Clinical trial NCT03214874: Within Subject Variability Study of ER Torsemide 20 mg Tablet in Healthy Subjects
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Congestive Heart Failure
Chronic Kidney Diseases
Lead sponsor: Sarfez Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2017-07-12
Enrollment: 24
Sex: MALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Fully Replicate double-crossover
Primary purpose: TREATMENT

Brief 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). 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.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Peak plasma concentration
timeFrame: 24 hour
measure: Total plasma concentration
timeFrame: 24 hour
measure: Urinary excretion
timeFrame: 24 hour
Secondary outcomes:
measure: Urinary sodium excretion
timeFrame: 24 hour
measure: Urine output
timeFrame: 24 hour
Other outcomes:
Locations:
city: Bangalore
country: India
facility: I.E.C. Consultants
Study officials:
affiliation: Georgetown University
name: Christopher Wilcox, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.