A Food-Drug Interaction Study of Serum Urate After Oral Inosine

Study Overview
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Brief Summary
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The purpose of this study is to assess the effects of food on the amount of urate in the body after a single oral dose of inosine.

Detailed Description
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Eighteen (18) eligible healthy male subjects will be randomly assigned to two groups with 9 subjects per group to receive a single oral dose of 1000 mg inosine with or without food on day 1 after an overnight fast. Subjects who receive inosine with food on day 1 will receive a second dose of inosine without food on day 8 after an overnight fast. Subjects who receive inosine without food on day 1 after an overnight fast will receive a second dose of inosine with food on day 8 after an overnight fast. Subjects will be admitted to the clinic before dinner on days 0 and 7, the days before dosing, and will stay in the clinic for 48-h post-dose. During the clinic stay, blood samples will be taken for urate measurements.

Official Title
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A Phase 1, Open-label, Randomized, Two-period, Two-treatment, Crossover Study to Evaluate the Effects of Food on the Pharmacokinetics of Urate After a Single Dose of Inosine in Healthy Male Subjects

Conditions
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Healthy

Intervention / Treatment
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* Drug: Inosine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male subjects between the ages of 18 and 65 years Body-mass index between 18.0 kg/m2 and 32.0 kg/m2 If not surgically sterile, willing to refrain from donating sperm and willing to use appropriate birth control when engaging in sexual intercourse for a period of 90 days following the last dose of the study medication Serum urate < 6.1 mg/dL (approximately 360 μM) at screening Non-smokers for at least 6 months prior to screening Adequate venous access at multiple sites in both arms Exclusion Criteria: History of alcohol or drug dependence in the past 2 years Had 400 mL of whole blood collection within four months or 200 mL of whole blood collection or who had blood component collection within one month of the screening test Used prescription or over-the-counter (OTC) drugs within 14 days prior to screening Used vitamin preparations or supplements (including St. John's Wort and ginseng) within 28 days prior to the screening test Not willing to refrain from alcohol, grapefruit, grapefruit juice or related products, caffeine consumption (including chocolate), and strenuous exercise within 72 h prior to day 1 and through the end of the PK study Treated with an investigational drug within 30 days or 7 half-lives of the investigational drug, whichever is longer, prior to the first dose of study drug Previously received inosine supplement within three months from the screening or subjects who have had any inosine and suffered an adverse reaction due to it Known HIV disease Had a febrile illness within 5 days prior to the first dose of study medication Vaccinated within 30 days prior to the first dose of medication Has gout or a history or suspicion of kidney stones Determined by the investigator or sub-investigator to be unsuitable for participating in the study based on medical conditions

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1, Inosine with Food<br>Group 1 subjects will take inosine with food on day 1 after an overnight fast and will take a second dose of inosine without food on day 8 after an overnight fast. | Drug: Inosine<br>* Inosine, 1000 mg<br>|
| Experimental: Group 2, Inosine without Food<br>Group 2 subjects will take inosine without food on day 1 after an overnight fast and will take a second dose of inosine with food on day 8 after an overnight fast. | Drug: Inosine<br>* Inosine, 1000 mg<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax: Maximum Observed Serum Urate Concentration |  | -12 to 0 hrs pre-dose and 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36 and 48 hrs post-dose | 
| AUC (0-t): Area Under the Serum Concentration-time Curve From Time 0 to Time t (Time of Last Quantifiable Plasma Concentration) |  | -12 to 0 hr pre-dose and 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48 hrs post-dose | 
| AUC (0-inf): Area Under the Serum Concentration-time Curve From Time 0 to Infinity |  | -12 to 0 hr pre-dose and 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48 hrs post-dose | 
| Tmax: Time of Maximum Serum Concentration |  | -12 to 0 hr pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48 hrs post-dose | 
| T1/2: Apparent Terminal Half-life |  | -12 to 0 pre-dose and 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48 hrs post-dose | 
| Baseline Corrected Cmax: Baseline Corrected Maximum Serum Concentration | Correction for individual endogenous urate levels was done by subtracting the individual mean endogenous baseline concentration prior to dosing from each post-dose concentration in the profile. The two samples collected at -12 h and 0 h (pre-dose) before the meal were used to measure the mean endogenous baseline concentrations in each dosing period (periods 1 and 2). Negative concentrations were set to zero. | -12 to 0 hr pre-dose and 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48 hrs post-dose | 
| Baseline Corrected AUC (0-t): Baseline Corrected Area Under the Serum Concentration-time Curve From Time 0 to Time t (Time of Last Quantifiable Serum Concentration) | Correction for individual endogenous urate levels was done by subtracting the individual mean endogenous baseline concentration prior to dosing from each post-dose concentration in the profile. The two samples collected at -12 h and 0 h (pre-dose) before the meal were used to measure the mean endogenous baseline concentrations in each dosing period (periods 1 and 2). Negative concentrations were set to zero. | -12 to 0 hr pre-dose and 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48 hrs post-dose | 
| Baseline Corrected AUC (0-inf): Baseline Corrected Area Under the Serum Concentration-time Curve From Time 0 to Infinity | Correction for individual endogenous urate levels was done by subtracting the individual mean endogenous baseline concentration prior to dosing from each post-dose concentration in the profile. The two samples collected at -12 h and 0 h (pre-dose) before the meal were used to measure the mean endogenous baseline concentrations in each dosing period (periods 1 and 2). | -12 to 0 hr pre-dose and 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, and 48 hrs post-dose | 
| Baseline Corrected Tmax: Baseline Corrected Time of Maximum Serum Concentration | Correction for individual endogenous urate levels was done by subtracting the individual mean endogenous baseline concentration prior to dosing from each post-dose concentration in the profile. The two samples collected at -12 h and 0 h (pre-dose) before the meal were used to measure the mean endogenous baseline concentrations in each dosing period (periods 1 and 2). | -12 to 0 h pre-dose and 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, and 48 hrs post-dose | 
| Baseline Corrected T1/2: Baseline Corrected Apparent Terminal Half-life | Correction for individual endogenous urate levels was done by subtracting the individual mean endogenous baseline concentration prior to dosing from each post-dose concentration in the profile. The two samples collected at -12 h and 0 h (pre-dose) before the meal were used to measure the mean endogenous baseline concentrations in each dosing period (periods 1 and 2). | -12 to 0 hr pre-dose and 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48 hrs post-dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety Assessment (Vital Signs) | Number of participants with clinically significant findings in vital signs by investigator after study drug administration. | Up to 10 days after first study drug administration at Day 1 of Period 1 | 
| Safety Assessment: Adverse Events | Number of participants with adverse events after study drug administration | Up to 10 days after first study drug administration at Day 1 of Period 1 |