Within Subject Variability Study of ER Torsemide 20 mg Tablet in Healthy Subjects

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

Status

Completed

Phases

Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT03214874

Enrollment

Registered

2017-07-12

Start date

2017-06-19

Completion date

2017-07-20

Last updated

2018-04-18

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Chronic Kidney Diseases, Congestive Heart Failure

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.

Interventions

DRUGDemadex 20mg Tablet

Immediate Release (IR) Torsemide

DRUGER Torsemide 20mg Tablet

Extended Release Torsemide 20 mg tablet given once daily

Study design

Allocation

RANDOMIZED

Intervention model

CROSSOVER

Primary purpose

TREATMENT

Masking

NONE

Intervention model description

Fully Replicate double-crossover

Eligibility

Sex/Gender

MALE

Age

18 Years to 45 Years

Healthy volunteers

Yes

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.

Design outcomes

Primary

Measure	Time frame	Description
Peak plasma concentration	24 hour	Peak tosremide plasma concentration (Cmax) (ng/ml)
Total plasma concentration	24 hour	Area under the plasma concentration versus time curve (AUC) (hr/ng/ml)
Urinary excretion	24 hour	Torsemide excretion in urine (microgram/min) over 24h post dose

Secondary

Measure	Time frame	Description
Urinary sodium excretion	24 hour	24h sodium (mmol/min)
Urine output	24 hour	24h total urinary output (l/day)

Countries

India

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026