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| Name | Class |
|---|---|
| Michael J. Fox Foundation for Parkinson's Research | OTHER |
| The Parkinson Alliance | OTHER |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Group 1, Inosine with Food | Experimental | 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 | Experimental | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Inosine | Drug | Inosine, 1000 mg |
|
| 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. |
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Mason Freeman, M.D. | Massachusetts General Hospital | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Covance Clinical Research Unit Inc. | Evansville | Indiana | 47710 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 3959904 | Background | 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. | |
| 23457767 | Background | 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. |
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Subjects took part in the study at one investigative site in the United States from 15 March 2016 to 10 April 2016.
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| ID | Title | Description |
|---|---|---|
| FG000 | Group 1, Inosine With Food Then Without Food | Group 1 subjects will take inosine with food on day 1 after an overnight fast and after a 7 day washout, will take a second dose of inosine without food on day 8 after an overnight fast. Inosine: Inosine, 1000 mg |
| FG001 | Group 2, Inosine Without Food Then With Food | Group 2 subjects will take inosine without food on day 1 after an overnight fast and after a 7 day washout, will take a second dose of inosine with food on day 8 after an overnight fast. Inosine: Inosine, 1000 mg |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Period 1 |
| |||||||||||||
| Period 2 |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Group 1, Inosine With Food Then Without 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. Inosine: Inosine, 1000 mg |
| BG001 | Group 2, Inosine Without Food Then With Food |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Cmax: Maximum Observed Serum Urate Concentration | Posted | Mean | Standard Deviation | mg/dL | -12 to 0 hrs pre-dose and 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36 and 48 hrs post-dose |
|
|
Up to 9 days after first dosing at Day 1 of Period 1, or Day 10 of Period 2
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Inosine Fed | Inosine, 1000 mg tablet, in fed condition, orally once on Day 1 in Period 1 or Day 8 in Period 2. |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Michael Schwarzschild | Massachusetts General Hospital | 617-764-9611 | michaels@helix.mgh.harvard.edu |
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| ID | Term |
|---|---|
| D007288 | Inosine |
| ID | Term |
|---|---|
| D011684 | Purine Nucleosides |
| D011687 | Purines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
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| -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 |
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 |
| Background | Dirar AM, A.D., Abdelsalam KEA. Effect of Storage Time and Temperature on some Serum Analytes. International Journal of Pathology 8: 68-71, 2010. |
| 24366103 | Background | 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. |
| 11724447 | Background | 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. |
| 11912550 | Background | 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. |
| NOT COMPLETED |
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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. Inosine: Inosine, 1000 mg |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Number | participants |
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| Region of Enrollment | Number | participants |
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| Participants |
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| Primary | AUC (0-t): Area Under the Serum Concentration-time Curve From Time 0 to Time t (Time of Last Quantifiable Plasma Concentration) | Posted | Mean | Standard Deviation | mg*hr/dL | -12 to 0 hr pre-dose and 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48 hrs post-dose |
|
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|
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| Primary | AUC (0-inf): Area Under the Serum Concentration-time Curve From Time 0 to Infinity | AUC (0-inf) of 1 subject was not able to be calculated based on the serum concentration-time curve of the subject. | Posted | Mean | Standard Deviation | mg*hr/dL | -12 to 0 hr pre-dose and 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48 hrs post-dose |
|
|
|
| Primary | Tmax: Time of Maximum Serum Concentration | Posted | Median | Full Range | hr | -12 to 0 hr pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48 hrs post-dose |
|
|
|
| Primary | T1/2: Apparent Terminal Half-life | T 1/2 of 1 subject was not able to be calculated based on the serum concentration-time curve of the subject. | Posted | Mean | Standard Deviation | hr | -12 to 0 pre-dose and 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48 hrs post-dose |
|
|
|
| Primary | 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. | Posted | Mean | Standard Deviation | mg/dL | -12 to 0 hr pre-dose and 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48 hrs post-dose |
|
|
|
|
| Primary | 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. | Posted | Mean | Standard Deviation | mg*hr/dL | -12 to 0 hr pre-dose and 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48 hrs post-dose |
|
|
|
|
| Primary | 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). | Baseline Corrected AUC (0-inf) values of 2 subjects were not able to be calculated based on the serum concentration-time curve of these subjects. | Posted | Mean | Standard Deviation | mg*hr/dL | -12 to 0 hr pre-dose and 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, and 48 hrs post-dose |
|
|
|
| Primary | 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). | Posted | Median | Full Range | hr | -12 to 0 h pre-dose and 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, and 48 hrs post-dose |
|
|
|
| Primary | 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). | Baseline Corrected T 1/2 values for 2 subjects were not able to be calculated based on the serum concentration-time curve of these subjects. | Posted | Mean | Standard Deviation | hr | -12 to 0 hr pre-dose and 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48 hrs post-dose |
|
|
|
| Secondary | Safety Assessment (Vital Signs) | Number of participants with clinically significant findings in vital signs by investigator after study drug administration. | Posted | Number | participants | Up to 10 days after first study drug administration at Day 1 of Period 1 |
|
|
|
| Secondary | Safety Assessment: Adverse Events | Number of participants with adverse events after study drug administration | Posted | Number | participants | Up to 10 days after first study drug administration at Day 1 of Period 1 |
|
|
|
| 0 |
| 18 |
| 0 |
| 18 |
| EG001 | Inosine Fasted | Inosine, 1000 mg tablet, in fasted condition, orally once on Day 1 in Period 1 or Day 8 in Period 2. | 0 | 18 | 0 | 18 |
All data and results and all intellectual-property rights in the data and results derived from the study will be the property of the sponsor. No publication or disclosure of study results will be permitted except as specified in a separate, written agreement between the Sponsor and the Investigator. If results of this study are reported in medical journals or at meetings, all subjects' identities will remain confidential.
| D006571 | Heterocyclic Compounds |
| D009705 | Nucleosides |
| D009706 | Nucleic Acids, Nucleotides, and Nucleosides |
| D012263 | Ribonucleosides |