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CompletedNCT02614469Updated Mar 29, 2017Results posted

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

A Phase 1 interventional study of Inosine in Healthy, sponsored by Michael Alan Schwarzschild. Completed at 1 site in United States. Open to male participants aged 18 Years to 65 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2017-03-29.

Sponsored by Michael Alan Schwarzschild · Phase 1, Interventional, and Treatment

Phase
Phase 1
Study type
Interventional
Enrollment
18
Allocation
Randomized
Ages
18 Years to 65 Years
Sex
Male
01

Study 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.

Read the 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.

02

Conditions studied

  • Healthy
03

In context

Lead sponsor

Michael Alan Schwarzschild is the lead sponsor of 2 studies on the registry; none are open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 65 Years
Sexes eligible
Male
Accepts healthy volunteers
Yes

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

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
05

Study design

Phase
Phase 1
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Crossover assignment
Masking
None (open label)
Enrollment
18 participants (actual)

Study arms

  • Experimental
    Group 1, Inosine with Food

    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

  • Experimental
    Group 2, Inosine without Food

    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

Interventions

  • DrugInosine

    Inosine, 1000 mg

06

What researchers measure

Primary outcomes

  1. Cmax: Maximum Observed Serum Urate Concentration

    Time frame: -12 to 0 hrs pre-dose and 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36 and 48 hrs post-dose

  2. AUC (0-t): Area Under the Serum Concentration-time Curve From Time 0 to Time t (Time of Last Quantifiable Plasma Concentration)

    Time frame: -12 to 0 hr pre-dose and 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48 hrs post-dose

  3. AUC (0-inf): Area Under the Serum Concentration-time Curve From Time 0 to Infinity

    Time frame: -12 to 0 hr pre-dose and 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48 hrs post-dose

  4. Tmax: Time of Maximum Serum Concentration

    Time frame: -12 to 0 hr pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48 hrs post-dose

  5. T1/2: Apparent Terminal Half-life

    Time frame: -12 to 0 pre-dose and 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48 hrs post-dose

  6. 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.

    Time frame: -12 to 0 hr pre-dose and 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48 hrs post-dose

  7. 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.

    Time frame: -12 to 0 hr pre-dose and 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48 hrs post-dose

  8. 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).

    Time frame: -12 to 0 hr pre-dose and 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, and 48 hrs post-dose

  9. 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).

    Time frame: -12 to 0 h pre-dose and 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, and 48 hrs post-dose

  10. 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).

    Time frame: -12 to 0 hr pre-dose and 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48 hrs post-dose

Secondary outcomes

  1. Safety Assessment (Vital Signs)

    Number of participants with clinically significant findings in vital signs by investigator after study drug administration.

    Time frame: Up to 10 days after first study drug administration at Day 1 of Period 1

  2. Safety Assessment: Adverse Events

    Number of participants with adverse events after study drug administration

    Time frame: Up to 10 days after first study drug administration at Day 1 of Period 1

07

Results

Posted Feb 24, 2017

Participant flow

Subjects took part in the study at one investigative site in the United States from 15 March 2016 to 10 April 2016.

Period 1
Participant flow — Period 1
MilestoneGroup 1, Inosine With Food Then Without FoodGroup 2, Inosine Without Food Then With Food
Started99
Completed99
Not completed00
Period 2
Participant flow — Period 2
MilestoneGroup 1, Inosine With Food Then Without FoodGroup 2, Inosine Without Food Then With Food
Started99
Completed99
Not completed00

Outcome measures

PrimaryCmax: Maximum Observed Serum Urate Concentration
Time frame:
-12 to 0 hrs pre-dose and 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36 and 48 hrs post-dose
Reported as:
Mean · mg/dL
Cmax: Maximum Observed Serum Urate Concentration
mg/dLInosine FedInosine Fasted
Cmax: Maximum Observed Serum Urate Concentration6.6 ± 0.76.4 ± 0.6
Statistical analysis
  • Inosine Fed vs Inosine Fasted · Ratio of geometric means: 103 · 90% CI 98.0 to 108Fed/Fasting Ratio
PrimaryAUC (0-t): Area Under the Serum Concentration-time Curve From Time 0 to Time t (Time of Last Quantifiable Plasma Concentration)
Time frame:
-12 to 0 hr pre-dose and 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48 hrs post-dose
Reported as:
Mean · mg*hr/dL
AUC (0-t): Area Under the Serum Concentration-time Curve From Time 0 to Time t (Time of Last Quantifiable Plasma Concentration)
mg*hr/dLInosine FedInosine Fasted
AUC (0-t): Area Under the Serum Concentration-time Curve From Time 0 to Time t (Time of Last Quantifiable Plasma Concentration)267 ± 30.2268 ± 26.4
Statistical analysis
  • Inosine Fed vs Inosine Fasted · Ratio of geometric means: 99.3 · 90% CI 96.9 to 102Fed/Fasted Ratio
PrimaryAUC (0-inf): Area Under the Serum Concentration-time Curve From Time 0 to Infinity
Time frame:
-12 to 0 hr pre-dose and 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48 hrs post-dose
Reported as:
Mean · mg*hr/dL
AUC (0-inf): Area Under the Serum Concentration-time Curve From Time 0 to Infinity
mg*hr/dLInosine FedInosine Fasted
AUC (0-inf): Area Under the Serum Concentration-time Curve From Time 0 to Infinity2040 ± 22612031 ± 2278
PrimaryTmax: Time of Maximum Serum Concentration
Time frame:
-12 to 0 hr pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48 hrs post-dose
Reported as:
Median · hr
Tmax: Time of Maximum Serum Concentration
hrInosine FedInosine Fasted
Tmax: Time of Maximum Serum Concentration3.0 (1.0 to 6.0)3.0 (1.0 to 24.0)
PrimaryT1/2: Apparent Terminal Half-life
Time frame:
-12 to 0 pre-dose and 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48 hrs post-dose
Reported as:
Mean · hr
T1/2: Apparent Terminal Half-life
hrInosine FedInosine Fasted
T1/2: Apparent Terminal Half-life242 ± 341241 ± 331
PrimaryBaseline 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.

Time frame:
-12 to 0 hr pre-dose and 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48 hrs post-dose
Reported as:
Mean · mg/dL
Baseline Corrected Cmax: Baseline Corrected Maximum Serum Concentration
mg/dLInosine FedInosine Fasted
Baseline Corrected Cmax: Baseline Corrected Maximum Serum Concentration1.73 ± 0.461.65 ± 0.37
Statistical analysis
  • Inosine Fed vs Inosine Fasted · Ratio of geometric means: 103 · 90% CI 90.9 to 118Fed/Fasted Ratio
PrimaryBaseline 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.

Time frame:
-12 to 0 hr pre-dose and 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48 hrs post-dose
Reported as:
Mean · mg*hr/dL
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)
mg*hr/dLInosine FedInosine Fasted
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)36.1 ± 15.139.3 ± 13.3
Statistical analysis
  • Inosine Fed vs Inosine Fasted · Ratio of geometric means: 83.4 · 90% CI 62.1 to 112Fed/Fasted Ratio
PrimaryBaseline 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).

Time frame:
-12 to 0 hr pre-dose and 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, and 48 hrs post-dose
Reported as:
Mean · mg*hr/dL
Baseline Corrected AUC (0-inf): Baseline Corrected Area Under the Serum Concentration-time Curve From Time 0 to Infinity
mg*hr/dLInosine FedInosine Fasted
Baseline Corrected AUC (0-inf): Baseline Corrected Area Under the Serum Concentration-time Curve From Time 0 to Infinity80.4 ± 84.283.0 ± 86.3
PrimaryBaseline 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).

Time frame:
-12 to 0 h pre-dose and 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, and 48 hrs post-dose
Reported as:
Median · hr
Baseline Corrected Tmax: Baseline Corrected Time of Maximum Serum Concentration
hrInosine FedInosine Fasted
Baseline Corrected Tmax: Baseline Corrected Time of Maximum Serum Concentration3.0 (1.0 to 6.0)3.0 (1.0 to 24.0)
PrimaryBaseline 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).

Time frame:
-12 to 0 hr pre-dose and 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48 hrs post-dose
Reported as:
Mean · hr
Baseline Corrected T1/2: Baseline Corrected Apparent Terminal Half-life
hrInosine FedInosine Fasted
Baseline Corrected T1/2: Baseline Corrected Apparent Terminal Half-life44.3 ± 71.544.7 ± 76.2
SecondarySafety Assessment (Vital Signs)

Number of participants with clinically significant findings in vital signs by investigator after study drug administration.

Time frame:
Up to 10 days after first study drug administration at Day 1 of Period 1
Reported as:
Number · participants
Safety Assessment (Vital Signs)
participantsInosine FedInosine Fasted
Safety Assessment (Vital Signs)00
SecondarySafety Assessment: Adverse Events

Number of participants with adverse events after study drug administration

Time frame:
Up to 10 days after first study drug administration at Day 1 of Period 1
Reported as:
Number · participants
Safety Assessment: Adverse Events
participantsInosine FedInosine Fasted
Safety Assessment: Adverse Events00

Adverse events

Collected over Up to 9 days after first dosing at Day 1 of Period 1, or Day 10 of Period 2. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Inosine Fed—0/18 (0%)0/18 (0%)
Inosine Fasted—0/18 (0%)0/18 (0%)

Baseline characteristics

Age, Continuous
Age, Continuous(years)Group 1, Inosine With Food Then Without FoodGroup 2, Inosine Without Food Then With FoodTotal
Mean41.44 ± 16.3734.67 ± 5.9238.06 ± 12.44
Sex: Female, Male
Sex: Female, Male(Participants)Group 1, Inosine With Food Then Without FoodGroup 2, Inosine Without Food Then With FoodTotal
Female000
Male9918
Race/Ethnicity, Customized
Race/Ethnicity, Customized(participants)Group 1, Inosine With Food Then Without FoodGroup 2, Inosine Without Food Then With FoodTotal
White549
Black or African American448
Other011
Region of Enrollment
Region of Enrollment(participants)Group 1, Inosine With Food Then Without FoodGroup 2, Inosine Without Food Then With FoodTotal
United States9918
08

Study locations

1 site
  • Covance Clinical Research Unit Inc.
    Evansville, Indiana 47710, United States
09

References and documents

Publications

  • Anton FM, Garcia Puig J, Ramos T, Gonzalez P, Ordas J. Sex differences in uric acid metabolism in adults: evidence for a lack of influence of estradiol-17 beta (E2) on the renal handling of urate. Metabolism. 1986 Apr;35(4):343-8. doi: 10.1016/0026-0495(86)90152-6. PubMed 3959904 ↗
  • Cuhadar S, Koseoglu M, Atay A, Dirican A. The effect of storage time and freeze-thaw cycles on the stability of serum samples. Biochem Med (Zagreb). 2013;23(1):70-7. doi: 10.11613/bm.2013.009. PubMed 23457767 ↗
  • Dirar AM, A.D., Abdelsalam KEA. Effect of Storage Time and Temperature on some Serum Analytes. International Journal of Pathology 8: 68-71, 2010.
  • Parkinson Study Group SURE-PD Investigators; Schwarzschild MA, Ascherio A, Beal MF, Cudkowicz ME, Curhan GC, Hare JM, Hooper DC, Kieburtz KD, Macklin EA, Oakes D, Rudolph A, Shoulson I, Tennis MK, Espay AJ, Gartner M, Hung A, Bwala G, Lenehan R, Encarnacion E, Ainslie M, Castillo R, Togasaki D, Barles G, Friedman JH, Niles L, Carter JH, Murray M, Goetz CG, Jaglin J, Ahmed A, Russell DS, Cotto C, Goudreau JL, Russell D, Parashos SA, Ede P, Saint-Hilaire MH, Thomas CA, James R, Stacy MA, Johnson J, Gauger L, Antonelle de Marcaida J, Thurlow S, Isaacson SH, Carvajal L, Rao J, Cook M, Hope-Porche C, McClurg L, Grasso DL, Logan R, Orme C, Ross T, Brocht AF, Constantinescu R, Sharma S, Venuto C, Weber J, Eaton K. Inosine to increase serum and cerebrospinal fluid urate in Parkinson disease: a randomized clinical trial. JAMA Neurol. 2014 Feb;71(2):141-50. doi: 10.1001/jamaneurol.2013.5528. PubMed 24366103 ↗
  • Spitsin S, Hooper DC, Leist T, Streletz LJ, Mikheeva T, Koprowskil H. Inactivation of peroxynitrite in multiple sclerosis patients after oral administration of inosine may suggest possible approaches to therapy of the disease. Mult Scler. 2001 Oct;7(5):313-9. doi: 10.1177/135245850100700507. PubMed 11724447 ↗
  • Yamamoto T, Moriwaki Y, Cheng J, Takahashi S, Tsutsumi Z, Ka T, Hada T. Effect of inosine on the plasma concentration of uridine and purine bases. Metabolism. 2002 Apr;51(4):438-42. doi: 10.1053/meta.2002.31322. PubMed 11912550 ↗

Individual participant data

Plan to share: No

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Mar 29, 2017, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT02614469
Lead sponsor
Michael Alan Schwarzschild
Collaborators
Michael J. Fox Foundation for Parkinson's Research, The Parkinson Alliance
Responsible party
Michael Alan Schwarzschild (Director, Molecular Neurobiology Laboratory, Massachusetts General Hospital) — Sponsor-investigator
First posted
Nov 25, 2015
Start date
Mar 2015
Primary completion
Apr 2016
Completion
May 2016
Results posted
Feb 24, 2017
Last update
Mar 29, 2017

Study contacts

Mason Freeman, M.D.
study director · Massachusetts General Hospital

Oversight

Data monitoring committee
No
View the source record on ClinicalTrials.gov ↗

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