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

NCT02614469 | Completed Phase 1 Results

• 1 other identifier: INO-PD-P3-2015-FE
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy

Outcome Measures

Primary Outcomes (10)

• 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 Outcomes (2)

• Safety Assessment (Vital Signs)

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

• Safety Assessment: Adverse Events

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

Study Arms (2)

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.

Drug: Inosine

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.

Drug: Inosine

Interventions

Inosine DRUG

Inosine, 1000 mg

Group 1, Inosine with Food; Group 2, Inosine without Food

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Michael Alan Schwarzschild: lead
• Michael J. Fox Foundation for Parkinson's Research: collaborator
• The Parkinson Alliance: collaborator

Study Sites (1)

Covance Clinical Research Unit Inc.

Evansville, Indiana, 47710, United States

Location

Related Publications (6)

• 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.

  PMID: 3959904 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.

  PMID: 23457767 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.

  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.

  PMID: 24366103 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.

  PMID: 11724447 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.

  PMID: 11912550 BACKGROUND

MeSH Terms

Interventions

Inosine

Intervention Hierarchy (Ancestors)

Purine Nucleosides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Results Point of Contact

• Title: Dr. Michael Schwarzschild
• Organization: Massachusetts General Hospital

michaels@helix.mgh.harvard.edu

617-764-9611

Study Officials

• Mason Freeman, M.D.

  Massachusetts General Hospital

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Director, Molecular Neurobiology Laboratory

Study Record Dates

• First Submitted: November 23, 2015
• First Posted: November 25, 2015
• Study Start: March 1, 2015
• Primary Completion: April 1, 2016
• Study Completion: May 1, 2016
• Last Updated: March 29, 2017
• Results First Posted: February 24, 2017

Record last verified: 2017-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)