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| Name | Class |
|---|---|
| Massachusetts General Hospital | OTHER |
| Harvard School of Public Health (HSPH) | OTHER |
| University of Rochester | OTHER |
| Michael J. Fox Foundation for Parkinson's Research |
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The purpose of this study is to determine the safety and tolerability of inosine and its ability to raise urate levels in blood and cerebral spinal fluid in individuals with early Parkinson disease. This will determine whether it is appropriate to proceed with a larger study of inosine's ability to modify the rate of disability progression in PD.
Background & Rationale:
Convergent epidemiological and clinical observations have identified urate - a major antioxidant and the end product of purine metabolism in humans - as the first molecular predictor of both the risk and the progression of typical Parkinson's disease (PD). Among some 1600 early PD patients enrolled in prior clinical trials, those with baseline serum urate levels in the highest quintile (i.e., in the upper normal range) displayed a 40% slower rate of clinical (disability) progression compared to those with baseline urate at or below the median (with p<0.000001 for trend across quintiles). Similarly, amongst those who underwent serial SPECT brain scans for changes in dopamine transporter (DAT) binding, those with higher baseline serum urate levels displayed a slower rate of radiographic progression (loss of striatal DAT). Moreover, urate levels in baseline cerebrospinal fluid (CSF) samples also correlate inversely with rates of clinical progression. Although this link between urate and a slower decline in PD appears reproducible and robust, the critical question of causality remains to be answered by a well-designed clinical trial. The biological plausibility of neuroprotection by urate strengthens the rationale for expedient pursuit of a trial. The availability of established pharmacological approaches to elevating urate makes such a trial feasible. In particular, inosine, an orally bioavailable, central nervous system (CNS)-penetrant purine precursor of urate, offers a practical strategy as it can readily elevate serum urate, has been widely consumed as a nutritional supplement, and has been administered chronically in several multi-year clinical trials for multiple sclerosis. Before embarking on a neuroprotection trial of inosine for PD, careful assessment of the safety, validity and methodology of this approach in PD patients is warranted.
Specific Aims:
The main goal of the study is to determine whether inosine is suitable for phase III evaluation of its ability to modify the rate of disability progression in PD. Specific primary aims entail the determination of the safety and tolerability of oral inosine, and its ability to elevate urate levels in serum or CSF; and the selection of an optimal dosing regimen. Secondary aims entail the further optimization of a possible phase III study design.
Methods:
A placebo-controlled double-blind dose-ranging randomized trial of inosine will be conducted in early PD. Ninety untreated subjects diagnosed with idiopathic PD and with a serum urate below the population mean (~6 mg/dL) will be enrolled at 17 North American sites and randomized to one of three treatment groups (n=30): 1) placebo, 2) inosine dosed to produce a mild elevation in serum urate, and 3) inosine dosed to produce a moderate elevation. Tolerability, validity (urate elevation), dosage and symptomatic efficacy will be assessed after 12 weeks of treatment. Contingent on adequate tolerability and validity as assessed in this short-term analysis, the study will continue for 2 years total duration with 2 groups (placebo and a merged single inosine dosing group) or the original 3 to assess long-term tolerability and safety, which will focus on main known risks of urolithiasis and gouty arthritis and the theoretical risk of cardiovascular disease.
Significance:
This study will determine whether a phase III trial of inosine as a potential neuroprotectant in PD is warranted. If it is, then the present study could shorten substantially the lead time, and through optimization of key design features would enhance the likelihood of its safety and success.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| [A:] | Placebo Comparator | Placebo to produce no urate elevation |
|
| [B:] | Experimental | Inosine to produce a mild urate elevation 500 mg of active substance per capsule; 1 to 6 capsules per day (in up to 3 divided doses) for 2 years; dosing titrated to a mildly elevated serum urate range of 6.1 - 7.0 mg/dL |
|
| [C.] | Experimental | Inosine to produce a moderate urate elevation 500 mg of active substance per capsule; 1 to 6 capsules per day (in up to 3 divided doses) for 2 years; dosing titrated to a moderately elevated serum urate range of 7.1 - 8.0 mg/dL |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Placebo | Drug | 500 mg of inactive substance per capsule; 1 to 6 capsules per day (in up to 3 divided doses) for 2 years; dosing adjusted algorithmically to parallel that in the inosine arms |
| Measure | Description | Time Frame |
|---|---|---|
| Tolerability | Defined as the extent to which assigned treatment could continue without prolonged dose reduction (>48 consecutive days or >73 cumulative days, which is 10% of total 2-year follow-up) due to adverse experiences (AEs), and was assessed after 6 and 24 months on study drug. Units of measure are percentage points (i.e., % of participants in the group). | 6 months |
| Tolerability | Defined as the extent to which assigned treatment could continue without prolonged dose reduction (>48 consecutive days or >73 cumulative days, which is 10% of total 2-year follow-up) due to AEs, and was assessed after 6 and 24 months on study drug. Units of measure are percentage points (i.e., % of participants in the group). | 24 months |
| Safety | Defined as absence of serious adverse experiences (SAEs) that warranted terminating an inosine treatment arm or the trial, as determined by the Data and Safety Monitoring Committee. | 24 months |
| Measure | Description | Time Frame |
|---|---|---|
| CSF Urate (All Patients) | Urate concentration in cerebrospinal fluid (CSF) | 12 weeks |
| CSF Urate (Females) | 12 weeks | |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Michael A Schwarzschild, MD, PhD | Massachusetts General Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Southern California | Los Angeles | California | 90083 | United States | ||
| Eastern Connecticut Neurology Specialists, LLC |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 31484712 | Derived | Schwarzschild MA, Macklin EA, Bakshi R, Battacharyya S, Logan R, Espay AJ, Hung AY, Bwala G, Goetz CG, Russell DS, Goudreau JL, Parashos SA, Saint-Hilaire MH, Rudolph A, Hare JM, Curhan GC, Ascherio A; Parkinson Study Group SURE-PD Investigators. Sex differences by design and outcome in the Safety of Urate Elevation in PD (SURE-PD) trial. Neurology. 2019 Oct 1;93(14):e1328-e1338. doi: 10.1212/WNL.0000000000008194. Epub 2019 Sep 4. | |
| 24366103 |
| Label | URL |
|---|---|
| Related Info | View source |
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| ID | Title | Description |
|---|---|---|
| FG000 | [A:]Placebo | Placebo to produce no urate elevation |
| FG001 | [B:]Mild | Inosine to produce a mild urate elevation |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| OTHER |
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| inosine | Drug | 500 mg of active substance per capsule; 1 to 6 capsules per day (in up to 3 divided doses) for 2 years; dosing titrated to a mildly elevated serum urate range of 6.1 - 7.0 mg/dL |
|
|
| inosine | Drug | 500 mg of active substance per capsule; 1 to 6 capsules per day (in up to 3 divided doses) for 2 years; dosing titrated to a moderately elevated serum urate range of 7.1 - 8.0 mg/dL |
|
|
| CSF Urate (Males) |
| 12 weeks |
| CSF Urate as a Proportion of Baseline Serum Urate (All Patients) | Although CSF urate was not measured at baseline, the change of CSF urate from baseline may be indirectly estimated by the ratio of CSF urate (at the 12 week visit when a lumbar puncture was performed) to the serum urate measured in the same subject at baseline. Baseline serum urate and CSF urate concentrations are directly correlated with one another (i.e., individuals with higher serum urate concentrations tend to have higher CSF urate concentrations) even though the concentration of urate in CSF is typically ~10% of that in serum. The ratio of CSF urate to baseline serum urate can be expressed as the percentage of the value of urate concentration measured in serum at baseline that is measured in CSF (at week 12). | 12 weeks |
| CSF Urate as a Proportion of Baseline Serum Urate (Females) | Although CSF urate was not measured at baseline, the change of CSF urate from baseline may be indirectly estimated by the ratio of CSF urate (at the 12 week visit when a lumbar puncture was performed) to the serum urate measured in the same subject at baseline. Baseline serum urate and CSF urate concentrations are directly correlated with one another (i.e., individuals with higher serum urate concentrations tend to have higher CSF urate concentrations) even though the concentration of urate in CSF is typically ~10% of that in serum. The ratio of CSF urate to baseline serum urate can be expressed as the percentage of the value of urate concentration measured in serum at baseline that is measured in CSF (at week 12). | 12 weeks |
| CSF Urate as a Proportion of Baseline Serum Urate (Males) | Although CSF urate was not measured at baseline, the change of CSF urate from baseline may be indirectly estimated by the ratio of CSF urate (at the 12 week visit when a lumbar puncture was performed) to the serum urate measured in the same subject at baseline. Baseline serum urate and CSF urate concentrations are directly correlated with one another (i.e., individuals with higher serum urate concentrations tend to have higher CSF urate concentrations) even though the concentration of urate in CSF is typically ~10% of that in serum. The ratio of CSF urate to baseline serum urate can be expressed as the percentage of the value of urate concentration measured in serum at baseline that is measured in CSF (at week 12). | 12 weeks |
| Serum Urate | From blood sample drawn prior to enrollment | Screening Visits, up to 45 days prior to Baseline Visit. Specifically, Screening Visit 1 occurred between day -45 and -4; Screening Visit 2 occurred between day -43 and -2. |
| Serum Urate | From blood sample drawn prior to enrollment | Baseline Visit |
| Serum Urate | From blood sample drawn after taking study drug that day | Visit 01 (Week 2; 14 +/- 3 days after Baseline Visit) |
| Serum Urate | From blood sample drawn after taking study drug that day | Visit 02 (Week 4; 28 +/- 3 days after Baseline Visit) |
| Serum Urate | From blood sample drawn after taking study drug that day | Visit 03 (Week 6; 42 +/- 3 days after Baseline Visit) |
| Serum Urate | From blood sample drawn after taking study drug that day | Visit 04 (Week 9; 63 +/- 5 days after Baseline Visit) |
| Serum Urate | From blood sample drawn before taking study drug that day | Visit 05 (Week 12; 84 +/- 7 days after Baseline Visit) |
| Serum Urate | From blood sample drawn after taking study drug that day | Visit 06 (Month 6; 180 +/- 7 days after Baseline Visit) |
| Serum Urate | From blood sample drawn after taking study drug that day | Visit 07 (Month 9; 270 +/- 7 days after Baseline Visit) |
| Serum Urate | From blood sample drawn after taking study drug that day | Visit 08 (Month 12; 360 +/- 7 days after Baseline Visit) |
| Serum Urate | From blood sample drawn after taking study drug that day | Visit 09 (Month 15; 450 +/- 7 days after Baseline Visit) |
| Serum Urate | From blood sample drawn after taking study drug that day | Visit 10 (Month 18; 540 +/- 7 days after Baseline Visit) |
| Serum Urate | From blood sample drawn after taking study drug that day | Visit 11 (Month 21; 630 +/- 7 days after Baseline Visit) |
| Serum Urate | From blood sample drawn after taking study drug that day | Visit 12 (Month 24; 720 +/- 7 days after Baseline Visit) |
| Serum Urate | From blood sample drawn after taking study drug that day | End of Study Drug Visit (ESD) (Month 9-24; 263-727 days after Baseline Visit) |
| Serum Urate | From blood sample drawn a month after stopping study drug | Safety Visit (SV); 30 +/- 3 days following ESD or Month 24 Visit |
| Change in Serum Urate | Change from an Average of Baseline and Screening Visits | Visit 01 from Baseline (i.e., between -45 days and +2 weeks) |
| Change in Serum Urate | Change from an Average of Baseline and Screening Visits | Visit 02 from Baseline (i.e., between -45 days and +4 weeks) |
| Change in Serum Urate | Change from an Average of Baseline and Screening Visits | Visit 03 from Baseline (i.e., between -45 days and +6 weeks) |
| Change in Serum Urate | Change from an Average of Baseline and Screening Visits | Visit 04 from Baseline (i.e., between -45 days and +9 weeks) |
| Change in Serum Urate | Change from an Average of Baseline and Screening Visits | Visit 05 from Baseline (i.e., between -45 days and +12 weeks) |
| Change in Serum Urate | Change from an Average of Baseline and Screening Visits | Visit 06 from Baseline (i.e., between -45 days and +6 months) |
| Change in Serum Urate | Change from an Average of Baseline and Screening Visits | Visit 07 from Baseline (i.e., between -45 days and +9 months) |
| Change in Serum Urate | Change from an Average of Baseline and Screening Visits | Visit 08 from Baseline (i.e., between -45 days and +12 months) |
| Change in Serum Urate | Change from an Average of Baseline and Screening Visits | Visit 09 from Baseline (i.e., between -45 days and +15 months) |
| Change in Serum Urate | Change from an Average of Baseline and Screening Visits | Visit 10 from Baseline (i.e., between -45 days and +18 months) |
| Change in Serum Urate | Change from an Average of Baseline and Screening Visits | Visit 11 from Baseline (i.e., between -45 days and +21 months) |
| Change in Serum Urate | Change from an Average of Baseline and Screening Visits | Visit 12 from Baseline (i.e., between -45 days and +24 months) |
| Change in Serum Urate | Change from an Average of Baseline and Screening Visits | Safety Visit (SV) from Baseline (i.e., between -45 days and +760 days [+1 month after ESD Visit]) |
| Change in Serum Urate | Change from Last Visit on Study Drug | Safety Visit (SV) from End of Study Drug Visit (ESD); i.e., between +263 and +760 days) |
| Manchester |
| Connecticut |
| 06040 |
| United States |
| Institute for Neurodegenerative Disorders | New Haven | Connecticut | 06510 | United States |
| Parkinson's Disease and Movement Disorders Center of Boca Raton | Boca Raton | Florida | 33486 | United States |
| Rush University Medical Center | Chicago | Illinois | 60612 | United States |
| Ochsner Clinic Foundation | New Orleans | Louisiana | 70121 | United States |
| Massachusetts General Hospital | Boston | Massachusetts | 02114 | United States |
| Boston University Medical Center | Boston | Massachusetts | 02118 | United States |
| Michigan State University | East Lansing | Michigan | 48824 | United States |
| Struthers Parkinson's Center | Golden Valley | Minnesota | 55427 | United States |
| Duke University School of Medicine | Durham | North Carolina | 27705 | United States |
| University of Cincinnati | Cincinnati | Ohio | 45219 | United States |
| Cleveland Clinic | Cleveland | Ohio | 44195 | United States |
| Oregon Health and Science University | Portland | Oregon | 97239 | United States |
| Butler Hospital Movement Disorder Program | Providence | Rhode Island | 02906 | United States |
| Scott & White Hospital | Temple | Texas | 76508 | United States |
| Derived |
| 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. |
| FG002 |
| [C.]Moderate |
Inosine to produce a moderate urate elevation |
| COMPLETED |
|
| NOT COMPLETED |
|
|
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | [A:]Placebo | Placebo to produce no urate elevation |
| BG001 | [B:]Mild | Inosine to produce a mild urate elevation |
| BG002 | [C.]Moderate | Inosine to produce a moderate urate elevation |
| BG003 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Region of Enrollment | Number | participants |
| ||||||||||||||||
| Years since symptom onset | Mean | Standard Deviation | Years |
| |||||||||||||||
| Years since diagnosis | Mean | Standard Deviation | Years |
| |||||||||||||||
| Serum Urate | Mean | Standard Deviation | mg/dL |
| |||||||||||||||
| Serum urate in women | Mean | Standard Deviation | mg/dL |
| |||||||||||||||
| Serum urate in men | Mean | Standard Deviation | mg/dL |
| |||||||||||||||
| United Parkinson's Disease Rating Scale (UPDRS) score total | The UPDRS is designed to monitor disability and impairment due to Parkinson's disease. It comprises several parts. Part I evaluates "Mentation, Behavior, and Mood" (with a maximum of 16 points; more points are worse); Part II evaluates "Activities of Daily Living" (with a maximum of 52 points); Part III entails a "Motor Examination" (with a maximum of 108 points). Total score of Parts I-III sums the points from all parts and thus can range from a minimum of 0 (best) to a maximum of 176 (worst). | Mean | Standard Deviation | points |
| ||||||||||||||
| Montreal Cognitive Assessment (MoCA) | The MoCA assesses short term and working memory, visual-spatial abilities, executive function, attention, concentration, language and orientation. The total score ranges from 0 to 30 (highest function). | Mean | Standard Deviation | Score |
| ||||||||||||||
| Geriatric Depression Scale-short form (GDS-S) | GDS-S is a short 15 'yes/no' question instrument for assessing depression in older adults. Questions are answered by the research participant (i.e., self-rater). Scores range range from 0 to 15 and higher scores represent greater depression. Scores of 5-9 and >9 have been correlated with mild and moderate-severe depression, respectively. | Mean | Standard Deviation | Score |
|
| 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 | Tolerability | Defined as the extent to which assigned treatment could continue without prolonged dose reduction (>48 consecutive days or >73 cumulative days, which is 10% of total 2-year follow-up) due to adverse experiences (AEs), and was assessed after 6 and 24 months on study drug. Units of measure are percentage points (i.e., % of participants in the group). | Posted | Number | percentage of participants | 6 months |
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| Primary | Tolerability | Defined as the extent to which assigned treatment could continue without prolonged dose reduction (>48 consecutive days or >73 cumulative days, which is 10% of total 2-year follow-up) due to AEs, and was assessed after 6 and 24 months on study drug. Units of measure are percentage points (i.e., % of participants in the group). | Posted | Number | percentage of participants | 24 months |
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| Secondary | CSF Urate (All Patients) | Urate concentration in cerebrospinal fluid (CSF) | Posted | Mean | Standard Deviation | mcg/dL | 12 weeks |
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| Secondary | CSF Urate (Females) | Posted | Mean | Standard Deviation | mcg/dL | 12 weeks |
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| Secondary | CSF Urate (Males) | Posted | Mean | Standard Deviation | mcg/dL | 12 weeks |
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| Secondary | CSF Urate as a Proportion of Baseline Serum Urate (All Patients) | Although CSF urate was not measured at baseline, the change of CSF urate from baseline may be indirectly estimated by the ratio of CSF urate (at the 12 week visit when a lumbar puncture was performed) to the serum urate measured in the same subject at baseline. Baseline serum urate and CSF urate concentrations are directly correlated with one another (i.e., individuals with higher serum urate concentrations tend to have higher CSF urate concentrations) even though the concentration of urate in CSF is typically ~10% of that in serum. The ratio of CSF urate to baseline serum urate can be expressed as the percentage of the value of urate concentration measured in serum at baseline that is measured in CSF (at week 12). | Posted | Mean | Standard Deviation | percentage of baseline serum urate | 12 weeks |
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| Secondary | CSF Urate as a Proportion of Baseline Serum Urate (Females) | Although CSF urate was not measured at baseline, the change of CSF urate from baseline may be indirectly estimated by the ratio of CSF urate (at the 12 week visit when a lumbar puncture was performed) to the serum urate measured in the same subject at baseline. Baseline serum urate and CSF urate concentrations are directly correlated with one another (i.e., individuals with higher serum urate concentrations tend to have higher CSF urate concentrations) even though the concentration of urate in CSF is typically ~10% of that in serum. The ratio of CSF urate to baseline serum urate can be expressed as the percentage of the value of urate concentration measured in serum at baseline that is measured in CSF (at week 12). | Posted | Mean | Standard Deviation | percentage of baseline serum urate | 12 weeks |
| ||||||||||||||||||||||||||||||||||
| Secondary | CSF Urate as a Proportion of Baseline Serum Urate (Males) | Although CSF urate was not measured at baseline, the change of CSF urate from baseline may be indirectly estimated by the ratio of CSF urate (at the 12 week visit when a lumbar puncture was performed) to the serum urate measured in the same subject at baseline. Baseline serum urate and CSF urate concentrations are directly correlated with one another (i.e., individuals with higher serum urate concentrations tend to have higher CSF urate concentrations) even though the concentration of urate in CSF is typically ~10% of that in serum. The ratio of CSF urate to baseline serum urate can be expressed as the percentage of the value of urate concentration measured in serum at baseline that is measured in CSF (at week 12). | Posted | Mean | Standard Deviation | percentage of baseline serum urate | 12 weeks |
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| Secondary | Serum Urate | From blood sample drawn prior to enrollment | Posted | Mean | Standard Deviation | mg/dL | Screening Visits, up to 45 days prior to Baseline Visit. Specifically, Screening Visit 1 occurred between day -45 and -4; Screening Visit 2 occurred between day -43 and -2. |
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| Secondary | Serum Urate | From blood sample drawn prior to enrollment | Posted | Mean | Standard Deviation | mg/dL | Baseline Visit |
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| Primary | Safety | Defined as absence of serious adverse experiences (SAEs) that warranted terminating an inosine treatment arm or the trial, as determined by the Data and Safety Monitoring Committee. | Posted | Number | Events | 24 months |
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| Secondary | Serum Urate | From blood sample drawn after taking study drug that day | Posted | Mean | Standard Deviation | mg/dL | Visit 01 (Week 2; 14 +/- 3 days after Baseline Visit) |
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| Secondary | Serum Urate | From blood sample drawn after taking study drug that day | Posted | Mean | Standard Deviation | mg/dL | Visit 02 (Week 4; 28 +/- 3 days after Baseline Visit) |
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| Secondary | Serum Urate | From blood sample drawn after taking study drug that day | Posted | Mean | Standard Deviation | mg/dL | Visit 03 (Week 6; 42 +/- 3 days after Baseline Visit) |
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| Secondary | Serum Urate | From blood sample drawn after taking study drug that day | Posted | Mean | Standard Deviation | mg/dL | Visit 04 (Week 9; 63 +/- 5 days after Baseline Visit) |
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| Secondary | Serum Urate | From blood sample drawn before taking study drug that day | Posted | Mean | Standard Deviation | mg/dL | Visit 05 (Week 12; 84 +/- 7 days after Baseline Visit) |
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| Secondary | Serum Urate | From blood sample drawn after taking study drug that day | Posted | Mean | Standard Deviation | mg/dL | Visit 06 (Month 6; 180 +/- 7 days after Baseline Visit) |
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| Secondary | Serum Urate | From blood sample drawn after taking study drug that day | Posted | Mean | Standard Deviation | mg/dL | Visit 07 (Month 9; 270 +/- 7 days after Baseline Visit) |
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| Secondary | Serum Urate | From blood sample drawn after taking study drug that day | Posted | Mean | Standard Deviation | mg/dL | Visit 08 (Month 12; 360 +/- 7 days after Baseline Visit) |
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| Secondary | Serum Urate | From blood sample drawn after taking study drug that day | Posted | Mean | Standard Deviation | mg/dL | Visit 09 (Month 15; 450 +/- 7 days after Baseline Visit) |
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| Secondary | Serum Urate | From blood sample drawn after taking study drug that day | Posted | Mean | Standard Deviation | mg/dL | Visit 10 (Month 18; 540 +/- 7 days after Baseline Visit) |
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| Secondary | Serum Urate | From blood sample drawn after taking study drug that day | Posted | Mean | Standard Deviation | mg/dL | Visit 11 (Month 21; 630 +/- 7 days after Baseline Visit) |
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| Secondary | Serum Urate | From blood sample drawn after taking study drug that day | Posted | Mean | Standard Deviation | mg/dL | Visit 12 (Month 24; 720 +/- 7 days after Baseline Visit) |
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| Secondary | Serum Urate | From blood sample drawn after taking study drug that day | Posted | Mean | Standard Deviation | mg/dL | End of Study Drug Visit (ESD) (Month 9-24; 263-727 days after Baseline Visit) |
|
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| Secondary | Serum Urate | From blood sample drawn a month after stopping study drug | Posted | Mean | Standard Deviation | mg/dL | Safety Visit (SV); 30 +/- 3 days following ESD or Month 24 Visit |
|
| |||||||||||||||||||||||||||||||||
| Secondary | Change in Serum Urate | Change from an Average of Baseline and Screening Visits | Posted | Mean | Standard Deviation | mg/dL | Visit 01 from Baseline (i.e., between -45 days and +2 weeks) |
|
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| Secondary | Change in Serum Urate | Change from an Average of Baseline and Screening Visits | Posted | Mean | Standard Deviation | mg/dL | Visit 02 from Baseline (i.e., between -45 days and +4 weeks) |
|
| |||||||||||||||||||||||||||||||||
| Secondary | Change in Serum Urate | Change from an Average of Baseline and Screening Visits | Posted | Mean | Standard Deviation | mg/dL | Visit 03 from Baseline (i.e., between -45 days and +6 weeks) |
|
| |||||||||||||||||||||||||||||||||
| Secondary | Change in Serum Urate | Change from an Average of Baseline and Screening Visits | Posted | Mean | Standard Deviation | mg/dL | Visit 04 from Baseline (i.e., between -45 days and +9 weeks) |
|
| |||||||||||||||||||||||||||||||||
| Secondary | Change in Serum Urate | Change from an Average of Baseline and Screening Visits | Posted | Mean | Standard Deviation | mg/dL | Visit 05 from Baseline (i.e., between -45 days and +12 weeks) |
|
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| Secondary | Change in Serum Urate | Change from an Average of Baseline and Screening Visits | Posted | Mean | Standard Deviation | mg/dL | Visit 06 from Baseline (i.e., between -45 days and +6 months) |
|
| |||||||||||||||||||||||||||||||||
| Secondary | Change in Serum Urate | Change from an Average of Baseline and Screening Visits | Posted | Mean | Standard Deviation | mg/dL | Visit 07 from Baseline (i.e., between -45 days and +9 months) |
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| Secondary | Change in Serum Urate | Change from an Average of Baseline and Screening Visits | Posted | Mean | Standard Deviation | mg/dL | Visit 08 from Baseline (i.e., between -45 days and +12 months) |
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| Secondary | Change in Serum Urate | Change from an Average of Baseline and Screening Visits | Posted | Mean | Standard Deviation | mg/dL | Visit 09 from Baseline (i.e., between -45 days and +15 months) |
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| Secondary | Change in Serum Urate | Change from an Average of Baseline and Screening Visits | Posted | Mean | Standard Deviation | mg/dL | Visit 10 from Baseline (i.e., between -45 days and +18 months) |
|
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| Secondary | Change in Serum Urate | Change from an Average of Baseline and Screening Visits | Posted | Mean | Standard Deviation | mg/dL | Visit 11 from Baseline (i.e., between -45 days and +21 months) |
|
| |||||||||||||||||||||||||||||||||
| Secondary | Change in Serum Urate | Change from an Average of Baseline and Screening Visits | Posted | Mean | Standard Deviation | mg/dL | Visit 12 from Baseline (i.e., between -45 days and +24 months) |
|
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| Secondary | Change in Serum Urate | Change from an Average of Baseline and Screening Visits | Posted | Mean | Standard Deviation | mg/dL | Safety Visit (SV) from Baseline (i.e., between -45 days and +760 days [+1 month after ESD Visit]) |
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| Secondary | Change in Serum Urate | Change from Last Visit on Study Drug | Posted | Mean | Standard Deviation | mg/dL | Safety Visit (SV) from End of Study Drug Visit (ESD); i.e., between +263 and +760 days) |
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|
Not provided
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | [A:]Placebo | Placebo to produce no urate elevation | 9 | 25 | 18 | 25 | ||
| EG001 | [B:]Mild | Inosine to produce a mild urate elevation | 2 | 24 | 22 | 24 | ||
| EG002 | [C.]Moderate | Inosine to produce a moderate urate elevation | 4 | 26 | 20 | 26 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Acute coronary syndrome | Cardiac disorders | MedDRA | Systematic Assessment |
| |
| Arthritis | Musculoskeletal and connective tissue disorders | MedDRA | Systematic Assessment |
| |
| Cerebrovascular accident | Nervous system disorders | MedDRA | Systematic Assessment |
| |
| Cervical vertebral fracture | Injury, poisoning and procedural complications | MedDRA | Systematic Assessment |
| |
| Cholecystitis | Hepatobiliary disorders | MedDRA | Systematic Assessment |
| |
| Coronary artery disease | Cardiac disorders | MedDRA | Systematic Assessment |
| |
| Depression | Psychiatric disorders | MedDRA | Systematic Assessment |
| |
| Human ehrlichiosis | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Nephrolithiasis | Renal and urinary disorders | MedDRA | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Pulmonary fibrosis | Respiratory, thoracic and mediastinal disorders | MedDRA | Systematic Assessment |
| |
| Radiculopathy | Nervous system disorders | MedDRA | Systematic Assessment |
| |
| Suicidal ideation | Psychiatric disorders | MedDRA | Systematic Assessment |
| |
| Synovial cyst | Musculoskeletal and connective tissue disorders | MedDRA | Systematic Assessment |
| |
| Urosepsis | Infections and infestations | MedDRA | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anxiety | Psychiatric disorders | MedDRA (11.0) | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA (11.0) | Systematic Assessment |
| |
| Arthritis | Musculoskeletal and connective tissue disorders | MedDRA (11.0) | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA (11.0) | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA (11.0) | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (11.0) | Systematic Assessment |
| |
| Dehydration | Metabolism and nutrition disorders | MedDRA (11.0) | Systematic Assessment |
| |
| Depression | Psychiatric disorders | MedDRA (11.0) | Systematic Assessment |
| |
| Dermatitis contact | Skin and subcutaneous tissue disorders | MedDRA (11.0) | Systematic Assessment |
| |
| Dry Mouth | Gastrointestinal disorders | MedDRA (11.0) | Systematic Assessment |
| |
| Dyspepsia | Gastrointestinal disorders | MedDRA (11.0) | Systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA (11.0) | Systematic Assessment |
| |
| Fall | Injury, poisoning and procedural complications | MedDRA (11.0) | Systematic Assessment |
| |
| Fatigue | General disorders | MedDRA (11.0) | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA (11.0) | Systematic Assessment |
| |
| Insomnia | Psychiatric disorders | MedDRA (11.0) | Systematic Assessment |
| |
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA (11.0) | Systematic Assessment |
| |
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA (11.0) | Systematic Assessment |
| |
| Musculoskeletal stiffness | Musculoskeletal and connective tissue disorders | MedDRA (11.0) | Systematic Assessment |
| |
| Nephrolithiasis | Renal and urinary disorders | MedDRA (11.0) | Systematic Assessment |
| |
| Oedema peripheral | General disorders | MedDRA (11.0) | Systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA (11.0) | Systematic Assessment |
| |
| Pharyngolaryngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA (11.0) | Systematic Assessment |
| |
| Sinusitis | Infections and infestations | MedDRA (11.0) | Systematic Assessment |
| |
| Suicidal ideation | Psychiatric disorders | MedDRA (11.0) | Systematic Assessment |
| |
| Tremor | Nervous system disorders | MedDRA (11.0) | Systematic Assessment |
| |
| Upper respiratory track infection | Infections and infestations | MedDRA (11.0) | Systematic Assessment |
|
Not provided
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Michael A. Schwarzschild, MD, PhD | The Parkinson Study Group | 617-724-9611 | mschwarzschild@partners.org |
| ID | Term |
|---|---|
| D010300 | Parkinson Disease |
| ID | Term |
|---|---|
| D020734 | Parkinsonian Disorders |
| D001480 | Basal Ganglia Diseases |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D009069 | Movement Disorders |
| D000080874 | Synucleinopathies |
| D019636 | Neurodegenerative Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D007288 | Inosine |
| ID | Term |
|---|---|
| D011684 | Purine Nucleosides |
| D011687 | Purines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| D009705 | Nucleosides |
| D009706 | Nucleic Acids, Nucleotides, and Nucleosides |
| D012263 | Ribonucleosides |
Not provided
Not provided
| Male |
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| Not Hispanic or Latino |
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| Unknown or Not Reported |
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| Asian |
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| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
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| More than one race |
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| Unknown or Not Reported |
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