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| ID | Type | Description | Link |
|---|---|---|---|
| H-27877 | Other Identifier | University of Maryland Baltimore |
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| Name | Class |
|---|---|
| Stanley Medical Research Institute | OTHER |
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This is a study of a new medication for the treatment of cognitive impairments (thinking difficulties) and negative symptoms in people with schizophrenia. The new medication is rasagiline. Rasagiline is a drug which has been approved by the Food and Drug Administration for the treatment of Parkinson's disease. It is used to treat cognitive problems.
The study will consist of two phases: a 4-week continued stability phase (lead-in phase) and a 12-week double-blind treatment phase. In the lead-in phase, subjects receiving antipsychotic medication, who manifest moderate to severe and persistent negative symptoms, will remain on their maintenance regimen for at least four weeks. The treatment phase will be a 12-week, parallel groups, double-blind, placebo-controlled trial of adjunctive rasagiline (1 mg/day), a selective MAO-B oxidase inhibitor.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Rasagiline | Active Comparator | Treatment with Rasagiline |
|
| Inactive pill | Placebo Comparator | Treatment with Placebo |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| rasagiline (Pharmacodynamics) | Drug | Rasagiline 1 mg/day for 12 weeks |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Negative Symptoms | The Scale for the Assessment of Negative Symptoms (SANS) rating scale was used to assess the negative symptoms of schizophrenia. Scores on the subscales are combined (summed) to compute a total score. There are a total of 17 subscales. Each subscale ranges from 0="Not at all" to 5="Severe". Every 4 weeks the summed subscale scores provide a total score for that week (0-85). Higher scores indicate more severe negative symptoms. | Every 4 weeks over a 12 week period |
| Cognitive Testing - Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Total Score | The RBANS is a brief, individually administered test designed to evaluate neuropsychological status of adults, ages 20-89. The 12 subtests measure attention, language, visuospatial/constructional abilities, and immediate and delayed memory. The raw scores from the subtests are scaled together to create index scores, and these are summed for conversion to a total scale score. Higher score equals a better outcome. The total index score range for the RBANS is 40-160. | Beginning of treatment phase (week 0) and end of treatment phase (week 12) |
| Cognitive Testing - N-Back Neurocognitive Task | The N-Back task is a sequential letter working memory task. D-prime was used to measure accuracy on the 0-back, 1-back, and 2-back conditions. D-prime scores range from 0 to 8.6. Higher scores are better. As memory load increases from 0 to 1, from 1 to 2, D-prime scores are expected to be lower. | Beginning of treatment phase (week 0) and end of treatment phase (week 12) |
| Cognitive Testing - Probabilistic Learning Task | To assess reward learning, participants used performance feedback to choose the most frequently rewarded item in each of three pairs of stimuli (one pair had reward probabilities: 80% vs 20%; one pair had reward probabilities of 70% vs 30%; one pair had the probabilities of 60% vs 40 %) (PL; Frank et al, 2004). A total of 240 trials were administered so each pair was seen 80 times. Higher scores represent more frequent choices of the optimal stimulus in each pair. The frequencies with which participants repeated an item choice that was rewarded on the previous presentation (win-stay) is also presented as a percentage. Similarly, the lose-shift score is the percentage of times that participants changed their choice for unrewarded items (lose-shift). The win-stay score serves as a measure of the impact of positive feedback on subsequent choices while the lost-shift score serves as a measure of the impact of negative feedback on subsequent choices. |
| Measure | Description | Time Frame |
|---|---|---|
| Extrapyramidal Symptoms | The Simpson Angus Scale (SAS; Simpson and Angus, 1970) was used to assess extrapyramidal symptoms (EPS). The assessment consists of 11 items, each rating the severity of potential symptoms of movement disorders. Total scores are calculated by summing the scores of each of the 11 items for a potential total score of 0-44, with higher scores indicating more severe EPS. | Baseline (Week 0) and End of Study (Week 12) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Robert W Buchanan, M.D. | University of Maryland, College Park | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Baltimore VA Medical Center | Baltimore | Maryland | 21201 | United States | ||
| Keypoint Mental health Center |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 25368372 | Derived | Buchanan RW, Weiner E, Kelly DL, Gold JM, Keller WR, Waltz JA, McMahon RP, Gorelick DA. Rasagiline in the Treatment of the Persistent Negative Symptoms of Schizophrenia. Schizophr Bull. 2015 Jul;41(4):900-8. doi: 10.1093/schbul/sbu151. Epub 2014 Nov 2. |
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Participants were excluded before assignment to treatment groups if they met any of the exclusion criteria, if they became clinically unstable, or they decided that the demands of the study were too great. 84 participants were enrolled into active participation; 57 started study treatment.
Subjects were recruited between May 2007-October 2011 from mental health clinics throughout the community.
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| ID | Title | Description |
|---|---|---|
| FG000 | Rasagiline | Treatment with Rasagiline |
| FG001 | Inactive Pill | Treatment with Placebo |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Rasagiline | Treatment with Rasagiline |
| BG001 | Inactive Pill | Treatment with Placebo |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| 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 Negative Symptoms | The Scale for the Assessment of Negative Symptoms (SANS) rating scale was used to assess the negative symptoms of schizophrenia. Scores on the subscales are combined (summed) to compute a total score. There are a total of 17 subscales. Each subscale ranges from 0="Not at all" to 5="Severe". Every 4 weeks the summed subscale scores provide a total score for that week (0-85). Higher scores indicate more severe negative symptoms. | Number of participants available for symptom efficacy analyses. | Posted | Mean | Standard Deviation | units on a scale | Every 4 weeks over a 12 week period |
|
During the 12-week Treatment Phase of the study.
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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 | Rasagiline | Treatment with Rasagiline | 0 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hospitalization | Psychiatric disorders | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| suicidal ideation | Psychiatric disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Robert Buchanan, M.D. | Maryland Psychiatric Research Center | 410-402-7876 | rbuchanan@som.umaryland.edu |
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| ID | Term |
|---|---|
| D012559 | Schizophrenia |
| D060825 | Cognitive Dysfunction |
| ID | Term |
|---|---|
| D019967 | Schizophrenia Spectrum and Other Psychotic Disorders |
| D001523 | Mental Disorders |
| D003072 | Cognition Disorders |
| D019965 | Neurocognitive Disorders |
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| ID | Term |
|---|---|
| C031967 | rasagiline |
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| Placebo |
| Drug |
Placebo 1 tablet each day |
|
| Beginning of treatment phase (week 0) and end of treatment phase (week 12) |
| Cognitive Testing - Delayed Discounting | The monetary choice questionnaire for hypothetical monetary rewards was used to assess delayed discounting (Kirby et al, 1999). The measure includes 27 items in which participants choose between a smaller, immediate reward (SIR) and a larger, delayed reward (LDR). There are three LDR sizes: small ($25-35), medium ($50-60) and large ($75-85). By examining the pattern of choices that participants make across the set of 27 items it is possible to calculate their delay discounting rate, termed K. The discount rate determines the steepness of the reduction in the present value of a reward with increases in the delay to the possible receipt of that reward. Thus, higher values in K represent greater discounting of the value of future rewards. With this measure K values can range between a low of 0.00016 to a high of 0.25. Higher K values have been linked to measures of impulsivity. Shown in the table are the K values observed when the future rewards were small, medium, or large. | Beginning of treatment phase (week 0) and end of treatment phase (week 12) |
| Number of Participants With Akathisia | The Barnes Akathisia Scale (BAS; Barnes, 1989) was used to assess akathisia, a type of extrapyramidal symptom. The global clinical assessment of akathisia score is rated on a scale from 0=Absent to 5=Severe Akathisia. | Baseline and every two weeks throughout the double-blind phase of the study, for up to 12 weeks. |
| Change in Persistent Positive Symptoms | The Brief Psychiatric Rating Scale (BPRS) positive symptom item total score was used to assess positive symptom change. The BPRS positive symptom items are: conceptual disorganization, hallucinatory behavior, unusual thought content, and suspiciousness. The total score is calculated by adding the scores for each item. Each scale ranges from "1=Not Present" to "7=Very Severe". The minimum score is 4 and the maximum score is 28. A higher score indicates a more severe positive symptom rating. | Every 4 weeks for 12 weeks. |
| Depressive Symptoms | The Calgary Depression Scale (CDS; Addington et al, 1997) total score was used to assess depressive symptoms over the course of the study. Total scores were calculated by summing the scores of each of the 9 items. Total scores can range from 0-27, with higher scores indicating more severe depressive symptoms. | Every 4 weeks for 12 weeks. |
| Global Change in Illness Severity | The Clinical Global Impression (CGI) severity of illness item was used to assess global changes. Scores on this item range from 1="Normal, not at all ill" to 7="Among the most extremely ill". | Every 4 weeks for 12 weeks. |
| Number of Participants Exhibiting Side Effects | The Side Effect Checklist (SEC) was used to assess side effects. The SEC is comprised of 22 common side effects, which are rated on a 1 (none)-4 (severe) scale. Side effects are determined to be clinically significant if there is a two or more point increase in severity from baseline, or any side effect that receives a severity rating of "4" (severe) at any point in the treatment phase of the study. | Every week for 12 weeks |
| Catonsville |
| Maryland |
| 21228 |
| United States |
| Maryland Psychiatric REsearch Center | Catonsville | Maryland | 21228 | United States |
| Mosaic Community Mental health Center | Catonsville | Maryland | 21228 | United States |
| Keypoint Mental health Center | Dundalk | Maryland | 21222 | United States |
| BG002 |
| Total |
Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
Treatment with Placebo
|
|
| Primary | Cognitive Testing - Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Total Score | The RBANS is a brief, individually administered test designed to evaluate neuropsychological status of adults, ages 20-89. The 12 subtests measure attention, language, visuospatial/constructional abilities, and immediate and delayed memory. The raw scores from the subtests are scaled together to create index scores, and these are summed for conversion to a total scale score. Higher score equals a better outcome. The total index score range for the RBANS is 40-160. | Subjects completing the cognitive testing at both time points. | Posted | Mean | Standard Deviation | units on a scale | Beginning of treatment phase (week 0) and end of treatment phase (week 12) |
|
|
|
| Primary | Cognitive Testing - N-Back Neurocognitive Task | The N-Back task is a sequential letter working memory task. D-prime was used to measure accuracy on the 0-back, 1-back, and 2-back conditions. D-prime scores range from 0 to 8.6. Higher scores are better. As memory load increases from 0 to 1, from 1 to 2, D-prime scores are expected to be lower. | Subjects completing the cognitive testing at both time points. | Posted | Mean | Standard Deviation | units on a scale | Beginning of treatment phase (week 0) and end of treatment phase (week 12) |
|
|
|
| Primary | Cognitive Testing - Probabilistic Learning Task | To assess reward learning, participants used performance feedback to choose the most frequently rewarded item in each of three pairs of stimuli (one pair had reward probabilities: 80% vs 20%; one pair had reward probabilities of 70% vs 30%; one pair had the probabilities of 60% vs 40 %) (PL; Frank et al, 2004). A total of 240 trials were administered so each pair was seen 80 times. Higher scores represent more frequent choices of the optimal stimulus in each pair. The frequencies with which participants repeated an item choice that was rewarded on the previous presentation (win-stay) is also presented as a percentage. Similarly, the lose-shift score is the percentage of times that participants changed their choice for unrewarded items (lose-shift). The win-stay score serves as a measure of the impact of positive feedback on subsequent choices while the lost-shift score serves as a measure of the impact of negative feedback on subsequent choices. | Subjects completing the cognitive testing at both time points. Results for lose shifts are calculated for 24 Rasagiline and 22 Placebo participants, due to missing data created by participants who had zero losses (and hence no need to shift) during both the 3rd and 4th blocks of trials. | Posted | Mean | Standard Deviation | percentage of optimal stimuli chosen | Beginning of treatment phase (week 0) and end of treatment phase (week 12) |
|
|
|
| Primary | Cognitive Testing - Delayed Discounting | The monetary choice questionnaire for hypothetical monetary rewards was used to assess delayed discounting (Kirby et al, 1999). The measure includes 27 items in which participants choose between a smaller, immediate reward (SIR) and a larger, delayed reward (LDR). There are three LDR sizes: small ($25-35), medium ($50-60) and large ($75-85). By examining the pattern of choices that participants make across the set of 27 items it is possible to calculate their delay discounting rate, termed K. The discount rate determines the steepness of the reduction in the present value of a reward with increases in the delay to the possible receipt of that reward. Thus, higher values in K represent greater discounting of the value of future rewards. With this measure K values can range between a low of 0.00016 to a high of 0.25. Higher K values have been linked to measures of impulsivity. Shown in the table are the K values observed when the future rewards were small, medium, or large. | Subjects completing the cognitive testing at both time points. | Posted | Geometric Mean | 95% Confidence Interval | units on a scale | Beginning of treatment phase (week 0) and end of treatment phase (week 12) |
|
|
|
| Secondary | Extrapyramidal Symptoms | The Simpson Angus Scale (SAS; Simpson and Angus, 1970) was used to assess extrapyramidal symptoms (EPS). The assessment consists of 11 items, each rating the severity of potential symptoms of movement disorders. Total scores are calculated by summing the scores of each of the 11 items for a potential total score of 0-44, with higher scores indicating more severe EPS. | SAS scores were collected at baseline on 28 Rasagiline and 29 Placebo patients. End of study scores were collected on 27 Rasagiline and 27 Placebo patients, including 5 patients who withdrew before Week 12 (1 Rasagiline patient at Week 4, 1 Placebo participant each at Weeks 3 and 6, and two Placebo participants at Week 8). | Posted | Mean | Standard Deviation | units on a scale | Baseline (Week 0) and End of Study (Week 12) |
|
|
|
| Secondary | Number of Participants With Akathisia | The Barnes Akathisia Scale (BAS; Barnes, 1989) was used to assess akathisia, a type of extrapyramidal symptom. The global clinical assessment of akathisia score is rated on a scale from 0=Absent to 5=Severe Akathisia. | Barnes Akathisia Scales at baseline and end of study were collected for 26 participants each in the rasagiline and placebo groups. End of study ratings were collected at week 12, except for 4 placebo participants (1 participant each at weeks 3 and 6, and two at week 8). | Posted | Count of Participants | Participants | Baseline and every two weeks throughout the double-blind phase of the study, for up to 12 weeks. |
|
|
|
| Secondary | Change in Persistent Positive Symptoms | The Brief Psychiatric Rating Scale (BPRS) positive symptom item total score was used to assess positive symptom change. The BPRS positive symptom items are: conceptual disorganization, hallucinatory behavior, unusual thought content, and suspiciousness. The total score is calculated by adding the scores for each item. Each scale ranges from "1=Not Present" to "7=Very Severe". The minimum score is 4 and the maximum score is 28. A higher score indicates a more severe positive symptom rating. | Number of participants available for symptom efficacy analyses. | Posted | Mean | Standard Deviation | units on a scale | Every 4 weeks for 12 weeks. |
|
|
|
| Secondary | Depressive Symptoms | The Calgary Depression Scale (CDS; Addington et al, 1997) total score was used to assess depressive symptoms over the course of the study. Total scores were calculated by summing the scores of each of the 9 items. Total scores can range from 0-27, with higher scores indicating more severe depressive symptoms. | Number of participants available for symptom efficacy analyses. | Posted | Mean | Standard Deviation | units on a scale | Every 4 weeks for 12 weeks. |
|
|
|
| Secondary | Global Change in Illness Severity | The Clinical Global Impression (CGI) severity of illness item was used to assess global changes. Scores on this item range from 1="Normal, not at all ill" to 7="Among the most extremely ill". | Number of participants available for symptom efficacy analyses. | Posted | Mean | Standard Deviation | units on a scale | Every 4 weeks for 12 weeks. |
|
|
|
| Secondary | Number of Participants Exhibiting Side Effects | The Side Effect Checklist (SEC) was used to assess side effects. The SEC is comprised of 22 common side effects, which are rated on a 1 (none)-4 (severe) scale. Side effects are determined to be clinically significant if there is a two or more point increase in severity from baseline, or any side effect that receives a severity rating of "4" (severe) at any point in the treatment phase of the study. | One placebo patient for whom a baseline side effects checklist was excluded from these analyses. | Posted | Count of Participants | Participants | Every week for 12 weeks |
|
|
|
| 28 |
| 1 |
| 28 |
| 1 |
| 28 |
| EG001 | Inactive Pill | Treatment with Placebo | 0 | 29 | 0 | 29 | 3 | 29 |
| increased urinary frequency | Renal and urinary disorders | Systematic Assessment |
|
| conceptual disorganization | Psychiatric disorders | Systematic Assessment |
|
| tooth problems | General disorders | Systematic Assessment |
|
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| Change |
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| 0-Back: Change |
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| 1-Back: Week 0 |
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| 1-Back: Week 12 |
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| 1-Back: Change |
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| 2-Back: Week 0 |
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| 2-Back: Week 12 |
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| 2-Back: Change |
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| 80 vs 20: Week 12 |
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| 80 vs 20: Change |
|
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| 70 vs 30: Week 0 |
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| 70 vs 30: Week 12 |
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| 70 vs 30: Change |
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| 60 vs 40: Week 0 |
|
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| 60 vs 40: Week 12 |
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| 60 vs 40: Change |
|
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| Lose Shifts: Week 0 |
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| Lose Shifts: Week 12 |
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| Lose Shifts: Change |
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| Win Stays: Week 0 |
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| Win Stays: Week 12 |
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| Win Stays: Change |
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| Medium Reward: Week 0 |
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| Medium Reward: Week 12 |
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| Small Reward: Week 0 |
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| Small Reward: Week 12 |
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| Week 12 |
|
|
| Change |
|
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| Score 1=Questionable : Baseline |
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| Score 1=Questionable : End of Study |
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| Score 2=Mild Akathisia : Baseline |
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| Score 2=Mild Akathisia : End of Study |
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| Score 3=Moderate Akathisia : Baseline |
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| Score 3=Moderate Akathisia : End of Study |
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| Week 4 |
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| Week 8 |
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| Week 12 |
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| Week 4 |
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| Week 8 |
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| Week 12 |
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| Week 4 |
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| Week 8 |
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| Week 12 |
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| Bruising Easily |
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| Constipation |
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| Diarrhea |
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| Dizziness |
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| Dry Mouth |
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| Enuresis |
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| Fever |
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| Headache |
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| Hypersalivation |
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| Insomnia |
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| Malaise |
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| Mucosal Ulceration |
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| Nausea |
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| Rash |
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| Restlessness |
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| Sedation |
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| Sore Throat |
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| Stiffness |
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| Tremor |
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| Urticaria |
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| Vomiting |
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| Weight Loss |
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