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

Sarfez Pharmaceuticals

Status and phase: Completed; Phase 1

Conditions: Chronic Kidney Diseases; Congestive Heart Failure

Treatments: Drug: ER Torsemide 20mg Tablet; Drug: Demadex 20mg Tablet

Study type: Interventional

Funder types: Industry

Identifiers

NCT03214874

CLCD-058-15

Details and patient eligibility

About

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.

Full 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.

Enrollment: 24 patients

Sex: Male

Ages: 18 to 45 years old

Volunteers: Accepts Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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24 participants in 2 patient groups

Demadex 20mg Tablet

Active Comparator group

Description:

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

Treatment:

Drug: Demadex 20mg Tablet

ER Torsemide 20mg Tablet

Experimental group

Description:

ER Torsemide 20mg tablet once daily is is the new formulation that will release the active ingredient over an extended period

Treatment:

Drug: ER Torsemide 20mg Tablet