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

Chronic Kidney Diseases Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03214874
• Other study ID #: CLCD-058-15
• Status: Completed
• Phase: Phase 1
• First received: July 8, 2017
• Last updated: April 17, 2018
• Start date: June 19, 2017
• Est. completion date: July 20, 2017

Study information

• Verified date: April 2018
• Source: Sarfez Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: July 20, 2017
• Est. primary completion date: July 20, 2017
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 45 Years

Eligibility

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.

Related Conditions & MeSH terms

• Chronic Kidney Diseases
• Congestive Heart Failure
• Heart Failure
• Kidney Diseases
• Renal Insufficiency, Chronic

Intervention

Drug:
• Demadex 20mg Tablet
Immediate Release (IR) Torsemide
• ER Torsemide 20mg Tablet
Extended Release Torsemide 20 mg tablet given once daily

Locations

Country	Name	City	State
India	I.E.C. Consultants	Bangalore

Sponsors (1)

Lead Sponsor	Collaborator
Sarfez Pharmaceuticals, Inc.

Country where clinical trial is conducted

India, 

References & Publications (1)

Murray MD, Deer MM, Ferguson JA, Dexter PR, Bennett SJ, Perkins SM, Smith FE, Lane KA, Adams LD, Tierney WM, Brater DC. Open-label randomized trial of torsemide compared with furosemide therapy for patients with heart failure. Am J Med. 2001 Nov;111(7):51 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Peak plasma concentration	Peak tosremide plasma concentration (Cmax) (ng/ml)	24 hour
Primary	Total plasma concentration	Area under the plasma concentration versus time curve (AUC) (hr/ng/ml)	24 hour
Primary	Urinary excretion	Torsemide excretion in urine (microgram/min) over 24h post dose	24 hour
Secondary	Urinary sodium excretion	24h sodium (mmol/min)	24 hour
Secondary	Urine output	24h total urinary output (l/day)	24 hour