• Study Completion: June 12, 2021
• Last Updated: September 20, 2021

Record last verified: 2021-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)