Parkinson's Disease
Conditions
Keywords
Rasagiline, Azilect, Parkinson´s Disease, Motor fluctuations
Brief summary
Rasagiline has been developed for the treatment of Parkinson's Disease (PD), as monotherapy in early PD patients not treated with levodopa, and as adjunct therapy to levodopa in levodopa-treated PD patients with motor fluctuations. The rationale for conducting this study is to evaluate the efficacy, tolerability, and safety of rasagiline compared to placebo in Chinese PD patients not treated with levodopa.
Interventions
DRUGrasagiline
1 mg/day, tablets, once daily, orally
DRUGplacebo
tablets, once daily, orally
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
35 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients with idiopathic PD. * Patients with a Modified Hoehn and Yahr stage \<3.
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 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 to Week 26 in UPDRS Total Score | Baseline to Week 26 | The Unified Parkinson's Disease Rating Scale (UPDRS) is a 42-item rating scale designed to assess Parkinson's disease-related disability and impairment. The scale comprises four parts: Part I evaluates mentation, behaviour, and mood symptoms; Part II evaluates activities of daily living (ADL); Part III evaluates motor function; and Part IV evaluates complications of dopaminergic therapy. The total score is the sum of the subscale scores for Parts I to III and ranges from 0 (no disability) to 176 (total dependence). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Week 26 in Subscale Scores of the UPDRS (Part III) | Baseline to Week 26 | The Unified Parkinson's Disease Rating Scale (UPDRS) Part III evaluates motor function, it comprises 14 parts and the score ranges from 0 (normal) to 108 (severe impairement and disability) |
| Time to Onset of Levodopa Therapy | Baseline to Week 26 | It was stated in the statistical analysis plan (SAP) that if \>10% of FAS patients were considered to have taken levodopa during the treatment period, the endpoint, time to onset of levodopa treatment was to be analysed. However, since only one patient (in the placebo group) had levodopa administered during the treatment period, this endpoint was not analysed, as had been defined a priori in the SAP. |
| Change From Baseline to Week 26 in Subscale Scores of the UPDRS (Part I) | Baseline to Week 26 | The Unified Parkinson's Disease Rating Scale (UPDRS) Part I evaluates mentation, behaviour and mood symptoms, it comprises 4 parts and the score ranges from 0 (normal) to 16 (severe impairement) |
| Change From Baseline to Week 26 in Subscale Scores of the UPDRS (Part II) | Baseline to Week 26 | The Unified Parkinson's Disease Rating Scale (UPDRS) Part II evaluates activities of daily living, it comprises 13 parts and the score ranges from 0 (normal) to 52 (severe impairement and disability) |
| Levodopa Administration Within 26 Weeks | Baseline to Week 26 | It was stated in the statistical analysis plan (SAP) that if \>10% of FAS patients were considered to have taken levodopa during the treatment period, the endpoint, levodopa administration within 26 Weeks was to be analysed. However, since only one patient (in the placebo group) had levodopa administered during the treatment period, this endpoint was not analysed, as had been defined a priori in the SAP. |
Countries
China
Participant flow
Recruitment details
Outpatients aged 35 years or older, who had idiopathic Parkinson's disease and were not treated with levodopa or other antiparkinsonian medications, were recruited for this study from China.
Pre-assignment details
A Screening Visit was held approximately 28 days prior to group assignment (group assignment was held during the Baseline Visit). Patients who met each of the inclusion criteria and none of the exclusion criteria were eligible to participate in this study.
Participants by arm
| Arm | Count |
|---|---|
| Placebo placebo: tablets, once daily, orally | 65 |
| Rasagiline rasagiline: 1 mg/day, tablets, once daily, orally | 65 |
| Total | 130 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 5 | 3 |
| Overall Study | Protocol Violation | 0 | 3 |
| Overall Study | Withdrawal of Consent | 7 | 1 |
Baseline characteristics
| Characteristic | Rasagiline | Total | Placebo |
|---|---|---|---|
| Age, Continuous | 58.5 years STANDARD_DEVIATION 8.72 | 59.0 years STANDARD_DEVIATION 8.95 | 59.5 years STANDARD_DEVIATION 9.22 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 65 Participants | 130 Participants | 65 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 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 | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 30 Participants | 55 Participants | 25 Participants |
| Sex: Female, Male Male | 35 Participants | 75 Participants | 40 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 6 / 65 | 8 / 65 |
| serious Total, serious adverse events | 4 / 65 | 0 / 65 |
Outcome results
Primary
Change From Baseline to Week 26 in UPDRS Total Score
The Unified Parkinson's Disease Rating Scale (UPDRS) is a 42-item rating scale designed to assess Parkinson's disease-related disability and impairment. The scale comprises four parts: Part I evaluates mentation, behaviour, and mood symptoms; Part II evaluates activities of daily living (ADL); Part III evaluates motor function; and Part IV evaluates complications of dopaminergic therapy. The total score is the sum of the subscale scores for Parts I to III and ranges from 0 (no disability) to 176 (total dependence).
Time frame: Baseline to Week 26
Population: The full-analysis set (FAS) comprised all patients in the APTS who had a valid baseline assessment and at least one valid post-baseline assessment of the primary efficacy variable.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to Week 26 in UPDRS Total Score | -0.18 units on a scale | Standard Error 0.98 |
| Rasagiline | Change From Baseline to Week 26 in UPDRS Total Score | -3.18 units on a scale | Standard Error 0.95 |
Comparison: This study was designed to show a trend, that is, to show a clinical difference in the primary efficacy analysis, at a two-sided significance level of 0.25. Assuming a difference between rasagiline and placebo of a 3-point change in the UPDRS total score and a standard deviation on the change from baseline of 7 points, a sample size of 60 patients per treatment group gave an 88% probability of showing a trend. LOCF (last observation carried forward) was used.p-value: 0.025475% CI: [-4.53, -1.47]ANCOVA
Secondary
Change From Baseline to Week 26 in Subscale Scores of the UPDRS (Part I)
The Unified Parkinson's Disease Rating Scale (UPDRS) Part I evaluates mentation, behaviour and mood symptoms, it comprises 4 parts and the score ranges from 0 (normal) to 16 (severe impairement)
Time frame: Baseline to Week 26
Population: The full-analysis set (FAS) comprised all patients in the APTS who had a valid baseline assessment and at least one valid post-baseline assessment of the primary efficacy variable.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to Week 26 in Subscale Scores of the UPDRS (Part I) | 0.08 units on a scale | Standard Error 0.15 |
| Rasagiline | Change From Baseline to Week 26 in Subscale Scores of the UPDRS (Part I) | -0.54 units on a scale | Standard Error 0.15 |
Comparison: LOCF (last observation carried forward) was used.p-value: 0.003295% CI: [-1.03, -0.21]ANCOVA
Secondary
Change From Baseline to Week 26 in Subscale Scores of the UPDRS (Part II)
The Unified Parkinson's Disease Rating Scale (UPDRS) Part II evaluates activities of daily living, it comprises 13 parts and the score ranges from 0 (normal) to 52 (severe impairement and disability)
Time frame: Baseline to Week 26
Population: The full-analysis set (FAS) comprised all patients in the APTS who had a valid baseline assessment and at least one valid post-baseline assessment of the primary efficacy variable.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to Week 26 in Subscale Scores of the UPDRS (Part II) | 0.25 units on a scale | Standard Error 0.38 |
| Rasagiline | Change From Baseline to Week 26 in Subscale Scores of the UPDRS (Part II) | -0.43 units on a scale | Standard Error 0.37 |
Comparison: LOCF (last observation carried forward) was used.p-value: 0.196395% CI: [-1.7, 0.35]ANCOVA
Secondary
Change From Baseline to Week 26 in Subscale Scores of the UPDRS (Part III)
The Unified Parkinson's Disease Rating Scale (UPDRS) Part III evaluates motor function, it comprises 14 parts and the score ranges from 0 (normal) to 108 (severe impairement and disability)
Time frame: Baseline to Week 26
Population: The full-analysis set (FAS) comprised all patients in the APTS who had a valid baseline assessment and at least one valid post-baseline assessment of the primary efficacy variable.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to Week 26 in Subscale Scores of the UPDRS (Part III) | -0.52 units on a scale | Standard Error 0.68 |
| Rasagiline | Change From Baseline to Week 26 in Subscale Scores of the UPDRS (Part III) | -2.23 units on a scale | Standard Error 0.65 |
Comparison: LOCF (last observation carried forward) was used.p-value: 0.064195% CI: [-3.52, 0.1]ANCOVA
Secondary
Levodopa Administration Within 26 Weeks
It was stated in the statistical analysis plan (SAP) that if \>10% of FAS patients were considered to have taken levodopa during the treatment period, the endpoint, levodopa administration within 26 Weeks was to be analysed. However, since only one patient (in the placebo group) had levodopa administered during the treatment period, this endpoint was not analysed, as had been defined a priori in the SAP.
Time frame: Baseline to Week 26
Secondary
Time to Onset of Levodopa Therapy
It was stated in the statistical analysis plan (SAP) that if \>10% of FAS patients were considered to have taken levodopa during the treatment period, the endpoint, time to onset of levodopa treatment was to be analysed. However, since only one patient (in the placebo group) had levodopa administered during the treatment period, this endpoint was not analysed, as had been defined a priori in the SAP.
Time frame: Baseline to Week 26