Parkinson's Disease
Conditions
Keywords
Parkinson's Disease, UPDRS, Clinical Global Evaluation Illness Severity score, Clinical Global Evaluation Improvement, B-SIT, SCOPA - Sleep Daytime Sleepiness, PDQ -39, SCOPA - Cognition, Levodopa, rasagiline, Dopamine Agonist Therapy, monoamine oxidase type B inhibitor
Brief summary
To assess the efficacy of rasagiline 1 mg as a first add-on treatment to dopamine agonist therapy in early Parkinson Disease (PD) patients, , not optimally controlled on dopamine agonists as compared to placebo.
Interventions
DRUGRasagiline
1mg tablet daily for 18 weeks
DRUGPlacebo
one tablet daily for 18 weeks
Sponsors
H. Lundbeck A/S
Teva Neuroscience, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
30 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* receiving stable dose of oral ropinirole or pramipexole whose symptoms are not optimally controlled or whose oral dopamine agonist titration regimen was truncated due to intolerability: * 1\) Minimum dose of agonist will be 6 mg/day for ropinirole and 1.0 mg/day for pramipexole * 2\) Stable dopamine agonist treatment must have been ongoing for ≥ 30 days, no longer than 5 years preceding baseline * Males and females. Women of childbearing potential must agree to practice an acceptable method of birth control. * Idiopathic Parkinson Disease confirmed at baseline by presence of at least 2 cardinal signs (resting tremor, bradykinesia, rigidity), w/o other known or suspected cause of Parkinsonism * Hoehn & Yahr \> 1 (symptoms on only one side of the body) with treatment and \< 3 (mild to moderate bilateral disease; some postural instability; physically independent). * Dopamine agonist dose must be stable for ≥30 days preceding the baseline visit. * For patients who are receiving amantadine or anticholinergics, the dose must have been stable for ≥30 days prior to screening. * Medically stable outpatients (Investigator's judgment).
Exclusion criteria
* receive rasagiline or other monoamine oxidase (MAO) inhibitors 60 days preceding baseline * receive levodopa \> 21 consecutive days within 90 days prior baseline * moderate to severe motor fluctuations * hepatic impairment * investigational medications 30 days preceding baseline * dopamine agonist use \> 5 years prior to baseline * major depression as defined by Beck Depression Inventory (BDI) short form score greater than 14 * significant cognitive impairment as defined by Mini-Mental State Exam (MMSE) score less than 26. * impulse control disorder (ICD) based on the Questionnaire for Impulsive-compulsive Disorders in Parkinson's Disease form (QUIP). * pregnant or lactating or planning on becoming pregnant in the next 18 weeks * uncontrolled hypertension. Patients whose hypertension is controlled with medications are eligible. * Concomitant monoamine oxidase (MAO) inhibitors or medicines contraindicated w/ MAO inhibitors not allowed
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Week 18 in the Unified Parkinson's Disease Rating Scale (UPDRS) Total Score for Parts I, II and III | Day 0 (baseline), Week 18 | The UPDRS was developed as a comprehensive tool to monitor the impact of Parkinson's Disease and the degree of disability caused. Version 3 of UPDRS contains four parts, three of which are totaled and reported in this outcome. Part I is a clinician's evaluation of mentation (mental activity or state of mind), cognition (ability to acquire knowledge), behaviour and mood. Part II is the participants' evaluation of the disease's impact on normal activities. Part III is a clinician's evaluation of motor function. Parts I, II, and III contain a total of 31 questions, which are each rated on a scale of 0 (normal or no disease effect) to 4 (maximum negative effect), for a total scale of 0-124. Negative change from baseline values indicate improvement. All site raters (medical doctor \[MD\], doctor of osteopathy \[DO\], nurse practitioner, or physician assistant) received training on how to complete the UPDRS. The same site rater completed the UPDRS at all visits. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Week 18 in the Unified Parkinson's Disease Rating Scale (UPDRS) Total Score for Part II - Activities of Daily Living | Day 0 (baseline), Week 18 | The UPDRS was developed as a comprehensive tool to monitor the impact of Parkinson's Disease and the degree of disability caused. UPDRS contains four parts, the second of which is reported in this outcome. Part II is the participants' evaluation of the disease's impact on normal activities. Part II contains a total of 13 questions, which are each rated on a scale of 0 (normal or no disease effect) to 4 (maximum negative effect), for a total scale of 0-52. Negative change from baseline values indicate improvement. |
| Change From Baseline to Week 18 in the Unified Parkinson's Disease Rating Scale (UPDRS) Total Score for Part III - Motor Function | Day 0 (baseline), Week 18 | The UPDRS was developed as a comprehensive tool to monitor the impact of Parkinson's Disease and the degree of disability caused. Version 3 of UPDRS contains four parts, the third of which is reported in this outcome. Part III is a clinician's evaluation of motor function. Part III contains 14 questions, which are each rated on a scale of 0 (normal or no disease effect) to 4 (maximum negative effect), for a total scale of 0-56. Negative change from baseline values indicate improvement. All site raters (medical doctor \[MD\], doctor of osteopathy \[DO\], nurse practitioner, or physician assistant) received training on how to complete the UPDRS. The same site rater completed the UPDRS at all visits |
| Clinical Global Improvement (CGI) Score at Week 18 As Assessed by the Site Rater | 18 weeks | CGI is used by the site rater to rate participants total improvement during the study whether or not, in the investigators' judgment, it is due entirely to drug treatment. Specifically, site raters are asked to compare the participants condition at the beginning of the study to his/her condition at Week 18, how much has he/she changed? Answers are 0 (not assessed), 1 (very much improved), 2 (much improved), 3 (minimally improved), 4 (no change), 5 (minimally worse), 6 (much worse), 7(very much worse). Site raters can be the medical doctor \[MD\], doctor of osteopathy \[DO\], nurse practitioner, or physician assistant. |
| Clinical Global Improvement (CGI) Score at Week 18 As Assessed by the Participant | 18 weeks | CGI is used by the participant to rate his/her total improvement during the study. Specifically, participants are asked to compare their condition at the beginning of the study to his/her condition at Week 18, how much has he/she changed? Answers are 0 (not assessed), 1 (very much improved), 2 (much improved), 3 (minimally improved), 4 (no change), 5 (minimally worse), 6 (much worse), 7(very much worse). |
| Illness Severity Score at Day 0 and Week 18 As Assessed by the Site Rater | Day 0 (baseline), Week 18 | Site raters were asked: Considering your total clinical experience with the particular population, how ill is the patient at this time? Answers were based on a 0-7 scale, with 0=not assessed, 1= normal, not at all ill, and 7= among the most extremely ill of patients. Site raters can be the medical doctor \[MD\], doctor of osteopathy \[DO\], nurse practitioner, or physician assistant. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Rasagiline 1 mg Participants took a 1 mg rasagiline tablet orally each day for 18 weeks. | 162 |
| Placebo Participants took a matching placebo tablet once daily for 18 weeks. | 164 |
| Total | 326 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 13 | 7 |
| Overall Study | Lost to Follow-up | 2 | 1 |
| Overall Study | Protocol Violation | 3 | 4 |
| Overall Study | Treatment failure | 0 | 2 |
| Overall Study | Withdrawal by Subject | 1 | 5 |
Baseline characteristics
| Characteristic | Rasagiline 1 mg | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 62.3 years STANDARD_DEVIATION 9.27 | 62.8 years STANDARD_DEVIATION 10.06 | 62.5 years STANDARD_DEVIATION 9.67 |
| Age, Customized 30 to <65 years | 97 participants | 89 participants | 186 participants |
| Age, Customized 65 to <75 years | 49 participants | 60 participants | 109 participants |
| Age, Customized >=75 years | 16 participants | 15 participants | 31 participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 7 Participants | 9 Participants | 16 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 154 Participants | 155 Participants | 309 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants |
| Parkinson's Disease Duration | 2.19 years STANDARD_DEVIATION 2.224 | 2.07 years STANDARD_DEVIATION 1.94 | 2.13 years STANDARD_DEVIATION 2.083 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 3 Participants | 5 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 7 Participants | 10 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 156 Participants | 151 Participants | 307 Participants |
| Sex: Female, Male Female | 53 Participants | 53 Participants | 106 Participants |
| Sex: Female, Male Male | 109 Participants | 111 Participants | 220 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 44 / 164 | 55 / 162 |
| serious Total, serious adverse events | 5 / 164 | 8 / 162 |
Outcome results
Primary
Change From Baseline to Week 18 in the Unified Parkinson's Disease Rating Scale (UPDRS) Total Score for Parts I, II and III
The UPDRS was developed as a comprehensive tool to monitor the impact of Parkinson's Disease and the degree of disability caused. Version 3 of UPDRS contains four parts, three of which are totaled and reported in this outcome. Part I is a clinician's evaluation of mentation (mental activity or state of mind), cognition (ability to acquire knowledge), behaviour and mood. Part II is the participants' evaluation of the disease's impact on normal activities. Part III is a clinician's evaluation of motor function. Parts I, II, and III contain a total of 31 questions, which are each rated on a scale of 0 (normal or no disease effect) to 4 (maximum negative effect), for a total scale of 0-124. Negative change from baseline values indicate improvement. All site raters (medical doctor \[MD\], doctor of osteopathy \[DO\], nurse practitioner, or physician assistant) received training on how to complete the UPDRS. The same site rater completed the UPDRS at all visits.
Time frame: Day 0 (baseline), Week 18
Population: Modified intent to treat population - all randomized participants who took at least 1 dose of study drug and had both a baseline and at least 1 post-baseline efficacy assessment. Several participants had missing UPDRS items at baseline and during treatment; therefore the total UPDRS for these participants was set as missing.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Rasagiline 1 mg | Change From Baseline to Week 18 in the Unified Parkinson's Disease Rating Scale (UPDRS) Total Score for Parts I, II and III | -3.6 units on a scale | Standard Error 0.68 |
| Placebo | Change From Baseline to Week 18 in the Unified Parkinson's Disease Rating Scale (UPDRS) Total Score for Parts I, II and III | -1.2 units on a scale | Standard Error 0.68 |
p-value: 0.01295% CI: [-4.3, -0.5]ANCOVA
Secondary
Change From Baseline to Week 18 in the Unified Parkinson's Disease Rating Scale (UPDRS) Total Score for Part II - Activities of Daily Living
The UPDRS was developed as a comprehensive tool to monitor the impact of Parkinson's Disease and the degree of disability caused. UPDRS contains four parts, the second of which is reported in this outcome. Part II is the participants' evaluation of the disease's impact on normal activities. Part II contains a total of 13 questions, which are each rated on a scale of 0 (normal or no disease effect) to 4 (maximum negative effect), for a total scale of 0-52. Negative change from baseline values indicate improvement.
Time frame: Day 0 (baseline), Week 18
Population: Modified intent to treat population - all randomized participants who took at least 1 dose of study drug and had both a baseline and at least 1 post-baseline efficacy assessment. Several participants had missing UPDRS items at baseline and during treatment for subscale II, and therefore that subscale was set as missing.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Rasagiline 1 mg | Change From Baseline to Week 18 in the Unified Parkinson's Disease Rating Scale (UPDRS) Total Score for Part II - Activities of Daily Living | -0.1 units on a scale | Standard Error 0.27 |
| Placebo | Change From Baseline to Week 18 in the Unified Parkinson's Disease Rating Scale (UPDRS) Total Score for Part II - Activities of Daily Living | 0.3 units on a scale | Standard Error 0.27 |
p-value: 0.30195% CI: [-1.1, 0.3]ANCOVA
Secondary
Change From Baseline to Week 18 in the Unified Parkinson's Disease Rating Scale (UPDRS) Total Score for Part III - Motor Function
The UPDRS was developed as a comprehensive tool to monitor the impact of Parkinson's Disease and the degree of disability caused. Version 3 of UPDRS contains four parts, the third of which is reported in this outcome. Part III is a clinician's evaluation of motor function. Part III contains 14 questions, which are each rated on a scale of 0 (normal or no disease effect) to 4 (maximum negative effect), for a total scale of 0-56. Negative change from baseline values indicate improvement. All site raters (medical doctor \[MD\], doctor of osteopathy \[DO\], nurse practitioner, or physician assistant) received training on how to complete the UPDRS. The same site rater completed the UPDRS at all visits
Time frame: Day 0 (baseline), Week 18
Population: Modified intent to treat population - all randomized participants who took at least 1 dose of study drug and had both a baseline and at least 1 post-baseline efficacy assessment. Several participants had missing UPDRS items at baseline and during treatment for subscale III, and therefore that subscale was set as missing.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Rasagiline 1 mg | Change From Baseline to Week 18 in the Unified Parkinson's Disease Rating Scale (UPDRS) Total Score for Part III - Motor Function | -3.4 units on a scale | Standard Error 0.48 |
| Placebo | Change From Baseline to Week 18 in the Unified Parkinson's Disease Rating Scale (UPDRS) Total Score for Part III - Motor Function | -1.6 units on a scale | Standard Error 0.48 |
p-value: 0.00795% CI: [-3.1, -0.5]ANCOVA
Secondary
Clinical Global Improvement (CGI) Score at Week 18 As Assessed by the Participant
CGI is used by the participant to rate his/her total improvement during the study. Specifically, participants are asked to compare their condition at the beginning of the study to his/her condition at Week 18, how much has he/she changed? Answers are 0 (not assessed), 1 (very much improved), 2 (much improved), 3 (minimally improved), 4 (no change), 5 (minimally worse), 6 (much worse), 7(very much worse).
Time frame: 18 weeks
Population: Modified intent to treat
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rasagiline 1 mg | Clinical Global Improvement (CGI) Score at Week 18 As Assessed by the Participant | Not assessed (0) | 0 participants |
| Rasagiline 1 mg | Clinical Global Improvement (CGI) Score at Week 18 As Assessed by the Participant | Very much improved (1) | 7 participants |
| Rasagiline 1 mg | Clinical Global Improvement (CGI) Score at Week 18 As Assessed by the Participant | Much improved (2) | 18 participants |
| Rasagiline 1 mg | Clinical Global Improvement (CGI) Score at Week 18 As Assessed by the Participant | Minimally improved (3) | 39 participants |
| Rasagiline 1 mg | Clinical Global Improvement (CGI) Score at Week 18 As Assessed by the Participant | No change (4) | 52 participants |
| Rasagiline 1 mg | Clinical Global Improvement (CGI) Score at Week 18 As Assessed by the Participant | Minimally worse (5) | 36 participants |
| Rasagiline 1 mg | Clinical Global Improvement (CGI) Score at Week 18 As Assessed by the Participant | Much worse (6) | 5 participants |
| Rasagiline 1 mg | Clinical Global Improvement (CGI) Score at Week 18 As Assessed by the Participant | Very much worse (7) | 2 participants |
| Placebo | Clinical Global Improvement (CGI) Score at Week 18 As Assessed by the Participant | Very much worse (7) | 1 participants |
| Placebo | Clinical Global Improvement (CGI) Score at Week 18 As Assessed by the Participant | Not assessed (0) | 1 participants |
| Placebo | Clinical Global Improvement (CGI) Score at Week 18 As Assessed by the Participant | No change (4) | 52 participants |
| Placebo | Clinical Global Improvement (CGI) Score at Week 18 As Assessed by the Participant | Very much improved (1) | 7 participants |
| Placebo | Clinical Global Improvement (CGI) Score at Week 18 As Assessed by the Participant | Much worse (6) | 8 participants |
| Placebo | Clinical Global Improvement (CGI) Score at Week 18 As Assessed by the Participant | Much improved (2) | 18 participants |
| Placebo | Clinical Global Improvement (CGI) Score at Week 18 As Assessed by the Participant | Minimally worse (5) | 35 participants |
| Placebo | Clinical Global Improvement (CGI) Score at Week 18 As Assessed by the Participant | Minimally improved (3) | 40 participants |
p-value: 0.996Cochran-Mantel-Haenszel
Secondary
Clinical Global Improvement (CGI) Score at Week 18 As Assessed by the Site Rater
CGI is used by the site rater to rate participants total improvement during the study whether or not, in the investigators' judgment, it is due entirely to drug treatment. Specifically, site raters are asked to compare the participants condition at the beginning of the study to his/her condition at Week 18, how much has he/she changed? Answers are 0 (not assessed), 1 (very much improved), 2 (much improved), 3 (minimally improved), 4 (no change), 5 (minimally worse), 6 (much worse), 7(very much worse). Site raters can be the medical doctor \[MD\], doctor of osteopathy \[DO\], nurse practitioner, or physician assistant.
Time frame: 18 weeks
Population: Modified intent to treat
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rasagiline 1 mg | Clinical Global Improvement (CGI) Score at Week 18 As Assessed by the Site Rater | Not assessed (0) | 0 participants |
| Rasagiline 1 mg | Clinical Global Improvement (CGI) Score at Week 18 As Assessed by the Site Rater | Very much improved (1) | 5 participants |
| Rasagiline 1 mg | Clinical Global Improvement (CGI) Score at Week 18 As Assessed by the Site Rater | Much improved (2) | 21 participants |
| Rasagiline 1 mg | Clinical Global Improvement (CGI) Score at Week 18 As Assessed by the Site Rater | Minimally improved (3) | 45 participants |
| Rasagiline 1 mg | Clinical Global Improvement (CGI) Score at Week 18 As Assessed by the Site Rater | No change (4) | 63 participants |
| Rasagiline 1 mg | Clinical Global Improvement (CGI) Score at Week 18 As Assessed by the Site Rater | Minimally worse (5) | 21 participants |
| Rasagiline 1 mg | Clinical Global Improvement (CGI) Score at Week 18 As Assessed by the Site Rater | Much worse (6) | 3 participants |
| Rasagiline 1 mg | Clinical Global Improvement (CGI) Score at Week 18 As Assessed by the Site Rater | Very much worse (7) | 1 participants |
| Placebo | Clinical Global Improvement (CGI) Score at Week 18 As Assessed by the Site Rater | Very much worse (7) | 1 participants |
| Placebo | Clinical Global Improvement (CGI) Score at Week 18 As Assessed by the Site Rater | Not assessed (0) | 1 participants |
| Placebo | Clinical Global Improvement (CGI) Score at Week 18 As Assessed by the Site Rater | No change (4) | 53 participants |
| Placebo | Clinical Global Improvement (CGI) Score at Week 18 As Assessed by the Site Rater | Very much improved (1) | 5 participants |
| Placebo | Clinical Global Improvement (CGI) Score at Week 18 As Assessed by the Site Rater | Much worse (6) | 1 participants |
| Placebo | Clinical Global Improvement (CGI) Score at Week 18 As Assessed by the Site Rater | Much improved (2) | 20 participants |
| Placebo | Clinical Global Improvement (CGI) Score at Week 18 As Assessed by the Site Rater | Minimally worse (5) | 42 participants |
| Placebo | Clinical Global Improvement (CGI) Score at Week 18 As Assessed by the Site Rater | Minimally improved (3) | 39 participants |
p-value: 0.255Cochran-Mantel-Haenszel
Secondary
Illness Severity Score at Day 0 and Week 18 As Assessed by the Site Rater
Site raters were asked: Considering your total clinical experience with the particular population, how ill is the patient at this time? Answers were based on a 0-7 scale, with 0=not assessed, 1= normal, not at all ill, and 7= among the most extremely ill of patients. Site raters can be the medical doctor \[MD\], doctor of osteopathy \[DO\], nurse practitioner, or physician assistant.
Time frame: Day 0 (baseline), Week 18
Population: Modified intent to treat
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rasagiline 1 mg | Illness Severity Score at Day 0 and Week 18 As Assessed by the Site Rater | Week 18: Not assessed (0) | 0 participants |
| Rasagiline 1 mg | Illness Severity Score at Day 0 and Week 18 As Assessed by the Site Rater | Day 0: Moderately Ill (4) | 39 participants |
| Rasagiline 1 mg | Illness Severity Score at Day 0 and Week 18 As Assessed by the Site Rater | Week 18: Normal, not at all ill (1) | 10 participants |
| Rasagiline 1 mg | Illness Severity Score at Day 0 and Week 18 As Assessed by the Site Rater | Day 0: Borderline ill (2) | 18 participants |
| Rasagiline 1 mg | Illness Severity Score at Day 0 and Week 18 As Assessed by the Site Rater | Week 18: Borderline ill (2) | 28 participants |
| Rasagiline 1 mg | Illness Severity Score at Day 0 and Week 18 As Assessed by the Site Rater | Day 0: Markedly ill (5) | 1 participants |
| Rasagiline 1 mg | Illness Severity Score at Day 0 and Week 18 As Assessed by the Site Rater | Week 18: Mildly ill (3) | 90 participants |
| Rasagiline 1 mg | Illness Severity Score at Day 0 and Week 18 As Assessed by the Site Rater | Day 0: Not assessed (0) | 0 participants |
| Rasagiline 1 mg | Illness Severity Score at Day 0 and Week 18 As Assessed by the Site Rater | Week 18: Moderately ill (4) | 29 participants |
| Rasagiline 1 mg | Illness Severity Score at Day 0 and Week 18 As Assessed by the Site Rater | Day 0: Severely ill (6) | 0 participants |
| Rasagiline 1 mg | Illness Severity Score at Day 0 and Week 18 As Assessed by the Site Rater | Week 18: Markedly ill (5) | 2 participants |
| Rasagiline 1 mg | Illness Severity Score at Day 0 and Week 18 As Assessed by the Site Rater | Day 0: Mildly Ill (3) | 95 participants |
| Rasagiline 1 mg | Illness Severity Score at Day 0 and Week 18 As Assessed by the Site Rater | Week 18: Severely ill (6) | 0 participants |
| Rasagiline 1 mg | Illness Severity Score at Day 0 and Week 18 As Assessed by the Site Rater | Day 0: Among the most extremely ill (7) | 0 participants |
| Rasagiline 1 mg | Illness Severity Score at Day 0 and Week 18 As Assessed by the Site Rater | Week 18: Among the most extremely ill (7) | 0 participants |
| Rasagiline 1 mg | Illness Severity Score at Day 0 and Week 18 As Assessed by the Site Rater | Day 0: Normal, not at all ill (1) | 4 participants |
| Placebo | Illness Severity Score at Day 0 and Week 18 As Assessed by the Site Rater | Week 18: Among the most extremely ill (7) | 0 participants |
| Placebo | Illness Severity Score at Day 0 and Week 18 As Assessed by the Site Rater | Day 0: Not assessed (0) | 0 participants |
| Placebo | Illness Severity Score at Day 0 and Week 18 As Assessed by the Site Rater | Day 0: Borderline ill (2) | 26 participants |
| Placebo | Illness Severity Score at Day 0 and Week 18 As Assessed by the Site Rater | Day 0: Mildly Ill (3) | 100 participants |
| Placebo | Illness Severity Score at Day 0 and Week 18 As Assessed by the Site Rater | Day 0: Moderately Ill (4) | 28 participants |
| Placebo | Illness Severity Score at Day 0 and Week 18 As Assessed by the Site Rater | Day 0: Markedly ill (5) | 2 participants |
| Placebo | Illness Severity Score at Day 0 and Week 18 As Assessed by the Site Rater | Day 0: Severely ill (6) | 0 participants |
| Placebo | Illness Severity Score at Day 0 and Week 18 As Assessed by the Site Rater | Day 0: Among the most extremely ill (7) | 0 participants |
| Placebo | Illness Severity Score at Day 0 and Week 18 As Assessed by the Site Rater | Week 18: Not assessed (0) | 2 participants |
| Placebo | Illness Severity Score at Day 0 and Week 18 As Assessed by the Site Rater | Week 18: Normal, not at all ill (1) | 5 participants |
| Placebo | Illness Severity Score at Day 0 and Week 18 As Assessed by the Site Rater | Week 18: Borderline ill (2) | 33 participants |
| Placebo | Illness Severity Score at Day 0 and Week 18 As Assessed by the Site Rater | Week 18: Mildly ill (3) | 89 participants |
| Placebo | Illness Severity Score at Day 0 and Week 18 As Assessed by the Site Rater | Week 18: Moderately ill (4) | 31 participants |
| Placebo | Illness Severity Score at Day 0 and Week 18 As Assessed by the Site Rater | Week 18: Markedly ill (5) | 1 participants |
| Placebo | Illness Severity Score at Day 0 and Week 18 As Assessed by the Site Rater | Week 18: Severely ill (6) | 1 participants |
| Placebo | Illness Severity Score at Day 0 and Week 18 As Assessed by the Site Rater | Day 0: Normal, not at all ill (1) | 5 participants |
p-value: 0.967Cochran-Mantel-Haenszel