Congestive Heart FailurePhase 1NCT03214874
Within Subject Variability Study of ER Torsemide 20 mg Tablet in Healthy Subjects
A Phase 1 study testing Demadex 20mg Tablet and ER Torsemide 20mg Tablet in people with Congestive Heart Failure and Chronic Kidney Diseases, run by Sarfez Pharmaceuticals, Inc. at 1 site in India.
Trial summary
The study will evaluate the within-subject variability of 20mg ER torsemide as compared to 20mg IR torsemide (Demadex) in fully replicate double-crossover trial in healthy volunteers, who are consuming a high-salt diet (300 mmol/day). Read more about this study
- Who is it for?
- Ages 18 to 45 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Congestive Heart Failure, Chronic Kidney Diseases
- What is being tested?
- Demadex 20mg Tablet and ER Torsemide 20mg Tablet
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteIndia
- Study dates
- 19 Jun 2017to 20 Jul 2017
- Phase
- Phase 1
- 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 to 45 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Healthy male or female, non-smoker, weight 50 kg for male and 45 kg for female, clinically acceptable laboratory profiles with ECG and chest X-ray performed within 6 months
Who cannot join
- participation in bioavailability/bioequivalence studies,
- history of drug abuse or alcohol dependence,
- history of allergies including drug allergies,
- known hypersensitivity to Torsemide or related drugs,
- presence of clinically significant disorder,
- systolic blood pressure <90 mm Hg or > 140 mm Hg diastolic blood pressure,
- history of incontinence,
- positive urine drug screening etc.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Randomized,Open Label,Balanced,Two Treatment, Four Period, Two Sequence, Single Oral Dose, Crossover, Replicate Study Under Fasting Conditions to Test Within Subject Variability of 20mg ER Torsemide and Demadex Tablets in Healthy Adults
The study will evaluate the within-subject variability of 20mg ER torsemide as compared to 20mg IR torsemide (Demadex) in fully replicate double-crossover trial in healthy volunteers, who are consuming a high-salt diet (300 mmol/day). The study will also evaluate the effects of ER torsemide and IR torsemide on 24h sodium excretion and total urinary excretion.
Read the detailed description
Immediate Release (IR) Torsemide is a highly effective natriuretic drug but its short duration of action is a major drawback, which allows significant post-dose sodium retention, and as consequence, limits salt loss in patients with heart failure, unless dietary salt intake is severely restricted. Extended Release (ER) torsemide is being developed to address the drawback by prolonging the duration of action to increase sodium excretion even in patients who consume high salt diet (300 mmol/day).
In addition, IR torsemide induces large and abrupt urination that, in some patients, causes incontinence, and as a result, compliance becomes challenging. ER torsemide is formulated to cause robust but gradual urination over an extended period to reduce accidental wetting and improve compliance.
In this study, ER torsemide is tested for within-subject variability in fully replicate design double-crossover trial in healthy volunteers who are on a 300 mmol/day sodium diet (high salt diet). The primary endpoint of the study is full pharmacokinetics measurements after a single dose of either ER torsemide or IR torsemide (Demadex). The secondary endpoints are 24h sodium excretion and total urinary excretion.
- Conditions
- Congestive Heart Failure, Chronic Kidney Diseases
- Being tested
- Demadex 20mg Tablet, ER Torsemide 20mg Tablet
- Medical subject headings
- Heart Failure, Renal Insufficiency, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Demadex 20mg TabletDrug
Also called Torsemide
Immediate Release (IR) Torsemide
ER Torsemide 20mg TabletDrug
Also called ER Torsemide
Extended Release Torsemide 20 mg tablet given once daily
| Study group | Role | What they receive |
|---|---|---|
| Demadex 20mg Tablet | Active comparator | Demadex (IR Torsemide) 20mg tablet once daily is the reference listed drug (RLD) and is marketed for decades to treat edema in Chronic Congestive Heart Failure (CHF) and Chronic Kidney Disease (CKD) patients Receives: Drug: Demadex 20mg Tablet |
| ER Torsemide 20mg Tablet | Experimental | ER Torsemide 20mg tablet once daily is is the new formulation that will release the active ingredient over an extended period Receives: Drug: ER Torsemide 20mg Tablet |
What is being measured
The primary outcome is the main question the study is designed to answer.
Peak plasma concentration
Peak tosremide plasma concentration (Cmax) (ng/ml)
Measured: 24 hour
Total plasma concentration
Area under the plasma concentration versus time curve (AUC) (hr/ng/ml)
Measured: 24 hour
Urinary excretion
Torsemide excretion in urine (microgram/min) over 24h post dose
Measured: 24 hour
Secondary outcomes (2)
Urinary sodium excretion
24h sodium (mmol/min)
Measured: 24 hour
Urine output
24h total urinary output (l/day)
Measured: 24 hour
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jul 2017
- Study start19 Jun 2017
- Primary completion20 Jul 2017
- Study completion20 Jul 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Congestive 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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- Fully Replicate double-crossover
- Masking
- None (open label)
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sarfez Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Christopher Wilcox, MD, PhD, Principal investigator, Georgetown University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03214874
- Sponsor's protocol ID
- CLCD-058-15
- Status last verified
- Apr 2018
- First submitted
- 8 Jul 2017
- Last updated
- 18 Apr 2018
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Murray MD, Deer MM, Ferguson JA, Dexter PR, Bennett SJ, Perkins SM, Smith FE, Lane KA, Adams LD, Tierney WM, Brater DC. Open-label randomized trial of torsemide compared with furosemide therapy for patients with heart failure. Am J Med. 2001 Nov;111(7):513-20. doi: 10.1016/s0002-9343(01)00903-2.
PubMed 11705426
Study at a glance
From the registry record, last updated by the sponsor on 18 Apr 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized,Open Label,Balanced,Two Treatment, Four Period, Two Sequence, Single Oral Dose, Crossover, Replicate Study Under Fasting Conditions to Test Within Subject Variability of 20mg ER Torsemide and Demadex Tablets in Healthy Adults
- ClinicalTrials.gov ID
- NCT03214874
- Acronym / sponsor ID
- CLCD-058-15
- Conditions
- Congestive Heart Failure, Chronic Kidney Diseases
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- Sarfez Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Study start
- 19 Jun 2017 (actual)
- Primary completion
- 20 Jul 2017 (actual)
- Study completion
- 20 Jul 2017 (actual)
- First posted
- 12 Jul 2017 (actual)
- 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 study will evaluate the within-subject variability of 20mg ER torsemide as compared to 20mg IR torsemide (Demadex) in fully replicate double-crossover trial in healthy volunteers, who are consuming a high-salt diet (300 mmol/day). The study will also evaluate the effects of ER torsemide and IR torsemide on 24h sodium excretion and total urinary excretion.
Detailed description
Immediate Release (IR) Torsemide is a highly effective natriuretic drug but its short duration of action is a major drawback, which allows significant post-dose sodium retention, and as consequence, limits salt loss in patients with heart failure, unless dietary salt intake is severely restricted. Extended Release (ER) torsemide is being developed to address the drawback by prolonging the duration of action to increase sodium excretion even in patients who consume high salt diet (300 mmol/day).
In addition, IR torsemide induces large and abrupt urination that, in some patients, causes incontinence, and as a result, compliance becomes challenging. ER torsemide is formulated to cause robust but gradual urination over an extended period to reduce accidental wetting and improve compliance.
In this study, ER torsemide is tested for within-subject variability in fully replicate design double-crossover trial in healthy volunteers who are on a 300 mmol/day sodium diet (high salt diet). The primary endpoint of the study is full pharmacokinetics measurements after a single dose of either ER torsemide or IR torsemide (Demadex). The secondary endpoints are 24h sodium excretion and total urinary excretion.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Fully Replicate double-crossover
| Arm | Type | Receives |
|---|---|---|
| Demadex 20mg Tablet | Active comparator | Drug: Demadex 20mg TabletDemadex (IR Torsemide) 20mg tablet once daily is the reference listed drug (RLD) and is marketed for decades to treat edema in Chronic Congestive Heart Failure (CHF) and Chronic Kidney Disease (CKD) patients |
| ER Torsemide 20mg Tablet | Experimental | Drug: ER Torsemide 20mg TabletER Torsemide 20mg tablet once daily is is the new formulation that will release the active ingredient over an extended period |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (1 listed)
- Healthy male or female, non-smoker, weight 50 kg for male and 45 kg for female, clinically acceptable laboratory profiles with ECG and chest X-ray performed within 6 months
Key exclusion criteria (8 listed)
- participation in bioavailability/bioequivalence studies,
- history of drug abuse or alcohol dependence,
- history of allergies including drug allergies,
- known hypersensitivity to Torsemide or related drugs,
- presence of clinically significant disorder,
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 |
|---|---|---|
| Demadex 20mg TabletAlso: TorsemideImmediate Release (IR) Torsemide | Drug | Demadex 20mg Tablet |
| ER Torsemide 20mg TabletAlso: ER TorsemideExtended Release Torsemide 20 mg tablet given once daily | Drug | ER Torsemide 20mg Tablet |
Primary outcome
Peak plasma concentration
Time frame: 24 hour
Peak tosremide plasma concentration (Cmax) (ng/ml)
Total plasma concentration
Time frame: 24 hour
Area under the plasma concentration versus time curve (AUC) (hr/ng/ml)
Urinary excretion
Time frame: 24 hour
Torsemide excretion in urine (microgram/min) over 24h post dose
2 secondary outcomes
Urinary sodium excretion
Time frame: 24 hour
Urine output
Time frame: 24 hour
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 18 Apr 2018.
- Results publication: PubMed 11705426Murray MD, Deer MM, Ferguson JA, Dexter PR, Bennett SJ, Perkins SM, Smith FE, Lane KA, Adams LD, Tierney WM, Brater DC. Open-label randomized trial of torsemide compared with furosemide therapy for patients with heart failure. Am J Med. 2001 Nov;111(7):513-20. doi: 10.1016/s0002-9343(01)00903-2.
- Individual participant dataSharing planned: No
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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.
Christopher Wilcox, MD, PhD principal investigator
Georgetown University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Demadex 20mg Tablet and ER Torsemide 20mg Tablet in people with Congestive Heart Failure and Chronic Kidney Diseases, run by Sarfez Pharmaceuticals, Inc. at 1 site in India.
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 1 inclusion and 8 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 18 Apr 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 India. 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 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.
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?
Peak plasma concentration (time frame: 24 hour). The study lists 3 primary outcomes in all. 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 NCT03214874, 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 18 Apr 2018.