Effect of Azimilide Dihydrochloride on Renal Function

Study Overview
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Brief Summary
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This study will assess the effect of multiple dosing of 125 mg azimilide on glomerular filtration rate (GFR) and total creatinine clearance (GFR + active secretion) in healthy subjects. Also, it will assess the effect of multiple dosing of 125 mg azimilide on renal hemodynamics (RPF) in healthy subjects.

Detailed Description
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This is a double-blind, parallel-group, placebo-controlled, multiple-dose, single-site study in healthy male and female volunteers. Oral azimilide 125 mg or placebo will be administered every 12 hours for 3 days, followed by 125 mg every 24 hours for 3 days. The study will include a total of 21 healthy subjects (14 active and 7 placebo), all of whom will be confined at the study center for 9 nights.

Official Title
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A Double-blind, Randomized, Parallel-group, Placebo-controlled, Multiple-dose Study to Assess the Effect of 125 mg/Day Orally Administered Azimilide Dihydrochloride on Renal Function and Hemodynamics in Healthy Volunteers

Conditions
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Healthy

Intervention / Treatment
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* Drug: Azimilide dihydrochloride
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or hysterectomized or post-menopausal (last menstrual period > 1 year) female Between 18 and 45 years of age, inclusive, at screening In good general health based on medical history, physical examination and laboratory evaluation Body mass index between 18 and 32 (kg/m2), inclusive Willing and able to fulfill the requirements of the protocol and provide written consent Exclusion Criteria: History of diabetes, cardiovascular, hepatic, renal, or gastrointestinal disease History of use of tobacco or nicotine-containing products within the past 3 months Alcohol or illicit drug abuse or a reported habitual alcohol intake greater than 1.5 oz. (ethanol equivalent) per day (e.g., 24 ozs. of beer, 10 ozs. of wine, or 3 ozs. of hard liquor) within the past 2 years. History of a clinically significant (in the opinion of the investigator) allergic reaction to any drug or multiple food/drug, contrast media agents, PAH, iodine or shell fish. Clinically significant abnormality upon physical examination that, in the investigator's opinion, would interfere with the conduct of the study Corrected QT-interval (QTc) > 440 msec (QT interval corrected for heart rate using Bazett's formula). Clinically significant abnormality on screening 12-lead electrocardiogram (ECG); presence of discernable U wave that (in the investigator's opinion) would interfere with accurate measurement of QT at baseline and/or after treatment. Personal or family history of long QT syndrome Absolute neutrophil count < 1500/mm3 Potassium or magnesium value(s) outside the laboratory normal range Any other laboratory value(s) outside the laboratory normal range considered clinically significant by the investigator (serum chemistry, hematology, coagulation, or urinalysis. Serology positive for hepatitis B surface antigen, hepatitis C antibody, or human immunodeficiency virus (HIV) screen. If female, positive urine or serum pregnancy test Positive urine screen for drugs of abuse Reported use of any prescription drug or herbal preparations within 14 days prior to dosing or any non-prescription drug or vitamin within 7 days prior to dosing. Reported use of any known enzyme-inducer, enzyme-inhibitor, or other investigational drug within 30 days prior to dosing, or reported chronic exposure to enzyme-inducers such as paint solvents or pesticides within 30 days of dosing. Blood donation of approximately 400 mL or more within 4 weeks or plasma donation of 200 mL or more within 2 weeks prior to dosing. Acute illness within 2 weeks prior to dosing History or presence, upon clinical evaluation, of any illness that might impact the safety of test product administration or evaluability of drug effect based on the investigator's discretion. Has participated in another investigational drug study protocol within 30 days of admission.

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

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: 1<br>Placebo tablet every 12 hours for 3 days followed by placebo tablet every 24 hours for three days | Drug: Placebo<br>* Placebo tablet every 12 hours for 3 days followed by placebo tablet every 24 hours for three days<br>|
| Experimental: 2<br>125 mg azimilide tablet every 12 hours for 3 days followed by 125 mg azimilide tablet every 24 hours for three days | Drug: Azimilide dihydrochloride<br>* 125 mg azimilide tablet every 12 hours for 3 days followed by 125 mg azimilide tablet every 24 hours for three days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess the effect of multiple dosing of 125 mg azimilide on glomerular filtration rate and total creatinine clearance in healthy subjects |  | 6 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess the effect of multiple dosing of 125 mg azimilide on renal hemodynamics in healthy subjects |  | 6 days |