Heart FailurePhase 1/2NCT04384653
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
A Phase 1/2 study testing Furosemide Injection Solution for subcutaneous administration (80 mg), Furosemide Injection, USP and Medfusion 3500 (v6) precision infusion pump in people with Heart Failure, run by SQ Innovation, Inc. at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Heart Failure
- What is being tested?
- Furosemide Injection Solution for subcutaneous administration (80 mg), Furosemide Injection, USP and Medfusion 3500 (v6) precision infusion pump
- Type of treatment
- Injection or infusion, Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- 17 Oct 2020to 12 Jun 2021
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 25Show fewer
- 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.
- Any surgical or medical condition, which in the opinion of the Investigator may pose an undue risk to the subject, interfere with participation in the study, or which may affect the integrity of the study data.
- Positive test for hepatitis B (HBsAg), hepatitis C (HCV), or human immunodeficiency virus (HIV) at Screening.
- Any positive urine drug screen at Screening or clinic admission.
- Concomitant use of any drugs known to interact with furosemide.
- History of alcohol abuse within 6 months prior to Screening and/or signs or symptoms of alcoholism, as determined by the Investigator.
- Any positive alcohol 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.
- Been informed of possible COVID-19 exposure in past 4 weeks, or recent onset of signs or symptoms of possible COVID-19 infection, including cough, shortness of breath, or temperature ≥ 38°C .
- Traveled via airplane or cruiseship within the last 14 days.
Trial locations and contacts
1 site in 1 country.
United States1 site
Accel Research Sites - DeLand Clinical Research Unit
DeLand, Florida, 32720
About this study
Official title: An 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 (80 mg) 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 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.
Read the detailed description
This study will be an open-label, single-dose, randomized, two-way, two-period crossover study in 20 adult subjects previously diagnosed with mild to moderate heart failure (New York Health Association [NYHA] class II/III) being treated with oral furosemide therapy at a dose of ≥40 mg/day. Each subject will complete Screening, Admission, Treatment, and Follow-up Phone Call phases. The Screening Phase will be conducted on an outpatient basis between 28 and 3 days prior to admission. Subjects will be instructed to reduce sodium intake (target <2 g sodium/day) starting 3 days prior to each of the clinical research unit (CRU) admissions. Admission (Day -1) consists of CRU admission and final qualification assessments. The Treatment Phase will comprise two crossover periods separated by a 7-day outpatient fluid re-equilibration washout. Subjects will discontinue oral furosemide at least 24 hours prior to administration of study drug for each Crossover Period (e.g., no oral furosemide should be administered after 10pm the night prior to CRU admission). Subjects will be randomly assigned in a 1:1 ratio to 1 of 2 treatment sequences (AB or BA) to receive both subcutaneous furosemide (Treatment A; Test) and IV furosemide (Treatment B; Reference) in Crossover Periods (i.e., subcutaneous followed by IV or vice versa). Subjects will remain domiciled in the CRU for each treatment Period during the Treatment Phase through 24 hours after administration of study drug, after which time they will be discharged from the CRU if safety parameters are acceptable to the Investigator. Oral furosemide therapy will be re-initiated at discharge after Treatment 1 (i.e., during the 7-day fluid re-equilibration washout) and after Treatment 2 (i.e., between discharge and Follow-up Phone Call). The Follow-up Phone Call Phase will occur 7 days (± 1) after discharge from the CRU following Treatment 2, completing subjects' study participation.
- Conditions
- Heart Failure
- Being tested
- Furosemide Injection Solution for subcutaneous administration (80 mg), Furosemide Injection, USP, Medfusion 3500 (v6) precision infusion pump
- Medical subject headings
- Heart Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Furosemide Injection Solution for subcutaneous administration (80 mg)Drug
Furosemide Injection Solution for subcutaneous administration (80 mg)
Furosemide Injection, USPDrug
Furosemide Injection, USP (10 mg/mL), 80 mg by intravenous administration
Medfusion 3500 (v6) precision infusion pumpDevice
Furosemide Injection Solution for subcutaneous administration (80 mg)
| Study group | Role | What they receive |
|---|---|---|
| Treatment A | Experimental | Furosemide Injection Solution for subcutaneous administration (80 mg) over 5 hours Receives: Drug: Furosemide Injection Solution for subcutaneous administration (80 mg); Device: Medfusion 3500 (v6) precision infusion pump |
| Treatment B | Active comparator | IV Furosemide Injection, USP (80 mg) by IV bolus Receives: Drug: Furosemide Injection, USP; Device: Medfusion 3500 (v6) precision infusion pump |
What is being measured
The primary outcome is the main question the study is designed to answer.
AUC Last
Relative absolute bioavailability of furosemide based on AUC last
Measured: 0 to 24 hours
Secondary outcomes (7)
Cmax
Cmax over 24 hours
Measured: 0 to 24 hours
Tmax
Tmax over 24 hours. Time to maximum plasma concentration was analyzed using non-parametric rank-based testing. Due to the nature of the statistical analysis, data are presented as Sum Scores rather than traditional descriptive time frames.
Measured: 0-24 hours
t1/2
half-life
Measured: 0-24 hours
Urine Volume at 8 Hours
Urine volume collected at 8 hours post dose
Measured: 0-8 hours
Urine Volume at 24 Hours
Urine volume collected from 8 to 24 hours post dose
Measured: 8-24 hours
Sodium Concentration in Urine at 8 Hours
Sodium concentration in urine collected from 0 to 8 hours post dose
Measured: 0 to 8 hours
Sodium Concentration in Urine at 8 to 24 Hours
Sodium concentration in urine collected from 8 to 24 hours post dose
Measured: 8 to 24 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 May 2020
- Study start17 Oct 2020
- Primary completion12 Jun 2021
- Study completion12 Jun 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Heart FailureStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- SQ Innovation, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Accel Clinical Services
- Responsible party
- Sponsor
- Investigators
- Bruce G Rankin, DO, CPI, FACOFP, Principal investigator, Accel Research Sites - DeLand Clinical Research Unit
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04384653
- Sponsor's protocol ID
- SQI-01-01
- Status last verified
- Mar 2023
- First submitted
- 30 Apr 2020
- Last updated
- 15 Jun 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- Yes
- Individual data sharing
- No
Publications
Osmanska J, Brooksbank K, Docherty KF, Robertson S, Wetherall K, McConnachie A, Hu J, Gardner RS, Clark AL, Squire IB, Kalra PR, Jhund PS, Muntendam P, McMurray JJV, Petrie MC, Campbell RT. A novel, small-volume subcutaneous furosemide formulation delivered by an abdominal patch infusor device in patients with heart failure: results of two phase I studies. Eur Heart J Cardiovasc Pharmacother. 2024 Jan 5;10(1):35-44. doi: 10.1093/ehjcvp/pvad073.
PubMed 37804170
Study at a glance
From the registry record, last updated by the sponsor on 15 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An 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 (80 mg) Administered Intravenously in Subjects With Chronic Heart Failure
- ClinicalTrials.gov ID
- NCT04384653
- Acronym / sponsor ID
- SQI-01-01
- Conditions
- Heart Failure
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- SQ Innovation, Inc.Industry (pharma, biotech, devices)
- Collaborators
- Accel Clinical Services
- Study start
- 17 Oct 2020 (actual)
- Primary completion
- 12 Jun 2021 (actual)
- Study completion
- 12 Jun 2021 (actual)
- First posted
- 12 May 2020 (actual)
- Results
- Posted 15 Jun 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This study will be an open-label, single-dose, randomized, two-way, two-period crossover study in 20 adult subjects previously diagnosed with mild to moderate heart failure (New York Health Association [NYHA] class II/III) being treated with oral furosemide therapy at a dose of ≥40 mg/day. Each subject will complete Screening, Admission, Treatment, and Follow-up Phone Call phases. The Screening Phase will be conducted on an outpatient basis between 28 and 3 days prior to admission. Subjects will be instructed to reduce sodium intake (target <2 g sodium/day) starting 3 days prior to each of the clinical research unit (CRU) admissions. Admission (Day -1) consists of CRU admission and final qualification assessments. The Treatment Phase will comprise two crossover periods separated by a 7-day outpatient fluid re-equilibration washout. Subjects will discontinue oral furosemide at least 24 hours prior to administration of study drug for each Crossover Period (e.g., no oral furosemide should be administered after 10pm the night prior to CRU admission). Subjects will be randomly assigned in a 1:1 ratio to 1 of 2 treatment sequences (AB or BA) to receive both subcutaneous furosemide (Treatment A; Test) and IV furosemide (Treatment B; Reference) in Crossover Periods (i.e., subcutaneous followed by IV or vice versa). Subjects will remain domiciled in the CRU for each treatment Period during the Treatment Phase through 24 hours after administration of study drug, after which time they will be discharged from the CRU if safety parameters are acceptable to the Investigator. Oral furosemide therapy will be re-initiated at discharge after Treatment 1 (i.e., during the 7-day fluid re-equilibration washout) and after Treatment 2 (i.e., between discharge and Follow-up Phone Call). The Follow-up Phone Call Phase will occur 7 days (± 1) after discharge from the CRU following Treatment 2, completing subjects' study participation.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Treatment A | Experimental | Drug: Furosemide Injection Solution for subcutaneous administration (80 mg), Device: Medfusion 3500 (v6) precision infusion pumpFurosemide Injection Solution for subcutaneous administration (80 mg) over 5 hours |
| Treatment B | Active comparator | Drug: Furosemide Injection, USP, Device: Medfusion 3500 (v6) precision infusion pumpIV Furosemide Injection, USP (80 mg) by IV bolus |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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.
Key exclusion criteria (25 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Furosemide Injection Solution for subcutaneous administration (80 mg)Furosemide Injection Solution for subcutaneous administration (80 mg) | Drug | Treatment A |
| Furosemide Injection, USPFurosemide Injection, USP (10 mg/mL), 80 mg by intravenous administration | Drug | Treatment B |
| Medfusion 3500 (v6) precision infusion pumpFurosemide Injection Solution for subcutaneous administration (80 mg) | Device | Treatment A, Treatment B |
Primary outcome
AUC Last
Time frame: 0 to 24 hours
Relative absolute bioavailability of furosemide based on AUC last
7 secondary outcomes
Cmax
Time frame: 0 to 24 hours
Tmax
Time frame: 0-24 hours
t1/2
Time frame: 0-24 hours
Urine Volume at 8 Hours
Time frame: 0-8 hours
Urine Volume at 24 Hours
Time frame: 8-24 hours
Sodium Concentration in Urine at 8 Hours
Time frame: 0 to 8 hours
Sodium Concentration in Urine at 8 to 24 Hours
Time frame: 8 to 24 hours
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Jun 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 37804170Osmanska J, Brooksbank K, Docherty KF, Robertson S, Wetherall K, McConnachie A, Hu J, Gardner RS, Clark AL, Squire IB, Kalra PR, Jhund PS, Muntendam P, McMurray JJV, Petrie MC, Campbell RT. A novel, small-volume subcutaneous furosemide formulation delivered by an abdominal patch infusor device in patients with heart failure: results of two phase I studies. Eur Heart J Cardiovasc Pharmacother. 2024 Jan 5;10(1):35-44. doi: 10.1093/ehjcvp/pvad073.
- Individual participant dataSharing planned: No
Related trials for Heart Failure
RecruitingPhase 4
The Effects of Ferric Derisomaltose in Patients With Acute Heart Failure and Iron Deficiency on Exercise Capacity and Quality of Life(COREVIVE-HFrEF)
Heart Failure With Reduced Ejection Fraction, Iron Deficiency
Not yet recruitingPhase 2
A Study of Bimagrumab in Participants With HFpEF
Heart Failure, Diastolic, Diastolic Heart Failure
Recruiting
Evaluation of a French Hospital Discharge Therapeutic Education Program by Nurses for Heart Failure Patient (EduSor)
Heart Failure
Active, not recruiting
Assessment of Combined CCM and ICD Device in HFrEF
Heart Failure, Heart Failure With Reduced Ejection Fraction
Not yet recruiting
RELIEVE-HFrEF TRIAL: REducing Lung congestIon Symptoms Using the v-wavE Shunt in adVancEd Heart Failure With Reduced EF
Heart Failure and Reduced Ejection Fraction, Heart Failure Chronic
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Bruce G Rankin, DO, CPI, FACOFP principal investigator
Accel Research Sites - DeLand Clinical Research Unit
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Furosemide Injection Solution for subcutaneous administration (80 mg), Furosemide Injection, USP and Medfusion 3500 (v6) precision infusion pump in people with Heart Failure, run by SQ Innovation, Inc. at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 15 Jun 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
AUC Last (time frame: 0 to 24 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04384653, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Jun 2026.