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| ID | Type | Description | Link |
|---|---|---|---|
| P30MH075673-05 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Institute of Mental Health (NIMH) | NIH |
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The purpose of this study is to see if paroxetine and fluconazole are safe and effective as a treatment for problems with memory, concentration, thinking, and judgment in people who are infected with HIV. Paroxetine is an antidepressant approved by the FDA to treat major depression. Fluconazole is an antifungal medication approved by the FDA to treat fungal infections.
The study will be a 24 week double-blind, placebo-controlled 2x2 factorial design pilot Phase I/II study in 60 HIV+ individuals with HAND. Participants will be randomly assigned to one of four groups: 1) fluconazole 100 mg every 12 hours orally per day, 2) paroxetine 20mg every evening orally per day, 3) fluconazole 100mg every 12 hours orally per day and paroxetine 20mg every evening orally per day and 4) placebo.
Primary Aim: To obtain preliminary data to evaluate the efficacy of fluconazole and/or paroxetine to decrease CSF lipid and protein markers of oxidative stress [CSF ceramide and (C18:0 levels) and 3-nitrosylated proteins].
Secondary Aims:
i) To evaluate the safety and tolerability of fluconazole and/or paroxetine in HIV+ individuals with HAND ii) To evaluate the effect of fluconazole and/or paroxetine on neurocognitive performance in HIV+ individuals with HAND iii) To evaluate the effect of fluconazole and/or paroxetine on functional performance in HIV+ individuals with HAND iv) To evaluate the CNS penetration of fluconazole and paroxetine after 24 weeks of treatment v) To obtain preliminary data to evaluate the efficacy of fluconazole and/or paroxetine to improve abnormal imaging markers as measured by magnetic resonance spectroscopy (MRS) and arterial spin labeling
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Fluconazole | Experimental | Fluconazole 100 mg every 12 hours orally per day; placebo in place of paroxetine |
|
| Paroxetine | Experimental | Paroxetine 20 mg orally once per day; placebo in place of fluconazole |
|
| Paroxetine and Fluconazole | Experimental | Fluconazole 100 mg every 12 hours orally per day and paroxetine 20 mg every evening orally per day |
|
| Placebo | Placebo Comparator | Placebo in place of both fluconazole and paroxetine |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Fluconazole | Drug | One 100 MG capsule taken twice daily, 12 hour dosing |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Change in CSF Ceramide Between Baseline and Week 24 (C18:0 Levels) - Intent to Treat | CSF lipid and protein markers of oxidative stress: Change in CSF ceramide (C18:0 levels) between baseline and week 24 for all participants for whom baseline and follow-up CSF data are available (intent to treat analysis). | 24 Weeks |
| Change in CSF Ceramide Between Baseline and Week 24 (C18:0 Levels) - Per Protocol | CSF lipid and protein markers of oxidative stress: Change in CSF ceramide (C18:0 levels) between baseline and week 24 for participants with 90% or greater study drug adherence and for whom baseline and follow-up CSF data are available (per protocol analysis). | 24 Weeks |
| Change in CSF 3-nitrosylated Protein Levels Between Baseline and Week 24 - Intent to Treat | CSF lipid and protein markers of oxidative stress: Change in 3-nitrosylated protein levels between baseline and week 24 for all participants for whom CSF data are available (intent to treat analysis). | 24 Weeks |
| Change in CSF 3-nitrosylated Protein Levels Between Baseline and Week 24 - Per Protocol | CSF lipid and protein markers of oxidative stress: Change in 3-nitrosylated protein levels between baseline and week 24 for participants with 90% or greater adherence to study drug and for whom CSF data are available (per protocol analysis). | 24 Weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Change in CSF sCD14 Between Baseline and Week 24 - Intent to Treat | CSF immune and neuronal injury markers: Change in CSF sCD14 between baseline and week 24 for all participants for whom baseline and follow-up CSF data are available (intent to treat analysis). | 24 Weeks |
| Change in CSF sCD14 Between Baseline and Week 24 - Per Protocol |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Ned Sacktor, MD | Johns Hopkins University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| The Johns Hopkins Institute for Clinical and Translational Research, Adult Outpatient Clinical Research Unit | Baltimore | Maryland | 21287 | United States |
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| ID | Title | Description |
|---|---|---|
| FG000 | Paroxetine and Fluconazole | Fluconazole 100 mg every 12 hours orally per day and paroxetine 20 mg every evening orally per day Paroxetine and Fluconazole: One capsule 100 MG fluconazole every 12 hours orally per day; Two 10 MG capsules paroxetine orally once daily in the evening |
| FG001 | Paroxetine | Paroxetine 20 mg orally once per day; placebo in place of fluconazole every 12 hours orally per day Paroxetine: Two 10 MG capsules paroxetine once daily in the evening |
| FG002 | Fluconazole | Fluconazole 100 mg every 12 hours orally per day; placebo in place of paroxetine every evening orally per day Fluconazole: One 100 MG capsule taken twice daily, 12 hour dosing |
| FG003 | Placebo | Placebos in place of fluconazole and paroxetine Placebos: One capsule placebo #1 every 12 hours orally per day; Two capsules placebo #2 orally once daily in the evening |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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|
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| ID | Title | Description |
|---|---|---|
| BG000 | Paroxetine and Fluconazole | Fluconazole 100 mg every 12 hours orally per day and paroxetine 20 mg every evening orally per day Paroxetine and Fluconazole: One capsule 100 MG fluconazole every 12 hours orally per day; Two 10 MG capsules paroxetine orally once daily in the evening |
| BG001 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change in CSF Ceramide Between Baseline and Week 24 (C18:0 Levels) - Intent to Treat | CSF lipid and protein markers of oxidative stress: Change in CSF ceramide (C18:0 levels) between baseline and week 24 for all participants for whom baseline and follow-up CSF data are available (intent to treat analysis). | 31 participants, out of the total 45 enrolled, completed the trial with follow-up CSF primary outcome measures. | Posted | Median | Inter-Quartile Range | ng/mL | 24 Weeks |
|
Adverse event data were collected during the 24 week clinical trial period for each subject, and if pertinent, during the follow-up period, which was at least 14 days and up to 60 days after discontinuation of the intervention. When applicable, some adverse event data were collected between the screening visit and baseline visit (e.g., safety data pertaining to the lumbar puncture procedure).
Routine safety blood tests were performed at screening, baseline, week 4, week 12, and week 24 visits. A combination of open-ended questioning, medical chart review, and standard questionnaires was used to collect adverse event data at each of the visits. A study clinician performed standard neuro-medical physical exams at baseline, week 12, and week 24. If warranted, data collection occurred between visits, ad hoc, to track ongoing adverse events, as well as after stopping the intervention.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Paroxetine and Fluconazole | Fluconazole 100 mg every 12 hours orally per day and paroxetine 20 mg every evening orally per day Paroxetine and Fluconazole: One capsule 100 MG fluconazole every 12 hours orally per day; Two 10 MG capsules paroxetine orally once daily in the evening |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Surgery, knee replacement | Surgical and medical procedures | Systematic Assessment | Inpatient elective surgery followed by complications |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal cramping or pain | Gastrointestinal disorders | Systematic Assessment | Generalized abdominal cramping or pain (non-focalized) |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Ned Sacktor | The Johns Hopkins University | 410-550-1045 | sacktor@jhmi.edu |
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| ID | Term |
|---|---|
| D003704 | Dementia |
| ID | Term |
|---|---|
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D019965 | Neurocognitive Disorders |
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| ID | Term |
|---|---|
| D015725 | Fluconazole |
| D017374 | Paroxetine |
| ID | Term |
|---|---|
| D014230 | Triazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
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| Paroxetine |
| Drug |
Two 10 MG capsules paroxetine once daily in the evening |
|
| Paroxetine and Fluconazole | Drug | One capsule 100 MG fluconazole every 12 hours orally per day; Two 10 MG capsules paroxetine orally once daily in the evening |
|
| Placebo | Drug | One capsule in the morning, three capsules in the evening |
|
CSF immune and neuronal injury markers: Change in CSF sCD14 between baseline and week 24 for participants with 90% or greater study drug adherence and for whom baseline and follow-up CSF data are available (per protocol analysis). |
| 24 Weeks |
| Change in CSF CD163 Between Baseline and Week 24 - Intent to Treat | CSF immune and neuronal injury markers: Change in CSF CD163 between baseline and week 24 for all participants for whom baseline and follow-up CSF data are available (intent to treat analysis). | 24 Weeks |
| Change in CSF CD163 Between Baseline and Week 24 - Per Protocol | CSF immune and neuronal injury markers: Change in CSF CD163 between baseline and week 24 for participants with 90% or greater study drug adherence and for whom baseline and follow-up CSF data are available (per protocol analysis). | 24 Weeks |
| Change in CSF Neurofilament Protein Light Chain (NFL) Between Baseline and Week 24 - Intent to Treat | CSF immune and neuronal injury markers: Change in CSF neurofilament protein light chain (NFL) between baseline and week 24 for all participants for whom baseline and follow-up CSF data are available (intent to treat analysis). | 24 Weeks |
| Change in CSF Neurofilament Protein Light Chain (NFL) Between Baseline and Week 24 - Per Protocol | CSF immune and neuronal injury markers: Change in CSF neurofilament protein light chain (NFL) between baseline and week 24 for participants with 90% or greater study drug adherence and for whom baseline and follow-up CSF data are available (per protocol analysis). | 24 Weeks |
| Change in CSF Neurofilament Protein Heavy Chain (pNFL) Between Baseline and Week 24 - Intent to Treat | CSF immune and neuronal injury markers: Change in CSF neurofilament protein heavy chain (pNFL) between baseline and week 24 for all participants for whom baseline and follow-up CSF data are available (intent to treat analysis). | 24 Weeks |
| Change in CSF Neurofilament Protein Heavy Chain (pNFH) Between Baseline and Week 24 - Per Protocol | CSF immune and neuronal injury markers: Change in CSF neurofilament protein heavy chain (pNFH) between baseline and week 24 for participants with 90% or greater study drug adherence and for whom baseline and follow-up CSF data are available (per protocol analysis). | 24 Weeks |
| Neurocognitive Performance: Trail Making A - Intent to Treat | Baseline to Week 24 change in neurocognitive performance as measured by the Trail-making test, part A speed of completion (Z scores). | 24 Weeks |
| Neurocognitive Performance: Trail Making A - Per Protocol | Baseline to Week 24 change in neurocognitive performance as measured by the Trail-making test, part A speed of completion (Z scores). | 24 Weeks |
| Neurocognitive Performance: Trail Making B - Intent to Treat | Baseline to Week 24 change in neurocognitive performance as measured by the Trail-making test, part B speed of completion (Z scores). | 24 Weeks |
| Neurocognitive Performance: Trail Making B - Per Protocol | Baseline to Week 24 change in neurocognitive performance as measured by the Trail-making test, part B speed of completion (Z scores). | 24 Weeks |
| Neurocognitive Performance: Grooved Pegboard, Dominant - Intent to Treat | Baseline to Week 24 change in neurocognitive performance as measured by the Grooved Pegboard test, dominant hand speed of completion (Z scores). | 24 Weeks |
| Neurocognitive Performance: Grooved Pegboard, Dominant - Per Protocol | Baseline to Week 24 change in neurocognitive performance as measured by the Grooved Pegboard test, dominant hand speed of completion (Z scores). | 24 Weeks |
| Neurocognitive Performance: Grooved Pegboard, Non-Dominant - Intent to Treat | Baseline to Week 24 change in neurocognitive performance as measured by the Grooved Pegboard test, non-dominant hand speed of completion (Z scores). | 24 Weeks |
| Neurocognitive Performance: Grooved Pegboard, Non-Dominant - Per Protocol | Baseline to Week 24 change in neurocognitive performance as measured by the Grooved Pegboard test, non-dominant hand speed of completion (Z scores). | 24 Weeks |
| Neurocognitive Performance: CalCAP, Choice - Intent to Treat | Baseline to Week 24 change in neurocognitive performance as measured by the CalCAP Choice test, mean reaction time (Z scores). | 24 Weeks |
| Neurocognitive Performance: CalCAP, Choice - Per Protocol | Baseline to Week 24 change in neurocognitive performance as measured by the CalCAP Choice test, mean reaction time (Z scores). | 24 Weeks |
| Neurocognitive Performance: CalCAP, Sequential - Intent to Treat | Baseline to Week 24 change in neurocognitive performance as measured by the CalCAP Sequential test, mean reaction time (Z scores). | 24 Weeks |
| Neurocognitive Performance: CalCAP, Sequential - Per Protocol | Baseline to Week 24 change in neurocognitive performance as measured by the CalCAP Sequential test, mean reaction time (Z scores). | 24 Weeks |
| Neurocognitive Performance: Symbol-Digit Test - Intent to Treat | Baseline to Week 24 change in neurocognitive performance as measured by Symbol-Digit Test score, number correct in 120 seconds (Z scores). | 24 Weeks |
| Neurocognitive Performance: Symbol-Digit Test - Per Protocol | Baseline to Week 24 change in neurocognitive performance as measured by Symbol-Digit Test score, number correct in 120 seconds (Z scores). | 24 Weeks |
| Neurocognitive Performance: Timed Gait - Intent to Treat | Baseline to Week 24 change in neurocognitive performance as measured by Timed Gait, three-trial average time (Z scores). | 24 Weeks |
| Neurocognitive Performance: Timed Gait - Per Protocol | Baseline to Week 24 change in neurocognitive performance as measured by Timed Gait, three-trial average time (Z scores). | 24 Weeks |
| Neurocognitive Performance: NPZ-8 - Intent to Treat | Baseline to Week 24 change in neurocognitive performance as measured by NPZ-8 scores calculated for all participants who completed the trial with measurable Baseline and Week 24 data for at least 6 of the 8 data points. The data points that comprise the NPZ-8 include timed gait, symbol-digit, grooved pegboard dominant and non-dominant, CalCAP Choice reaction time and Sequential reaction time, Trail-making Test A and B. The baseline to week 24 changes for each test were averaged to get each change in NPZ-8 score. | 24 Weeks |
| Neurocognitive Performance: NPZ-8 - Per Protocol | Baseline to Week 24 change in neurocognitive performance as measured by NPZ-8 scores calculated for all participants who completed the trial with measurable Baseline and Week 24 data for at least 6 of the 8 data points. The data points that comprise the NPZ-8 include timed gait, symbol-digit, grooved pegboard dominant and non-dominant, CalCAP Choice reaction time and Sequential reaction time, Trail-making Test A and B. The baseline to week 24 changes for each test were averaged to get each change in NPZ-8 score. | 24 Weeks |
| Change in CES-D Score - Intent to Treat | Functional assessment: Change in Center for Epidemiologic Studies Depression Scale (CES-D) score between baseline and week 24 for all participants for whom baseline and follow-up CES-D data are available (intent to treat analysis). | 24 Weeks |
| Change in CES-D Score - Per Protocol | Functional assessment: Change in Center for Epidemiologic Studies Depression Scale (CES-D) score between baseline and week 24 for all participants for whom baseline and follow-up CES-D data are available (per protocol). | 24 Weeks |
| Withdrawal by Subject |
|
| Adverse Event |
|
| Protocol Violation |
|
| Less than 90% Adherence |
|
| Paroxetine |
Paroxetine 20 mg orally once per day; placebo in place of fluconazole every 12 hours orally per day Paroxetine: Two 10 MG capsules paroxetine once daily in the evening |
| BG002 | Fluconazole | Fluconazole 100 mg every 12 hours orally per day; placebo in place of paroxetine every evening orally per day Fluconazole: One 100 MG capsule taken twice daily, 12 hour dosing |
| BG003 | Placebo | Placebos in place of fluconazole and paroxetine Placebos: One capsule placebo #1 every 12 hours orally per day; Two capsules placebo #2 orally once daily in the evening |
| BG004 | Total | Total of all reporting groups |
| Years |
|
| Age, Customized | Number | Years |
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| Sex/Gender, Customized | Number | participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
|
| Education | Mean | Standard Deviation | Years Completed |
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| Years Since HIV Diagnosis | Based on self-report from participants. | Mean | Standard Deviation | Years |
|
| Absolute CD4 Count | Mean | Standard Deviation | Cells per cubic mm |
|
| Plasma HIV Viral Load | Number | participants |
|
| Hepatitis C Infection Status | Number | participants |
|
| Paroxetine |
Paroxetine 20 mg orally once per day; placebo in place of fluconazole every 12 hours orally per day Paroxetine: Two 10 MG capsules paroxetine once daily in the evening |
| OG002 | Fluconazole | Fluconazole 100 mg every 12 hours orally per day; placebo in place of paroxetine every evening orally per day Fluconazole: One 100 MG capsule taken twice daily, 12 hour dosing |
| OG003 | Placebo | Placebos in place of fluconazole and paroxetine Placebos: One capsule placebo #1 every 12 hours orally per day; Two capsules placebo #2 orally once daily in the evening |
|
|
|
| Primary | Change in CSF Ceramide Between Baseline and Week 24 (C18:0 Levels) - Per Protocol | CSF lipid and protein markers of oxidative stress: Change in CSF ceramide (C18:0 levels) between baseline and week 24 for participants with 90% or greater study drug adherence and for whom baseline and follow-up CSF data are available (per protocol analysis). | For per protocol analysis, 18 participants (out of the 22 who completed the trial with 90% or greater study drug adherence) had follow-up CSF for primary outcome measures. | Posted | Median | Inter-Quartile Range | ng/mL | 24 Weeks |
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| Primary | Change in CSF 3-nitrosylated Protein Levels Between Baseline and Week 24 - Intent to Treat | CSF lipid and protein markers of oxidative stress: Change in 3-nitrosylated protein levels between baseline and week 24 for all participants for whom CSF data are available (intent to treat analysis). | For intention to treat analysis, 31 participants, out of the total 45 enrolled, completed the trial with follow-up CSF primary outcome measures. | Posted | Median | Inter-Quartile Range | pi*mm^2 | 24 Weeks |
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| Primary | Change in CSF 3-nitrosylated Protein Levels Between Baseline and Week 24 - Per Protocol | CSF lipid and protein markers of oxidative stress: Change in 3-nitrosylated protein levels between baseline and week 24 for participants with 90% or greater adherence to study drug and for whom CSF data are available (per protocol analysis). | For per protocol analysis, 18 participants (out of the total 22 who completed the trial with 90% or greater study drug adherence) had follow-up CSF for primary outcome measures. | Posted | Median | Inter-Quartile Range | pi*mm^2 | 24 Weeks |
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| Secondary | Change in CSF sCD14 Between Baseline and Week 24 - Intent to Treat | CSF immune and neuronal injury markers: Change in CSF sCD14 between baseline and week 24 for all participants for whom baseline and follow-up CSF data are available (intent to treat analysis). | 31 participants, out of the total 45 enrolled, completed the trial with follow-up CSF primary outcome measures. | Posted | Median | Inter-Quartile Range | pg/mL | 24 Weeks |
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| Secondary | Change in CSF sCD14 Between Baseline and Week 24 - Per Protocol | CSF immune and neuronal injury markers: Change in CSF sCD14 between baseline and week 24 for participants with 90% or greater study drug adherence and for whom baseline and follow-up CSF data are available (per protocol analysis). | For per protocol analysis, 18 participants (out of the 22 who completed the trial with 90% or greater study drug adherence) had follow-up CSF for primary outcome measures. | Posted | Median | Inter-Quartile Range | pg/mL | 24 Weeks |
|
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| Secondary | Change in CSF CD163 Between Baseline and Week 24 - Intent to Treat | CSF immune and neuronal injury markers: Change in CSF CD163 between baseline and week 24 for all participants for whom baseline and follow-up CSF data are available (intent to treat analysis). | 31 participants, out of the total 45 enrolled, completed the trial with follow-up CSF primary outcome measures. | Posted | Median | Inter-Quartile Range | ng/mL | 24 Weeks |
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| Secondary | Change in CSF CD163 Between Baseline and Week 24 - Per Protocol | CSF immune and neuronal injury markers: Change in CSF CD163 between baseline and week 24 for participants with 90% or greater study drug adherence and for whom baseline and follow-up CSF data are available (per protocol analysis). | For per protocol analysis, 18 participants (out of the 22 who completed the trial with 90% or greater study drug adherence) had follow-up CSF for primary outcome measures. | Posted | Median | Inter-Quartile Range | ng/mL | 24 Weeks |
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| Secondary | Change in CSF Neurofilament Protein Light Chain (NFL) Between Baseline and Week 24 - Intent to Treat | CSF immune and neuronal injury markers: Change in CSF neurofilament protein light chain (NFL) between baseline and week 24 for all participants for whom baseline and follow-up CSF data are available (intent to treat analysis). | 31 participants, out of the total 45 enrolled, completed the trial with follow-up CSF primary outcome measures. | Posted | Median | Inter-Quartile Range | pg/mL | 24 Weeks |
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| Secondary | Change in CSF Neurofilament Protein Light Chain (NFL) Between Baseline and Week 24 - Per Protocol | CSF immune and neuronal injury markers: Change in CSF neurofilament protein light chain (NFL) between baseline and week 24 for participants with 90% or greater study drug adherence and for whom baseline and follow-up CSF data are available (per protocol analysis). | For per protocol analysis, 18 participants (out of the 22 who completed the trial with 90% or greater study drug adherence) had follow-up CSF for primary outcome measures. | Posted | Median | Inter-Quartile Range | pg/mL | 24 Weeks |
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| Secondary | Change in CSF Neurofilament Protein Heavy Chain (pNFL) Between Baseline and Week 24 - Intent to Treat | CSF immune and neuronal injury markers: Change in CSF neurofilament protein heavy chain (pNFL) between baseline and week 24 for all participants for whom baseline and follow-up CSF data are available (intent to treat analysis). | 31 participants, out of the total 45 enrolled, completed the trial with follow-up CSF primary outcome measures. | Posted | Median | Inter-Quartile Range | pg/mL | 24 Weeks |
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| Secondary | Change in CSF Neurofilament Protein Heavy Chain (pNFH) Between Baseline and Week 24 - Per Protocol | CSF immune and neuronal injury markers: Change in CSF neurofilament protein heavy chain (pNFH) between baseline and week 24 for participants with 90% or greater study drug adherence and for whom baseline and follow-up CSF data are available (per protocol analysis). | For per protocol analysis, 18 participants (out of the 22 who completed the trial with 90% or greater study drug adherence) had follow-up CSF for primary outcome measures. | Posted | Median | Inter-Quartile Range | pg/mL | 24 Weeks |
|
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| Secondary | Neurocognitive Performance: Trail Making A - Intent to Treat | Baseline to Week 24 change in neurocognitive performance as measured by the Trail-making test, part A speed of completion (Z scores). | Includes all participants who completed the study with test data available at the Baseline and Week 24 visits for Intention to Treat analysis. | Posted | Mean | Standard Deviation | Z score | 24 Weeks |
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| Secondary | Neurocognitive Performance: Trail Making A - Per Protocol | Baseline to Week 24 change in neurocognitive performance as measured by the Trail-making test, part A speed of completion (Z scores). | Per protocol analysis: Includes all participants who completed the study per protocol and with test data available at the Baseline and Week 24 visits. | Posted | Mean | Standard Deviation | Z score | 24 Weeks |
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| Secondary | Neurocognitive Performance: Trail Making B - Intent to Treat | Baseline to Week 24 change in neurocognitive performance as measured by the Trail-making test, part B speed of completion (Z scores). | Includes all participants who completed the study with test data available at the Baseline and Week 24 visits for Intention to Treat analysis. | Posted | Mean | Standard Deviation | Z score | 24 Weeks |
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| Secondary | Neurocognitive Performance: Trail Making B - Per Protocol | Baseline to Week 24 change in neurocognitive performance as measured by the Trail-making test, part B speed of completion (Z scores). | Per protocol analysis: Includes all participants who completed the study per protocol and with test data available at the Baseline and Week 24 visits. | Posted | Mean | Standard Deviation | Z score | 24 Weeks |
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| Secondary | Neurocognitive Performance: Grooved Pegboard, Dominant - Intent to Treat | Baseline to Week 24 change in neurocognitive performance as measured by the Grooved Pegboard test, dominant hand speed of completion (Z scores). | Includes all participants who completed the study with test data available at the Baseline and Week 24 visits for Intention to Treat analysis. | Posted | Mean | Standard Deviation | Z score | 24 Weeks |
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| Secondary | Neurocognitive Performance: Grooved Pegboard, Dominant - Per Protocol | Baseline to Week 24 change in neurocognitive performance as measured by the Grooved Pegboard test, dominant hand speed of completion (Z scores). | Per protocol analysis: Includes all participants who completed the study per protocol and with test data available at the Baseline and Week 24 visits. | Posted | Mean | Standard Deviation | Z score | 24 Weeks |
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| Secondary | Neurocognitive Performance: Grooved Pegboard, Non-Dominant - Intent to Treat | Baseline to Week 24 change in neurocognitive performance as measured by the Grooved Pegboard test, non-dominant hand speed of completion (Z scores). | Includes all participants who completed the study with test data available at the Baseline and Week 24 visits for Intention to Treat analysis. | Posted | Mean | Standard Deviation | Z score | 24 Weeks |
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| Secondary | Neurocognitive Performance: Grooved Pegboard, Non-Dominant - Per Protocol | Baseline to Week 24 change in neurocognitive performance as measured by the Grooved Pegboard test, non-dominant hand speed of completion (Z scores). | Per protocol analysis: Includes all participants who completed the study per protocol and with test data available at the Baseline and Week 24 visits. | Posted | Mean | Standard Deviation | Z score | 24 Weeks |
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| Secondary | Neurocognitive Performance: CalCAP, Choice - Intent to Treat | Baseline to Week 24 change in neurocognitive performance as measured by the CalCAP Choice test, mean reaction time (Z scores). | Includes all participants who completed the study with test data available at the Baseline and Week 24 visits for Intention to Treat analysis. | Posted | Mean | Standard Deviation | Z score | 24 Weeks |
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| Secondary | Neurocognitive Performance: CalCAP, Choice - Per Protocol | Baseline to Week 24 change in neurocognitive performance as measured by the CalCAP Choice test, mean reaction time (Z scores). | Per protocol analysis: Includes participants who completed the study per protocol and with test data available at the Baseline and Week 24 visits. | Posted | Mean | Standard Deviation | Z score | 24 Weeks |
|
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| Secondary | Neurocognitive Performance: CalCAP, Sequential - Intent to Treat | Baseline to Week 24 change in neurocognitive performance as measured by the CalCAP Sequential test, mean reaction time (Z scores). | Includes all participants who completed the study with test data available at the Baseline and Week 24 visits for Intention to Treat analysis. | Posted | Mean | Standard Deviation | Z score | 24 Weeks |
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| Secondary | Neurocognitive Performance: CalCAP, Sequential - Per Protocol | Baseline to Week 24 change in neurocognitive performance as measured by the CalCAP Sequential test, mean reaction time (Z scores). | Per protocol analysis: Includes participants who completed the study per protocol and with test data available at the Baseline and Week 24 visits. | Posted | Mean | Standard Deviation | Z score | 24 Weeks |
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| Secondary | Neurocognitive Performance: Symbol-Digit Test - Intent to Treat | Baseline to Week 24 change in neurocognitive performance as measured by Symbol-Digit Test score, number correct in 120 seconds (Z scores). | Includes all participants who completed the study with test data available (no data substitution) at the Baseline and Week 24 visits for Intention to Treat analysis. | Posted | Mean | Standard Deviation | Z score | 24 Weeks |
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| Secondary | Neurocognitive Performance: Symbol-Digit Test - Per Protocol | Baseline to Week 24 change in neurocognitive performance as measured by Symbol-Digit Test score, number correct in 120 seconds (Z scores). | Per protocol analysis: Includes participants who completed the study per protocol and with test data available (no data substitution) at the Baseline and Week 24 visits. | Posted | Mean | Standard Deviation | Z score | 24 Weeks |
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| Secondary | Neurocognitive Performance: Timed Gait - Intent to Treat | Baseline to Week 24 change in neurocognitive performance as measured by Timed Gait, three-trial average time (Z scores). | Includes all participants who completed the study with test data available at the Baseline and Week 24 visits for Intention to Treat analysis. | Posted | Mean | Standard Deviation | Z score | 24 Weeks |
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| Secondary | Neurocognitive Performance: Timed Gait - Per Protocol | Baseline to Week 24 change in neurocognitive performance as measured by Timed Gait, three-trial average time (Z scores). | Per protocol analysis: Includes participants who completed the study per protocol and with test data available at the Baseline and Week 24 visits. | Posted | Mean | Standard Deviation | Z score | 24 Weeks |
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| Secondary | Neurocognitive Performance: NPZ-8 - Intent to Treat | Baseline to Week 24 change in neurocognitive performance as measured by NPZ-8 scores calculated for all participants who completed the trial with measurable Baseline and Week 24 data for at least 6 of the 8 data points. The data points that comprise the NPZ-8 include timed gait, symbol-digit, grooved pegboard dominant and non-dominant, CalCAP Choice reaction time and Sequential reaction time, Trail-making Test A and B. The baseline to week 24 changes for each test were averaged to get each change in NPZ-8 score. | Includes all participants who completed the study with test data available at the Baseline and Week 24 visits for Intention to Treat analysis. | Posted | Mean | Standard Deviation | Z score | 24 Weeks |
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| Secondary | Neurocognitive Performance: NPZ-8 - Per Protocol | Baseline to Week 24 change in neurocognitive performance as measured by NPZ-8 scores calculated for all participants who completed the trial with measurable Baseline and Week 24 data for at least 6 of the 8 data points. The data points that comprise the NPZ-8 include timed gait, symbol-digit, grooved pegboard dominant and non-dominant, CalCAP Choice reaction time and Sequential reaction time, Trail-making Test A and B. The baseline to week 24 changes for each test were averaged to get each change in NPZ-8 score. | Per protocol analysis: Includes participants who completed the study per protocol and with test data available at the Baseline and Week 24 visits. | Posted | Mean | Standard Deviation | Z score | 24 Weeks |
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| Secondary | Change in CES-D Score - Intent to Treat | Functional assessment: Change in Center for Epidemiologic Studies Depression Scale (CES-D) score between baseline and week 24 for all participants for whom baseline and follow-up CES-D data are available (intent to treat analysis). | Includes all participants who completed the study with test data available at the Baseline and Week 24 visits for Intention to Treat analysis. | Posted | Mean | Standard Deviation | units on a scale | 24 Weeks |
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| Secondary | Change in CES-D Score - Per Protocol | Functional assessment: Change in Center for Epidemiologic Studies Depression Scale (CES-D) score between baseline and week 24 for all participants for whom baseline and follow-up CES-D data are available (per protocol). | Per protocol analysis: Includes participants who completed the study per protocol and with test data available at the Baseline and Week 24 visits. | Posted | Mean | Standard Deviation | units on a scale | 24 Weeks |
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|
| 0 |
| 12 |
| 2 |
| 12 |
| 11 |
| 12 |
| EG001 | Paroxetine | Paroxetine 20 mg orally once per day; placebo in place of fluconazole every 12 hours orally per day Paroxetine: Two 10 MG capsules paroxetine once daily in the evening | 0 | 11 | 0 | 11 | 10 | 11 |
| EG002 | Fluconazole | Fluconazole 100 mg every 12 hours orally per day; placebo in place of paroxetine every evening orally per day Fluconazole: One 100 MG capsule taken twice daily, 12 hour dosing | 0 | 11 | 3 | 11 | 10 | 11 |
| EG003 | Placebo | Placebos in place of fluconazole and paroxetine Placebos: One capsule placebo #1 every 12 hours orally per day; Two capsules placebo #2 orally once daily in the evening | 0 | 11 | 3 | 11 | 10 | 11 |
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| Heroin abuse, relapse | Injury, poisoning and procedural complications | Systematic Assessment |
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| Small bowel obstruction | Gastrointestinal disorders | Systematic Assessment |
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| Glucose, non-fasting, high | Endocrine disorders | Systematic Assessment | Grade 4 (DAIDS); hyperglycemia in the context of acute uncontrolled diabetes |
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| Surgery, neck | Surgical and medical procedures | Systematic Assessment | Elective surgery to treat cervical stenosis |
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| Depression, acute | Psychiatric disorders | Systematic Assessment | Grade 3 (DAIDS); Acute episode, resolved |
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| Absolute neutrophil count (ANC), low | Immune system disorders | Systematic Assessment | Blood test, grade 2 (DAIDS 2.0) |
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| Acute bronchospasm | Respiratory, thoracic and mediastinal disorders | Systematic Assessment | Grade 2 (DAIDS 2.0); context of chronic obstructive pulmonary disease requiring visit to emergency department |
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| Agitation | General disorders | Systematic Assessment |
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| Alanine aminotransferase (ALT), high | Hepatobiliary disorders | Systematic Assessment | Blood test, grade 2 (DAIDS 2.0) |
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| Aspartate aminotransferase (AST), high | Hepatobiliary disorders | Systematic Assessment | Blood test, grade 2 (DAIDS 2.0) |
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| Alkaline phosphatase, high | Hepatobiliary disorders | Systematic Assessment | Blood test, grade 2 (DAIDS 2.0) |
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| Alopecia | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| Altered taste | General disorders | Systematic Assessment |
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| Automobile accident | Injury, poisoning and procedural complications | Systematic Assessment | Passenger, visit to ED, back injury, discharged home |
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| Back pain, generalized | Musculoskeletal and connective tissue disorders | Systematic Assessment |
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| Bilirubin, total, high | Hepatobiliary disorders | Systematic Assessment | Blood test, grade 2 or 3 (DAIDS 2.0) |
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| Blood urea nitrogen (BUN), high | Metabolism and nutrition disorders | Systematic Assessment | Blood test, range: 23-41 mg/dL |
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| Blood urea nitrogen (BUN), low | Metabolism and nutrition disorders | Systematic Assessment | Blood test, range: 5-6 mg/dL |
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| Chlamydia, new infection/exposure | Infections and infestations | Systematic Assessment | Treated for infection |
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| Constipation | Gastrointestinal disorders | Systematic Assessment | Grade 2 or 3 (DAIDS 2.0) |
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| Creatinine, blood, high | Hepatobiliary disorders | Systematic Assessment | Blood test, grade 2 (DAIDS 2.0) |
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| Cyst, subcutaneous | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| Darkening of urine | General disorders | Systematic Assessment |
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| Depressed mood | Psychiatric disorders | Systematic Assessment | Self-reported |
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| Diarrhea | Gastrointestinal disorders | Systematic Assessment | Grade 2 (DAIDS 2.0) |
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| Dizziness | General disorders | Systematic Assessment | Self-reported, intermittent |
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| Dry mouth | General disorders | Systematic Assessment | Self-reported |
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| Fatigue | General disorders | Systematic Assessment | Grade 2 (DAIDS 2.0) |
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| Flank pain, unilateral | General disorders | Systematic Assessment | Non-specific, self-limited |
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| Gastroenteritis, foodborne illness | Gastrointestinal disorders | Systematic Assessment | Self-reported |
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| Glucose, blood, high | Endocrine disorders | Systematic Assessment | Blood test, non-fasting, grade 2 or 3 (DAIDS 2.0) |
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| Glucose, blood, low | General disorders | Systematic Assessment | Blood test, non-fasting, grade 2 (DAIDS 2.0) |
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| Headache, non-specific | General disorders | Systematic Assessment | Intermittent, grade 2 (DAIDS 2.0) |
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| Headache, post-lumbar puncture | Nervous system disorders | Systematic Assessment | Post-LP postural headache requiring follow-up care |
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| Hypokalemia | General disorders | Systematic Assessment | Grade 2 (DAIDS 2.0) |
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| Incontinence, acute nocturnal | General disorders | Systematic Assessment | Self-limited |
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| Insomnia | General disorders | Systematic Assessment |
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| Joint pain, generalized | Musculoskeletal and connective tissue disorders | Systematic Assessment |
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| Joint pain, hip, unilateral | Musculoskeletal and connective tissue disorders | Systematic Assessment |
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| Joint pain, shoulder, unilateral | Musculoskeletal and connective tissue disorders | Systematic Assessment |
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| Lightheadedness | General disorders | Systematic Assessment |
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| Lymph node infection, neck | Infections and infestations | Systematic Assessment | Treated for infection |
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| Lymphadenopathy, cervical | Blood and lymphatic system disorders | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | Systematic Assessment | Grade 2 or 3 (DAIDS 2.0) |
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| Nephrolithiasis (kidney stone) | Renal and urinary disorders | Systematic Assessment |
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| Hypertensive episode | Cardiac disorders | Systematic Assessment | Grade 3 (DAIDS); context of diagnosed/treated hypertension, participant had not taken morning medications |
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| Nose bleed | General disorders | Systematic Assessment | Self-limited |
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| Polyuria | General disorders | Systematic Assessment | Self-limited |
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| Prostitis | Renal and urinary disorders | Systematic Assessment |
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| Psychotropic effects, non-specific | General disorders | Systematic Assessment |
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| Rash | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| Sexual dysfunction | Reproductive system and breast disorders | Systematic Assessment |
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| Sprain, ankle | Injury, poisoning and procedural complications | Systematic Assessment |
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| Syphilis, new infection/exposure | Infections and infestations | Systematic Assessment | Treated for infection |
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| Tinnitus, bilateral | General disorders | Systematic Assessment |
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| Tooth infection | Infections and infestations | Systematic Assessment | Treated for infection |
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| Upper respiratory infection | Infections and infestations | Systematic Assessment |
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| Urinary hesitancy | Renal and urinary disorders | Systematic Assessment |
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| Visual changes | Eye disorders | Systematic Assessment |
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| Vivid or disturbing dreams | General disorders | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | Systematic Assessment | Grade 2 (DAIDS 2.0) |
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| Weight loss | General disorders | Systematic Assessment | Grade 2 (DAIDS 2.0) |
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Not provided
Not provided
Not provided
| D001523 | Mental Disorders |
| D010880 |
| Piperidines |
| Superiority |
| Regression, Linear | 0.282 | Superiority |
| Superiority |
| Regression, Linear | 0.480 | Superiority |
| Superiority |
| Regression, Linear | 0.672 | Superiority |