- ICH GCP
- US Clinical Trials Registry
- Clinical Trial 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
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.
Study Overview
Status
Conditions
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 2
- Phase 3
Contacts and Locations
Study Locations
-
-
Florida
-
DeLand, Florida, United States, 32720
- Avail Clinical Research, LLC
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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
- Positive test for hepatitis B, hepatitis C, or HIV at Screening
- Positive urine drug screen at Screening or Baseline
- Concomitant use of any drugs known to interact with furosemide
- History of alcohol abuse within 6 months prior to screening, as determined by the Investigator
- Positive alcohol breath test on admission to the CRU
- History of severe allergic or hypersensitivity reactions to furosemide
- Donation of greater than 100 mL of either whole blood or plasma within 30 days prior to study drug administration
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Treatment Sequence 1
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
|
Furosemide Injection Solution, 10mL of undiluted buffered furosemide solution (8mg/mL)
Furosemide Injection, USP (10mg/mL), 80 mg by intravenous administration.
|
Experimental: Treatment Sequence 2
Furosemide Injection, USP (80 mg) by i.v.
bolus, followed by Furosemide Injection Solution for subcutaneous administration (80mg) over 5 hours in second period.
|
Furosemide Injection Solution, 10mL of undiluted buffered furosemide solution (8mg/mL)
Furosemide Injection, USP (10mg/mL), 80 mg by intravenous administration.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Cmax
Time Frame: 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
|
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 Frame: 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
|
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
Time Frame: 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
|
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
Time Frame: 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
|
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
Time Frame: 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
|
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
Time Frame: 24 hours
|
Apparent plasma terminal-phase elimination rate constant
|
24 hours
|
t 1/2
Time Frame: 24 hours
|
Terminal-phase half life
|
24 hours
|
Volume of Distribution, Terminal Phase
Time Frame: 24 hours
|
Systemic Volume of distribution, terminal phase for IV furosemide and Apparent Volume of distribution, terminal phase for SC furosemide
|
24 hours
|
CL
Time Frame: 24 hours
|
Systemic Clearance for IV furosemide and Apparent Systemic Clearance for SC furosemide
|
24 hours
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Bruce G. Rankin, DO, CPI, MRO, FACOFP, Avail Clnical Research, LLC
Publications and helpful links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- scP-01-002
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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