Parkinson's Disease
Conditions
Keywords
Rasagiline, Azilect, Parkinson´s Disease, Motor fluctuations
Brief summary
The rationale for conducting this study is to evaluate the efficacy, tolerability, and safety of rasagiline compared to placebo in levodopa-treated Parkinson's Disease (PD) Chinese patients with motor fluctuations. Azilect® (Rasagiline) is indicated for the treatment of idiopathic PD as monotherapy (without levodopa) or as adjunct therapy (with levodopa) in patients with end of dose fluctuations.
Interventions
DRUGPlacebo
Once daily; tablet; orally; 16 weeks
DRUGAzilect®
1 mg daily; tablet; orally; 16 weeks
Sponsors
H. Lundbeck A/S
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
30 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients with idiopathic PD. * Patients with motor fluctuations averaging at least 1 hour daily in the OFF state during the waking hours. * Patients with a Modified Hoehn and Yahr stage ≤3 in the ON state. * Patients taking optimised levodopa or dopa decarboxylase inhibitor (DDI) therapy; they must be stable for at least 14 days prior to baseline. * Patients receiving at least 3 daily doses of levodopa and not more than 8 daily doses of levodopa. * Patients who have demonstrated the ability to keep accurate 24-hour diaries prior to randomisation.
Exclusion criteria
* Patients with a clinically significant or unstable medical or surgical condition that would preclude his/her safe and complete study participation. * Patients with a clinically significant or unstable vascular disease. * Patients who have undergone a neurosurgical intervention of PD. * Patients with severe disabling dyskinesias. * Patients with a clinically significant psychiatric illness, including a major depression, which compromises their ability to provide consent or participate fully in the study. * Patients with a Mini Mental State Examination (MMSE) score ≤24. * Patients with a diagnosis of melanoma or a history of melanoma, or a suspicious lesion. Other inclusion and
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Mean Total Daily OFF Time Using Parkinson's Disease Patient Diary | Baseline and Weeks 4, 8, 12, and 16 | Parkinson's Disease Patient Diary is a self-administered diary designed to assess motor fluctuations throughout the day. It is divided into 30-minute intervals, and the patient selects one of four options for each interval: asleep; off; on with no dyskinesia or without troublesome dyskinesia; or on with troublesome dyskinesia. The Change From Baseline in Mean Total Daily OFF time is calculated by taking the difference between the average of the total daily OFF time at Weeks 4, 8, 12, and 16, and the Baseline Total Daily OFF Time. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Status Using CGI-I Score During ON Time | Week 16 | Clinical Global Impression - Global Improvement (CGI-I) is a single-item rating scale used to evaluate a patient's condition relative to baseline on a 7-point scale, regardless of whether the improvement is related to the investigational medicinal product (IMP). The scale ranges from 1 (very much improved) to 7 (very much worse). |
| Change From Baseline in UPDRS-ADL Score During OFF Time | Baseline and Week 16 | Unified Parkinson's Disease Rating Scale (UPDRS) is a 42-item rating scale designed to assess Parkinson's Disease-related disability and impairment using a patient interview and a physical examination. It has 4 parts and 4 subsection scores. A higher score indicates a worse outcome. I: mentation, behaviour and mood symptoms - 0 to 16; II: activities of daily living (ADL) - 0 to 52; III: motor function - 0 to 108; IV: complications of dopaminergic therapy - 0 to 23. Subsection scores for I to III are used to calculate a total score that ranges from 0 (no disability) to 176 (total dependence). |
| Change From Baseline in UPDRS Motor Score During ON Time | Baseline and Week 16 | UPDRS is a 42-item rating scale designed to assess Parkinson's Disease-related disability and impairment using a patient interview and a physical examination. It has 4 parts and 4 subsection scores. A higher score indicates a worse outcome. I: mentation, behaviour and mood symptoms - 0 to 16; II: ADL - 0 to 52; III: motor function - 0 to 108; IV: complications of dopaminergic therapy - 0 to 23. Subsection scores for I to III are used to calculate a total score that ranges from 0 (no disability) to 176 (total dependence). |
Countries
China
Participant flow
Recruitment details
Outpatients with a primary diagnosis of idiopathic Parkinson's disease.
Pre-assignment details
The study consisted of a 2-week Screening Period during which the levodopa dose was optimised (if required), a 2-week Screening Period during which the levodopa dose was stabilised, a 16-week double-blind treatment period with rasagiline or placebo once daily (patients were randomised in a 1:1 ratio), and a 4-week Safety Follow-up Period.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Once daily; tablet; orally; 16 weeks | 158 |
| Azilect® 1 mg daily; tablet; orally; 16 weeks | 163 |
| Total | 321 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 5 | 6 |
| Overall Study | Lack of Efficacy | 0 | 1 |
| Overall Study | Protocol Violation | 2 | 3 |
| Overall Study | Withdrawal of Consent | 3 | 2 |
Baseline characteristics
| Characteristic | Total | Placebo | Azilect® |
|---|---|---|---|
| Age, Continuous | 62.2 years STANDARD_DEVIATION 9.4 | 61.7 years STANDARD_DEVIATION 9.9 | 62.7 years STANDARD_DEVIATION 8.9 |
| CGI-S | 4.00 units on a scale STANDARD_DEVIATION 0.77 | 4.07 units on a scale STANDARD_DEVIATION 0.77 | 3.94 units on a scale STANDARD_DEVIATION 0.76 |
| Sex: Female, Male Female | 109 Participants | 49 Participants | 60 Participants |
| Sex: Female, Male Male | 212 Participants | 109 Participants | 103 Participants |
| Total Daily OFF Time | 6.12 hours STANDARD_DEVIATION 2.66 | 6.13 hours STANDARD_DEVIATION 2.72 | 6.10 hours STANDARD_DEVIATION 2.6 |
| UPDRS-ADL Score During OFF Time | 16.01 units on a scale STANDARD_DEVIATION 7.34 | 16.45 units on a scale STANDARD_DEVIATION 7.54 | 15.59 units on a scale STANDARD_DEVIATION 7.15 |
| UPDRS Motor Score During ON time | 24.70 units on a scale STANDARD_DEVIATION 10.5 | 25.62 units on a scale STANDARD_DEVIATION 10.48 | 23.82 units on a scale STANDARD_DEVIATION 10.47 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 12 / 158 | 11 / 163 |
| serious Total, serious adverse events | 5 / 158 | 7 / 163 |
Outcome results
Primary
Change From Baseline in Mean Total Daily OFF Time Using Parkinson's Disease Patient Diary
Parkinson's Disease Patient Diary is a self-administered diary designed to assess motor fluctuations throughout the day. It is divided into 30-minute intervals, and the patient selects one of four options for each interval: asleep; off; on with no dyskinesia or without troublesome dyskinesia; or on with troublesome dyskinesia. The Change From Baseline in Mean Total Daily OFF time is calculated by taking the difference between the average of the total daily OFF time at Weeks 4, 8, 12, and 16, and the Baseline Total Daily OFF Time.
Time frame: Baseline and Weeks 4, 8, 12, and 16
Population: Full-analysis set (FAS); observed cases (OC)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Mean Total Daily OFF Time Using Parkinson's Disease Patient Diary | -0.76 hours | Standard Error 0.16 |
| Azilect® | Change From Baseline in Mean Total Daily OFF Time Using Parkinson's Disease Patient Diary | -1.25 hours | Standard Error 0.16 |
p-value: 0.022895% CI: [-0.92, -0.07]ANCOVA
Secondary
Change From Baseline in UPDRS-ADL Score During OFF Time
Unified Parkinson's Disease Rating Scale (UPDRS) is a 42-item rating scale designed to assess Parkinson's Disease-related disability and impairment using a patient interview and a physical examination. It has 4 parts and 4 subsection scores. A higher score indicates a worse outcome. I: mentation, behaviour and mood symptoms - 0 to 16; II: activities of daily living (ADL) - 0 to 52; III: motor function - 0 to 108; IV: complications of dopaminergic therapy - 0 to 23. Subsection scores for I to III are used to calculate a total score that ranges from 0 (no disability) to 176 (total dependence).
Time frame: Baseline and Week 16
Population: FAS; LOCF
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in UPDRS-ADL Score During OFF Time | -1.20 units on a scale | Standard Error 0.28 |
| Azilect® | Change From Baseline in UPDRS-ADL Score During OFF Time | -2.21 units on a scale | Standard Error 0.28 |
p-value: 0.007595% CI: [-1.75, -0.27]ANCOVA
Secondary
Change From Baseline in UPDRS Motor Score During ON Time
UPDRS is a 42-item rating scale designed to assess Parkinson's Disease-related disability and impairment using a patient interview and a physical examination. It has 4 parts and 4 subsection scores. A higher score indicates a worse outcome. I: mentation, behaviour and mood symptoms - 0 to 16; II: ADL - 0 to 52; III: motor function - 0 to 108; IV: complications of dopaminergic therapy - 0 to 23. Subsection scores for I to III are used to calculate a total score that ranges from 0 (no disability) to 176 (total dependence).
Time frame: Baseline and Week 16
Population: FAS; LOCF
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in UPDRS Motor Score During ON Time | -1.75 units on a scale | Standard Error 0.55 |
| Azilect® | Change From Baseline in UPDRS Motor Score During ON Time | -3.34 units on a scale | Standard Error 0.55 |
p-value: 0.031795% CI: [-3.05, -0.14]ANCOVA
Secondary
Clinical Status Using CGI-I Score During ON Time
Clinical Global Impression - Global Improvement (CGI-I) is a single-item rating scale used to evaluate a patient's condition relative to baseline on a 7-point scale, regardless of whether the improvement is related to the investigational medicinal product (IMP). The scale ranges from 1 (very much improved) to 7 (very much worse).
Time frame: Week 16
Population: FAS; last observation carried forward (LOCF)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Clinical Status Using CGI-I Score During ON Time | 3.56 units on a scale | Standard Error 0.07 |
| Azilect® | Clinical Status Using CGI-I Score During ON Time | 3.15 units on a scale | Standard Error 0.07 |
p-value: <0.000195% CI: [-0.61, -0.22]ANCOVA