Heart FailurePhase 1/2FUROPHARM-HFNCT02350725
Furosemide Pharmacodynamics and Pharmacokinetics After Subcutaneous or Oral Administration
A Phase 1/2 study testing Furosemide injection solution for subcutaneous administration (80 mg) and Oral Furosemide tablets (80 mg) in people with Heart Failure, run by scPharmaceuticals, Inc. at 1 site in Netherlands.
Trial summary
The purpose of this pilot study is to investigate the pharmacodynamic and pharmacokinetic parameters of a novel furosemide formulation administered subcutaneously as compared to oral furosemide. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Heart Failure
- What is being tested?
- Furosemide injection solution for subcutaneous administration (80 mg) and Oral Furosemide tablets (80 mg)
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteNetherlands
- Study dates
- Dec 2014to Jun 2015
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Written informed consent obtained before any assessment is performed
- Male and female subjects ≥18 years of age, with body weight <120 kg and body mass index (BMI) <30 kg/m2
- Female subjects must be at least 2 years post-menopausal
- Participant must have been on oral furosemide (40 mg oid or bid) or therapeutic equivalent (bumetanide 1 mg oid or bid) for a period 90 days before the first dose of study medication
- History of chronic heart failure according to 2012 ESC guidelines with presence of moderate symptoms of chronic fluid overload. Chronic fluid overload is defined as presence of stable signs and symptoms of heart failure and congestion, like dyspnea at mild exertion or minimal exertion, pulmonary congestion and/or peripheral edema at the time of presentation in combination with elevated levels on natriuretic peptides (NT-proBNP > 300 ng/L)
- In the opinion of the investigator, able to participate in the study
Who cannot join
- Acute Decompensated Heart Failure (ADHF) or recent history of ADHF or significant worsening in their HF symptoms (within prior 2 weeks)
- Contraindication to furosemide
- Systolic BP (SBP) < 90 mm Hg
- Temperature > 38°C (oral or equivalent) or sepsis or active infection requiring i.v. anti-microbial treatment
- Serum sodium < 130 mmol/L and Serum potassium < 3.0 mmol/L
- Current or planned (throughout the completion of study drug infusion) treatment with any i.v. 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)
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- History of gastric or intestinal surgery that may affect absorption of oral medication
- Presence or need for urinary catheterization
- Current or planned ultrafiltration, hemofiltration, or dialysis
- Impaired renal function defined as an estimated glomerular filtration rate (eGFR) on admission < 30 mL/min/1.73 m2 will be calculated as per standard at local laboratory
- 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 trial, within 30 days before screening
- Inability to follow instructions or comply with procedures
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Single Center, Randomized, Open-label, Cross-over Exploratory Study to Evaluate the Pharmacodynamic and Pharmacokinetic Response to a Subcutaneous Administration or Oral Administration of Furosemide in Subjects With Heart Failure Presenting With Chronic Fluid Overload
The purpose of this pilot study is to investigate the pharmacodynamic and pharmacokinetic parameters of a novel furosemide formulation administered subcutaneously as compared to oral furosemide.
- Conditions
- Heart Failure
- Being tested
- Furosemide injection solution for subcutaneous administration (80 mg), Oral Furosemide tablets (80 mg)
- Keywords
- Chronic Fluid Overload
- 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
Oral Furosemide tablets (80 mg)Drug
| Study group | Role | What they receive |
|---|---|---|
| Group 1 | Experimental | Furosemide injection solution for subcutaneous administration (80 mg) over 5 hours followed by Oral Furosemide tablets (80 mg) in second period. Receives: Drug: Furosemide injection solution for subcutaneous administration (80 mg); Drug: Oral Furosemide tablets (80 mg) |
| Group 2 | Experimental | Oral Furosemide tablets (80 mg) followed by Furosemide injection solution for subcutaneous administration (80 mg) over 5 hours in second period. Receives: Drug: Furosemide injection solution for subcutaneous administration (80 mg); Drug: Oral Furosemide tablets (80 mg) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Diuresis and natriuresis
Statistical summaries with a graphical presentation will show mean and individual diuresis and natriuresis time profiles such as time to first void, volume of first void, diuresis and natriuresis measured at 60 minute intervals up to 480 minutes following furosemide injection solution for subcutaneous administration or oral tablets. The diuretic response will be compared between therapies using t-tests or Wilcoxon test.
Measured: 8 hours
Secondary outcomes (5)
Body Water Content
The correlation (Pearson coefficient) between bioimpedance (body water content) and diuresis will be investigated including bioimpedance measurement of fluid overload as a predictor diuretic response.
Measured: 8 hours
Pharmacokinetic profiles
A graphical presentation showing mean and individual plasma furosemide concentration-time profiles for comparison between subcutaneous or oral administration. Plasma furosemide concentration-time data will be analyzed using a non-compartmental method and population PK approach (non-linear mixed-effect model). Furosemide concentrations will be summarized using descriptive statistics (including N, mean, standard deviation (SD), coefficient of variation (CV%), median, minimum and maximum) for each treatment.
Measured: 8 hours
Cardiac Markers (NTpro-BNP, hs-Trop T, galectin-3)
Correlation methods to investigate interaction between cardiac makers (NTpro-BNP, hs-Trop T, galectin-3) and pharmacodynamic parameters (diuresis and natriuresis).
Measured: 8 hours
Dypsnea Scores on Visual Analog Scale and Likert Scale
Dyspnea score (Dyspnea Visual Analog Scale and Likert Scale), the New York Heart Association (NYHA) Functional Classification and thirst distress and grading assessments by subjects in response to subcutaneous or oral administration.
Measured: 8 hours
Injection site reaction on Draize Scale and Visual Analog Pain Scale
Visual inspection of injection site, 5-point Draize Scale and Visual Analog pain assessment recorded during subcutaneous administration.
Measured: 8 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jan 2015 (estimated)
- Study startDec 2014
- Primary completionJun 2015
- Study completionJun 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- scPharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Rudolf A. de Boer, MD, PhD, Principal investigator, University Medical Center Groningen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02350725
- Sponsor's protocol ID
- SCP-01-001
- Other IDs
- 2014-002546-49, 2014
- Acronym
- FUROPHARM-HF
- Status last verified
- Dec 2014
- First submitted
- 9 Dec 2014
- Last updated
- 27 Jun 2018
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Jun 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Single Center, Randomized, Open-label, Cross-over Exploratory Study to Evaluate the Pharmacodynamic and Pharmacokinetic Response to a Subcutaneous Administration or Oral Administration of Furosemide in Subjects With Heart Failure Presenting With Chronic Fluid Overload
- ClinicalTrials.gov ID
- NCT02350725
- Acronym / sponsor ID
- FUROPHARM-HF / SCP-01-001
- Conditions
- Heart Failure
- Keywords
- Chronic Fluid Overload
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- scPharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Study start
- Dec 2014
- Primary completion
- Jun 2015 (actual)
- Study completion
- Jun 2015 (actual)
- First posted
- 30 Jan 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this pilot study is to investigate the pharmacodynamic and pharmacokinetic parameters of a novel furosemide formulation administered subcutaneously as compared to oral furosemide.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Group 1 | Experimental | Drug: Furosemide injection solution for subcutaneous administration (80 mg), Drug: Oral Furosemide tablets (80 mg)Furosemide injection solution for subcutaneous administration (80 mg) over 5 hours followed by Oral Furosemide tablets (80 mg) in second period. |
| Group 2 | Experimental | Drug: Furosemide injection solution for subcutaneous administration (80 mg), Drug: Oral Furosemide tablets (80 mg)Oral Furosemide tablets (80 mg) followed by Furosemide injection solution for subcutaneous administration (80 mg) over 5 hours in second period. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Written informed consent obtained before any assessment is performed
- Male and female subjects ≥18 years of age, with body weight <120 kg and body mass index (BMI) <30 kg/m2
- Female subjects must be at least 2 years post-menopausal
- Participant must have been on oral furosemide (40 mg oid or bid) or therapeutic equivalent (bumetanide 1 mg oid or bid) for a period 90 days before the first dose of study medication
- History of chronic heart failure according to 2012 ESC guidelines with presence of moderate symptoms of chronic fluid overload. Chronic fluid overload is defined as presence of stable signs and symptoms of heart failure and congestion, like dyspnea at mild exertion or minimal exertion, pulmonary congestion and/or peripheral edema at the time of presentation in combination with elevated levels on natriuretic peptides (NT-proBNP > 300 ng/L)
Key exclusion criteria (15 listed)
- Acute Decompensated Heart Failure (ADHF) or recent history of ADHF or significant worsening in their HF symptoms (within prior 2 weeks)
- Contraindication to furosemide
- Systolic BP (SBP) < 90 mm Hg
- Temperature > 38°C (oral or equivalent) or sepsis or active infection requiring i.v. anti-microbial treatment
- Serum sodium < 130 mmol/L and Serum potassium < 3.0 mmol/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) | Drug | Group 1, Group 2 |
| Oral Furosemide tablets (80 mg) | Drug | Group 1, Group 2 |
Primary outcome
Diuresis and natriuresis
Time frame: 8 hours
Statistical summaries with a graphical presentation will show mean and individual diuresis and natriuresis time profiles such as time to first void, volume of first void, diuresis and natriuresis measured at 60 minute intervals up to 480 minutes following furosemide injection solution for subcutaneous administration or oral tablets. The diuretic response will be compared between therapies using t-tests or Wilcoxon test.
5 secondary outcomes
Body Water Content
Time frame: 8 hours
Pharmacokinetic profiles
Time frame: 8 hours
Cardiac Markers (NTpro-BNP, hs-Trop T, galectin-3)
Time frame: 8 hours
Dypsnea Scores on Visual Analog Scale and Likert Scale
Time frame: 8 hours
Injection site reaction on Draize Scale and Visual Analog Pain Scale
Time frame: 8 hours
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jun 2018.
- Subcutaneous Furosemide in Heart Failure: Pharmacokinetic Characteristics of a Newly Buffered SolutionLink provided by the sponsor.
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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.
Rudolf A. de Boer, MD, PhD principal investigator
University Medical Center Groningen
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) and Oral Furosemide tablets (80 mg) in people with Heart Failure, run by scPharmaceuticals, Inc. at 1 site in Netherlands.
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 6 inclusion and 15 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 27 Jun 2018. 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 Netherlands. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Diuresis and natriuresis (time frame: 8 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 27 Jun 2018.