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

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.

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.