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

Phase 1

Completed

Conditions: Healthy

Interventions: Drug: Inosine

Registration Number: NCT02614469

Lead Sponsor: Michael Alan Schwarzschild

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: Male

Target Recruitment: 18

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Group 1, Inosine with Food	Inosine	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.
Group 2, Inosine without Food	Inosine	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.

Primary Outcome Measures

Name	Time	Method
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	-12 to 0 hr pre-dose and 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48 hrs post-dose	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.
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)	-12 to 0 hr pre-dose and 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48 hrs post-dose	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.
Baseline Corrected AUC (0-inf): Baseline Corrected 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, and 48 hrs post-dose	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).
Baseline Corrected Tmax: Baseline Corrected Time of Maximum Serum Concentration	-12 to 0 h pre-dose and 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, and 48 hrs post-dose	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).
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
Baseline Corrected T1/2: Baseline Corrected Apparent Terminal Half-life	-12 to 0 hr pre-dose and 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48 hrs post-dose	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).

Secondary Outcome Measures

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