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Study of Urate Elevation in Parkinson's Disease, Phase 3 (SURE-PD3)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02642393
Recruitment Status : Completed
First Posted : December 30, 2015
Results First Posted : July 28, 2020
Last Update Posted : July 28, 2020
Sponsor:
Collaborators:
The Parkinson Study Group
Michael J. Fox Foundation for Parkinson's Research
University of Rochester
National Institute of Neurological Disorders and Stroke (NINDS)
Information provided by (Responsible Party):
Michael Alan Schwarzschild, Massachusetts General Hospital

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Other
Condition Parkinson's Disease
Interventions Drug: Inosine
Drug: Placebo
Enrollment 298
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Inosine Placebo
Hide Arm/Group Description

Inosine will be dosed by titrating the number of capsules taken daily to achieve an elevation of serum urate to trough levels of 7.1 to 8.0 mg/dL.

Inosine: capsules containing 500 mg of inosine

Placebo will be dosed to match the capsule titrations of the inosine group.

Placebo: capsules containing ~500 mg of lactose and appearing indistinguishable from inosine capsules

Period Title: Overall Study
Started 149 149
Completed 50 [1] 57 [2]
Not Completed 99 92
[1]

Participants who completed the study:

On-drug: 31; In-person off-drug:13; By telephone off-drug: 6

[2]

Participants who completed the study:

On-drug: 40; In-person off-drug: 16; By telephone off-drug: 1

Arm/Group Title Inosine Placebo Total
Hide Arm/Group Description

Inosine will be dosed by titrating the number of capsules taken daily to achieve an elevation of serum urate to trough levels of 7.1 to 8.0 mg/dL.

Inosine: capsules containing 500 mg of inosine

Placebo will be dosed to match the capsule titrations of the inosine group.

Placebo: capsules containing ~500 mg of lactose and appearing indistinguishable from inosine capsules

Total of all reporting groups
Overall Number of Baseline Participants 149 149 298
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 149 participants 149 participants 298 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
76
  51.0%
75
  50.3%
151
  50.7%
>=65 years
73
  49.0%
74
  49.7%
147
  49.3%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 149 participants 149 participants 298 participants
63.0  (9.7) 63.6  (9.4) 63.3  (9.5)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 149 participants 149 participants 298 participants
Female
80
  53.7%
67
  45.0%
147
  49.3%
Male
69
  46.3%
82
  55.0%
151
  50.7%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 149 participants 149 participants 298 participants
Hispanic or Latino
5
   3.4%
4
   2.7%
9
   3.0%
Not Hispanic or Latino
144
  96.6%
145
  97.3%
289
  97.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 149 participants 149 participants 298 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
2
   1.3%
1
   0.7%
3
   1.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
2
   1.3%
0
   0.0%
2
   0.7%
White
143
  96.0%
145
  97.3%
288
  96.6%
More than one race
1
   0.7%
1
   0.7%
2
   0.7%
Unknown or Not Reported
1
   0.7%
2
   1.3%
3
   1.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 149 participants 149 participants 298 participants
Puerto Rico 1 0 1
United States 148 149 297
1.Primary Outcome
Title Rate of Clinical Decline
Hide Description The primary outcome of the trial is rate of change in the Movement Disorders Society Unified PD Rating Scale (MDS-UPDRS) I-III total score over 24 months estimated from a shared-baseline, random-slopes mixed model, censoring follow-up of subjects after initiation of dopaminergic therapy. Parts I-III of the MDS-UPDRS include ratings of non-motor experiences of daily living, motor experiences of daily living, and a motor examination. The MDS-UPDRS is assessed on a 5-point Likert scale ranging from 0 to 4 where higher scores imply worse symptoms. Parts I-III contain 59 total questions (13 in Part I, 13 in Part II, and 33 in Part III). Total scores for Parts I-III are calculated as simple sums of component items with mean imputation by Part if no more than 1, 2, or 7 items are missing for Parts I through III, respectively. Total scores may range from 0 to 236, with 0 meaning no symptoms and 236 meaning worse symptoms.
Time Frame two years
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Inosine Placebo
Hide Arm/Group Description:

Inosine will be dosed by titrating the number of capsules taken daily to achieve an elevation of serum urate to trough levels of 7.1 to 8.0 mg/dL.

Inosine: capsules containing 500 mg of inosine

Placebo will be dosed to match the capsule titrations of the inosine group.

Placebo: capsules containing ~500 mg of lactose and appearing indistinguishable from inosine capsules

Overall Number of Participants Analyzed 149 149
Mean (95% Confidence Interval)
Unit of Measure: score per year
11.116
(9.669 to 12.563)
9.860
(8.410 to 11.310)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Inosine, Placebo
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.183
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Slope
Estimated Value 1.256
Confidence Interval (2-Sided) 95%
-0.594 to 3.106
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.943
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Rate of Developing Adverse Effects
Hide Description Safety also will be evaluated by comparing active vs. placebo treatment with respect to overall adverse event (AE) and serious AE (SAE) rate.
Time Frame two years
Hide Outcome Measure Data
Hide Analysis Population Description
Only 147 of 149 participants in the inosine group were analyzed because 2 participants never initiated study drug.
Arm/Group Title Inosine Placebo
Hide Arm/Group Description:

Inosine will be dosed by titrating the number of capsules taken daily to achieve an elevation of serum urate to trough levels of 7.1 to 8.0 mg/dL.

Inosine: capsules containing 500 mg of inosine

Placebo will be dosed to match the capsule titrations of the inosine group.

Placebo: capsules containing ~500 mg of lactose and appearing indistinguishable from inosine capsules

Overall Number of Participants Analyzed 147 149
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Events per 100 patient-years
354.05
(330.18 to 379.64)
327.73
(305.76 to 351.29)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Inosine, Placebo
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.124
Comments [Not Specified]
Method Poisson Regression
Comments [Not Specified]
Method of Estimation Estimation Parameter Rate Ratio
Estimated Value 1.080
Confidence Interval (2-Sided) 95%
0.979 to 1.192
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Percentage Developing Adverse Effects
Hide Description Safety of oral inosine titrated to elevate trough serum urate to 7.1 - 8.0 mg/dL will be evaluated by comparing active vs. placebo treatment with respect to the percentage of subjects experiencing individual types of AE, as classified by Medical Dictionary for Regulatory Activities (MedDRA) preferred term and system organ class.
Time Frame two years
Hide Outcome Measure Data
Hide Analysis Population Description
Only 147 of 149 participants in the inosine group were analyzed because 2 participants never initiated study drug.
Arm/Group Title Inosine Placebo
Hide Arm/Group Description:

Inosine will be dosed by titrating the number of capsules taken daily to achieve an elevation of serum urate to trough levels of 7.1 to 8.0 mg/dL.

Inosine: capsules containing 500 mg of inosine

Placebo will be dosed to match the capsule titrations of the inosine group.

Placebo: capsules containing ~500 mg of lactose and appearing indistinguishable from inosine capsules

Overall Number of Participants Analyzed 147 149
Measure Type: Count of Participants
Unit of Measure: Participants
129
  87.8%
137
  91.9%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Inosine, Placebo
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.004
Comments [Not Specified]
Method Poisson Regression
Comments [Not Specified]
Method of Estimation Estimation Parameter Rate Ratio
Estimated Value 1.154
Confidence Interval (2-Sided) 95%
1.046 to 1.273
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Percentage of Subjects Tolerant of the Treatment
Hide Description Tolerability of a treatment will be defined as a percentage of all subjects in a treatment group who are tolerant of the treatment at 12 weeks (short-term tolerability) and 24 months (long-term tolerability). A subject who is tolerant of treatment will be defined as one who remains on-study and on the assigned treatment without one or more dose reductions lasting more than 4 weeks cumulative due to AEs. A treatment will be declared tolerable if the percentage who are tolerant is significantly greater than 50% by one-tailed testing at p < 0.05.
Time Frame three months; two years
Hide Outcome Measure Data
Hide Analysis Population Description
Only 147 of 149 participants in the inosine group were analyzed because 2 participants never initiated study drug.
Arm/Group Title Inosine Placebo
Hide Arm/Group Description:

Inosine will be dosed by titrating the number of capsules taken daily to achieve an elevation of serum urate to trough levels of 7.1 to 8.0 mg/dL.

Inosine: capsules containing 500 mg of inosine

Placebo will be dosed to match the capsule titrations of the inosine group.

Placebo: capsules containing ~500 mg of lactose and appearing indistinguishable from inosine capsules

Overall Number of Participants Analyzed 147 149
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of subjects
12 weeks
93.2
(87.7 to 96.3)
98.7
(94.7 to 99.7)
12 months
76.1
(68.3 to 82.2)
91.3
(85.4 to 94.8)
24 months
50.3
(39.2 to 60.5)
70.8
(60.8 to 78.7)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Inosine, Placebo
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.002
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
5.Secondary Outcome
Title Percentage of Participants Developing Disability Warranting Dopaminergic Therapy Over Time
Hide Description The percentage of participants with disability warranting the initiation of dopaminergic therapy in each treatment group at time from baseline visit (in 180 day increments).
Time Frame two years
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Inosine Placebo
Hide Arm/Group Description:

Inosine will be dosed by titrating the number of capsules taken daily to achieve an elevation of serum urate to trough levels of 7.1 to 8.0 mg/dL.

Inosine: capsules containing 500 mg of inosine

Placebo will be dosed to match the capsule titrations of the inosine group.

Placebo: capsules containing ~500 mg of lactose and appearing indistinguishable from inosine capsules

Overall Number of Participants Analyzed 149 149
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
0 Days
0
(0 to 0)
0
(0 to 0)
180 Days
30.81
(23.93 to 39.11)
32.42
(25.53 to 40.61)
360 Days
59.01
(50.99 to 67.21)
56.32
(48.50 to 64.44)
540 Days
72.21
(64.16 to 79.77)
78.55
(71.12 to 85.16)
720 Days
84.57
(75.66 to 91.62)
88.27
(81.29 to 93.54)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Inosine, Placebo
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.497
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
6.Secondary Outcome
Title Clinical Efficacy: Rate of Change in Parkinson's Disease Questionnaire - 39 Item Version (PDQ-39) Scale
Hide Description Rate of change in Parkinson's Disease Questionnaire - 39 item version (PDQ-39) scale points (over the time between baseline visit and final visit on study drug) will be assessed for subjects in each treatment group. The PDQ-39 asks 39 questions organized over eight domains (scales): mobility (10 items), activities of daily living (6 items), emotional well-being (6 items), stigma (4 items), social support (3 items), cognition (4 items), communication (3 items), and bodily discomfort (3 items). Each item has five possible ordinal responses, from never to always, depending on frequency of the symptom over the preceding month. The eight scales' scores are generated by Likert's method of summated ratings and then transformed to a single figure that ranges from 0 to 100. Higher scores are associated with more symptoms.
Time Frame two years
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Inosine Placebo
Hide Arm/Group Description:

Inosine will be dosed by titrating the number of capsules taken daily to achieve an elevation of serum urate to trough levels of 7.1 to 8.0 mg/dL.

Inosine: capsules containing 500 mg of inosine

Placebo will be dosed to match the capsule titrations of the inosine group.

Placebo: capsules containing ~500 mg of lactose and appearing indistinguishable from inosine capsules

Overall Number of Participants Analyzed 149 149
Mean (95% Confidence Interval)
Unit of Measure: score per year
0.686
(0.094 to 1.278)
0.756
(0.197 to 1.314)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Inosine, Placebo
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.856
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Slope
Estimated Value -0.070
Confidence Interval (2-Sided) 95%
-0.825 to 0.685
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.385
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Clinical Efficacy: Rate of Change in Quality of Life in Neurological Disorders (Neuro-QOL)
Hide Description Rate of change in Quality of Life in Neurological Disorders (Neuro-QOL) scale points (over the time between baseline visit and final visit on study drug) will be assessed for subjects in each treatment group. Neuro-QOL is a set of patient-reported outcome (PRO) measures that assess health-related quality of life (HRQoL) of people with neurological disorders. It comprises 17 domains of HRQL covering physical, psychological and social health. Domains tested include anxiety, cognitive function, communication, depression, emotional and behavioral dyscontrol, fatigue, lower extremity function- mobility, positive affect and well- being, stigma, upper extremity function- fine motor and ADL, sleep disturbance, satisfaction with social roles and activities, and ability to participate in social roles and activities. Higher raw scores are associated with more of the concept being measured. All scales range from 8 to 40 except for Positive Affect and Well-Being which ranges from 9 to 45.
Time Frame two years
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Inosine Placebo
Hide Arm/Group Description:

Inosine will be dosed by titrating the number of capsules taken daily to achieve an elevation of serum urate to trough levels of 7.1 to 8.0 mg/dL.

Inosine: capsules containing 500 mg of inosine

Placebo will be dosed to match the capsule titrations of the inosine group.

Placebo: capsules containing ~500 mg of lactose and appearing indistinguishable from inosine capsules

Overall Number of Participants Analyzed 149 149
Mean (95% Confidence Interval)
Unit of Measure: score per year
Anxiety
-0.397
(-0.757 to -0.037)
-0.473
(-0.818 to -0.129)
Cognitive Function
0.014
(-0.300 to 0.328)
-0.282
(-0.579 to 0.016)
Communication
0.055
(-0.106 to 0.215)
-0.201
(-0.353 to -0.049)
Emotional and Behavioral Dyscontrol
-0.229
(-0.505 to 0.047)
-0.324
(-0.589 to -0.058)
Fatigue
-0.049
(-0.482 to 0.383)
-0.040
(-0.455 to 0.375)
Lower Extremity Function
-0.092
(-0.288 to 0.104)
-0.261
(-0.449 to -0.074)
Positive Affect and Well-Being
-0.240
(-0.683 to 0.202)
0.094
(-0.326 to 0.514)
Stigma
-0.060
(-0.266 to 0.147)
0.021
(-0.176 to 0.217)
Upper Extremity Function
-0.026
(-0.243 to 0.191)
-0.238
(-0.446 to -0.030)
Sleep Disturbance
0.091
(-0.208 to 0.391)
0.020
(-0.266 to 0.305)
Satisfaction with Social Roles and Activities
-0.387
(-0.824 to 0.049)
-0.381
(-0.796 to 0.033)
Participation in Social Roles and Activities
-0.382
(-0.883 to 0.118)
-0.130
(-0.611 to 0.352)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Inosine, Placebo
Comments Anxiety
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.736
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Slope
Estimated Value 0.076
Confidence Interval (2-Sided) 95%
-0.368 to 0.521
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.226
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Inosine, Placebo
Comments Cognitive Function
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.167
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Slope
Estimated Value 0.295
Confidence Interval (2-Sided) 95%
-0.124 to 0.714
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.213
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Inosine, Placebo
Comments Communication
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.022
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Slope
Estimated Value 0.256
Confidence Interval (2-Sided) 95%
0.038 to 0.474
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.111
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Inosine, Placebo
Comments Emotional and Behavioral Dyscontrol
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.584
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Slope
Estimated Value 0.095
Confidence Interval (2-Sided) 95%
-0.245 to 0.435
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.173
Estimation Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Inosine, Placebo
Comments Fatigue
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.973
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Slope
Estimated Value -0.010
Confidence Interval (2-Sided) 95%
-0.560 to 0.541
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.280
Estimation Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Inosine, Placebo
Comments Lower Extremity Function
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.214
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Slope
Estimated Value 0.169
Confidence Interval (2-Sided) 95%
-0.098 to 0.437
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.136
Estimation Comments [Not Specified]
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Inosine, Placebo
Comments Positive Affect and Well-Being
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.271
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Slope
Estimated Value -0.334
Confidence Interval (2-Sided) 95%
-0.931 to 0.262
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.304
Estimation Comments [Not Specified]
Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Inosine, Placebo
Comments Stigma
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.566
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Slope
Estimated Value -0.080
Confidence Interval (2-Sided) 95%
-0.355 to 0.194
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.140
Estimation Comments [Not Specified]
Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Inosine, Placebo
Comments Upper Extremity Function
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.130
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Slope
Estimated Value 0.212
Confidence Interval (2-Sided) 95%
-0.063 to 0.487
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.140
Estimation Comments [Not Specified]
Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Inosine, Placebo
Comments Sleep Disturbance
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.723
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Slope
Estimated Value 0.072
Confidence Interval (2-Sided) 95%
-0.325 to 0.468
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.202
Estimation Comments [Not Specified]
Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Inosine, Placebo
Comments Satisfaction with Social Roles and Activities
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.984
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Slope
Estimated Value -0.006
Confidence Interval (2-Sided) 95%
-0.592 to 0.579
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.298
Estimation Comments [Not Specified]
Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Inosine, Placebo
Comments Participation in Social Roles and Activities
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.426
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Slope
Estimated Value -0.253
Confidence Interval (2-Sided) 95%
-0.877 to 0.371
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.317
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Clinical Efficacy: Rate of Change in Quality of Life in Neurological Disorders (Neuro-QOL) Depression Module
Hide Description Rate of change in Quality of Life in Neurological Disorders (Neuro-QOL) depression module scale points (over the time between baseline visit and final visit on study drug) will be assessed for subjects in each treatment group. Neuro-QOL is a set of patient-reported outcome (PRO) measures that assess health-related quality of life (HRQoL) of people with neurological disorders. Higher raw scores are associated with more of the concept being measured. The depression module score ranges from 8 to 40.
Time Frame two years
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Inosine Placebo
Hide Arm/Group Description:

Inosine will be dosed by titrating the number of capsules taken daily to achieve an elevation of serum urate to trough levels of 7.1 to 8.0 mg/dL.

Inosine: capsules containing 500 mg of inosine

Placebo will be dosed to match the capsule titrations of the inosine group.

Placebo: capsules containing ~500 mg of lactose and appearing indistinguishable from inosine capsules

Overall Number of Participants Analyzed 149 149
Mean (95% Confidence Interval)
Unit of Measure: score per year
-0.023
(-0.234 to 0.188)
0.083
(-0.114 to 0.280)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Inosine, Placebo
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.454
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Slope
Estimated Value -0.106
Confidence Interval (2-Sided) 95%
-0.382 to 0.171
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.141
Estimation Comments [Not Specified]
9.Secondary Outcome
Title Clinical Efficacy: Rate of Change in Schwab and England Scale
Hide Description Rate of change in percentage points on the Schwab and England scale for functional disability (over the time between baseline visit and final visit on study drug) will be assessed for subjects in each treatment group. The Schwab and England scale is a Site Investigator and subject assessment of the subject's level of independence. The subject will be scored on a percentage scale reflective of his/her ability to perform acts of daily living. Printed scores with associated descriptors range from 0% to 100% in increments of 5%, with higher percentages associated with more independence. A score of 0% implies "vegetative functions such as swallowing, bladder and bowel functions are not functioning; bedridden". A score of 100% implies "subject has full ability and is completely independent; essentially normal".
Time Frame two years
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Inosine Placebo
Hide Arm/Group Description:

Inosine will be dosed by titrating the number of capsules taken daily to achieve an elevation of serum urate to trough levels of 7.1 to 8.0 mg/dL.

Inosine: capsules containing 500 mg of inosine

Placebo will be dosed to match the capsule titrations of the inosine group.

Placebo: capsules containing ~500 mg of lactose and appearing indistinguishable from inosine capsules

Overall Number of Participants Analyzed 149 149
Mean (95% Confidence Interval)
Unit of Measure: score per year
-0.833
(-1.536 to -0.131)
-0.880
(-1.555 to -0.206)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Inosine, Placebo
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.910
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Slope
Estimated Value 0.047
Confidence Interval (2-Sided) 95%
-0.764 to 0.858
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.413
Estimation Comments [Not Specified]
10.Secondary Outcome
Title Clinical Efficacy: Rate of Change in Montreal Cognitive Assessment (MoCA)
Hide Description Rate of change in points on the Montreal Cognitive Assessment (MoCA) scale (for cognition; over the time between baseline visit and final visit on study drug) will be assessed for subjects in each treatment group. The MoCA assesses attention and concentration, executive functions, memory, language, visuoconstructional skills, conceptual thinking, calculations, and orientation. Points are awarded for the correct completion of MoCA tasks. Scores for each task are summed for a total score (range 0-30). Higher scores indicate greater cognitive capacity.
Time Frame two years
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Inosine Placebo
Hide Arm/Group Description:

Inosine will be dosed by titrating the number of capsules taken daily to achieve an elevation of serum urate to trough levels of 7.1 to 8.0 mg/dL.

Inosine: capsules containing 500 mg of inosine

Placebo will be dosed to match the capsule titrations of the inosine group.

Placebo: capsules containing ~500 mg of lactose and appearing indistinguishable from inosine capsules

Overall Number of Participants Analyzed 149 149
Mean (95% Confidence Interval)
Unit of Measure: score per year
0.186
(-0.012 to 0.384)
0.226
(0.040 to 0.412)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Inosine, Placebo
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.758
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Slope
Estimated Value -0.040
Confidence Interval (2-Sided) 95%
-0.295 to 0.215
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.130
Estimation Comments [Not Specified]
11.Secondary Outcome
Title Symptomatic Effects
Hide Description Symptomatic effects will be estimated by changes in motor and other features (e.g., as assessed by short-term change in Movement Disorders Society Unified PD Rating Scale [MDS-UPDRS] I-III total score) during the first 3 months of wash-in at the start of period 1 and during the 3-month wash-out of period 2. The MDS-UPDRS includes ratings of non-motor experiences of daily living, motor experiences of daily living, and a motor examination. The MDS-UPDRS is assessed on a 5-point Likert scale ranging from 0 to 4 where higher scores imply worse features. Parts I-III contain 59 total questions (13 in Part I, 13 in Part II, and 33 in Part III). Total scores are calculated as simple sums of component items with mean imputation by Part if no more than 1, 2, or 7 items are missing for Parts I through III, respectively. Total scores may range from 0 to 236, with 0 meaning no symptoms and 236 meaning worse symptoms.
Time Frame three months (after both initiation and discontinuation of study drug)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Inosine Placebo
Hide Arm/Group Description:

Inosine will be dosed by titrating the number of capsules taken daily to achieve an elevation of serum urate to trough levels of 7.1 to 8.0 mg/dL.

Inosine: capsules containing 500 mg of inosine

Placebo will be dosed to match the capsule titrations of the inosine group.

Placebo: capsules containing ~500 mg of lactose and appearing indistinguishable from inosine capsules

Overall Number of Participants Analyzed 149 149
Mean (95% Confidence Interval)
Unit of Measure: score per period
Period 1: BL to V03
-1.509
(-2.656 to -0.362)
-1.301
(-2.433 to -0.169)
Period 2: V10 to SV
-2.729
(-7.746 to 2.289)
-0.328
(-4.762 to 4.105)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Inosine, Placebo
Comments BL to V01
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.796
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Slope
Estimated Value -0.208
Confidence Interval (2-Sided) 95%
-1.783 to 1.367
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.803
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Inosine, Placebo
Comments V10 to SV
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.486
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Slope
Estimated Value -2.400
Confidence Interval (2-Sided) 95%
-9.156 to 4.355
Parameter Dispersion
Type: Standard Error of the Mean
Value: 3.443
Estimation Comments [Not Specified]
Time Frame 27 months
Adverse Event Reporting Description Only 147 of 149 participants in the inosine group were analyzed because 2 participants never initiated study drug.
 
Arm/Group Title Inosine Placebo
Hide Arm/Group Description

Inosine will be dosed by titrating the number of capsules taken daily to achieve an elevation of serum urate to trough levels of 7.1 to 8.0 mg/dL.

Inosine: capsules containing 500 mg of inosine

Placebo will be dosed to match the capsule titrations of the inosine group.

Placebo: capsules containing ~500 mg of lactose and appearing indistinguishable from inosine capsules

All-Cause Mortality
Inosine Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   1/147 (0.68%)      0/149 (0.00%)    
Hide Serious Adverse Events
Inosine Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   16/147 (10.88%)      21/149 (14.09%)    
Cardiac disorders     
Atrial fibrillation  1  0/147 (0.00%)  0 2/149 (1.34%)  2
Cardiomyopathy  1  0/147 (0.00%)  0 1/149 (0.67%)  1
Gastrointestinal disorders     
Abdominal pain  1  0/147 (0.00%)  0 1/149 (0.67%)  1
Abdominal pain upper  1  1/147 (0.68%)  1 0/149 (0.00%)  0
Constipation  1  0/147 (0.00%)  0 1/149 (0.67%)  1
Gastric ulcer  1  0/147 (0.00%)  0 1/149 (0.67%)  1
Hiatus hernia  1  0/147 (0.00%)  0 1/149 (0.67%)  1
Intestinal obstruction  1  0/147 (0.00%)  0 1/149 (0.67%)  1
Small intestinal obstruction  1  0/147 (0.00%)  0 1/149 (0.67%)  1
General disorders     
Chest pain  1  0/147 (0.00%)  0 2/149 (1.34%)  2
Death  1  1/147 (0.68%)  1 0/149 (0.00%)  0
Hepatobiliary disorders     
Cholecystitis acute  1  0/147 (0.00%)  0 1/149 (0.67%)  1
Infections and infestations     
Cellulitis  1  0/147 (0.00%)  0 1/149 (0.67%)  1
Corona virus infection  1  0/147 (0.00%)  0 1/149 (0.67%)  1
Diverticulitis  1  1/147 (0.68%)  1 0/149 (0.00%)  0
Extradural abscess  1  0/147 (0.00%)  0 1/149 (0.67%)  1
Gastroenteritis  1  0/147 (0.00%)  0 1/149 (0.67%)  1
Pneumonia  1  0/147 (0.00%)  0 1/149 (0.67%)  1
Urinary tract infection  1  1/147 (0.68%)  1 0/149 (0.00%)  0
Injury, poisoning and procedural complications     
Concussion  1  0/147 (0.00%)  0 1/149 (0.67%)  1
Hip fracture  1  1/147 (0.68%)  1 0/149 (0.00%)  0
Procedural pain  1  0/147 (0.00%)  0 1/149 (0.67%)  1
Spinal compression fracture  1  0/147 (0.00%)  0 1/149 (0.67%)  1
Investigations     
Blood sodium decreased  1  1/147 (0.68%)  1 0/149 (0.00%)  0
Musculoskeletal and connective tissue disorders     
Back pain  1  0/147 (0.00%)  0 1/149 (0.67%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Bile duct cancer  1  0/147 (0.00%)  0 1/149 (0.67%)  1
Prostate cancer  1  1/147 (0.68%)  1 0/149 (0.00%)  0
Transitional cell carcinoma  1  1/147 (0.68%)  1 0/149 (0.00%)  0
Nervous system disorders     
Encephalopathy  1  1/147 (0.68%)  1 0/149 (0.00%)  0
Syncope  1  1/147 (0.68%)  1 2/149 (1.34%)  3
Transient ischaemic attack  1  0/147 (0.00%)  0 1/149 (0.67%)  1
Renal and urinary disorders     
Nephrolithiasis  1  6/147 (4.08%)  6 0/149 (0.00%)  0
Urinary retention  1  0/147 (0.00%)  0 1/149 (0.67%)  1
Reproductive system and breast disorders     
Testicular mass  1  1/147 (0.68%)  1 0/149 (0.00%)  0
Surgical and medical procedures     
Hip arthroplasty  1  0/147 (0.00%)  0 2/149 (1.34%)  2
Knee arthroplasty  1  1/147 (0.68%)  1 0/149 (0.00%)  0
Vascular disorders     
Hypotension  1  0/147 (0.00%)  0 1/149 (0.67%)  1
1
Term from vocabulary, MedDRA 19.0
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Inosine Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   125/147 (85.03%)      135/149 (90.60%)    
Gastrointestinal disorders     
Constipation  1  7/147 (4.76%)  7 16/149 (10.74%)  16
Diarrhoea  1  9/147 (6.12%)  11 9/149 (6.04%)  12
Nausea  1  22/147 (14.97%)  25 20/149 (13.42%)  31
General disorders     
Fatigue  1  8/147 (5.44%)  9 11/149 (7.38%)  11
Infections and infestations     
Nasopharyngitis  1  12/147 (8.16%)  14 10/149 (6.71%)  13
Sinusitis  1  10/147 (6.80%)  11 7/149 (4.70%)  9
Upper respiratory tract infection  1  7/147 (4.76%)  8 13/149 (8.72%)  16
Urinary tract infection  1  17/147 (11.56%)  24 10/149 (6.71%)  16
Investigations     
Blood creatinine increased  1  13/147 (8.84%)  13 3/149 (2.01%)  3
Crystal urine present  1  8/147 (5.44%)  9 7/149 (4.70%)  9
Mean cell volume increased  1  12/147 (8.16%)  13 7/149 (4.70%)  7
Musculoskeletal and connective tissue disorders     
Arthralgia  1  9/147 (6.12%)  9 13/149 (8.72%)  13
Back pain  1  18/147 (12.24%)  19 10/149 (6.71%)  12
Muscle spasms  1  9/147 (6.12%)  10 7/149 (4.70%)  7
Pain in extremity  1  9/147 (6.12%)  9 21/149 (14.09%)  25
Nervous system disorders     
Dizziness  1  14/147 (9.52%)  16 16/149 (10.74%)  22
Headache  1  8/147 (5.44%)  9 14/149 (9.40%)  16
Somnolence  1  4/147 (2.72%)  4 8/149 (5.37%)  9
Psychiatric disorders     
Insomnia  1  9/147 (6.12%)  9 6/149 (4.03%)  6
Renal and urinary disorders     
Haematuria  1  13/147 (8.84%)  13 12/149 (8.05%)  12
Nephrolithiasis  1  12/147 (8.16%)  12 4/149 (2.68%)  4
Proteinuria  1  9/147 (6.12%)  9 12/149 (8.05%)  14
1
Term from vocabulary, MedDRA 19.0
Indicates events were collected by systematic assessment
A prespecified interim analysis determined futility for demonstrating the hypothesized inosine effect of a slower rate of change in the primary outcome and prompted early completion of the trial after an average study drug exposure of 17 months.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Dr. Michael Schwarzschild
Organization: Massachusetts General Hospital
Phone: 617-724-9611
EMail: michaels@helix.mgh.harvard.edu
Layout table for additonal information
Responsible Party: Michael Alan Schwarzschild, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT02642393    
Other Study ID Numbers: INO-PD-P3-2014
1U01NS090259-01A1 ( U.S. NIH Grant/Contract )
First Submitted: December 19, 2015
First Posted: December 30, 2015
Results First Submitted: May 26, 2020
Results First Posted: July 28, 2020
Last Update Posted: July 28, 2020