Trial Outcomes & Findings for Study of Urate Elevation in Parkinson's Disease, Phase 3 (NCT NCT02642393)
NCT ID: NCT02642393
Last Updated: 2020-07-28
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
298 participants
Primary outcome timeframe
two years
Results posted on
2020-07-28
Participant Flow
Participant milestones
| Measure |
Inosine
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
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 Study
STARTED
|
149
|
149
|
|
Overall Study
COMPLETED
|
50
|
57
|
|
Overall Study
NOT COMPLETED
|
99
|
92
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Study of Urate Elevation in Parkinson's Disease, Phase 3
Baseline characteristics by cohort
| Measure |
Inosine
n=149 Participants
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
n=149 Participants
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
n=298 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
76 Participants
n=5 Participants
|
75 Participants
n=7 Participants
|
151 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
73 Participants
n=5 Participants
|
74 Participants
n=7 Participants
|
147 Participants
n=5 Participants
|
|
Age, Continuous
|
63.0 years
STANDARD_DEVIATION 9.7 • n=5 Participants
|
63.6 years
STANDARD_DEVIATION 9.4 • n=7 Participants
|
63.3 years
STANDARD_DEVIATION 9.5 • n=5 Participants
|
|
Sex: Female, Male
Female
|
80 Participants
n=5 Participants
|
67 Participants
n=7 Participants
|
147 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
69 Participants
n=5 Participants
|
82 Participants
n=7 Participants
|
151 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
5 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
9 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
144 Participants
n=5 Participants
|
145 Participants
n=7 Participants
|
289 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
2 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
2 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
143 Participants
n=5 Participants
|
145 Participants
n=7 Participants
|
288 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Region of Enrollment
Puerto Rico
|
1 participants
n=5 Participants
|
0 participants
n=7 Participants
|
1 participants
n=5 Participants
|
|
Region of Enrollment
United States
|
148 participants
n=5 Participants
|
149 participants
n=7 Participants
|
297 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: two yearsThe 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.
Outcome measures
| Measure |
Inosine
n=149 Participants
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
n=149 Participants
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
|
|---|---|---|
|
Rate of Clinical Decline
|
11.116 score per year
Interval 9.669 to 12.563
|
9.860 score per year
Interval 8.41 to 11.31
|
SECONDARY outcome
Timeframe: two yearsPopulation: Only 147 of 149 participants in the inosine group were analyzed because 2 participants never initiated study drug.
Safety also will be evaluated by comparing active vs. placebo treatment with respect to overall adverse event (AE) and serious AE (SAE) rate.
Outcome measures
| Measure |
Inosine
n=147 Participants
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
n=149 Participants
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
|
|---|---|---|
|
Rate of Developing Adverse Effects
|
354.05 Events per 100 patient-years
Interval 330.18 to 379.64
|
327.73 Events per 100 patient-years
Interval 305.76 to 351.29
|
SECONDARY outcome
Timeframe: two yearsPopulation: Only 147 of 149 participants in the inosine group were analyzed because 2 participants never initiated study drug.
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.
Outcome measures
| Measure |
Inosine
n=147 Participants
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
n=149 Participants
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
|
|---|---|---|
|
Percentage Developing Adverse Effects
|
129 Participants
|
137 Participants
|
SECONDARY outcome
Timeframe: three months; two yearsPopulation: Only 147 of 149 participants in the inosine group were analyzed because 2 participants never initiated study drug.
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.
Outcome measures
| Measure |
Inosine
n=147 Participants
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
n=149 Participants
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
|
|---|---|---|
|
Percentage of Subjects Tolerant of the Treatment
12 weeks
|
93.2 percentage of subjects
Interval 87.7 to 96.3
|
98.7 percentage of subjects
Interval 94.7 to 99.7
|
|
Percentage of Subjects Tolerant of the Treatment
12 months
|
76.1 percentage of subjects
Interval 68.3 to 82.2
|
91.3 percentage of subjects
Interval 85.4 to 94.8
|
|
Percentage of Subjects Tolerant of the Treatment
24 months
|
50.3 percentage of subjects
Interval 39.2 to 60.5
|
70.8 percentage of subjects
Interval 60.8 to 78.7
|
SECONDARY outcome
Timeframe: two yearsThe percentage of participants with disability warranting the initiation of dopaminergic therapy in each treatment group at time from baseline visit (in 180 day increments).
Outcome measures
| Measure |
Inosine
n=149 Participants
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
n=149 Participants
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
|
|---|---|---|
|
Percentage of Participants Developing Disability Warranting Dopaminergic Therapy Over Time
0 Days
|
0 percentage of participants
Interval 0.0 to 0.0
|
0 percentage of participants
Interval 0.0 to 0.0
|
|
Percentage of Participants Developing Disability Warranting Dopaminergic Therapy Over Time
180 Days
|
30.81 percentage of participants
Interval 23.93 to 39.11
|
32.42 percentage of participants
Interval 25.53 to 40.61
|
|
Percentage of Participants Developing Disability Warranting Dopaminergic Therapy Over Time
360 Days
|
59.01 percentage of participants
Interval 50.99 to 67.21
|
56.32 percentage of participants
Interval 48.5 to 64.44
|
|
Percentage of Participants Developing Disability Warranting Dopaminergic Therapy Over Time
540 Days
|
72.21 percentage of participants
Interval 64.16 to 79.77
|
78.55 percentage of participants
Interval 71.12 to 85.16
|
|
Percentage of Participants Developing Disability Warranting Dopaminergic Therapy Over Time
720 Days
|
84.57 percentage of participants
Interval 75.66 to 91.62
|
88.27 percentage of participants
Interval 81.29 to 93.54
|
SECONDARY outcome
Timeframe: two yearsRate 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.
Outcome measures
| Measure |
Inosine
n=149 Participants
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
n=149 Participants
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
|
|---|---|---|
|
Clinical Efficacy: Rate of Change in Parkinson's Disease Questionnaire - 39 Item Version (PDQ-39) Scale
|
0.686 score per year
Interval 0.094 to 1.278
|
0.756 score per year
Interval 0.197 to 1.314
|
SECONDARY outcome
Timeframe: two yearsRate 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.
Outcome measures
| Measure |
Inosine
n=149 Participants
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
n=149 Participants
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
|
|---|---|---|
|
Clinical Efficacy: Rate of Change in Quality of Life in Neurological Disorders (Neuro-QOL)
Anxiety
|
-0.397 score per year
Interval -0.757 to -0.037
|
-0.473 score per year
Interval -0.818 to -0.129
|
|
Clinical Efficacy: Rate of Change in Quality of Life in Neurological Disorders (Neuro-QOL)
Cognitive Function
|
0.014 score per year
Interval -0.3 to 0.328
|
-0.282 score per year
Interval -0.579 to 0.016
|
|
Clinical Efficacy: Rate of Change in Quality of Life in Neurological Disorders (Neuro-QOL)
Communication
|
0.055 score per year
Interval -0.106 to 0.215
|
-0.201 score per year
Interval -0.353 to -0.049
|
|
Clinical Efficacy: Rate of Change in Quality of Life in Neurological Disorders (Neuro-QOL)
Emotional and Behavioral Dyscontrol
|
-0.229 score per year
Interval -0.505 to 0.047
|
-0.324 score per year
Interval -0.589 to -0.058
|
|
Clinical Efficacy: Rate of Change in Quality of Life in Neurological Disorders (Neuro-QOL)
Fatigue
|
-0.049 score per year
Interval -0.482 to 0.383
|
-0.040 score per year
Interval -0.455 to 0.375
|
|
Clinical Efficacy: Rate of Change in Quality of Life in Neurological Disorders (Neuro-QOL)
Lower Extremity Function
|
-0.092 score per year
Interval -0.288 to 0.104
|
-0.261 score per year
Interval -0.449 to -0.074
|
|
Clinical Efficacy: Rate of Change in Quality of Life in Neurological Disorders (Neuro-QOL)
Positive Affect and Well-Being
|
-0.240 score per year
Interval -0.683 to 0.202
|
0.094 score per year
Interval -0.326 to 0.514
|
|
Clinical Efficacy: Rate of Change in Quality of Life in Neurological Disorders (Neuro-QOL)
Stigma
|
-0.060 score per year
Interval -0.266 to 0.147
|
0.021 score per year
Interval -0.176 to 0.217
|
|
Clinical Efficacy: Rate of Change in Quality of Life in Neurological Disorders (Neuro-QOL)
Upper Extremity Function
|
-0.026 score per year
Interval -0.243 to 0.191
|
-0.238 score per year
Interval -0.446 to -0.03
|
|
Clinical Efficacy: Rate of Change in Quality of Life in Neurological Disorders (Neuro-QOL)
Sleep Disturbance
|
0.091 score per year
Interval -0.208 to 0.391
|
0.020 score per year
Interval -0.266 to 0.305
|
|
Clinical Efficacy: Rate of Change in Quality of Life in Neurological Disorders (Neuro-QOL)
Satisfaction with Social Roles and Activities
|
-0.387 score per year
Interval -0.824 to 0.049
|
-0.381 score per year
Interval -0.796 to 0.033
|
|
Clinical Efficacy: Rate of Change in Quality of Life in Neurological Disorders (Neuro-QOL)
Participation in Social Roles and Activities
|
-0.382 score per year
Interval -0.883 to 0.118
|
-0.130 score per year
Interval -0.611 to 0.352
|
SECONDARY outcome
Timeframe: two yearsRate 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.
Outcome measures
| Measure |
Inosine
n=149 Participants
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
n=149 Participants
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
|
|---|---|---|
|
Clinical Efficacy: Rate of Change in Quality of Life in Neurological Disorders (Neuro-QOL) Depression Module
|
-0.023 score per year
Interval -0.234 to 0.188
|
0.083 score per year
Interval -0.114 to 0.28
|
SECONDARY outcome
Timeframe: two yearsRate 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".
Outcome measures
| Measure |
Inosine
n=149 Participants
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
n=149 Participants
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
|
|---|---|---|
|
Clinical Efficacy: Rate of Change in Schwab and England Scale
|
-0.833 score per year
Interval -1.536 to -0.131
|
-0.880 score per year
Interval -1.555 to -0.206
|
SECONDARY outcome
Timeframe: two yearsRate 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.
Outcome measures
| Measure |
Inosine
n=149 Participants
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
n=149 Participants
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
|
|---|---|---|
|
Clinical Efficacy: Rate of Change in Montreal Cognitive Assessment (MoCA)
|
0.186 score per year
Interval -0.012 to 0.384
|
0.226 score per year
Interval 0.04 to 0.412
|
SECONDARY outcome
Timeframe: three months (after both initiation and discontinuation of study drug)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.
Outcome measures
| Measure |
Inosine
n=149 Participants
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
n=149 Participants
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
|
|---|---|---|
|
Symptomatic Effects
Period 1: BL to V03
|
-1.509 score per period
Interval -2.656 to -0.362
|
-1.301 score per period
Interval -2.433 to -0.169
|
|
Symptomatic Effects
Period 2: V10 to SV
|
-2.729 score per period
Interval -7.746 to 2.289
|
-0.328 score per period
Interval -4.762 to 4.105
|
Adverse Events
Inosine
Serious events: 16 serious events
Other events: 125 other events
Deaths: 1 deaths
Placebo
Serious events: 21 serious events
Other events: 135 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Inosine
n=147 participants at risk
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
n=149 participants at risk
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
|
|---|---|---|
|
Cardiac disorders
Atrial fibrillation
|
0.00%
0/147 • 27 months
Only 147 of 149 participants in the inosine group were analyzed because 2 participants never initiated study drug.
|
1.3%
2/149 • Number of events 2 • 27 months
Only 147 of 149 participants in the inosine group were analyzed because 2 participants never initiated study drug.
|
|
Cardiac disorders
Cardiomyopathy
|
0.00%
0/147 • 27 months
Only 147 of 149 participants in the inosine group were analyzed because 2 participants never initiated study drug.
|
0.67%
1/149 • Number of events 1 • 27 months
Only 147 of 149 participants in the inosine group were analyzed because 2 participants never initiated study drug.
|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/147 • 27 months
Only 147 of 149 participants in the inosine group were analyzed because 2 participants never initiated study drug.
|
0.67%
1/149 • Number of events 1 • 27 months
Only 147 of 149 participants in the inosine group were analyzed because 2 participants never initiated study drug.
|
|
Gastrointestinal disorders
Abdominal pain upper
|
0.68%
1/147 • Number of events 1 • 27 months
Only 147 of 149 participants in the inosine group were analyzed because 2 participants never initiated study drug.
|
0.00%
0/149 • 27 months
Only 147 of 149 participants in the inosine group were analyzed because 2 participants never initiated study drug.
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/147 • 27 months
Only 147 of 149 participants in the inosine group were analyzed because 2 participants never initiated study drug.
|
0.67%
1/149 • Number of events 1 • 27 months
Only 147 of 149 participants in the inosine group were analyzed because 2 participants never initiated study drug.
|
|
Gastrointestinal disorders
Gastric ulcer
|
0.00%
0/147 • 27 months
Only 147 of 149 participants in the inosine group were analyzed because 2 participants never initiated study drug.
|
0.67%
1/149 • Number of events 1 • 27 months
Only 147 of 149 participants in the inosine group were analyzed because 2 participants never initiated study drug.
|
|
Gastrointestinal disorders
Hiatus hernia
|
0.00%
0/147 • 27 months
Only 147 of 149 participants in the inosine group were analyzed because 2 participants never initiated study drug.
|
0.67%
1/149 • Number of events 1 • 27 months
Only 147 of 149 participants in the inosine group were analyzed because 2 participants never initiated study drug.
|
|
Gastrointestinal disorders
Intestinal obstruction
|
0.00%
0/147 • 27 months
Only 147 of 149 participants in the inosine group were analyzed because 2 participants never initiated study drug.
|
0.67%
1/149 • Number of events 1 • 27 months
Only 147 of 149 participants in the inosine group were analyzed because 2 participants never initiated study drug.
|
|
Gastrointestinal disorders
Small intestinal obstruction
|
0.00%
0/147 • 27 months
Only 147 of 149 participants in the inosine group were analyzed because 2 participants never initiated study drug.
|
0.67%
1/149 • Number of events 1 • 27 months
Only 147 of 149 participants in the inosine group were analyzed because 2 participants never initiated study drug.
|
|
General disorders
Chest pain
|
0.00%
0/147 • 27 months
Only 147 of 149 participants in the inosine group were analyzed because 2 participants never initiated study drug.
|
1.3%
2/149 • Number of events 2 • 27 months
Only 147 of 149 participants in the inosine group were analyzed because 2 participants never initiated study drug.
|
|
General disorders
Death
|
0.68%
1/147 • Number of events 1 • 27 months
Only 147 of 149 participants in the inosine group were analyzed because 2 participants never initiated study drug.
|
0.00%
0/149 • 27 months
Only 147 of 149 participants in the inosine group were analyzed because 2 participants never initiated study drug.
|
|
Hepatobiliary disorders
Cholecystitis acute
|
0.00%
0/147 • 27 months
Only 147 of 149 participants in the inosine group were analyzed because 2 participants never initiated study drug.
|
0.67%
1/149 • Number of events 1 • 27 months
Only 147 of 149 participants in the inosine group were analyzed because 2 participants never initiated study drug.
|
|
Infections and infestations
Cellulitis
|
0.00%
0/147 • 27 months
Only 147 of 149 participants in the inosine group were analyzed because 2 participants never initiated study drug.
|
0.67%
1/149 • Number of events 1 • 27 months
Only 147 of 149 participants in the inosine group were analyzed because 2 participants never initiated study drug.
|
|
Infections and infestations
Corona virus infection
|
0.00%
0/147 • 27 months
Only 147 of 149 participants in the inosine group were analyzed because 2 participants never initiated study drug.
|
0.67%
1/149 • Number of events 1 • 27 months
Only 147 of 149 participants in the inosine group were analyzed because 2 participants never initiated study drug.
|
|
Infections and infestations
Diverticulitis
|
0.68%
1/147 • Number of events 1 • 27 months
Only 147 of 149 participants in the inosine group were analyzed because 2 participants never initiated study drug.
|
0.00%
0/149 • 27 months
Only 147 of 149 participants in the inosine group were analyzed because 2 participants never initiated study drug.
|
|
Infections and infestations
Extradural abscess
|
0.00%
0/147 • 27 months
Only 147 of 149 participants in the inosine group were analyzed because 2 participants never initiated study drug.
|
0.67%
1/149 • Number of events 1 • 27 months
Only 147 of 149 participants in the inosine group were analyzed because 2 participants never initiated study drug.
|
|
Infections and infestations
Gastroenteritis
|
0.00%
0/147 • 27 months
Only 147 of 149 participants in the inosine group were analyzed because 2 participants never initiated study drug.
|
0.67%
1/149 • Number of events 1 • 27 months
Only 147 of 149 participants in the inosine group were analyzed because 2 participants never initiated study drug.
|
|
Infections and infestations
Pneumonia
|
0.00%
0/147 • 27 months
Only 147 of 149 participants in the inosine group were analyzed because 2 participants never initiated study drug.
|
0.67%
1/149 • Number of events 1 • 27 months
Only 147 of 149 participants in the inosine group were analyzed because 2 participants never initiated study drug.
|
|
Infections and infestations
Urinary tract infection
|
0.68%
1/147 • Number of events 1 • 27 months
Only 147 of 149 participants in the inosine group were analyzed because 2 participants never initiated study drug.
|
0.00%
0/149 • 27 months
Only 147 of 149 participants in the inosine group were analyzed because 2 participants never initiated study drug.
|
|
Injury, poisoning and procedural complications
Concussion
|
0.00%
0/147 • 27 months
Only 147 of 149 participants in the inosine group were analyzed because 2 participants never initiated study drug.
|
0.67%
1/149 • Number of events 1 • 27 months
Only 147 of 149 participants in the inosine group were analyzed because 2 participants never initiated study drug.
|
|
Injury, poisoning and procedural complications
Hip fracture
|
0.68%
1/147 • Number of events 1 • 27 months
Only 147 of 149 participants in the inosine group were analyzed because 2 participants never initiated study drug.
|
0.00%
0/149 • 27 months
Only 147 of 149 participants in the inosine group were analyzed because 2 participants never initiated study drug.
|
|
Injury, poisoning and procedural complications
Procedural pain
|
0.00%
0/147 • 27 months
Only 147 of 149 participants in the inosine group were analyzed because 2 participants never initiated study drug.
|
0.67%
1/149 • Number of events 1 • 27 months
Only 147 of 149 participants in the inosine group were analyzed because 2 participants never initiated study drug.
|
|
Injury, poisoning and procedural complications
Spinal compression fracture
|
0.00%
0/147 • 27 months
Only 147 of 149 participants in the inosine group were analyzed because 2 participants never initiated study drug.
|
0.67%
1/149 • Number of events 1 • 27 months
Only 147 of 149 participants in the inosine group were analyzed because 2 participants never initiated study drug.
|
|
Investigations
Blood sodium decreased
|
0.68%
1/147 • Number of events 1 • 27 months
Only 147 of 149 participants in the inosine group were analyzed because 2 participants never initiated study drug.
|
0.00%
0/149 • 27 months
Only 147 of 149 participants in the inosine group were analyzed because 2 participants never initiated study drug.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/147 • 27 months
Only 147 of 149 participants in the inosine group were analyzed because 2 participants never initiated study drug.
|
0.67%
1/149 • Number of events 1 • 27 months
Only 147 of 149 participants in the inosine group were analyzed because 2 participants never initiated study drug.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bile duct cancer
|
0.00%
0/147 • 27 months
Only 147 of 149 participants in the inosine group were analyzed because 2 participants never initiated study drug.
|
0.67%
1/149 • Number of events 1 • 27 months
Only 147 of 149 participants in the inosine group were analyzed because 2 participants never initiated study drug.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Prostate cancer
|
0.68%
1/147 • Number of events 1 • 27 months
Only 147 of 149 participants in the inosine group were analyzed because 2 participants never initiated study drug.
|
0.00%
0/149 • 27 months
Only 147 of 149 participants in the inosine group were analyzed because 2 participants never initiated study drug.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Transitional cell carcinoma
|
0.68%
1/147 • Number of events 1 • 27 months
Only 147 of 149 participants in the inosine group were analyzed because 2 participants never initiated study drug.
|
0.00%
0/149 • 27 months
Only 147 of 149 participants in the inosine group were analyzed because 2 participants never initiated study drug.
|
|
Nervous system disorders
Encephalopathy
|
0.68%
1/147 • Number of events 1 • 27 months
Only 147 of 149 participants in the inosine group were analyzed because 2 participants never initiated study drug.
|
0.00%
0/149 • 27 months
Only 147 of 149 participants in the inosine group were analyzed because 2 participants never initiated study drug.
|
|
Nervous system disorders
Syncope
|
0.68%
1/147 • Number of events 1 • 27 months
Only 147 of 149 participants in the inosine group were analyzed because 2 participants never initiated study drug.
|
1.3%
2/149 • Number of events 3 • 27 months
Only 147 of 149 participants in the inosine group were analyzed because 2 participants never initiated study drug.
|
|
Nervous system disorders
Transient ischaemic attack
|
0.00%
0/147 • 27 months
Only 147 of 149 participants in the inosine group were analyzed because 2 participants never initiated study drug.
|
0.67%
1/149 • Number of events 1 • 27 months
Only 147 of 149 participants in the inosine group were analyzed because 2 participants never initiated study drug.
|
|
Renal and urinary disorders
Nephrolithiasis
|
4.1%
6/147 • Number of events 6 • 27 months
Only 147 of 149 participants in the inosine group were analyzed because 2 participants never initiated study drug.
|
0.00%
0/149 • 27 months
Only 147 of 149 participants in the inosine group were analyzed because 2 participants never initiated study drug.
|
|
Renal and urinary disorders
Urinary retention
|
0.00%
0/147 • 27 months
Only 147 of 149 participants in the inosine group were analyzed because 2 participants never initiated study drug.
|
0.67%
1/149 • Number of events 1 • 27 months
Only 147 of 149 participants in the inosine group were analyzed because 2 participants never initiated study drug.
|
|
Reproductive system and breast disorders
Testicular mass
|
0.68%
1/147 • Number of events 1 • 27 months
Only 147 of 149 participants in the inosine group were analyzed because 2 participants never initiated study drug.
|
0.00%
0/149 • 27 months
Only 147 of 149 participants in the inosine group were analyzed because 2 participants never initiated study drug.
|
|
Surgical and medical procedures
Hip arthroplasty
|
0.00%
0/147 • 27 months
Only 147 of 149 participants in the inosine group were analyzed because 2 participants never initiated study drug.
|
1.3%
2/149 • Number of events 2 • 27 months
Only 147 of 149 participants in the inosine group were analyzed because 2 participants never initiated study drug.
|
|
Surgical and medical procedures
Knee arthroplasty
|
0.68%
1/147 • Number of events 1 • 27 months
Only 147 of 149 participants in the inosine group were analyzed because 2 participants never initiated study drug.
|
0.00%
0/149 • 27 months
Only 147 of 149 participants in the inosine group were analyzed because 2 participants never initiated study drug.
|
|
Vascular disorders
Hypotension
|
0.00%
0/147 • 27 months
Only 147 of 149 participants in the inosine group were analyzed because 2 participants never initiated study drug.
|
0.67%
1/149 • Number of events 1 • 27 months
Only 147 of 149 participants in the inosine group were analyzed because 2 participants never initiated study drug.
|
Other adverse events
| Measure |
Inosine
n=147 participants at risk
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
n=149 participants at risk
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
|
|---|---|---|
|
Gastrointestinal disorders
Constipation
|
4.8%
7/147 • Number of events 7 • 27 months
Only 147 of 149 participants in the inosine group were analyzed because 2 participants never initiated study drug.
|
10.7%
16/149 • Number of events 16 • 27 months
Only 147 of 149 participants in the inosine group were analyzed because 2 participants never initiated study drug.
|
|
Gastrointestinal disorders
Diarrhoea
|
6.1%
9/147 • Number of events 11 • 27 months
Only 147 of 149 participants in the inosine group were analyzed because 2 participants never initiated study drug.
|
6.0%
9/149 • Number of events 12 • 27 months
Only 147 of 149 participants in the inosine group were analyzed because 2 participants never initiated study drug.
|
|
Gastrointestinal disorders
Nausea
|
15.0%
22/147 • Number of events 25 • 27 months
Only 147 of 149 participants in the inosine group were analyzed because 2 participants never initiated study drug.
|
13.4%
20/149 • Number of events 31 • 27 months
Only 147 of 149 participants in the inosine group were analyzed because 2 participants never initiated study drug.
|
|
General disorders
Fatigue
|
5.4%
8/147 • Number of events 9 • 27 months
Only 147 of 149 participants in the inosine group were analyzed because 2 participants never initiated study drug.
|
7.4%
11/149 • Number of events 11 • 27 months
Only 147 of 149 participants in the inosine group were analyzed because 2 participants never initiated study drug.
|
|
Infections and infestations
Nasopharyngitis
|
8.2%
12/147 • Number of events 14 • 27 months
Only 147 of 149 participants in the inosine group were analyzed because 2 participants never initiated study drug.
|
6.7%
10/149 • Number of events 13 • 27 months
Only 147 of 149 participants in the inosine group were analyzed because 2 participants never initiated study drug.
|
|
Infections and infestations
Sinusitis
|
6.8%
10/147 • Number of events 11 • 27 months
Only 147 of 149 participants in the inosine group were analyzed because 2 participants never initiated study drug.
|
4.7%
7/149 • Number of events 9 • 27 months
Only 147 of 149 participants in the inosine group were analyzed because 2 participants never initiated study drug.
|
|
Infections and infestations
Upper respiratory tract infection
|
4.8%
7/147 • Number of events 8 • 27 months
Only 147 of 149 participants in the inosine group were analyzed because 2 participants never initiated study drug.
|
8.7%
13/149 • Number of events 16 • 27 months
Only 147 of 149 participants in the inosine group were analyzed because 2 participants never initiated study drug.
|
|
Infections and infestations
Urinary tract infection
|
11.6%
17/147 • Number of events 24 • 27 months
Only 147 of 149 participants in the inosine group were analyzed because 2 participants never initiated study drug.
|
6.7%
10/149 • Number of events 16 • 27 months
Only 147 of 149 participants in the inosine group were analyzed because 2 participants never initiated study drug.
|
|
Investigations
Blood creatinine increased
|
8.8%
13/147 • Number of events 13 • 27 months
Only 147 of 149 participants in the inosine group were analyzed because 2 participants never initiated study drug.
|
2.0%
3/149 • Number of events 3 • 27 months
Only 147 of 149 participants in the inosine group were analyzed because 2 participants never initiated study drug.
|
|
Investigations
Crystal urine present
|
5.4%
8/147 • Number of events 9 • 27 months
Only 147 of 149 participants in the inosine group were analyzed because 2 participants never initiated study drug.
|
4.7%
7/149 • Number of events 9 • 27 months
Only 147 of 149 participants in the inosine group were analyzed because 2 participants never initiated study drug.
|
|
Investigations
Mean cell volume increased
|
8.2%
12/147 • Number of events 13 • 27 months
Only 147 of 149 participants in the inosine group were analyzed because 2 participants never initiated study drug.
|
4.7%
7/149 • Number of events 7 • 27 months
Only 147 of 149 participants in the inosine group were analyzed because 2 participants never initiated study drug.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
6.1%
9/147 • Number of events 9 • 27 months
Only 147 of 149 participants in the inosine group were analyzed because 2 participants never initiated study drug.
|
8.7%
13/149 • Number of events 13 • 27 months
Only 147 of 149 participants in the inosine group were analyzed because 2 participants never initiated study drug.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
12.2%
18/147 • Number of events 19 • 27 months
Only 147 of 149 participants in the inosine group were analyzed because 2 participants never initiated study drug.
|
6.7%
10/149 • Number of events 12 • 27 months
Only 147 of 149 participants in the inosine group were analyzed because 2 participants never initiated study drug.
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
6.1%
9/147 • Number of events 10 • 27 months
Only 147 of 149 participants in the inosine group were analyzed because 2 participants never initiated study drug.
|
4.7%
7/149 • Number of events 7 • 27 months
Only 147 of 149 participants in the inosine group were analyzed because 2 participants never initiated study drug.
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
6.1%
9/147 • Number of events 9 • 27 months
Only 147 of 149 participants in the inosine group were analyzed because 2 participants never initiated study drug.
|
14.1%
21/149 • Number of events 25 • 27 months
Only 147 of 149 participants in the inosine group were analyzed because 2 participants never initiated study drug.
|
|
Nervous system disorders
Dizziness
|
9.5%
14/147 • Number of events 16 • 27 months
Only 147 of 149 participants in the inosine group were analyzed because 2 participants never initiated study drug.
|
10.7%
16/149 • Number of events 22 • 27 months
Only 147 of 149 participants in the inosine group were analyzed because 2 participants never initiated study drug.
|
|
Nervous system disorders
Headache
|
5.4%
8/147 • Number of events 9 • 27 months
Only 147 of 149 participants in the inosine group were analyzed because 2 participants never initiated study drug.
|
9.4%
14/149 • Number of events 16 • 27 months
Only 147 of 149 participants in the inosine group were analyzed because 2 participants never initiated study drug.
|
|
Nervous system disorders
Somnolence
|
2.7%
4/147 • Number of events 4 • 27 months
Only 147 of 149 participants in the inosine group were analyzed because 2 participants never initiated study drug.
|
5.4%
8/149 • Number of events 9 • 27 months
Only 147 of 149 participants in the inosine group were analyzed because 2 participants never initiated study drug.
|
|
Psychiatric disorders
Insomnia
|
6.1%
9/147 • Number of events 9 • 27 months
Only 147 of 149 participants in the inosine group were analyzed because 2 participants never initiated study drug.
|
4.0%
6/149 • Number of events 6 • 27 months
Only 147 of 149 participants in the inosine group were analyzed because 2 participants never initiated study drug.
|
|
Renal and urinary disorders
Haematuria
|
8.8%
13/147 • Number of events 13 • 27 months
Only 147 of 149 participants in the inosine group were analyzed because 2 participants never initiated study drug.
|
8.1%
12/149 • Number of events 12 • 27 months
Only 147 of 149 participants in the inosine group were analyzed because 2 participants never initiated study drug.
|
|
Renal and urinary disorders
Nephrolithiasis
|
8.2%
12/147 • Number of events 12 • 27 months
Only 147 of 149 participants in the inosine group were analyzed because 2 participants never initiated study drug.
|
2.7%
4/149 • Number of events 4 • 27 months
Only 147 of 149 participants in the inosine group were analyzed because 2 participants never initiated study drug.
|
|
Renal and urinary disorders
Proteinuria
|
6.1%
9/147 • Number of events 9 • 27 months
Only 147 of 149 participants in the inosine group were analyzed because 2 participants never initiated study drug.
|
8.1%
12/149 • Number of events 14 • 27 months
Only 147 of 149 participants in the inosine group were analyzed because 2 participants never initiated study drug.
|
Additional Information
Dr. Michael Schwarzschild
Massachusetts General Hospital
Phone: 617-724-9611
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place