The Effect of PAS on the Pharmacokinetics of Tenofovir in Healthy Subjects

Study Overview
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Brief Summary
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The main purpose of this study is to evaluate whether PAS will change the PK parameters of tenofovir.

Official Title
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An Open-label, Randomized, Crossover Study to Evaluate the Effect of PAS on the Pharmacokinetics of Tenofovir in Healthy Subjects

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Drug: Tenofovir disoproxil fumarate 300mg
* Drug: Para-aminosalicylic acid Ca granule 5.28 g


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy adult male volunteers, ages 19 to 45 years at the time of screening test inclusive. Subjects who did not have congenital or chronic diseases and sign and symptom after medical examinations Body Mass Index (BMI) of 18 to 25 kg/m2, inclusive. BMI = weight (kg)/ [height (m)]2. Volunteers deemed as appropriate subjects by investigators, after passing medical screening, including assessment of medical history, vital signs, 12-lead ECG, physical examination, laboratory tests etc. according to the characteristics of the investigational products. Subjects who can participate in the whole clinical trial. Subjects who voluntarily sign a written consent form after having received information regarding the objectives and contents of the trial, and characteristics of the study drug drugs prior to signing. Exclusion Criteria: Medical History Subjects with any disease or history of clinically significant liver, kidney, digestive system, respiratory system, musculoskeletal system, endocrine system, neuropsychiatric system, hemato-oncologic system, urinary system, cardiovascular system including arrhythmia. Subjects with any history of gastrointestinal diseases/conditions that could impact on the absorption of study drug. Laboratory Test and ECG Findings Subjects who show, or have had clinical abnormalities detected through laboratory tests prior to the trial commencement date. Criteria for liver and renal function test are shown below: AST or ALT above 1.25×ULN Total bilirubin above 1.5×ULN Serum creatinine clearance calculated by CKD-EPI below 80mL/min Subjects who show a clinically significant abnormalities detected through ECG History of hypersensitivity to the drug including study drug ingredients and other medications (aspirin, antibiotics, etc.) or clinically significant hypersensitivity Prohibition on Concomitant Drug/Food Use of ethical-the-counter/herbal preparations or use of over-the-counter medications/vitamin medications within 2 weeks or 1 week prior to study drug administration, respectively Subjects on any diet which could affected study drug's pharmacokinetics Subjects who administered the Probenecid, Penicillin G and other drugs which already known has an effect on OAT1 Transporter activity within 2 weeks prior to the first dose. Blood Donation and Transfusion Donation of blood or plasma to a blood bank or in a clinical study (except a screening visit) within 60 days prior to study drug administration. Blood transfusion within 30 days prior to study drug administration. Other Exclusion Criteria Alcohol over intake (alcohol > 30g/day) and screening positive for alcohol Subjects who smoke within 3 months before initiation of clinical trial and subjects who cannot stop smoking during the participation of clinical study Subjects who cannot stop taking caffeine-containing foods (e.g. coffee, tea, green tea, cocoa, chocolate, soda, coffee milk, energy supplementary beverage, etc.) and alcoholic beverage during the participation of clinical study Subjects deemed to be inappropriate for the trial as determined by the investigator.

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

Sexes Eligible for Study
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Male

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: Screening
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Tenofovir<br>Tenofovir disoproxil fumarate 300mg single dose administration | Drug: Tenofovir disoproxil fumarate 300mg<br>* Single oral dose on the first day of each period<br>* Other names: viread;|
| Experimental: Tenofovir + PAS<br>Tenofovir disoproxil fumarate 300mg single dose, Para-aminosalicylic acid Ca Granule 5.28 g BID seven dose administration | Drug: Tenofovir disoproxil fumarate 300mg<br>* Single oral dose on the first day of each period<br>* Other names: viread;Drug: Para-aminosalicylic acid Ca granule 5.28 g<br>* Twice daily oral administration from the first day of each period to the seventh dose<br>* Other names: Pas Granule Dongindang;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Peak plasma concentration (Cmax) of tenofovir | Cmax of Tenofovir will be compared between test and reference arms. | 0-84 hours in test and 0-72 hours in reference arm | 
| Area under the plasma concentration versus time curve (AUC) of tenofovir | AUC of tenofovir will be compared between test and reference arms. | 0-84 hours in test and 0-72 hours in reference arm | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Volume of distribution of tenofovir |  | 0-84 hours in test and 0-72 hours in reference arm | 
| Time of peak plasma concentration(Tmax) of tenofovir |  | 0-84 hours in test and 0-72 hours in reference arm | 
| Plasma half-life of tenofovir |  | 0-84 hours in test and 0-72 hours in reference arm | 
| Renal clearance of tenofovir |  | 0-24 hours | 
| Amount of tenofovir excreted in urine |  | 0-24 hours | 
| Peak plasma concentration of PAS |  | 0-12 hours | 
| Area under the plasma concentration versus time curve (AUC) of PAS |  | 0-12 hours | 
| Renal clearance of PAS |  | 0-12 hours | 
| Volume of distribution of PAS |  | 0-12 hours | 
| Time of peak plasma concentration of PAS |  | 0-12 hours | 
| Plasma half-life of PAS |  | 0-12 hours | 
| Amount of PAS excreted in urine |  | 0-12 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Tenofovir Disoproxil Fumarate, 4-Aminosalicylic Acid, Tuberculosis, HIV