A Food Effect Study of 60mg ER Torsemide

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

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.

Study Overview

• Status: Completed
• Conditions: Food-drug Interaction
• Intervention / Treatment: Drug: Fed- 60mg ER Torsemide; Drug: Fasting- 60mg ER Torsemide

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.

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Phase 1

Contacts and Locations

Study Locations

• India
  • Bangalore, India, 560003
    • I.E.C. Consultants

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: NONE

Number of Arms

2

Arms and Interventions

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

Collaborators and Investigators

• Sponsor: Sarfez Pharmaceuticals, Inc.
• Investigators: Principal Investigator: Christopher Wilcox, MD, PhD, Sarfez Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 17, 2017
• Primary Completion (ACTUAL): March 31, 2018
• Study Completion (ACTUAL): March 31, 2018

Study Registration Dates

• First Submitted: July 9, 2017
• First Submitted That Met QC Criteria: July 11, 2017
• First Posted (ACTUAL): July 12, 2017

Study Record Updates

• Last Update Posted (ACTUAL): April 18, 2018
• Last Update Submitted That Met QC Criteria: April 17, 2018
• Last Verified: April 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Natriuretic Agents; Membrane Transport Modulators; Diuretics; Sodium Potassium Chloride Symporter Inhibitors; Torsemide
• Other Study ID Numbers: CLCD-061-17

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No