Idiopathic Parkinson Disease
Conditions
Keywords
Parkinson disease, Safinamide
Brief summary
Primary objective: • To evaluate the potential efficacy of safinamide 100 mg once daily (OD), compared with placebo, as add-on therapy for PD-related chronic pain Secondary objectives: * Percentage of pain responders * Clinical Global Impression for pain * Patient Global Impression for pain * Reduction in use of pain drugs * Mood * Motor and non-motor symptoms Safety Objectives: • Safety and tolerability
Detailed description
This is a Phase IV, international, multicentre, randomised, double-blind, placebo controlled study in idiopathic Parkinson's disease (IPD) patients, experiencing motor fluctuations and PD-related chronic pain while on stable doses of levodopa (L-Dopa), to Evaluate the Efficacy and Safety of Safinamide 100 mg Once Daily, as Add-On Therapy. The study consisted of: * A screening period of up to 1 to 2 weeks. * A treatment period of 16 weeks. * A telephone follow-up call at 1 week after the end of treatment. Eligible subjects were randomly assigned in a ratio of 2:1 to receive either safinamide (50 mg or 100 mg) or matching placebo. At Day 1, eligible subjects entered the treatment period to receive safinamide 50 mg (from Day 1 to Day 7) and then 100 mg (from Day 8 onwards) orally OD. After completion of all baseline assessments, subjects received the first dose of study drug at the study center and, thereafter, study drug was to be taken at home each morning along with their first morning dose of L-DOPA and other (if any) PD medications. On Day 8, the dose of study drug was increased, at home, to 100 mg OD. Each subject received treatment for 16 weeks, with visits at Week 0/Day 1 (baseline) and at Weeks 4, 8, and 16 (or early termination). From Day 1 onwards, subjects recorded the use of as-needed (PRN) medications along with indicating the worst pain they experienced on a daily basis.
Interventions
50 mg, 100 mg
50 mg, 100 mg
Sponsors
Zambon SpA
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
30 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Participant must be 30 years of age or older, at the time of signing the informed consent. 2. Diagnosed with IPD by using the United Kingdom Parkinson's Disease Society Brain Bank criteria for more than 5 years duration. 3. Receiving treatment with a stable dose of oral L-Dopa (including controlled release \[CR\], immediate release \[IR\] or a combination of CR/IR), with and without benserazide/carbidopa, with or without addition of a catechol O-methyltransferase (COMT) inhibitor and may be receiving concomitant treatment with stable doses of a dopamine agonist, an anticholinergic and/or amantadine for at least 4 weeks prior to the randomisation (baseline visit). 4. Hoehn and Yahr stage between 2-3 (inclusive) during the ON phase at the screening visit. 5. Experiencing motor fluctuations following optimum titration of treatment medications and within the 4 weeks immediately prior to randomisation. 6. Experiencing chronic pain (i.e. ongoing for ≥3 months prior to screening visit); the Investigator must consider chronic pain directly related to PD and not explained by any other health problem (e.g. peripheral neuropathy, organ disease or arthritis pain) OR consider the intensity of chronic pain specifically aggravated by PD. 7. If taking regular analgesics, the treatment regimen should be stable in the 4 weeks prior to the randomisation visit. 8. Able to maintain an accurate and complete electronic diary with the help of a caregiver. 9. Male or female •A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies: i.Not a woman of childbearing potential (WOCBP) OR ii.A WOCBP who agrees to follow the contraceptive guidance 10. Capable of giving signed informed consent
Exclusion criteria
1. Any form of Parkinsonism other than IPD. 2. Diagnosis of chronic migraine (\>15 days per month) or cancer pain. 3. History of bipolar disorder, depression, schizophrenia or other psychotic disorder requiring treatment with neuroleptics. 4. History of dementia or cognitive dysfunction. 5. Severe, peak dose or biphasic dyskinesia. 6. Unpredictable or widely swinging fluctuations. 7. Ophthalmologic history including any of the following conditions: albinism, uveitis, retinitis pigmentosa, retinal degeneration, active retinopathy, severe progressive diabetic retinopathy, inherited retinopathy or family history of hereditary retinal disease. 8. Moderate or severe liver failure using the Child-Pugh classification score. 9. History of drug and/or alcohol abuse within 12 months prior to screening as defined by the current edition of the Diagnostic and Statistical Manual of Mental Disorders. 10. Allergy/sensitivity, intolerance or contraindications to Safinamide. 11. Treatment with monoamine oxidase inhibitors (MAOIs), levodopa infusion, pethidine, fluoxetine, fluvoxamine less than 4 weeks prior to the randomisation visit 12. Use of any investigational drug or device within 30 days prior to screening or 5 half-lives, whichever is the longest 13. Previous treatment with Safinamide in the 9 months before the screening visit 14. Mini-Mental State Exam (MMSE) total score \<24 at screening. 15. NRS score ≤ 4 points at randomization visit. 16. Any clinically significant condition which, in the opinion of the Investigator, would not be compatible with study participation or represent a risk for participants while in the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Week 16 in Pain Severity (NRS-11 Scale) - Full Analysis Set | Baseline and Week 16 | To evaluate the potential efficacy of safinamide 100 (mg od), compared to placebo, as add-on therapy, for change pain severity (average worst pain experienced in the last 7 days), as assessed by an 11-point Numerical Rating Scale (NRS). Based on this scale, 0 point is the minimum and 10 point is the maximum. The higher the score, the more severe the pain. |
| Change From Baseline to Week 16 in Pain Severity (NRS-11 Scale) - Per Protocol Set | Baseline and Week 16 | To evaluate the potential efficacy of safinamide 100 (mg od), compared to placebo, as add-on therapy, for change pain severity (average worst pain experienced in the last 7 days), as assessed by an 11-point Numerical Rating Scale (NRS). Based on this scale, 0 point is the minimum and 10 point is the maximum. The higher the score, the more severe the pain. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Global Impression of Severity (CGI-S) Score for Pain at Week 16 | Baseline and Week 16 | The CGI-S (Clinical Global Impression - Severity) score is a seven-point scale which asks the clinician one question: considering your total clinical experience with this particular population, how mentally ill is the patient at this time? which is rated as follow: 1. = normal, not at all ill; 2. = borderline mentally ill; 3. = mildly ill; 4. = moderately ill; 5. = markedly ill; 6. = severely ill; 7. = among the most severely ill patients. of course the higher the score, the worse the outcome. |
| The Change From Baseline to Week 16 in the Patient Global Impression of Change (PGI-C) Score for Pain | Baseline and Week 16 | The Patients' Global Impression of Change (PGI-C) scale is designed to capture the subject's perception of change in activity limitations, symptoms, emotions, an overall quality of life. These areas are captured using a 7- point scale, indicating: 1. = no change (or condition has got worse); 2. = almost the same, hardly any change at all; 3. = a little better, but not noticeable change; 4. = somewhat better, but the change has not made any real difference; 5. = moderately better, and a slight but noticeable change; 6. = better and a definite improvement that has made a real and worthwhile difference; 7. = a great deal better, and a considerable improvement that has made all the difference. Of course, the higher the score, the better the outcome. |
| Number of Subjects With Concomitant Use of Pain Drugs at Different Timepoints | Baseline, weeks 4, 8 and 16 | This outcome describes the number of subjects which had concomitant assumption of pain drugs at different timepoints. |
| Number of Subjects With a Reduction of ≥2 Points in Pain Severity at Week 16, Compared to Baseline | Week 16 | Reduction in pain severity (based on the average worst pain experienced in the last 7 days) of ≥ 2 points was assessed by an 11-point NRS (numerical rating scale), compared to baseline. Based on this scale, 0 point is the minimum and 10 point is the maximum. The higher the score, the more severe the pain. |
| Amount of PRN PD Pain Medication: Number of Days on Which PRN PD Pain Medication Was Taken at Different Timepoints | At Baseline and weeks 4, 8 and 16 | The analysis of amount of concomitant PRN PD pain medications as reported in the subject diary was summarized: * as the number of days on which PRN PD pain medication was taken at different timepoints. * as the number of subjects who were taking pain medication in the 7 days preceding visits at different timepoints. |
| Change From Baseline to Week 16 in the Hospital Anxiety and Depression Scale (HADS) Score | Baseline and Week 16 | The Hospital Anxiety and Depression Scale (HADS) was devised to measure anxiety and depression in a general medical population of patients through a unique questionnaire which takes 2-5 min to be completed. The questionnaire consists of a total of 14 items: seven items for the anxiety subscale (HADS Anxiety) and seven items for the depression subscale (HADS Depression). HADS Anxiety focus mainly on symptoms of generalized anxiety disorder and HADS Depression is focused on anhedonia, the main symptom of depression. Each item on the questionnaire is scored from 0-3 and this means that a person can score between 0 and 21 for anxiety subscale and the same for depression subscale, where: 0-7 = Normal 8-10 = Borderline abnormal (borderline case). 11-21 = Abnormal (case) The two subscores are then summed up to obtain a total Hospital Anxiety and Depression Scale (HADS). The total scale range is 0-42. The higher the score, the worse the anxiety/depression status. |
| The Change From Baseline to Week 16 in MDS-UPDRS | Baseline and Week 16 | Change in the MDS-UPDRS = Movement Disorder Society-Unified Parkinson's Disease Rating Scale The MDS-UPDRS is defined by 4 Parts, each composed by a different number of items. Each item is rated on a 5-point Likert-type scale (ranging from 0 to 4); Part I (non-motor experiences of daily living; 13 items) Part II (motor experiences of daily living;13 items) Part III (motor examination; 33 items) Part IV (motor complications; 6 items) The MDS-UPDRS has a minimum score of 0 and a maximum score of 260. The higher the score, the more severe the impairment. |
| Amount of PRN PD Pain Medication: Count of Subjects Who Used PRN PD Pain Medication in the 7 Days Preceding Visits | at Baseline and weeks 4, 8 and 16 | Total count of patients who used PRN (meaning when necessary) Parkinson's Disease Pain Medications was expressed both in number and in percentage. The analysis of amount of concomitant PRN PD pain medications as reported in the subject diary was summarized: * as the number of subjects who were taking pain medication in the 7 days preceding visits at different timepoints; * in the number of days on which PRN PD pain medication was taken at different timepoints. |
| The Change From Baseline to Week 16 in the Clinical Global Impression of Change (CGI-C) Score for Pain | Baseline and Week 16 | CGI-C (Clinical Global Impression - Change) score for pain is a seven-point scale that indicates the patient's impression of change for relevant symptoms. It ranges from substantial improvement to substantial worsening: 1. = substantial improvement; 2. = moderate improvement; 3. = minimum improvement; 4. = No change; 5. = Minimum worsening; 6. = moderate worsening; 7. = substantial worsening. of course the higher the score, the worse the outcome. |
Countries
Austria, France, Germany, Italy, Spain
Participant flow
Pre-assignment details
A total of 94 subjects were enrolled in the study; 46 subjects were randomly assigned to safinamide and 25 subjects to placebo. Overall, 23 subjects were screen failures. Overall, 60 subjects (83.3%) completed the study, and 11 subjects discontinued from the study.
Participants by arm
| Arm | Count |
|---|---|
| Experimental Safinamide methanesulfonate film coated tablets once daily
Safinamide Methanesulfonate: 50 mg, 100 mg | 46 |
| Placebo Safinamide methanesulfonate matching placebo film coated tablets once daily
Safinamide methanesulfonate matching placebo: 50 mg, 100 mg | 25 |
| Total | 71 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 4 | 2 |
| Overall Study | Physician Decision | 1 | 0 |
| Overall Study | Withdrawal by Subject | 3 | 1 |
Baseline characteristics
| Characteristic | Total | Experimental | Placebo |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 41 Participants | 27 Participants | 14 Participants |
| Age, Categorical Between 18 and 65 years | 30 Participants | 19 Participants | 11 Participants |
| Age, Continuous | 66.3 years STANDARD_DEVIATION 10.93 | 66.3 years STANDARD_DEVIATION 10.55 | 66.4 years STANDARD_DEVIATION 11.82 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 68 Participants | 44 Participants | 24 Participants |
| Sex: Female, Male Female | 37 Participants | 25 Participants | 12 Participants |
| Sex: Female, Male Male | 34 Participants | 21 Participants | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 46 | 0 / 25 |
| other Total, other adverse events | 19 / 46 | 12 / 25 |
| serious Total, serious adverse events | 0 / 46 | 2 / 25 |
Outcome results
Primary
Change From Baseline to Week 16 in Pain Severity (NRS-11 Scale) - Full Analysis Set
To evaluate the potential efficacy of safinamide 100 (mg od), compared to placebo, as add-on therapy, for change pain severity (average worst pain experienced in the last 7 days), as assessed by an 11-point Numerical Rating Scale (NRS). Based on this scale, 0 point is the minimum and 10 point is the maximum. The higher the score, the more severe the pain.
Time frame: Baseline and Week 16
Population: Full Analysis Set:All randomized subjects in the study, with at least one measurement of the primary efficacy variable following at least one dose of study drug. Please note that n (39 and 20) above reported is the number of subjects with observed average worst pain score.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Experimental | Change From Baseline to Week 16 in Pain Severity (NRS-11 Scale) - Full Analysis Set | -1.6 score on a scale | Standard Deviation 2.01 |
| Placebo | Change From Baseline to Week 16 in Pain Severity (NRS-11 Scale) - Full Analysis Set | -0.8 score on a scale | Standard Deviation 1.29 |
p-value: 0.169595% CI: [-1.75, 0.32]Mixed Model Repeated Measures
Primary
Change From Baseline to Week 16 in Pain Severity (NRS-11 Scale) - Per Protocol Set
To evaluate the potential efficacy of safinamide 100 (mg od), compared to placebo, as add-on therapy, for change pain severity (average worst pain experienced in the last 7 days), as assessed by an 11-point Numerical Rating Scale (NRS). Based on this scale, 0 point is the minimum and 10 point is the maximum. The higher the score, the more severe the pain.
Time frame: Baseline and Week 16
Population: Per Protocol Set : The PP set was a subset of subjects in the FAS who completed the study and for whom no relevant protocol deviations were documented
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Experimental | Change From Baseline to Week 16 in Pain Severity (NRS-11 Scale) - Per Protocol Set | -1.6 score on a scale | Standard Error 2.05 |
| Placebo | Change From Baseline to Week 16 in Pain Severity (NRS-11 Scale) - Per Protocol Set | -0.8 score on a scale | Standard Error 1.33 |
p-value: 0.078495% CI: [-2.1, 0.12]Mixed Model Repeated Measures
Secondary
Amount of PRN PD Pain Medication: Count of Subjects Who Used PRN PD Pain Medication in the 7 Days Preceding Visits
Total count of patients who used PRN (meaning when necessary) Parkinson's Disease Pain Medications was expressed both in number and in percentage. The analysis of amount of concomitant PRN PD pain medications as reported in the subject diary was summarized: * as the number of subjects who were taking pain medication in the 7 days preceding visits at different timepoints; * in the number of days on which PRN PD pain medication was taken at different timepoints.
Time frame: at Baseline and weeks 4, 8 and 16
Population: Full Analysis Set:All randomized subjects in the study, with at least one measurement of the primary efficacy variable following at least one dose of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Experimental | Amount of PRN PD Pain Medication: Count of Subjects Who Used PRN PD Pain Medication in the 7 Days Preceding Visits | Subjects with PRN PD Pain Medication at Baseline | 12 Participants |
| Experimental | Amount of PRN PD Pain Medication: Count of Subjects Who Used PRN PD Pain Medication in the 7 Days Preceding Visits | Subjects with PRN PD Pain Medication at week 4 | 8 Participants |
| Experimental | Amount of PRN PD Pain Medication: Count of Subjects Who Used PRN PD Pain Medication in the 7 Days Preceding Visits | Subjects with PRN PD Pain Medication at week 16 | 5 Participants |
| Experimental | Amount of PRN PD Pain Medication: Count of Subjects Who Used PRN PD Pain Medication in the 7 Days Preceding Visits | Subjects with PRN PD Pain Medication at week 8 | 5 Participants |
| Placebo | Amount of PRN PD Pain Medication: Count of Subjects Who Used PRN PD Pain Medication in the 7 Days Preceding Visits | Subjects with PRN PD Pain Medication at week 16 | 4 Participants |
| Placebo | Amount of PRN PD Pain Medication: Count of Subjects Who Used PRN PD Pain Medication in the 7 Days Preceding Visits | Subjects with PRN PD Pain Medication at Baseline | 7 Participants |
| Placebo | Amount of PRN PD Pain Medication: Count of Subjects Who Used PRN PD Pain Medication in the 7 Days Preceding Visits | Subjects with PRN PD Pain Medication at week 4 | 5 Participants |
| Placebo | Amount of PRN PD Pain Medication: Count of Subjects Who Used PRN PD Pain Medication in the 7 Days Preceding Visits | Subjects with PRN PD Pain Medication at week 8 | 4 Participants |
p-value: 0.512295% CI: [-0.13, 0.26]Cochran-Mantel-Haenszel
Secondary
Amount of PRN PD Pain Medication: Number of Days on Which PRN PD Pain Medication Was Taken at Different Timepoints
The analysis of amount of concomitant PRN PD pain medications as reported in the subject diary was summarized: * as the number of days on which PRN PD pain medication was taken at different timepoints. * as the number of subjects who were taking pain medication in the 7 days preceding visits at different timepoints.
Time frame: At Baseline and weeks 4, 8 and 16
Population: Full Analysis Set: All randomized subjects in the study, with at least one measurement of the primary efficacy variable following at least one dose of study drug.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Experimental | Amount of PRN PD Pain Medication: Number of Days on Which PRN PD Pain Medication Was Taken at Different Timepoints | Baseline | 3.2 number of days | Standard Deviation 2.44 |
| Experimental | Amount of PRN PD Pain Medication: Number of Days on Which PRN PD Pain Medication Was Taken at Different Timepoints | week 4 | 4.8 number of days | Standard Deviation 2.76 |
| Experimental | Amount of PRN PD Pain Medication: Number of Days on Which PRN PD Pain Medication Was Taken at Different Timepoints | week 8 | 6.0 number of days | Standard Deviation 2 |
| Experimental | Amount of PRN PD Pain Medication: Number of Days on Which PRN PD Pain Medication Was Taken at Different Timepoints | week 16 | 4.5 number of days | Standard Deviation 1.73 |
| Placebo | Amount of PRN PD Pain Medication: Number of Days on Which PRN PD Pain Medication Was Taken at Different Timepoints | week 16 | 5.3 number of days | Standard Deviation 1.71 |
| Placebo | Amount of PRN PD Pain Medication: Number of Days on Which PRN PD Pain Medication Was Taken at Different Timepoints | Baseline | 4.1 number of days | Standard Deviation 2.34 |
| Placebo | Amount of PRN PD Pain Medication: Number of Days on Which PRN PD Pain Medication Was Taken at Different Timepoints | week 8 | 4.5 number of days | Standard Deviation 1 |
| Placebo | Amount of PRN PD Pain Medication: Number of Days on Which PRN PD Pain Medication Was Taken at Different Timepoints | week 4 | 4.3 number of days | Standard Deviation 3.2 |
Secondary
Change From Baseline to Week 16 in the Hospital Anxiety and Depression Scale (HADS) Score
The Hospital Anxiety and Depression Scale (HADS) was devised to measure anxiety and depression in a general medical population of patients through a unique questionnaire which takes 2-5 min to be completed. The questionnaire consists of a total of 14 items: seven items for the anxiety subscale (HADS Anxiety) and seven items for the depression subscale (HADS Depression). HADS Anxiety focus mainly on symptoms of generalized anxiety disorder and HADS Depression is focused on anhedonia, the main symptom of depression. Each item on the questionnaire is scored from 0-3 and this means that a person can score between 0 and 21 for anxiety subscale and the same for depression subscale, where: 0-7 = Normal 8-10 = Borderline abnormal (borderline case). 11-21 = Abnormal (case) The two subscores are then summed up to obtain a total Hospital Anxiety and Depression Scale (HADS). The total scale range is 0-42. The higher the score, the worse the anxiety/depression status.
Time frame: Baseline and Week 16
Population: Full Analysis Set: All randomized subjects in the study, with at least one measurement of the primary efficacy variable following at least one dose of study drug. Please note that n (33 and 20) is the number of subjects with observed HADS score.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Experimental | Change From Baseline to Week 16 in the Hospital Anxiety and Depression Scale (HADS) Score | -1.5 score on a scale | Standard Deviation 6.03 |
| Placebo | Change From Baseline to Week 16 in the Hospital Anxiety and Depression Scale (HADS) Score | -2.0 score on a scale | Standard Deviation 4.36 |
p-value: 0.737695% CI: [-3.03, 2.16]ANCOVA
Secondary
Number of Subjects With a Reduction of ≥2 Points in Pain Severity at Week 16, Compared to Baseline
Reduction in pain severity (based on the average worst pain experienced in the last 7 days) of ≥ 2 points was assessed by an 11-point NRS (numerical rating scale), compared to baseline. Based on this scale, 0 point is the minimum and 10 point is the maximum. The higher the score, the more severe the pain.
Time frame: Week 16
Population: Full Analysis Set: All randomized subjects in the study, with at least one measurement of the primary efficacy variable following at least one dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Experimental | Number of Subjects With a Reduction of ≥2 Points in Pain Severity at Week 16, Compared to Baseline | 15 Participants |
| Placebo | Number of Subjects With a Reduction of ≥2 Points in Pain Severity at Week 16, Compared to Baseline | 3 Participants |
p-value: 0.074495% CI: [-0.45, -0.01]Cochran-Mantel-Haenszel
Secondary
Number of Subjects With Concomitant Use of Pain Drugs at Different Timepoints
This outcome describes the number of subjects which had concomitant assumption of pain drugs at different timepoints.
Time frame: Baseline, weeks 4, 8 and 16
Population: Full Analysis Set: All randomized subjects in the study, with at least one measurement of the primary efficacy variable following at least one dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Experimental | Number of Subjects With Concomitant Use of Pain Drugs at Different Timepoints | Subjects with Concomitant Pain Drug at baseline | 0 participants |
| Experimental | Number of Subjects With Concomitant Use of Pain Drugs at Different Timepoints | Subjects with Concomitant Pain Drug at week 8 | 0 participants |
| Experimental | Number of Subjects With Concomitant Use of Pain Drugs at Different Timepoints | Subjects with Concomitant Pain Drug at week 4 | 0 participants |
| Experimental | Number of Subjects With Concomitant Use of Pain Drugs at Different Timepoints | Subjects with Concomitant Pain Drug at week 16 | 0 participants |
| Placebo | Number of Subjects With Concomitant Use of Pain Drugs at Different Timepoints | Subjects with Concomitant Pain Drug at week 16 | 0 participants |
| Placebo | Number of Subjects With Concomitant Use of Pain Drugs at Different Timepoints | Subjects with Concomitant Pain Drug at baseline | 0 participants |
| Placebo | Number of Subjects With Concomitant Use of Pain Drugs at Different Timepoints | Subjects with Concomitant Pain Drug at week 4 | 1 participants |
| Placebo | Number of Subjects With Concomitant Use of Pain Drugs at Different Timepoints | Subjects with Concomitant Pain Drug at week 8 | 0 participants |
p-value: 0.196795% CI: [-0.04, 0.12]Cochran-Mantel-Haenszel
Secondary
The Change From Baseline to Week 16 in MDS-UPDRS
Change in the MDS-UPDRS = Movement Disorder Society-Unified Parkinson's Disease Rating Scale The MDS-UPDRS is defined by 4 Parts, each composed by a different number of items. Each item is rated on a 5-point Likert-type scale (ranging from 0 to 4); Part I (non-motor experiences of daily living; 13 items) Part II (motor experiences of daily living;13 items) Part III (motor examination; 33 items) Part IV (motor complications; 6 items) The MDS-UPDRS has a minimum score of 0 and a maximum score of 260. The higher the score, the more severe the impairment.
Time frame: Baseline and Week 16
Population: Full Analysis Set: All randomized subjects in the study, with at least one measurement of the primary efficacy variable following at least one dose of study drug. Please note that n (31 and 19) is the number of subjects with observed MDS-UPDRS score
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Experimental | The Change From Baseline to Week 16 in MDS-UPDRS | -6.8 score on a scale | Standard Deviation 13.79 |
| Placebo | The Change From Baseline to Week 16 in MDS-UPDRS | -4.8 score on a scale | Standard Deviation 11.68 |
p-value: 0.534995% CI: [-10.33, 5.43]Mixed Model Repeated Measures
Secondary
The Change From Baseline to Week 16 in the Clinical Global Impression of Change (CGI-C) Score for Pain
CGI-C (Clinical Global Impression - Change) score for pain is a seven-point scale that indicates the patient's impression of change for relevant symptoms. It ranges from substantial improvement to substantial worsening: 1. = substantial improvement; 2. = moderate improvement; 3. = minimum improvement; 4. = No change; 5. = Minimum worsening; 6. = moderate worsening; 7. = substantial worsening. of course the higher the score, the worse the outcome.
Time frame: Baseline and Week 16
Population: Full Analysis Set: Full Analysis Set: All randomized subjects in the study, with at least one measurement of the primary efficacy variable following at least one dose of study drug. Please note that n above reported (37 and 20) is the number of subjects with observed CGI-C score.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Experimental | The Change From Baseline to Week 16 in the Clinical Global Impression of Change (CGI-C) Score for Pain | 3.4 score on a scale | Standard Deviation 1.09 |
| Placebo | The Change From Baseline to Week 16 in the Clinical Global Impression of Change (CGI-C) Score for Pain | 3.5 score on a scale | Standard Deviation 1 |
p-value: 0.724795% CI: [-0.7, 0.49]Mixed Model Repeated Measures
Secondary
The Change From Baseline to Week 16 in the Patient Global Impression of Change (PGI-C) Score for Pain
The Patients' Global Impression of Change (PGI-C) scale is designed to capture the subject's perception of change in activity limitations, symptoms, emotions, an overall quality of life. These areas are captured using a 7- point scale, indicating: 1. = no change (or condition has got worse); 2. = almost the same, hardly any change at all; 3. = a little better, but not noticeable change; 4. = somewhat better, but the change has not made any real difference; 5. = moderately better, and a slight but noticeable change; 6. = better and a definite improvement that has made a real and worthwhile difference; 7. = a great deal better, and a considerable improvement that has made all the difference. Of course, the higher the score, the better the outcome.
Time frame: Baseline and Week 16
Population: Full Analysis Set: All randomized subjects in the study, with at least one measurement of the primary efficacy variable following at least one dose of study drug. Please note that n (33 and 20) here reported is the number of subjects with observed PGI-C score.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Experimental | The Change From Baseline to Week 16 in the Patient Global Impression of Change (PGI-C) Score for Pain | 2.7 score on a scale | Standard Deviation 1.33 |
| Placebo | The Change From Baseline to Week 16 in the Patient Global Impression of Change (PGI-C) Score for Pain | 2.5 score on a scale | Standard Deviation 1.28 |
p-value: 0.711595% CI: [-0.61, 0.88]Mixed Model Repeated Measures
Secondary
The Global Impression of Severity (CGI-S) Score for Pain at Week 16
The CGI-S (Clinical Global Impression - Severity) score is a seven-point scale which asks the clinician one question: considering your total clinical experience with this particular population, how mentally ill is the patient at this time? which is rated as follow: 1. = normal, not at all ill; 2. = borderline mentally ill; 3. = mildly ill; 4. = moderately ill; 5. = markedly ill; 6. = severely ill; 7. = among the most severely ill patients. of course the higher the score, the worse the outcome.
Time frame: Baseline and Week 16
Population: Full Analysis Set: All randomized subjects in the study, with at least one measurement of the primary efficacy variable following at least one dose of study drug. Please note that n (44 and 22) here reported is the number of subjects with observed CGI-S score.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Experimental | The Global Impression of Severity (CGI-S) Score for Pain at Week 16 | Baseline | 3.8 score on a scale | Standard Deviation 0.65 |
| Experimental | The Global Impression of Severity (CGI-S) Score for Pain at Week 16 | Week 16 | 3.4 score on a scale | Standard Deviation 0.76 |
| Placebo | The Global Impression of Severity (CGI-S) Score for Pain at Week 16 | Baseline | 3.8 score on a scale | Standard Deviation 0.66 |
| Placebo | The Global Impression of Severity (CGI-S) Score for Pain at Week 16 | Week 16 | 3.5 score on a scale | Standard Deviation 0.76 |
p-value: 0.905295% CI: [-0.43, 0.38]Mixed Model Repeated Measures