A Food Effect Study of 60mg ER Torsemide

Study Overview
=================
Brief Summary
-----------------
This study will evaluate the effects of a high-fat meal (food effect) on the bioavailability and pharmacokinetics of 60mg ER Torsemide tablet after single dose oral administration in healthy volunteers. The study will be conducted as a two-sequence to period crossover study to compare 60mg ER Torsemide ER bioavailability under fed and fasting conditions. 60mg ER torsemide is a new strength and dosage form.

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 this drawback by prolonging the duration of action to increase sodium excretion even in patients who consume high salt diet. Since 60mg ER torsemide is a new strength and dosage form, this study will test 60mg ER torsemide for a food effect in healthy volunteers who are either fasting or consuming a high-fat meal (fed). The primary endpoint of the study is full pharmacokinetics measurements after a single dose of 60mg ER torsemide. The secondary endpoints are 24h sodium excretion and total urinary excretion.

Official Title
-----------------
A Randomized, Balanced, Single Dose, Two-treatment (Fed vs. Fasting), Two-period, Two-sequence, Crossover Study to Evaluate the Effects of Food on the Bioavailability of 60 mg ER Torsemide Tablet in Healthy Human Adult Subjects

Conditions
-----------------
Food-drug Interaction

Intervention / Treatment
-----------------
* Drug: Fed- 60mg ER Torsemide
* Drug: Fasting- 60mg ER Torsemide


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: healthy male or female non-smoker weight ≥ 50 kg for male and ≥ 45 for female clinically acceptable laboratory profiles with ECG and chest x-ray performed within 6 months Exclusion Criteria: participation in bioavailability/bioequivalence studies in past six months history of drug abuse or alcohol dependence history of allergies, known hypersensitivity to Torsemide and related drugs presence of clinically significant disorder suffer from high/low blood pressure (<90 and >140 mm Hg) positive urine drug screening, and history of incontinence

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: 60mg ER Torsemide study in fed and fasting conditions
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fed- 60mg ER Torsemide<br>Adult healthy subjects will be given standardized high-fat, high-calorie meal prior to dosing | Drug: Fed- 60mg ER Torsemide<br>* 60mg ER Torsemide will be given after high fat, high-calorie meal<br>* Other names: High fat/high-calorie fed conditions;|
| Experimental: Fasting- 60mg ER Torsemide<br>Adult healthy subjects will fast overnight (at least 10h) prior to dosing | Drug: Fasting- 60mg ER Torsemide<br>* 60mg ER Torsemide will be given after overnight fasting<br>* Other names: Fasting conditions;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Peak torsemide plasma concentration | Peak plasma concentration (Cmax) (ng/ml) in fed and fasting conditions | 36 hours | 
| Total torsemide plasma concentration | Area under the plasma concentration versus time curve (AUC) (hr/ng/ml) in fed and fasting conditions | 36 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Urinary torsemide excretion | torsemide will be measured in urine over 36 hours post-dose (microgram/min) | 36 hours | 
| Urinary sodium excretion | 36-hour sodium excretion will be measure (mmol/min) | 36 hours |