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Safety of Urate Elevation in Parkinson's Disease

A Randomized, Double-blind, Placebo-controlled, Dose-ranging Trial of Oral Inosine to Assess Safety and Ability to Elevate Urate in Early Parkinson's Disease

Status
Completed
Phases
Phase 2
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT00833690
Acronym
SURE-PD
Enrollment
75
Registered
2009-02-02
Start date
2009-06-30
Completion date
2012-12-31
Last updated
2014-06-05

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Parkinson Disease

Keywords

Parkinson's disease, Parkinson disease, PD, inosine, urate, uric acid, cerebrospinal fluid

Brief summary

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.

Detailed description

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.

Interventions

DRUGPlacebo

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

DRUGinosine

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

Sponsors

Massachusetts General Hospital
CollaboratorOTHER
Harvard School of Public Health (HSPH)
CollaboratorOTHER
University of Rochester
CollaboratorOTHER
Michael J. Fox Foundation for Parkinson's Research
CollaboratorOTHER
The Parkinson Study Group
Lead SponsorNETWORK

Study design

Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)

Eligibility

Sex/Gender
ALL
Age
30 Years to No maximum
Healthy volunteers
No

Inclusion criteria

* Idiopathic PD with at least two of the cardinal signs of PD (resting tremor, bradykinesia, rigidity) * Currently not taking or needing any treatment for PD other than an monoamine oxidase-B (MAO-B) inhibitor * Age 30 or older at the time of PD diagnosis * Diagnosis of PD made within past 3 years * Serum urate ≤ 5.8 mg/dL at initial screening

Exclusion criteria

* History of kidney stones, gout, stroke, or heart attack * History of renal disease or certain cardiovascular problems within the past year * Acidic urine (pH ≤ 5.0), uric acid, or urate crystalluria at screening * Use of certain medications including co-enzyme Q, creatine, more than 50 IU of vitamin E daily, and more than 300 mg of vitamin C daily. (A standard daily multivitamin is permitted.) * Use of anti-PD and other medications targeting central nervous system dopamine transmission * Known unstable medical or psychiatric condition that may compromise participation in the study * Women who are pregnant or lactating

Design outcomes

Primary

MeasureTime frameDescription
Tolerability6 monthsDefined 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).
Safety24 monthsDefined 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.

Secondary

MeasureTime frameDescription
CSF Urate (Males)12 weeks—
CSF Urate as a Proportion of Baseline Serum Urate (All Patients)12 weeksAlthough 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).
CSF Urate as a Proportion of Baseline Serum Urate (Females)12 weeksAlthough 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).
CSF Urate (All Patients)12 weeksUrate concentration in cerebrospinal fluid (CSF)
Serum UrateScreening 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.From blood sample drawn prior to enrollment
Change in Serum UrateVisit 01 from Baseline (i.e., between -45 days and +2 weeks)Change from an Average of Baseline and Screening Visits
CSF Urate as a Proportion of Baseline Serum Urate (Males)12 weeksAlthough 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).
CSF Urate (Females)12 weeks—

Countries

United States

Participant flow

Participants by arm

ArmCount
[A:]Placebo
Placebo to produce no urate elevation
25
[B:]Mild
Inosine to produce a mild urate elevation
24
[C.]Moderate
Inosine to produce a moderate urate elevation
26
Total75

Withdrawals & dropouts

PeriodReasonFG000FG001FG002
Overall StudyDiscontinued study drug320
Overall StudyWithdrawal by Subject100

Baseline characteristics

Characteristic[B:]MildTotal[C.]Moderate[A:]Placebo
Age, Continuous62 years
STANDARD_DEVIATION 10
62 years
STANDARD_DEVIATION 10
62 years
STANDARD_DEVIATION 11
61 years
STANDARD_DEVIATION 11
Ethnicity (NIH/OMB)
Hispanic or Latino
2 Participants2 Participants0 Participants0 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
22 Participants73 Participants26 Participants25 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
0 Participants0 Participants0 Participants0 Participants
Geriatric Depression Scale-short form (GDS-S)1.4 Score
STANDARD_DEVIATION 1.7
1.5 Score
STANDARD_DEVIATION 2.1
1.8 Score
STANDARD_DEVIATION 2.6
1.5 Score
STANDARD_DEVIATION 1.9
Montreal Cognitive Assessment (MoCA)28 Score
STANDARD_DEVIATION 1.8
28 Score
STANDARD_DEVIATION 1.9
28 Score
STANDARD_DEVIATION 2
28 Score
STANDARD_DEVIATION 1.9
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants0 Participants0 Participants0 Participants
Race (NIH/OMB)
Asian
0 Participants0 Participants0 Participants0 Participants
Race (NIH/OMB)
Black or African American
0 Participants0 Participants0 Participants0 Participants
Race (NIH/OMB)
More than one race
0 Participants0 Participants0 Participants0 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants1 Participants1 Participants0 Participants
Race (NIH/OMB)
Unknown or Not Reported
2 Participants4 Participants1 Participants1 Participants
Race (NIH/OMB)
White
22 Participants70 Participants24 Participants24 Participants
Region of Enrollment
United States
24 participants75 participants26 participants25 participants
Serum Urate4.3 mg/dL
STANDARD_DEVIATION 1.2
4.5 mg/dL
STANDARD_DEVIATION 0.9
4.6 mg/dL
STANDARD_DEVIATION 0.9
4.5 mg/dL
STANDARD_DEVIATION 0.7
Serum urate in men5.0 mg/dL
STANDARD_DEVIATION 0.8
4.8 mg/dL
STANDARD_DEVIATION 0.7
4.9 mg/dL
STANDARD_DEVIATION 0.9
4.7 mg/dL
STANDARD_DEVIATION 0.5
Serum urate in women3.9 mg/dL
STANDARD_DEVIATION 1.3
4.2 mg/dL
STANDARD_DEVIATION 1
4.4 mg/dL
STANDARD_DEVIATION 0.8
4.4 mg/dL
STANDARD_DEVIATION 0.8
Sex: Female, Male
Female
14 Participants41 Participants14 Participants13 Participants
Sex: Female, Male
Male
10 Participants34 Participants12 Participants12 Participants
United Parkinson's Disease Rating Scale (UPDRS) score total20 points
STANDARD_DEVIATION 9
22 points
STANDARD_DEVIATION 10
21 points
STANDARD_DEVIATION 10
23 points
STANDARD_DEVIATION 10
Years since diagnosis1.3 Years
STANDARD_DEVIATION 1
1.0 Years
STANDARD_DEVIATION 1.1
0.6 Years
STANDARD_DEVIATION 0.7
1.1 Years
STANDARD_DEVIATION 1.3
Years since symptom onset2.8 Years
STANDARD_DEVIATION 1.9
2.4 Years
STANDARD_DEVIATION 1.8
2.2 Years
STANDARD_DEVIATION 2
2.4 Years
STANDARD_DEVIATION 1.3

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
EG002
affected / at risk
deaths
Total, all-cause mortality
— / —— / —— / —
other
Total, other adverse events
18 / 2522 / 2420 / 26
serious
Total, serious adverse events
9 / 252 / 244 / 26

Outcome results

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.

Time frame: 24 months

ArmMeasureValue (NUMBER)
[A:]PlaceboSafety11 Events
[B:]MildSafety2 Events
[C.]ModerateSafety4 Events
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).

Time frame: 6 months

ArmMeasureValue (NUMBER)
[A:]PlaceboTolerability96 percentage of participants
[B:]MildTolerability96 percentage of participants
[C.]ModerateTolerability100 percentage of participants
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).

Time frame: 24 months

ArmMeasureValue (NUMBER)
[A:]PlaceboTolerability86 percentage of participants
[B:]MildTolerability92 percentage of participants
[C.]ModerateTolerability96 percentage of participants
Secondary

Change in Serum Urate

Change from Last Visit on Study Drug

Time frame: Safety Visit (SV) from End of Study Drug Visit (ESD); i.e., between +263 and +760 days)

ArmMeasureValue (MEAN)Dispersion
[A:]PlaceboChange in Serum Urate0.12 mg/dLStandard Deviation 0.51
[B:]MildChange in Serum Urate-1.8 mg/dLStandard Deviation 1.33
[C.]ModerateChange in Serum Urate-3.2 mg/dLStandard Deviation 1.63
Secondary

Change in Serum Urate

Change from an Average of Baseline and Screening Visits

Time frame: Visit 01 from Baseline (i.e., between -45 days and +2 weeks)

ArmMeasureValue (MEAN)Dispersion
[A:]PlaceboChange in Serum Urate0.15 mg/dLStandard Deviation 0.41
[B:]MildChange in Serum Urate2.1 mg/dLStandard Deviation 0.83
[C.]ModerateChange in Serum Urate2.44 mg/dLStandard Deviation 1.07
Secondary

Change in Serum Urate

Change from an Average of Baseline and Screening Visits

Time frame: Visit 02 from Baseline (i.e., between -45 days and +4 weeks)

ArmMeasureValue (MEAN)Dispersion
[A:]PlaceboChange in Serum Urate0.09 mg/dLStandard Deviation 0.48
[B:]MildChange in Serum Urate2.24 mg/dLStandard Deviation 1.13
[C.]ModerateChange in Serum Urate3.41 mg/dLStandard Deviation 1.22
Secondary

Change in Serum Urate

Change from an Average of Baseline and Screening Visits

Time frame: Visit 03 from Baseline (i.e., between -45 days and +6 weeks)

ArmMeasureValue (MEAN)Dispersion
[A:]PlaceboChange in Serum Urate0.22 mg/dLStandard Deviation 0.51
[B:]MildChange in Serum Urate2.35 mg/dLStandard Deviation 1.03
[C.]ModerateChange in Serum Urate3.02 mg/dLStandard Deviation 1.13
Secondary

Change in Serum Urate

Change from an Average of Baseline and Screening Visits

Time frame: Visit 04 from Baseline (i.e., between -45 days and +9 weeks)

ArmMeasureValue (MEAN)Dispersion
[A:]PlaceboChange in Serum Urate-0.02 mg/dLStandard Deviation 0.35
[B:]MildChange in Serum Urate2.47 mg/dLStandard Deviation 1.34
[C.]ModerateChange in Serum Urate3.13 mg/dLStandard Deviation 1.16
Secondary

Change in Serum Urate

Change from an Average of Baseline and Screening Visits

Time frame: Visit 05 from Baseline (i.e., between -45 days and +12 weeks)

ArmMeasureValue (MEAN)Dispersion
[A:]PlaceboChange in Serum Urate0.1 mg/dLStandard Deviation 0.42
[B:]MildChange in Serum Urate1.51 mg/dLStandard Deviation 0.8
[C.]ModerateChange in Serum Urate2.42 mg/dLStandard Deviation 1.08
Secondary

Change in Serum Urate

Change from an Average of Baseline and Screening Visits

Time frame: Visit 06 from Baseline (i.e., between -45 days and +6 months)

ArmMeasureValue (MEAN)Dispersion
[A:]PlaceboChange in Serum Urate0.21 mg/dLStandard Deviation 0.86
[B:]MildChange in Serum Urate2.55 mg/dLStandard Deviation 1.4
[C.]ModerateChange in Serum Urate3.78 mg/dLStandard Deviation 0.95
Secondary

Change in Serum Urate

Change from an Average of Baseline and Screening Visits

Time frame: Visit 07 from Baseline (i.e., between -45 days and +9 months)

ArmMeasureValue (MEAN)Dispersion
[A:]PlaceboChange in Serum Urate0.14 mg/dLStandard Deviation 0.68
[B:]MildChange in Serum Urate2.43 mg/dLStandard Deviation 1.56
[C.]ModerateChange in Serum Urate3.56 mg/dLStandard Deviation 1.51
Secondary

Change in Serum Urate

Change from an Average of Baseline and Screening Visits

Time frame: Visit 08 from Baseline (i.e., between -45 days and +12 months)

ArmMeasureValue (MEAN)Dispersion
[A:]PlaceboChange in Serum Urate0.2 mg/dLStandard Deviation 0.78
[B:]MildChange in Serum Urate2.46 mg/dLStandard Deviation 1.24
[C.]ModerateChange in Serum Urate2.96 mg/dLStandard Deviation 1.28
Secondary

Change in Serum Urate

Change from an Average of Baseline and Screening Visits

Time frame: Visit 09 from Baseline (i.e., between -45 days and +15 months)

ArmMeasureValue (MEAN)Dispersion
[A:]PlaceboChange in Serum Urate0 mg/dLStandard Deviation 0.67
[B:]MildChange in Serum Urate2.9 mg/dLStandard Deviation 0.98
[C.]ModerateChange in Serum Urate3.19 mg/dLStandard Deviation 1.18
Secondary

Change in Serum Urate

Change from an Average of Baseline and Screening Visits

Time frame: Visit 10 from Baseline (i.e., between -45 days and +18 months)

ArmMeasureValue (MEAN)Dispersion
[A:]PlaceboChange in Serum Urate-0.07 mg/dLStandard Deviation 0.43
[B:]MildChange in Serum Urate2.49 mg/dLStandard Deviation 1.07
[C.]ModerateChange in Serum Urate3.26 mg/dLStandard Deviation 1.25
Secondary

Change in Serum Urate

Change from an Average of Baseline and Screening Visits

Time frame: Visit 11 from Baseline (i.e., between -45 days and +21 months)

ArmMeasureValue (MEAN)Dispersion
[A:]PlaceboChange in Serum Urate-0.07 mg/dLStandard Deviation 0.59
[B:]MildChange in Serum Urate2.53 mg/dLStandard Deviation 1.12
[C.]ModerateChange in Serum Urate3.11 mg/dLStandard Deviation 1.46
Secondary

Change in Serum Urate

Change from an Average of Baseline and Screening Visits

Time frame: Visit 12 from Baseline (i.e., between -45 days and +24 months)

ArmMeasureValue (MEAN)Dispersion
[A:]PlaceboChange in Serum Urate-0.29 mg/dLStandard Deviation 1.08
[B:]MildChange in Serum Urate2.22 mg/dLStandard Deviation 0.96
[C.]ModerateChange in Serum Urate2.93 mg/dLStandard Deviation 1.38
Secondary

Change in Serum Urate

Change from an Average of Baseline and Screening Visits

Time frame: Safety Visit (SV) from Baseline (i.e., between -45 days and +760 days [+1 month after ESD Visit])

ArmMeasureValue (MEAN)Dispersion
[A:]PlaceboChange in Serum Urate0.1 mg/dLStandard Deviation 0.62
[B:]MildChange in Serum Urate0.35 mg/dLStandard Deviation 0.88
[C.]ModerateChange in Serum Urate-0.11 mg/dLStandard Deviation 0.61
Secondary

CSF Urate (All Patients)

Urate concentration in cerebrospinal fluid (CSF)

Time frame: 12 weeks

ArmMeasureValue (MEAN)Dispersion
[A:]PlaceboCSF Urate (All Patients)427 mcg/dLStandard Deviation 190
[B:]MildCSF Urate (All Patients)544 mcg/dLStandard Deviation 148
[C.]ModerateCSF Urate (All Patients)594 mcg/dLStandard Deviation 175
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).

Time frame: 12 weeks

ArmMeasureValue (MEAN)Dispersion
[A:]PlaceboCSF Urate as a Proportion of Baseline Serum Urate (All Patients)9.6 percentage of baseline serum urateStandard Deviation 4
[B:]MildCSF Urate as a Proportion of Baseline Serum Urate (All Patients)13.1 percentage of baseline serum urateStandard Deviation 4
[C.]ModerateCSF Urate as a Proportion of Baseline Serum Urate (All Patients)13.4 percentage of baseline serum urateStandard Deviation 4.3
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).

Time frame: 12 weeks

ArmMeasureValue (MEAN)Dispersion
[A:]PlaceboCSF Urate as a Proportion of Baseline Serum Urate (Females)6.7 percentage of baseline serum urateStandard Deviation 1.8
[B:]MildCSF Urate as a Proportion of Baseline Serum Urate (Females)13.5 percentage of baseline serum urateStandard Deviation 5
[C.]ModerateCSF Urate as a Proportion of Baseline Serum Urate (Females)13.3 percentage of baseline serum urateStandard Deviation 5
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).

Time frame: 12 weeks

ArmMeasureValue (MEAN)Dispersion
[A:]PlaceboCSF Urate as a Proportion of Baseline Serum Urate (Males)12.0 percentage of baseline serum urateStandard Deviation 3.8
[B:]MildCSF Urate as a Proportion of Baseline Serum Urate (Males)12.4 percentage of baseline serum urateStandard Deviation 2.2
[C.]ModerateCSF Urate as a Proportion of Baseline Serum Urate (Males)13.4 percentage of baseline serum urateStandard Deviation 3.5
Secondary

CSF Urate (Females)

Time frame: 12 weeks

ArmMeasureValue (MEAN)Dispersion
[A:]PlaceboCSF Urate (Females)285 mcg/dLStandard Deviation 69
[B:]MildCSF Urate (Females)517 mcg/dLStandard Deviation 169
[C.]ModerateCSF Urate (Females)575 mcg/dLStandard Deviation 176
Secondary

CSF Urate (Males)

Time frame: 12 weeks

ArmMeasureValue (MEAN)Dispersion
[A:]PlaceboCSF Urate (Males)546 mcg/dLStandard Deviation 178
[B:]MildCSF Urate (Males)586 mcg/dLStandard Deviation 113
[C.]ModerateCSF Urate (Males)619 mcg/dLStandard Deviation 184
Secondary

Serum Urate

From blood sample drawn after taking study drug that day

Time frame: Visit 12 (Month 24; 720 +/- 7 days after Baseline Visit)

ArmMeasureValue (MEAN)Dispersion
[A:]PlaceboSerum Urate4.41 mg/dLStandard Deviation 0.99
[B:]MildSerum Urate6.84 mg/dLStandard Deviation 0.76
[C.]ModerateSerum Urate7.19 mg/dLStandard Deviation 1.19
Secondary

Serum Urate

From blood sample drawn after taking study drug that day

Time frame: End of Study Drug Visit (ESD) (Month 9-24; 263-727 days after Baseline Visit)

ArmMeasureValue (MEAN)Dispersion
[A:]PlaceboSerum Urate4.66 mg/dLStandard Deviation 0.79
[B:]MildSerum Urate6.48 mg/dLStandard Deviation 1.25
[C.]ModerateSerum Urate7.55 mg/dLStandard Deviation 1.6
Secondary

Serum Urate

From blood sample drawn a month after stopping study drug

Time frame: Safety Visit (SV); 30 +/- 3 days following ESD or Month 24 Visit

ArmMeasureValue (MEAN)Dispersion
[A:]PlaceboSerum Urate4.74 mg/dLStandard Deviation 0.77
[B:]MildSerum Urate4.69 mg/dLStandard Deviation 1.28
[C.]ModerateSerum Urate4.38 mg/dLStandard Deviation 0.78
Secondary

Serum Urate

From blood sample drawn prior to enrollment

Time frame: 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.

ArmMeasureGroupValue (MEAN)Dispersion
[A:]PlaceboSerum UrateScreening Visit 14.63 mg/dLStandard Deviation 0.62
[A:]PlaceboSerum UrateScreening Visit 24.78 mg/dLStandard Deviation 0.6
[B:]MildSerum UrateScreening Visit 14.28 mg/dLStandard Deviation 0.86
[B:]MildSerum UrateScreening Visit 24.4 mg/dLStandard Deviation 0.88
[C.]ModerateSerum UrateScreening Visit 14.39 mg/dLStandard Deviation 0.78
[C.]ModerateSerum UrateScreening Visit 24.48 mg/dLStandard Deviation 0.75
Secondary

Serum Urate

From blood sample drawn prior to enrollment

Time frame: Baseline Visit

ArmMeasureValue (MEAN)Dispersion
[A:]PlaceboSerum Urate4.54 mg/dLStandard Deviation 0.69
[B:]MildSerum Urate4.32 mg/dLStandard Deviation 1.2
[C.]ModerateSerum Urate4.62 mg/dLStandard Deviation 0.86
Secondary

Serum Urate

From blood sample drawn after taking study drug that day

Time frame: Visit 01 (Week 2; 14 +/- 3 days after Baseline Visit)

ArmMeasureValue (MEAN)Dispersion
[A:]PlaceboSerum Urate4.8 mg/dLStandard Deviation 0.65
[B:]MildSerum Urate6.44 mg/dLStandard Deviation 1.29
[C.]ModerateSerum Urate6.93 mg/dLStandard Deviation 1.42
Secondary

Serum Urate

From blood sample drawn after taking study drug that day

Time frame: Visit 02 (Week 4; 28 +/- 3 days after Baseline Visit)

ArmMeasureValue (MEAN)Dispersion
[A:]PlaceboSerum Urate4.73 mg/dLStandard Deviation 0.65
[B:]MildSerum Urate6.58 mg/dLStandard Deviation 0.87
[C.]ModerateSerum Urate7.9 mg/dLStandard Deviation 1.29
Secondary

Serum Urate

From blood sample drawn after taking study drug that day

Time frame: Visit 03 (Week 6; 42 +/- 3 days after Baseline Visit)

ArmMeasureValue (MEAN)Dispersion
[A:]PlaceboSerum Urate4.85 mg/dLStandard Deviation 0.77
[B:]MildSerum Urate6.69 mg/dLStandard Deviation 0.78
[C.]ModerateSerum Urate7.51 mg/dLStandard Deviation 1.24
Secondary

Serum Urate

From blood sample drawn after taking study drug that day

Time frame: Visit 04 (Week 9; 63 +/- 5 days after Baseline Visit)

ArmMeasureValue (MEAN)Dispersion
[A:]PlaceboSerum Urate4.62 mg/dLStandard Deviation 0.58
[B:]MildSerum Urate6.81 mg/dLStandard Deviation 1.22
[C.]ModerateSerum Urate7.62 mg/dLStandard Deviation 1.02
Secondary

Serum Urate

From blood sample drawn after taking study drug that day

Time frame: Visit 06 (Month 6; 180 +/- 7 days after Baseline Visit)

ArmMeasureValue (MEAN)Dispersion
[A:]PlaceboSerum Urate4.85 mg/dLStandard Deviation 1
[B:]MildSerum Urate6.94 mg/dLStandard Deviation 1.6
[C.]ModerateSerum Urate8.27 mg/dLStandard Deviation 0.74
Secondary

Serum Urate

From blood sample drawn before taking study drug that day

Time frame: Visit 05 (Week 12; 84 +/- 7 days after Baseline Visit)

ArmMeasureValue (MEAN)Dispersion
[A:]PlaceboSerum Urate4.74 mg/dLStandard Deviation 0.59
[B:]MildSerum Urate5.85 mg/dLStandard Deviation 1.02
[C.]ModerateSerum Urate6.91 mg/dLStandard Deviation 1.09
Secondary

Serum Urate

From blood sample drawn after taking study drug that day

Time frame: Visit 07 (Month 9; 270 +/- 7 days after Baseline Visit)

ArmMeasureValue (MEAN)Dispersion
[A:]PlaceboSerum Urate4.77 mg/dLStandard Deviation 0.89
[B:]MildSerum Urate6.77 mg/dLStandard Deviation 1.51
[C.]ModerateSerum Urate8.06 mg/dLStandard Deviation 1.2
Secondary

Serum Urate

From blood sample drawn after taking study drug that day

Time frame: Visit 08 (Month 12; 360 +/- 7 days after Baseline Visit)

ArmMeasureValue (MEAN)Dispersion
[A:]PlaceboSerum Urate4.79 mg/dLStandard Deviation 0.89
[B:]MildSerum Urate6.87 mg/dLStandard Deviation 1.05
[C.]ModerateSerum Urate7.41 mg/dLStandard Deviation 0.96
Secondary

Serum Urate

From blood sample drawn after taking study drug that day

Time frame: Visit 09 (Month 15; 450 +/- 7 days after Baseline Visit)

ArmMeasureValue (MEAN)Dispersion
[A:]PlaceboSerum Urate4.62 mg/dLStandard Deviation 0.69
[B:]MildSerum Urate7.26 mg/dLStandard Deviation 0.96
[C.]ModerateSerum Urate7.64 mg/dLStandard Deviation 1.2
Secondary

Serum Urate

From blood sample drawn after taking study drug that day

Time frame: Visit 10 (Month 18; 540 +/- 7 days after Baseline Visit)

ArmMeasureValue (MEAN)Dispersion
[A:]PlaceboSerum Urate4.58 mg/dLStandard Deviation 0.76
[B:]MildSerum Urate7 mg/dLStandard Deviation 0.97
[C.]ModerateSerum Urate7.64 mg/dLStandard Deviation 0.98
Secondary

Serum Urate

From blood sample drawn after taking study drug that day

Time frame: Visit 11 (Month 21; 630 +/- 7 days after Baseline Visit)

ArmMeasureValue (MEAN)Dispersion
[A:]PlaceboSerum Urate4.6 mg/dLStandard Deviation 0.47
[B:]MildSerum Urate7.12 mg/dLStandard Deviation 1.21
[C.]ModerateSerum Urate7.56 mg/dLStandard Deviation 1.08

Source: ClinicalTrials.gov · Data processed: Mar 8, 2026