Clinical trial NCT02614469: A Food-Drug Interaction Study of Serum Urate After Oral Inosine
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
Collaborators: name: Michael J. Fox Foundation for Parkinson's Research
name: The Parkinson Alliance
First posted: 2015-11-25
Enrollment: 18
Sex: MALE
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

1. Healthy male subjects between the ages of 18 and 65 years
2. Body-mass index between 18.0 kg/m2 and 32.0 kg/m2
3. 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
4. Serum urate \< 6.1 mg/dL (approximately 360 μM) at screening
5. Non-smokers for at least 6 months prior to screening
6. Adequate venous access at multiple sites in both arms

Exclusion Criteria:

1. History of alcohol or drug dependence in the past 2 years
2. 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
3. Used prescription or over-the-counter (OTC) drugs within 14 days prior to screening
4. Used vitamin preparations or supplements (including St. John's Wort and ginseng) within 28 days prior to the screening test
5. 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
6. 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
7. 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
8. Known HIV disease
9. Had a febrile illness within 5 days prior to the first dose of study medication
10. Vaccinated within 30 days prior to the first dose of medication
11. Has gout or a history or suspicion of kidney stones
12. Determined by the investigator or sub-investigator to be unsuitable for participating in the study based on medical conditions

Primary outcomes:
measure: Cmax: Maximum Observed Serum Urate Concentration
timeFrame: -12 to 0 hrs pre-dose and 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36 and 48 hrs post-dose
measure: AUC (0-t): Area Under the Serum Concentration-time Curve From Time 0 to Time t (Time of Last Quantifiable Plasma Concentration)
timeFrame: -12 to 0 hr pre-dose and 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48 hrs post-dose
measure: AUC (0-inf): Area Under the Serum Concentration-time Curve From Time 0 to Infinity
timeFrame: -12 to 0 hr pre-dose and 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48 hrs post-dose
measure: Tmax: Time of Maximum Serum Concentration
timeFrame: -12 to 0 hr pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48 hrs post-dose
measure: T1/2: Apparent Terminal Half-life
timeFrame: -12 to 0 pre-dose and 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48 hrs post-dose
measure: Baseline Corrected Cmax: Baseline Corrected Maximum Serum Concentration
timeFrame: -12 to 0 hr pre-dose and 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48 hrs post-dose
measure: 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)
timeFrame: -12 to 0 hr pre-dose and 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48 hrs post-dose
measure: Baseline Corrected AUC (0-inf): Baseline Corrected Area Under the Serum Concentration-time Curve From Time 0 to Infinity
timeFrame: -12 to 0 hr pre-dose and 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, and 48 hrs post-dose
measure: Baseline Corrected Tmax: Baseline Corrected Time of Maximum Serum Concentration
timeFrame: -12 to 0 h pre-dose and 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, and 48 hrs post-dose
measure: Baseline Corrected T1/2: Baseline Corrected Apparent Terminal Half-life
timeFrame: -12 to 0 hr pre-dose and 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48 hrs post-dose
Secondary outcomes:
measure: Safety Assessment (Vital Signs)
timeFrame: Up to 10 days after first study drug administration at Day 1 of Period 1
measure: Safety Assessment: Adverse Events
timeFrame: Up to 10 days after first study drug administration at Day 1 of Period 1
Other outcomes:
Locations:
city: Evansville
country: United States
facility: Covance Clinical Research Unit Inc.
state: Indiana
Study officials:
affiliation: Massachusetts General Hospital
name: Mason Freeman, M.D.
role: STUDY_DIRECTOR
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